Neuro-Ophthalmology and Neuro-Otology: A Case-Based Guide for Clinicians and Scientists 3030768740, 9783030768744

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NeuroOphthalmology and NeuroOtology A Case-Based Guide for Clinicians and Scientists Daniel Gold

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Neuro-Ophthalmology and Neuro-Otology

Daniel Gold

Neuro-­ Ophthalmology and Neuro-Otology A Case-Based Guide for Clinicians and Scientists

Daniel Gold Division of Neuro-Visual & Vestibular Disorders The Johns Hopkins University School of Medicine Baltimore, MD USA

ISBN 978-3-030-76874-4    ISBN 978-3-030-76875-1 (eBook) https://doi.org/10.1007/978-3-030-76875-1 © Springer Nature Switzerland AG 2021, corrected publication 2022 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

As a first-year neurology resident, I saw my first patient with spontaneous nystagmus and a skew deviation due to the acute vestibular syndrome with Dr. Stephen Reich (a fellow eye movement enthusiast), and I immediately fell in love with the bedside ocular motor and vestibular exam. I wanted to learn more about eye movements and read about the “HINTS” exam to diagnose stroke in the acute vestibular syndrome (Drs. Jorge Kattah and David Newman-Toker). I was then introduced to Walsh & Hoyt’s Clinical Neuro-Ophthalmology (edited by Drs. Neil Miller, Nancy Newman, Valerie Biousse, and John Kerrison), and The Neurology of Eye Movements (by Drs. John Leigh and David Zee), Neuro-Ophthalmology Illustrated (by Drs. Valérie Biousse and Nancy Newman), and Liu, Volpe, and Galetta’s Neuro-­ Ophthalmology: Diagnosis & Management became my prized possessions (little did I know that these authors would become my future mentors and colleagues). While I came across excellent neuro-ophthalmology and neuro-otology textbooks and review guides, I couldn’t locate a single clinically based resource that married these two subspecialties. While it was apparent to me that there was considerable overlap between visual and vestibular disorders, there appeared to be a significant knowledge gap at the interface of neuro-ophthalmology and neuro-otology. Additionally, while visual and vestibular symptoms are so common, remarkably few clinicians seemed comfortable evaluating patients with these complaints.

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Preface

Throughout my training, I had the great fortune of being surrounded by master clinicians, and I was inspired not only by their clinical acumen and bedside manner, but also their penchant for recording eye movements. When I became an attending myself, the lines between “neuro-ophthalmology” and “neuro-otology” blurred within my practice, and I began to record videos of everything I felt had educational value. My burgeoning database of videos turned into my own collection through the North American Neuro-Ophthalmology Society’s (NANOS) Neuro-Ophthalmology Virtual Education Library (NOVEL), with substantial assistance and encouragement from Nancy Lombardo and Dr. Kathleen Digre. My passion for clinical care, the bedside exam, and the desire to formalize my NOVEL Collection became the impetus for this book – a onestop shop for clinical neuro-ophthalmology and neuro-otology using a case (and video)-based approach. While all of the basics are included here, there are enough clinical pearls, figures, and video examples throughout to keep even the most advanced and experienced readers satiated. In addition to going through this book chapter by chapter, it can also be used when the reader is in a pinch – e.g., my patient has acute onset prolonged vertigo … what do I ask or examine first? For these real-time situations, start with the symptombased tables. Not sure what neuro-ophthalmic or audiovestibular testing is necessary for your patient? There are tables and electronic supplemental materials for that. Not sure how to examine saccades or use your new Maddox rod? It’s all here for you in the form of videos and other interactive resources. I hope this practical resource can be used to enthuse and educate current and future neurologists, ophthalmologists, otolaryngologists, neurosurgeons, audiologists, physical therapists, internists, emergency medicine providers, as well as scientists looking for a clinical perspective, and I hope to inspire others as my mentors and colleagues have inspired me. I would also like to dedicate this book to my family for their support and patience, and to my patients for their generosity in sharing their stories (as well as their eyes).

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How to use this book: To access the videos and electronic supplemental materials (ESM), you have two options: 1. Visit the web link under the “Supplementary Information” heading on the first page of each chapter. This will take you to the electronic version of the chapter 2. Visit my Neuro-Ophthalmology Virtual Education Library (NOVEL) collection through the North American NeuroOphthalmology Society (NANOS) at https://novel.utah.edu/ Gold/ – here you will find a chapter-by-chapter list of correspondingly numbered ESM and video links to accompany the book. The electronic content that is accessible via “Supplementary Information” and through NOVEL is identical, how you choose to access it simply depends on your preference. Please note that while the video legends (found in the front matter or in the electronic materials) expound on the videos and/ or text, many of them also explore more advanced ocular motor and vestibular concepts. Baltimore, MD, USA

Daniel Gold

Acknowledgments

I would like to acknowledge and thank the following mentors, colleagues, and trainees for their advice, guidance, and feedback throughout this process. Their willingness to contribute their valuable time and expertise has been essential to the creation of this book: Dr. Stephen Reich (for inspiring and encouraging me to write a book in the first place, also content review and contribution of figures); Dr. David Zee (for inspiration, content review, and contribution of ideas); Dr. Neil Miller (for content review, contribution of figures and ideas); Dr. Collin McClelland (for content review, contribution of figures and ideas); Dr. Victoria Pelak (for content review and contribution of ideas); Dr. Vivek Patel (for content review); Dr. Veeral Shah (for content review and contribution of figures); Dr. Marc Levin (for content review); Dr. Ari Shemesh (for content review); Dr. Tony Brune (for content review, and for helping create many videos); Dr. Olwen Murphy (for helping create several figures and for content review); Dr. David Hale (for content review); Dr. Elizabeth Fracica (for content review); Dr. Paul Chang (for content review); Dr. Nicholas Hac (for content review); Justin Bosley (our ophthalmic/vestibular technician, for being excellent at what he does)

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Contents

1 Preparing for the Exam������������������������������������������������  1 1.1 Equipment for the Afferent Neuro-Ophthalmology Bedside Exam ��������������������������������������������������������  1 1.1.1 Vision����������������������������������������������������������  1 1.1.2 Pupils, Eyelids, Orbits��������������������������������  2 1.2 Equipment for the Efferent Neuro-Ophthalmic/ Vestibular Bedside Exam����������������������������������������  2 Reference ������������������������������������������������������������������������  3 2 Disorders of the Pupils, Eyelids, and Orbits����������������  5 2.1 Pupil������������������������������������������������������������������������  5 2.1.1 Anisocoria—The History����������������������������  5 2.1.2 Anisocoria—The Exam������������������������������ 15 2.1.3 Pharmacologic Testing�������������������������������� 16 2.1.4 Horner’s Syndrome ������������������������������������ 17 2.1.5 Aneursymal Third Nerve Palsy������������������ 22 2.1.6 Tonic Pupil�������������������������������������������������� 25 2.2 Eyelid (Ptosis and Spasm)�������������������������������������� 28 2.2.1 Ptosis—The History������������������������������������ 28 2.2.2 Ptosis—The Exam�������������������������������������� 28 2.2.3 Levator Dehiscence������������������������������������ 29 2.2.4 Myasthenia Gravis�������������������������������������� 34 2.2.5 Eyelid Spasms�������������������������������������������� 38 2.3 Orbit/Globe ������������������������������������������������������������ 41 2.3.1 Orbital Disorders—The History ���������������� 42 2.3.2 Orbital Disorders—The Exam�������������������� 42

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2.3.3 Thyroid Eye Disease ���������������������������������� 44 2.3.4 Eye Pain (Acute Angle Closure Glaucoma)�������������������������������������������������� 46 2.3.5 Red Eye (Carotid Cavernous Fistula) �������� 49 References������������������������������������������������������������������������ 52 3 Loss of Vision and Other Visual Symptoms���������������� 55 3.1 Vision Loss—The History�������������������������������������� 55 3.2 Vision Loss—The Examination������������������������������ 55 3.3 Interpretation of Monocular or Binocular Visual Fields—Dr. Neil Miller’s 10 Visual Field Rules to Live by�������������������������������������������� 68 3.4 Ancillary Testing in Neuro-Ophthalmology ���������� 74 3.5 Prechiasmal (Monocular Vision Loss) ������������������  74 3.5.1 Retina���������������������������������������������������������� 76 3.5.2 Optic Nerve������������������������������������������������ 85 3.6 Chiasmal Visual Disorders��������������������������������������102 3.6.1 Pituitary Tumor ������������������������������������������102 3.7 Retrochiasmal Visual Disorders������������������������������105 3.7.1 The History ������������������������������������������������105 3.7.2 The Exam����������������������������������������������������105 3.7.3 Treatment Options��������������������������������������105 3.7.4 Optic Tract��������������������������������������������������105 3.7.5 Lateral Geniculate Nucleus (LGN)������������106 3.7.6 Optic Radiations�����������������������������������������108 3.7.7 Occipital Lobe/Striate Cortex ��������������������110 3.8 Higher Cortical Visual Disorders����������������������������111 3.8.1 Posterior Cortical Atrophy��������������������������111 3.8.2 Hallucinations ��������������������������������������������117 3.8.3 Visual Snow������������������������������������������������119 References������������������������������������������������������������������������121 4 Motility and Ocular Motor Disorders��������������������������125 4.1 The History ������������������������������������������������������������125 4.2 The Exam����������������������������������������������������������������126

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4.3 Subarachnoid Space, Cavernous Sinus, Orbital Apex������������������������������������������������������������135 4.3.1 Subarachnoid Space������������������������������������135 4.3.2 Cavernous Sinus������������������������������������������137 4.3.3 Orbital Apex������������������������������������������������141 4.4 Medulla ������������������������������������������������������������������142 4.4.1 Lateral Medullary (Wallenberg) Syndrome (Including Skew Deviation and Saccadic Dysmetria)����������������������������142 4.5 Pons������������������������������������������������������������������������151 4.5.1 Medial Longitudinal Fasciculus Syndrome����������������������������������������������������151 4.5.2 Horizontal Gaze Palsies������������������������������156 4.5.3 Sixth Nerve ������������������������������������������������160 4.6 Midbrain������������������������������������������������������������������164 4.6.1 Third Nerve������������������������������������������������164 4.6.2 Fourth Nerve ����������������������������������������������167 4.6.3 Vertical Gaze Palsies����������������������������������174 4.6.4 Progressive Supranuclear Palsy������������������179 4.7 Cerebellum��������������������������������������������������������������182 4.7.1 Syndrome of the Flocculus and Paraflocculus (Tonsil) ��������������������������������184 4.7.2 Syndrome of the Nodulus and Ventral Uvula����������������������������������������������������������187 4.7.3 Syndrome of the Dorsal Vermis and Posterior Fastigial Nucleus������������������188 References������������������������������������������������������������������������189 5 Oscillopsia, Nystagmus, and Other Abnormal Movements����������������������������������������������������������������������191 5.1 The History—How to Approach Oscillopsia and Nystagmus��������������������������������������������������������191 5.2 The Exam—Does My Patient Have Nystagmus or Something Else? ������������������������������������������������192

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5.3 Nystagmus��������������������������������������������������������������194 5.3.1 Horizontal Nystagmus (Bruns Nystagmus) ������������������������������������������������194 5.3.2 Periodic Alternating Nystagmus ����������������205 5.3.3 Downbeat Nystagmus ��������������������������������206 5.3.4 Upbeat Nystagmus��������������������������������������210 5.3.5 Torsional Nystagmus����������������������������������214 5.3.6 Oculopalatal Tremor ����������������������������������216 5.3.7 Multiple Sclerosis Acquired Pendular Nystagmus��������������������������������������������������219 5.4 Saccadic Intrusions, Oscillations, and Other Nystagmoid Movements ����������������������������������������222 5.4.1 Square Wave Jerks (SWJ) and Related Saccadic Intrusions ����������������222 5.4.2 Opsoclonus/Ocular Flutter��������������������������223 5.4.3 Superior Oblique Myokymia����������������������226 References������������������������������������������������������������������������228 6 Vestibular Disorders������������������������������������������������������231 6.1 The Vestibular History��������������������������������������������231 6.1.1 TRIAGE������������������������������������������������������231 6.1.2 TiTrATE������������������������������������������������������231 6.1.3 Test��������������������������������������������������������������233 6.2 The Vestibular Examination������������������������������������233 6.3 Bedside Auditory Testing����������������������������������������239 6.4 Laboratory Testing of Audiovestibular Disorders ����������������������������������������������������������������240 6.5 Vestibular Syndromes ��������������������������������������������240 6.5.1 Acute Vestibular Syndrome������������������������240 6.5.2 Episodic Vestibular Syndrome��������������������252 6.5.3 Chronic Vestibular Syndrome ��������������������285 References������������������������������������������������������������������������298 7 Pediatric Clinical Pearls������������������������������������������������305 7.1 Neuroblastoma��������������������������������������������������������305 7.2 Neurofibromatosis Type 1 (NF-1)��������������������������306

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7.3 Abnormal Development of the Visual Pathways (Optic Nerve Hypoplasia)����������������������307 7.4 Infantile Nystagmus (IN)����������������������������������������307 7.5 Abnormal (but Characteristic) Eye Movements��������������������������������������������������������������308 7.6 Esotropia—Infantile or Acquired?��������������������������310 7.7 Idiopathic Intracranial Hypertension����������������������310 7.8 Optic Neuritis����������������������������������������������������������312 7.9 Myasthenia Gravis��������������������������������������������������312 7.10 Ocular Motor Palsies (Third, Fourth, Sixth Nerve Palsies)������������������������������������������������313 7.11 Retinal Disorders Mimicking Neurologic Disease��������������������������������������������������������������������314 7.12 Vertigo and Dizziness ��������������������������������������������315 References������������������������������������������������������������������������315 Correction to: Vestibular Disorders ������������������������������������� C1 Index����������������������������������������������������������������������������������������317

List of Figures

Fig. 2.1

Fig. 2.2

Oculosympathetic pathway for pupillary dilation: The oculosympathetic tract is an uncrossed pathway that begins in the hypothalamus, with fibers descending in the brainstem (first order, commonly affected in a lateral medullary syndrome), synapsing in the lower cervical/upper thoracic spinal cord (interomediolateral cell columns of C8–T2, also referred to as the ciliospinal center of budge) and continuing on as the second order fibers (in proximity to the lung apex). The tract ascends and then synapses in the superior cervical ganglion. The third order neuron leaves the ganglion, with sudomotor fibers following the external carotid artery (explanation for absence of anhidrosis with an internal carotid artery dissection), while the remaining fibers ascend with the internal carotid artery (explanation for dissection causing a painful Horner’s syndrome). The third order fibers innervate the eyelid (superior [Muller muscle] and inferior tarsal muscles) and pupillary dilator muscles to open the eyelids and dilate the pupils, respectively. A lesion along the oculosympathetic tract causes a Horner’s syndrome with ptosis and miosis, and sometimes clinically apparent anhidrosis (with first or second order but not third order)��������������������������������������������������������������������� 13 Parasympathetic pathway for pupillary constriction: When a bright light is shone in one eye, light xvii

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Fig. 2.3

Fig. 2.4

Fig. 2.5

Fig. 2.6

List of Figures

enters the pupil and hyperpolarizes retinal ­photoreceptors that activate retinal ganglion cells. These signals propagate along the optic nerves, chiasm, optic tracts, and fibers responsible for the light reflex then synapse in the dorsal midbrain (prior to reaching the lateral geniculate nucleus) at the pretectal nuclei, then to the Edinger–Westphal nucleus (EWN) of the oculomotor nucleus. From here, efferent fibers travel with the oculomotor nerve to the ciliary ganglion and, finally, innervate the constrictor (­ sphincter) muscles for bilateral pupillary constriction�������������������������������������������� 14 Structures of the eye and ocular adnexa: Seen here is a normal right eye, with clinically relevant ­structures and landmarks labeled. Also note that the position of the corneal light reflex can assist in ocular alignment evaluation in a patient with poor vision (i.e., Hirschberg and Krimsky tests)���������������������� 15 Dilute (0.1%) pilocarpine testing to diagnose a tonic pupil: This is a patient with a slightly mydriatic left pupil that constricted to a near stimulus but not to light. There was also segmental constriction of the iris appreciated with slit lamp exam. Dilute pilocarpine was instilled OU, and 45 minutes later, there was no effect on the normal (right) pupil but clear constriction of the mydriatic (left) pupil, supporting the diagnosis of a left tonic pupil. (Photos courtesy of Dr. Collin McClelland)����������������������� 17 Apraclonidine testing to diagnose a Horner’s syndrome: Apraclonidine (0.5%) testing was performed within 1 week of onset of Horner’s syndrome. Testing was positive in that anisocoria reversed (as well as ptosis)—i.e., the previously miotic right (Horner’s syndrome) pupil was now slightly mydriatic�������������������������������������������������� 18 Right Horner’s syndrome due to right internal carotid artery (ICA) dissection: More prominent anisocoria in dark versus light is apparent in this

List of Figures

Fig. 2.7

Fig. 2.8

Fig. 2.9

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case, which is highly suggestive of a Horner’s pupil (related to poor sympathetic activation causing a “dilation lag” in the miotic [right] pupil). There is also mild upper lid ptosis but no anhidrosis (which is typical of a third order lesion). MR images include axial fluid attenuated inversion recovery (FLAIR) and time of flight (TOF) MR angiogram demonstrating a crescent sign in the right ICA����������������������� 19 The eyelid exam—marginal reflex distance (MRD) 1 and 2: For documentation and comparative ­purposes, the MRD1 (upper eyelid margin to corneal light reflex, normal is ~4–5 mm) and MRD2 (corneal light reflex to lower eyelid margin, normal is ~5 mm) should be recorded, especially when ptosis is ­suspected. The palpebral fissure is simply the MRD1 + MRD2 and will be widened with a seventh NP and narrowed with ptosis (from any etiology). A light source and measuring device are all that are needed������������������������������������������������������������� 20 Right third NP due to right posterior communicating (PCOM) artery aneurysm: The combination of severe ptosis, mydriasis, and a “down and out” appearance OD are all typical of a right third NP, which in this case was due to right PCOM aneurysm seen on the axial CT angiogram (left) and CTA 3D reconstruction (right). Because the pupillary fibers travel in the outer portion of the third nerve, the pupil is almost always involved with aneurysmal (or other) compression and is typically spared with a microvascular insult. (CT images courtesy of Dr. Judy Huang)����� 22 Clinical features of a left tonic pupil: Seen here is a patient with anisocoria with a mydriatic pupil OS that constricted poorly to light but much better to a near target. Additionally, when asked to look from a near to a distant target, slow (tonic) dilation was observed. Dilute (0.1% pilocarpine) constricted the mydriatic (left) pupil but not the normal (right) pupil���������������������������������������������������������������������� 26

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List of Figures

Fig. 2.10 The eyelid exam—levator function (LF) and lid crease: For documentation and comparative purposes, the lid crease (upper eyelid margin to the insertion of the levator palpebrae muscle, normal ~6–10 mm) and LF (the white dotted line represents the LF, or the distance between the upper lid in downgaze [yellow arrowhead] compared to upgaze, while ensuring that the frontalis muscle does not contribute to the eyelid movement, normal ~14–16 mm) should be recorded in millimeters. A high lid crease is typical of disinsertion (dehiscence) of the levator muscle, while diminished LF is suggestive of extraocular muscle weakness (e.g., third NP, myasthenia gravis, or myopathy)����������������������������������� 30 Fig. 2.11 Levator dehiscence—a common cause of mechanical ptosis: Look for the combination of upper lid ptosis and a high lid crease, with lack of fatigability and normal levator function. It is typically bilateral and may be associated with other signs (e.g., prominent superior sulcus, “sagging eye syndrome” [esotropia greater at distance]) in the aging population, and when unilateral, also consider trauma, ocular surgery, or contact lens wear/eye rubbing������������������������������������������������������������������ 30 Fig. 2.12 Structures relevant to eyelid opening and closing: The seventh cranial nerve is responsible for eyelid closure and innervates the orbicularis oculi (OO) muscles, while eyelid opening depends mainly on the third cranial nerve (levator palpebrae, i.e., severe ptosis with a third NP) as well as the oculosympathetic tract (superior and inferior tarsal muscles, i.e., mild upper lid [and sometimes lower lid or upside down] ptosis with a Horner’s syndrome)�������������� 31 Fig. 2.13 Chronic right facial nerve palsy with aberrant regeneration (synkinesia): The top left photo shows the patient at rest with a slightly flattened right nasolabial fold (suggestive of weakness) and narrowed right palpebral fissure (typical of synkine-

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sia months later, whereas there’s widening of the ipsilateral palpebral fissure with an acute facial palsy). The top right photo demonstrates poor right eyelid closure (orbicularis oculi weakness) with abnormal activation (synkinesia) of the lower face (orbicularis oris) on the right. The bottom left photo demonstrates inability to elevate the right brow (frontalis weakness), again with abnormal right o. oris activation (synkinesia). The bottom right photo demonstrates an asymmetric smile (due to right o. oris weakness) with abnormal activation (synkinesia) of the right o. oculi��������������������������� 32 Fig. 2.14 Bilateral ptosis and ophthalmoplegia in myasthenia gravis: In this montage, the top photo represents primary gaze where right ptosis (yellow asterisk) and an outward deviation of the eyes (exotropia) can be seen. The ptosis was variable, fatigable, and there was mild orbicularis oculi weakness bilaterally. In the bottom photos, bilateral adduction pareses (white asterisks) are apparent in lateral gaze. In the bottom right photo there is more ptosis OD in right gaze, with resultant left eyelid retraction (black asterisk, note that the superior sclera is visible) due to Hering’s law���������������������������������������������������������� 35 Fig. 2.15 Left hemifacial spasm: Between spasms, the face was symmetric and facial muscle strength (innervated by the seventh nerve) was normal. During spasms, there was contraction mainly of the left orbicularis oculi (eyelid closure) as well as the left orbicularis oris and risorius (causing an upward and leftward deviation of the mouth). Despite the contraction of the o. oculi, the left eyebrow does not depress (instead, there is slight elevation due to simultaneous frontalis contraction), a finding known as the “other Babinski sign.” (Photo courtesy of Dr. Stephen Reich)�������������������������������������������� 39 Fig. 2.16 Bony structures relevant to the orbit: The frontal, sphenoid, maxillary, ethmoid, and lacrimal bones

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make up the orbit. Structures passing through the optic canal include the optic nerve, oculosympathetic tract, and ophthalmic artery. Structures passing through the superior orbital fissure include the superior ophthalmic vein and cranial nerves 3, 4, 6, and V1 (ophthalmic branch of the trigeminal nerve). Structures passing through the foramen rotundum include V2 (maxillary branch of the trigeminal nerve)��������������������������������������������������������������������� 42 Fig. 2.17 Typical orbital and neuroimaging signs in thyroid eye disease (TED): Seen in the top left photo are typical orbital signs of TED. Additionally, she had proptosis as demonstrated by abnormal Hertel exophthalmometer measurements (27 mm OU) as well as anterior globe displacement on axial CT relative to the interzygomatic (yellow) line. Orbital CT and MRI are both effective modalities to visualize enlarged extraocular muscles in TED. Typically, the muscles tend to be involved in the following order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus, followed by occasional involvement of the oblique muscles. In the images above, bilateral medial rectus (white asterisk) enlargement is most prominent, but there is also mild enlargement of bilateral inferior rectus (yellow asterisk) and superior rectus muscles (black asterisk), a slightly larger lateral rectus on the right (black arrowhead) compared to the left and normal appearing bilateral superior oblique muscles (yellow arrowhead). (Photo and images courtesy of Dr. Amanda Henderson) Seen in the bottom left photo is an example of severe proptosis in another patient with TED. Viewing the globes from above or from below (as in this case) allows for a qualitative assessment of globe position when an exophthalmometer is unavailable. (Photo courtesy of Dr. Ryan Walsh)���������������������������������������������������� 43

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Fig. 2.18 How can I tell if it’s safe to dilate my patient? Evaluation of the angle is best performed with a slit lamp (using the Van Herick’s technique, where the depth of the peripheral anterior chamber is compared to the corneal thickness) or during gonioscopy. However, a rapid (albeit less accurate) way to assess the anterior chamber depth is to shine a (temporal) light source parallel to the plane of the iris and to look for a shadow on the nasal iris. If a shadow appears nasal to the pupil, the patient should not be dilated without first seeing an ophthalmologist. The patient above had a normal anterior chamber depth (i.e., no shadow was seen), and was safely dilated�������������������������������������������������������������������� 47 Fig. 2.19 Red eye due to carotid-cavernous fistula (CCF): Note the appearance of small, tortuous conjunctival vessels with extension to the limbus (arrowheads). These “corkscrew” vessels (yellow arrow points to one example) result from arterialization of the veins. The time of flight (TOF) MR angiogram images demonstrate abnormal filling of the cavernous sinus (white arrow) and arterialization of the superior ophthalmic vein (yellow arrowhead), while the T1 contrast-enhancement image shows an enlarged medial rectus muscle (due to congestion, white dashed arrow) in the affected, proptotic left eye. (Photos and images courtesy of Dr. Collin McClelland)����������������������������������������� 50 Fig. 3.1 The fundus exam—structures to identify and evaluate: During routine ophthalmoscopy, the following structures are of particular interest: the optic disc and cup (and record the cup:disc ratio when able), neuroretinal rim (e.g., is it pale due to optic neuropathy? is there a thin rim due to a large cup from glaucoma?), and follow the course of the retinal arteries and veins (e.g., A-V nicking due to hypertension? arterial plaque due to retinal occlusion?). The fovea/macula and peripheral retina are

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more difficult to visualize on undilated examination, but evaluation is important when maculopathy or retinopathy is suspected. The papillomacular bundle may be preferentially affected by certain conditions including Leber’s hereditary optic neuropathy or nutritional disorders (e.g., B12 deficiency), resulting in temporal optic nerve pallor and central or centrocecal scotomas. A cilioretinal artery is a normal variant, and if present in a patient with a central retinal artery occlusion, it can be responsible for relatively preserved central visual function as a portion of the macula continues to be perfused by the unaffected choroidal circulation���������������� 67 Layers of the retina as seen with optical coherence tomography (OCT): In order from inner to outer retina: RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ELM, external limiting membrane; EZ, ellipsoid zone; RPE, retinal pigment epithelium. Note that the GCL gives rise to the RNFL, which then makes up the optic nerve (ON) (Images courtesy of Dr. Kara Della Torre)������������ 71 Abnormal monocular visual fields with automated static perimetry—is it retina or optic nerve? A monocular visual field defect is almost always pre-chiasmal, but the appearance of the visual field cannot distinguish optic neuropathy from retinal/macular disease without additional information (e.g., optic nerve is normal, swollen, or pale; dyschromatopsia and relative afferent pupillary defect are present with optic neuropathy; e.g., metamorphopsia with macular disease, abnormal fundus exam with retinopathy/maculopathy). Each abnormal visual field above could be due to optic nerve or retinal disease, and an example of each has been given (IIH, idiopathic intracranial hypertension; LHON, Leber’s hereditary optic neuropathy; BRVO,

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branch retinal vein occlusion; NAION, nonarteritic anterior ischemic optic neuropathy; BRAO, branch retinal artery occlusion; RP, retinitis pigmentosa; ON, optic neuropathy; CRAO, central retinal artery occlusion)�������������������������������������������������������������� 71 Typical visual field defects associated with discrete lesions along the visual pathways: Specific monocular or binocular visual field defects can be highly localizing when the neuroanatomy of the visual pathways is understood. The temporal visual field corresponds to the nasal retina, while the nasal visual field corresponds to the temporal retina. (1) Left optic nerve lesion—while an optic neuropathy can cause a variety of monocular visual field defects (see Fig. 3.3), a complete lesion will cause no light perception vision loss in the affected eye (the violet color = a combination of damage to both nasal and temporal fibers). (2) Lesion at the junction of proximal left optic nerve and chiasm—a junctional lesion, when complete, can cause complete monocular vision loss OS due to optic neuropathy, but because some fibers originating in the right inferonasal retina decussate in the chiasm and then bulge forward into the left anterior chiasm/proximal nerve (anatomically known as “Wilbrand’s knee,” a somewhat controversial concept), a small superotemporal (“junctional”) scotoma can be seen in the right eye. (3) Chiasmal lesion—due to involvement of the crossing fibers (responsible for temporal visual fields) coming from right and left eyes, bitemporal hemianopia is the result. (4) Left optic tract lesion—since this is a retrochiasmal lesion, a right homonymous hemianopia (HH, and usually a mild right relative afferent pupillary defect) is the result. When incomplete, these tend to be incongruous (asymmetric). When complete, the HH is nonlocalizing (e.g., it could be tract or could be occipital). (5) Left lateral geniculate nucleus lesion—there are two characteris-

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tic visual field patterns: (a) right homonymous quadruple sectoranopia and (b) right homonymous horizontal sectoranopia. (6) Left temporal lobe (Meyer’s loop)—right superior quadrantic defect (“pie in the sky”), which when incomplete, may be incongruous. (7) Left parietal lobe—right HH that is more dense inferiorly (“pie on the floor”) and often incomplete. (8) Left occipital lobe, superior to calcarine fissure—right inferior quadrantic defect, congruous (symmetric) when incomplete, often with macular sparing (i.e., sparing of the occipital pole/tip due to dual vascular circulation). (9) Left occipital lobe, inferior to calcarine fissure—right superior quadrantic defect, congruous, often with macular sparing. (10) Right complete occipital lesion with sparing of the pole can be a complete left HH, or congruous when incomplete, macular sparing. (11) Right occipital pole lesion—left homonymous central scotoma������������������������������������������������������� 72 Relative afferent pupillary defect (rAPD) and other findings of a unilateral optic neuropathy: Patients with unilateral optic nerve disease typically have loss of visual acuity, dyschromatopsia, visual field loss, the optic nerve itself may appear normal (e.g., acute retrobulbar optic neuritis) or abnormal (e.g., optic nerve pallor months after an optic neuritis attack), and a relative afferent pupillary defect (rAPD) is a prominent feature of an optic neuropathy (unless there is bilateral optic nerve involvement). This patient has a compressive left optic neuropathy due to a meningioma, and aside from hand motions visual acuity and inability to see any color plates during testing, there was diffuse visual field loss OS, optic nerve pallor, and a clear left rAPD as seen with the swinging flashlight test. It’s as if the patient is in a bright room OD (i.e., the pupil constricts), but then when moving the light

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from the right to the left eye, it’s as if the patient is moving into a darker room (i.e., the pupil dilates). The light should be held for the same duration on each eye; if the light is held on one eye longer than the fellow eye, this may cause a false positive in a normal patient. The examiner must be careful when looking for a rAPD in a patient with anisocoria because less light is entering the smaller pupil; occasionally, this can create the false appearance of a rAPD on the side of the miosis�������������� 75 Hollenhorst plaque in a patient with retinal TIA: While the patient had normal vision by the time he was evaluated, an asymptomatic cholesterol embolus (Hollenhorst plaque) was seen in the affected eye����������������������������������������������������������� 76 Vascular supply of the optic nerve head, choroid, and retina: The ophthalmic artery is a branch of the internal carotid artery, which in turn, supplies the posterior ciliary (to choroid and outer retina) and central retinal (to inner retina) arteries. The central retinal artery (CRA) enters the optic nerve about 1 cm posterior to the globe, and an embolus may become lodged as the CRA pierces the dural sheath of the nerve, or posterior to the lamina cribosa, resulting in a CRA occlusion (CRAO, involvement of inner retinal layers, sparing of optic nerve head, outer retina, and choroid). The arterial circle of Zinn–Haller supplies the optic nerve head, which is made up of anastomoses from branches of short posterior ciliary arteries (from posterior ciliary artery, PCA), the adjacent pial network, and choroidal vessels. Hypoperfusion of the PCA is the likely cause for nonarteritic anterior ischemic optic neuropathy. Ophthalmic artery pathology (e.g., thromboembolic and giant cell arteritis) results in ischemia of the retina, choroid, and optic nerve. (Redrawn and modified with permission from: Digre

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KB, Corbett JJ Practical Viewing of the optic Disc. Boston: Butterworth-Heineman 2003)����������������� 78 Fig. 3.8 The fundus appearance of nonarteritic anterior ischemic optic neuropathy (NAION): Seen here is a patient with typical neuro-ophthalmic signs of NAION including (1) ipsilateral (OS) optic nerve swelling, slightly more superiorly with associated splinter hemorrhage (arrow), no discernible cup OS; (2) ipsilateral (OS) inferior arcuate defect (correlating with the superior optic nerve head being most affected); and (3) contralateral (OD) “disc at risk,” crowded with small cup:disc ratio (about 0.2). Several months later, optic nerve atrophy had developed OS, which was visible as superior segmental pallor (arrowhead)�������������������������������� 86 Fig. 3.9 The fundus appearance of giant cell arteritis (GCA): Several typical features of GCA are seen in this patient with bilateral involvement. Right eye: pallid/chalky-white severe optic nerve head edema with multiple splinter hemorrhages (arrows); Left eye: mild segmental (superior) swelling and inferior hemorrhage. The bilaterality and pallid swelling OD are very concerning for GCA and would be highly atypical for nonarteritic anterior ischemic optic neuropathy (NAION). Additionally, if there is optic nerve (unilateral or bilateral) and retinal involvement (branch or central retinal artery occlusion; cotton wool spots), GCA should be assumed until proven otherwise. Vision did not recover despite high dose steroids, and severe bilateral optic nerve pallor and retinal vessel attenuation was apparent months later��������������������������������������������������������� 89 Fig. 3.10 Clinical and radiologic features of typical optic neuritis: Despite vision loss in the right eye (severe field loss in the right eye, with an artifactual rim defect seen inferiorly in the left eye, i.e., disappeared when the patient was repositioned and retested) associated with pain, the right optic nerve appeared

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normal due to the retrobulbar location of the optic neuritis (“the patient sees nothing and you see nothing”). T2 hyperintensity of the right optic nerve was apparent (top MRI), which can be seen acutely or chronically in a variety of optic neuropathies. However, contrast enhancement of the right optic nerve was also demonstrated, a finding that is common with an acute inflammatory/autoimmune optic neuropathy���������������������������������������������������� 91 Fig. 3.11 Atypical fundus features in optic neuritis: Consider an atypical cause (e.g., neuromyelitis optica, anti-myelin oligodendrocyte glycoprotein [MOG], neurosarcoidosis) when any of the following features are present in an adult with optic neuritis: (1) bilateral involvement, (2) severe swelling, (3) hemorrhage (arrow), (4) light perception or no light perception vision, (5) retinal exudates, and/or (6) steroid dependence������������������������������������������������ 92 Fig. 3.12 Radiologic features of atypical optic neuritis: A 50-year-old woman with neuromyelitis optica (previous attack of myelitis and + aquaporin antibodies) presented with severe bilateral eye pain and vision loss (diffuse depression OD and mainly temporal loss OS). MRI demonstrated asymmetrically enlarged and T2 hypertense optic chiasm (right > left, white arrow) with contrast enhancement of the chiasm (yellow arrow), prechiasmatic right optic nerve, infundibulum, and bilateral optic nerve sheaths (orange arrows, a finding that is generally more typical of anti-MOG)����������������������������������� 93 Fig. 3.13 Clinical features of papilledema: Visual acuity and color vision are almost always normal early in the course of idiopathic intracranial hypertension (IIH), and automated static visual field perimetry should be followed closely. Enlarged blind spots (due to distortion of the peripapillary retina by the swollen optic nerve) are commonly seen, as well as nasal and peripheral inferior and superior defects as the disease

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progresses. The fundus photos above the visual fields come from the same patient, with the white arrows pointing to several examples of vessels on the disc being partially obscured by edema (Frisen grade 4). The arrowheads point to temporal concentric peripapillary wrinkles (the fundus photo to the left comes from another patient, with chronic [Frisen grade 2] papilledema who had developed optic atrophy—note the optic nerve pallor), another potential manifestation of elevated intracranial pressure (along with retinal and choroidal folds). Hemorrhages are also commonly seen in patients with active papilledema. Fundus photography is an excellent way to document the fundus examination when available, and the Frisen papilledema grading scale should be used when possible: Grade 0—no halo of obscuration of the peripapillary nerve fiber layer; Grade 1—obscuration of the peripapillary retina with a C-shaped halo (sparing temporal margin) of retinal nerve fiber layer edema; Grade 2—circumferential halo without obscuration of blood vessels; Grade 3—major vessel(s) are obscured by edema as they exit the disc; Grade 4—major vessel(s) are obscured by edema on the disc; Grade 5—partial or complete obscuration of all vessels�������������������������������������� 96 Fig. 3.14 Clinical features of advanced papilledema: While visual acuity and color vision are spared in early idiopathic intracranial hypertension (IIH), in more advanced disease, they are often involved. This patient has 20/50 acuity OU and mild dyschromatopsia. Additionally, there was severe peripheral visual field loss/constriction. While there were no active features of papilledema (e.g., hemorrhage, obscuration of blood vessels, edema), this was because they were severely atrophic and unable to swell. The arrows point to gliotic changes that give the disc margins a greyish appearance, and the arrowhead

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points to a retinochoroidal collateral vessel. These collateral vessels may develop in certain conditions, typically due to retinal venous outflow impairment— i.e., blood will drain via the choroidal venous system instead. In addition to chronic papilledema, collaterals may also be seen with optic nerve meningiomas, gliomas, sarcoidosis, central retinal venous occlusion, and glaucoma������������������������������������������������ 98 Fig. 3.15 Optic nerve head drusen—a common cause of pseudo-­papilledema: This patient was referred out of concern for papilledema, after being found to have an abnormal optic nerve appearance on routine ophthalmoscopy. Visual acuity and color vision were normal, there was no relative afferent pupillary defect, and static automated perimetry demonstrated bilateral nasal step defects (more inferior OS and more superior OD, black arrows), compatible with retinal nerve fiber layer (RNFL) injury. The white arrows point out the typical “lumpy bumpy” (i.e., yellow elevations) appearance of optic nerve head drusen, which can damage the RNFL, leading to (generally, mild and asymptomatic) visual field loss. Because the optic nerve can be elevated by the drusen (visible or buried drusen), and because the disc margins can be obscured, patients may be misdiagnosed with papilledema, when in fact this is a common cause of “pseudo-papilledema.” While the drusen are clearly visible in this patient, oftentimes this is not the case and the examiner should look for other features of an anomalous optic disc (e.g., small and crowded, anomalous vascular branching patterns [early branching and trifurcations], lack of venous engorgement, irregular elevation of the optic disc, lack of vessel or RNFL obscuration, and intact spontaneous venous pulsations). Orbital ultrasound and enhanced depth optical coherence tomography are often used to aid in the diagnosis (especially for the more challenging to diagnose buried drusen), and

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occasionally drusen can also be seen on a CT scan (yellow arrow, note that CT should not be ordered specifically for this purpose)��������������������������������� 99 Fig. 3.16 Radiologic features of elevated intracranial pressure: The following neuroimaging signs support the diagnosis of elevated intracranial pressure: (1) distention of the optic nerve sheaths (white arrowhead); (2) flattening of the posterior sclera (white dashed arrows); (3) empty sella (white arrow); and (4) transverse venous sinus stenosis (black arrow, bilateral in this case). Protrusion of the swollen optic nerve head into the vitreous (black arrowhead) is a finding that may be seen with optic nerve edema/ elevation due to a variety of etiologies. Tortuosity of the optic nerve is another common finding with elevated intracranial pressure������������������������������� 101 Fig. 3.17 Clinical and radiologic features of chiasmal compression: This patient was found to have a bitemporal hemianopia and bilateral optic nerve pallor on clinical exam. The grayscale maps (top) demonstrate left > right and superior > inferior visual field loss, suggestive of greater compression of the left and inferior aspect (respectively) of the optic chiasm, and MRI demonstrated a pituitary macroadenoma (white arrows). The grayscale maps demonstrate lower visual sensitivity as darker regions, although these are not compared to any normative database. The total deviation maps (bottom) are generated by comparing the measured thresholds to an age-corrected normal. In this example, the total deviation maps more clearly demonstrate the bitemporal nature of the defect than the grayscale maps. Analysis of the entire report allows for more accurate interpretation and localization�������������� 103 Fig. 3.18 Typical visual field and optical coherence tomography (OCT) features of an optic tract syndrome: While visual acuity and color vision were normal, this patient had a very incongruous (asymmet-

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ric) right homonymous hemianopia (only able to demonstrate right temporal field loss OD to confrontation and only a mild nasal defect was seen OS with automated static perimetry), in addition to a mild right relative afferent pupillary defect (rAPD). The combination of an incongruous right homonymous hemianopia and right rAPD was highly localizing to the right left optic tract, which was felt to be due to a chronic infarct seen on MRI. A characteristic OCT pattern of ganglion cell layer-inner plexiform layer homonymous hemiatrophy was also demonstrated (black arrows demonstrate the focal sectoral thinning—nasal OD and temporal OS—outside the 99% limit of normal). This pattern may be seen with any chronic retrochiasmal lesion as retrograde transsynaptic degeneration occurs but is more common (and faster to develop) with optic tract lesions�������������������������������������������� 107 Fig. 3.19 Lateral geniculate nucleus (LGN) lesions cause distinct homonymous visual field defects: The top visual field is an example of a homonymous horizontal sectoranopia, which can be a manifestation of lateral choroidal artery territory ischemia (posterior circulation). The bottom visual field is an example of a homonymous quadruple sectoranopia, which can be a manifestation of anterior choroidal artery territory ischemia (anterior circulation). (Visual fields courtesy of Dr. Neil Miller)����������������������� 108 Fig. 3.20 A “pie in the sky” defect due to temporal lobe (Meyer’s loop) injury: This is a patient with remote history of traumatic brain injury with associated right temporal lobe encephalomalacia (white arrows). Since the inferior optic radiations travel through the (right) temporal lobe (Meyer’s loop), injury can cause a (left) incongruous (asymmetric) homonymous superior quadrantic visual field defect, as seen here���������������������������������������������� 109 Fig. 3.21 Congruous visual field defects due to occipital injury: (A) This patient was found to have a (mainly

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left) parieto-occipital parasagittal meningioma with associated right homonymous visual field defect, which worsened slightly following partial resection. Postoperative automated static perimetry demonstrated a very congruous (symmetric, white asterisk indicates the physiologic blind spot OD; otherwise, the two visual fields are identical) right incomplete inferior quadrantic visual field defect, correlating with the left occipital hyperintensity (black dashed line, superior to the calcarine fissure) seen on the ­postoperative MRI (black solid arrow points to residual meningioma). (B) This patient had a severe cardiomyopathy and experienced several cardioembolic strokes, two of which involved the left occipital lobe causing two distinct congruous visual field defects: (1) an incomplete right homonymous hemianopia (black dashed line) and (2) a right homonymous central scotoma (from left occipital tip ischemia)����������������������������������������� 112 Fig. 3.22 Bilateral homonymous visual field defects and parieto-occipital atrophy in a patient with posterior cortical atrophy (PCA): At the top, the black arrows point to a left homonymous hemianopia, that is slightly more dense inferiorly and suggestive of right parietal and/or right occipital lobe (superior to the calcarine fissure) involvement. The black dashed arrows point to a right homonymous inferior quadrantic visual field defect, due to left parieto-occipital involvement. On the bottom left are two fluorodeoxyglucose (FDG)-positron emission tomography (PET) images, with the white arrows pointing to bilateral parieto-occipital hypometabolism, while the dashed arrows point to bilateral parieto-occipital atrophy seen on MRI���������������� 113 Fig. 3.23 How the brain makes sense of what it sees—the dorsal and ventral visual pathways, and a three-tiered approach to vision: (1) Ventral (“what”) stream—this begins with the ‘P’ retinal

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ganglion cells ➔ parvocellular layers of the lateral geniculate nucleus (LGN, 3–6) ➔ V1/striate cortex (in blue) ➔ V4/V4a (fusiform and lingual gyri) ➔ occipitotemporal regions. (2) Dorsal (“where”) stream—this begins with the ‘M’ retinal ganglion cells ➔ magnocellular layers of the LGN (1, 2) ➔ V1/striate cortex ➔ V5/V5a ➔ occipitoparietal regions. *For objective identification (general visual agnosia)—in the left hemisphere, think “words” (pure alexia) and in the right hemisphere, think “faces and places” (prosopagnosia, topographagnosia). (The classification of cerebral visual dysfunction using a three-tiered approach is courtesy of Dr. Jason Barton. The figure was developed with the input of Dr. Victoria Pelak)�������������������������������� 114 Evaluating ocular alignment using Hirschberg and Krimsky tests: This patient suffered severe vision loss in the right eye due to optic neuritis which led to an exotropia (XT) over several years. When a penlight is shone in both eyes, the left eye (white arrow) is the fixating eye because the light reflex is centered in the pupil, while the light reflex in the right eye is more medial than it should be (white dashed line), owing to the fact that the right eye is deviated outward. This is the Hirschberg test, and is a quick and easy method to evaluate for strabismus, especially effective in kids, uncooperative patients, or patients with poor monocular or binocular vision. The Krimsky test was then performed where base-in prism was placed on the fixating (left) eye until the light reflex was centered in the (previously exotropic) right eye (yellow arrow). Because this was achieved once 35 prism diopters (PD) of base in prism were placed, she had a ~ 35 PD exotropia (approximate because this is not as accurate a test as alternate cover or cover–uncover using prism)��������������������������������������������������������� 128

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Multiple contralateral ocular motor palsies due to neoplastic seeding of the subarachnoid space: This patient had (1) an abduction paresis OD (white asterisk) due to right lateral rectus (sixth nerve) palsy, and (2) poor depression OS (black asterisk) in down/right gaze, suggestive of a left superior oblique (fourth nerve) palsy. There was a slight rightward head tilt which cannot be appreciated in this montage. Ocular alignment examination demonstrated an esotropia that was worse in right gaze (due to right sixth NP), and a left hypertropia that was worse in right and downgaze, as well as with left head tilt (due to left fourth NP)������������ 136 The course of the sixth (VI) nerve: The sixth nucleus is located dorsally, adjacent to the fourth ventricle, in the lower pons. The genu of the facial (seventh) nerve wraps around the sixth nucleus, creating the facial colliculus, which bulges into the fourth ventricle. After the sixth nerve leaves the pons, it follows a vertical course along the clivus and then to the petrous apex where it penetrates the dura, passing under the petroclinoid (Gruber’s) ligament in Dorello’s canal, where it is tethered and particularly susceptible to low or elevated intracranial pressure states. It then enters the cavernous sinus (adjacent to the sympathetic plexus which surrounds the internal carotid artery), travels through the superior orbital fissure to enter the orbit, and then passes through the annulus of Zinn to finally innervate the ipsilateral lateral rectus muscle�������������������������������������������� 137 Ocular motility and alignment findings in a left third NP: This patient (with hypertension and diabetes) suffered a microvascular left third NP. In primary gaze, there is complete ptosis OS (levator palpebrae, black asterisk), and with the left eyelid manually elevated, there was also adduction paresis OS and exotropia in right gaze (medial rectus, MR,

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yellow asterisk), supraduction paresis OS and right hypertropia in upgaze (superior rectus, SR, white asterisk), infraduction paresis OS, and left hypertropia in downgaze (inferior rectus, IR, red asterisk). There was additional poor pupillary reactivity OS (with mild left mydriasis) due to mild involvement of the pupillary sphincter muscle (PCOM aneurysm and structural lesions had been ruled out, and her third NP resolved over 2–3 months as expected; however, patients with a microvascular third can occasionally have minimal pupil involvement, typically with adduction and milder vertical motility deficits OU, and given the constellation of sluggish pupils, ataxia, areflexia and ptosis with ophthalmoparesis in the setting of the preceding respiratory illness, MFS was suspected and anti-Gq1b antibodies returned very elevated several days later. Although there was ophthalmoparesis with a Cogan’s lid twitch, fatigable and enhanced ptosis (based on Herring’s law of equal innervation of bilateral levator palpebrae muscles – these are features that are highly suspicious for myasthenia gravis), from an ocular standpoint, the sluggish pupils should make the clinician think of MFS or even botulism. This case also highlights the fact that the Cogan’s lid twitch is not exclusively seen with MG. In her case, there was also intermittent lid retraction OD. Since she had ptosis mainly OS, more levator tone was required to elevate the left eyelid. However, given Herring’s law of equal levator innervation, there was corresponding increased levator tone on the right which resulted

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in an eyelid retraction. However, as she became more fatigued throughout the exam, ptosis became apparent OU. (Video and legend created with the assistance of Drs. Roksolyana Tourkevich, William Tsao, Jiaying Zhang, William Motley) Video 2.7 The triad of Miller Fisher syndrome: This is a young man who presented with ptosis, ophthalmoplegia and gait imbalance several weeks after a GI illness. MFS was diagnosed, IVIG therapy was initiated, and anti-Gq1b antibodies came back extremely elevated. The typical triad of MFS includes ophthalmoplegia, ataxia, and hyporeflexia which were all present in this case. https:// collections.lib.utah.edu/ark:/87278/s66m6w3z ESM 3.1 Expanded acute onset persistent vision loss differential Video 3.1 Clinical features of a unilateral optic neuropathy: This video depicts the common features of an optic neuropathy, including relative afferent pupillary defect (rAPD), with ipsilateral pallor and loss of visual field due to a compressive meningioma. https://collections.lib.utah.edu/ark:/87278/ s6m95jb6 Video 3.2 Parieto-occipital tumor causing loss of ipsilesional optokinetic nystagmus and contralesional homonymous hemianopia: A normal optokinetic nystagmus (OKN) response is seen with an optokinetic drum that was directed contralesionally (to the left), but OKN was poor when the drum was directed ipsilesionally (to the right). The patient had a right parieto-occipital anaplastic astrocytoma, which also caused a complete left homonymous hemianopia. (Video and legend created with the assistance of Dr. Tony Brune). https://collections.lib.utah.edu/ark:/87278/s6h45w40 ESM 4.1 Midbrain structures relevant to normal eyelid function

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Video 4.1 Evaluating the range of eye movements: Assess versions (both eyes viewing) and ductions (each eye individually viewing), especially in patients with diplopia or when a motility deficit is suspected. Look for spontaneous nystagmus or saccadic intrusions/oscillations in primary gaze and gaze-evoked nystagmus in eccentric gaze. https://collections.lib.utah.edu/ark:/87278/s6vt51rq Video 4.2 Evaluating ocular alignment: Alternate cover test allows for detection of the total deviation (eso, exo or hyper) – i.e., phoria (misalignment with one eye viewing) + tropia (misalignment with both eyes viewing). Use the cover-uncover test to see what component of the total deviation is due to a tropia. Neurologic causes of diplopia including ocular motor palsies and skew deviation will typically cause a tropia, although the presence of a tropia does not necessarily mean that the patient’s strabismus is neurologic (e.g., an infantile esotropia syndrome). https://collections.lib.utah.edu/ ark:/87278/s67400kp Video 4.3 Evaluating convergence: The assessment of convergence includes measuring alignment at near versus distance, near point of convergence and convergence amplitude. Near point of convergence is assessed by bringing a fixation target toward the bridge of the patient’s nose. The distance at which binocular fixation is lost or diplopia is experienced is recorded. Convergence amplitude is determined by placing base out prisms of increasing power over one eye while the patient views a near target. The highest prism power before binocular fixation is lost or diplopia is experienced is the convergence amplitude. Although the specific diagnostic criteria for convergence insufficiency may differ, typically the diagnosis is made when: 1) the near point of convergence is greater than 10 centimeters, 2) the convergence amplitude is less than 15 prism

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diopters, and 3) there is an exodeviation greater than 10 PD at near, or the exodeviation at near is at least four prism diopters greater than what is recorded at distance. (Video and legend created with the assistance of Dr. Tony Brune and Justin Bosley) https://collections.lib.utah.edu/ark:/87278/ s6zd22m0 Video 4.4 Convergence insufficiency in progressive supranuclear palsy: This is a 70-year-old woman with progressive supranuclear palsy with complaints of difficulty reading. Her husband noticed that she would frequently close one eye when attempting to read while she noticed that words were not clear on the page, although this improved by covering one eye. On her exam, she was orthophoric at distance and had a symptomatic (experienced diplopia) exotropia at near (>10 prism diopters). Additionally, her near point of convergence was about 20 cm (normal is 15 PD). Convergence insufficiency is common following concussion/TBI or with parkinsonism. Square wave jerks are common in PSP, and hers are shown here as well. https:// collections.lib.utah.edu/ark:/87278/s6m07z61 Video 4.5 Evaluating saccades: The examiner should note: conjugacy (a lag of the adducting eye may be seen with an internuclear ophthalmoplegia); accuracy (posterior fossa lesions commonly produce saccadic dysmetria [overshooting or undershooting]); velocity (if slow, may suggest a lesion of the burst neurons in the pons [paramedian pontine reticular formation, PPRF – horizontally] or midbrain [rostral interstitial medial longitudinal fasciculus, riMLF – vertically]). https://collections. lib.utah.edu/ark:/87278/s6md27q9 Video 4.6 Saccadic dysmetria and ipsipulsion in lateral medullary (Wallenberg) syndrome: This patient

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suffered a right lateral medullary stroke, and examination demonstrated saccadic hypermetria to the right (ipsilesional), hypometria to the left (contralesional) and rightward ocular lateropulsion (ipsilesional, also known as ipsipulsion). The pattern of saccadic dysmetria can be highly localizing to the lateral medulla due to inferior cerebellar peduncle involvement. https://collections.lib.utah.edu/ark:/87278/s65176w6 Video 4.7 Slow ipsiversive horizontal saccades in a brainstem syndrome due to paramedian pontine reticular formation (PPRF) involvement: This is a patient with a complicated brainstem syndrome that developed following head and neck cancer diagnosis (status post surgery and radiation), that included left (lower motor neuron) 7th and 8th nerve palsies, in addition to slow saccades to the left with normal saccades in other directions. With an optokinetic stimulus moved to the right, there were no leftward fast phases. Leftward eye movements with pursuit and the head impulse test to the right (the vestibulo-ocular reflex is responsible for conjugate eye movements to the left) appeared to be of normal speed. This constellation of findings (i.e., normal pursuit and VOR, abnormal saccades) argued for a left PPRF lesion and against a left 6th nuclear lesion, although MRI did not demonstrate a discrete pontine lesion. (Video and legend created with the assistance of Dr. Tony Brune) https://collections.lib.utah.edu/ark:/87278/ s6n058z5 Video 4.8 Three cases of internuclear ophthalmoplegia (INO) in multiple sclerosis, brought out by testing horizontal saccades: This video includes 3 patients each with a known history of MS found to have unilateral or bilateral INOs on their exam. In the first 2 patients, the INOs are relatively subtle, without an adduction paresis. However, with rapid

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horizontal saccades, an adduction lag is apparent which is suggestive of an INO. In the 3rd patient, there were bilateral INOs with bilateral adduction paresis. https://collections.lib.utah.edu/ark:/87278/ s6tj1wb3 Video 4.9 Evaluating smooth pursuit: Use a small fixation target and move it slowly in horizontal and vertical planes. https://collections.lib.utah.edu/ark:/87278/ s6r24925 Video 4.10 Saccadic pursuit and skew deviation due to a middle cerebellar peduncle stroke: This is a 50-year-old woman who underwent resection of a left-sided acoustic neuroma, and post-operatively, she had vertigo, binocular diplopia, left hemiataxia and severe gait ataxia. MR diffusion weighted imaging demonstrated an acute stroke involving the left middle cerebellar peduncle (MCP) and lateral pons, which was responsible for her left-sided appendicular and gait ataxia, skew deviation, mild left fascicular 6th nerve palsy, gaze-evoked nystagmus (right-beating nystagmus [RBN] in right gaze and left-beating nystagmus [LBN] in left), and impaired smooth pursuit. There was mild spontaneous RBN that was accentuated with the ‘penlight-cover test’, where fixation is partially removed by occluding one eye while shining a bright light in the fellow (un-occluded) eye, in this case using the light of the video camera. The RBN increased in right gaze in accordance with Alexander’s Law (nystagmus increases in the direction of the fast phase – gazeevoked nystagmus to the left and vestibular nystagmus to the right can also be referred to as Bruns nystagmus), and there was left unilateral vestibular loss with an abnormal head impulse test to the left due to left CN 8 injury from the acoustic neuroma and/or its resection. However, fascicular involvement of CN 8 in the pons could not be

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excluded. https://collections.lib.utah.edu/ ark:/87278/s6kh4n5k Video 4.11 Ipsilesional smooth pursuit and vestibulo-ocular reflex suppression (VORS) impairment due to hemispheric stroke: This is a 20 year-old man who suffered a left middle cerebral artery stroke years prior. Smooth pursuit and VORS were saccadic/choppy in appearance to the left (ipsilesional) and normal to the right. When pursuit and VORS are asymmetrically impaired, the lesion will be ipsilateral to the direction of the eye movement abnormality. https://collections.lib.utah.edu/ ark:/87278/s6j70rkm Video 4.12 Evaluating vestibulo-ocular reflex suppression (VORS): Impairment in pursuit and VORS are almost always both normal or both abnormal, except when the VOR is absent or markedly diminished in which case there is no VOR to suppress, so that VORS appears more normal than pursuit. When this is the case, consider conditions that cause both cerebellar impairment (i.e., saccadic smooth pursuit) and vestibular loss (i.e., the same patient can have normal/near normalappearing VORS, also with an abnormal head impulse test) such as cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). https:// collections.lib.utah.edu/ark:/87278/s6bw0r9q Video 4.13 Gaze-evoked nystagmus and saccadic vestibuloocular reflex suppression (VORS) in spinocerebellar ataxia type 6: On exam, there was no clear spontaneous downbeat nystagmus (DBN) in primary gaze, although DBN could clearly be provoked by convergence. Other ocular motor features included saccadic pursuit and VORS (suggestive of a normal VOR – i.e., there was a VOR to suppress, but given the pursuit deficit, VORS was saccadic) horizontally and vertically, in addition to an alternating skew deviation (right

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hypertropia in right gaze and left hypertropia in left gaze), gaze-evoked and rebound nystagmus. Saccades were normal. Head impulse test was normal. These are all typical ocular motor features of a flocculus/paraflocculus syndrome. https:// collections.lib.utah.edu/ark:/87278/s6vx45m7 Video 4.14 Saccadic smooth pursuit with (near) normal vestibulo-ocular reflex suppression (VORS): This is a 70 year-old woman with the subacute onset of severe imbalance and dizziness. On her initial examination, she had prominent gazeevoked nystagmus and bilateral vestibular loss. Smooth pursuit was saccadic, although VORS looked much less saccadic (nearly normal). Usually pursuit and VORS are both normal or both saccadic, but when pursuit is impaired and there is bilateral vestibular loss, there is no VOR to suppress, so VORS can look normal or better than pursuit. Her visually-enhanced VOR (slowly rotating the head side to side while the patient fixates on the examiner’s nose) was also saccadic given the combination of impaired pursuit and bilateral vestibular loss. She was diagnosed with an anti-GAD-related cerebellar syndrome, and there was marked improvement in ocular motor and vestibular abnormalities following treatment with intravenous immunoglobulin. Neoplastic work-up was unrevealing. https://collections.lib.utah.edu/ ark:/87278/s6wx1bgp Video 4.15 Evaluating optokinetic nystagmus (OKN): During the bedside evaluation of optokinetic nystagmus (OKN), the patient is instructed to look at each red (or white) square as it moves past. Because this is not a full-field visual stimuli, using an optokinetic flag mainly allows the examiner to quickly evaluate for right/left and up/down symmetry and for impairment of smooth pursuit (slow phases) and saccades (fast phases) in horizontal

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and vertical directions. Or, a patient with poor vertical saccades may only generate a horizontal nystagmus when the OK stimulus is oriented diagonally. The optokinetic flag can be helpful at the bedside to: 1) bring out a subtle adduction lag suggestive of internuclear ophthalmoplegia, 2) better appreciate convergence-retraction nystagmus in Parinaud’s syndrome, 3) determine whether downward fast phases are present or absent in someone with parkinsonism (loss of the downward fast phases is one of the first ocular motor signs of progressive supranuclear palsy), among other afferent uses (e.g., abnormal ipsilateral OKN in a patient with unilateral parietal pathology; in the assessment of a patient with functional vision loss, etc). This differs from the ‘true’ OKN caused by full-field visual stimuli (e.g., looking out of the window of a moving train), which normally acts to supplement the vestibular response during prolonged rotation. (Video and legend created with the assistance of Dr. Tony Brune and Justin ­Bosley). https://collections.lib.utah.edu/ark:/87278/s6k68htv Video 4.16 The virtual (telemedicine) ocular motor examination: This video demonstrates one approach to performing the ocular motor examination virtually in a normal subject. (Video created with the assistance of Dr. Olwen Murphy) https://collections.lib.utah.edu/ark:/87278/s6x9815p Video 4.17 Contralateral 4th and 6th nerve palsies due to leukemic meningitis: This patient experienced diagonal diplopia (with both horizontal and vertical components) due to a right 6th NP and left 4th NP. While the 6th NP is marked, the evaluation of ocular alignment is essential to make the diagnosis of a 4th NP Also note the mild depression deficit OS in down/right gaze due to left superior oblique paresis. https://collections.lib.utah.edu/ark:/87278/ s63n5tg3

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Video 4.18 Cavernous sinus mass causing ipsilateral 3rd and 4th nerve palsies: This patient had a known right cavernous sinus mass due to Ewing’s sarcoma, and presented with diplopia. He had a right 3rd NP, right 4th NP, and mild right 6th NP. This video demonstrates that in addition to the right 3rd (ptosis, mydriasis, impaired adduction, supra- and infraduction), in downgaze, there is no clear incycloduction of the right eye, suggesting that the right 4th nerve is also involved. This is a subtle sign, but should be sought since a 3rd NP + an ipsilateral 4th NP is suggestive of a cavernous sinus localization. https://collections.lib.utah.edu/ ark:/87278/s6186g5w Video 4.19 Multiple ipsilateral ocular motor palsies and aberrant regeneration of the 3rd nerve due to cavernous sinus meningioma: This is a 50-yearold woman presenting with a partial 3rd nerve palsy (mild pupil involvement), partial 6th nerve palsy, and no clear incycloduction in downgaze, suggestive of additional 4th nerve palsy, all on the left. With compressive lesions involving the 3rd nerve, often aberrant regeneration develops – in this case, injury to the left 3rd nerve caused miswiring so that some of the fibers destined for the left medial rectus instead went to the left levator palpebrae. When adducting the left eye, the eyelid elevated slightly. There was no evidence of aberrant regeneration involving the pupil or ocular motility. https://collections.lib.utah.edu/ark:/87278/ s6wx16kc Video 4.20 A central HINTS exam in the acute vestibular syndrome due to a lateral medullary stroke: This patient experienced the acute vestibular syndrome due to left lateral medullary stroke from left vertebral artery dissection. Two months later he was examined and the following ocular motor/ vestibular findings were observed: 1) with fixation-

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removed, there was right-beating nystagmus (with a slight torsional component, top poles beating towards the right ear), 2) head impulse testing HIT in the planes of the horizontal canals was normal, 3) there was a skew deviation with a left (ipsilesional) hypotropia. Therefore, the HINTS (Head Impulse, Nystagmus, Test of Skew) exam was consistent with a central localization based on the normal HIT and presence of a skew deviation. Additionally, there was saccadic dysmetria, with hypermetric saccades to the (ipsilesional) left side and hypometric saccades to the (contralesional) right side. Although not shown here, there was also leftward ocular lateropulsion, a finding which is usually seen ipsilateral to hypermetric saccades. (Video courtesy of Dr. Tzu-Pu Chang) https:// collections.lib.utah.edu/ark:/87278/s6546m8r Video 4.21 Dysmetric saccades and ipsipulsion with eyelid closure and vertical saccades due to lateral medullary lesion: This patient experienced oscillopsia and vertical diplopia, due to spontaneous torsional nystagmus and a skew deviation (right hypotropia), respectively. The pattern of saccadic dysmetria and ocular lateropulsion localized to the right lateral medulla including: 1) hypermetric saccades to the right, 2) a rightward trajectory with vertical saccades, and 3) rightward ocular lateropulsion (i.e., eyes drift to the right with eyelid closure, also apparent on her MRI), as well as the torsional nystagmus. These are features that are commonly seen with a (right) lateral medullary syndrome (in addition to her right hypotropia), as the climbing fibers connecting (left) inferior olive to (right) dorsal vermis are injured in the (right) inferior cerebellar peduncle. https://collections.lib.utah.edu/ark:/87278/ s64r24wd

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Video 4.22 A complete lateral medullary (Wallenberg) syndrome: This patient experienced the acute onset of vertigo, dysarthria, dysphagia and dysphonia/hoarseness (nucleus ambiguus), ptosis and imbalance. Her examination localized to a left lateral medullary (Wallenberg) syndrome – there was decreased sensation on the left side of the face (spinal trigeminal nucleus and tract) and the right arm and leg (spinothalamic tract), a left Horner’s syndrome (oculosympathetic tract), left hemiataxia (inferior cerebellar peduncle), leftward ocular lateropulsion (apparent throughout the video during blinks – during eyelid closure, there is conjugate deviation to the left, and when the eyelids open, the eyes move to the right into primary gaze) which is usually seen with ipsilesional (left) hypermetric saccades and contralesional (right) hypometric saccades, due to injury of the climbing fibers traveling through the inferior cerebellar peduncle on the left side. An ipsiversive (leftward) ocular tilt reaction is also commonly seen due to involvement of the utriculo-ocular motor pathway (e.g., left hypotropia from skew deviation, left head tilt, leftward ocular counterroll). (Video courtesy of Dr. Stephen Reich) https:// collections.lib.utah.edu/ark:/87278/s6963fhm Video 4.23 Ocular motor and vestibular features of the medial longitudinal fasciculus (MLF) syndrome: This patient suffered a left MLF stroke causing 1) left internuclear ophthalmoplegia (INO) due to involvement of the interneurons traveling from right 6th nucleus to left medial rectus subnucleus via the MLF (responsible for conjugate rightward gaze) 2) contraversive (rightward) ocular tilt reaction (OTR – skew deviation causing a left hypertropia; ocular counterroll with the top poles rotated toward the right ear; right head tilt) due to involvement of the utriculo-ocular motor pathways

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(originating in the right labyrinth), 3) spontaneous (primarily) torsional nystagmus, with quick phases of the superior poles directed towards the ipsilesional (left) side (due to involvement of the central anterior and posterior semicircular canal pathways that originated in the right labyrinth – acute nystagmus is usually mixed upbeat-torsional or downbeat-torsional), 4) vestibulo-ocular reflex (VOR) loss in the planes of the vertical semicircular canals (posterior canal [PC] > anterior canal [AC] pathway involvement because there’s only 1 brainstem pathway for PC compared to 3 pathways for AC), 5) horizontal VOR – with the horizontal head impulse test, the velocity of the adducting eye (ipsilateral to an MLF lesion) movement can be relatively preserved – i.e., much better than what would be expected based on bedside testing with a significant adduction lag due to an INO. This is presumably due to an extra-MLF pathway, the ascending tract of Dieters, which goes directly from the vestibular nucleus to the ipsilateral medial rectus subnucleus, thus bypassing the MLF pathways, 6) vertical gaze-evoked nystagmus – there was upbeat nystagmus (UBN) in upgaze and downbeat nystagmus (DBN) in downgaze, although it’s not clear whether this results from descending fibers going from interstitial nucleus of Cajal (INC) to the medullary nucleus of Roller and/or involvement of the nearby paramedian tract (PMT) cell groups (thought to receive inputs from the INC that are transmitted to the cerebellar flocculus). (Video and legend created with the assistance of Dr. Tony Brune) https://collections. lib.utah.edu/ark:/87278/s68m15w9 Video 4.24 Acute medial longitudinal fasciculus (MLF) stroke with prominent spontaneous verticaltorsional nystagmus: This patient suffered a left MLF stroke, and had a skew deviation causing a

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left hypertropia (due to utriculo-ocular motor pathway involvement in the MLF), in addition to a left internuclear ophthalmoplegia causing an exotropia and adduction paresis OS (due to involvement of the interneurons connecting right 6th nucleus to left medial rectus subnucleus by the left MLF). There was particularly prominent spontaneous upbeat-torsional nystagmus in this case as well (due to involvement of the central vertical semicircular canal pathways in the MLF). The torsional component of MLF-related spontaneous nystagmus is almost always ipsiversive – e.g., with a left MLF stroke, the top poles will beat towards the left ear, and this is because of damage to central fibers that originated in the 1) right posterior semicircular canal (SCC), 2) right anterior SCC or 3) right posterior and anterior SCCs. Because of unopposed left anterior and posterior SCC afferents (when normally stimulated, the left anterior and posterior SCCs cause the top poles to move towards the right ear), the slow torsional phase will be towards the right ear, and the fast phase will cause the top poles to beat towards the left ear. Additionally, there are often dissociated vertical components, again mainly due to central vertical (anterior and posterior) SCC injury. The most common pattern is upbeat-torsional (ipsiversive) nystagmus, where there is more upbeat in the contralesional eye than in the ipsilesional eye. This is the pattern seen in the video. Because the right anterior SCC, when normally stimulated, causes excitation of the right superior rectus and left inferior oblique, a lesion involving the right anterior SCC pathway (at the level of the left MLF in this case) will lead to less excitation of the elevators and relative hyperactivity of the antagonist depressors. Because the right inferior rectus is a strong depressor, there is a more

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of a downward slow phase OD compared to OS and therefore, a more marked upbeat component OD compared to OS. The other patterns of spontaneous nystagmus are: downbeat-torsional (ipsiversive) nystagmus, where there is more downbeat in the ipsilesional eye than in the contralesional eye (related to posterior SCC pathway damage, or the opposite of the situation described above); hemi-see saw or jerky see saw nystagmus where the torsional component is ipsiversive, there is upbeat OD and downbeat OS, related to injury of the posterior and anterior SCC pathways and/or utricle-ocular motor pathways (that are also responsible for skew deviation – i.e., slow phase up in the hypertropic left eye (fast phase down, or downbeat OS), and slow phase down in the hypotropic right eye (fast phase up, or upbeat OD). (Video and legend created with the assistance of Dr. Roksolyana Tourkevich) https:// collections.lib.utah.edu/ark:/87278/s6rz39rq Video 4.25 Three cases of internuclear ophthalmoplegia (INO) due to stroke: This video shows 3 patients with vascular risk factors who suffered strokes of the MLF resulting in unilateral INO in each case. In the second case, INO was diagnosed status post cardiac catherization and MRI was found to be normal. In the third case, the patient had a clear left medial rectus palsy several days prior, but at the time of this exam, there was no adduction paresis and only a subtle adduction lag OD with horizontal saccades. https://collections.lib.utah. edu/ark:/87278/s65t6v56 Video 4.26 Two patients with dorsal pontine strokes causing horizontal gaze palsy and one-and-ahalf syndromes: The first patient presented with double vision and hemiparesis due to a right pontine ischemic stroke. His exam was significant for a right horizontal gaze palsy due to right 6th

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nucleus involvement and right internuclear ophthalmoplegia (INO) (together, a one-and-a-half syndrome). There was also a right lower motor neuron (LMN) facial palsy from a fascicular right 7th NP (also known as “eight-and-a-half syndrome” given the 7th + one-and-a-half syndrome). There was also upbeating nystagmus in upgaze due to involvement of the vertical gaze holding pathways (possibly from the paramedian tracts). Convergence only improved adduction deficits mildly. The second patient presented with facial weakness, hemiparesis, and vertigo with oscillopsia due to a left dorsal pontine hemorrhage. He was unable to look left (with pursuit, saccades, or with the vestibular-ocular reflex), which localized to the left 6th nucleus; there was a left LMN 7th NP (together with the gaze palsy, an “eight syndrome”). There was also upbeat-torsional nystagmus towards the right ear, presumably due to involvement of the vertical semicircular canal pathways (mainly involving the anterior pathways given downward slow and upward fast phase). The anterior canal pathways travel through the superior conjunctivum, ventral tegmental tract, and medial longitudinal fasciculus (MLF), whereas the posterior canal pathways travel through the MLF only. Convergence only improved his adduction deficit mildly. https://collections.lib.utah.edu/ ark:/87278/s6g48ckf Video 4.27 Microvascular 6th nerve palsy: This is a 90 year-man with HTN, HLD, DM who woke up with horizontal diplopia. Two years prior, he was diagnosed with a microvascular right 6th nerve palsy that resolved over several months. There was little concern for giant cell arteritis, myasthenia gravis, or a mass lesion in the absence of typical symptoms or accompanying signs, and a new microvascular left 6th nerve palsy was diagnosed.

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With saccades to the left, not only was abduction severely limited OS, but there was significant slowing of the leftward abducting saccades even when looking from the right to center, which is typical of a paretic process. In contrast, if an abducting saccade were made from the right to center with normal/near normal speed and it stopped abruptly (due to an abduction deficit OS), this should raise suspicion for a restrictive process such as thyroid eye disease. https://collections.lib. utah.edu/ark:/87278/s62v6km4 Video 4.28 Duane’s retraction syndrome, type 1: During an evaluation for vestibular complaints, this patient was incidentally found to have impaired abduction OS. In adduction, there was narrowing of the palpebral fissure OS, a result of globe retraction due to co-contraction of the medial and lateral rectus muscles. This constellation of findings was consistent with a longstanding history of Duane syndrome type 1, and argues strongly against an acquired sixth nerve palsy for instance. There were no complaints of diplopia, and she was already aware of this diagnosis. https://collections.lib.utah. edu/ark:/87278/s6cz6x1g Video 4.29 Miller Fisher syndrome (MFS) causing ophthalmoparesis, sluggish pupils and imbalance: This is a 45 year-old woman who presented with mild imbalance and diplopia. There had been a preceding viral illness several weeks prior. Examination demonstrated horizontal gaze paresis (sparing unilateral adduction), mild gait ataxia (no clear appendicular ataxia), and hyperreflexia. Pupils were sluggish OU. Her anti-Gq1b antibodies came back very high and MFS was diagnosed. IVIG was given, and there was gradual improvement (of all symptoms/signs) back to her baseline over 3–6 months. While the typical triad includes ophthalmoplegia, ataxia, and HYPOreflexia, occasionally,

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HYPERreflexia is seen instead as in our patient. There may also be overlap between MFS and Bickerstaff’s brainstem encephalitis – however, our patient had no symptoms or signs (aside from potentially her hyperreflexia) referable to the brainstem. Brain MRI was normal. https://collections. lib.utah.edu/ark:/87278/s62v64d2 Video 4.30 Midbrain strokes causing bilateral 3rd nerve and pseudo-6th nerve palsies: This is a man who suffered right>left midbrain strokes due to endocarditis, who complained of the inability to move his eyes as well as dream-like hallucinations (due to peduncular hallucinosis). There was a presumed nuclear 3rd nerve palsy on the right (i.e., responsible for his mydriatic pupil, absent supra- and infraduction, adduction, complete ptosis OD and incomplete ptosis OS, and probably responsible for at least some of his supraduction paresis OS), with partial 3rd (fascicular) nerve palsy possibly explaining infra- and supraduction paresis, unreactive pupil OS and perhaps incomplete ptosis OS. In addition to adduction and vertical deficits attributable to midbrain ischemia, he also had right>left abduction pareses that were attributed to pseudo-6th or pseudoabducens palsies in the absence of pontine ischemia on several MRIs (done weeks apart), and no pontine neurologic/ ocular motor signs on his examination. Interestingly, despite his pseudoabducens pareses being due to a presumed “supranuclear” etiology, they could not be overcome by VOR. This has been reported, and perhaps due to the fact that the VOR/ head impulse test is simply not a strong enough vestibular stimulus (compared to cold water calorics for instance) https://collections.lib.utah. edu/ark:/87278/s6642zc1 Video 4.31 A ‘central’ 4th nerve palsy due to midbrain hemorrhage: This patient had a right hypertropia

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that worsened in left and down gaze in addition to right head tilt, and improved in left head tilt. There was subjective excyclotorsion OD with double Maddox rod testing. This was consistent with a right 4th nerve palsy. He had experienced a left midbrain hemorrhage which had bled several years prior to this evaluation making the localization of his 4th nerve palsy “central”. Given the proximity of the left 4th nucleus and its fascicle to the left medial longitudinal fasciculus (MLF) and oculosympathetic tract, when a left internuclear ophthalmoplegia (INO) and/or left Horner’s syndrome, respectively, is seen with a right (CONTRALATERAL) 4th nerve palsy, a ‘central’ 4th NP is strongly suggested relating to the decussating course of the 4th nerve. However, an isolated 4th NP can also be central and related to nuclear and/or fascicular injury, and will be contralesional as in this case. (Video and legend created with the assistance of Dr. Kemar Green) https://collections. lib.utah.edu/ark:/87278/s6hf1tbf Video 4.32 Alternating hypertropias in two patient due to bilateral 4th nerve palsies and alternating skew deviation: Seen here are two patients with alternating hypertropias. The first is a 70-year-old woman with a diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In the video, both spontaneous downbeat nystagmus (DBN) and gaze-evoked nystagmus (GEN) are apparent, in addition to a right hypertropia in right gaze and a left hypertropia in left gaze, also referred to as an alternating skew deviation or an abducting hypertropia. The combination of these three findings (DBN, GEN, alternating skew) is highly suggestive of cerebellar flocculus/paraflocculus disease. The second patient is a 40-year-old woman who also has an alternating hypertropia, although in her case this is an adducting hypertropia due to bilateral 4th nerve palsies. In her case,

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there is a right hypertropia in left gaze and a left hypertropia in right gaze. https://collections.lib. utah.edu/ark:/87278/s6d83n91 Video 4.33 Neuro-ophthalmic features of the dorsal midbrain (Parinaud’s) syndrome: This patient presented with diplopia, headaches, and difficulty looking up, and was found to have a mass involving the pineal gland – pathology led to the diagnosis of glioblastoma multiforme. Major features of a Parinaud’s syndrome were present including: upgaze palsy, convergence retraction nystagmus, light-near dissociation, and mild eyelid retraction. Lesions involving the posterior commissure (PC) often affect upward eye movements (PC doesn’t carry fibers responsible for downward movements). The pupillary light reflex pathway can be affected as the result of damage to the pretectal nucleus or the fibers from pretectal nucleus to Edinger-Westphal (EW) nucleus. The pathways responsible for pupillary constriction during the near reflex do not travel through the pretectal nucleus, and synapse directly on EW. Because they are spared, lightnear dissociation is the result. https://collections. lib.utah.edu/ark:/87278/s62263dq Video 4.34 Bilateral rostral interstitial nucleus of Cajal (riMLF) strokes causing vertical saccadic palsy: This is a 65 year-old-man who suffered the abrupt onset of loss of consciousness followed by difficulty looking down. MRI demonstrated bilateral rostral midbrain strokes in the distribution of the artery of Percheron. He could not initiate downward saccades and had fair upward saccades. However, downward vestibulo-ocular reflex and smooth pursuit was preserved, thus supporting the supranuclear origin of his downward motility issues. Although the riMLF is responsible for initiation of vertical saccades, projections to the

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depressor muscles are ipsilateral whereas projections to the elevator muscles are bilateral – therefore, unilateral riMLF damage will cause difficulty with initiation of downward>>upward saccades, while bilateral damage generally abolishes all vertical and torsional saccadic movements. In his case, injury to the riMLFs was felt to be incomplete given fair upward saccades. https://collections.lib.utah.edu/ark:/87278/s6qg2g63 Video 4.35 A rostral midbrain stroke causing unilateral riMLF and INC syndromes: This is a 65 year-old man who experienced the sudden onset of diplopia, dysarthria and imbalance. An MRI performed the following day showed a left rostral midbrain stroke. The patient was seen in clinic 10 days later (when the video was taken), and by that time the diplopia was purely vertical. The patient had ocular motor findings due to involvement of two distinct rostral midbrain structures: 1) Left interstitial nucleus of Cajal (INC) a. Incomplete ocular tilt reaction including a left hypertropia from skew deviation (25 prism diopters) and ocular counterroll (top poles rotated toward the right ear on dilated fundus exam), but without a head tilt – this was due to involvement of the utriculo-ocular motor pathway. b. Vertical gaze-evoked nystagmus – the INC is responsible for vertical and torsional gaze holding, while the medullary nucleus prepositus hypoglossi-medial vestibular nucleus complex is responsible for horizontal gaze holding. 2) Left rostral interstitial MLF (riMLF) a. Torsional nystagmus, top poles beating toward the RIGHT ear (with torsional nystagmus associated with a LEFT INC, the top poles should beat ipsilaterally, or top poles toward the LEFT ear). With a unilateral riMLF lesion, if torsional nystagmus is seen, it will beat contralaterally as in this case. b. Slow vertical saccades, slower

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downward compared to upward. This is because the innervation for upward saccades is bilateral (i.e., unilateral riMLF innervates bilateral superior rectus and inferior oblique) while the innervation for downward saccades is unilateral (i.e., unilateral riMLF innervates ipsilateral inferior rectus and superior oblique). c. Absent ipsitorsional quick phases in the roll plane when the patient’s head was slowly tilted to the left side. When his head is tilted slowly to the right, the eyes will counterroll with top poles toward the left ear due to the physiologic ocular tilt reaction, but as the head continues to tilt, a quick torsional phase will need to be generated toward the right ear. Since the riMLF contains the vertical and torsional burst neurons, quick torsional phases toward the left (ipsilesional) ear cannot be generated with a left head tilt in this patient, although they were normal with head tilt to the right side due to the intact right riMLF. Three months after the stroke, there was no vertical misalignment in straight ahead gaze, although there was still a small left hypertropia in downgaze. However, his slow vertical saccades remained. The patient also happened to have asteroid hyalosis in the vitreous OD much more than OS (apparent in the video). https://collections. lib.utah.edu/ark:/87278/s6mm0pz4 Video 4.36 Paroxysmal ocular tilt reaction: This patient suffered a left sided hypertensive hemorrhagic stroke 2 years prior, resulting in right hemiparesis, dysarthria and vertical diplopia. The initial vertical diplopia resolved completely and about 6 months following the hemorrhage the patient began to experience many episodes of vertical diplopia and oscillopsia throughout the day, lasting minutes to hours at a time. MRI demonstrated hemosiderin deposition in the left corona radiata, globus pallidus, and rostral left midbrain. She was

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evaluated in clinic about 1 year following the hemorrhage, and the video was taken at that time. Her exam was consistent with a paroxysmal OTR (pOTR) due to presumed left interstitial nucleus of Cajal (INC) excitation/irritation (in this case, presumably related to hemosiderin products), and her pOTR was ipsiversive and included a large right hypertropia from skew deviation, ocular counterroll (top poles toward left ear), and left head tilt. The pOTR occurred every few seconds, and then the head and eye position would return to normal, followed by another combined eye/head (OTR) movement. At the time of the initial stroke, it was reported that there was a 25 prism diopter hypertropia, although the side of the hypertropia could not be found in the notes. Presumably, there was initial dysfunction of the left INC, causing a skew deviation with left hypertropia and a pathological OTR resulting from damage to the utriculoocular motor (or graviceptive-ocular motor – i.e., utricle and vertical semicircular canal afferents) pathway rostral to the decussation of these fibers. With a left INC lesion (e.g., stroke), a contraversive OTR would be expected, including left hypertropia from skew deviation, ocular counterroll (top poles toward right ear), and right head tilt. There was no improvement with carbamazepine and its use was limited by side effects. Gabapentin resulted in a reduction in the duration and frequency of pOTR episodes (e.g. the pOTR would cycle on and off for minutes at a time, and then abrupt stop – when she was asymptomatic and there was no evidence of pOTR, her alignment was normal and there was no abnormal head position or nystagmus). However, the appearance of the pOTR during episodes was the same while being treated with gabapentin as it was prior to any medication

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therapy. https://collections.lib.utah.edu/ark:/87278/ s6gt9z78 Video 4.37 Complete saccadic palsy following pulmonary thrombectomy: This patient underwent pulmonary thrombectomy for a pulmonary embolus. Immediately following the procedure, she was unable to move her eyes. This video exam (she is the passenger in a car during a telemedicine appointment) was performed 4 months after the onset. She was unable to make saccades horizontally or vertically, although horizontal and vertical smooth pursuit and the vestibulo-ocular reflexes (VOR) were intact, as was the range of eye movements. When asked to look out the window at passing scenery (i.e., an optokinetic stimulus), the slow phase was clearly present, but because she could not generate a fast phase (saccades), the eyes were pinned to the right side. This could happen while walking and looking to the sides as well. She had a pure saccadic palsy in both horizontal and vertical planes; therefore, this did not localize to the paramedian pontine reticular formation (PPRF) or rostral interstitial medial longitudinal fasciculus (riMLF), respectively. Because the excitatory burst neurons (EBN, responsible for saccades) and the omnipause cells are both ensheathed by the perineuronal nets, and because a patient with this rare disorder at autopsy (typically due to cardiac surgery) was shown to have normal EBN and omnipause cells, the prevailing theory for a post-surgery saccadic palsy is that ischemia of the perineuronal nets may be the culprit. Fortunately, she was able to adapt by using head movements (the VOR) to move the eyes in the intended direction. https://collections.lib.utah.edu/ ark:/87278/s68h45z9 Video 4.38 Ocular motor signs in early progressive supranuclear palsy (PSP): Exam demonstrated square

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wave jerks, supranuclear downward>upward palsy (i.e., improved with the vertical vestibulo-ocular reflex [VOR]), slow and hypometric horizontal saccades with very slow down>up saccades (especially apparent with optokinetic tape), convergence insufficiency, and saccadic smooth pursuit and VOR suppression. Since upgaze can become impaired to some degree with normal aging (whether this is related to changes involving the orbital tissues or whether this is in part supranuclear is not clear), poor downgaze in a patient with a gait/balance disorder is more diagnostically meaningful. (Video and legend created with the assistance of Dr. Roksolyana Tourkevich) https://collections.lib.utah.edu/ ark:/87278/s6gr0vxw Video 4.39 Advanced progressive supranuclear palsy (PSP) with complete ophthalmoplegia but preservation of the horizontal vestibulo-ocular reflex (VOR): This patient had complete vertical and horizontal ophthalmoplegia, although the VOR could overcome the horizontal gaze palsy (but not the vertical gaze palsy). When VOR suppression was tested by having the patient look at the light of the camera while rotating (combined eye-head movement) in a chair, the intact VOR drove the eyes to the right when the chair was turned to the left and to the left when the chair was turned to the right. In this case, she was completely unable to suppress her VOR. Normally, when VOR suppression (VORS) is impaired, the appearance is choppy or saccadic – this is explained by saccades supplementing the impaired pursuit/VORS response. In her case, she was unable to generate saccades, so the eyes drifted laterally (due to an intact VOR) without a mechanism (i.e., saccades) to get them back to the fixation target. MRI demonstrated ‘Mickey mouse sign’, an appearance created by

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midbrain tegmentum atrophy on axial images. https://collections.lib.utah.edu/ark:/87278/s6wx2sks Video 4.40 Vertical gaze palsy, abnormal optokinetic nystagmus and inability to suppress blinking to light in progressive supranuclear palsy (PSP): This patient had a vertical supranuclear gaze palsy (i.e., it could be overcome by the vertical vestibulo-ocular reflex [VOR]), saccadic smooth pursuit and VOR suppression (not shown), and hypometric and slow horizontal saccades, and with an optokinetic flag, there were weak fast phases (saccades) horizontally, and absent fast phases vertically. Slowing of downward saccades and loss of the downward fast phase with an optokinetic flag are commonly early signs in PSP, which tend to precede the development of the downgaze/vertical palsy. Additionally, patients with PSP tend to have difficulty suppressing blinks when a bright light is shone into the eyes – a finding akin to the glabellar reflex, which is often present in neurodegenerative conditions such as Parkinson’s disease. https:// collections.lib.utah.edu/ark:/87278/s6810bdv Video 4.41 Downbeat and gaze-evoked nystagmus, impaired smooth pursuit, and saccadic hypermetria in spinocerebellar ataxia type 8: This patient also had a symptomatic esotropia at distance consistent with divergence insufficiency, which is a common cause of strabismus (due to involvement of ocular motor vermis and/or flocculus) in cerebellar degenerations. https:// collections.lib.utah.edu/ark:/87278/s6dj8q9h Video 4.42 Gaze-evoked and rebound nystagmus, saccadic pursuit and vestibulo-ocular reflex suppression (VORS) in a cerebellar degeneration: This patient experienced a several year long history of imbalance due to cerebellar ataxia of unclear

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etiology. Seen in this video are common ocular motor signs in patients with advanced cerebellar dysfunction including: 1) saccadic smooth pursuit, 2) saccadic VORS (a combined eye-head movement; the fact that pursuit and VORS appear to be equally saccadic also tells the examiner that the VOR is present – i.e., if VORS was normal/ near-normal appearing but pursuit was saccadic, this would imply that there is no VOR to suppress), 3) gaze-evoked and rebound nystagmus. https:// collections.lib.utah.edu/ark:/87278/s6907ch7 Video 4.43 Paraflocculus (tonsillar) ocular motor syndrome and saccadic dysmetria in a patient with Chiari malformation: This is a 25-year-old woman presenting with 6 months or progressive imbalance, binocular vertical diplopia, and occipital headaches, which were brought on or aggravated by coughing or sneezing. Examination demonstrated hyperreflexia in the arms and legs with sustained clonus at the ankles and Babinski reflexes bilaterally in addition to gait and limb ataxia. There were a variety of ocular motor abnormalities as well (see below). Contrast-enhanced MRI demonstrated peg-like cerebellar tonsils extending 2.9 cm below the foramen magnum (more tonsillar herniation on the right), and flattening of the dorsal medulla (right>left). There was also syringohydromyelia of the cervical and proximal thoracic spinal cord with cord parenchymal thinning. Taken together, this was consistent with a Chiari type I malformation. While there was bilateral tonsillar herniation, it was worse on the right. In fact, the following findings were suggestive of a right paraflocculus (tonsillar) ocular motor syndrome: 1) weak right-beating (ipsilateral) spontaneous nystagmus (not seen in the video); 2) strong and (slightly) asymmetric right more than left gaze-evoked nystagmus (ipsilateral>contralateral) – in her case, there was also downbeat and torsion in

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lateral and down/lateral gaze (perhaps due to bilateral paraflocculus compression); 3) impaired smooth pursuit and vestibulo-ocular reflex suppression (VORS) toward the right (ipsilateral); 4) there was also a fairly comitant right hypertropia (a skew deviation), ocular counterroll (top poles toward the left ear), and subjective visual vertical tilt 5 degrees to the left with the bucket test – taken together, this was consistent with a contraversive partial ocular tilt reaction (no clear head tilt). Head impulse test was normal. There was also saccadic dysmetria with hypermetria to the right and hypometria to the left (limb ataxia was worse on the right side as well). It was felt that this was due to compression of the right inferior cerebellar peduncle, affecting climbing fibers from left inferior olive to right dorsal vermis. She underwent suboccipital craniectomy and C1 laminectomy, and when she was seen 6 months following surgery, all ocular motor findings had resolved with the exception of mild residual gaze-evoked nystagmus. https://collections.lib.utah. edu/ark:/87278/s64r3f70 Video 4.44 Periodic Alternating Nystagmus and Central Head-Shaking Nystagmus from Nodulus Injury: This patient suffered a gunshot wound to the cerebellum. When he regained consciousness days later, he experienced oscillopsia due to periodic alternating nystagmus (PAN). He was started on baclofen 10 mg bid, and had a dramatic response and only had moderate spontaneous left-beating nystagmus (without PAN) along with gaze-evoked nystagmus. The dose was increased to 20 mg 4 times/day which was tolerated well, and nystagmus and oscillopsia resolved completely. However, following 10–15 seconds of 2–3 Hz horizontal head-shaking, there was robust left-beating nystagmus. This could be explained by injury to the nodulus, a localization that explains both PAN

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and certain central patterns of head-­shaking nystagmus (HSN) such as this (i.e., robust HSN in the absence of unilateral vestibular loss). Neuronal circuits responsible for velocity storage (which normally prolong the vestibulo-ocular reflex response beyond the mechanical limitations of the semicircular canal cupula) are mainly located in the vestibular nucleus and nodulus. Disinhibition of velocity storage due to nodulus injury can therefore contribute to PAN or central HSN as in this case. https://collections.lib.utah.edu/ ark:/87278/s64b892v Video 4.45 Paraneoplastic cerebellar degeneration causing severe saccadic hypermetria: This is a patient who was diagnosed with anti-Yo antibody-related cerebellar syndrome due to ovarian cancer 2 years prior to this video. She complained of oscillopsia due to spontaneous upbeat nystagmus (presumably the result of brainstem involvement), and on examination, she had intermittent saccadic intrusions, hypermetric saccades (in all planes), saccadic smooth pursuit and vestibulo-ocular reflex suppression. MRI demonstrated severe brainstem and cerebellar a­ trophy. https://collections.lib.utah. edu/ark:/87278/s6bz9v92 ESM 5.1 Expanded nystagmus & saccadic intrusions/ oscillations ­differential Video 5.1 Head movement independent (‘sitting’) ­oscillopsia – a common symptom of nystagmus and s­ accadic intrusions/oscillations: This video is an example of what a patient with spontaneous nystagmus or saccadic intrusions/oscillations experiences visually during the abnormal eye movements – i.e., oscillopsia (illusion of movement of the stationary environment) is the result. Compare this to head movement dependent (‘walking’) oscillopsia, which is typically due bilateral vestibular loss

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Jerk nystagmus: This is an example of jerk nystagmus due to a central vestibular lesion. The slow phase is the pathologic phase (to the left) which initiates the movement, and is followed by a fast position reset mechanism (to the right). Jerk nystagmus is named after the fast phase. This patient presented with the acute vestibular syndrome due to a demyelinating brainstem lesion, which led to the diagnosis of neuromyelitis optica. She has spontaneous right-beating nystagmus (RBN), that stays unidirectional (RB) in all directions of gaze, even to the left. To the right, there is more intense RBN in accordance with Alexander’s law (i.e., vestibular nystagmus will increase in the direction of the fast fast) Pendular nystagmus: This is an example of pendular nystagmus, where like jerk nystagmus, the slow phase initiates the movement. However, unlike jerk nystagmus, there is no fast phase, but rather back to back slow phases resembling a pendulum. Pendular nystagmus is named after the vector, making this mainly a horizontal (with a slight elliptical trajectory) pendular nystagmus. This patient presented with ‘sitting’ oscillopsia (from her nystagmus) due to a progressive neurodegenerative disorder (of unknown etiology) that led to severe atrophy of the brainstem and cerebellum over years Saccadic intrusions (square wave jerks, SWJ): Seen here are SWJ, which is the most common example of a saccadic intrusion. Here the patient is fixating on the camera, and all of the sudden a saccade takes the eyes off the fixation target, there’s a brief intersaccadic interval, and then the eyes return to the target. Therefore, the saccade is the culprit that initiates the movement, rather than the slow phase (which is the culprit with jerk or pendular nystagmus). The intrusions occur quite

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frequently (many more than would be expected given his age alone), and these prominent SWJ were related to a progressive cerebellar degeneration in his case Head movement dependent (‘walking’) oscillopsia – a common symptom of bilateral vestibular loss: This video is an example of what a patient with bilateral vestibular loss experiences while walking. Without a vestibulo-ocular reflex (VOR), there is no mechanism to ensure retinal stability of the world with each head movement, and oscillopsia (illusion of movement of the stationary environment) is the result. Jumpy vision during ambulation or when driving on a bumpy road for example is highly suggestive of bilateral vestibular loss, and head impulse testing and evaluation of the VOR are warranted. Head movement independent (‘sitting’) oscillopsia is typically due nystagmus or saccadic intrusions/ oscillations. https://collections.lib.utah.edu/ details?id=1213442 Bruns nystagmus due to a cerebellopontine angle vestibular schwannoma: This patient experienced headache and imbalance leading to an MRI which showed a left sided cerebellopontine angle (CPA) vestibular schwannoma. Because of involvement of the left brainstem/cerebellum (e.g., dysfunction of the neural integrator/gaze holding apparatus) by the CPA mass, there was left-beating ipsilesional “gaze-evoked” nystagmus in left gaze. Note the larger amplitude and lower frequency gaze-evoked nystagmus in left gaze. Because of involvement of the left 8th cranial nerve, there was right-beating contralesional “vestibular” nystagmus in right gaze (in accordance with Alexander’s law). Note the smaller amplitude and higher frequency vestibular nystagmus in right gaze. https://collec-

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tions.lib.utah.edu/ark:/87278/s60p4p3j (Video courtesy of Dr. Veeral Shah) Latent nystagmus due to infantile esotropia: This patient had a history of amblyopia and intermittent eye crossing. On exam, he had a large angle esotropia, and other features of an infantile esotropia syndrome including: latent nystagmus (right-beating nystagmus when fixating with the right eye and left-beating nystagmus when fixating with the left eye), inferior oblique overaction OU, and monocular nasotemporal optokinetic asymmetry (not included in the video). https://collections. lib.utah.edu/ark:/87278/s6k393bz Periodic alternating nystagmus (PAN) and cross-coupled head-shaking nystagmus in cerebellar degeneration: This patient presented with progressive imbalance and oscillopsia over years, and examination demonstrated alternating right-beating and left-beating nystagmus every 90–120 seconds (with a null period in between) consistent with PAN. PAN localizes to the nodulus/ ventral uvula, and is occasionally seen with cerebellar degenerations (SCA 6 among others). Baclofen can be helpful for PAN, and therapy was initiated in this particular patient with mild improvement. She also had hypermetric saccades, saccadic smooth pursuit and vestibulo-ocular reflex suppression, gaze-evoked nystagmus, as well as a cross-coupled response with head-shaking – i.e., with horizontal head-shaking, vertical nystagmus (downbeating) was apparent). This is another central vestibular/ocular motor sign, and can also be seen with nodulus/uvula pathology as well as with flocculus/paraflocculus involvement – this finding can be seen at the end of the video. This patient had a pan-cerebellar syndrome involving the vestibulocerebellum as well as the fastigial nucleus (saccadic hypermetria) and other regions.

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https://collections.lib.utah.edu/ark:/87278/ s62k013r Video 5.9 Periodic alternating nystagmus (PAN) due to spinocerebellar ataxia type 6: This patient presented with imbalance for several years and more recently oscillopsia. On examination, there was saccadic pursuit in addition to gaze-evoked nystagmus with rebound, raising suspicion for a cerebellar flocculus/paraflocculus localization. Additionally, there was PAN, which localizes to the nodulus/ventral uvula. Every 90–120 seconds there was a transition from right-beating to left-beating, etc. Baclofen lessened his oscillopsia, and genetic testing for SCA 6 was positive. https:// collections.lib.utah.edu/ark:/87278/s6np5spp Video 5.10 Paraneoplastic downbeat nystagmus (DBN) and cerebellar ataxia due to small cell lung carcinoma: This patient experienced the subacute progression of imbalance and oscillopsia over weeks, due to a paraneoplastic cerebellar syndrome from lung cancer. Examination demonstrated spontaneous DBN and gaze-evoked nystagmus (causing a ‘side pocket’ appearance), hypermetric saccades, saccadic smooth pursuit and vestibuloocular reflex suppression (not shown in this video). DBN improved significantly following intravenous immunoglobulin and treatment of the cancer. (Video and legend created with the assistance of Drs. Tony Brune and Kelly Sloane) https://collections.lib.utah.edu/ark:/87278/s6dn80mw Video 5.11 Downbeat nystagmus causing severe oscillopsia: This patient experienced progressive ataxia and oscillopsia over two years of unknown etiology. Unfortunately, trials of 4-aminopyridine, clonazepam, baclofen, and chlorzoxazone were ineffective. After 2 years, significant cerebellar atrophy was apparent on his MRI. https://collections.lib. utah.edu/ark:/87278/s6wq42f0

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Video 5.12 Abnormal visually-enhanced vestibulo-ocular reflex (vVOR) in cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): This patient complained of chronic (unexplained cough), progressive numbness in the legs and feet, gait instability, and oscillopsia when walking or with head movements. Examination showed excessive square-wave jerks, bilateral horizontal gaze-evoked nystagmus, bilaterally abnormal head impulse testing, saccadic vVOR (seen with slow head turning to the right and left, abnormal due to combination of poor pursuit and bilateral vestibular loss). A clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) was made. An impaired or saccadic vVOR suggests that there is failure of both the pursuit and (usually bilateral) vestibular systems, and CANVAS should be considered, especially when neuropathy and chronic cough are also present Video 5.13 Positional downbeat nystagmus due to a cerebellar degeneration: This patient mainly complained of dizziness and vertical oscillopsia when assuming a supine position. She was found to have a significant exacerbation in her (very mild) baseline downbeat nystagmus with straight head hanging, and in right and left Dix-Hallpike. Although positional downbeat nystagmus (pDBN) can be seen with the uncommon anterior canal variant of BPPV, usually it is seen with disorders of the cerebellum or cervicomedullary junction. When pDBN is seen in a patient with parkinsonism, multiple system atrophy should be a consideration. In this patient, the downbeat was in isolation, there was no cerebellar ataxia, and extensive evaluation was unrevealing. She did well with 4-aminopyridine and there was no progression over

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at least 2 years. https://collections.lib.utah.edu/ ark:/87278/s66t3w9k Video 5.14 Spontaneous upbeat nystagmus (UBN) in acute Wernicke’s encephalopathy: Always consider the possibility of Wernicke’s encephalopathy when a patient presents acutely with spontaneous UBN, in addition to a brainstem stroke, demyelinating lesion, or encephalitis. (Video and legend created with the assistance of Dr. Julia Carlson) https:// collections.lib.utah.edu/ark:/87278/s6h74j6d Video 5.15 Reversal of vertical nystagmus over time and with convergence in anti-DPPX encephalitis – a similar pathophysiology to Wernicke’s encephalopathy?: This is a man who initially presented with spontaneous upbeat and torsional nystagmus, which led to the diagnosis of anti-DPPX encephalitis. Over 6–12 months, his spontaneous (mainly) upbeat nystagmus (UBN) transitioned to spontaneous downbeat nystagmus (DBN). In this video, he has gaze-evoked nystagmus (e.g., right-beating in right gaze and left-beating nystagmus in left gaze) with a downbeat component. While spontaneous downbeat nystagmus was present in primary gaze, with convergence, this transitioned to upbeat nystagmus. Vertical nystagmus reversing with convergence is a finding often seen in patients with Wernicke’s encephalopathy. While the semicircular canals (posterior, horizontal, and anterior) are the angular acceleration detectors in the labyrinth, the otoliths (utricle and saccule) are the linear acceleration detectors and are responsible for the translational vestibulo-ocular reflex (t-VOR). In order for the t-VOR to generate appropriate eye movements, orbital position and vergence angle must be taken into account. Brainstem structures responsible for processing otolithic inputs include the medial and inferior vestibular nuclei (MVN and LVN), which

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have projections to the cerebellar nodulus (which also has a role in modulating the t-VOR). In patients with acute Wernicke’s encephalopathy, gaze-evoked nystagmus can be attributed to damage involving the MVN-nucleus prepositus hypoglossi (NPH) complex, while the horizontal (angular) VOR is commonly impaired since the horizontal semicircular canal afferents synapse in the MVN. With Wernicke’s the transition from spontaneous upbeat nystagmus (attributed to damage involving the nucleus of Roller and nucleus intercalatus, which both inhibit the flocculus) to downbeat nystagmus with convergence can also be explained by damage to the MVN and LVN given their role in the t-VOR. In this patient with anti-DPPX encephalitis, impairment of MVN-LVN and/or nodulus are all possible explanation for the transition of DBN to UBN with convergence. It is possible that the initial spontaneous upbeat-torsional nystagmus resulted from asymmetric pontomedullary damage involving the vertical semicircular canal (SCC) pathways (multiple MRIs showed no clear T2/FLAIR or T1-enhancing posterior fossa lesions). Several theories for the transition of spontaneous UBN (acutely) to spontaneous DBN (chronically) in this patient include: 1) Given the proximity of the paramedian tract nuclei (PTN), the chronic downbeat nystagmus could relate to vertical SCC pathway recovery with persistent PTN damage – i.e., a similar (or identical) mechanism to the prevailing theory for transition of acute UBN to chronic DBN in Wernicke’s encephalopathy. Since the PTN normally excites the flocculus, damage to the PTN can cause relative hypoactivity of the flocculus and an upward bias (slow phase drift since anterior canal [upward or anti-gravity] pathways are overactive) with resultant downbeat nystagmus. 2) The patient also developed gaze-evoked nystagmus

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in lateral and up and down gaze after 6–12 months, likely related to dysfunction of the flocculus/ paraflocculus rather than the MVN-NPH given its presence in horizontal and vertical gaze. The spontaneous DBN and saccadic pursuit and VOR suppression that also developed are also suggestive of a flocculus/paraflocculus syndrome. It is therefore possible that the acute asymmetric vertical SCC pathway injury recovered, but flocculus/paraflocculus impairment developed ­chronically. https:// collections.lib.utah.edu/ark:/87278/s6bg75c3 Video 5.16 Ocular motor signs in brainstem demyelinating disease – spontaneous upbeat nystagmus (UBN), vertical gaze-evoked nystagmus, slow saccades, bilateral vestibular loss, internuclear ophthalmoplegia (INO): Salient findings included the following, which could be correlated with MRI hyperintensities throughout the brainstem (no involvement of the cerebellum): 1) Spontaneous UBN: this caused vertical oscillopsia that was independent of head movements. UBN often localizes to the dorsal caudal medulla (nucleus of Roller and nucleus intercalatus), and in fact, hyperintense T2/FLAIR signal was present bilaterally in this region (see arrows in figure). Visual acuities were impaired in part due to bilateral optic neuritis, but also given her spontaneous nystagmus. 2) Hypoactive VOR: this caused oscillopsia that depended on head movements (e.g., walking) and bilateral vestibular loss was shown on bedside and video head impulse testing (HIT). Afferents from the horizontal semicircular canals (SCC) synapse in the medial vestibular nucleus (hyperintense T2/FLAIR signal was present in the region of the MVN-nucleus prepositus hypoglossi complex bilaterally; see arrows in figure), while afferents from the vertical SCC synapse on other vestibular subnuclei that in turn

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project rostrally via the medial longitudinal fasciculus (MLF) to the trochlear and oculomotor nuclei. Bilateral dorsal pontine hyperintense T2/ FLAIR signal was present in the region of the MLFs (see arrows in the figure). 3) Bilateral adduction paresis: this was responsible for horizontal diplopia from bilateral internuclear ophthalmoplegia (INO) with adduction deficits and abducting nystagmus OU from bilateral lesions in the MLF. Notably, even when unilateral or bilateral INOs are present, HIT/video HIT in the plane of the horizontal SCCs is typically normal/near normal. As an example, a patient with a right INO can have a right adduction deficit (or lag) with leftward gaze. However, when a HIT is performed to the right (requiring activation of the right medial rectus), the afferents from the horizontal SCC can bypass the MLF lesion (via the ascending tract of Deiters), allowing for preservation of the efferent limb of the horizontal VOR. In this patient’s case, hypofunction in the planes of the horizontal SCC could be explained by bilateral MVN lesions. 4) Vertical gaze-evoked nystagmus: this was due to vertical gaze holding impairment from either lesions in the interstitial nucleus of Cajal (INC) involvement in the rostral midbrain (see arrows in figure), or from lesions in the medially located pontomedullary paramedian tracts (receive vertical gaze holding signals from INC and relay to cerebellar flocculus). 5) Slow horizontal saccades: while the slow adducting saccades could be explained by bilateral INOs, the abducting saccades were also slow and fast phases were poor with an optokinetic stimulus. Vertical saccades appeared to be normal when taking into account her significant UBN. Given widespread dorsal pontine disease (see arrows in figure on sagittal FLAIR), it is likely that paramedian pontine

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reticular formation (PPRF) was involved. https:// collections.lib.utah.edu/ark:/87278/s64517rm Video 5.17 Lateral pontine stroke involving the superior vestibular nucleus causing spontaneous upbeattorsional nystagmus: A 65-year-old man presented to the emergency department with spontaneous vertigo and unsteadiness, and was noted to have spontaneous upbeat nystagmus (UBN), also with a torsional component (top poles beating toward the right ear) that was most noticeable in right and up gaze. General neurologic exam was non-focal although there was severe imbalance. Brain MRI demonstrated a small left dorsolateral pontine stroke (see end of video for diffusion-weighted imaging on the left and FLAIR on the right), that involved the left superior vestibular nucleus. While the posterior semicircular canal (SCC) afferents synapse in the vestibular nucleus and then ascend the medial longitudinal fasciculus (MLF) only, the anterior SCC afferents synapse in the vestibular nucleus and ascend via one of three pathways: 1) MLF, 2) ventral tegmental tract, and 3) brachium conjunctivum (BC, aka, superior cerebellar peduncle). Anterior SCC afferents synapse in the rostral SVN on their way to join the BC, and in this patient’s case, it was thought that ischemia in this region was responsible for his UB-torsional nystagmus. Anterior SCC afferents destined for the BC would originate in the left labyrinth and synapse in the left SVN prior to their decussation. If left anterior SCC afferents were injured – normally responsible for torsional slow phase with top poles rotating toward the right ear and an upward slow phase (sometimes referred to as the “anti-gravity” pathway) – there would be a relative predominance of posterior SCC tone (causing downward slow phase) and right sided anterior and posterior SCC tone (causing

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torsional slow phase with top poles toward the left ear). These slow phases in turn generate fast phases upward (UBN) and torsional toward the right ear, which is what is seen in this patient. While UBN is typically thought to localize to the midline medulla or to paramedian pontomesencephalic regions (MLF, BC), this patient demonstrates that a lateral pontine insult can also cause this finding. (Video courtesy of Dr. Tzu-Pu Chang) https://collections. lib.utah.edu/ark:/87278/s6kx02v4 Video 5.18 Torsional nystagmus due to medullary tumor: This patient experienced headaches which led to an MRI and the diagnosis of a right medullary pilocytic astrocytoma, confirmed pathologically. Examination was performed a year after the initial diagnosis, and several months prior to this exam oscillopsia was experienced for the first time. MRI demonstrated that the cystic portion had increased in size and it was thought that her newly appreciated nystagmus and resultant oscillopsia were related to this interval change. On exam, she had spontaneous torsional nystagmus, which was unidirectional in right and left gaze, with the top poles beating towards the right ear in each position. Saccades, smooth pursuit and the vestibulo-ocular reflex were unremarkable. Pure torsional nystagmus is almost always central in origin. An acute destructive lesion (e.g., vestibular neuritis) causing unilateral vestibular loss will cause contralesional horizontal-torsional nystagmus related to unopposed semicircular canal (SCC) afferents contralaterally. For pure torsional nystagmus to result from a peripheral lesion, certain SCCs must be spared (e.g., both horizontal SCCs, which will cancel out so that a horizontal jerk component is not seen; both vertical SCCs on one side) while others must be strategically damaged (e.g., both vertical SCCs on the opposite side). In contrast, damaging the

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central fibers originating from both vertical SCCs on one side due to a medullary lesion is a much more common cause of torsional nystagmus. Pure torsional nystagmus may also result from unilateral interstitial nucleus of Cajal (ipsiversive nystagmus) or rostral interstitial medial longitudinal fasciculus (contraversive) injury, while vertical-torsional nystagmus may result from medullary (direction can be less predictable depending on how caudal or rostral the injury occurs), medial longitudinal fasciculus (ipsiversive), or superior cerebellar peduncle localizations, among others. https:// collections.lib.utah.edu/ark:/87278/s6n62k3m Video 5.19 Oculopalatal tremor (OPT) and internuclear ophthalmoplegia (INO) due to a hemorrhagic pontine cavernoma: This is a 60-year-old woman who experienced 2 episodes of vertigo, nausea and vomiting, which was felt to be related to recurrent hemorrhage of a pontine cavernoma that was adjacent to the fourth ventricle. The cavernoma was resected, and diplopia and left facial palsy were noted after the surgery. About 6 months later, balance worsened and oscillopsia was experienced for the first time. At the time that this video was taken, more than 12 months had passed since the surgery. Deficits included left lower motor neuron (LMN) facial palsy (damage to the left fascicle of CN7), left INO (damage to the left medial longitudinal fasciculus), in addition to vertical-torsional pendular nystagmus and palatal tremor, consistent with oculopalatal tremor. Review of a recently obtained MRI showed bilateral hyperintensity of the inferior olives (IO) on MRI T2/FLAIR sequences due to hypertropic olivary degeneration (HOD). In her case, HOD was related to injury of the descending central tegmental tract (CTT) as it passed through the pons, thereby removing normal inhibition of the IO by the CTT. (Video and legend

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created with the assistance of Dr. Tony Brune) https://collections.lib.utah.edu/ark:/87278/ s618790z Video 5.20 Acute vestibular neuritis with unidirectional nystagmus and abnormal video head impulse test (vHIT): This patient presented to the emergency department (ED) 2 days prior to the video recording with acute onset prolonged vertigo, nausea, head motion intolerance, unsteadiness and spontaneous nystagmus, consistent with the acute vestibular syndrome. Video-oculography examination in the ED demonstrated mixed left-beating and torsional (top poles beating toward left ear) nystagmus that was unidirectional (i.e., left-beating in all directions of gaze) and increased in left gaze in accordance with Alexander’s law. There was no loss of hearing, video head impulse test was abnormal to the right (low gain and corrective saccades), and test of skew was normal (i.e., vertical alignment was normal with alternate cover test). Per the HINTS exam (Head Impulse, Nystagmus, Test of Skew) and in the absence of hearing loss, he was diagnosed with right-sided vestibular neuritis. He was given steroids and presented for follow-up 2 days later (the day of this recording). Nystagmus was much less intense than it had been in the ED, and symptomatically, he was much improved. https://collections.lib.utah.edu/ ark:/87278/s6pg73w3 Video 5.21 Spontaneous torsional nystagmus and ocular tilt reaction (OTR): This patient experienced “a delay in focusing” with “some twisting movement” that began about 18 months prior to this video with mild progression over days or weeks. For the same period of time, he experienced intermittent vertical diplopia. MRI done months after the onset was unremarkable, as was a second contrast-enhanced MRI done several months prior to this video.

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Evaluation for neoplastic/paraneoplastic, infectious, inflammatory, autoimmune disorders was unrevealing and his symptoms had been subjectively stable for over a year. Oscillopsia – There was spontaneous torsional nystagmus (top poles beating toward the right ear) in primary gaze with a very slight downbeat (DB) component. The torsional nystagmus is unidirectional in all directions of gaze, although there was more DB in right gaze. Gabapentin or baclofen trial was discussed and deferred given the mild nature of his oscillopsia (mainly experienced in right gaze). Diplopia – There was a small-angle right hypertropia of 1 PD in primary gaze that measured 2 PD in right gaze and was otherwise comitant on 3-step testing. Ocular counterroll (OCR, top poles toward the left ear) was present on fundus photos, and with bucket test, there was a 5 degree leftward tilt in subjective visual vertical (SVV). Taken together, he had evidence of a partial ocular tilt reaction (OTR) including skew deviation, OCR, and SVV (a perceptual consequence of the OTR), but without a noticeable static head tilt. The slow phase of his torsional nystagmus caused the top poles to rotate toward the left ear, which was also in the direction of the OCR from his partial OTR – therefore, imbalance in the utricle-ocular motor pathways explained his OTR and could be an explanation for his torsional nystagmus as well (no clear jerky or hemi-seesaw nystagmus was seen). Or, in addition to central utricle pathway damage, fairly symmetric central damage to posterior and anterior semicircular pathways could be responsible for his mainly torsional nystagmus. Otherwise, there were no other neuro-ophthalmic or neurologic signs to suggest a lesion in the lateral medulla, medial longitudinal fasciculus or interstitial nucleus of Cajal (any of which could cause

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OTR and spontaneous torsional or vertical-torsional nystagmus). https://collections.lib.utah.edu/ ark:/87278/s6vt71tc Video 5.22 Oculopalatal tremor (OPT) with prominent pendular nystagmus, bilateral horizontal gaze palsy, and bilateral facial palsies: Seen here are classic features of OPT, including vertical pendular nystagmus, palatal myoclonus, and MRI evidence of inferior (medullary) olivary hypertrophy. Given the proximity of the central tegmental tract to the abducens nuclei and facial nerve fascicles, she also had horizontal gaze palsy and facial diplegia. (Video and legend created with the assistance of Dr. Tony Brune) https://collections.lib.utah.edu/ ark:/87278/s6mh1mnm Video 5.23 Oculopalatal tremor (OPT) and one-and-a-half syndrome due to pontine hemorrhage: This patient suffered a midline pontine hemorrhage (left>right) shortly after being put on a blood thinner. Immediately afterwards, right hemiparesis and hemi-anesthesia, left lower motor neuron (LMN) facial palsy and ophthalmoparesis were noted. Months later, he experienced oscillopsia as well. At the time that this video was taken, he was about 6 months from the pontine hemorrhage. There was mainly vertical pendular nystagmus noted in the left eye, and there were vertical and horizontal (convergent-divergent) components in the right eye, along with palatal tremor, which is known as oculopalatal tremor (OPT). Vertical movements were normal and horizontal motility exam demonstrated a left internuclear ophthalmoplegia (INO -damage to the left medial longitudinal fasciculus [MLF]) and left horizontal gaze palsy (damage to left 6th nucleus affecting fibers destined for left lateral rectus and interneurons destined for right medial rectus via right MLF),

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and a partial right 6th nerve palsy, related to injury of the right 6th fascicle. The combination of left INO and left horizontal gaze palsy is also referred to as a one-and-a-half syndrome. Disjunctive nystagmus is common in OPT, and given the proximity of the descending central tegmental tract (CTT) to the fascicle/nucleus of CN6 and MLF, horizontal motility deficits may cause disjunctive horizontal components as in this patient who couldn’t adduct or abduct OS (i.e., nystagmus was pure vertical OS). Typically, pendular nystagmus in OPT is vertical, torsional, or vertical-torsional, although there may be horizontal components as well, sometimes with a convergent-divergent pattern. Review of a recently obtained MRI showed hyperintensity of the left inferior olive (IO) on MRI T2/FLAIR sequences due to hypertropic olivary degeneration (HOD). In his case, HOD was related to injury of the descending central tegmental tract (CTT) as it passed through the pons, thereby removing normal inhibition of the IO by the CTT. (Video and legend created with the assistance of Dr. Tony Brune) https://collections. lib.utah.edu/ark:/87278/s6wh6sfc Video 5.24 Subtle torsional pendular nystagmus in oculopalatal tremor (OPT): This patient presented with imbalance, and MRI demonstrated a right cerebellar cavernous malformation. She underwent surgery to resect the malformation, and post-operatively experienced right hemiparesis and ataxia. Six months after the surgery, balance worsened and vision became “blurry” despite normal afferent function. Exam demonstrated mild torsional pendular nystagmus OU and subtle rhythmic twitching of the right mentalis (not seen in the video). Palatal tremor was also seen, synchronous with the facial muscle twitching. When the patient was asked to gently close her eyes, vertical ocular

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oscillations (again synchronous with the palatal tremor) were apparent. Even when nystagmus due to oculopalatal tremor (OPT) is subtle or absent, eyelid closure will usually bring out (e.g., palatal tremor without nystagmus is usually seen with progressive ataxia and palatal tremor [PAPT], although rhythmic oscillations can still be brought out with gentle eyelid closure) or accentuate vertical ocular oscillations, a finding that is sometimes referred to as ocular synchrony. MRI T2/FLAIR sequences demonstrated a hyperintense left inferior olivary nucleus (figure), consistent with the theory of olivary hypertrophy, which is thought to generate OPT. When pendular nystagmus of unclear origin is appreciated, regardless of whether it is subtle, monocular, disjunctive, dissociated or conjugate, the examiner must have a suspicion for OPT and view the palate at rest. https://collections.lib.utah.edu/ark:/87278/s6rc1227 Video 5.25 Eyelid closure and oculopalatal tremor (ocular synchrony): The first patient in this video suffered a traumatic brain injury with brainstem injury resulting in damage to Mollaret’s triangle and palatal tremor. Inferior olivary hypertrophy was noted on her MRI, although no vertical and/or torsional pendular nystagmus was present even when observing closely with the ophthalmoscope. However, when she was asked to close her eyes, large amplitude vertical ocular oscillations were appreciated. When her eyes were observed with infrared video goggles in the dark, no oscillations were present; therefore, the oscillations seem to result from the eyelid closure itself rather than removal of visual inputs. A second patient with progressive ataxia and palatal tremor (PAPT) demonstrated the same finding of palato-ocular or simply ocular synchrony, and the exact mechanism is not well understood. It can be seen in patients

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who have pendular nystagmus at baseline, or in patients with palatal tremor and inferior olivary hypertrophy who have no spontaneous nystagmus, as in these two patients. https://collections.lib.utah. edu/ark:/87278/s68665bw Video 5.26 Acquired pendular nystagmus (APN) multiple sclerosis (MS): This patient had a 15 year history of MS, and for the last 12 months, he experienced horizontal oscillopsia. On examination, there were central ocular motor abnormalities including gaze-evoked nystagmus, saccadic smooth pursuit, and hypermetric saccades which were attributable to his posterior fossa demyelinating disease. Additionally, there was horizontal pendular nystagmus, and this abated briefly with the termination of saccades and with blinks, both of which commonly suppress APN (albeit transiently). His vision was 20/100 OU with 0/10 HRR plates OU with temporal pallor OU. Because pendular nystagmus is commonly seen in MS patients, it has been suggested that the nystagmus might result from a prolonged response time for visual processing, supported by the fact that nystagmus is commonly more intense in the eye with poorer vision. However, pendular nystagmus doesn’t change with visual feedback removed, and inducing visual delays by itself is not capable of causing the oscillations seen in MS. Therefore, it’s likely that instability in the neural integrator (gaze holding machinery) plays a significant role in many cases, and his severe posterior fossa disease was likely to have contributed to neural integrator dysfunction. https://collections.lib.utah.edu/ ark:/87278/s6nc9v0z Video 5.27 Elliptical acquired pendular nystagmus (APN) in multiple sclerosis (MS): This patient with a 10+ year history of MS and bilateral optic nerve disease presented oscillopsia for 1 year, due to

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elliptical APN which seen on exam. The appearance of elliptical nystagmus is the result of out of phase horizontal and vertical (pendular) components, and can be especially visually debilitating. She had a variety of posterior fossa lesions on MRI, and there was mild improvement with gabapentin. https://collections.lib.utah.edu/ ark:/87278/s6qn9w2n Video 5.28 Elliptical acquired pendular nystagmus (APN) of unknown etiology suppressed by blinks and saccades: This is a 70-year-old man who experienced the gradual onset of oscillopsia over weeks about 3 months prior to this video recording. Examination demonstrated elliptical pendular nystagmus which was atypical for infantile nystagmus or oculopalatal tremor (no palatal tremor on exam, and no inferior olivary hyperintensity on MRI). The remainder of the ocular motor and neurologic exam was normal. Contrastenhanced MRI months prior was normal. Consistent with APN, the movements briefly suppressed following blinks, and suppressed to a more significant degree following saccades. One theory for APN is that it is due to an unstable neural integrator. In this case, blinking and saccades may serve to reset this unstable system, albeit transiently. This patient remained stable and work-up remained unremarkable for at least 6 months. https://collections.lib.utah.edu/ark:/87278/ s6673nxw Video 5.29 Monocular horizontal acquired pendular nystagmus in multiple sclerosis (MS): Seen here are two patients, both with MS and monocular (OS) horizontal pendular nystagmus causing monocular oscillopsia. The first patient seen in the video has normal afferent function and no evidence of optic nerve disease in either eye, while the second patient has severe OS>OD optic nerve

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disease related to multiple episodes of optic neuritis (there was also a slight torsional pendular nystagmus component). Although rare, when APN occurs it is typically due to MS (or oculopalatal tremor), it has been suggested that the nystagmus might result from a prolonged response time for visual processing, supported by the fact that nystagmus is commonly more intense in the eye with poorer vision. However, APN doesn’t change with visual feedback removed, and inducing visual delays by itself is not capable of causing the oscillations seen in MS. Therefore, it’s likely that instability in the neural integrator (gaze holding machinery) also plays a significant role in many cases. Explanations for monocular pendular nystagmus in these patients includes 1) ipsilateral afferent dysfunction or 2) perhaps within the unstable neural integrator, certain monocular-projecting cell populations are preferentially damaged. https://collections.lib.utah.edu/ark:/87278/s6q852cf Video 5.30 The appearance of infantile nystagmus in adults: Seen here are two adult patients with infantile nystagmus demonstrating characteristic features including: mixed pendular and jerk nystagmus (usually gaze-evoked) waveforms; nystagmus is horizontal even in vertical gaze; nystagmus damps with convergence; strabismus and a latent nystagmus component (common but not always present); association with albinism. Also, there is often a null point where nystagmus is minimal, and optokinetic nystagmus may be in the opposite direction of what would be expected given the direction of an optokinetic stimulus. https://collections.lib.utah. edu/ark:/87278/s67693mg Video 5.31 Common ocular motor and neurologic signs in progressive supranuclear palsy (PSP): Seen in this video are convergence insufficiency (frequent closure of the right eye to minimize diplopia),

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supranuclear gaze palsy (with sparing of the vertical vestibulo-ocular reflex), saccadic smooth pursuit and VOR suppression, hypometric horizontal saccades, square wave jerks, astonished facies with eyelid retraction, procerus sign, and the applause sign. https://collections.lib.utah.edu/ ark:/87278/s60p4nv0 Video 5.32 Saccadic intrusions and oscillations with an intersaccadic interval: Seen here are patients with saccadic intrusions that have intersaccadic intervals. When square wave jerks are prominent or when they interfere with visual fixation, neurodegenerative conditions should be considered, mainly those involving the posterior fossa (e.g., cerebellar degeneration, tumors) and the basal ganglia (e.g., progressive supranuclear palsy, Parkinson’s disease). Macrosaccadic oscillations are often associated with significant saccadic hypermetria due to cerebellar pathology, which was true of the last patient in this video. https://collections.lib.utah. edu/ark:/87278/s6gr0mmz Video 5.33 Ocular bobbing: This patient with hepatic encephalopathy developed abnormal eye movements consistent with ocular bobbing. Head CT did not show any acute changes. Ocular bobbing almost always localizes to the pons, although cerebellar pathology has also (rarely) been identified as a cause. Typical bobbing consists of rhythmic, downward jerks followed by a slower return to primary position. Horizontal eye movements are usually absent. Other patterns may be seen include: atypical bobbing, which is similar to typical bobbing, but with some residual horizontal gaze; pretectal V-pattern pseudo-bobbing, which consists of downward and convergent jerks with a slow return to primary gaze (usually related to obstructive hydrocephalus; reverse bobbing, which consists of a rapid upward jerks with a slow return

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to primary position; ocular dipping or inverse bobbing, which consists of slow downward movements over 2 seconds, remaining in downgaze for 2–10 seconds followed by a rapid movement upward to primary gaze; converse bobbing, which consists of an initial slow upward movement over 1–5 seconds, remaining in upgaze for 1–10 seconds followed by a rapid movement downward to primary gaze. (Video courtesy of Dr. Stephen Reich) https://collections.lib.utah.edu/ark:/87278/ s6vx45c3 Video 5.34 Post-infectious ocular flutter and myoclonus syndrome: This patient presented with oscillopsia following a viral illness. She described being easily startled, with “shakiness” of the head/neck and body. She had myoclonus and ocular flutter (no intersaccadic interval), with the latter especially evident following saccades. Convergence and gentle eyelid closure are other ways to provoke flutter or opsoclonus. https://collections.lib.utah. edu/ark:/87278/s6fr3jwj Video 5.35 Opsoclonus provoked by convergence: This patient experienced a parainfectious opsoclonusmyoclonus syndrome. Opsoclonus was intermittently evident in primary position, but was consistently provoked by convergence. Occasionally, opsoclonus (back-to-back saccades in horizontal, vertical, torsional planes without an intersaccadic interval) or ocular flutter (in the horizontal plane only) can be subtle or even difficult to distinguish from high frequency jerk nystagmus. However, these saccadic oscillations can be provoked with certain maneuvers such as eyelid closure (i.e., observing the corneal bulge under eyelids), following voluntary saccades, or with convergence. The underlying pathophysiology of opsoclonus/flutter is thought to relate to one or more of the following: heightened membrane

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excitability of the glutaminergic excitatory burst neurons (EBN); increasing firing when EBNs are released from inhibitory release from omnipause cells (which inhibit burst neurons during fixation), referred to as post-inhibitory rebound; decreased glycinergic (omnipause cell) inhibition. https:// collections.lib.utah.edu/ark:/87278/s6b02t5j Video 5.36 Voluntary ocular flutter: This patient experienced intermittent complaints of horizontal oscillopsia for 1 year. On examination, all classes of eye movements were normal, and neurologic examination was normal. MRI of the brain had been performed previously and was normal. When viewing any visual target at near, rapid horizontal back-to-back saccades without a clear intersaccadic interval were seen. The flutter-like movements only occurred with a convergence effort, and miosis was noted as well. They could only be sustained for several seconds at a time and voluntary flutter was diagnosed. https://collections. lib.utah.edu/ark:/87278/s6t18rxj Video 5.37 Superior oblique myokymia (SOM): This patient presented with episodes of monocular oscillopsia and vertical diplopia due to right SOM. The primary action of the superior oblique (SO) is incycloduction, which generated the quick phase of these movements resulting in oscillopsia OD. The secondary action of the SO is depression, which was responsible for a right hypotropia resulting in binocular vertical diplopia. https://collections.lib. utah.edu/ark:/87278/s69w3q5b Video 5.38 Prominent monocular elliptical pendular nystagmus in multiple sclerosis (MS): This is a patient who experienced bilateral attacks of optic neuritis (OS>OD) decades prior, was subsequently diagnosed with MS, and more recently experienced monocular oscillopsia due to elliptical pendular nystagmus in the left eye only. Even with ophthal-

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moscopy OD, there was no trace of nystagmus. https://collections.lib.utah.edu/ark:/87278/s6352s3s Video 5.39 Superior oblique myokymia (SOM) as seen with videooculography and Frenzel goggles: Patients with superior oblique myokymia (SOM) commonly present with complaints of monocular oscillopsia and/or vertical diplopia, which are related to the primary and secondary actions of the SO (incycloduction and depression, respectively). In many cases, SOM represents a neurovascular compression syndrome involving the 4th cranial nerve, although irritation by a compressive mass lesion is also possible. Additionally, the clinician should consider SOM in any patient complaining of transient visual symptoms or blurriness that last for 1 to the right mainly due to goggle slippage during the vHIT. This may have increased the gain on the impaired side as well. With horizontal head-shaking and vibration, the baseline RBN increased substantially. Seen in the video is the vibration-induced RBN. Skull vibration induces nystagmus with unilateral vestibular loss (slow phase toward the paretic ear) that is time-locked to the vibratory stimulation. It also beats in the same direction regardless of whether the right or left mastoid is stimulated, or whether the vibrator is placed over the vertex. This is because the stimulus is effectively transmitted to both labyrinths. Since vibration is a stimulus that excites semicircular neurons, when vestibular asymmetry exists (e.g., left peripheral vestibulopathy due to vestibular neuritis), the unaffected (right) side will be activated normally while the affected (left) side will not. This will create a slow phase drift toward the paretic ear as in this patient with a contralesional nystagmus https://collections. lib.utah.edu/ark:/87278/s66t541n

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Head-shaking-induced nystagmus in a patient with previous vestibular neuritis: This patient experienced the abrupt onset of imbalance, dizziness and left-sided hearing loss 4 months prior to this examination. He was found to have herpetic vesicles in the left external auditory canal and diagnosed with Ramsay Hunt syndrome. On exam (4 months after the onset), there was an abnormal head impulse test (HIT) to the left side, and with fixation-removed, there was very mild right-beating nystagmus. However, following 15 seconds of 2–3 Hz horizontal head-shaking, there was robust right-beating nystagmus. Video HIT showed left-sided vestibular loss with low gains ( i­nhibitory pattern of nystagmus (excitatory in this case with contralesional, leftward slow phase, and ipsilesional, rightward

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fast phases). MRI demonstrated a right-sided vestibular schwannoma which explained both the right hypofunction (LBN with vibration), and the excitatory pattern (RBN) of her hyperventilationinduced nystagmus https://collections.lib.utah.edu/ details?id=1213447 Video 6.14 Hyperventilation-induced downbeat nystagmus in a cerebellar disorder: This patient presented with a chronic progressive cerebellar degeneration of unclear etiology (worsening over at least 10 years) characterized by gait and limb ataxia, gaze-evoked nystagmus, saccadic pursuit and vestibulo-ocular reflex suppression, an esotropia greater at distance, along with very mild downbeat nystagmus (DBN), mainly seen with the ophthalmoscope. This constellation of ocular motor signs localizes well to the flocculus/paraflocculus. Following 40 seconds of hyperventilation, which induces alkalosis and alters intra- and extracellular calcium concentrations, she demonstrated prominent DBN. This finding has been described in patients with cerebellar pathology, and has been theorized to relate to sensitivity of cerebellar voltage-gated calcium channels (e.g., P/Q-type or other abnormal ion channels) to the alkalosis induced by hyperventilation https://collections.lib. utah.edu/ark:/87278/s6g77x3f Video 6.15 The virtual (telemedicine) vestibular examination: This video demonstrates one approach to performing the vestibular examination virtually in a normal subject https://collections.lib.utah.edu/ ark:/87278/s6sj78fz. (Video created with the assistance of Dr. Olwen Murphy) Video 6.16 Evaluating auditory function with Rinne and Weber tests: The Rinne test is an assessment of auditory thresholds to air and bone conduction of sound. The Weber test is a comparison of bone conducted sound of either ear. Conductive hearing

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loss results in a loss of air conducted greater than bone conducted sound, whereas sensorineural hearing loss results in the loss of both air and bone conducted sound. Peripheral vestibular disease affecting the labyrinth or the eighth cranial nerve can be associated with sensorineural hearing loss. In these cases, the sensitivity to air conduction will remain greater than to bone conduction. Weber will lateralize away from the side of sensorineural hearing loss. As an example, destruction of the right labyrinth (e.g., bacterial labyrinthitis) will cause decreased hearing in the right ear, and air conduction will be greater than bone conduction in the right (affected) and left (unaffected) ears. Weber will lateralize to the left (unaffected) ear. In the case of superior semicircular canal dehiscence (SCDS), there may be increased sensitivity to bony transmission of sound through a (third mobile window) as well as conductive hearing loss, with bone conduction greater than air conduction and Weber lateralizing to the side of the dehiscence. A bedside test used for SCDS that highlights this increased sensitivity to bony transmission of sound involves placing a tuning fork on the malleolus, and in patients with SCDS, it may be heard in the affected ear https://collections.lib.utah.edu/ details?id=1307288. (Video and legend created with the assistance of Dr. Tony Brune and Justin Bosley) Video 6.17 A “peripheral” HINTS exam in acute vestibular neuritis: This patient presented with the acute vestibular syndrome, and on examination, had left-beating nystagmus and an abnormal head impulse test to the right (a catch-up saccade can be seen as her head is moved quickly to the right—her eyes move with the head to the right for a split second given loss of the vestibulo-ocular reflex, and there is a catch-up saccade back to the left so

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she can refixate on the target) are both explained by acute loss of vestibular function on the right side (right-sided vestibular neuritis). There was no skew deviation and no hearing loss. As the vestibular neuritis decreases the baseline tonic activity of the affected (right) eighth cranial nerve, there is relative hyperactivity involving the left eighth cranial nerve, which leads to the false perception of leftward head turning. In response, rightward slow phases are generated, which represents the slow (pathologic) phase of her nystagmus. The rightward fast phase is the position reset mechanism and creates the rhythmic slow and fast phases. Her left-beating nystagmus (LBN) is unidirectional—i.e., it remains LB in all directions of gaze—and follows Alexander’s law where the nystagmus increases in intensity in the direction of the fast phase (to the left in this case). If unidirectional nystagmus is seen beating to the left, an abnormal head impulse to the right must be seen to reassure the clinician that this is a peripheral etiology. Additionally, a skew deviation must be absent, and unilateral hearing loss (ipsilateral to the side of the unilateral vestibular loss) should be absent. When acute unilateral hearing loss is present, labyrinthine ischemia should be considered, which is the rationale for the 4-step HINTS+ exam (Head Impulse, Nystagmus, Test of Skew, + evaluation of auditory function). This patient had a “peripheral” HINTS pattern, and MRI (while not necessary, was already completed) was unrevealing https://collections.lib.utah.edu/ark:/87278/ s6546h55s Video 6.18 A “central” HINTS exam in an acute lateral pontine/middle cerebellar peduncle (MCP) demyelinating lesion: This patient presented with vertigo, diplopia and mild left facial weakness (not seen in the video). On exam, there was right-beat-

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ing nystagmus (RBN) in primary gaze that increased in right gaze (in accordance with Alexander’s law), and the RBN stayed unidirectional, but lessened, in left gaze. This is a pattern of nystagmus that is usually peripheral, especially when nystagmus increases when fixation is removed. However, this can also be central, especially when there is no change in nystagmus with removal of fixation. There was a positive or abnormal head impulse test (HIT) with leftward impulses of the head, which is also usually a sign of peripheral pathology. With alternate cover testing, there was a right hyperdeviation, which was comitant and associated with a left head tilt and leftward ocular counterroll (top poles of the eyes toward the left ear). Taken together, this was thought to be related to utricle pathway pathology causing an ocular tilt reaction, with the skew deviation responsible for his diplopia. Using HINTS (Head Impulse, Nystagmus, Test of Skew), the presence of a skew deviation should lead the examiner to assume a “central” etiology until proven otherwise, despite the “peripheral” appearance of the nystagmus and HIT. It is important to note that while unidirectional nystagmus and an abnormal HIT can suggest a peripheral etiology, either one can be seen with a central etiology. A skew deviation may result from peripheral utricle pathology (at the level of labyrinth or eighth cranial nerve—e.g., post acoustic neuroma resection), although generally these “peripheral” skews tend to be small in magnitude and shortlived. Regardless, since peripheral skews are rare, when present, a central etiology must first be ruled out. This patient was found to have a demyelinating lesion (leading to the diagnosis of MS) in the region of the MCP/root entry zone of cranial nerves 7 and 8. MCP lesions are common in MS,

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and patients typically present with vertigo and nystagmus. The ocular tilt reactions seen in demyelinating and ischemic lesions involving the MCP are almost always ipsiversive as it was in this case. Finally, there was a mild left lower motor neuron facial palsy, which along with the abnormal HIT is suggestive of a root entry zone localization if due to a central etiology. Or, an inflammatory, neoplastic or infectious process (e.g., herpes zoster/Ramsay Hunt syndrome) causing multiple cranial neuropathies should be considered when peripheral. Our patient’s RBN and abnormal HIT to the left could have been explained by a left eighth cranial neuropathy, although the prominent skew deviation would have been atypical. In this patient’s case, possible localizations for the abnormal HIT to the left include (in order of most to least likely): root entry zone of CN 7/8; intraaxial eighth nerve fascicle; vestibular nucleus complex. Had this patient suffered a stroke, left labyrinthine ischemia (due to AICA-territory ischemia) would be another explanation for abnormal HIT on the left and unidirectional RBN, although ipsilesional hearing loss is generally present due to cochlear ischemia https://collections.lib.utah.edu/details?id=1291717. (Video courtesy of Dr. Tzu-Pu Chang) Video 6.19 A “peripheral” skew deviation causing vertical diplopia in acute vestibular neuritis—a rare occurrence: This hypertensive man developed acute onset continuous vertigo and presented to the Emergency Department (ED) after several hours of symptoms. He was noted to have spontaneous nystagmus and had a normal brain MRI within the first 24 hours. The first portion of the video was recorded during his hospitalization, and if his head was in any position other than left ear down, he experienced severe vertigo and nausea. Nystagmus

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was left-beating (LB) with a torsional component (top poles beating toward left ear), the LB lessened in right gaze, remained LB in vertical gaze, and increased in left gaze (in accordance with Alexander’s law). Nystagmus also increased in intensity with fixation removed, which combined with his unidirectional and mixed horizontal-torsional nystagmus, were features suggestive of a peripheral vestibular localization (but could still be seen with a central disorder). The patient was extremely symptomatic but allowed the examiner to perform one single head impulse test (HIT), which was abnormal to the right side (i.e., when the head was moved quickly to the right, the eyes initially moved with the head to the right due to a deficient vestibulo-ocular reflex involving the right horizontal canal, and this was followed by a catch-up saccade back to the left to the examiner’s nose). The patient also experienced binocular vertical diplopia, and a right hypotropia was apparent in primary gaze with cover-uncover testing, which was consistent with a skew deviation. Finally, while there was no clear ocular lateropulsion to the right while upright, rightward horizontal gaze deviation was noted on the MRI. However, this finding does not predict a central localization. Examination at 1 week showed much improved LB nystagmus, although the right hypotropia persisted. This was measured as 4 prism diopters, and was constant in right, left, up, down gaze and with right and left head tilt. Fundus photos showed a mild ocular counterroll with top poles toward the right ear, which paired with his skew deviation (right hypotropia) suggested a partial ocular tilt reaction (in the absence of a clear head tilt) from utriculoocular pathway (or graviceptive-ocular motor pathway [mediating inputs from vertical semicircular canals and the utricle]) involvement. His HIT to

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the right remained abnormal and video HIT demonstrated low gains and overt saccades in the planes of the right horizontal and anterior canals, both of which are innervated by the superior division of the vestibular nerve. The utricle is also innervated by the superior division of the vestibular nerve, and while a skew is possible in a peripheral vestibular disorder, this is rare, and a peripheral skew deviation tends to be small and transient. Although right-sided vestibular neuritis with a “peripheral” skew deviation was suspected as the cause, given the possibility of a false-negative MRI as an inpatient (MRI was done within 24 hours of symptom onset), a second MRI with and without contrast was ordered. This was normal, and the diagnosis of right vestibular neuritis was confirmed. The patient improved significantly over the following months. Of note, patients with vestibular neuritis tend to have more intense nystagmus and vertigo with the bad (affected) ear down, which is why the patient maintained a left ear down position throughout most of his hospitalization https://collections.lib.utah.edu/ark:/87278/ s6ht70fx Video 6.20 A “central” HINTS exam in a lateral medullary syndrome: This patient presented with the acute vestibular syndrome in addition to vertical diplopia. Examination demonstrated several aspects of the left lateral medullary (Wallenberg) syndrome to an acute demyelinating lesion: ipsilesional (left) ocular lateropulsion (ipsipulsion, as well as hypermetric saccades to the left, hypo to the right, not seen in the video), ipsilesional (left) hypotropia from skew deviation, and subtle right-beating nystagmus (not seen in the video). There was also an abnormal head impulse test, which although typically seen as a “peripheral” sign, can be central in origin as in this case (due to left vestibular

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nucleus involvement) https://collections.lib.utah. edu/details?id=187730 Video 6.21 Gaze-evoked and rebound nystagmus in a cerebellar syndrome: This patient presented with a cerebellar degeneration of unknown etiology, and had a variety of cerebellar ocular motor findings, including gaze-evoked nystagmus with rebound (e.g., left-beating nystagmus in left gaze, transitioning to right-beating when he looks back to primary), saccadic smooth pursuit and failure of VOR suppression, and saccadic dysmetria. In some cases, the distinction between physiologic end point nystagmus (EPN) and pathologic gazeevoked nystagmus (GEN) can be difficult. Findings suggestive of EPN include relatively small amplitude, fatigues, abates in ¾ eccentric position (far enough in that both eyes can view the target), and the absence of rebound nystagmus (occasionally, normal people may have a beat or two), often with a horizontal-slight torsional (toward the ipsilateral ear) component. Findings suggestive of GEN include larger amplitude, doesn’t fatigue, still present in ¾ eccentric position (far enough in that both eyes can view the target), and presence of rebound or centripetal nystagmus. Centripetal nystagmus is a nystagmus in eccentric gaze, in which the fast phase beats “centripetally” toward primary gaze https://collections.lib.utah.edu/ ark:/87278/s6089dz6 Video 6.22 Posterior canal BPPV—nystagmus provoked by the Dix—Hallpike maneuver: When the patient was moved into the right Dix–Hallpike maneuver, after a brief latency, upbeat-torsional (toward the lowermost or affected [right] ear) nystagmus was seen. The patient was then treated with an Epley maneuver, and was later rechecked with the right Dix–Hallpike maneuver. At that point, the maneuver did not provoke nystagmus and vertigo,

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demonstrating that the Epley maneuver had been successful in moving the otoconia out of the right posterior canal. Examination features in this case that reassure the examiner that they are dealing with BPPV (as opposed to a central positional nystagmus variant) include the following: fatigability (not shown here, but with repetitive Dix–Hallpike maneuvers, the vertigo and nystagmus become less and less prominent); a brief latency between Dix–Hallpike and the onset of vertigo/ nystagmus (as the otoconia moves to the most dependent part of the canal during Dix–Hallpike, it drags the endolymph with it, and this endolymph flow deflects the cupula causing vestibular excitation—because deflection of the cupula does not occur instantaneously during the Dix–Hallpike, a brief latency is the consequence); a crescendodecrescendo nystagmus; the expected pattern of nystagmus is observed given the laterality of the specific Dix–Hallpike maneuver performed (e.g., right Dix–Hallpike produces nystagmus with an upbeat component and with a torsional component, with the top poles beating toward the lowermost/ affected [right] ear); vertigo and nystagmus respond to properly performed repositioning (Epley or other) maneuvers https://collections.lib. utah.edu/ark:/87278/s6s79d1w. (Video courtesy of Dr. Marco Mandala) Video 6.23 Posterior canal BPPV—reversal of nystagmus when going from Dix–Hallpike to seated: This is a patient with typical posterior canal (PC) benign paroxysmal positional vertigo (BPPV), which was provoked by the Dix–Hallpike maneuver. When the patient is moved into the right Dix–Hallpike maneuver, after a brief latency, upbeat-torsional (toward the lowermost or affected [right] ear) nystagmus is seen. There is a crescendo-decrescendo pattern and nystagmus and vertigo resolve.

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With the right Dix–Hallpike maneuver, the right PC is stimulated by movement of the otoconial particles and an excitatory pattern of nystagmus results. In this case, the right superior oblique and left inferior rectus muscles are stimulated which initiates the downward and torsional (toward left ear) slow phase. An upbeat-torsional (toward right ear) fast phase is then generated until the otoconia fall to the most dependent portion of the PC and there is no longer flow of endolymph or deflection of the cupula. However, when the patient is brought from right Dix–Hallpike back to a seated position, the otoconia move in the opposite (inhibitory) direction, and a downbeat-torsional nystagmus is then seen https://collections.lib.utah. edu/details?id=1281864. (Video courtesy of Dr. Marco Mandala) Video 6.24 Posterior canal BPPV—treatment with Epley and Semont maneuvers: (1) Epley/canalith repositioning maneuver (CRP)—to treat right posterior canal (PC)-BPPV (each position maintained for at least 30 seconds or until nystagmus and/or vertigo cease): (a) First the patient is placed in the long-sitting position, (b) The head is rotated 45 degrees to the right, (c) Then the patient is lowered quickly into the supine position with the head in 30 degrees of cervical extension, (d) Then the patient’s head is 90 degrees to the left, (e) The patient is rolled into a left-side lying position with the head maintained in 45 degrees of rotation to the left so that the head is facing the floor, (f) Then the patient sits up slowly with the head still facing down toward the floor and rotated 45 degrees to the left, (g) Slowly, the head is moved back to neutral. (2) Semont maneuver—to treat right posterior canal (PC)-BPPV: (a) The patient is placed in a seated position on the treatment table, (b) The head is turned 45 degrees to the left, (c) The patient is

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quickly brought into a right side-lying position which is maintained for 1 minute, (d) The patient is then guided quickly from right to left side-lying positions within 1.5 seconds without stopping in the center, (e) The head is maintained in 45 degrees of leftward rotation so that the head is facing the ground and this is position is held for 1 minute, (f) The patient is guided into a seated position slowly with the head maintained in 45 degrees of leftward rotation, (g) The head is moved slowly back to neutral https://collections.lib.utah.edu/ details?id=187680. (Video created with the assistance of Drs. Michael Schubert, Amir Kheradmand, and Laura Morris) Video 6.25 Horizontal canal BPPV (geotropic variant)— nystagmus provoked by the supine roll test: This is a patient with the geotropic (nystagmus beating toward the ground) variant of left horizontal canal (HC) benign paroxysmal positional vertigo (BPPV). In a patient with geotropic (nystagmus beating toward the ground) HC BPPV, by rapidly moving from a sitting to a supine position with the head straight, particles will move away from the ampulla to the most dependent portion of the canal, resulting in an ampullofugal flow and nystagmus that beats away from the affected side. If otoconia are located close to the ampulla as they typically are with apogeotropic HC BPPV, particles will move toward the cupula and provoke an ampullopetal flow and nystagmus that beats toward the affected side. The right-beating nystagmus (RBN) when going from upright to supine position in this patient with geotropic HC BPPV suggested that the left HC was involved. With supine roll testing (where the head is rolled 90 degrees to the right and to the left), there was weaker right-beating nystagmus (RBN) with right roll test, and stronger LBN with left roll test—this also suggests that the

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left HC was involved. Since the otoconia are typically located in the most dependent part of the canal in geotropic HC BPPV, when the left side is affected, rotating the head 90 degrees to the left allows particles to move toward the ampulla, producing an ampullopetal flow which is an excitatory stimulus—i.e., a robust LBN will result. Rotating the head 90 degrees to the right allows particles move away from the cupula (ampullofugal), which is an inhibitory stimulus—i.e., a weaker RBN will result. In contrast, supine roll testing in apogeotropic HC BPPV results in nystagmus that is stronger toward the unaffected side (e.g., stronger LBN with right roll compared to RBN with left roll suggests left HC involvement). The opposite is true of the geotropic variant, where nystagmus is stronger with the affected ear down (e.g., left ear was the affected side, and left roll test demonstrated stronger nystagmus as compared to right roll test). Or more simply, when dealing with geo- or apogeo-HC BPPV, the nystagmus is more intense when beating toward the affected ear https://collections.lib.utah.edu/ details?id=1281862. (Video courtesy of Dr. Marco Mandala) Video 6.26 Horizontal canal BPPV (apogeotropic variant)—nystagmus provoked by the supine roll test: This is a patient with the apogeotropic (nystagmus beating toward the sky) variant of right horizontal canal (HC) benign paroxysmal positional vertigo (BPPV). In a patient with geotropic (nystagmus beating toward the ground) HC BPPV, by rapidly moving from a sitting to a supine position with the head straight, particles will move away from the ampulla to the most dependent portion of the canal, resulting in an ampullofugal flow and nystagmus that beats away from the affected side. If otoconia are located close to the

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ampulla as they typically are with apogeotropic HC BPPV, particles will move toward the cupula and provoke an ampullopetal flow and nystagmus that beats toward the affected side. The right-beating nystagmus (RBN) when going from upright to supine position in this patient with apogeotropic HC BPPV suggested that the right HC was involved. With supine roll testing (where the head is rolled 90 degrees to the right and to the left), there was weaker left-beating nystagmus (LBN) with right roll test, and stronger RBN with left roll test—this also suggests that the right HC was involved. Since the otoconia are typically located close to the ampulla with apogeotropic HC BPPV, when the right side is affected, rotating the head 90 degrees to the left allows particles to move toward the cupula (ampullopetal), which is an excitatory stimulus—i.e., a robust RBN will result. Rotating the head 90 degrees to the right allows particles move away from the cupula, which is an inhibitory stimulus (ampullofugal)—i.e., a weaker LBN will result. In contrast, supine roll testing in geotropic nystagmus results in nystagmus that is stronger toward the affected side (e.g., stronger RBN with right roll compared to LBN with left roll suggests right HC involvement). The opposite is true of the apogeotropic variant, where nystagmus is weaker with the affected ear down (e.g., right ear was the affected side, and right roll test demonstrated weaker nystagmus as compared to left roll test). Or more simply, when dealing with geo- or apogeoHC BPPV, the nystagmus is more intense when beating toward the affected ear https://collections. lib.utah.edu/details?id=1281861. (Video courtesy of Dr. Marco Mandala) Video 6.27 Horizontal canal BPPV (apogeotropic variant)—pseudo-spontaneous nystagmus and localization with bow and lean: This is a 70-year-old

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woman presenting to the Emergency Department with positional vertigo that was determined to be due to the apogeotropic variant of right horizontal canal (HC) benign paroxysmal positional vertigo (BPPV). When her head is in a neutral position with the head in axis with the trunk, there is a pseudo-spontaneous nystagmus. The term “pseudospontaneous” is used because the nystagmus is created by otoconia within the HC sliding down to the most dependent portion of the canal, owing to its orientation—i.e., the most anterior portion of the HC is at about 20–30 degree higher than the posterior portion. Therefore, some patients with HC-BPPV may have an unprovoked “pseudo-spontaneous” nystagmus (unrelated to damage to the vestibular system) when the head is in a neutral position. In the case of right apogeotropic HC BPPV, leaning the head backward (the lean portion of the bow and lean test) will cause otoconial particles to slide posteriorly in an ampullopetal (excitatory) direction, which will generate a (strong) slow phase to the left and a fast phase to the right (right-beating nystagmus toward the affected ear). Because the orientation of the HC is in a similar (but less vertical) position with the head in axis with the trunk, for the same reasons, the pseudo-spontaneous nystagmus will be right-beating (toward the affected ear). Bowing the head forward (the bow portion of the bow and lean test) will cause otoconial particles to slide anteriorly in an ampullofugal (inhibitory) direction, creating a (weak) slow phase to the right and a fast phase to the left (left-beating nystagmus toward the healthy ear) https://collections.lib.utah.edu/ ark:/87278/s68h2wk9. (Video created with the assistance of Dr. Ari Shemesh) Video 6.28 Horizontal canal BPPV—treatment with the BBQ roll maneuver: To treat right horizontal

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canal (HC)-BPPV (each position maintained for at least 30 seconds or until nystagmus and/or vertigo cease): (a) First the patient is placed in the longsitting position, (b) Then in a supine position with the head elevated 30 degrees, (c) Then the patient’s head (or whole body) is rotated 90 degrees to the right, (d) Then the patient’s head (or whole body) is rotated back to neutral, (e) Then the patient’s head (or whole body) is rotated 90 degrees to the left, (f) Then the patient’s whole body is rotated into a prone position, (g) To move the patient out of the BBQ roll maneuver, the patient should be rolled another 90 degrees so that the patient’s head (or whole body) is rotated 90 degrees to the right, (h) Finally, the patient is brought back into the long-sitting position https://collections.lib.utah. edu/details?id=187682. (Video created with the assistance of Drs. Michael Schubert, Amir Kheradmand, and Laura Morris) Video 6.29 Horizontal canal BPPV—treatment with the Gufoni maneuver: (1) To treat right apogeotropic (beating toward the sky with right ear down and with left ear down—e.g., left beating nystagmus with right supine roll test or with right ear down; right beating nystagmus with left supine roll test or with left ear down) horizontal canal (HC) BPPV: (a) The patient is placed in a seated position on the treatment table, (b) With the head in a neutral spine orientation, the patient is quickly moved onto the side ipsilateral to the weaker nystagmus (to the right side in the right apogeotropic variant) and this position is held for 2 minutes, (c) The patient’s head is rotated 45 degrees toward the ceiling and this position is held for 2 minutes, (d) Finally, the patient is brought back into a seated position. (2) To treat right geotropic (beating toward the ground with right ear down and with left ear down—e.g., right beating nystagmus with right supine roll test

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or with right ear down; left beating nystagmus with left supine roll test or with left ear down) horizontal canal (HC) BPPV: (a) The patient is placed in a seated position on the treatment table, (b) With the head in a neutral spine orientation, the patient is quickly moved onto the side ipsilateral to the weaker nystagmus (to the left side in the right geotropic variant) and this position is held for 2 minutes, (c) The patient’s head is rotated 45 degrees toward the ground and this position is held for 2 minutes, (d) Finally, the patient is brought back into a seated position https://collections.lib. utah.edu/ark:/87278/s6q55z98. (Video created with the assistance of Drs. Michael Schubert, Amir Kheradmand, and Laura Morris) Video 6.30 Central positional nystagmus due to a posterior fossa tumor—when to worry: This patient presented with positional dizziness and nystagmus, and examination with video Frenzel goggles and removal of fixation demonstrated the following: when upright, there was no nystagmus; in bow (head flexed forward), there was down- and right-beating nystagmus (RBN); in lean (head extended back) there was upbeat- and left-beating nystagmus (LBN); when supine, there was initially RBN, which transitioned slowly to upbeat nystagmus and finally LBN; in right supine roll test (head rotated 90 degrees to the right with head slightly flexed) there was initially LB apogeotropic nystagmus (i.e., beating away from the earth) that slowed over seconds and transitioned to RBN; and in left supine roll test (head rotated 90 degrees to the left), there was initially RB apogeotropic nystagmus that slowed and gradually transitioned to LBN (the video cuts off before this can be seen). MRI was obtained, which demonstrated a tumor originating in the fourth ventricle, which was eventually diagnosed as a subependymoma. When positional

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vertigo and nystagmus are central in origin, apogeotropic positional nystagmus is usually related to pathology involving the nodulus/uvula, geotropic positional nystagmus is usually related to pathology involving the paraflocculus (tonsil), and positional downbeat nystagmus is often caused by bilateral flocculus impairment. Central apogeotropic nystagmus is much more common than central geotropic nystagmus. Other ocular motor abnormalities are usually present and/or there is gait imbalance, but rarely central positional nystagmus/ vertigo occurs in isolation. In this particular case, neuroimaging was indicated due to the following red flags: (1) The nystagmus was not in the plane of a particular semicircular canal and changed unpredictably with various head position (e.g., bow and lean caused down- and upbeat nystagmus, respectively); (2) The typical crescendo-decrescendo pattern of upbeat-torsional nystagmus triggered by Dix–Hallpike, which would suggest PC BPPV (the most common type of BPPV, especially common following head trauma), was lacking; (3) Repeated, properly performed Epley maneuvers (treatment for PC BPPV) did not resolve the symptoms or nystagmus; (4) Vomiting persisted even as positional vertigo improved; (5) Mild gaze-evoked nystagmus was present laterally (regardless of the otherwise normal neurologic exam), which suggests dysfunction of the neural integrators—nucleus prepositus hypoglossi-medial vestibular nucleus complex or its connections with the cerebellar flocculus/paraflocculus; (6) While there was apogeotropic nystagmus with supine roll test, which could suggest HC BPPV, the nystagmus occurred without a clear latency, and quickly transitioned to nystagmus in the opposite direction. The mechanism for central positional apogeotropic nystagmus may relate to impaired ability of the

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vestibulocerebellum (mainly nodulus/uvula) to accurately estimate the direction of gravity due to abnormal otolithic (utricular) inputs. This can result in a directional error away from true earth vertical, and this bias is thought to cause erroneous head rotation signals that lead to pathological nystagmus https://collections.lib.utah.edu/ark:/87278/ s6hj0x9w. (Video courtesy of Dr. Tzu-Pu Chang) Video 6.31 Anterior canal BPPV—nystagmus provoked in straight head-hanging position: Although the anterior canal (AC) variant of benign paroxysmal positional vertigo (BPPV) is rare, mainly owing to its orientation relative to gravity (which makes otoconial debris much less likely to enter it), it can occur. Because of the relatively para-sagittal orientation of the AC (more so than the posterior canal), in a patient with AC BPPV, nystagmus may be provoked by the right or left Dix–Hallpike maneuvers, as well as with straight head hanging, as it was in this particular patient. A right Dix–Hallpike maneuver will stimulate the right posterior canal (PC) as well as the left AC. This patient was diagnosed with left AC BPPV—left AC excitation causes stimulation of left superior rectus and right inferior oblique muscles, initiating an upward and torsional (toward right ear) slow phase. This generates downward-torsional (toward left ear) fast phases, as seen here. She was treated with repositioning maneuvers, but there was no response in the office. Her neurologic and ocular motor/vestibular examinations were otherwise unremarkable, and when she returned 1 week later, the positional nystagmus had spontaneously resolved. Alternatively, there are some patients who may have otoconia in the distal, non-ampullary arm of the PC. If this is the case, it may be possible to produce an inhibitory pattern of nystagmus, so that some cases labeled as AC BPPV may actual be an

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atypical variant of PC BPPV. This possibility could not be excluded in her case https://collections.lib. utah.edu/ark:/87278/s6hq7wmw. (Video courtesy of Dr. Marco Mandala) Video 6.32 Anterior Canal BPPV—treatment with the deep head hanging maneuver: Regardless of whether it is thought that the patient has right or left anterior canal (AC) involvement, the deep head hanging maneuver is performed in the same way. (a) First the patient is placed in the long-sitting position; (b) Then the patient is moved into a supine position with the head in at least 30 degrees of cervical extension; (c) Allow nystagmus and vertigo to resolve (at least 30 seconds); (d) Bring the head into cervical flexion with the chin touching the chest; (e) After 30 seconds the patient is brought back to a seated position with cervical flexion maintained; (f) The head is brought back into a neutral position https://collections.lib.utah.edu/ ark:/87278/s6fn4fv6. (Video created with the assistance of Drs. Michael Schubert, Amir Kheradmand, and Laura Morris) Video 6.33 Positional downbeat nystagmus due to a cerebellar degeneration: This patient experienced vertical oscillopsia for 6+ months, and on examination, was found to have very mild downbeat nystagmus (DBN) in primary gaze, with a slight increase in lateral gaze. She mainly complained of dizziness and oscillopsia when laying down. She was found to have significant provocation of her DBN with straight head hanging and in right and left Dix–Hallpike. Although positional downbeat nystagmus (pDBN) can be seen with the uncommon anterior canal variant of BPPV, usually it is seen with disorders of the cerebellum or cervicomedullary junction. When pDBN is seen in a patient with parkinsonism, multiple system atrophy should be a consideration. In this patient, the

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downbeat was in isolation, there was no cerebellar ataxia, and extensive evaluation was unrevealing. She had a dramatic response to 4-aminopyridine and remained stable over several years https:// collections.lib.utah.edu/ark:/87278/s66t3w9k Video 6.34 Positional nystagmus during an attack of vestibular migraine: A 50-year-old woman presented to clinic after experiencing multiple episodes of hours-long vertigo attacks that were associated with headache, photophobia, and phonophobia. She had a history of motion sickness and migraine headaches in her teenage years. She was diagnosed with vestibular migraine. She presented to the emergency department during a typical attack at which time video-oculography (VOG) recordings were performed. Video head impulse test was normal, and VOG (with removal of fixation) showed no spontaneous, gaze-evoked, or head-shaking-induced nystagmus. However, there was persistent positional (7 degree/second peak slow phase velocity) downbeat-torsional (top poles toward the right ear) nystagmus in right and left Dix–Hallpike, with milder downbeat-torsional nystagmus with straight head-hanging and prone positions. While her vertigo was continuous, head movements (including positional maneuvers) aggravated her vestibular symptoms rather than triggering them. It was felt that her positional nystagmus was “central”—not due to benign paroxysmal positional vertigo (BPPV)—for the following reasons: (1) nystagmus was not in the plane of a particular semicircular canal (e.g., no difference in the nystagmus vector with right versus left Dix–Hallpike), (2) there was no crescendo-decrescendo pattern to the nystagmus, (3) the nystagmus persisted for as long as the patient was kept in each position, (4) while downbeat-torsional nystagmus may represent

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List of Videos\Electronic Supplemental Materials (ESM)

anterior canal BPPV or apogeotropic posterior canal BPPV, her nystagmus did not behave as would be expected in either of these variants. A variety of patterns of nystagmus can be seen during vestibular migraine attacks including spontaneous horizontal, upbeat, or downbeat nystagmus, with positional nystagmus being especially common. Because she was otherwise in the midst of a typical vestibular migraine attack, it was felt that her nystagmus was also migrainous https://collections. lib.utah.edu/ark:/87278/s6f249xk Video 6.35 Spinocerebellar ataxia type 3 with gaze-evoked nystagmus and bilateral vestibular loss: This patient, with a known diagnosis of spinocerebellar ataxia type 3 (SCA 3), presented with severe imbalance and head movement-induced oscillopsia. On examination, she had (1) bilateral vestibular loss (BVL) demonstrated by bilaterally abnormal head impulse test (HIT, with corrective saccades and low gains seen bilaterally with bedside and video HIT), as well as (2) cerebellopathy demonstrated by gaze-evoked nystagmus and saccadic smooth pursuit. Her vestibulo-ocular reflex suppression (VORS) was nearly normal appearing because there was no VOR to suppress (given her BVL). SCA 3 is in the differential diagnosis of chronic, progressive imbalance due to BVL and cerebellopathy in addition to other SCAs (mainly 1, 4, 6, 25), as well as multiple system atrophy, superficial siderosis (also with bilateral hearing loss), CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome), and Friedreich’s ataxia among others https://collections.lib.utah.edu/ark:/87278/s60k7jb4 Video 6.36 Bilateral vestibular loss and head tremor causing a “pseudonystagmus”: This patient presented with complaints of imbalance, dizziness, and horizontal oscillopsia. On exam, she had a

List of Videos\Electronic Supplemental Materials (ESM)

Video 7.1

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high frequency, low amplitude (mainly horizontal) head tremor, and with ophthalmoscopy, the optic nerve was clearly oscillating back and forth at the same frequency as her head tremor, which was responsible for her horizontal oscillopsia. In her case, she also had bilateral vestibular loss demonstrated by abnormal head impulse testing in the planes of right and left horizontal canals (also in anterior and posterior canals, not seen in this video). If a patient with a head tremor has an impaired or absent vestibulo-ocular reflex (VOR), the eyes will move with the head with each head oscillation, and oscillopsia will result. The term “pseudonystagmus” has been used to indicate oscillopsia (not due to nystagmus) that results from the combination of bilateral vestibular loss and head tremor https://collections.lib.utah.edu/ ark:/87278/s62z4z8g Oculogyric crisis: This is a patient with neurolepticinduced oculogyric crisis. (Video courtesy of Dr. Stephen Reich) https://collections.lib.utah.edu/ ark:/87278/s6r53dvc

1

Preparing for the Exam

1.1

 quipment for the Afferent NeuroE Ophthalmology Bedside Exam

1.1.1 Vision • Near card (near) or Snellen chart or computer monitor (distance) • Reading glasses (+2.00 or +3.00)—for best corrected near ­acuity in a patient with presbyopia (who does not have their spectacles) • Pinhole—for best corrected acuity, to account for refractive error (can poke a hole in paper with a safety pin) • A red object can be presented to each eye individually to see if the red looks less bright or “desaturated” in one eye compared to the other. Two (identical) red objects can also be presented simultaneously in different visual hemifields or quadrants for color comparison when a subtle field defect is suspected • Striped ribbon, paper, flag/tape, drum for optokinetic nystagmus—can be helpful in some cases where functional vision loss is suspected Supplementary Information The online version of this chapter (https://doi. org/10.1007/978-­3-­030-­76875-­1_1) contains supplementary material, which is available to authorized users.

© Springer Nature Switzerland AG 2021 D. Gold, Neuro-Ophthalmology and Neuro-Otology, https://doi.org/10.1007/978-3-030-76875-1_1

1

1  Preparing for the Exam

2

• Amsler grid—when macular disease is present, metamorphopsia (wavy lines on the grid) is common (this can be easily printed out from the internet). This can also help characterize central field defects at the bedside • A transilluminator or penlight—to evaluate pupil reactivity and to look for a relative afferent pupillary defect (rAPD) • Direct ophthalmoscope or Panoptic with spare batteries for fundus exam • Short lasting dilating drops (typically phenylephrine 2.5% and tropicamide 1%, usually combined with slit lamp examination to evaluate the anterior segment, optic nerve, and macula as well as indirect ophthalmoscope to evaluate the periphery)

1.1.2 Pupils, Eyelids, Orbits • Measurement tool for pupil diameter, palpebral fissures, and lid creases (in mm). There is usually a ruler and/or pupil gauge on a near visual acuity card. • A transilluminator or penlight—to assess pupillary reactivity and size in light and dark • Hertel exophthalmometer (when available) to evaluate for proptosis

1.2

 quipment for the Efferent NeuroE Ophthalmic/Vestibular Bedside Exam

• Ocular motor/motility –– A small fixation target for saccades, smooth pursuit, convergence –– Occluder for alternate cover test/cover-uncover ± Maddox rod (ESM 1.1) to evaluate ocular alignment (it is also helpful to quantify strabismus with prism when possible) –– Striped ribbon, paper, flag/tape, drum for optokinetic nystagmus (can use your fingertips too)—for example, a quick screen to see if pursuit/saccades are present and symmetric; to assist in the diagnosis of subtle internuclear ophthalmo-

Reference

3

plegia (adduction lag), convergence-retraction nystagmus, progressive supranuclear palsy (poor or absent downward fast phase) • Vestibular –– Near card or eye chart—static (monocular) and dynamic (binocular) visual acuity –– A transilluminator or penlight—penlight cover test to remove fixation –– Direct ophthalmoscope or Panoptic with spare batteries— occlusive fundoscopy to remove fixation –– Frenzel goggles (+20/+30 diopter lenses, provides magnification and illumination)—removal of fixation for vestibular (e.g., Dix-Hallpike) exam –– Foam pad—a patient with bilateral vestibular loss may be able to maintain balance while standing on the pad with eyes open, but will experience severe imbalance with eyes closed –– Bucket test—you can make one of these yourself! The bucket test is an easy bedside method of evaluating the subjective visual vertical (SVV), which can be thought of as a perceptual consequence of the ocular tilt reaction (e.g., left lateral medullary stroke causes an ipsiversive OTR—left head tilt, ocular counterroll with top poles of both eyes rotated toward the left ear, left hypotropia, leftward SVV tilt). The SVV is usually much more tilted with a central utriculo-ocular motor pathway lesion (lateral medullary stroke) as compared to a peripheral lesion (vestibular neuritis). The bucket test can also assess each eye individually to get an idea of subjective torsion—for example, a patient with an acute left fourth nerve palsy (NP) has normal SVV OD (right eye), but a slight leftward SVV tilt OS (left eye), due to the fact that the paretic left superior oblique is held in relative excycloduction [1].

Reference 1. Zwergal A, Rettinger N, Frenzel C, Dieterich M, Brandt T, Strupp M. A bucket of static vestibular function. Neurology. 2009;72(19):1689–92.

2

Disorders of the Pupils, Eyelids, and Orbits

2.1

Pupil (Tables 2.1, 2.2, and 2.3; ESM 2.1)

2.1.1 Anisocoria—The History A few pearls: • Pain + ptosis and anisocoria—consider aneurysmal third NP or Horner’s syndrome due to carotid dissection • Anisocoria of unclear duration—review old photos to establish chronicity • Anisocoria + ptosis and/or other neurologic symptoms/signs— think about the course of the oculosympathetics (Fig. 2.1) and the third nerve (Table 2.3; ESM 2.1; Fig. 2.2) • Do not forget about the possibility of an ocular disorder—ask about ocular history including prior surgeries, injections, laser treatments, trauma, inflammation (uveitis) • Do not forget about the possibility of pharmacologic d­ ilation— ask about current medications, recent unintentional exposure (e.g., a pet’s eye drops), medications with anti-­cholinergic

Supplementary Information The online version of this chapter (https://doi. org/10.1007/978-­3-­030-­76875-­1_2) contains supplementary material, which is available to authorized users.

© Springer Nature Switzerland AG 2021 D. Gold, Neuro-Ophthalmology and Neuro-Otology, https://doi.org/10.1007/978-3-030-76875-1_2

5

Poor or none (except in the rare case of aberrant regeneration of the 3rd N) Normal (light-near dissociation)

Poor or Mydriatic Light (large pupil none constricts poorly)

Poor or Mydriatic Light (large pupil none constricts poorly)

Tonic pupil (PNS)

Anisocoria Constriction Constriction worse in… to light to near Normal Normal Dark (small pupil dilates poorly)

Third nerve (PNS)

Horner pupil (SNS)

Affected pupil Miotic Pain + (dissection) or −

None

–

Mild IR, SR, + (PCOM aneurysm) MR to or − severe paresis common

Ptosis Motility Mild Normal

“Tonic”, None slow

Normal

Pupil dilation Lag, slow

Table 2.1  Help me now with anisocoria: What to examine and urgent diagnostic considerations Other Lower lid (upside down) ptosis; anhidrosis; reversal of anisocoria and ptosis with apraclonidinea Mydriasis due to 3rd NP without lid or EOM involvement is rare; 1% pilocarpine constrictsb Dilute (0.1%) pilocarpine constrictsb; sectoral constriction of the iris

6 2  Disorders of the Pupils, Eyelids, and Orbits

Normal

Normal

Neither

Physiologic (normally unequal pupils)

Normal

None

None

None

None

None

–

–

1% pilocarpine does not constrictb; consider ocular causes tood Normally

MR > SR > LR > oblique muscles

Unilateral or Any pattern bilateral ptosis common

Normal

Normal

Normal LR (unless cavernous sinus with ipsi- Horner’s)

(continued)

Usually from MLF stroke or demyelinating lesion, “pseudo-INO” in MG Think brainstem lesion; commonly an acute MLF lesion will cause skew and INO Any pattern Look for fatiguability, eyelid twitch or hopping, proximal limb and neck weakness Any pattern History of hyperthyroid is common, but patient may be hypo- or euthyroid

Exo- worse in contragaze Hyper- that is usually comitant

Eso- worse Consider intracranial in ipsi- gaze pressure (high or (LR) low), microvascular, head trauma, mimics*

Pupil 11

Horizontal

Divergence insufficiency

Distance only

Near only

Effect of distance and direction

Normal

Normal

Head position

Normal

Normal

Pupils

Normal

Normal

Eyelids

Non-­paralytic

Non-­paralytic

EOM paresis

Other

Common with head trauma, Parkinson’s, PSP Esotropia at Can be due to distance “sagging eye” with high lid creases; due to cerebellar disease with gaze-evoked nystagmus

Exotropia at near

Ocular alignment

NP  nerve palsy, MR  medial rectus, LR  lateral rectus, SR  superior rectus, IR  inferior rectus, IO  inferior oblique, GCA  giant cell arteritis, PCOM posterior communicating artery, MG myasthenia gravis, SO superior oblique, INO internuclear ophthalmoplegia, PSP progressive supranuclear palsy * With pupil-sparing, always include thyroid eye disease and myasthenia gravis on the differential.

Horizontal

Convergence insufficiency

Image separation

Table 2.3  (continued)

12 2  Disorders of the Pupils, Eyelids, and Orbits

Pupil

13

Trigeminal nerve (V1) Hypothalamus Sympathetics to eyelid Midbrain Pons Medulla

Sympathetics to the pupil Long ciliary nerve Nasociliary nerve Sudomotor fibers

Cervical spinal cord

External carotid artery Internal carotid artery Superior cervical ganglion

C8-T2 Inferior cervical ganglion 1st order 2nd order 3rd order

Fig. 2.1  Oculosympathetic pathway for pupillary dilation: The oculosympathetic tract is an uncrossed pathway that begins in the hypothalamus, with fibers descending in the brainstem (first order, commonly affected in a lateral medullary syndrome), synapsing in the lower cervical/upper thoracic spinal cord (interomediolateral cell columns of C8–T2, also referred to as the ciliospinal center of budge) and continuing on as the second order fibers (in proximity to the lung apex). The tract ascends and then synapses in the superior cervical ganglion. The third order neuron leaves the ganglion, with sudomotor fibers following the external carotid artery (explanation for absence of anhidrosis with an internal carotid artery dissection), while the remaining fibers ascend with the internal carotid artery (explanation for dissection causing a painful Horner’s syndrome). The third order fibers innervate the eyelid (superior [Muller muscle] and inferior tarsal muscles) and pupillary dilator muscles to open the eyelids and dilate the pupils, respectively. A lesion along the oculosympathetic tract causes a Horner’s syndrome with ptosis and miosis, and sometimes clinically apparent anhidrosis (with first or second order but not third order)

2  Disorders of the Pupils, Eyelids, and Orbits

14

Pretectal Posterior nucleus commissure

Superior colliculus

EWN

Lateral geniculate nucleus

Red nucleus

Oculomotor nerve (III) Optic tract

Chiasm

Ciliary ganglion

Optic nerve

Fig. 2.2  Parasympathetic pathway for pupillary constriction: When a bright light is shone in one eye, light enters the pupil and hyperpolarizes retinal photoreceptors that activate retinal ganglion cells. These signals propagate along the optic nerves, chiasm, optic tracts, and fibers responsible for the light reflex then synapse in the dorsal midbrain (prior to reaching the lateral geniculate nucleus) at the pretectal nuclei, then to the Edinger–Westphal nucleus (EWN) of the oculomotor nucleus. From here, efferent fibers travel with the oculomotor nerve to the ciliary ganglion and, finally, innervate the constrictor (sphincter) muscles for bilateral pupillary constriction

Pupil

15

properties (e.g., scopolamine patch, ipratropium inhaler [in a hospitalized patient])

2.1.2 Anisocoria—The Exam A few pearls: • The pupil responses (constriction, dilation—see below) and cranial nerve exam are most important here, but thorough ophthalmic/neuro-ophthalmic (e.g., slit lamp to diagnose iris tear or visualize segmental constriction) and neurologic (e.g., Adie’s syndrome with tonic pupil + absent deep tendon reflexes) exams can offer additional clues. • Two muscles that control the size of the pupil (Fig. 2.3): (1) dilator muscle → mydriasis (dilation via sympathetics, Fig. 2.1), and (2) sphincter muscle → miosis (constriction via parasympathetics, Fig. 2.2).

Sclera (covered by conjunctiva) Iris

Pupil

Lateral

Caruncle

canthus

Medial canthus Limbus Conjunctival vessel

Corneal light reflex

Fig. 2.3  Structures of the eye and ocular adnexa: Seen here is a normal right eye, with clinically relevant structures and landmarks labeled. Also note that the position of the corneal light reflex can assist in ocular alignment evaluation in a patient with poor vision (i.e., Hirschberg and Krimsky tests)

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2  Disorders of the Pupils, Eyelids, and Orbits

• Anisocoria with normal constriction OU (both eyes)—consider oculosympathetic lesion or physiologic anisocoria. • Anisocoria with poor dilation in the miotic pupil—high suspicion for oculosympathetic lesion. Consider apraclonidine topical drop testing. • Anisocoria with poor constriction in the mydriatic pupil—consider third NP, tonic pupil, pharmacologic. • Light-near dissociation: If one or both pupils constricts poorly to light, evaluate their response to near (i.e., activation of the near triad of accommodation, miosis, and convergence). If a near stimulus causes more constriction than light, there is “light-near dissociation.” Include on the differential of light-­ near dissociation (when small and irregular, sometimes referred to as Argyll Robertson pupils): bilateral—dorsal midbrain (Parinaud) syndrome, severe bilateral optic neuropathies; unilateral or bilateral— neurosyphilis, diabetes/dysautonomia, previous retinal laser ­photocoagulation; unilateral—aberrant regeneration of the third nerve (e.g., adduction of the affected eye will constrict the affected pupil due to pupillary sphincter innervation by some of the fibers originally destined for the medial rectus).

2.1.3 Pharmacologic Testing • Pilocarpine—helpful with a mydriatic, poorly reactive pupil… is it a third NP, tonic pupil, or pharmacologic? A cholinergic agonist that should constrict a normal pupil at 1% concentration, including a mydriatic pupil due to third nerve palsy or a tonic pupil. However, 1% will not constrict a pharmacologically dilated pupil (unless the offending medication—e.g., nebulized ipratropium—is wearing off). Dilute pilocarpine at 0.1% will not constrict a pupil unless denervation hypersensitivity has occurred, as with a tonic pupil (Fig. 2.4). • Apraclonidine—helpful to determine whether a miotic pupil is due to Horner’s syndrome. 0.5% or 1% drops will dilate the Horner’s pupil (causing a reversal in anisocoria) due to denervation hypersensitivity (weak alpha-1 agonist action), often with improvement in pto-

Pupil

17 OD

OS

Mydriasis OS with light-near dissociation

45 minutes after instillation of dilute pilocarpine OU

Fig. 2.4  Dilute (0.1%) pilocarpine testing to diagnose a tonic pupil: This is a patient with a slightly mydriatic left pupil that constricted to a near stimulus but not to light. There was also segmental constriction of the iris appreciated with slit lamp exam. Dilute pilocarpine was instilled OU, and 45  minutes later, there was no effect on the normal (right) pupil but clear constriction of the mydriatic (left) pupil, supporting the diagnosis of a left tonic pupil. (Photos courtesy of Dr. Collin McClelland)

sis as well. It may take days for this hypersensitivity to develop. Apraclonidine will not dilate a normal pupil (Fig. 2.5).

2.1.4 Horner’s Syndrome Case:  A 45-year-old man presented to the emergency department (ED) with 5  days of right-sided face and neck pain, and droopiness of the right eyelid. Several days prior to ptosis, he was in a car accident causing a whiplash injury without loss of consciousness. Examination demonstrated normal afferent function, motility/ocular alignment, and neurologic examination. Both ptosis and miosis were observed on the right, with normal pupillary

18

2  Disorders of the Pupils, Eyelids, and Orbits

Right (upper and lower lid) ptosis and miosis

45 minutes after instillation of apraclonidine OU – reversal of anisocoria and ptosis

Fig. 2.5  Apraclonidine testing to diagnose a Horner’s syndrome: Apraclonidine (0.5%) testing was performed within 1 week of onset of Horner’s syndrome. Testing was positive in that anisocoria reversed (as well as ptosis)—i.e., the previously miotic right (Horner’s syndrome) pupil was now slightly mydriatic

constriction OU, but poor dilation (in the dark) OD. There was no subjective or objective indication of diminished sweating on the right face (i.e., anhidrosis). Concern was very high for a right Horner’s syndrome, and MR angiogram performed in the ED demonstrated narrowing of the right internal carotid artery (ICA) with an intimal flap consistent with a dissection. IV heparin therapy was initiated and MRI of the brain did not demonstrate diffusion-­weighted imaging hyperintensities. Video:  Video 2.1. Relevant Figures, Tables:  Figs. 2.1, 2.5, 2.6, and 2.7; Tables 2.1 and 2.2. Key questions to ask:  Acute and painful Horner’s syndrome is especially concerning. With a more chronic, painless Horner’s syndrome, consider the anatomy of the oculosympathetic tract. • Any symptoms referable to the brainstem (e.g., diplopia, ataxia, numbness in lateral medullary syndrome—first order)? • Smoking history (e.g., Pancoast lung tumor—second order)? • Surgeries/procedures in or around the neck and cervical spine (first, second, or third order)? • Head or neck trauma that could be responsible for carotid dissection (third order)?

Pupil

19 Axial FLAIR

TOF MRA

Light: mild ptosis and miosis OD

Right internal carotid artery dissection Dark: more anisocoria due to dilation lag OD

Fig. 2.6  Right Horner’s syndrome due to right internal carotid artery (ICA) dissection: More prominent anisocoria in dark versus light is apparent in this case, which is highly suggestive of a Horner’s pupil (related to poor sympathetic activation causing a “dilation lag” in the miotic [right] pupil). There is also mild upper lid ptosis but no anhidrosis (which is typical of a third order lesion). MR images include axial fluid attenuated inversion recovery (FLAIR) and time of flight (TOF) MR angiogram demonstrating a crescent sign in the right ICA

Key findings to elicit:  A miotic Horner’s pupil will dilate slower than the fellow pupil (i.e., a dilation lag). Anisocoria due to an oculosympathetic tract lesion will be more pronounced in the dark (owing to the dilation lag). There will be mild upper lid ptosis (superior tarsal or Mueller’s muscle—milder ptosis than a third NP), although lower lid ptosis (i.e., inverse or upside-down ptosis) is commonly seen as well. While the clinician may be confronted with an isolated Horner’s syndrome, the presence of a unilateral Horner’s  +  other findings allow for precise localization—for example, contralateral fourth nerve palsy indicates midbrain; features of the Wallenberg syndrome (ipsilateral hypotropia due to skew deviation; ipsilateral body and ocular lateropulsion; limb ataxia; ipsilateral saccadic hypermetria and contralateral hypometria; decreased sensation of ipsilateral face and contralateral arm/leg); upper and lower limb hyperreflexia, ankle clonus, + Babinski indicates cervical spinal cord; ipsilateral V1, V2, third, fourth, sixth nerve palsy indicates cavernous sinus. Because the sudomotor fibers travel separately with the external carotid artery, anhidrosis can be seen with first- and sec-

20

2  Disorders of the Pupils, Eyelids, and Orbits

Palpebral fissure

MRD1

MRD2

Fig. 2.7  The eyelid exam—marginal reflex distance (MRD) 1 and 2: For documentation and comparative purposes, the MRD1 (upper eyelid margin to corneal light reflex, normal is ~4–5 mm) and MRD2 (corneal light reflex to lower eyelid margin, normal is ~5 mm) should be recorded, especially when ptosis is suspected. The palpebral fissure is simply the MRD1 + MRD2 and will be widened with a seventh NP and narrowed with ptosis (from any etiology). A light source and measuring device are all that are needed

ond-order lesions, but not with third-order lesion (e.g., internal carotid artery ­dissection). How do I approach (history and exam) the patient with anisocoria or ptosis when Horner’s syndrome is a consideration?  See Tables 2.1 and 2.2. Pitfalls:  A patient with mild ptosis (e.g., mechanical ptosis from disinsertion of the levator palpebrae muscle—so-called levator

Pupil

21

dehiscence, which is common with aging) + physiologic anisocoria (also common, usually 50–55 years old. • Ask about ptosis, dysphagia, and weakness, which could suggest a neuromuscular junction disorder (myasthenia gravis) when pupils are spared. Key findings to elicit:  • Evaluate function of the muscles innervated by the third nerve—that is, unilateral ptosis (levator palpebrae), adduction paresis (MR), supraduction paresis (SR), infraduction paresis (IR), inferior oblique (IO—usually not clinically apparent unless in isolation, which is a rare occurrence), mydriasis (due to impaired pupillary constriction). • Evaluate limb strength and coordination (e.g., midbrain stroke can cause third NP and contralateral hemi-ataxia, and/or hemiparesis), function of other cranial nerves (e.g., meningitis involving multiple cranial neuropathies in the subarachnoid space), function of V1/V2, fourth, and sixth NP (e.g., mass or inflammation of the cavernous sinus), and optic nerve function (e.g., pituitary apoplexy, orbital mass, or infection). How do I approach (history and exam) the patient with anisocoria, ptosis, or diplopia when third NP is a consideration?  Tables 2.1 and 2.2; ESM 2.1. Pitfalls:  Slight anisocoria (generally 1 mm or less of ipsilateral mydriasis) can be seen with a vasculopathic third NP, but is a

24

2  Disorders of the Pupils, Eyelids, and Orbits

diagnosis of exclusion. While complete ptosis and motility deficits involving ipsilateral MR, SR, and IR without pupil involvement in an older patient with vascular risk factors is usually microvascular/vasculopathic, this can still be the initial presentation of a PCOM aneurysm or mass lesion. A patient with a mydriatic unreactive pupil in isolation (i.e., without ptosis, SR, IR, MR paresis) almost never has a third NP. Instead, consider: • Pharmacologic causes (e.g., recent atropine or other anti-­ cholinergic drops belonging to relatives or pets, contact with a scopolamine patch, nebulizers/inhalers in an inpatient—­ ­ pilocarpine 1% drops will constrict a mydriatic pupil due to a third NP, but not a pharmacologically dilated pupil) • Adie’s tonic pupil (check pupillary constriction to a near stimulus) • Iris tear due to trauma • Previous ocular surgery • Infection (uveitis). Do not miss this!  When ptosis, SR, IR, or MR function is partial or when the pupil is involved, PCOM aneurysm/structural causes must be excluded urgently. When there is no pupil involvement, also consider myasthenia gravis. Miller Fisher syndrome is another cause of ophthalmoparesis and a mydriatic poorly responsive pupil(s), and the mydriasis can rarely occur in isolation. With bilateral ptosis and superior rectus paresis, consider a unilateral nuclear third NP. Also look for evidence of aberrant regeneration of the third nerve (Fig. 4.5), which suggests a chronic compressive lesion (e.g., meningioma, PCOM aneurysm) or previous trauma (see example Video 2.2). Aberrant regeneration does not occur due to a microvascular third NP. What is next?  Urgent CT or MR angiogram in most cases, in addition to (or followed by) contrast-enhanced MRI when ­diagnostic uncertainty remains. When the clinician indicates the correct side of the suspected third NP and in the hands of an experienced radiologist, CTA or MRA is almost always sufficient to diagnose a PCOM aneurysm. Rarely is catheter angiography necessary.

Pupil

25

Treatment options:  A microvascular (diabetic) third NP is most common in the older population, and this should resolve completely within 3 months (sometimes up to 6 months). Other etiologies may result in more permanent deficits in which case ptosis and/or strabismus surgery or prism therapy should be considered. When the ptosis is severe, diplopia is not experienced by the patient. If you can only remember one thing…  While a third NP due to a PCOM aneurysm usually involves the pupil, any pattern of internal (pupil) or external (extraocular muscle) ophthalmoplegia can be aneurysmal. Always exclude an aneurysm first and foremost! Want to know more?  [3]

2.1.6 Tonic Pupil Case:  A 65-year-old woman was referred for anisocoria. She noticed that for at least the last 6 months, there was increased sensitivity to light and there had been a noticeable change in the appearance of her pupils. On examination, she had a 5 mm mydriatic pupil OS that constricted minimally to light, but constricted much better to a near stimulus. However, after constricting to a near target, the pupil was slow to re-dilate to its original size when looking at distance. The right pupil was 3  mm in diameter and constricted briskly to light and near stimuli. Examination of motility and eyelid function was unremarkable with normal alignment and no ptosis. Upon review of old photos, it seemed that the right pupil had been slightly mydriatic for at least 12  months. With a slit lamp, it was apparent that there was sectoral constriction of the right pupil, with the inferior iris constricting slightly, while the superior segment did not constrict. Figure:  Fig. 2.9 (Video 2.3).

2  Disorders of the Pupils, Eyelids, and Orbits

26

Mydriasis OS

Constriction OU to a near target

No constriction to light OS

Slow (tonic) dilation, near to distance

Fig. 2.9  Clinical features of a left tonic pupil: Seen here is a patient with anisocoria with a mydriatic pupil OS that constricted poorly to light but much better to a near target. Additionally, when asked to look from a near to a distant target, slow (tonic) dilation was observed. Dilute (0.1% pilocarpine) constricted the mydriatic (left) pupil but not the normal (right) pupil

Key questions to ask:  Trying to establish the chronicity is important and review of old photos is usually the best way. • Have you experienced double vision or droopy eyelid (consider third NP)? • Any sweating/flushing asymmetry (consider Ross and related dysautonomia syndromes)? • Any recent exposure to eye drops (belonging to a family member or pet)? • Preceding trauma (may damage the ciliary ganglion also think about a traumatic third NP or traumatic iris tear)? • Past infection/inflammation/surgeries (consider previous uveitis causing synechia [iris may adhere to cornea or lens], or a surgical pupil can be caused by a variety of ocular procedures)? Key findings to elicit:  • Light-near dissociation (poor or no constriction to light with much better response to a near stimulus [use the patient’s finger as the target]); • Slow (tonic) dilation of the affected eye following constriction to a near stimulus;

Pupil

27

• Look for sectoral constriction with a slit lamp or with magnification (ophthalmoscope) when possible; • Evaluate deep tendon reflexes (Adie’s, Ross, and related dysautonomia syndromes). How do I approach (history and exam) the patient with anisocoria when tonic pupil is a consideration?  Table 2.1. Pitfalls:  A third NP almost never presents with an isolated unilateral mydriatic pupil in the complete absence of motility or lid deficits. However, if the onset seems to be acute, there is no sectoral constriction or light-near dissociation, no clear ocular cause (e.g., iris tear, uveitis), and no exposure to eye drops, it is reasonable to treat this as a possible acute third NP and rule out PCOM aneurysm and lesion involving the third nerve. Do not miss this!  Other causes of mydriasis: Pharmacologically dilated pupil, third NP. Other causes of light-near dissociation: Neurosyphilis (usually bilateral and pupils can be small), dorsal midbrain localization (Parinaud’s syndrome, bilateral), following retinal photocoagulation in diabetic retinopathy (unilateral or bilateral). What is next?  If light-near dissociation is appreciated in addition to tonic dilation of the involved mydriatic pupil, no further testing is required when lid and extraocular function is normal. If the onset is acute and third NP cannot be excluded, CTA or MRA to rule out PCOM aneurysm is warranted in addition to contrast-­ enhanced MRI if angiogram is unrevealing. Treatment options:  A higher power  +  diopter lens may be required for reading. Over time, the mydriatic pupil will usually decrease in size. If you can only remember one thing…  It is extremely rare to have a third NP present with a mydriatic pupil that is unreactive to light in complete isolation. Evaluate for light-near dissociation and consider the possibility of a pharmacologic pupil prior to MRI and MRA/CTA.

2  Disorders of the Pupils, Eyelids, and Orbits

28

Want to know more?  [4]

2.2

 yelid (Ptosis and Spasm) (Tables 2.1, 2.2, E and 2.3; ESM 2.1)

2.2.1 Ptosis—The History A few pearls: • When the exact onset is unknown, review old photos • Ptosis + pain—consider third NP (e.g., aneurysmal) or Horner’s syndrome due to carotid artery dissection • Ptosis + diplopia—consider third NP, myasthenia gravis (MG), Miller Fisher syndrome • Ptosis with variability or diurnal variation—consider MG • Isolated ptosis in the elderly, or in a patient who wears contact lenses, rubs the eyes, or is status post ocular surgery—consider levator dehiscence syndrome

2.2.2 Ptosis—The Exam A few pearls: • Evaluate ocular motility and alignment—abnormal in third NP, normal in isolated Horner’s syndrome • Measure marginal reflex distance 1 and 2 (distance from corneal light reflex to upper lid [MRD1, normal ~4–5 mm] and to lower lid [MRD2, normal ~5 mm]) –– Can have upper and lower lid ptosis (and reduced MRD 1 and 2) in Horner’s syndrome; severe ptosis (and greater MRD1 reduction) is typical in third NP as compared to Horner’s; –– Reduced MRD1 (often bilateral) in levator dehiscence; –– Variable MRD1 and 2 measurements in myasthenia gravis (MG) (Fig. 2.7).

Eyelid

29

• Measure palpebral fissure (distance from upper to lower lid or MRD1 + MRD2) –– Widened in facial nerve (orbicularis oculi) palsy. • Measure levator function (upper lid position when looking down compared to when looking up when minimizing frontalis contraction, normal ~14–16 mm) –– Reduced with neuropathic (third NP) and neuromuscular (MG) ptosis; –– Intact with levator dehiscence/mechanical ptosis. • Measure lid crease height (normal ~6–10 mm) –– Increased with levator dehiscence/mechanical ptosis (Figs. 2.10 and 2.11). • Evaluate facial nerve function—CN7 is responsible for eyelid closure (orbicularis), while CN3 is responsible for eyelid opening (levator palpebrae). If a patient has facial/orbicularis weakness and ptosis, consider myasthenia gravis or multiple cranial neuropathies (Fig.  2.12). A facial palsy will cause ipsilateral widening of the palpebral fissure due to weakness of eyelid closure (i.e., orbicularis oculi muscles), which can make the normal eye look relatively ptotic (so-called pseudo-ptosis). Aberrant regeneration (facial synkinesia) is a common occurrence, and this can lead to ipsilateral narrowing of the palpebral fissure, giving the appearance of ipsilateral relative ptosis (Fig. 2.13).

2.2.3 Levator Dehiscence Case:  A 70-year-old woman presented with bilateral ptosis and intermittent diplopia. The ptosis was first noted about 5 years ago and had been stable over time. The diplopia began 6 months ago, and was binocular, horizontal, and only experienced at distance. There was no diurnal variation to the ptosis or diplopia. Cranial nerve exam was unremarkable, ductions were normal and ocular alignment demonstrated normal alignment at near with a comitant (i.e., the same in all directions of gaze) symptomatic esotropia at distance, leading to the diagnosis of divergence i­nsufficiency (DI). Eyelid examination demonstrated high lid creases OU with mar-

2  Disorders of the Pupils, Eyelids, and Orbits

30

Lid crease

White dotted line represents levator function - distance between upper eyelid margin in downgaze (yellow arrowhead) and then in upgaze

Fig. 2.10  The eyelid exam—levator function (LF) and lid crease: For documentation and comparative purposes, the lid crease (upper eyelid margin to the insertion of the levator palpebrae muscle, normal ~6–10 mm) and LF (the white dotted line represents the LF, or the distance between the upper lid in downgaze [yellow arrowhead] compared to upgaze, while ensuring that the frontalis muscle does not contribute to the eyelid movement, normal ~14–16 mm) should be recorded in millimeters. A high lid crease is typical of disinsertion (dehiscence) of the levator muscle, while diminished LF is suggestive of extraocular muscle weakness (e.g., third NP, myasthenia gravis, or myopathy) Prominent superior sulcus Small MRD1

Normal MRD2

High lid crease

Fig. 2.11  Levator dehiscence—a common cause of mechanical ptosis: Look for the combination of upper lid ptosis and a high lid crease, with lack of fatigability and normal levator function. It is typically bilateral and may be associated with other signs (e.g., prominent superior sulcus, “sagging eye syndrome” [esotropia greater at distance]) in the aging population, and when unilateral, also consider trauma, ocular surgery, or contact lens wear/eye rubbing

Eyelid

31

OO Orbital m. Levator palpebrae m.

Orbital septum OO Preseptal m.

Conjunctiva

Levator aponeurosis Superior tarsal (Muller) m.

OO Pretarsal m.

Tarsus

OO Preseptal m. OO Pretarsal m. OO Orbital m.

Fig. 2.12  Structures relevant to eyelid opening and closing: The seventh cranial nerve is responsible for eyelid closure and innervates the orbicularis oculi (OO) muscles, while eyelid opening depends mainly on the third cranial nerve (levator palpebrae, i.e., severe ptosis with a third NP) as well as the oculosympathetic tract (superior and inferior tarsal muscles, i.e., mild upper lid [and sometimes lower lid or upside down] ptosis with a Horner’s syndrome)

32

2  Disorders of the Pupils, Eyelids, and Orbits

ginal reflex distance 1 (MRD1) measurements of 1–2  mm (decreased from normal) and MRD2 measurements of 4–5  mm (normal). Orbicularis strength was normal and there was no fatigability with prolonged upgaze, no enhanced ptosis or Cogan’s lid twitch, and normal levator function OU.  There was a prominent superior sulcus bilaterally. Taken together, she was diagnosed with mechanical ptosis due to levator dehiscence. The combination of levator dehiscence/disinsertion, DI (also referred to as “sagging eye syndrome” in this context), and prominent superior sulci were compatible with age-related orbital involutional changes. Figure:  Fig. 2.11.

Fig. 2.13  Chronic right facial nerve palsy with aberrant regeneration (synkinesia): The top left photo shows the patient at rest with a slightly flattened right nasolabial fold (suggestive of weakness) and narrowed right palpebral fissure (typical of synkinesia months later, whereas there’s widening of the ipsilateral palpebral fissure with an acute facial palsy). The top right photo demonstrates poor right eyelid closure (orbicularis oculi weakness) with abnormal activation (synkinesia) of the lower face (orbicularis oris) on the right. The bottom left photo demonstrates inability to elevate the right brow (frontalis weakness), again with abnormal right o. oris activation (synkinesia). The bottom right photo demonstrates an asymmetric smile (due to right o. oris weakness) with abnormal activation (synkinesia) of the right o. oculi

Eyelid

33

Key questions to ask:  • Ask about diurnal variation, diplopia, and other symptoms suggestive of myasthenia gravis (MG, see case below). • When abrupt, unilateral and associated with diplopia, consider third NP. • When abrupt, isolated, and unilateral, consider Horner’s syndrome. • Try to establish chronicity—oftentimes reviewing old photos can be helpful. • Also ask about contact lens use, frequent eye rubbing, ocular surgery or trauma, any of which can damage the levator muscle causing disinsertion. Key findings to elicit:  • In this case, other signs were present to suggest orbital changes due to aging (e.g., prominent superior sulcus, “sagging eye syndrome” causing esotropia greater at distance). • Look closely for anisocoria, especially when levator dehiscence is unilateral or asymmetric, considering Horner’s (ptosis + miosis), third NP (ptosis + mydriasis), as well as physiologic anisocoria. • With levator dehiscence, look for normal levator function, reduced MRD1 and normal MRD2, normal orbicularis function, and high lid creases. • If aging-related eyelid/orbital signs are absent in a patient with DI, look closely for gaze-­evoked nystagmus and other “cerebellar” signs—DI is common in patients with cerebellar ataxia (Video 2.4). How do I approach (history and exam) the patient with ptosis?  See Tables 2.1 and 2.2. Pitfalls:  Not every patient with ptosis needs an MRI! Almost always, a focused history and exam will lead to the correct diagnosis. If ptosis is isolated (i.e., no motility/alignment, pupillary abnormalities) and unilateral, and there is suspicion for MG, try the ice test and other bedside maneuvers (see “Myasthenia Gravis” below).

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2  Disorders of the Pupils, Eyelids, and Orbits

Do not miss this!  When acute, Horner’s syndrome and third NP are the most dangerous etiologies, but pupils and/or motility are almost always abnormal. MG should be considered in any patient with ptosis and/or diplopia without pupil involvement. Consider chronic progressive external ophthalmoplegia (CPEO) with ­progressive bilateral ptosis and ophthalmoparesis. These patients will not have diplopia if ophthalmoparesis is symmetric. What is next?  The diagnosis of levator dehiscence can easily be made with a focused history and examination, and in such cases, the patient can be reassured and no further testing is needed. When there is suspicion for third NP or Horner’s syndrome, neuroimaging is often indicated (see Tables 2.1 and 2.2 regarding clinical differentiation). If there are eyelid signs (or ice test) suggestive of MG, acetylcholine receptor antibodies should be checked first. Treatment options:  If the ptosis impacts visual function (i.e., affects the superior visual field), eyelid surgery is often an option. If you can only remember one thing…  Remember that not all ptosis is neurologic! Levator dehiscence is a common mechanical cause of ptosis. Want to know more?  [5]

2.2.4 Myasthenia Gravis Case:  A 50-year-old woman presented to clinic with several months of fluctuating ptosis and diplopia. The horizontal binocular diplopia was initially intermittent, but became more constant in the last few weeks, seeming to be worse by the end of the day. The ptosis was minimal in the morning and also increased throughout the day. She denied proximal weakness, dysphagia, or dysarthria. Visual function was normal, general neurologic exam was normal, but there was a large angle exotropia due to severe

Eyelid

35

bilateral adduction deficits, which could not be overcome by convergence. There was no abducting nystagmus in right or left gaze. The ptosis OD was variable, fatigable, and there was right > left frontalis contraction to assist with keeping her eyes open. Orbicularis oculi strength was also impaired OD > OS. Vertical ductions appeared normal, although there were also intermittent complaints of a vertical component to her diplopia. When looking from down to straight ahead, there was a subtle overshoot of the eyelid consistent with a Cogan’s lid twitch. After sitting with her eyes closed and with an ice pack (ice test) over the right (ptotic) eye for several minutes, there was a brief improvement in her ptosis, but not her strabismus. Suspicion was very high for myasthenia gravis, and acetylcholine receptor antibodies (binding) returned positive, confirming the diagnosis. CT of the chest did not demonstrate a thymoma. Pyridostigmine was tried with partial improvement in the ptosis (not the strabismus), and she was then put on prednisone with significant improvement over weeks. Figure:  Fig. 2.14.

R

L

*

*

*

*

Fig. 2.14  Bilateral ptosis and ophthalmoplegia in myasthenia gravis: In this montage, the top photo represents primary gaze where right ptosis (yellow asterisk) and an outward deviation of the eyes (exotropia) can be seen. The ptosis was variable, fatigable, and there was mild orbicularis oculi weakness bilaterally. In the bottom photos, bilateral adduction pareses (white asterisks) are apparent in lateral gaze. In the bottom right photo there is more ptosis OD in right gaze, with resultant left eyelid retraction (black asterisk, note that the superior sclera is visible) due to Hering’s law

36

2  Disorders of the Pupils, Eyelids, and Orbits

Key questions to ask:  Diplopia and/or ptosis are very common in the initial presentation of MG, and can be seen in isolation about 50% of the time. Diurnal variation is typical for ocular and generalized MG (weakness, dysphagia, dysarthria). Ask about a history of other autoimmune disease, or recent use of immune checkpoint inhibitor medications for cancer. When a partial (pupil-sparing) third NP or internuclear ophthalmoplegia is possible, inquire about risk factors and associated symptoms for these respective disorders. Key findings to elicit:  • Fatigue in proximal muscles (deltoids, hip and neck flexors). • Ptosis and/or diplopia induced by prolonged upgaze. • Other eyelid signs (e.g., curtaining and enhanced ptosis) are based on Hering’s law of equal innervation where bilateral levator palpebrae muscles receive equal innervation. By manually elevating the ptotic (right) lid, innervation will be reduced bilaterally, which can result in drooping (curtaining) of the non-ptotic (left) lid. By manually elevating the non-ptotic (left) lid, innervation will be reduced bilaterally, which can result in more drooping of the ptotic lid (enhanced ptosis). Hering’s law may also result in eyelid retraction that is contralateral to the ptotic eyelid (Fig. 2.14). • Look for Cogan’s lid twitch—have the patient look down and then back to primary gaze, and the lid may overshoot the target or appear to twitch. • Similarly, the examiner may see an eyelid twitch with pursuit or saccades, which is known as lid hopping (Video 2.5). However, these lid signs can be seen in other disorders causing ptosis (Video 2.6). • Rest test and/or ice test can transiently improve ptosis and/or diplopia as well. How do I approach (history and exam) the patient with ptosis or diplopia when MG is a consideration?  See Tables 2.2 and 2.3; ESM 2.1.

Eyelid

37

Pitfalls:  Keep in mind that (when the pupils are uninvolved) MG can mimic any ocular motor disorder including: third, fourth, sixth, internuclear ophthalmoplegia (note that in this case specifically, the adduction paresis could not be overcome by convergence and there was no abducting nystagmus), horizontal gaze palsy, one-and-a-half syndrome. All of the eyelid signs above (twitch, enhanced ptosis, etc.) can be seen in other disorders causing ptosis. Do not miss this!  Always consider mechanical causes of ptosis (levator dehiscence in the aging population, contact lens wearers, history of surgery or eyelid trauma, frequent eye rubbing, etc.) and evaluate old photos to establish chronicity; • Consider Lambert Eaton syndrome (often paraneoplastic and associated with voltage-­ gated calcium channel antibodies) with autonomic features, pupil involvement, hyperreflexia; • Miller Fisher syndrome with preceding viral illness, ophthalmoparesis, ataxia, hyporeflexia, poor pupillary constriction (Video 2.7); • Botulism with pupil involvement and risk factors (e.g., black tar heroin). What is next?  • Acetylcholine receptor antibodies (ACHR, always order binding, rarely modulating and/or blocking antibodies are positive when binding is negative) should be ordered when there is any suspicion for MG. • If ACHR antibodies are negative, consider anti-MUSK (especially with prominent bulbar symptoms) and anti-LRP4 antibodies. • Consider single-fiber EMG (frontalis muscles) or edrophonium/neostigmine tests (measuring ptosis and/or ocular alignment and motility pre and post) when antibodies are negative. • CT chest to evaluate for thymoma.

38

2  Disorders of the Pupils, Eyelids, and Orbits

Treatment options:  Pyridostigmine can help with symptoms (ptosis, weakness, etc.), but it tends not to be as effective for diplopia. Usually, immunosuppression is required in the form of prednisone or steroid-sparing agents. IVIG or plasma exchange are often indicated during severe exacerbations or crises. ­Thymectomy is always indicated when thymoma is present, but it has been shown to be beneficial in cases where thymoma is absent as well (mainly younger ACHR+ patients with generalized disease early in the course, although the ocular MG population has been less well studied). If you can only remember one thing…  MG can cause any (pupil-sparing) combination of ptosis and strabismus! Always consider this diagnosis. Want to know more?  [6, 7]

2.2.5 Eyelid Spasms Case:  A 55-year-old man presented with episodes of involuntary left eyelid closure, worsening in frequency and intensity over the past 6 months. Episodes occurred many times throughout the day and were provoked by stress, smiling, or other voluntary facial movements. Neurologic and neuro-ophthalmic examinations were normal. During the exam, there was intermittent spasm of the left eyelid (orbicularis oculi), as well as simultaneous involvement of muscles of the left lower face (especially orbicularis oris and risorius). This was typical of left hemifacial spasm (HFS), which in his case was due to left facial nerve (neurovascular) compression by the left anterior inferior cerebellar artery in the internal auditory canal. Therapy with onabotulinumtoxinA injections was initiated, with very good results. Figure:  Fig. 2.15.

Eyelid

39

Frontalis

O. Oculi

O. Oris and risorius

Fig. 2.15  Left hemifacial spasm: Between spasms, the face was symmetric and facial muscle strength (innervated by the seventh nerve) was normal. During spasms, there was contraction mainly of the left orbicularis oculi (eyelid closure) as well as the left orbicularis oris and risorius (causing an upward and leftward deviation of the mouth). Despite the contraction of the o. oculi, the left eyebrow does not depress (instead, there is slight elevation due to simultaneous frontalis contraction), a finding known as the “other Babinski sign.” (Photo courtesy of Dr. Stephen Reich)

Key questions to ask:  HFS • Any other symptoms referable to the brainstem, specifically the pons (e.g., horizontal double vision due to an ipsilateral sixth NP; • Sensory loss due to trigeminal involvement)? • If the eyelid spasms are unilateral, is the lower face spared (think about eyelid myokymia, which is extremely ­common)? Blepharospasm

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2  Disorders of the Pupils, Eyelids, and Orbits

• Are both eyes involved? • History of other forms of dystonia, parkinsonism (or medications such as anti-­psychotics cause parkinsonism or other iatrogenic movement disorders)? • Is photophobia present? Key findings to elicit:  HFS—typical spasms will almost always be seen in the office, and can usually be triggered by having the patient forcefully close the eyes and then open them (eyelid spasms) or following a smile (lower face). Evaluate the function of adjacent cranial nerves. The “other Babinski sign” may also be seen in HFS, where orbicularis oculi spasm causes eyelid closure, but because of simultaneous frontalis contraction (probably a consequence of peripheral co-activation and not seen in blepharospasm), the eyebrow may rise or at least fail to depress (as in this case). Blepharospasm—spasms are bilateral and forceful eyelid closure can often trigger spasms in the clinic. Blepharospasm can be associated with photophobia, and can be reactive in response to dry eye or ocular surface disease—ophthalmic exam should be performed. Patients often have a sensory trick (e.g., pushing on a certain part of the face or head) to diminish spasms. Evaluate for signs of parkinsonism, other areas of dystonia involvement. Evaluate for bilateral lower facial involvement that could suggest Meige syndrome. Pitfalls:  Very early HFS may only affect the orbicularis oculi and can mimic eyelid myokymia (i.e., subtle upper and/or eyelid contractions that are benign and usually occur in the setting of sleep deprivation, stress, or caffeine). If typical spasms are not observed in the clinic, have the patient take videos of their spasms at home. Synkinesia of the seventh CN (suggestive of prior damage to the seventh CN with aberrant regeneration) can sometimes be mistaken for HFS—for example, with o oculi contraction (blinking), there can be involuntary o oris contraction, and with o oris contraction (smiling), there can be involuntary o oculi contraction (Fig. 2.15). Blepharospasm is almost never due to a structural lesion, but can rarely be associated with neurodegenerative

Orbit/Globe

41

diseases (more common with progressive supranuclear palsy than Parkinson’s disease). Do not miss this!  While HFS is usually due to neurovascular contact involving the seventh CN, it can be due to a pontine/cerebellopontine angle mass or lesion. Consider synkinesia/aberrant regeneration of CN7 (Fig. 2.13) and eyelid myokymia in the differential of unilateral lid spasms, and consider ocular surface disease (reactive) and functional etiologies in the differential of blepharospasm. What is next?  MRI in HFS with thin cuts through the internal auditory canal, which is not usually necessary in typical cases of blepharospasm. Treatment options:  Botulinum toxin is usually first line for both and various toxins are effective for HFS/blepharospasm, and pretarsal may be more efficacious than preseptal injections (Fig. 2.12). The side effects of medications (e.g., carbamazepine, benzodiazepines) may outweigh the benefits of such medications, but can occasionally be beneficial. Surgical options can also be considered in refractory cases—neurovascular decompression for HFS; deep brain stimulation for blepharospasm (rarely performed), or eyelid myomectomy for both. Consider FL-41 tinted lenses when photophobia is present in blepharospasm. If you can only remember one thing…  The diagnoses of HFS and blepharospasm can be made with a high degree of certainty at the bedside, and botulinum toxin injections are usually highly efficacious. Want to know more?  [8–10]

2.3

Orbit/Globe

Table 2.3, Fig. 2.16 and ESM 2.1.

2  Disorders of the Pupils, Eyelids, and Orbits

42

Frontal bone Sphenoid bone lesser wing

Optic canal

Optic strut Superior orbital fissure

Lacrimal bone

Sphenoid bone, greater wing

Ethmoid bone

Foramen rotundum

Maxillary bone

Fig. 2.16  Bony structures relevant to the orbit: The frontal, sphenoid, maxillary, ethmoid, and lacrimal bones make up the orbit. Structures passing through the optic canal include the optic nerve, oculosympathetic tract, and ophthalmic artery. Structures passing through the superior  orbital  fissure include the superior ophthalmic vein and cranial nerves 3, 4, 6, and V1 (ophthalmic branch of the trigeminal nerve). Structures passing through the foramen rotundum include V2 (maxillary branch of the trigeminal nerve)

2.3.1 Orbital Disorders—The History A few pearls: • Typical symptoms of orbital disease include protrusion of one or both globes (proptosis), peri-ocular swelling, blurriness or loss of vision, diplopia (due to mass effect on the globe, ­extraocular muscles and/or ocular motor nerves), pain, injection and “red eye,” and/or ptosis. • Consider an orbital lesion with gaze-evoked amaurosis, where eye movement in a particular direction results in transient vision loss—this can be due to direct mass effect of the optic nerve or vascular compromise. This phenomenon may also occur with papilledema—that is, a less common type of transient visual obscuration.

2.3.2 Orbital Disorders—The Exam A few pearls:

Orbit/Globe

43

• A comprehensive ophthalmic/neuro-ophthalmic examination is essential. Knowledge of the bony anatomy and neurovascular structures traveling through the orbit (e.g., superior orbital fissure) allow for accurate localization, even when obvious orbital signs such as proptosis are absent (Fig. 2.17). • Evaluate retropulsion by having the patient close the eyes, and with your thumbs, push gently backward on the upper eyelids. Normally, this should feel soft, without resistance. In patients

Superior scleral show Temporal flare

Inferior scleral show

Injected vessels

*

Axial CT

* * *

Coronal CT

Fig. 2.17  Typical orbital and neuroimaging signs in thyroid eye disease (TED): Seen in the top left photo are typical orbital signs of TED. Additionally, she had proptosis as demonstrated by abnormal Hertel exophthalmometer measurements (27  mm OU) as well as anterior globe displacement on axial CT relative to the interzygomatic (yellow) line. Orbital CT and MRI are both effective modalities to visualize enlarged extraocular muscles in TED. Typically, the muscles tend to be involved in the following order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus, followed by occasional involvement of the oblique muscles. In the images above, bilateral medial rectus (white asterisk) enlargement is most prominent, but there is also mild enlargement of bilateral inferior rectus (yellow asterisk) and superior rectus muscles (black asterisk), a slightly larger lateral rectus on the right (black arrowhead) compared to the left and normal appearing bilateral superior oblique muscles (yellow arrowhead). (Photo and images courtesy of Dr. Amanda Henderson) Seen in the bottom left photo is an example of severe proptosis in another patient with TED. Viewing the globes from above or from below (as in this case) allows for a qualitative assessment of globe position when an exophthalmometer is unavailable. (Photo courtesy of Dr. Ryan Walsh)

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2  Disorders of the Pupils, Eyelids, and Orbits

with thyroid eye disease or other orbital pathology, resistance is often appreciated in one or both eyes. • Relative globe position can be evaluated by simply comparing the position of the two eyes by looking from above (e.g., patient is 45° reclined, while the examiner is at the head of the patient looking down) or looking from below (e.g., have the patient assume a chin-up head position with the examiner looking up from the chin toward the eyes). This will allow for asymmetric exophthalmos (e.g., proptosis due to orbital inflammation or thyroid eye disease) or enophthalmos (e.g., retraction of the globe due to metastatic breast cancer) to be appreciated. However, the globe position should be quantified (and compared over time) using a Hertel exophthalmometer, whenever possible.

2.3.3 Thyroid Eye Disease Case:  A 45-year-old woman presented with a complaint of “bulging” eyes for the past 3 months. She also complained of a sandy/gritty sensation OU and double vision when looking far to the right and to the left. She had experienced recent unintentional weight loss, palpitations, and heat intolerance. Exam demonstrated mild abduction deficits OU with a corresponding esotropia worse in right and left gaze, while abducting saccades appeared normal in velocity, but terminated abruptly due to the motility deficits. There was eyelid retraction OU with scleral show inferiorly and superiorly, elevated position of the lateral upper lid (temporal flare), and when having the patient look down, the upper eyelid was slower to depress than the globe itself (lid lag). Slit lamp exam demonstrated punctate epithelial erosions (due to dry eye/ocular surface irritation from corneal exposure), and measurements using a Hertel exophthalmometer were 27  mm OU (normal is typically 50–55

Usually bilateral

Eye pain and/or headache common

Bilateral > unilateral Normal

Laterality Unilateral (bilateral is rare)

Usually present

Usually present

Pain Prominent

Table 3.1  Help me now with acute onset persistent vision loss Distinguishing feature Evolving over hours to days; prominent rAPD and dyschromatopsia; MR ON enhancement common, OCB present in majority Evolving over hours to days; no rAPD if bilateral and symmetric; MR ON enhancement common Mainly anti-MOG (optic nerve sheath enhancement) and NMO (chiasmal involvement), consider sarcoidosis, syphilis and othersa Rapid onset over seconds, minutes or hours; headaches, temporal/scalp tenderness, jaw claudication, constitutional symptoms, symptoms of polymyalgia rheumatica, diplopia

56 3  Loss of Vision and Other Visual Symptoms

>50–55

Older patient with vascular risk factors

NAION

BRAO/ CRAOb

Normal (swollen if ophthalmic artery involvement)

Swollen

Unilateral (bilateral is rare)

Unilateral “Absent (unless due to GCA)”

If present, mild

(continued)

Rapid onset over seconds, minutes or hours; the fellow eye should be crowded and have a small cup:disc ratio (“disc at risk”); vascular risk factors present; if vision loss is mild, swelling is bilateral and diabetes retinopathy is present, consider diabetic papillopathy Retinal pallor/ Rapid onset over seconds, minutes or hours; central whitening, vision may be relatively cherry red spared in CRAO if a spot, box car appearance in cilioretinal artery is present; vessels, retinal if there is only mild vision loss due to a BRAO, rAPD emboli may be absent; retinal vein occlusion can have nerve swelling, tortuous vessels, hemorrhage, CWS

Normal (rare macular star)

Vision loss—the examination… 57

Pain Absent

Laterality Unilateral or bilateral

Retinal exam Normal

Distinguishing feature A diagnosis of exclusion (i.e., rule out visual pathway disease) and inclusion (i.e., there are a variety of bedside techniques that can demonstrate the non-­ physiologic nature of the vision loss)

rAPD relative afferent pupillary defect, ON optic nerve, anti-MOG myelin oligodendrocyte glycoprotein, NMO neuromyelitis optica, GCA giant cell arteritis, AAION arteritic anterior ischemic optic neuropathy, PION posterior ischemic optic neuropathy, CWS cotton wool spots, BRAO branch retinal artery occlusion, NAION non-arteritic anterior ischemic optic neuropathy, CRAO central retinal artery occlusion a Infectious etiologies to consider in the differential of optic neuropathy: Lyme, syphilis, tuberculosis, HIV, Epstein-Barr virus, cytomegalovirus, coronavirus b Other retinal disorders to consider: Central serous retinopathy—central loss and photopsia, abnormal exam and macular OCT; retinal detachment—flashes, floaters, then vision loss (usually peripheral to central); macular edema or macular hole—central vision loss, metamorphopsia; acute zonal occult outer retinopathy (AZOOR)—enlarged blind spot(s), photopsias, can have optic nerve swelling

Functional vision lossc

Optic nerve Age exam Any age, may or Normal may not have psychiatric co-morbidities

Table 3.1 (continued)

58 3  Loss of Vision and Other Visual Symptoms

If the patient complains of peripheral visual field loss, be sure to exclude conditions that affect the optic nerves such as glaucoma or papilledema (both should be apparent with ophthalmoscopy), retinal disorders such as retinitis pigmentosa, and rarely bilateral homonymous hemianopias with bilateral macular sparing can be responsible (rare, and a vertical step should be seen). With organic peripheral vision loss (e.g., glaucoma), when the stimulus size is doubled and the target distance is doubled (e.g., test each eye individually, and move 1 finger from peripheral to central in each quadrant at 3 feet taking note of when the patient can see the target, then do the same with 2 fingers at 6 feet), the visual fields should double in size (a cone shape). With functional peripheral field loss, the fields will often stay the same despite doubling the stimulus and distance (a tunnel shape). If the patient claims complete blindness in one or both eyes if an optokinetic stimulus generates nystagmus in the affected eye(s), then this tells you that the vision is probably 20/400 or better but doesn’t prove that the vision is normal

c

Vision loss—the examination… 59

Chiasmal

Optic nerve compression

Progressive bilateral vision loss

History Progressive unilateral vision loss

Bilateral ON Normal pallor is common (temporal thinning with OCT RNFL and nasal thinning with OCT GCL OU)

Bilateral (bitemporal) >  unilateral (monocular temporal)

Optic nerve exam Retinal exam Laterality Pallor (but can Normal Unilateral >  have unilateral bilateral ON swelling if the compression is anterior)

Table 3.2  Help me now with subacute to chronic vision loss MRI Compressive meningioma or other mass, optic nerve sheath meningioma (CT can be helpful here, look for linear calcification along the optic nerve, aka “tram-tracking”) Sellar/para-sellar mass lesion (meningioma, macro-adenoma, cranio-­ pharyngioma); enhancement (lymphocytic hypophysitis, sarcoidosis, Erdheim-Chester disease)

With slow chiasmal compression, temporal defects are often not recognized by the patient. These patients commonly have failed refraction, cataract surgery, etc.—visual fields are the key!

Other If optic nerve atrophy in one eye and swelling in the other (Foster-­Kennedy syndrome), think frontal mass lesion compressing one nerve and causing elevated ICP (papilledema in the fellow eye)

60 3  Loss of Vision and Other Visual Symptoms

Bilateral (unilateral or bilateral homonymous defects, inferior predominance given parietal involvement)

Normal

Normal

Posterior cortical atrophy

Progressive vague visual complaints, difficulty reading and navigating; simultanagnosia is commona

Bilateral (homonymous— more congruous with posterior lesions [occipital], incongruous with anterior lesions [optic tract])

Normal Normal (commonly see homonymous OCT GCL thinning with chronic optic tract lesions—can have mild pallor with tract pathology too)

Retro-­chiasmal Usually more acute/subacute, but can be chronic

Mass or inflammatory lesion involving optic tract, thalamus, optic radiations (through temporal, parietal lobes), occipital lobe—e.g., meningioma and other tumors, PML, posterior cortical atrophy (see below) May see parietal or parieto-occipital atrophy on MRI or hypometabolism on PET scan

(continued)

Usually due to Alzheimer’s dementia, often precedes significant cognitive symptoms. Consider other neurodegenerative disorders (Lewy body dementia) in the differential and prion disease when rapidly progressive

While the vision loss is homonymous, the patient often perceives vision loss to be on the side of the temporal loss—visual fields are the key for localization

Vision loss—the examination… 61

Nutritional or metabolic optic neuropathy

Elevated ICP/ papilledema

History Headaches, transient visual obscurations, pulsatile tinnitus, weight gain, peripheral vision loss when moderate-­severe, central vision loss when very advanced Progressive central vision loss, may also have neuropathy, myelopathy

Table 3.2 (continued)

Temporal pallor with thinning of the papillomacular bundle

Optic nerve exam Bilateral swelling, obscuration of blood vessels, papillary or peripapillary hemorrhage

Usually normal Bilateral ≫  unilateral central or cecocentral scotomas

Retinal exam Laterality Rare macular Bilateral ≫  star or unilateral macular edema

Other IIH is the most common cause, especially in an overweight female, but a mass lesion must be excluded expeditiously. Less commonly due to acute (e.g., viral or bacterial) or chronic (e.g., sarcoidosis) meningitis. Rarely  due to elevated protein from a schwannoma or spinal tumor (ependymoma)b Can see optic nerve Consider B12 (check level T2 hyperintensity, and methylmalonic acid); although this can folate (RBC folate level); occur with any optic thiamine; copper deficiency nerve disorder (copper and zinc levels); ask about bowel surgery, malnutrition, alcohol, smoking history, and medicationsd; dominant optic atrophy, Leber hereditary optic neuropathy

MRI In IIH: transverse sinus stenosis, flattening of posterior sclera, distension of optic nerve sheath, empty sella

62 3  Loss of Vision and Other Visual Symptoms

Varies depending on etiology— normal, pale, swollen; associated uveitis, vitritis, retinitis, etc.

Normal

Comprehensive medical and neurologic history and examination is especially important

There may or may not have been a specific inciting event

Other infectious, inflammatory, autoimmune optic neuropathy

Functional vision lossc

Normal

Bilateral or unilateral

Varies Unilateral or depending on bilateral etiology (e.g., macular star in syphilis, sarcoidosis)

Depends on etiology—e.g., optic nerve sheath involvement and/or optic nerve enhancement with syphilis or sarcoidosis Normal

(continued)

If the peripheral visual fields are affected, look for a “cloverleaf” pattern on automated perimetry, non-physiologic tunneling of fields (e.g., by doubling the target size and distance, the fields should double in size regardless of the degree of vision loss).

Consider Lyme, syphilis, sarcoidosis, fungal infections, tuberculosis, progressive optic neuropathies in MS

Vision loss—the examination… 63

Isolated progressive vision loss

History Ask about photophobia, photopsias, nyctalopia (night blindness)

Retinal exam Abnormal in advanced cases (bony spicules and hyper-­ pigmentation in the peripheral retina in retinitis pigmentosa)

Large cup:disc Normal ratio and elevated IOP in most

Optic nerve exam Normal or atrophy with advanced disease

Bilateral> unilateral

Laterality Bilateral > unilateral (consider a condition like RP with peripheral loss)

Normal

MRI Normal

Other When it is not clear whether the etiology is optic neuropathy or retinopathy, VEP (abnormal in the former) and ERG (abnormal in the latter) can be helpful. If diffuse constriction, check vitamin A level, and if normal appearance of optic nerves and retinae (especially with normal VEP/ERG and OCT), consider functional Consider glaucoma with cupped nerves with normal-­appearing neuroretinal rims (i.e., no pallor), and absence of dyschromatopsia and rAPD. Don’t forget about normal tension glaucoma with normal IOP

ON optic nerve, ICP intracranial pressure, OCT optical coherence tomography, RNFL retinal nerve fiber layer, GCL ganglion cell layer, OU both eyes, IIH idiopathic intracranial hypertension, PML progressive multifocal leukoencephalopathy, PET positron emission tomography, RP retinitis pigmentosa, VEP visual evoked potentials, ERG electroretinogram, IOP intraocular pressure

Glaucoma

Retinopathye

Table 3.2 (continued)

64 3  Loss of Vision and Other Visual Symptoms

Aside from being essential to evaluate for optic nerve disease, Ishihara or HRR (Hardy Rand and Rittler) color plates serve as a rapid screening test for simultanagnosia in posterior cortical atrophy—e.g., the patient will be able to identify the individual colors that make up the circles, but will not be able to put the pieces (circles) together to form the whole (numbers or shapes). If an older patient with normal ocular and anterior visual pathway examination and vague visual complaints performs poorly on color vision testing (that is not due to congenital color blindness), consider PCA b Rarely, the vision loss due to “fulminant” idiopathic intracranial hypertension is acute in onset; rule out mass lesion urgently whenever papilledema is present; typically vision loss consists of mild field loss (enlarged blind spots) with normal acuity and color vision and no rAPD. If central (acuity) and color vision are abnormal, damage to the optic nerves is quite advanced (be concerned!), or there is optic nerve injury due to another process (e.g., optic neuritis) c If the patient complains of peripheral visual field loss, be sure to exclude conditions that affect the optic nerves such as glaucoma or papilledema (both should be apparent with ophthalmoscopy), retinal disorders such as retinitis pigmentosa, and rarely bilateral homonymous hemianopias with bilateral macular sparing can be responsible (rare, and a vertical step is common in this situation). see Table 3.1 Help me now with acute onset persistent vision loss above for a description of some useful examination techniques when functional vision loss is suspected d Consider toxicity in the differential as well including ethambutol, methanol, amiodarone, lead, arsenic, tacrolimus, vigabatrin, among others e Other retinal disorders to consider: Central serous retinopathy—central loss and photopsia, abnormal exam and macular OCT; macular edema or macular hole—central vision loss, metamorphopsia; acute zonal occult outer retinopathy (AZOOR)—enlarged blind spot(s), photopsias, can have optic nerve swelling

a

Vision loss—the examination… 65

66

3  Loss of Vision and Other Visual Symptoms

• Visual fields to confrontation—line up eye to eye with the patient and have them look at your nose, evaluate one eye at a time by having them count your fingers (usually displaying 1, 2, or 5 fingers) on one hand at a time or both hands simultaneously while assessing all 4 quadrants within the central 20–30 degrees. Example: show 1 finger on your left hand in the superior temporal quadrant while simultaneously showing 2 fingers on your right hand in the inferior nasal quadrant of their right eye, and ask the patient, “how many fingers do you see?” If the patient sees 3 fingers, assess the other quadrants next, and if the patient says something other than 3, evaluate these 2 quadrants individually and more thoroughly. Use finger counting as an initial rapid screen although more detailed testing is often needed when a field defect is suspected, including finger/hand comparison or red color comparison, for example, if a monocular inferior altitudinal defect is suspected OD, have the patient cover OS while the examiner holds one finger/hand/red object above the horizontal meridian and the other (identical target) the same distance below the horizontal meridian while the patient looks at the examiner’s nose, and ask the patient if one target is seen less clearly than the other. This allows for comparison to the right and left of the vertical meridian (e.g., homonymous hemianopia and bitemporal hemianopia), above and below the horizontal meridian (e.g., arcuate or altitudinal defect), or for comparison of one quadrant to another. However, none of these is a substitute for automated static visual field perimetry (e.g., Humphrey or Octopus) or dynamic perimetry (e.g., Goldmann)! • Swinging flashlight test to evaluate for a rAPD—in a dark room with the patient fixating on a distant target (a near target will induce miosis), first evaluate the reactivity of each pupil. Then, shine the light in the right eye for several seconds (e.g., 2), then the left eye for the same period of time (e.g., 2  s—if the light is held on one eye longer than the other, this can create the false appearance of a rAPD in a normal patient), then the right eye, left eye, etc. Constriction of each pupil should be symmetric, and if dilation is seen in one pupil during the swinging flashlight test, this represents

Vision loss—the examination…

67

a rAPD in that eye and is typically attributed to optic nerve disease. • Perform a fundus examination with particular attention to the optic nerve head (e.g., swelling, pallor?), arteries (e.g., Hollenhorst or other plaques) and veins (e.g., arteriovenous nicking, tortuosity due to retinal vein occlusion, papilledema), as well as the macula (e.g., loss of foveal reflex, exudates, and pigmentary changes) (Fig. 3.1) (dilated slit lamp and indirect evaluation is often needed to evaluate for anterior segment

Optic disc

Papillomacular bundle

Cup Fovea Neuro-retinal rim

Macula

Cilioretinal artery

Artery Vein

Fig. 3.1  The fundus exam—structures to identify and evaluate: During routine ophthalmoscopy, the following structures are of particular interest: the optic disc and cup (and record the cup:disc ratio when able), neuroretinal rim (e.g., is it pale due to optic neuropathy? is there a thin rim due to a large cup from glaucoma?), and follow the course of the retinal arteries and veins (e.g., A-V nicking due to hypertension? arterial plaque due to retinal occlusion?). The fovea/macula and peripheral retina are more difficult to visualize on undilated examination, but evaluation is important when maculopathy or retinopathy is suspected. The papillomacular bundle may be preferentially affected by certain conditions including Leber’s hereditary optic neuropathy or nutritional disorders (e.g., B12 deficiency), resulting in temporal optic nerve pallor and central or centrocecal scotomas. A cilioretinal artery is a normal variant, and if present in a patient with a central retinal artery occlusion, it can be responsible for relatively preserved central visual function as a portion of the macula continues to be perfused by the unaffected choroidal circulation

3  Loss of Vision and Other Visual Symptoms

68

• • • •

d­ isease [as well as stereoscopic evaluation of the optic nerve and macula] and peripheral retinal pathology, respectively) Evaluate for orbital signs (injection, chemosis, and proptosis) Evaluate for anisocoria and eyelid function Evaluate the function of all cranial nerves (especially the third, fourth, sixth nerves, V1 and V2 given the possibility of a sphenocavernous or orbital localization) Neuro-ophthalmic evaluation commonly includes formal visual field testing and optical coherence tomography (Fig. 3.2) of the retinal nerve fiber layer (RNFL), macula and inner plexiform layer-ganglion cell layer (IPL-GCL), and fundus photography, although certain situations call for additional ophthalmic testing with fluorescein angiography, fundus autofluorescence imaging, orbital ultrasound, electroretinogram and visually evoked potentials (Table 3.3)

3.3

I nterpretation of Monocular or Binocular Visual Fields—Dr. Neil Miller’s 10 Visual Field Rules to Live by

1. Monocular visual field defects are almost always prechiasmal—think ophthalmic (anywhere from cornea to retina) or neuro-ophthalmic (optic nerve). Visual field defects due to retinal and optic nerve disease may respect the horizontal meridian and are indistinguishable; however, fundus exam is usually abnormal in retinal disease (see “Retina” and “Optic nerve”) (Figs. 3.3 and 3.4) 2. Bitemporal defects that respect the vertical meridian localize to the optic chiasm (see “Chiasm” below) (Fig. 3.4) 3. Homonymous (and bilateral) defects are due to retro-­chiasmal pathology (see “Retrochiasmal” below) (Fig. 3.4) 4. Complete homonymous defects are nonlocalizing, for example, this can be due to a retrochiasmal lesion anywhere from optic tract to occipital lobe (see “Retrochiasmal” below) (Fig. 3.4) 5. Visual acuity is unaffected by a homonymous visual field defect (the patient has use of half a macula; see “Retrochiasmal” below) (Fig. 3.4)

++ −

− − −

++ +

−

−

Optic nerve head drusen ++ + ++ + +

Optic nerve swelling (AION) ++ ++ + − ++

Optic nerve swelling (not AION) ++ ++ + − ++

−

− − ++ (mf/p)

− ++ ++ (ff)

− −

++ (p)

− −

Chronic retinal / BRAO Unexplained Unexplained macular disorder peripheral central or suspected vision loss CRAO vision loss + + + + + + + ++ ++ + ++ − + + ++ − ++ ++ ++ ++

−

− −

Chiasmal disorder + + − − ++

−

− +

Retro-­ chiasmal disorder − +b − − ++

BRAO branch retinal artery occlusion, CRAO central retinal artery occlusion, OCT optical coherence tomography, RNFL retinal nerve fiber layer, GCL ganglion cell layer, FA fluorescein angiography, FAF fundus autofluorescence imaging, mf multifocal electroretinogram, p pattern electroretinogram, ff full field electroretinogram, AION anterior ischemic optic neuropathy (vasculitic or non-vasculitic) − Not usually helpful + May be helpful ++ Very helpful (continued)

Test Fundus photos OCT RNFL/GCLa FA FAF Perimetry (static or dynamic)c Orbital ultrasound − Visual-evoked + potentialsd Electroretinogramd −

Optic nerve disorder (no swelling) + ++ − − ++

Table 3.3  Common neuro-ophthalmic ancillary tests

Interpretation of Monocular or Binocular Visual Fields… 69

OCT of the retinal nerve fiber layer (RNFL) is most beneficial when interpreted in conjunction with OCT of the macula and ganglion cell layer (GCL). When clear optic nerve swelling is present, OCT of the RNFL is less helpful and OCT of the GCL is most helpful since these measurements reflect the integrity/structure of the neurons without the confounding presence of optic nerve edema. OCT angiography is relatively new technology that is expensive, not widely available, and its benefits and pitfalls/artifacts are not as well understood as more established testing such as FA b OCT may be helpful in some cases of chronic retrochiasmal lesions following retrograde trans-synaptic degeneration. In these cases, a homonymous pattern of hemi-macular thinning may be demonstrated on the GCL analysis c Perimetric testing mainly consists of static (e.g., Humphrey, Octopus) or dynamic (e.g., Goldmann) testing. Static perimetry is more widely available, and tends to be less technician dependent and more reproducible. Typically, 10-2 field testing is for disorders affecting central vision (maculopathies) while 24-2 and 30-2 are excellent for optic nerve disorders (including glaucoma). Patients who are uncooperative, inattentive, cognitively impaired, or who perform poorly with static perimetry are usually better served by dynamic (Goldmann) testing. Dynamic testing can also evaluate the entire field of vision (e.g., 30-2 will only evaluate the central 30 degrees of vision because the vast majority of the neurons making up the optic nerve subserve this area), which can be helpful when complaints are mainly of peripheral vision loss (e.g., retinitis pigmentosa) d When the clinician is unsure as to whether vision loss is due to retinopathy/maculopathy or optic neuropathy, ordering an electroretinogram (ERG) along with visual-evoked potentials (VEP) is often beneficial. If the VEP is abnormal while ERG is normal, the localization is usually optic nerve. If the ERG is abnormal while the VEP is normal, the localization is usually retina/macula. More specifically, when central vision loss is present (but unclear if nerve or retina), multifocal and pattern ERG are the preferred tests while when peripheral vision loss is present (but unclear if nerve or retina), full field ERG is the preferred test

Table 3.3 (continued)

a

70 3  Loss of Vision and Other Visual Symptoms

Interpretation of Monocular or Binocular Visual Fields… RNFL GCL

71

IPL

ON INL

ONL

ELM

OPL

EZ

RPE

Fig. 3.2  Layers of the retina as seen with optical coherence tomography (OCT): In order from inner to outer retina: RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ELM, external limiting membrane; EZ, ellipsoid zone; RPE, retinal pigment epithelium. Note that the GCL gives rise to the RNFL, which then makes up the optic nerve (ON) (Images courtesy of Dr. Kara Della Torre)

Normal left visual field

Arcuate (Glaucoma or BRVO?)

Enlarged blind spot (Mild IIH or white dot syndrome?)

Altitudinal (NAION or BRAO?)

Centrocecal (LHON or cilioretinal A occlusion?)

Peripheral constriction (Advanced IIH or RP?)

Central (Optic neuritis or maculopathy?)

Diffuse depression (Compressive ON or CRAO?)

Fig. 3.3  Abnormal monocular visual fields with automated static perimetry—is it retina or optic nerve? A monocular visual field defect is almost always pre-chiasmal, but the appearance of the visual field cannot distinguish optic neuropathy from retinal/macular disease without additional information (e.g., optic nerve is normal, swollen, or pale; dyschromatopsia and relative afferent pupillary defect are present with optic neuropathy; e.g., metamorphopsia with macular disease, abnormal fundus exam with retinopathy/maculopathy). Each abnormal visual field above could be due to optic nerve or retinal disease, and an example of each has been given (IIH, idiopathic intracranial hypertension; LHON, Leber’s hereditary optic neuropathy; BRVO, branch retinal vein occlusion; NAION, nonarteritic anterior ischemic optic neuropathy; BRAO, branch retinal artery occlusion; RP, retinitis pigmentosa; ON, optic neuropathy; CRAO, central retinal artery occlusion)

3  Loss of Vision and Other Visual Symptoms

72 Right

Left

Optic nerve lesion

Optic nerve 1

Chiasmal lesion

Visual field defects Left Right

2 2

Meyer’s loop

3

6

4

Temporal lobe

Optic tract lesion

7

10 Optic radiation

3 4 5a

5

Occipital lobe lesion

1

Lateral geniculate body

5b 6 7

8

8 9 11

9 10 11

Fig. 3.4  Typical visual field defects associated with discrete lesions along the visual pathways: Specific monocular or binocular visual field defects can be highly localizing when the neuroanatomy of the visual pathways is understood. The temporal visual field corresponds to the nasal retina, while the nasal visual field corresponds to the temporal retina. (1) Left optic nerve lesion—while an optic neuropathy can cause a variety of monocular visual field defects (see Fig. 3.3), a complete lesion will cause no light perception vision loss in the affected eye (the violet color = a combination of damage to both nasal and temporal fibers). (2) Lesion at the junction of proximal left optic nerve and chiasm—a junctional lesion, when complete, can cause complete monocular vision loss OS due to optic neuropathy, but because some fibers originating in the right inferonasal retina decussate in the chiasm and then bulge forward into the left anterior chiasm/proximal nerve (anatomically known as “Wilbrand’s knee,” a somewhat controversial concept), a small superotemporal (“junctional”) scotoma can be seen in the right eye. (3) Chiasmal lesion—due to involvement of the crossing fibers (responsible for temporal visual fields) coming from right and left eyes, bitemporal hemianopia is the result. (4) Left optic tract lesion—since this is a retrochiasmal lesion, a right homonymous hemianopia (HH, and usually a mild right relative afferent pupillary defect) is the result. When incomplete, these tend to be (continued)

Interpretation of Monocular or Binocular Visual Fields…

73

incongruous (asymmetric). When complete, the HH is nonlocalizing (e.g., it could be tract or could be occipital). (5) Left lateral geniculate nucleus lesion—there are two characteristic visual field patterns: (a) right homonymous quadruple sectoranopia and (b) right homonymous horizontal sectoranopia. (6) Left temporal lobe (Meyer’s loop)—right superior quadrantic defect (“pie in the sky”), which when incomplete, may be incongruous. (7) Left parietal lobe—right HH that is more dense inferiorly (“pie on the floor”) and often incomplete. (8) Left occipital lobe, superior to calcarine fissure— right inferior quadrantic defect, congruous (symmetric) when incomplete, often with macular sparing (i.e., sparing of the occipital pole/tip due to dual vascular circulation). (9) Left occipital lobe, inferior to calcarine fissure— right superior quadrantic defect, congruous, often with macular sparing. (10) Right complete occipital lesion with sparing of the pole can be a complete left HH, or congruous when incomplete, macular sparing. (11) Right occipital pole lesion—left homonymous central scotoma Fig. 3.4 (continued)

6. Optic tract lesions cause incongruous (asymmetric) homonymous visual field defects. However, a complete homonymous hemianopia can also be seen with a tract lesion (see Rule #4 and “Retrochiasmal—Optic tract” below) (Fig. 3.4) 7. Lateral geniculate nucleus lesions cause incomplete homonymous visual field defects that are distinct from all other retrochiasmal defects (i.e., horizontal sectoranopia and quadruple sectoranopia; see “Retrochiasmal—LGN” below) (Fig. 3.4) 8. Temporal lobe lesions, when incomplete, produce incongruous superior quadrantic homonymous defects (so-called “pie in the sky”; see “Retrochiasmal—Optic radiations” below) (Fig. 3.4) 9. Parietal lobe lesions can produce incomplete homonymous visual field defects, more dense inferiorly (so-called “pie on the floor”). Other neurologic symptoms are typically present including neglect, (visual and tactile) extinction and other visuospatial abnormalities (consider posterior cortical atrophy, if progressive; see “Retrochiasmal—Optic radiations” below) (Fig. 3.4) 10. Occipital lobe lesions produce congruous (symmetric) homonymous visual field defects. However, a complete ­homonymous hemianopia can also be seen with an occipital lesion (see Rule #4). Macular sparing may be seen when the

3  Loss of Vision and Other Visual Symptoms

74

occipital pole is unaffected (probably due to dual circulation), and conversely, a homonymous central scotoma is highly suspicious for an occipital pole lesion. Bilateral congruous homonymous hemianopias are almost always due to bilateral occipital lesions and can affect visual acuity (see “Retrochiasmal—Occipital lobe” below) (Fig. 3.4)

3.4

Ancillary Testing in NeuroOphthalmology

Table 3.3

3.5

 rechiasmal (Monocular Vision Loss) P Tables 3.1 and 3.2; ESM 3.1

1 . It is monocular, what do I need to know first? (a) Acute, subacute, or chronic?—e.g. is this dangerous and urgent (e.g., giant cell arteritis causing ischemic optic neuropathy and central retinal artery occlusion)? (b) Painful or painless?—e.g. optic neuritis is usually painful. (c) Age of the patient?—e.g., optic neuritis is common in the young, nonarteritic ischemic optic neuropathy in the older population 2. It is monocular, but is there a rAPD? (a) Vision loss with moderate to severe rAPD (Fig. 3.5; Video 3.1) • Usually due to an optic neuropathy (see “Optic nerve” section below), less commonly due to significant retinal damage (e.g., central retinal artery occlusion)—with the latter, the retinal pathology is almost always visible on fundus exam. (b) Vision loss with mild or no rAPD • Consider bilateral optic nerve disease (either bilateral symmetric acute optic neuropathies or pre-existing field loss in one eye due to glaucoma, now with new optic neuropathy in the fellow eye); pupils are often sluggishly reactive to light bilaterally.

Prechiasmal (Monocular Vision Loss)

75

Swinging flashlight test R

L

Left Optic Nerve Pallor

OD constricts briskly

Left Optic Nerve Compression by Meningioma

L

R

OS dilates ( rAPD )

Fig. 3.5  Relative afferent pupillary defect (rAPD) and other findings of a unilateral optic neuropathy: Patients with unilateral optic nerve disease typically have loss of visual acuity, dyschromatopsia, visual field loss, the optic nerve itself may appear normal (e.g., acute retrobulbar optic neuritis) or abnormal (e.g., optic nerve pallor months after an optic neuritis attack), and a relative afferent pupillary defect (rAPD) is a prominent feature of an optic neuropathy (unless there is bilateral optic nerve involvement). This patient has a compressive left optic neuropathy due to a meningioma, and aside from hand motions visual acuity and inability to see any color plates during testing, there was diffuse visual field loss OS, optic nerve pallor, and a clear left rAPD as seen with the swinging flashlight test. It’s as if the patient is in a bright room OD (i.e., the pupil constricts), but then when moving the light from the right to the left eye, it’s as if the patient is moving into a darker room (i.e., the pupil dilates). The light should be held for the same duration on each eye; if the light is held on one eye longer than the fellow eye, this may cause a false positive in a normal patient. The examiner must be careful when looking for a rAPD in a patient with anisocoria because less light is entering the smaller pupil; occasionally, this can create the false appearance of a rAPD on the side of the miosis

• Consider neuroretinitis or other retinal/macular disease where dyschromatopsia and rAPD can be mild and proportional to field and acuity loss (while dyschromatopsia and rAPD are often quite prominent and can be out of proportion to acuity and field loss with optic neuropathy). A macular star may not be present at presentation but develop over weeks. • Consider functional with severe unilateral vision loss, normal nerve and retina/macula, and no rAPD. • Consider functional or bilateral occipital lesions (strokes causing bilateral homonymous hemianopias) with severe bilateral vision loss and brisk pupillary light reflexes.

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76

3.5.1 Retina 3.5.1.1  Retinal TIA (Amaurosis Fugax) Case  A 65-year-old man with a history of hypertension and hyperlipidemia experienced the abrupt onset of monocular vision loss OD, with onset “like a curtain coming down.” There was no headache, no positive visual phenomena, and vision returned completely 15  minutes later. Two weeks prior, he experienced mild unexplained left arm weakness for about 1  hour, which resolved spontaneously. Following his transient vision loss, he presented to the emergency department, at which time afferent examination was normal. There was no rAPD, and optic nerves and retinae appeared normal with the exception of a Hollenhorst plaque (i.e., a refractile cholesterol embolus) that was lodged in the inferior retinal artery. The diagnosis of a retinal transient ischemia attack (TIA) was made, and MRI of the brain with diffusionweighted imaging was normal without evidence of infarction, although MR angiography demonstrated severe (>90%) carotid stenosis on the right, which was thought to be causative. There were no symptoms or signs suggestive of giant cell arteritis (GCA), and CBC, ESR, and CRP were normal. He underwent urgent carotid endarterectomy (CEA) and experienced no further transient visual or neurologic symptoms.

R

R

L

Fig. 3.6  Hollenhorst plaque in a patient with retinal TIA: While the patient had normal vision by the time he was evaluated, an asymptomatic cholesterol embolus (Hollenhorst plaque) was seen in the affected eye

Prechiasmal (Monocular Vision Loss)

77

Video/Photo  Fig. 3.6 Key questions to ask  When amaurosis fugax is suspected, ask about symptoms related to GCA (headaches, jaw claudication, scalp tenderness, etc., see GCA section below) as well as about smoking and vascular risk factors. Sudden onset monocular vision loss, especially when ascending or descending (e.g., like a curtain), lasting minutes, and without headache or positive visual phenomena is highly suggestive of a vascular event. Key findings to elicit  If the vision loss is persistent at the time of the examination, look for a cherry red spot (due to a pale, ischemia retina surrounding the normally perfused maculae, which is supplied by the choroidal circulation), segmentation of blood (due to sluggish flow) in arterial columns (also referred to as boxcarring), and/or arterial attenuation suggestive of retinal artery occlusion (central or branch retinal artery occlusion, CRAO, or BRAO, respectively). If there is evidence of optic nerve (e.g., swelling) and retinal ischemia (CRAO, branch retinal artery occlusion, cotton wool spots), consider GCA. If the retina is pale (due to ischemia), but there is no cherry red spot and optic nerve swelling is also present, this is suggestive of ophthalmic artery occlusion, which affects both retinal and choroidal circulation (can also be GCA-related). If symptoms have resolved, look closely at the vasculature and for arterial plaques (Figs. 3.7 and 3.2) How do I approach (history and exam) the patient with acute and transient vision loss? Tables 3.1 and 3.4; ESM 3.1 Pitfalls  While migrainous visual aura can produce negative phenomena (e.g., loss of vision), monocular vision loss in a patient with vascular risk factors is highly concerning for retinal ischemia. Sudden onset of new visual phenomena in a patient without a long and strong migraine history deserves urgent workup. It is more important to distinguish vascular from non-vascular causes

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78

Retina

Choroid

Arterial circle of Zinn-Haller

Branch of retinal artery

Sclera

Optic nerve Posterior ciliary artery

Central retinal artery

Fig. 3.7  Vascular supply of the optic nerve head, choroid, and retina: The ophthalmic artery is a branch of the internal carotid artery, which in turn, supplies the posterior ciliary (to choroid and outer retina) and central retinal (to inner retina) arteries. The central retinal artery (CRA) enters the optic nerve about 1 cm posterior to the globe, and an embolus may become lodged as the CRA pierces the dural sheath of the nerve, or posterior to the lamina cribosa, resulting in a CRA occlusion (CRAO, involvement of inner retinal layers, sparing of optic nerve head, outer retina, and choroid). The arterial circle of Zinn–Haller supplies the optic nerve head, which is made up of anastomoses from branches of short posterior ciliary arteries (from posterior ciliary artery, PCA), the adjacent pial network, and choroidal vessels. Hypoperfusion of the PCA is the likely cause for nonarteritic anterior ischemic optic neuropathy. Ophthalmic artery pathology (e.g., thromboembolic and giant cell arteritis) results in ischemia of the retina, choroid, and optic nerve. (Redrawn and modified with permission from: Digre KB, Corbett JJ Practical Viewing of the optic Disc. Boston: Butterworth-Heineman 2003)

than it is to distinguish monocular from binocular transient vision loss. Do not miss this!  Occasionally, retinal ischemia can be due to vasospasm (migrainous or other). This is a diagnosis of exclusion as thromboembolic causes must first be evaluated for. Patients with acute onset vision loss need urgent ophthalmic/ neuro-ophthalmic evaluation to rule out an ocular cause, for

Giant cell arteritis (GCA)

Amaurosis fugax (retinal TIA)

Unilateral or bilateral May be normal, look for evidence of optic nerve and/or retinal ischemia

>50 years Abrupt onset, Eye pain or spontaneous or headache common can be bright light-induced

Examination Normal in between, may see Hollenhorst plaque

Laterality Unilateral

Age Timing Pain >50 years Abrupt onset, Absent ascending or descending, lasting minutes

(continued)

Other Anterior circulation: Ipsilateral carotid disease (atherosclerosis, dissection) is most common; consider cardioembolic and other stroke mechanisms including hypercoagulability; consider GCA or high-grade carotid stenosis with bright light amaurosis (i.e., patient cannot see after exposure to a bright light) Inflammation of the temporal artery; usually with associated headache, jaw claudication, constitutional symptoms, diplopia

Table 3.4  Help me now with transient vision loss: Historical and examination features to narrow the differential diagnosis

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Migrainous visual aura

Any age (but be concerned if new onset in someone >50 years old)

Table 3.4 (continued) Age Hypoperfusion Any age

Progression over minutes and lasting minutes to an hour or so, may be a typical (e.g., light-induced) migraine trigger

A headache may or may not follow visual aura

Timing Pain Absent Closely associated with postural changes (e.g., sitting to standing)

Examination Normal (check vital signs and evaluate for orthostatic hypotension)

Normal

Laterality Bilateral

Bilateral > unilateral

Other Associated orthostatic lightheadedness/dizziness, can have “tunnel” vision or diffuse vision loss bilaterally; associated with inadequate hydration, medications, or autonomic dysfunction; consider vertebrobasilar insufficiency in older patients with vascular risk factors and bilateral transient vision loss Positive visual phenomena (scintillating scotoma) are more common than negative (vision loss), although either is possible

80 3  Loss of Vision and Other Visual Symptoms

Laterality Bilateral

Examination Normal

A few transient vision loss caveats: consider ocular causes such as tear film abnormalities and corneal epithelial disease (e.g., dry eye), other corneal disease (e.g., erosion), anterior chamber abnormalities (e.g., uveitis, hyphema), vitreous floaters, acute angle closure glaucoma (topiramate can be a trigger for this). Patients may not be sure whether transient vision loss was unilateral or bilateral (e.g., etiologies causing homonymous involvement such as ischemia, migraine, seizure); however, the distinction between vascular or nonvascular is more important

Pain Absent

Other Positive visual phenomena (ictal) are more common than negative (ictal or postictal) There is typically a known Absent Unilateral > bilateral Evidence of Uhthoff’s Usually Associated optic atrophy history of optic neuritis (or phenomena 50–55 years old, even when typical symptoms are lacking (e.g., headaches). Want to know more?  [7, 9]

3.5.2.3  Optic Neuritis Case  A 20-year-old woman complained of eye pain OD that was aggravated by palpation and eye movements, followed by vision loss in the same eye hours later. The vision loss progressively worsened over the next 24 h until she presented to the emergency department. Examination demonstrated counting fingers vision centrally at 2 feet OD with normal vision OS. There was a prominent rAPD OD, and the optic nerves and retinae appeared normal OU. Clinically, the diagnosis of optic neuritis was made. MRI of the brain was performed which did not show any demyelinating lesions, although there was a T2 hyperintensity and T1 contrast

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Fig. 3.10  Clinical and radiologic features of typical optic neuritis: Despite vision loss in the right eye (severe field loss in the right eye, with an artifactual rim defect seen inferiorly in the left eye, i.e., disappeared when the patient was repositioned and retested) associated with pain, the right optic nerve appeared normal due to the retrobulbar location of the optic neuritis (“the patient sees nothing and you see nothing”). T2 hyperintensity of the right optic nerve was apparent (top MRI), which can be seen acutely or chronically in a variety of optic neuropathies. However, contrast enhancement of the right optic nerve was also demonstrated, a finding that is common with an acute inflammatory/autoimmune optic neuropathy

enhancement of the right optic nerve. Intravenous steroids were given for 3 days with improvement to 20/400 centrally OD. By 3 months, her vision was back to 20/25 OD with persistent dyschromatopsia and rAPD, and temporal pallor. Follow-up MRI at 1 year was also normal without evidence of lesions suggestive of multiple sclerosis (MS). Figure  Fig. 3.10 Key questions to ask • History of other vision loss/episodes? (previous optic neuritis) • History of neurologic symptoms? (symptomatic demyelinating lesions of brain or spinal cord) • Personal or family history of autoimmune disease? (MS or related)

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Key findings to elicit  Typical: Due to the retrobulbar location of the inflammation, the fundus exam will often appear normal. Mild-moderate unilateral optic nerve swelling can occur in about 1/3 of cases in adults (swelling and bilateral involvement more common in kids—see Chapter 7: Pediatric Clinical Pearls). Significant dyschromatopsia and rAPD are prominent features (compared to a maculopathy or neuroretinitis for instance). Atypical: Retinal/macular exudates, bilateral involvement, or severe swelling with hemorrhages in an adult, consider other etiologies (Fig. 3.11). How do I approach (history and exam) the patient with acute vision loss? Table 3.1; ESM 3.1 Pitfalls  While central vision is often involved with optic neuritis (involvement of the papillomacular bundle, Fig. 3.1), any pattern

Fig. 3.11  Atypical fundus features in optic neuritis: Consider an atypical cause (e.g., neuromyelitis optica, anti-myelin oligodendrocyte glycoprotein [MOG], neurosarcoidosis) when any of the following features are present in an adult with optic neuritis: (1) bilateral involvement, (2) severe swelling, (3) hemorrhage (arrow), (4) light perception or no light perception vision, (5) retinal exudates, and/or (6) steroid dependence

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of monocular vision loss can be seen (Fig. 3.3). Remember that a maculopathy can be responsible for central vision loss as well, so dilated examination is warranted in these patients. If a macular star (may be absent acutely or missed with undilated direct ophthalmoscopic exam) is seen or there is optic nerve edema with a mild or no rAPD, ask about recent exposure to kittens or cat scratches (neuroretinitis due to Bartonella henselae) Do not miss this!  Along with atypical findings on the fundus exam (see above), no light perception vision, steroid dependency (e.g., recurrence or worsening symptoms when coming off prednisone), and bilateral simultaneous or chiasmal involvement should lead the clinician to consider neuromyelitis optica (NMO), anti–myelin oligodendrocyte glycoprotein (anti-MOG), neurosarcoidosis, syphilis, neuroretinitis especially when a macular star is present among others (Fig. 3.12). If there is no pain and vision loss is unilateral, bilateral simultaneous, or sequential, consider Leber’s hereditary optic neuropathy.

T2 Coronal

T1 Coronal with contrast

T1 Coronal with contrast

Fig. 3.12  Radiologic features of atypical optic neuritis: A 50-year-old woman with neuromyelitis optica (previous attack of myelitis and + aquaporin antibodies) presented with severe bilateral eye pain and vision loss (diffuse depression OD and mainly temporal loss OS). MRI demonstrated asymmetrically enlarged and T2 hypertense optic chiasm (right > left, white arrow) with contrast enhancement of the chiasm (yellow arrow), prechiasmatic right optic nerve, infundibulum, and bilateral optic nerve sheaths (orange arrows, a finding that is generally more typical of anti-MOG)

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What is next?  Brain MRI to assess risk for multiple sclerosis— if no brain lesions, risk of developing MS is about 20% at 15 years. If 3 or more brain lesions, risk is about 90% at 15  years, or depending on other signs/symptoms, the patient may meet McDonald 2017 criteria for a diagnosis of MS at presentation. MRI of the cervical and thoracic cord may be helpful to search for asymptomatic lesions, and should always be performed when symptoms/signs indicative of a myelopathy are present. Lumbar puncture is often needed in atypical cases to exclude other etiologies and to look for oligoclonal bands (common in MS). When atypical features are present, other inflammatory, autoimmune, paraneoplastic, and infectious etiologies should be explored. Consider testing for NMO, a­ nti-­MOG, and other atypical etiologies when appropriate. Contrast-­enhancement involving the optic nerve(s) ± chiasm is typically seen with demyelinating diseases (MS, NMO, anti-MOG, and acute disseminated encephalomyelitis [ADEM]), but also consider neoplasm (lymphoma, leukemia, and glioma) and infection (viral, syphilis, and Lyme), as well as radiation-induced, sarcoidosis, and vasculitis in the differential. Treatment options  IV steroids for 3–5 days followed by an oral steroid taper can help to hasten visual recovery/mitigate pain, although the final visual outcome is likely to be the same with or without steroids in typical optic neuritis. Fortunately, visual prognosis for these patients is favorable, with >90% achieving 20/40 acuity or better. For NMO and MOG, more aggressive therapies are often needed acutely if there is no steroid response (e.g., plasma exchange). If you can only remember one thing…  Not all central vision loss in a young patient (especially female) is optic neuritis! A dilated fundus exam may provide important clues (e.g., macular star in neuroretinitis) or may lead to a non-neurologic diagnosis (central serous chorioretinopathy). Want to know more?  [10–12]

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3.5.2.4  Papilledema Case  A 30-year-old woman complained of headaches for the last 3 months with episodes of “graying out vision” OU for the last 2 weeks. Her BMI was 32, and she gained 15 pounds in the last 6 months. She also admitted to “whooshing” in both ears that was synchronous with her heartbeat. On examination, there was no rAPD, and normal acuity and color vision. Static visual field perimetry demonstrated enlarged blind spots OU. She had bilateral optic nerve swelling with obscuration (by edema) of several of the blood vessels on the optic nerve head, as well as those exiting the nerve. Contrast-enhanced MRI demonstrated distended optic nerve sheaths and flattening of the posterior sclera OU along with an empty sella. MR venogram demonstrated bilateral transverse sinus stenosis (TSS), without evidence of venous thrombosis. Opening pressure on lumbar puncture (measured in a lateral recumbent position with legs extended) was 42  cm of water. Idiopathic intracranial hypertension (IIH) was diagnosed, and the patient was started on acetazolamide and counseled on weight loss. Figure  Fig. 3.13 Key questions to ask • Persistent vision loss or transient visual obscurations (TVOs, postural change induces hypoperfusion of the swollen nerves as in this case)? • Headaches? • Double vision (sixth nerve palsy, unilateral or bilateral, is most common)? • Pulsatile tinnitus? • Recent weight gain? • Neck or arm pain (radicular irritation due to elevated ICP)? • Arm, leg or back pain, sensorimotor symptoms? (rarely a spinal tumor can cause elevated ICP)? • Obstructive sleep apnea?

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Fig. 3.13  Clinical features of papilledema: Visual acuity and color vision are almost always normal early in the course of idiopathic intracranial hypertension (IIH), and automated static visual field perimetry should be followed closely. Enlarged blind spots (due to distortion of the peripapillary retina by the swollen optic nerve) are commonly seen, as well as nasal and peripheral inferior and superior defects as the disease progresses. The fundus photos above the visual fields come from the same patient, with the white arrows pointing to several examples of vessels on the disc being partially obscured by edema (Frisen grade 4). The arrowheads point to temporal concentric peripapillary wrinkles (the fundus photo to the left comes from another patient, with chronic [Frisen grade 2] papilledema who had developed optic atrophy—note the optic nerve pallor), another potential manifestation of elevated intracranial pressure (along with retinal and choroidal folds). Hemorrhages are also commonly seen in patients with active papilledema. Fundus photography is an excellent way to document the fundus examination when available, and the Frisen papilledema grading scale should be used when possible: Grade 0—no halo of obscuration of the peripapillary nerve fiber layer; Grade 1—obscuration of the peripapillary retina with a C-shaped halo (sparing temporal margin) of retinal nerve fiber layer edema; Grade 2—circumferential halo without obscuration of blood vessels; Grade 3—major vessel(s) are obscured by edema as they exit the disc; Grade 4—major vessel(s) are obscured by edema on the disc; Grade 5—partial or complete obscuration of all vessels

• Anemia or hypertension? • Hypercoagulable state or use of oral contraceptive/hormonal drugs? (consider cerebral venous thrombosis)?

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• Use of tetra-, mino-, or doxycycline, nitrofurantoin, vitamin A (or retinoids), growth hormone, Addison’s disease, or other endocrine disorders? Key findings to elicit  Acuity and color vision are spared until late in the disease, and rAPD is uncommon unless there is severe and asymmetric field loss. Formal visual field testing is essential (most commonly Humphrey automated static perimetry), and the most common defects include enlarged blind spot, nasal defects, and/or peripheral loss. Papilledema is almost always present and should be photographed and graded using the Frisen grading scale (0–5, based mainly on obscuration of blood vessels, see Fig. 3.13) when possible. Splinter hemorrhages, located on or around the nerve, are often seen in acute cases, as well as obscuration of the blood vessels and retinal nerve fiber layer, in addition to peripapillary wrinkles and retinal/choroidal folds. Criteria exist for IIH without papilledema as well, although this rarely leads to vision loss (e.g., ICP may not be transmitted as well via a narrow optic canal or across the lamina cribrosa in certain patients due to anatomic variations). Macular exudate (or a star) may be seen when the papilledema is severe. Patients with chronic papilledema often develop gliotic changes on and around the optic nerve head, and retinochoroidal collateral vessels as well as atrophy/pallor can also develop (Fig. 3.14). Notably, a patient who has developed significant optic atrophy will be unable to swell if IIH recurs (headache and other ICP symptoms and visual exam must be relied upon in these cases). How do I approach (history and exam) the patient with acute, subacute, or chronic vision loss?  Tables 3.1 and 3.2 Pitfalls  Remember that not all bilateral optic nerve swelling is due to elevated ICP. If there is loss of vision, color, or atypical visual fields defects (e.g., central or centrocecal scotoma), consider other causes of optic neuropathy (e.g., optic neuritis including NMO and anti-MOG; bilateral anterior ischemic optic neuropathy in an older patient). Also, remember that optic nerve head drusen (a “lumpy bumpy” appearance, Fig.  3.15), can give the appearance of papilledema, so-called pseudopap-

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Fig. 3.14  Clinical features of advanced papilledema: While visual acuity and color vision are spared in early idiopathic intracranial hypertension (IIH), in more advanced disease, they are often involved. This patient has 20/50 acuity OU and mild dyschromatopsia. Additionally, there was severe peripheral visual field loss/constriction. While there were no active features of papilledema (e.g., hemorrhage, obscuration of blood vessels, edema), this was because they were severely atrophic and unable to swell. The arrows point to gliotic changes that give the disc margins a greyish appearance, and the arrowhead points to a retinochoroidal collateral vessel. These collateral vessels may develop in certain conditions, typically due to retinal venous outflow impairment—i.e., blood will drain via the choroidal venous system instead. In addition to chronic papilledema, collaterals may also be seen with optic nerve meningiomas, gliomas, sarcoidosis, central retinal venous occlusion, and glaucoma

illedema. Drusen can be superficial and visible on fundus exam (Fig.  3.15), or buried and more challenging to diagnosis (see Table 3.3).

Prechiasmal (Monocular Vision Loss)

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Fig. 3.15  Optic nerve head drusen—a common cause of pseudo-­papilledema: This patient was referred out of concern for papilledema, after being found to have an abnormal optic nerve appearance on routine ophthalmoscopy. Visual acuity and color vision were normal, there was no relative afferent pupillary defect, and static automated perimetry demonstrated bilateral nasal step defects (more inferior OS and more superior OD, black arrows), compatible with retinal nerve fiber layer (RNFL) injury. The white arrows point out the typical “lumpy bumpy” (i.e., yellow elevations) appearance of optic nerve head drusen, which can damage the RNFL, leading to (generally, mild and asymptomatic) visual field loss. Because the optic nerve can be elevated by the drusen (visible or buried drusen), and because the disc margins can be obscured, patients may be misdiagnosed with papilledema, when in fact this is a common cause of “pseudo-papilledema.” While the drusen are clearly visible in this patient, oftentimes this is not the case and the examiner should look for other features of an anomalous optic disc (e.g., small and crowded, anomalous vascular branching patterns [early branching and trifurcations], lack of venous engorgement, irregular elevation of the optic disc, lack of vessel or RNFL obscuration, and intact spontaneous venous pulsations). Orbital ultrasound and enhanced depth optical coherence tomography are often used to aid in the diagnosis (especially for the more challenging to diagnose buried drusen), and occasionally drusen can also be seen on a CT scan (yellow arrow, note that CT should not be ordered specifically for this purpose)

Do not miss this!  Especially when risk factors are present, venous thrombosis must be ruled out urgently. Be especially concerned with thin patients, papilledema in men, and look for secondary causes of elevated ICP (see below). The diagnosis of IIH

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cannot be made without excluding a mass lesion (with imaging) or vascular lesion (with contrast-enhanced MRI and MR venogram for cerebral venous thrombosis), meningitis (need imaging and lumbar puncture), or conditions that may cause abnormal CSF constituents (elevated CSF protein with a spinal ependymoma or Guillain–Barre syndrome). For this reason, papilledema is a finding that deserves urgent workup. Consider Vogt– Koyanagi–Harada disease when there is papilledema in addition to audiovestibular involvement, uveitis, vitiligo, and/or poliosis. What is next?  MRI w/wo and MR venogram to rule out mass lesion and thrombosis, respectively. Typical features of elevated ICP (distended optic nerve sheaths, flattening of the posterior sclera OU, empty sella, and TSS; Fig. 3.16) are commonly seen on MRI/MRV and support the diagnosis. Lumbar puncture should be performed to (1) measure the opening pressure and (2) ensure that the CSF analysis is normal without evidence of i­ nflammation/ infection (Lyme) or neoplasm (lymphoma). Patients must be followed serially for visual testing (especially with automated perimetry) and fundus exams. OCT can be helpful to monitor for damage to the ganglion cell layer and to evaluate the overall thickness of the RNFL, although the RNFL values tend to be less accurate when edema is significant. Treatment options  Acetazolamide is the most commonly used drug, and it is best to titrate up slowly when possible due to side effects. Other options include furosemide, methazolamide, zonisamide, and topiramate (the latter two may offer better headache protection but have less carbonic anhydrase effect). Counseling for weight management is essential. When acuity and color vision are affected and field loss is significant, invasive procedures may be indicated. Surgical options in those patients refractory to medical therapy or with significant vision loss include CSF shunting procedures (lumboperitoneal and ventriculoperitoneal), optic nerve sheath fenestration, venous sinus stenting, and bariatric surgery. These options depend on many factors

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T2 Axial

T1 Sagittal

MR Venography

Fig. 3.16  Radiologic features of elevated intracranial pressure: The following neuroimaging signs support the diagnosis of elevated intracranial pressure: (1) distention of the optic nerve sheaths (white arrowhead); (2) flattening of the posterior sclera (white dashed arrows); (3) empty sella (white arrow); and (4) transverse venous sinus stenosis (black arrow, bilateral in this case). Protrusion of the swollen optic nerve head into the vitreous (black arrowhead) is a finding that may be seen with optic nerve edema/elevation due to a variety of etiologies. Tortuosity of the optic nerve is another common finding with elevated intracranial pressure

(especially, the institution and available resources) and have not been compared in a large randomized controlled trial to date. If you can only remember one thing…  Patients with IIH must be followed closely for symptoms of ICP as well as for fundus exams and automated perimetry—checking visual acuity and color vision alone is inadequate! Want to know more?  [13, 14]

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3.6

Chiasmal Visual Disorders

3.6.1 Pituitary Tumor Case  A 70-year-old man presented with 6 months of visual changes. He initially noticed that vision in each eye just was not as good as it had been previously, although the exact onset of visual symptoms was unclear. He was prescribed new glasses, which did not help. He was referred for cataract evaluation, and it was felt that cataracts did not explain his visual symptoms. When looking at words, letters could go missing. Visual symptoms worsened, and he was referred to neuro-ophthalmology. Visual acuities were 20/25 OU with mild dyschromatopsia OU and no rAPD. Pupillary constriction in each eye was mildly sluggish. With fields to confrontation and static perimetry, there was a bitemporal hemianopia. He had not experienced neurologic symptoms (including headaches) to suggest a mass lesion, and he denied known endocrine disease or symptoms. MRI demonstrated a pituitary macroadenoma with compression of the chiasm, and he underwent transsphenoidal resection of his adenoma with immediate improvement in his bitemporal hemianopia. Endocrine evaluation was unrevealing, specifically with regard to growth hormone, prolactin, and ACTH levels. He was followed for years without further change in visual fields or MRI. Figure  Fig. 3.17 Key questions to ask • Are there headaches or focal neurologic symptoms/signs (hemiparesis and/or hemianesthesia) to suggest a mass lesion? • Are there endocrine symptoms to suggest pituitary compression or infiltration? (ask about excessive fatigue, weight change, mood changes, skin or hair changes, constipation, heat or cold insensitivity, excessive thirst, excessive urination, galactorrhea, impotence, change in ring, hat, or shoe size or coarsening of facial features) Key findings to elicit  Bitemporal defects that respect the vertical meridian localize to the optic chiasm. Furthermore, the specific pattern can have localizing value with a compressive lesion, for

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Fig. 3.17  Clinical and radiologic features of chiasmal compression: This patient was found to have a bitemporal hemianopia and bilateral optic nerve pallor on clinical exam. The grayscale maps (top) demonstrate left > right and superior > inferior visual field loss, suggestive of greater compression of the left and inferior aspect (respectively) of the optic chiasm, and MRI demonstrated a pituitary macroadenoma (white arrows). The grayscale maps demonstrate lower visual sensitivity as darker regions, although these are not compared to any normative database. The total deviation maps (bottom) are generated by comparing the measured thresholds to an age-corrected normal. In this example, the total deviation maps more clearly demonstrate the bitemporal nature of the defect than the grayscale maps. Analysis of the entire report allows for more accurate interpretation and localization

example, if the bitemporal hemianopia is most dense superiorly, the chiasm is being compressed inferiorly by a pituitary macroadenoma, as in this case. If the bitemporal loss is most dense inferiorly, think about compression superiorly (e.g., craniopharyngioma or third ventriculomegaly due to hydrocephalus). If the vision loss is bitemporal but only involves central vision (a central bitemporal hemianopic scotoma), the chiasmal compression must be posterior. Depending on the chronicity and severity of compression, there may be a loss of acuity, color vision, and optic nerve pallor can develop, each of which was demonstrated in this case. Pitfalls  If MRI of the brain with attention to the chiasm is normal, think about uncommon conditions that can also cause or mimic a bitemporal hemianopia including retinopathies (e.g., retinitis pigmentosa), ethambutol toxicity, or even significantly enlarged blind spots (e.g., papilledema).

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Do not miss this!  Usually, structural causes of a bitemporal hemianopia include pituitary macroadenoma, suprasellar meningioma, Rathke cyst, and craniopharyngioma. Occasionally, vascular contact/ compression of the chiasm can cause vision loss. In a child, consider an optic pathway glioma and neurofibromatosis type 1 (Lisch nodules are usually present on the irises). In the setting of severe headache and bitemporal vision loss (± third, fourth, and/or sixth nerve palsy), think about pituitary apoplexy. If a patient has bitemporal loss and diabetes insipidus, consider germinoma, sarcoidosis, lymphocytic hypophysitis, and Langerhans cell histiocytosis. Neuromyelitis optica, anti-MOG, and neurosarcoidosis are other causes of a chiasmopathy (see “optic neuritis” section above). Rarely, pendular seesaw nystagmus is also seen with a chiasmal lesion. What is next?  Any patient with a bitemporal hemianopia requires contrast-enhanced MRI with attention to the chiasm and pituitary region. Most etiologies will be identified with MRI. When MRI is normal, consider other etiologies above. With a suprasellar mass lesion, the most common etiologies can be remembered with the mnemonic SATCHMO—Sarcoid, pituitary Adenoma or Aneurysm, Teratoma (germ cell/germinoma), Craniopharyngioma, Histiocytosis (Langerhans), Metastasis, Optic glioma (hypothalamic-­chiasmal). Treatment options  Surgical when vision loss is due to a compressive lesion. If you can only remember one thing…  Always evaluate visual fields (preferably with static or dynamic perimetry), in each eye individually, in every patient with unexplained visual symptoms! Want to know more?  [15, 16]

Retrochiasmal Visual Disorders

3.7

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Retrochiasmal Visual Disorders

3.7.1 The History Patients with a homonymous hemianopia (HH) often feel that vision is impaired in the eye with the temporal defect, for example, a right HH may be perceived as a right eye problem. The key is whether this is a bilateral symptom, that is, on the right side of both eyes or the left side of both eyes.

3.7.2 The Exam While finger counting is a good visual field screen at the bedside, formal visual field testing using automated static (Humphrey or Octopus) or dynamic (Goldmann) perimetry is far more sensitive in detecting a subtle field defect. Comparison of hands/fingers or red targets presented in different visual hemifields and quadrants can help to identify relative visual field impairment for more accurate bedside localization.

3.7.3 Treatment Options Various yoked prism solutions have been proposed, but many patients do not tolerate these solutions well. There is currently no strong evidence for neuroplasticity-based vision therapy programs.

3.7.4 Optic Tract What makes this localization unique? • While optic tract lesions are fairly uncommon, consider etiologies including stroke, neoplasm/compression, and trauma (lesions affecting the tract can be easily overlooked on noncontrast MRI). • A homonymous hemianopia (HH) due to an optic tract lesion can be complete, which is nonlocalizing. When incomplete,

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homonymous defects due to tract lesions are incongruous (asymmetric). A rAPD is often seen in the eye with temporal loss, for example, a patient with a left optic tract lesion causing incongruous right HH will also have a (usually mild) right rAPD. The right rAPD is thought to be due to the fact that ~53% of the fibers cross in the chiasm (i.e., right optic nerve to left optic tract), whereas ~47% of fibers from the right optic nerve remain uncrossed in the chiasm and travel through the right optic tract. Bilateral optic nerve pallor can be seen due to the involvement of presynaptic (i.e., proximal to lateral geniculate nucleus) ganglion cell axons in the optic tract. For example, a left optic tract lesion may cause mild temporal pallor OS and mild temporal and nasal pallor OD (“bow tie” atrophy). Chronically, a characteristic OCT pattern of ganglion cell layer–inner plexiform layer homonymous hemiatrophy is often seen, due to retrograde transsynaptic degeneration. Fibers responsible for the pupillary light reflex leave the optic tract just prior to synapsing in the lateral geniculate nucleus, traveling to the midbrain pretectal nuclei and then to the Edinger–Westphal nucleus. Therefore, a lesion of the brachium of the superior colliculus can cause a rAPD without loss of acuity, color vision or field, and may be associated with other midbrain signs (e.g., a central fourth nerve palsy).

Figure  Figs. 3.18 and 3.4

3.7.5 Lateral Geniculate Nucleus (LGN) What makes this localization unique? • While a pure LGN lesion is uncommon, the associated visual field defects are unique and can be highly localizing. • Look for one of the following: (1) horizontal sectoranopia [lateral choroidal artery—posterior circulation] or (2) qua-

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Fig. 3.18  Typical visual field and optical coherence tomography (OCT) features of an optic tract syndrome: While visual acuity and color vision were normal, this patient had a very incongruous (asymmetric) right homonymous hemianopia (only able to demonstrate right temporal field loss OD to confrontation and only a mild nasal defect was seen OS with automated static perimetry), in addition to a mild right relative afferent pupillary defect (rAPD). The combination of an incongruous right homonymous hemianopia and right rAPD was highly localizing to the right left optic tract, which was felt to be due to a chronic infarct seen on MRI.  A characteristic OCT pattern of ganglion cell layer-inner plexiform layer homonymous hemiatrophy was also demonstrated (black arrows demonstrate the focal sectoral thinning—nasal OD and temporal OS—outside the 99% limit of normal). This pattern may be seen with any chronic retrochiasmal lesion as retrograde transsynaptic degeneration occurs but is more common (and faster to develop) with optic tract lesions

druple sectoranopia [anterior choroidal artery—anterior circulation]). If due to a stroke, identification of one of these homonymous patterns may provide a better understanding of stroke mechanism, for example, if there is a right horizontal sectoranopia due to left lateral choroidal artery (posterior circulation) ischemia and left hemiparesis due to right middle cerebral artery (anterior circulation) ischemia, the fact that there are bilateral strokes in two different vascular distributions is suggestive of a cardioembolic (e.g., atrial fibrillation) etiology.

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Homonymous horizontal sectoranopia (lateral choroidal artery)

Homonymous quadruple sectoranopia (anterior choroidal artery)

Fig. 3.19  Lateral geniculate nucleus (LGN) lesions cause distinct homonymous visual field defects: The top visual field is an example of a homonymous horizontal sectoranopia, which can be a manifestation of lateral choroidal artery territory ischemia (posterior circulation). The bottom visual field is an example of a homonymous quadruple sectoranopia, which can be a manifestation of anterior choroidal artery territory ischemia (anterior circulation). (Visual fields courtesy of Dr. Neil Miller)

• Similar to an optic tract lesion, OCT GCL-IPL homonymous hemiatrophy is often seen, as well as bilateral optic nerve pallor when the presynaptic ganglion cell axons are affected. Figure  Figs. 3.19 and 3.4

3.7.6 Optic Radiations What makes this localization unique? Temporal radiations (Meyer’s loop)

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• Meyer’s loop extends forward to within several centimeters of the tip of the temporal lobe, and an anterior temporal lesion can cause a superior quadrantic (“pie in the sky”) visual field defect. When incomplete, the defect is often incongruous (Figs. 3.20 and 3.4) • A temporal lobe lesion may be responsible for epilepsy as well as a HH, or a HH due to Meyer’s loop injury may result from epilepsy surgery. Parietal radiations • Lesions can cause incomplete homonymous visual field defects, more dense inferiorly (so-called “pie on the floor”)

L

R

T1 Axial images

Fig. 3.20  A “pie in the sky” defect due to temporal lobe (Meyer’s loop) injury: This is a patient with remote history of traumatic brain injury with associated right temporal lobe encephalomalacia (white arrows). Since the inferior optic radiations travel through the (right) temporal lobe (Meyer’s loop), injury can cause a (left) incongruous (asymmetric) homonymous superior quadrantic visual field defect, as seen here

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110

•

• • •

and often congruous (but not as congruous as occipital lesions). Often associated with neurologic or visuospatial symptoms/ signs (e.g., tactile or visual extinction when presented with bilateral simultaneous stimuli; visual neglect with a nondominant hemispheric lesion). There may also be absent optokinetic nystagmus when the optokinetic flag/drum is directed ipsilesionally (Video 3.2). Poor ipsilesional smooth pursuit is also commonly seen. With bilateral parietal injury, there may be bilateral (mainly) inferior defects with features of Balint’s syndrome (oculomotor apraxia, optic ataxia, and/or simultanagnosia). Strokes and compressive mass lesions are common etiologies for optic radiation injury (temporal and parietal).

Figure  Fig. 3.4

3.7.7 Occipital Lobe/Striate Cortex What makes this localization unique? • Occipital strokes usually cause very congruous (symmetric) homonymous hemianopias, with or without macular sparing (when present, presumably related to dual blood supply of the pole). Conversely, a homonymous central scotoma is almost always related to injury of the occipital pole/tip. • A lesion involving the occipital lobe inferior to the calcarine fissure can cause a defect resembling a “pie in the sky”/temporal defect, while a lesion involving the occipital lobe superior to the calcarine fissure can cause a defect resembling a “pie on the floor”/parietal defect. When homonymous defects are incomplete and very congruous, they are probably occipital in origin. Macular sparing is characteristic of an occipital lobe lesion.

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• Stroke is a common etiology, and bilateral homonymous hemianopias (a right HH and a left HH in the same patient) are often occipital in origin—bilateral defects affect visual acuity unless macular sparing is present. Pupillary light reflexes should be normal as these axons synapse in the dorsal midbrain prior to reaching the lateral geniculate nucleus. Bilateral HH due to occipital pathology can cause cortical blindness, sometimes associated with confabulation (e.g., patient will claim that they have vision even if they are effectively blind), the combination of which is known as Anton’s syndrome. • Higher cortical visual syndromes may be seen in association with temporo-occipital and parieto-occipital lesions (see “Higher cortical visual disorders” below). • The posterior occipital lobe subserves central vision, while the most anterior portion of the occipital lobe is responsible for the monocular temporal crescent from the contralateral eye (e.g., right anterior occipital lobe lesion can cause a small monocular crescent-­ shaped peripheral temporal defect in the left eye only). While this is a rare occurrence, it is an exception to the rule that any retrochiasmal visual field defect will be homonymous. Figure  Figs. 3.21 and 3.4

3.8

Higher Cortical Visual Disorders

3.8.1 Posterior Cortical Atrophy Case  A 65-year-old man presented to clinic with complaints of worsening vision and difficulty reading for the past 2 years. He also complained of “bumping into things” on a regular basis as large as a telephone pole but not necessarily on the right or on the left side. Frequently, he would have difficulty finding an object on the dinner table such as a spoon. He was told by one ophthalmologist that color vision was impaired, while another said that color vision was

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a

b

L

*

R

L

R

FLAIR Axial

Fig. 3.21  Congruous visual field defects due to occipital injury: (A) This patient was found to have a (mainly left) parieto-occipital parasagittal meningioma with associated right homonymous visual field defect, which worsened slightly following partial resection. Postoperative automated static perimetry demonstrated a very congruous (symmetric, white asterisk indicates the physiologic blind spot OD; otherwise, the two visual fields are identical) right incomplete inferior quadrantic visual field defect, correlating with the left occipital hyperintensity (black dashed line, superior to the calcarine fissure) seen on the postoperative MRI (black solid arrow points to residual meningioma). (B) This patient had a severe cardiomyopathy and experienced several cardioembolic strokes, two of which involved the left occipital lobe causing two distinct congruous visual field defects: (1) an incomplete right homonymous hemianopia (black dashed line) and (2) a right homonymous central scotoma (from left occipital tip ischemia)

normal. Cataract surgery OU improved visual acuity but not his visual difficulties which worsened over time. Examination demonstrated 20/25 visual acuities at distance OU (he had difficulty when a single or multiple lines were presented on the acuity chart but could see and name letters when presented individually, an example of “visual crowding”), 0/11 Ishihara color plates (although he was able to name and distinguish the individual colors on each plate, he could not see the numbers), there was no rAPD and dilated fundus exam was normal. Confrontation testing demonstrated impaired visual fields, especially inferiorly, which was confirmed with automated perimetry. Interpretation of a Navon figure was abnormal,

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for example, when presented with a large F made up of small S’s— he only saw the S’s. He was able to identify portions of the NIH Stroke Scale cookie theft drawing but could not provide a cogent interpretation of the scene. There was no optic ataxia (i.e., he could point to a target with visual guidance) and no oculomotor apraxia (i.e., saccades and pursuit were normal). A line cancellation task was performed normally, and there was no visual neglect. A previously performed MRI was reviewed, and bilateral parietal and occipital atrophy were prominent. He was diagnosed with posterior cortical atrophy (PCA). Figure  Figs. 3.22 and 3.23

L

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FDG PET scan

FLAIR Axial

Fig. 3.22  Bilateral homonymous visual field defects and parieto-occipital atrophy in a patient with posterior cortical atrophy (PCA): At the top, the black arrows point to a left homonymous hemianopia, that is slightly more dense inferiorly and suggestive of right parietal and/or right occipital lobe (superior to the calcarine fissure) involvement. The black dashed arrows point to a right homonymous inferior quadrantic visual field defect, due to left parieto-occipital involvement. On the bottom left are two fluorodeoxyglucose  (FDG)-positron emission tomography (PET) images, with the white arrows pointing to bilateral parieto-occipital hypometabolism, while the dashed arrows point to bilateral parieto-occipital atrophy seen on MRI

3  Loss of Vision and Other Visual Symptoms

114 Low-level vision Dorsal

Ventral

Intermediate-vision

High-level vision

Localization V1/Striate

V5/V5a

Deficit

Motion (akinetopsia) Space and time/Visuospatial action (Balint syndrome)

Inferior hemifield defects

Localization V1/Striate Deficit

V4/V4a

Superior hemifield defects Color (achromatopsia)

Occipitoparietal

Occipitotemporal Object identification (general visual agnosia: left – “words”; right–“faces and places”)*

Dorsal pathway (visuospatial action)

Posterior Parietal Cortex

Dors al V5/V5a

Ventral Inferior Temporal Cortex

V4/V4a

Striate Cortex (V1) Extrastriate Cortex (V2/3)

Ventral pathway (object identification)

Fig. 3.23  How the brain makes sense of what it sees—the dorsal and ventral visual pathways, and a three-tiered approach to vision: (1) Ventral (“what”) stream—this begins with the ‘P’ retinal ganglion cells ➔ parvocellular layers of the lateral geniculate nucleus (LGN, 3–6) ➔ V1/striate cortex (in blue) ➔ V4/V4a (fusiform and lingual gyri) ➔ occipitotemporal regions. (2) Dorsal (“where”) stream—this begins with the ‘M’ retinal ganglion cells ➔ magnocellular layers of the LGN (1, 2) ➔ V1/striate cortex ➔ V5/V5a ➔ occipitoparietal regions. *For objective identification (general visual agnosia)—in the left hemisphere, think “words” (pure alexia) and in the right hemisphere, think “faces and places” (prosopagnosia, topographagnosia). (The classification of cerebral visual dysfunction using a three-tiered approach is courtesy of Dr. Jason Barton. The figure was developed with the input of Dr. Victoria Pelak)

Key questions to ask  Commonly these patients have seen multiple optometrists and/or ophthalmologists over a period of months or years, have failed new spectacle prescriptions, and underwent cataract surgeries or other interventions without success. Therefore, a higher cortical visual disorder such as PCA should be considered in any older patient presenting with vague progressive visual symptoms, especially after clinically signifi-

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cant ophthalmic disease has been excluded. Ask about difficulties with cognitive function and memory. If the onset is acute, ask about vascular risk factors (e.g., watershed infarcts affecting biparieto-­occipital lobes). Key findings to elicit  One of the simplest screening tools for patients with suspected PCA is to use color plates. Assuming that the patient is not colorblind and having excluded significant bilateral anterior visual pathway disease, the inability to see the numbers (Ishihara plates) or shapes (HRR plates) despite being able to distinguish and identify the individual colors that make up the numbers/shapes may be due to simultanagnosia. Another quick screen is the Poppelreuter-Ghent overlapping figures test. If a higher cortical visual disorder is suspected, consider the following: • Look for simultanagnosia with Navon figure, cookie theft picture; • Evaluate hemi-attention with clock drawing, visual extinction, and line bisection; • Look for constructional apraxia with intersecting pentagons; • Evaluate the ability to read and write; • Evaluate fields to confrontation (and formal perimetry when possible—although often limited by attention/cognition). Patients with PCA can have “low-level” visual deficits including unilateral homonymous hemianopia (visual acuity should be spared) or bilateral homonymous hemianopias (acuity is often involved), in addition to visual crowding. Consider “intermediate level” deficits referable to dorsal and ventral streams including impaired motion discrimination (akinetopsia) and impaired color (hue) perception (achromatopsia), respectively. Consider “high-level” deficits including ventral stream—visual agnosia, topographagnosia, prosopagnosia, alexia, and dorsal stream—Balint syndrome, constructional apraxia (this organization and approach is courtesy of Drs. Victoria Pelak and Jason Barton). What are some common higher cortical visual disorder syndromes based on location?

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1. alexia without agraphia (patient can write but cannot read)— lesion of the left occipital lesion and splenium of the corpus callosum (visual field defect - right HH); 2. hemiachromatopsia (inability to recognize colors in one hemifield)—contralateral inferior occipitotemporal lobe (visual field defect - ipsilateral [to the affected hemifield] superior quadrantanopia); 3. prosopagnosia (inability to recognize faces)—bilateral occipitotemporal lobes (visual field defect - bilateral superior altitudinal defects); 4. optic aphasia (inability to name visual objects)—left occipital lobe (visual field defect - right HH); 5. topographagnosia (inability to identify familiar landmarks/ buildings)—right inferior occipitotemporal lobes; 6. akinetopsia (inability to perceive motion)—bilateral occipitotemporal cortex; 7. Balint syndrome (simultanagnosia, optic ataxia, and oculomotor apraxia)—bilateral parietooccipital lobes (visual field defect - bilateral inferior altitudinal defects); 8. Gerstmann’s syndrome (acalculia, agraphia, finger agnosia, and right-left confusion)—probably left angular gyrus with adjacent subcortical involvement. Pitfalls  When there is suspicion for a higher visual cortical disorder, a few basic visual and cognitive functions must also be evaluated [17]. If these functions are impaired, interpretation of the testing battery above can be particularly challenging and potentially misleading: 1) poor visual acuity (e.g., macular disease) may cause difficulty with reading and facial recognition; 2) abnormal visual fields (e.g., scattered bilateral hemifield defects due to strokes) can mimic simultanagnosia; 3) patients with aphasia or other language disturbances can have difficulty reading; 4) a patient with poor memory can have difficulty recognizing faces or places; 5) inattention can negatively impact any/all testing (these “general starting points” come from Dr. Jason Barton). Do not miss this!  If progressive over years, typically PCA is due to Alzheimer’s, Lewy body dementia (dementia with Lewy bodies

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and Parkinson’s disease dementia), or corticobasal degeneration, and memory disturbances and cognitive dysfunction may or may not have already developed. When acute/subacute in onset, consider a structural lesion (bihemispheric strokes or mass lesion) in the differential, as well as prion disease (Creutzfeldt–Jakob disease, look closely for cortical ribboning and hyperintensity of the deep cerebral nuclei on DWI or FLAIR). If you can only remember one thing…  Always think about PCA in an older patient with progressive, bilateral, unexplained vision loss in a person who has had normal ophthalmologic ­evaluations. Screening with color plates or Poppelreuter-Ghent overlapping figures is rapid and effective. Want to know more?  [18–21]

3.8.2 Hallucinations Case  An 80-year-old woman with moderate open angle glaucoma and visually symptomatic cataracts OU presented with 3  weeks of seeing “imaginary animals” such as monkeys that would appear and move across her vision bilaterally. There was no loss of time or awareness with these episodes, and they occurred for seconds to several minutes at a time. She denied auditory hallucinations or history of psychiatric disorders. Neuro-­ ophthalmic examination was unremarkable aside from 20/30 acuities OU (attributed mainly to cataracts) as well as moderate peripheral visual field loss and optic nerve cupping (attributed to glaucoma). There was no homonymous visual field defect with fields to confrontation or with automated perimetry. Ocular motor and motility exam was normal as well as assessment of cognitive and general neurologic function. Contrast-enhanced MRI was unremarkable, notably with normal-appearing occipital lobes. She was diagnosed with visual hallucinations due to Charles Bonnet syndrome (CBS).

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Key questions to ask  The onset and pattern is important since CBS may be due to a chronic benign ocular condition(s) such as cataracts or glaucoma, or hallucinations may occur within a homonymous hemianopia in the setting of acute/subacute stroke. If the latter, urgent neuroimaging is required. If the former, recognition of the inciting (ocular) event or disorder is important, for ­example, if cataracts are the culprit, surgery may resolve the hallucinations. Hallucinations can be unformed (e.g., a patient with bitemporal hemianopia due to pituitary macroadenoma with dots and flashes that are only bitemporal) or formed (e.g., the patient above who sees animals). Ask about medical and neurologic history as well as medications (e.g., a patient with Parkinson’s disease may experience hallucinations, which could be caused or aggravated by a dopamine agonist). Key findings to elicit  Detailed ophthalmic/neuro-ophthalmic evaluations are needed to rule out visual pathway disease. Vision loss can be mild (or absent), and cognitive function is often normal. Pitfalls  A detailed history and examination can almost always establish the diagnosis of CBS, and those with neuro-ophthalmic abnormalities (e.g., homonymous hemianopia) must be imaged. However, recognition of CBS due to cataracts or glaucoma or another ocular condition can prevent unnecessary workup. Do not miss this!  Prior to diagnosing unformed hallucinations, consider the possibility of photopsias caused by retinal disorders such as tear/detachment or posterior vitreous detachment, especially when unilateral; migraine or epilepsy with positive visual phenomena, especially when bilateral (and homonymous). Consider neurodegenerative disease when formed hallucinations are diagnosed. (Parkinson’s disease—related to or unrelated to dopaminergic medications—or Lewy body dementia). Consider peduncular hallucinosis (dream-like hallucinations) when associated with neurologic or ocular motor findings localizing to the midbrain (e.g., third nerve palsy). Consider Anton’s syndrome with bilateral occipital lesions, where the patient is functionally

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blind due to bilateral homonymous hemianopias (sparing of the anterior visual pathways, so pupillary responses are normal), but will deny being blind and instead confabulate visual scenes and objects (these are not hallucinations, nor does this represent a psychogenic disorder). What is next?  Patients with symptoms of neurologic (e.g., cognitive deficits, loss of time, or awareness) or neuro-ophthalmic (e.g., homonymous hemianopia) disease require contrast-­enhanced MRI and further workup. Patients with CBS due to an obvious ocular condition and typical history may not require further workup. Treatment options  Commonly, patients recognize that their hallucinations are not real, and the diagnosis of CBS and reassurance are enough. However, if the hallucinations are disturbing or bothersome enough the following are options, although evidence for their use is limited to case reports and series: antipsychotics, selective serotonin inhibitors, anticonvulsants, and cholinesterase-­ inhibitors. If you can only remember one thing…  This diagnosis can be made with a high degree of confidence based on a thorough history and comprehensive ophthalmic/neuro-ophthalmic examination alone. Want to know more?  [22]

3.8.3 Visual Snow Case  A 20-year-old woman presented with a complaint of her vision looking like “a broken tv.” This was first noticed at least 6  months ago, is diffuse and bilateral but not associated with vision loss. The tv “static” is most noticeable when looking at a solid background (e.g., blue sky or white wall), and while she does have a history of migraine, the visual symptoms do not seem to correlate with her headaches. She denies typical min-

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utes-long positive visual phenomena that might suggest visual aura, and her symptoms are constant. There was no exposure to illicit drugs recently or remotely (e.g., drugs with hallucinogenic properties). In the past 3  months, she has also noticed seeing afterimages at times, for example, after looking at a neon sign, the image can persist for seconds even after looking away. A diagnosis of visual snow (VS) was made with associated palinopsia. Key questions to ask  Patients with visual snow may see innumerable dots, static, or snow throughout their vision. While this does not disrupt their vision, the experience can be quite symptomatic. The VS syndrome (VSS) is characterized by dots, static, or snow symptoms and at least two of the following: (1) exaggerated entopic phenomena (the patient sees visual effects from within their own eye), (2) after-images (palinopsia), (3) photophobia, and (4) poor vision in low-light conditions (nyctalopia). Tinnitus and migraine headaches are other common associated symptoms. Key findings to elicit  Ophthalmic/neuro-ophthalmic exam should be normal without evidence of retinal or optic nerve ­disease. Pitfalls  Nyctalopia, photophobia, and photopsias are all symptoms that can be seen with the VS syndrome or with retinal disease. Therefore, dilated ophthalmologic exam is essential in these patients. Do not miss this!  Palinopsia can be a manifestation of an occipital lesion, certain medications (e.g., topiramate), or even epileptic seizures. What is next?  Typically electroretinogram, electroencephalogram, and MRI are low yield in patients with typical VS/VSS symptoms and normal ophthalmic/neuro-ophthalmic exam.

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Treatment options  Case series have suggested that lamotrigine, acetazolamide, and verapamil may help in certain cases, although no evidence-based guidelines exist. While a migraine history is common in these patients, typical migraine management (lifestyle/ dietary modifications, medications, etc.) is usually ineffective. If you can only remember one thing…  Although treatment of the visual symptoms is often unsatisfactory, making the correct diagnosis (and reassuring the patient that they will not lose their vision) can prevent potentially costly and unnecessary testing. Want to know more?  [23–25] Read these Books!  [26–29]

References 1. Petzold A, Islam N, Hu HH, Plant GT. Embolic and nonembolic transient monocular visual field loss: a clinicopathologic review. Surv Ophthalmol. 2013;58(1):42–62. 2. Biousse V, Nahab F, Newman NJ. Management of acute retinal ischemia: follow the guidelines! Ophthalmology. 2018;125(10):1597–607. 3. Sharma RA, Newman NJ, Biousse V. New concepts on acute ocular ischemia. Curr Opin Neurol. 2019;32(1):19–24. 4. Virdee J, Mollan SP. Photopsia. Pract Neurol. 2020;20(5):415–9. 5. Brown GC, Brown MM, Fischer DH.  Photopsias: a key to diagnosis. Ophthalmology. 2015;122(10):2084–94. 6. Masket S, Fram NR.  Pseudophakic dysphotopsia: review of incidence, cause, and treatment of positive and negative dysphotopsia. Ophthalmology. 2020;S0161–6420(20):30787–9. 7. Biousse V, Newman NJ.  Ischemic optic neuropathies. N Engl J Med. 2015;373(17):1677. 8. Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, et al. The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol. 2002;134(3):317–28. 9. Lyons HS, Quick V, Sinclair AJ, Nagaraju S, Mollan SP. A new era for giant cell arteritis. Eye (Lond). 2020;34(6):1013–26.

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10. Keltner JL, Johnson CA, Cello KE, Dontchev M, Gal RL, Beck RW, et al. Visual field profile of optic neuritis: a final follow-up report from the optic neuritis treatment trial from baseline through 15 years. Arch Ophthalmol. 2010;128(3):330–7. 11. Optic Neuritis Study Group. Visual function 15 years after optic neuritis: a final follow-up report from the optic neuritis treatment trial. Ophthalmology. 2008;115(6):1079–82.e5. 12. Gospe SM 3rd, Chen JJ, Bhatti MT. Neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disorder-optic neuritis: a comprehensive review of diagnosis and treatment. Eye (Lond). 2020;35(3):753–68. 13. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159–65. 14. NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014;311(16):1641–51. 15. Tantiwongkosi B, Mafee MF. Imaging of optic neuropathy and chiasmal syndromes. Neuroimaging Clin N Am. 2015;25(3):395–410. 16. Foroozan R.  Chiasmal syndromes. Curr Opin Ophthalmol. 2003;14(6):325–31. 17. Della Sala S, Laiacona M, Spinnler H, Trivelli C. Poppelreuter-Ghent’s overlapping figures test: its sensitivity to age, and its clinical use. Arch Clin Neuropsychol. 1995;10(6):511–34. 18. Crutch SJ, Schott JM, Rabinovici GD, Murray M, Snowden JS, van der Flier WM, et  al. Consensus classification of posterior cortical atrophy. Alzheimers Dement. 2017;13(8):870–84. 19. Holden SK, Bettcher BM, Pelak VS. Update on posterior cortical atrophy. Curr Opin Neurol. 2020;33(1):68–73. 20. Olds JJ, Hills WL, Warner J, Falardeau J, Alasantro LH, Moster ML, et al. Posterior cortical atrophy: characteristics from a clinical data registry. Front Neurol. 2020;11:358. 21. Barton JJ. Higher cortical visual deficits. Continuum. 2014;20(4 Neuro-­ ophthalmology):922–41. 22. Hamedani AG, Pelak VS.  The Charles Bonnet syndrome: a systematic review of diagnostic criteria. Curr Treat Options Neurol. 2019;21(9):41. 23. Puledda F, Schankin C, Goadsby PJ. Visual snow syndrome: a clinical and phenotypical description of 1,100 cases. Neurology. 2020;94(6):e564– e74. 24. Puledda F, Schankin C, Digre K, Goadsby PJ.  Visual snow syndrome: what we know so far. Curr Opin Neurol. 2018;31(1):52–8. 25. Bou Ghannam A, Pelak VS. Visual snow: a potential cortical hyperexcitability syndrome. Curr Treat Options Neurol. 2017;19(3):9.

References

123

26. Biousse V, Newman NJ.  Neuro-ophthalmology illustrated. 3rd ed. New York: Thieme; 2020. 27. Liu GT, Volpe NJ, Galetta SL.  Neuro-ophthalmology: diagnosis and management. 3rd ed. Philadelphia: Elsevier; 2019. 28. Miller NR, Subramanian PS, Patel VR. Walsh & Hoyt’s clinical neuro-­ ophthalmology: the essentials. 4th ed. Philadelphia: Wolters Kluwer; 2021. 29. Digre KB, Corbett JJ.  Practical viewing of the optic disc. Amsterdam: Butterworth-Heinemann; 2002.

4

Motility and Ocular Motor Disorders

4.1

The History

• Non-Neurologic Diplopia Do not forget (1) monocular double vision (refractive, dry eye, cataract, retinal, etc.) which is common, and (2) binocular double vision due to decompensated (childhood) strabismus in patients with intermittent or constant double vision and a full range of eye movements (i.e., normal versions and ductions). In these cases, there is usually a history of a longstanding abnormal head position (e.g., look for old photographs demonstrating head tilt in congenital fourth NP), known childhood strabismus, eye muscle surgery, or amblyopia (sometimes referred to as “lazy eye”). Decompensated strabismus is often horizontal and comitant (esotropia (eyes crossed) or exotropia (eyes deviated outward)), and a congenital fourth nerve palsy is often the cause of strabismus that is vertical and incomitant. While longstanding (childhood) strabismus may decompensate and cause diplopia (as a result of normal aging, medications, medical or neurologic illness, a new or worsening ophthalmic disorder), many patients will have no symptoms referable to their longstanding strabismus. Supplementary Information The online version of this chapter (https://doi. org/10.1007/978-­3-­030-­76875-­1_4) contains supplementary material, which is available to authorized users.

© Springer Nature Switzerland AG 2021 D. Gold, Neuro-Ophthalmology and Neuro-Otology, https://doi.org/10.1007/978-3-030-76875-1_4

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• Neurologic Binocular Diplopia Certain characteristics (vertical or horizontal; worse in near or far; right or left; abnormal head position, etc.—see Table 2.3 for further details) can often help to distinguish third vs. fourth vs. sixth NP when a single ocular motor palsy exists. • Acute/Subacute Ophthalmoplegia Myasthenia gravis can mimic any individual (or combination of) ocular motor palsies or gaze palsies; ptosis is common and pupils should be normal. Consider Miller Fisher syndrome, especially with preceding gastrointestinal illness followed by relatively acute onset of ataxia, hyporeflexia, poorly reactive pupils, and/or ptosis. Keep botulism toxicity on the differential diagnosis of ophthalmoplegia and sluggish pupils as well. Consider Wernicke’s encephalopathy in patients with ophthalmoparesis with confusion, ataxia, spontaneous upbeat, and/or gaze-evoked nystagmus. Also consider pituitary apoplexy with acute onset ocular motor palsy/palsies, vision loss (unilateral and/or bitemporal hemianopia) and headache. • Chronic Ophthalmoplegia Often due to mitochondrial disease such as chronic progressive external ophthalmoplegia (CPEO), which presents with gradually progressive ophthalmoplegia (if symmetric, diplopia is often absent) and ptosis.

4.2

The Exam

(a) Strabismus and motility basics • Range of Movements Video 4.1: in nine cardinal positions of gaze with both eyes viewing (versions). Always check the range of each individual eye (ductions) if there is diplopia or if a motility deficit is suspected. For example, a patient with an esotropia due to a (right) 6th NP will have a (right) abduction paresis, the extent of which can be best appreciated by assessing ductions. In contrast, a patient with infantile esotropia should not have an abduction deficit. Sometimes a patient with a large angle childhood strabismus (i.e., a big

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esotropia or exotropia) can appear to have a motility deficit with versions, but ductions will prove that the range of movements in each eye is in fact normal. • Alignment Video 4.2: in patients with normal appearing versions and ductions who do not have complaints of diplopia, at least assess ocular alignment in primary gaze at middistance/distance (if the visual target is too close, the examiner will always see a bit of an exodeviation). Start with alternate cover testing where one eye is occluded, and then the occluder (or examiner’s hand) is moved to the fellow eye, and then back and forth as the patient continues viewing the same visual target. If there is no movement as each eye is uncovered, ocular alignment can be said to be orthophoric in primary gaze at that particular distance. If the diplopia (or binocular symptoms) depends on target distance, evaluate alignment at near (symptomatic exotropia due to convergence insufficiency?) and at distance “(symptomatic esotropia due to divergency insufficiency?)”. The Maddox rod can be especially helpful (in a cooperative patient with normal binocular visual function) in identifying a small hyperdeviation, especially in patients with saccadic intrusions or spontaneous nystagmus—for example, appreciating an alternating skew deviation in lateral gaze in a patient with downbeat nystagmus (ESM 1.1). In children, uncooperative patients, or when poor monocular or binocular vision loss is present, the Hirschberg (corneal light reflex) test can be used as a quick screen, and the Krimsky test can then be used to quantify a deviation (Fig.  4.1). If a horizontal or vertical movement is seen with alternate cover test, proceed with further evaluation below: –– First determine whether the refixation movement seen with alternate cover test is horizontal (an eso or exo) or vertical (a hyper or hypo— technically, the misalignment should be named for the nonfixating eye [e.g., right eye is fixating on the target and the left eye is deviated downward would be a left hypotropia]), but it

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Hirschberg test – corneal light reflex demonstrates right exotropia

Krimsky test – base-in prism placed in front of the fixating eye until light reflex is centered in the non-fixating eye

Fig. 4.1  Evaluating ocular alignment using Hirschberg and Krimsky tests: This patient suffered severe vision loss in the right eye due to optic neuritis which led to an exotropia (XT) over several years. When a penlight is shone in both eyes, the left eye (white arrow) is the fixating eye because the light reflex is centered in the pupil, while the light reflex in the right eye is more medial than it should be (white dashed line), owing to the fact that the right eye is deviated outward. This is the Hirschberg test, and is a quick and easy method to evaluate for strabismus, especially effective in kids, uncooperative patients, or patients with poor monocular or binocular vision. The Krimsky test was then performed where base-in prism was placed on the fixating (left) eye until the light reflex was centered in the (previously exotropic) right eye (yellow arrow). Because this was achieved once 35 prism diopters (PD) of base in prism were placed, she had a ~ 35 PD exotropia (approximate because this is not as accurate a test as alternate cover or cover–uncover using prism)

is okay to just be consistent and always name the deviation for the hyper-phoric or tropic (higher) eye. Eso—eyes crossed, small phorias NORMAL Exo—eyes outward, small phorias NORMAL Hyper—one eye is higher, ABNORMAL –– Tropia or Phoria? Alternate cover test will allow you to see the total deviation, the tropia (if present) plus the phoria Cover–uncover test will allow you to determine what component of the deviation is due to a tropia (e.g., acquired/neurologic causes of paralytic strabismus will almost always cause a tropia)

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Tropia—misalignment with both eyes viewing— ABNORMAL Phoria—misalignment with one eye viewing— USUALLY NORMAL –– Comitant or Incomitant? Comitant—misalignment is independent of gaze direction—often NON-PARALYTIC (e.g., a hypertropia due to a skew deviation will appear the same in all directions of gaze, primary, right, left, up, down, right, and left head tilt) Incomitant—misalignment depends on gaze direction—often PARALYTIC (e.g., a right sixth NP will cause a larger esotropia in right gaze than in primary or left gaze) –– If ocular alignment testing is abnormal, see Table  4.1, and using the Maddox rod can also be helpful in certain situations - (refer to ESM 1.1) –– Look for associated signs—abnormalities on the neurologic exam (especially referable to the brainstem and other cranial neuropathies); anisocoria, ptosis –– When possible, measure the ocular misalignment in prism diopters using prism bars—quantifying the eso-, exo-, or hyper- in all directions of gaze assists in localization (e.g., right hyper increasing in left gaze and right head tilt is likely to be a right fourth NP); allows one to compare measurements at different points in time to monitor for improvement, worsening or stability; quantification also allows for accurate prescription of therapeutic prism (press-on or ground-in), when appropriate. –– Treatment of strabismus/diplopia—occlusion acutely (anything from semi-opaque tape placed over one spectacle lens to an eye patch), prism therapy, strabismus surgery when stable and recovery is incomplete. Regarding treatment for the underlying condition, this depends upon etiology. (b) The ocular motor exam

Exotropia worse in contralateral gaze, hypertropia worse in vertical gaze

Congenital esotropia is often associated with: latent nystagmus, IO overaction, DVD

Comitant

Esotropia or exotropia

Internuclear MR ophthalmoparesis (INO)* 3rd NP* MR, SR, IR, IO (ipsilateral ptosis and mydriasis are common) None Congenital (nonhorizontal paralytic) strabismus

Exotropia worse in contralateral gaze

Hyperphoria

Vertical phoria

None

Other Small comitant horizontal phorias are common (especially exo- when the visual target is at near) and usually normal; these can sometimes decompensate (e.g., with normal aging) causing an intermittent or constant tropia with diplopia Usually comitant A small vertical phoria may be normal; however, can represent a small skew (e.g., in vestibular neuritis with Maddox rod) if comitant and even if diplopia is absent; if incomitant, consider mild fourth NP Incomitant An acute MLF lesion commonly causes ipsilateral INO + ipsilateral hypertropia (due to skew deviation) Incomitant Can be complete or partial (either can represent a dangerous etiology such as PCOM aneurysm); MG may mimic a third NP when there is no pupil involvement

Comitance Comitant

Alignment Esophoria or exophoria

Localization/ Extraocular etiology paresis Horizontal phoria None

Table 4.1  My patient has ocular misalignment—where do I start?

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LR

Nonparalytic

Skew deviation

Esotropia worse in ipsilateral gaze Hypertropia usually worse in contralateral gaze and ipsilateral head tilt; may increase in upgaze Hypertropia worse in contralateral and down gaze and ipsilateral head tilt Hypertropia Hypertropia also increases in downgaze; look for excycloduction of the affected hypertropic eye (double Maddox rod, fundus photos, dilated eye exam) Usually comitant Occasionally, the hypertropia is incomitant and can mimic a fourth NP; look for incycloduction of the hypertropic eye (and excycloduction in the hypotropic eye) as part of the ocular tilt reaction

Incomitant

Can be falsely localizing due to low or high ICP—rule out papilledema Look at old photos to see if a longstanding head Incomitant (but can have “spread tilt is present; these patients usually have significant IO overaction in the affected eye in of comitance” contralateral gaze; may see SO atrophy on MRI over time)

Incomitant

INO internuclear ophthalmoplegia, MR medial rectus, MLF medial longitudinal fasciculus, NP nerve palsy, SR superior rectus, IR inferior rectus, IO inferior oblique, PCOM posterior communication artery, MG myasthenia gravis, DVD dissociated vertical deviation, ICP intracranial pressure, SO superior oblique * Always consider the ocular motor palsy mimics in patients with diplopia due to a motility defect, especially myasthenia gravis (often with ptosis, can mimic third, fourth, sixth NP, INO and other neurologic patterns of strabismus) and thyroid eye disease (often with lid retraction and lid lag in downgaze)

SO (may be too subtle to see)

4th NP, acquired*

4th NP, congenital SO (usually too subtle to see)

6th NP*

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• Convergence Video 4.3: may bring out or cause reversal of vertical nystagmus (e.g., bring out downbeat nystagmus (DBN) in a cerebellopathy, transition from upbeat nystagmus (UBN) to DBN in Wernicke’s encephalopathy), or may accentuate some acquired forms of nystagmus or damp infantile nystagmus. If the patient complains of binocular blurriness or double vision while reading and near viewing and the patient has a near point of convergence >10  cm, convergence insufficiency (CI) is likely, and assessment of alignment at distance vs near (exotropia at near but not at distance) and convergence amplitude can further support the diagnosis ­(CI is especially common with parkinsonism [Video 4.4: or TBI/concussion). • Saccades Video 4.5: have the patient rapidly look back and forth between 2 visual targets, noting the speed, conjugacy, latency, and accuracy. First have the patient look between an eccentric target and the examiner’s nose horizontally and vertically, making assessment of accuracy easier—for example, overshooting the nose (hypermetria) or undershooting the nose (hypometria). Then have the patient make larger amplitude saccades horizontally and vertically, which makes assessment of speed and conjugacy easier (e.g., adduction lag suggests an internuclear ophthalmoplegia [INO]). Saccadic dysmetria is seen in cerebellar disease (or brainstem connections with cerebellum). Ipsilateral hypermetria and contralateral hypometria occur in Wallenberg syndrome (Video 4.6). Slow saccades of normal amplitude occur in brainstem disease, typically involving burst neurons in the PPRF for horizontal saccades (e.g., SCA 1, 2, 3, 7 among others, Video 4.7) or riMILF for vertical saccades (e.g., progressive supranuclear palsy, PSP). Slow saccades

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of reduced amplitude occur in ocular motor nerve paresis or muscle weakness. With thyroid eye disease, saccade speed is normal but the movements may terminate abruptly due to motility deficits from extraocular muscle restriction. With myasthenia gravis, saccades tend to be of normal speed initially (sometimes faster than normal), but can fatigue with repeated testing. Slow adducting saccades are seen with an INO (lesion involving the MLF), which is typically accompanied by abducting nystagmus. INO may be due to MS, stroke, or structural and metabolic injuries (Video 4.8). • Smooth Pursuit Video 4.9: have the patient slowly track a target and note saccadic or “choppy” pursuit (saccades substitute for subnormal smooth pursuit gain to catch-up to the target, Video 4.10). Impaired pursuit horizontally and vertically is typically seen in cerebellar disease (or its connections). If impairment of pursuit is ­asymmetric, think about an ipsilesional process—for example, saccadic or choppy pursuit to the left due to a left hemispheric lesion (Video 4.11). • Vestibulo-Ocular Reflex Suppression (VORS) Video 4.12: the VOR will need to be suppressed or cancelled in many normal situations to allow for combined eye-head movements—for example, turning the eyes and head together to see in the rear view mirror while driving prior to a lane change. The VOR is stimulated by the turning the head toward the mirror, but the VOR will be suppressed so that the eyes can move in the same direction as the head to allow the foveae to reach the mirror as well. VORS will generally be saccadic when pursuit is saccadic and vice versa (Video 4.13), unless there is no VOR to suppress as in bilateral vestibular loss. In a condition such as CANVAS (cerebellar ataxia, neuropathy, vestibular

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a­reflexia syndrome), the cerebellopathy will result in impaired (saccadic) pursuit while the vestibulopathy will result in normal/near normal-appearing VOR suppression, because there is no VOR to suppress (Video 4.14). • Optokinetic Nystagmus Video 4.15: at the bedside, using an optokinetic stimulus can assist in the evaluation of smooth pursuit and saccades. The slow phases represent smooth pursuit while the fast phases represent saccades. Since the bedside optokinetic stimulus used (optokinetic tape/flag, examiner’s fingertips, or any alternating patterns/lines, optokinetic drum) does not involve full visual field stimulation (e.g., watching passing scenery from the window of a moving train), the optokinetic system is not truly being isolated. Situations in which bedside OKN can be helpful: (1) rapid assessment of symmetry and presence/absence of pursuit/saccades in an uncooperative or difficult to examine patient; (2) subtle adduction lag in INO; (3) one of the first ocular motor signs of PSP is loss of the downward fast phase to an optokinetic stimulus directed upward (goes along with downward saccades being slightly slower than upward saccades initially, and downgaze being more affected than upgaze); (4) if OKN is seen in a patient with functional monocular (when the good eye is occluded) or binocular blindness, this suggests that the patient has at least some vision; (5) since upward saccades are often affected in dorsal midbrain (Parinaud’s syndrome), vertical OKN can demonstrate poor upward saccades and convergence retraction nystagmus (when stimulus is directed downward and the examiner views the patient’s eyes from the side) • How to perform the telemedicine (virtual) ocular motor examination: Video 4.16.

Subarachnoid Space, Cavernous Sinus, Orbital Apex

4.3

135

 ubarachnoid Space, Cavernous Sinus, S Orbital Apex

4.3.1 Subarachnoid Space What makes this localization unique?  Patients can have a single cranial neuropathy or multiple (any combination of) ipsilateral or contralateral cranial neuropathies. Sixth nerve palsy can be a false localizing sign due to low or high intracranial pressure within the subarachnoid space. Consider intracranial pressure abnormalities, skull base tumors, infectious, inflammatory or carcinomatosis meningitis, among others. Enhancement of cranial nerves and enhancing brain lesions (i.e., multi-compartment enhancement) should raise suspicion for neoplastic diseases including leukemia, lymphoma, glioma, metastasis; inflammatory/autoimmune disease including neurosarcoidosis; or infectious etiologies including fungal infection, tuberculosis, Lyme disease. If the cranial nerves, brain parenchyma, and leptomeninges all demonstrate enhancement, lymphoma, leukemia, and ­sarcoidosis remain possibilities, and metastatic disease including glioblastoma multiforme should also be considered. Figure:  Example of a patient with leukemic meningitis causing right sixth NP and left fourth NP. Figure 4.2 and Video 4.17 How do I approach (history and exam) the patient with diplopia or ophthalmoplegia?  Table 2.3 and ESM 2.1 Pitfalls:  Bilateral (or unilateral) sixth NP in low or high ICP represents a false localizing sign—for example, in idiopathic intracranial hypertension, even though the elevated ICP is diffuse, the sixth nerves are particularly susceptible to changes in pressure as they ascend the clivus and then acutely bend forward to penetrate

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136

R

L

* * Fig. 4.2  Multiple contralateral ocular motor palsies due to neoplastic seeding of the subarachnoid space: This patient had (1) an abduction paresis OD (white asterisk) due to right lateral rectus (sixth nerve) palsy, and (2) poor depression OS (black asterisk) in down/right gaze, suggestive of a left superior oblique (fourth nerve) palsy. There was a slight rightward head tilt which cannot be appreciated in this montage. Ocular alignment examination demonstrated an esotropia that was worse in right gaze (due to right sixth NP), and a left hypertropia that was worse in right and downgaze, as well as with left head tilt (due to left fourth NP)

the dura under Gruber’s ligament (in Dorello’s canal). Figure 4.3 Lack of contrast and/or high-resolution thin cuts on MRI can result in missing subtle cranial nerve abnormalities. Do not miss this!  In the differential diagnosis of unilateral or contralateral ocular motor palsies should be myasthenia gravis (pupils spared), thyroid eye disease, and Miller Fisher syndrome (pupils involved or spared). What is next?  Patients with multiple cranial neuropathies require an urgent workup including contrast-enhanced brain MRI (preferably with thin, high resolution cuts through the posterior fossa), and usually lumbar puncture as well.

Subarachnoid Space, Cavernous Sinus, Orbital Apex Petroclinoid (Gruber’s) ligament

CN V

137

CN VI

V1

Superior orbital fissure

CN VII

Foramen rotundum

V2

Petrous temporal bone

V3 Subarachnoid space

Petrous apex

Orbit

Cavernous sinus

Foramen ovale

Internal carotid artery

Fig. 4.3  The course of the sixth (VI) nerve: The sixth nucleus is located dorsally, adjacent to the fourth ventricle, in the lower pons. The genu of the facial (seventh) nerve wraps around the sixth nucleus, creating the facial colliculus, which bulges into the fourth ventricle. After the sixth nerve leaves the pons, it follows a vertical course along the clivus and then to the petrous apex where it penetrates the dura, passing under the petroclinoid (Gruber’s) ligament in Dorello’s canal, where it is tethered and particularly susceptible to low or elevated intracranial pressure states. It then enters the cavernous sinus (adjacent to the sympathetic plexus which surrounds the internal carotid artery), travels through the superior orbital fissure to enter the orbit, and then passes through the annulus of Zinn to finally innervate the ipsilateral lateral rectus muscle

4.3.2 Cavernous Sinus What makes this localization unique?  Ipsilateral involvement of CN 3, 4, 6, V1, V2, or a combination of these, pain may or may not be a prominent feature. When a Horner’s syndrome is seen with an ipsilateral sixth NP, think cavernous sinus. The function

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138

of each cranial nerve must be evaluated. In a patient with a third NP, the function of the fourth nerve should be assessed by having the patient attempt downgaze and looking for incycloduction in the paretic eye. If clearly present, the function of the fourth nerve is spared (Fig. 4.4). If not present, this implies that there is a third

SO

SO

IO

MR

LR

IO

IR

MR

IR

LR

SR

LEFT

SR

RIGHT

* *

* *

Fig. 4.4  Ocular motility and alignment findings in a left third NP: This patient (with hypertension and diabetes) suffered a microvascular left third NP. In primary gaze, there is complete ptosis OS (levator palpebrae, black asterisk), and with the left eyelid manually elevated, there was also adduction paresis OS and exotropia in right gaze (medial rectus, MR, yellow asterisk), supraduction paresis OS and right hypertropia in upgaze (superior rectus, SR, white asterisk), infraduction paresis OS, and left hypertropia in downgaze (inferior rectus, IR, red asterisk). There was additional poor pupillary reactivity OS (with mild left mydriasis) due to mild involvement of the pupillary sphincter muscle (PCOM aneurysm and structural lesions had been ruled out, and her third NP resolved over 2–3  months as expected; however, patients with a microvascular third can occasionally have minimal pupil involvement, typically with anterior vestibulo-ocular reflex hypofunction;

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4  Motility and Ocular Motor Disorders

• Neurologic exam –– Evaluate for other neurologic deficits (especially brainstem) that might be due to stroke or MS; • Neuro-ophthalmic exam –– Evaluate for optic nerve disease/optic neuritis (MS); –– Evaluate for ptosis (third NP, MG), –– Poor pupil reactivity and mydriasis (third NP, rarely Miller Fisher syndrome) –– Test to see if motility/misalignment is fatigable or variable (MG). Pitfalls:  It’s rare to have a partial third NP present as medial rectus paresis in complete isolation…INO is much more likely! Do not miss this!  If there is also (even subtle) ipsilateral involvement of the lid, pupil (mydriasis and poor reactivity), superior or inferior rectus, rule out a posterior communicating artery aneurysm causing a partial third NP urgently. What is next?  Diagnosis of an INO (+/− a skew deviation) requires urgent neuroimaging, especially given the possibility of stroke. Contrast-enhanced MRI is preferable when MS or a related autoimmune/inflammatory disorder is on the differential. Treatment options  Usually, an INO will improve to a significant degree, and may resolve entirely (e.g., stroke). The skew deviation tends to recover even faster, and likewise, spontaneous vertical-­torsional nystagmus is typically only seen in the acute setting. If head movement-dependent oscillopsia is present (due to vertical VOR deficits), vestibular physical therapy can be beneficial. For persistent diplopia due to INO or skew, prism therapy or strabismus surgery can be considered. If you can only remember one thing…  INO is very common in MS, and can even be present in patients without diplopia and with normal motility and ocular alignment. The MLF ensures normal horizontal conjugate movements (Fig. 4.15). At the bedside, have the patient make horizontal saccades while looking very closely

Pons

155 Right INO

*

Left horizontal gaze palsy

*

*

*

*

Fig. 4.15  Anatomy of an internuclear ophthalmoplegia (INO) and horizontal gaze palsy: The patient to the left suffered a right medial longitudinal fasciculus (MLF) stroke that caused a right INO. The right MLF normally contains interneurons that travel from the left sixth nucleus to the right medial rectus (MR) subnucleus of III. This allows the left sixth nucleus to innervate not only the left lateral rectus (LR), but also the right MR via the MLF to ensure horizontal conjugate movements to the left. However, when there’s a right MLF lesion, the left LR is normally innervated by the intact sixth nucleus, while the right MR is not. This can lead to a complete adduction (MR) paresis as in this case, or sometimes there’s no obvious motility deficit but rather a slower adducting saccade (adduction lag) in the affected eye, most noticeable when assessing horizontal saccades. With a right MLF lesion, there is usually an abducting nystagmus in the left eye, likely reflecting an adaptive response in an attempt to adduct the eye. Because the right MR and left LR are a yoked pair that receive the same innervation, the normal left LR may be overactivated with a resultant abducting nystagmus. Because the descending convergence pathways that lead to bilateral MR contraction are unaffected by a (more caudal) MLF lesion, convergence may overcome the adduction paresis of the INO, which would not occur with a MR palsy due to a third nerve palsy. Note that the right MLF also contains utriculo-ocular motor and vertical (anterior and posterior) semicircular canal pathways that originate in the left labyrinth (these pathways decussate at the pontomedullary junction). For comparison, a patient with a left horizontal gaze palsy (due to multiple sclerosis) is included on the right. Note that the interneurons from the left sixth nucleus to the right MR subnucleus are still affected (but in the left sixth nucleus itself, not the right MLF), causing an adduction deficit in the right eye (just like the patient with right INO, which can also be overcome by adduction). However, because the fibers that would normally activate the left LR are also affected, the patient cannot abduct the left eye. This constellation of findings is known as a (left) horizontal gaze palsy

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for a subtle adduction lag. Using an optokinetic flag/drum/tape can often make a subtle lag even clearer. Want to know more?  [2, 3]

4.5.2 Horizontal Gaze Palsies What makes this localization unique from a neuro-­ophthalmic and ocular motor/vestibular standpoint?  Look for the ­following: (1) horizontal gaze palsy (unable to move the eyes toward the side of the lesion with saccades, pursuit, vestibuloocular reflex due to sixth nucleus involvement, can be unilateral or bilateral, adduction deficit(s) can often be overcome by convergence), (Fig. 4.16) (2) one-and-a-half syndrome (horizontal gaze palsy to one side and internuclear ophthalmoplegia to the other side, adduction deficits can often be overcome by convergence), (3) eight-and-a-­half syndrome (horizontal gaze palsy and lower motor neuron fascicular seventh NP on one side, internuclear ophthalmoplegia on the other side), (Fig.  4.17) (4) horizontal saccadic palsy (cannot make horizontal saccades toward the side of the lesion, but pursuit and VOR are spared, due to a paramedian pontine reticular formation, PPRF, lesion), (5) oculopalatal tremor may develop months later given the adjacent descending central tegmental tract (Fig. 4.18) Video:  Two stroke patients with horizontal gaze palsy and one-­ and-­a half syndrome: Video 4.26 How do I approach (history and exam) the patient with diplopia or ophthalmoplegia?  Table 2.3 and ESM 2.1 Key questions to ask:  When a patient suddenly develops a gaze palsy, stroke is the main consideration, either ischemic or hemorrhagic—ask about vascular risk factors. In a younger patient with-

Pons

157

L

FLAIR Sagittal

R

FLAIR Axial

*

*

Fig. 4.16  Horizontal gaze palsy due to multiple sclerosis (MS): This patient had a known history of MS with a previous attack of optic neuritis OD (central scotoma seen in the Humphrey visual field top right) and demyelinating periventricular white matter lesions (top left images) seen on MRI. She woke up with horizontal diplopia and the inability to move the eyes to the left. On exam, she had a left horizontal gaze palsy: (1) left horizontal gaze palsy (severe abduction paresis OS, yellow asterisk, and adduction paresis OD, white asterisk) due to left sixth nucleus injury (which would normally activate left lateral rectus directly as well as right medial rectus via interneurons travelling through the right medial longitudinal fasciculus, MLF); (2) normal right horizontal gaze; and (3) normal adduction OD with convergence (bottom photo). Because the convergence signals descend from supratentorial regions to synapse on the medial rectus subnuclei in the midbrain, adduction deficits due to lesions involving the MLF and/or sixth nucleus may be overcome by having the patient converge

out vascular risk factors, ask about previous neurologic attacks that might suggest demyelination. Key findings to elicit:  Evaluate the range of eye movements, pursuit, saccades, and the vestibulo-ocular reflex—if all are affected in one direction, the localization is likely to be the sixth nucleus. If ­saccades are the only class of eye movements affected unilaterally, the localization is paramedian pontine reticular formation (PPRF) Video 4.7. Evaluate facial nerve function as well—because the fascicles of the seventh CN wrap around the sixth nucleus, commonly a patient with a unilateral (right) horizontal gaze palsy (with or without an associated right INO) will

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158

T1 T1Axial Axial(contrast) (contrast)

*

*

FLAIR FLAIR Axial Axial

*

Fig. 4.17  Eight-and-a-half syndrome due to dorsal pontine tuberculoma: This patient had a mild right lower motor neuron facial palsy (demonstrated in the photos as a slightly widened right palpebral fissure, black double-sided arrow) due to right seventh fascicle injury. She also had a right one-and-a-half syndrome: (1) right horizontal gaze palsy (severe abduction paresis OD unable to cross the midline, gray asterisk, and milder adduction paresis OS, white asterisk) due to right sixth nucleus injury, (2) right internuclear ophthalmoplegia (INO, adduction paresis OD, yellow asterisk) due to right medial longitudinal fasciculus (MLF) injury. There was improved adduction OU with convergence. The combination of right seventh NP + right one-and-a-half syndrome is sometimes referred to as the eight-­and-­a-half syndrome, and is highly localizing to the region of the right facial colliculus/dorsal pons (region within red dashed circle). In fact, the patient was found to have a dorsal pontine ringenhancing lesion with surrounding vasogenic edema, which was diagnosed as a tuberculoma. This patient was seen acutely, but given the proximity of the descending central tegmental tract (CTT, a part of Mollaret’s triangle), patients with dorsal pontine pathology may develop oculopalatal tremor weeks or months following the initial injury. MCP middle cerebellar peduncle, VI cranial nerve 6, VII cranial nerve 7, VIII cranial nerve 8

also have a right lower motor neuron facial palsy. Evaluate all other cranial nerve function as well, especially CN5 and CN8. Pitfalls  Patients with strokes or seizures (especially those affecting the frontal eye fields) can have a horizontal gaze preference, which is usually ipsilesional with a stroke (e.g., left hemispheric stroke causing a left gaze preference due to unopposed right frontal eye fields) and contralesional with epileptic seizures (e.g., a left hemispheric seizure focus causing a transient right gaze preference due to activation of the left frontal eye fields). A gaze preference due to stroke may or may not be overcome by the horizontal vestibulo-ocular reflex acutely. Also consider myopathic and mitochondrial disorders (chronic pro-

Pons

159 Ventral

umfe Bas rential ilar A

VII T CT

AICA

P

MC

Paramedian Basilar A

VI

Circ

VIII

VI MLF

MLF

Dorsal

Fig. 4.18  Vascular distribution and anatomy (including sixth, seventh, eighth nerves, MLF) of the pons: In this axial section of the pons, the proximity of the seventh and eighth fascicles can be appreciated. A lateral inferior pontine syndrome (anterior inferior cerebellar artery, AICA territory), which could involve both of these fascicles, can cause acute prolonged vertigo accompanied by an abnormal ipsilateral horizontal head impulse test (HIT, fascicle of CN8) and ipsilateral lower motor neuron facial palsy (fascicle of CN7). Although a “central” acute vestibular syndrome typically has a normal HIT, exceptions exist where an abnormal HIT can be due to a stroke. Commonly, an abnormal HIT can be seen with lesions affecting the root entry zone of CN8, or those involving the vestibular nucleus or with labyrinthine ischemia (AICA territory). A lesion involving the middle cerebellar peduncle (MCP) itself can also result in acute prolonged vertigo, but if the fascicle of CN8 is spared, HIT will be normal. A dorsal midline lesion can cause unilateral or bilateral internuclear ophthalmoplegia (INO) due to medial longitudinal fasciculus injury (MLF, usually stroke or multiple sclerosis). Dorsal pontine injury can also cause a horizontal gaze palsy (sixth nucleus) or a gaze palsy + INO, causing a one-and-a-half syndrome (+/− seventh NP). Finally, the central tegmental tract (CTT) is in this vicinity as well, making oculopalatal tremor a finding to look for months after suffering a pontine lesion (e.g., hemorrhagic cavernoma). VI cranial nerve 6, VII cranial nerve 7, VIII cranial nerve 8

gressive external ophthalmoplegia), Miller Fisher syndrome, Wernicke’s encephalopathy in the differential diagnosis of horizontal gaze palsies. Do not miss this!  Remember that myasthenia gravis (MG) can mimic any ocular motor disorder including horizontal gaze palsy and one-and-a-half syndrome! What is next?  When associated with severe headache or change in mental status, consider hemorrhage and order urgent CT scan. Otherwise, MR with diffusion-weighted imaging is needed when

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160

stroke is suspected and contrast-enhanced MRI when demyelination is suspected. Consider MG workup with normal imaging. Given the proximity of the central tegmental tract (part of ­Mollaret’s triangle), months after the insult (usually due to hemorrhage) patients may develop oculopalatal tremor. Treatment options:  If adduction and abduction deficits are symmetric with a unilateral horizontal gaze palsy or if horizontal gaze palsies are symmetric with bilateral involvement, then diplopia may not be that bothersome. Fortunately, patients’ ocular motor deficits tend to improve or resolve, but prism and/or strabismus surgery can be options for some.

4.5.3 Sixth Nerve How do I diagnose a sixth NP?  Patients typically experience binocular horizontal diplopia, worse at distance and in the direction of the paretic lateral rectus. Figure 4.19 What localizations should I be aware of?  (1) (right) sixth nucleus—(right) horizontal gaze palsy (see “Horizontal gaze ­palsies” section above);

SO

SO

IO

MR

LR

IO

IR

MR

IR

LR

SR

LEFT

SR

RIGHT

*

Fig. 4.19  Ocular motility and alignment findings in a left sixth nerve palsy: This patient (with hypertension and diabetes) suffered a microvascular left sixth NP causing a complete abduction paresis OS (lateral rectus, LR, white asterisk) with an esotropia greater in left gaze

Pons

161

(2) (right) fascicle of the sixth nerve— (right) lateral rectus palsy, can have contralateral (left) hemiparesis (right corticospinal tract) and/or (right) lower motor neuron seventh NP often due to ischemia; (3) subarachnoid space— (right) sixth nerve is susceptible to injury from inflammatory/neoplastic/infectious meningitis, trauma, high or low intracranial pressure, mass lesion (skull base tumors); (4) (right) petrous apex—infection (Gradenigo syndrome) causing (right) sixth NP and/or (right) facial pain in the trigeminal distribution and/or ipsilateral (right) seventh NP and/or (right) eighth NP; (5) cavernous sinus/superior orbital fissure—compressive lesion, carotid-cavernous fistula among others can cause (right) sixth NP and/or (right) ipsilateral Horner’s syndrome and/or any combination of (right) third, fourth NP, V1, V2 (an isolated sixth NP due to microvascular ischemia probably occurs here as well); (6) orbital—can be an isolated sixth NP or associated with ipsilateral third, fourth NP, V1, orbital signs (proptosis, vision loss/optic neuropathy). Video:  Video 4.27 Figure:  Figures 4.3 and 4.19 How do I approach (history and exam) the patient with diplopia when a sixth NP is suspected, and how can I localize it?  Table 2.3 and ESM 2.1 Key questions to ask when a sixth NP is suspected:  • Previous trauma? • Vascular risk factors (especially diabetes—microvascular etiology)? • Inquire about headaches (low or high intracranial pressure [accompanied by transient visual obscurations, pulsatile tinnitus],

162

• • •

•

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aneurysmal compression or other mass lesion?) and other neurologic symptoms (e.g., unilateral weakness due to pontine stroke?) Is there a history of or suspicion for an infectious, inflammatory, or autoimmune disorder? Ask about giant cell arteritis symptoms (obtain ESR/CRP when present) in patients >50–55 years old. Ask about ptosis, dysphagia, and weakness that could suggest a neuromuscular junction disorder (myasthenia gravis [MG], Lambert Eaton myasthenic syndrome) or Miller Fisher syndrome (MFS). Ask about thyroid function (thyroid eye disease, TED - in TED, the lateral rectus is uncommonly involved, although medial rectus restriction will often cause an abduction deficit).

Key findings to elicit:  Thorough neurologic/neuro-ophthalmic exam as above in “What localizations should I be aware of?” discussion, also look for fatigable ptosis or proximal weakness (MG); proptosis, eyelid retraction (TED). If it is asymptomatic and incidentally seen on examination, look for eye retraction in adduction and consider Duane’s syndrome (Video 4.28). In MFS, pupils may be poorly reactive to light, there may be abduction deficit(s) or more severe ophthalmoparesis, deep tendon reflexes can be diminished or absent, and ataxia is common as well (Video 4.29). Pitfalls:  Remember that not everybody who has an abduction deficit has a sixth NP! Always consider MG and TED. Occasionally, a patient will present with an apparent abduction deficit in lateral gaze to one or both sides which is due to convergence spasm. In this situation, there is usually a voluntary crossing of the eyes in lateral gaze—for example, when asked to look to the left, the patient will cross the eyes (causing miosis OU as part of activation of the near triad) making adduction OD appear normal but giving the appearance of a left abduction paresis. Testing each eye individually (ductions) will usually prove that abduction is in fact normal and no

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workup is needed. Rarely, a patient will experience organic convergence spasm which is usually related to midbrain pathology, although other abnormal ocular motor signs are almost always present. Do not miss this!  Consider the most dangerous causes first, and always rule out papilledema, which if present, is an emergency! Pontine strokes causing an isolated sixth NP are rare, but this is another emergency situation. Most isolated sixth NP are microvascular (when vascular risk factors are present), although isolated sixth nerve palsies are commonly due to a structural or mass lesion as well. Consider GCA in patients >50–55 years old, which is a potentially vision-­threatening disorder. Rarely, a pseudoabducens (or pseudo-sixth) palsy can occur with a thalamic or midbrain stroke, despite sparing of the pons and course of the sixth nerve. However, these are almost always accompanied by other midbrain signs (Video 4.30). What is next?  Urgent neuroimaging when papilledema is present or stroke is suspected. Urgent ESR and CRP when GCA is suspected. Most other situations require contrast-enhanced MRI, although not as urgently. Acetylcholine receptor antibodies when MG is suspected, and thyroid function tests and thyroid stimulating immunoglobulin when TED is suspected. Treatment options:  A microvascular sixth NP should resolve completely over months (usually within 3, but definitely within 6 months). Depending on the etiology, occlusion (patch over one eye or semi-opaque tape over one lens), prism therapy, or strabismus surgery may be options. Want to know more?  [4]

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4.6

Midbrain

4.6.1 Third Nerve How do I diagnose a third NP?  Patients with a complete third NP won’t experience binocular diplopia due to severe ptosis until manually elevating the eyelid. Otherwise, a patient with predominant medial rectus paresis may experience horizontal diplopia worse at near, while a patient with predominant superior or inferior rectus paresis may experience vertical diplopia worse in up or down gaze, respectively. Or, diplopia may be more diagonal due to the combination of horizontal and vertical components. Figure 4.4 How do I approach (history and exam) the patient with diplopia when a third NP is suspected, and how can I localize it?  Table 2.3 and ESM 2.1 What localizations should I be aware of?  (1) (right) third nucleus—(right) third NP + left superior rectus paresis and left mild ptosis (Fig. 4.20); (2) (right) fascicle of the third nerve—can have a partial or complete right third NP with contralateral (left) hemiparesis (right corticospinal tract), ipsilateral (right) ataxia (superior cerebellar peduncle), and/or contralateral (left) tremor (red nucleus); (3) subarachnoid space—susceptible to injury from inflammatory/neoplastic/infectious meningitis, trauma, mass lesion (skull base tumors); (4) cavernous sinus/superior orbital fissure—compressive lesion, carotid-cavernous fistula among others can cause (right) third NP that can be associated with any combination of (right) fourth, sixth NP, V1, V2 (an isolated third NP due to microvascular ischemia probably occurs here as well). Because the superior and inferior divisions of the third NP probably separate completely by the anterior cavernous sinus, patients can have a divisional third NP with this localization—for example, a superior division third NP with superior rectus and

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Red nucleus Central caudal nucleus P IR LP MR SR IO Medial

Aemptedupgaze upgaze (lids Attempted (lids manually elevated) elevated) manually

Lateral

Severe ptosis ptosis OS Severe OS Mild ptosis ptosis OD Mild OD

Fig. 4.20  Central anatomy of the oculomotor nerve and characteristic features of a nuclear third NP: This patient has a complete left third NP (severe left ptosis, mydriatic unreactive pupil OS, left medial, superior, and inferior rectus palsies), which could either result from a central or peripheral left third NP. However, she also had a right superior rectus (SR) palsy as well as mild ptosis OD. Bilateral upgaze paresis can be explained by a left nuclear third NP due to the fact that the (1) left SR subnucleus is injured (left midbrain hemorrhage in the setting of a familial multiple cavernous malformation syndrome in this case) causing a right SR palsy due to the decussation of these fibers, and (2) fibers that originated in the right SR subnucleus and then decussated to join the left third nerve are also damaged, causing a left SR palsy. Finally, the central caudal nucleus (CCN), a midline structure that innervates bilateral levator palpebrae muscles, can also be partially injured by with a unilateral third nucleus lesion, causing ipsilateral greater than contralateral ptosis, as seen in this case. Given the orientation of the various fibers that make up the fascicle of the third nerve (seen in the figure above from medial to lateral), certain patterns of muscle and/or pupil involvement can have additional localizing value, although involvement or sparing can be variable, making this anatomy less clinically useful. P pupil, IR inferior rectus, LP levator palpebrae, MR medial rectus, SR superior rectus, IO inferior oblique

levator palpebrae involvement or an inferior division third NP with medial, inferior rectus, inferior oblique, and/or pupillary sphincter muscle involvement; (5) orbital—can be isolated or associated with ipsilateral fourth, sixth NP, V1, orbital signs (proptosis, vision loss/optic neuropathy), and this can be a superior or inferior divisional third NP. Figures 4.21 and 4.22

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166 Anterior

Optic canal Sphenoid ridge

Superior orbital fissure Cavernous sinus

Sella turcica Anterior clinoid process of sphenoid bone

Posterior clinoid process of sphenoid bone

Petrous ridge

Basilar a Posterior cerebral a Superior cerebellar a

Red nucleus Central caudal nucleus

III P

Posterior

Medial

IR

LP MR SR IO

Lateral

Fig. 4.21  The course of the third nerve: The third nucleus lies at the ventral border of the periaqueductal gray matter, at the level of the superior colliculus. In between the two nuclei is the midline central caudal nucleus (CCN), which innervates bilateral levator palpebrae muscles (explaining how a unilateral nuclear third can cause bilateral ptosis). The third nerve fascicle (which contains fibers responsible the pupillary sphincter [P], inferior rectus [IR], levator palpebrae [LP], medial rectus [MR], superior rectus [SR], and inferior oblique [IO] are located medial to lateral) travels anteriorly through the tegmentum, the red nucleus, the substantia nigra, and finally exits the midbrain medially from the cerebral peduncles. The peripheral portion of the third nerve courses between the superior cerebellar and posterior cerebral arteries and then passes the posterior communicating artery (PCOM aneurysm causes compression here) and the temporal lobe uncus (uncal herniation can cause compression here), then above the petroclinoid (Gruber’s) ligament (while the sixth nerve travels under) and into the cavernous sinus where it is located laterally. The separation into superior (SR, LP) and inferior (P and ciliary body, MR, IR, IO) divisions occurs in the anterior sinus, and these branches then travel through the superior orbital fissure to enter the orbit, passing through the annulus of Zinn before innervating their respective muscles. (Castro O, Johnson LN, Mamourian AC. Isolated inferior oblique paresis from brain-stem infarction. Perspective on oculomotor fascicular organization in the ventral midbrain tegmentum. Arch Neurol. 1990;47(2):235–7)

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PCA Basilar A

III

PCA & Posterior Choroidal A

PCA & SCA

Red nucleus

III

CCN

Fig. 4.22  Vascular distribution and anatomy (including third nerve) of the rostral midbrain: In this axial section of the midbrain at the level of the superior colliculus, the paired third nuclei are located ventral to the periaqueductal grey, and the midline central caudal nucleus (CCN) is located in between. PCA posterior cerebral artery, SCA superior cerebellar artery

4.6.2 Fourth Nerve How do I diagnose a fourth NP?  Patients typically experience binocular vertical, diagonal, or oblique diplopia, worse in contralateral and down gaze, and ipsilateral head tilt. Figure 4.23 How do I approach (history and exam) the patient with diplopia when a fourth NP is suspected, and how can I localize it?  Table 2.3 and ESM 2.1 What localizations should I be aware of?  (1) (left) fourth nucleus or (2) (left) fascicle (both prior to decussation)—(right) fourth NP +/− contralateral (left) internuclear ophthalmoplegia, (left) Horner’s syndrome, ipsi- or contralateral relative afferent pupillary defect, (left) hemi-ataxia (Fig. 4.24 and Video 4.31); (3) subarachnoid space—susceptible to injury from inflammatory/neoplastic/infectious meningitis, trauma, mass lesion (skull base tumors);

168

4  Motility and Ocular Motor Disorders Left 4th NP

Skew deviation (ocular counterroll)

* Fig. 4.23  Ocular motility and exam findings in a left fourth NP: The top left photos are from a patient with left hypertropia who had a Parks–Bielschowsky three-step test consistent with a left fourth NP: (1) left hypertropia (LHT), (2) LHT increased in contralateral (right) gaze, and (3) LHT increased in ipsilateral (left) head tilt. He had additional features of a congenital fourth NP including, (1) significant ipsilateral (left) inferior oblique overaction in right gaze (white arrow showing the upward deviation of the left eye in adduction), (2) large vertical fusional amplitude (e.g., able to fuse a large LHT of at least 15 prism diopters, which is why his fourth nerve palsy was asymptomatic), and (3) longstanding contralateral (right) compensatory head tilt (not seen in these images, but apparent in old photos dating back to childhood). The patient in the bottom photo also has a left fourth NP, with an apparent depression deficit in adduction OS (asterisks) due to left superior oblique (SO) paresis (secondary action of the SO is depression). Evaluation of fundus torsion can be very helpful in differentiating a left fourth NP from a skew deviation (either could cause a LHT) in that the hypertropic eye will be excycloducted in a fourth nerve palsy (owing to the primary action of the SO which is incycloduction). Compare this to the incycloducted hypertropic eye in a skew deviation, which will be accompanied by excycloduction of the hypotropic eye (both eyes rotate in the same direction, which is known as an ocular counterroll)

(4) cavernous sinus/superior orbital fissure—compressive lesion, carotid-cavernous fistula among others can cause (right) fourth NP and/or any combination of (right) third, sixth NP, V1, V2 (isolated fourth NP due to microvascular ischemia probably occurs here as well); (5) orbital—can be isolated or associated with ipsilateral third, sixth NP, V1, orbital signs (proptosis, vision loss/optic neuropathy).

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MLF OculoSympathetic Tract

Fig. 4.24  Central anatomy of the trochlear nerve and characteristic features of a nuclear fourth NP: This patient suffered a hemorrhage of the left caudal midbrain causing a right fourth NP. This is due to the fact that the left fourth nerve originates in the left dorsal midbrain, exits dorsally and decussates to the right side where it then wraps around the brainstem to eventually innervate the right superior oblique muscle. A (right) “central” fourth NP will often have associated neuro-ophthalmic features including, (1) (left) internuclear ophthalmoplegia from (left) medial longitudinal fasciculus (MLF) injury, (2) (left) Horner’s syndrome from (left) oculosympathetic tract injury, (3) ipsi- or contralateral relative afferent pupillary defect (without involvement of acuity, color or field) due to injury to the brachium of the superior colliculus, or neurologic signs including (4) (left) hemi-ataxia from (left) superior cerebellar peduncle/brachium conjunctivum injury

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170 Anterior

Optic canal Sphenoid ridge

Superior orbital fissure

Sella turcica

Cavernous sinus

Anterior clinoid process of sphenoid bone

Posterior clinoid process of sphenoid bone

Petrous ridge

Basilar a Posterior cerebral a Superior cerebellar a

Medial longitudinal fasciculus Oculosympathetic tract IV

Posterior

Fig. 4.25  The course of the fourth nerve: The fourth nucleus lies at the ventral border of the periaqueductal gray matter, at the level of the inferior colliculus. The fascicles exit the nucleus dorsally and decussate at the anterior medullary velum (anterior floor of the fourth ventricle), and then exit the brainstem dorsally. The peripheral portion of the fourth nerve (left fourth nerve originated in the right fourth nucleus and vice versa) runs laterally around the upper pons and then passes between the superior cerebellar and posterior cerebral arteries before reaching the prepontine cistern and then the cavernous sinus where it is located laterally. The fourth nerve travels through the superior orbital fissure and continues above the annulus of Zinn to then innervate the superior oblique muscle

Figure:  Figures 4.25 and 4.26 Key questions to ask when a fourth NP is suspected:  • Previous trauma? • Vascular risk factors (especially diabetes—microvascular etiology)?

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Basilar A

PCA

PCA & Posterior Choroidal A

MLF IV

PCA & SCA

MLF OculoSympathetic Tract

IV

Fig. 4.26  Vascular distribution and anatomy (including fourth nerve) of the caudal midbrain: In this axial section of the midbrain at the level of the inferior colliculus, the fourth nuclei are located ventral to the periaqueductal grey, dorsal to the medial longitudinal fasciculus (MLF) and medial to the oculosympathetic tract. Fascicles exit the nucleus dorsally and decussate at the anterior medullary velum before exiting the midbrain dorsally on the contralateral side. PCA posterior cerebral artery, SCA superior cerebellar artery

• Inquire about headaches (aneurysmal compression or other mass lesion?) and other neurologic symptoms (e.g., unilateral ataxia due to midbrain stroke?), • Is there a history of or suspicion for an infectious, inflammatory, or autoimmune disorder? • Ask about giant cell arteritis symptoms (ESR/CRP when present) in patients >50–55 years old. • Ask about ptosis, dysphagia, and weakness that could suggest a neuromuscular junction disorder (myasthenia gravis) when pupils are spared. • Longstanding head tilt (congenital fourth NP)? • Orbital signs or known history of thyroid disease (although isolated superior oblique involvement would be rare for thyroid eye disease)? Key findings to elicit:  The Parks–Bielschowsky three-step test: (1) the higher (hypertropic) eye will be ipsilateral to the fourth NP; (2) the hypertropia will increase in contralateral gaze, (3) the hypertropia will increase in ipsilateral head tilt. Patients with a congenital fourth NP often have a significant inferior oblique overaction, large vertical fusional amplitude and longstanding head tilt, and their hypertropia may also increase in up gaze, distinguishing it from the more typical pattern of increased hypertropia in down gaze that is commonly observed with an acquired

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fourth NP.  Trauma can also cause bilateral fourth NP with an alternating hypertropia—that is, right hyper in left gaze and left hyper in right gaze. Also look for bilateral excycloduction, and a V-pattern esotropia (i.e., more esotropia in downgaze) (Video 4.32). Ocular alignment – Is it a fourth NP or a skew deviation?  A skew deviation may rarely be significantly incomitant and mimic a fourth NP with the three-step test; instead, a skew deviation is typically comitant. If the vertical misalignment is significantly reduced in magnitude when rechecking when supine (using alternate cover, cover-uncover, or a Maddox rod), this is likely to be a skew deviation (i.e., because utriculo-ocular motor pathway asymmetry is responsible for a skew, reducing the effect of gravity on the utricles by assuming a supine position can reduce a skew). However, if there is no improvement in vertical misalignment when going from upright to supine, the vertical strabismus could still be due to a skew. Head tilt—Is it a fourth NP or a skew deviation?  Patients with a fourth NP have a compensatory head tilt to the opposite side—for example, a left fourth nerve palsy will cause a compensatory rightward head tilt. The reason is that by tilting the head to the right, the patient excites the right utricle which initiates the utriculo-­ocular motor reflex, resulting in minute elevation of the right eye and depression of the left eye and very slight ocular counterroll with top poles toward the left ear. This will help to minimize r­etinal image disparity resulting from the paretic left SO and improves diplopia (recall that the left eye will be too high and excycloducted, so the right head tilt will put the eye into a more favorable position). A patient with a left MLF lesion will have a contraversive OTR with right head tilt—in this case, the head tilt is pathologic, or an attempt to correct for an abnormal internal representation of where earth vertical is located. In other words, with a left MLF lesion (where the utricle pathways that are injured originated in the right labyrinth, and the utricle pathways that originated in the left labyrinth are intact and are relatively hyperactive), the brain thinks that the head/ body is tilting to the left and attempts to compensate. However, since the head started in a neutral position (rather than a left head tilt position), the final position will be to the right of earth vertical.

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Cycloduction—Is it a fourth NP or a skew deviation?  Measure cycloduction/ocular torsion subjectively with double Maddox rod, bucket test [5] or objectively by measuring the angle between the fovea and optic nerve—a patient with a left fourth will have left hypertropia and left excycloduction with no little to no abnormal cycloduction in the right eye acutely. A patient with a left MLF lesion will have a left hypertropia and left incycloduction in addition to right excycloduction—this results from the ocular counterroll portion of the OTR. Pitfalls:  Many patients have a congenital fourth NP as the cause for their diplopia, which decompensates with normal aging, medical/neurologic disorders, or medications. Ask look at old photos of the patient to see if a longstanding head tilt was present. Do not miss this!  In a patient presenting with a third NP, look for incycloduction in downgaze in the paretic eye (focus on a single conjunctival blood vessel)—if present, the fourth nerve is spared, and if there is no clear incycloduction, it is likely that there is also a fourth NP, which suggests a cavernous sinus localization. Also, a fourth NP + contralateral internuclear ophthalmoplegia and/or contralateral Horner’s syndrome is highly suggestive of a midbrain lesion (“central” fourth NP). Look for an alternating hypertropia (right hyper in left and left hyper in right) + esotropia in downgaze + bilateral excycloduction in bilateral fourth NP, which is almost always due to trauma. What is next?  The history and exam should guide the clinician, but if the patient does not clearly have a congenital fourth NP, contrast-enhanced MRI should be performed in most cases (unless a patient is likely to have a microvascular fourth NP and is already recovering). An atrophic unilateral superior oblique muscle seen on MRI is also suggest of a longstanding (usually congenital) process. ESR and CRP urgently when GCA is suspected. Treatment options:  Patching or occlusion with semi-opaque tape, prism therapy, and/or strabismus surgery. Want to know more?  [6, 7]

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4.6.3 Vertical Gaze Palsies Why can’t my patient look up?  First think about dorsal midbrain (Parinaud’s) syndrome: • upgaze palsy (posterior commissure carries fibers responsible for upgaze, not downgaze), • convergence-retraction nystagmus with attempted upgaze (asynchronous convergent saccades), • light-near dissociation (pretectal nuclei are involved while pathways responsible for the near triad are spared, see Fig. 2.2), • eyelid retraction (Collier’s sign, likely due to M-group involvement. Refer to ESM 4.1. Also consider unilateral central (nuclear) third NP (Fig.  4.20) causing bilateral superior rectus paresis as well as bilateral ptosis; bilateral third nerve palsies (again, with other features of a third NP); supranuclear disorders (i.e., usually overcome by a vertical vestibulo-ocular reflex, VOR, think about progressive supranuclear palsy [PSP], although downgaze is usually worse); myasthenia gravis and other conditions. Figures 4.27 and 4.28 Why can’t my patient look down?  If the onset is abrupt, first think about a unilateral or bilateral rostral interstitial medial longitudinal fasciculus (riMLF) lesion causing a down>upward saccadic palsy (projections from riMLF to depressor muscles are ipsilateral whereas projections to the elevator muscles are bilateral—that is, a unilateral riMLF lesion mainly affects downward saccades, while complete bilateral damage can abolish all vertical saccades) which may be due to an artery of Percheron stroke. In chronic progressive disorders, think about supranuclear disorders such as PSP, Niemann–Pick Type C, among others. Bilateral third NP can cause an inability to look down, but this will be accompanied by other features of an oculomotor palsy. Figures 4.27 and 4.28

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Fig. 4.27  Brainstem structures involved in normal ocular motor function: This is a sagittal representation of the brainstem demonstrating the relative locations of the ocular motor nuclei (III [including the midline central caudal nucleus or CCN], IV, VI), neural integrators (INC for vertical/torsional gaze holding, nucleus prepositus hypoglossi [NPH] for horizontal gaze holding), and saccadic burst neurons (riMLF for vertical/torsional, paramedian pontine reticular formation [PPRF] for horizontal). The posterior commissure (PC) plays a role in upward gaze as well, explaining the characteristic upgaze palsy in a dorsal midbrain (Parinaud’s) syndrome

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176

a

b .

Parinaud’s syndrome

riMLF syndrome

c.

d.

INC syndrome

PSP

Fig. 4.28  Common lesions and localizations for characteristic midbrain ocular motor syndromes as seen on MRI: (a) Dorsal midbrain (Parinaud’s) syndrome—complete upgaze palsy (among other findings) typically associated with extrinsic compression of the dorsal midbrain (dashed line), in this case due to a glioblastoma multiforme of the pineal gland seen on noncontrast sagittal T1 (arrow). (b) Rostral interstitial medial longitudinal fasciculus (riMLF) syndrome—complete downward saccadic palsy (and very slow upward saccades) typically associated with an intrinsic lesion, in this case bilateral riMLF infarcts (arrows) from artery of Percheron ischemia seen on axial MR-diffusion-weighted imaging (DWI). (c) (Left) interstitial nucleus of Cajal (INC) syndrome—complete contraversive (rightward) ocular tilt reaction (i.e., right head tilt, left hypertropia due to skew deviation, ocular counter roll with top poles of both eyes rotated toward the right ear) and spontaneous torsional nystagmus (top poles beating toward the left ear), in this case due to a left INC infarct (arrow) seen on axial MR-DWI. (d) Patients with progressive supranuclear palsy (PSP) often have significant midbrain atrophy, a feature that is not surprising based on the vertical saccadic and vertical gaze palsies that are so typical of this disorder. With axial (T1 in this patient) MRI views, the tegmentum atrophy (arrow) can create the “Mickey Mouse” sign. With sagittal MRI views, the midbrain atrophy may give the appearance of a hummingbird (where the pons is the body, midbrain is the head)

Video:  Parinaud’s syndrome: Video 4.33: riMLF syndrome: Video 4.34: a patient with INC and riMLF syndromes from a single midbrain stroke: Video 4.35 Figure:  Figure 4.29 Key questions to ask:  When the onset is acute, Parinaud’s syndrome is often due to extrinsic compression of the dorsal midbrain (e.g., tumor of the pineal gland, hydrocephalus, shunt

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Bilateral eyelid retraction and upgaze palsy Rostral midbrain hemorrhage

Fig. 4.29  Dorsal midbrain (Parinaud’s) syndrome due to mesodiencephalic hemorrhage: This patient demonstrated the main clinical features of Parinaud’s syndrome including, (1) eyelid retraction (Collier’s sign, note how much superior sclera is visible in the photo), (2) pupillary light-near dissociation (no constriction to light, brisk constriction to a near stimulus), (3) upgaze palsy, (4) convergence-retraction nystagmus during attempted upgaze. The CT on the right demonstrates the rostral midbrain location of the hemorrhage. (Video and image created with the assistance of Drs. Amir Kheradmand and Jiaying Zhang)

malfunction), but can be due to intrinsic lesions (e.g., ischemic or hemorrhagic stroke)—history of surgeries, tumors, and strokes must be questioned. A riMLF syndrome is often due to an intrinsic lesion (e.g., stroke). If chronic and progressive, consider neurodegenerative disease (e.g., PSP). Key findings to elicit:  A detailed evaluation of all classes of eye movements is essential—for example, despite what appears to be a vertical gaze palsy, VOR and smooth pursuit may be spared in PSP or a riMLF syndrome. Other ocular motor findings to localize to the midbrain include pseudo-abducens/sixth palsy (see sixth nerve section), skew deviation (and other features of interstitial nucleus of Cajal, INC, syndrome). Rarely, irritation of the INC (usually by hemosiderin products) can cause a paroxysmal ocular tilt reaction (Video 4.36). If there is a horizontal and vertical saccade palsy, consider neurodegenerative disorders or a lesion involving the perineuronal nets (e.g., post-cardiac surgery saccade palsy, Video 4.37).

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How do I approach (history and exam) the patient with diplopia and ophthalmoplegia?  Table 2.3 and ESM 2.1 Pitfalls:  Remember that myasthenia gravis can mimic any ocular motor disorder! Also consider myopathic and mitochondrial disorders (chronic progressive external ophthalmoplegia), Miller Fisher syndrome, Whipple’s disease, Wernicke’s encephalopathy in the differential diagnosis, although horizontal ophthalmoparesis and distinguishing symptoms/signs can usually be appreciated with each. Do not miss this!  The acute onset of Parinaud’s syndrome or riMLF syndrome is a consequence of dangerous pathology. What is next?  Urgent neuroimaging with an acute onset, initial CT to rule out hemorrhage/hydrocephalus, followed by MR with diffusion-weighted imaging. Treatment options  Prism and/or strabismus surgery in some depending on the disturbance—for example, not typically helpful for upgaze or downgaze paresis (although some yoked prism options exist), may be helpful for a skew deviation or if there is an associated third NP. If you can only remember one thing…  If the onset is acute and the patient cannot look up, think dorsal midbrain (Parinaud’s) syndrome, and if the patient cannot look down, think riMLF. When chronic, PSP (or another neurodegenerative syndrome) is usually to blame. Want to know more?  [8]

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4.6.4 Progressive Supranuclear Palsy Case:  A 65-year-old man presented with imbalance and falls for the last 1–2 years. He experienced difficulty navigating stairs, had become a messy eater, and developed hypophonia in the same period of time. Exam demonstrated small horizontal back and forth movements consistent with square wave jerks, and there was significant difficulty moving the eyes downward more than upward despite the fact that there was a normal vertical range of movements when assessing the vestibulo-ocular reflex (VOR). There were slow and hypometric horizontal saccades with very slow downward more than upward saccades, with a corresponding absence of a downward fast phase to an optokinetic flag that was moving upward. Some of the vertical saccades followed a curved arc-like trajectory to get to the target (“round-the-houses” sign). There were complaints of horizontal diplopia at near with a corresponding exotropia (consistent with convergence insufficiency (CI)), as well as saccadic smooth pursuit and VOR suppression (with a normal VOR and head impulse test). There was severe axial rigidity and postural instability with a tendency toward falling backward. He could not suppress blinking when a penlight was repeatedly shone in his eyes. MR axial images of the midbrain demonstrated significant atrophy of the tegmentum, consistent with the “Mickey Mouse sign.” He was diagnosed with PSP. Video:  Video 4.38: patient with ocular motor findings in early PSP; Video 4.39: patient with advanced PSP and complete ophthalmoplegia; Video 4.40: patient with PSP and absent fast phases with optokinetic flag and inability to suppress blinks to a bright light; Video 4.4: CI in a patient with progressive supranuclear palsy (PSP)

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Figure:  Figure 4.28 Key questions to ask:  Visual symptoms are very common in PSP, are often vague (aside from diplopia due to CI) although commonly related to reading or tasks requiring focus. • Ask about symptoms referable to CI (e.g., horizontal binocular diplopia at near), ask about spectacle correction (e.g., if the patient wears progressives, bifocals, or trifocals and a downward gaze palsy is present, it will be very difficult for the patient to see through the reading segment of their glasses), • Ask about ocular surface irritation/dry eye symptoms (which commonly causes monocular double vision), • Consider the possibility of a higher visual cortical disorder (given the potential for clinical overlap between PSP and other disorders such as cortical basal degeneration [CBD]— for example, a patient with CBD may experience simultanagnosia). Key findings to elicit:  • Square wave jerks (SWJ, saccadic intrusions that usually do not affect visual function); • Supranuclear vertical gaze palsy (down>up at least initially, complete vertical palsy as the disease progresses); • Inability to suppress blink to repetitive light stimulus (cannot habituate); • Saccades are hypometric horizontally, and are typically much slower vertically (down>up) than horizontally, and the “roundthe-houses” or the “zig-zag” signs may be seen with vertical saccades (a single curved arc trajectory or multiple slow oblique saccades in alternating directions, respectively) [9], • Saccadic pursuit and VOR suppression; • The first sign you may see (even before vertical gaze palsy) is slow (or absent) downward fast phases with an optokinetic stimulus; • Also by assessing saccades diagonally (e.g., targets are presented up-right and down-left) or by using a diagonal optokinetic stimulus, you might see pure horizontal saccades with the former or pure horizontal fast phases with the latter;

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• Eyelid retraction (M-group in the midbrain ESM 4.1 It is probably the combination of these efferent abnormalities in addition to ocular pathology (blepharitis, dry eye due to poor tear production and decreased blink rate) that explains reading/ focusing complaints. Upgaze can become impaired to some degree with normal aging (whether this is related to changes involving the orbital tissues or whether this is in part supranuclear is not clear), poor downgaze in a patient with a gait/balance disorder is more diagnostically meaningful. Pitfalls—when is it Parkinson’s disease (PD)?  In patients with PD, there are often mild-moderate ocular motor abnormalities (i.e., not nearly as severe or prominent compared to PSP) including SWJ, saccadic hypometria, mildly saccadic pursuit/VOR suppression, and convergence insufficiency (tends to be responsible for most efferent symptoms). However, much like PSP, ocular surface disease/blepharitis is often present as well, degrading monocular acuity and causing monocular double vision. PD patients tend to have tremor, (milder) postural instability, rigidity and bradykinesia, and other visual symptoms become common as the disease progresses including illusions (e.g., a pile of clothes looks like a dog) and hallucinations (e.g., seeing bugs crawling in the peripheral vision, especially in dimly lit environments), which can result from PD or dopaminergic drugs. Do not miss this!  If there are also cerebellar ocular motor signs (gaze-evoked nystagmus, downbeat nystagmus), consider multiple system atrophy or the possibility of the cerebellar variant of PSP. Clinically, CBD can also have similar features. Significant (and early) postural instability differentiates PSP from Parkinson’s disease. If the onset of a supranuclear gaze palsy and PSP-like features is subacute, consider paraneoplastic disorders (e.g., anti­Ma and anti-Ta), Whipple’s disease, Creutzfeldt-Jakob disease among others. Supranuclear vertical gaze disorders can be seen acutely with ischemia of midbrain structures including rostral interstitial medial longitudinal fasciculus (riMLF, affects downward>upward saccades), and the posterior commissure (PC, affects upward movements).

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182

What is next?  PSP is a clinical diagnosis, although MRI can provide additional clues (e.g., “Mickey Mouse sign” on axial views, “hummingbird sign” on sagittal views). Treatment options:  Patients with PD will have a favorable response to dopaminergic drugs, while patients with PSP usually will not. Artificial tears can help with ocular surface disease. Avoidance of progressives, bifocals, trifocals by using a stand to place reading material at eye level with full frame reading glasses. Convergence exercises and base in prism can be offered for CI. If you can only remember one thing…  A comprehensive ocular motor examination performed horizontally and vertically (including optokinetic nystagmus) should be performed in all patients with significant postural instability. Want to know more?  [10, 11]

4.7

Cerebellum

Three syndromes: (1) flocculus/paraflocculus (tonsil), (2) nodulus/ventral uvula, (3) dorsal vermis (ocular motor vermis, OMV) and posterior fastigial nucleus (fastigial ocular motor region, FOR) (Fig. 4.30). Note that the flocculus/paraflocculus and nodulus/uvula together make up the vestibulocerebellum. A case that brings the three syndromes together:  A 30-year-­ old man with a known diagnosis of spinocerebellar ataxia type (SCA) 8 presented for visual symptoms. Examination demonstrated features suggestive of involvement of the following structures:

Cerebellum

183 = Inhibitory projection Ocular Motor Vermis

FN

P

SC

MCP

ICP

Floc

culu

s lus

cu

loc

raf Pa

Nodulus/ Vental Uvula

Fig. 4.30  Cerebellar structures involved in normal vestibular and ocular motor function: Seen here is in inferior view of the flocculus, paraflocculus (tonsil), nodulus, and uvula, which together make up the vestibulocerebellum. The fastigial nucleus (FN) and ocular motor vermis play important roles in saccadic accuracy. MCP middle cerebellar peduncle, SCP superior cerebellar peduncle, ICP inferior cerebellar peduncle. (Modified and redrawn with permission from: Shemesh and Zee [12])

(1) flocculus/paraflocculus—saccadic smooth pursuit, saccadic vestibulo-ocular reflex (VOR) suppression (which was significant enough to cause head movement dependent oscillopsia), downbeat nystagmus (causing head movement independent oscillopsia), gaze-evoked nystagmus (causing oscillopsia in lateral gaze) with rebound nystagmus, alternating skew deviation (causing vertical diplopia in lateral gaze), (2) nodulus/uvula—apogeotropic positional nystagmus (causing positional dizziness and oscillopsia), (3) OMV/FOR FOR: bilateral saccadic hypermetria (causing difficulty seeing clearly after changing gaze); OMV: divergence insufficiency (esotropia worse at distance causing horizontal diplopia at distance but not at near, or may localize to flocculus/paraflocculus—not seen in the video). There was also severe gait and limb ataxia. Taken together, examination suggested widespread cerebellar involvement, which was confirmed on MRI by severe diffuse c­erebellar atrophy. Video 4.41

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Key questions to ask when you suspect a cerebellar disorder:  Most important is the onset and duration of disease. If acute in onset, consider vascular. If subacute in onset, consider infectious/inflammatory/autoimmune disorders in younger patients, in addition to paraneoplastic disorders in older patients. Typically, patients will present with years of progressive imbalance and/or oscillopsia due to a cerebellar degeneration. The presence or absence of visual symptoms (e.g., retinopathy in SCA7), parkinsonism (e.g., multiple system atrophy), gait and limb ataxia +/− myelopathy/corticospinal tract involvement (e.g., a variety of SCAs) can provide additional clues. Consider a cervicomedullary structural lesion (e.g., Chiari malformation, neoplasm) with a vestibulocerebellar disorder and headaches.

4.7.1 Syndrome of the Flocculus and Paraflocculus (Tonsil) Fig. 4.31 4.7.1.1  G  aze-Evoked and Rebound Nystagmus & Impaired Smooth Pursuit and VestibuloOcular Reflex Suppression (VORS) Symmetric involvement of the flocculus/paraflocculus due to cerebellar degeneration:  A 30-year-old woman presented with a several year long history of imbalance due to cerebellar ataxia of unclear etiology. Seen in this video are common ocular motor signs in patients with advanced cerebellar dysfunction including: (1) saccadic smooth pursuit, (2) saccadic vestibulo-ocular reflex suppression (VORS, a combined eye-head movement; the fact that pursuit and VORS appear to be equally saccadic also tells the examiner that the VOR is present—that is, if VORS was normal/near-normal appearing but pursuit was saccadic, this would suggest that there is no VOR to suppress due to significant vestibular loss), (3) gazeevoked and rebound nystagmus. When right-beating nystagmus (RBN) is seen in right gaze and left-beating nystagmus (LBN) is

Cerebellum

185

Paraflocculus (tonsil)

Flocculus

Nodulus

Uvula

Fig. 4.31  Structure and function of the vestibulocerebellum: Think of these four structures as two functional units: (1) flocculus/paraflocculus (tonsil), e.g., optimization of gaze-holding, smooth pursuit, modulate the high frequency vestibulo-ocular reflex, inhibit anterior semicircular canal pathways, and (2) nodulus/uvula, e.g., important role in velocity storage. The posterior inferior cerebellar artery (PICA) supplies the paraflocculus, nodulus, and uvula (labeled on T2 axial images), while the anterior inferior cerebellar artery (AICA) supplies the flocculus (labeled on a T1 axial image)

seen in left gaze, this can be due to physiologic (normal) end-point nystagmus (EPN) or pathologic gaze-evoked nystagmus (GEN). A normal patient with EPN will have very symmetric, relatively mild nystagmus in lateral gaze that fatigues to a degree as the eyes are kept in eccentric gaze. If the fixation target is brought back to ~75% of lateral gaze, EPN will resolve. When the eyes are brought back from lateral to primary gaze in a patient with EPN, rebound nystagmus should not be seen (or at least not more than a beat or two). With GEN, the nystagmus tends to be more intense and sustained in lateral gaze, and often persists when the eyes are brought back to a

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~75% position. Rebound nystagmus is common with GEN - e.g., RBN in right gaze is the GEN while a reversal to LBN when the eyes are brought back to center is the rebound nystagmus. Occasionally, mild upbeat nystagmus in upgaze can be seen with EPN as well, but this should be mild. Otherwise, vertical GEN is almost always pathologic. If there are other central ocular motor findings on the exam, nystagmus in lateral gaze is much more likely to represent GEN than EPN. (this patient—Video 4.42: Spinocerebellar ataxia type 6 patient with a flocculus/paraflocculus syndrome Video 4.13) Asymmetric involvement of the flocculus/paraflocculus due to a structural lesion (Chiari malformation):  A 25-year-old woman presented with 6  months of progressive imbalance and occipital headaches, which were brought on or aggravated by coughing or sneezing. Examination demonstrated hyperreflexia in the arms and legs with sustained clonus at the ankles and Babinski reflexes bilaterally in addition to gait and limb ataxia. On examination, there was subtle downbeat nystagmus (DBN) in primary gaze that could only be appreciated with the ophthalmoscope, although DBN was easily seen in lateral, down, and lateral/down gaze. In lateral gaze, there was also horizontal gaze-evoked nystagmus. The combination of DBN and GEN in lateral gaze produces an oblique or diagonal nystagmus that beats down and out, so-called “side-pocket” nystagmus. Contrast-enhanced MRI demonstrated peg-like cerebellar tonsils extending 2.9 cm below the foramen magnum (more tonsillar herniation on the right), and flattening of the dorsal medulla (right>left). There was also syringohydromyelia of the cervical and proximal thoracic spinal cord with parenchymal thinning. Taken together, this was consistent with a Chiari type I malformation. She underwent suboccipital craniectomy and C1 laminectomy, and when she was seen 6  months following surgery, all ocular motor findings had resolved with the exception of mild residual gaze-evoked nystagmus. Her balance remained quite impaired due to persistent myelopathy. Fig. 5.4 Video 4.43.

Cerebellum

187

4.7.1.2  Downbeat Nystagmus Case:  See “Downbeat nystagmus” in Chap. 5 4.7.1.3  Alternating Skew Deviation Case:  A 70-year-old woman with a diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) complained of vertical diplopia in lateral gaze. In the video, both spontaneous DBN and gaze-evoked nystagmus are apparent, in addition to a right hypertropia in right gaze and a left hypertropia in left gaze, also referred to as an alternating skew deviation or an abducting hypertropia. Compare this to a patient with bilateral fourth nerve palsies causing right hypertropia in left gaze (due to right fourth NP) and left hypertropia in right gaze (due to left fourth NP). Video 4.32.

4.7.2 S  yndrome of the Nodulus and Ventral Uvula Fig. 4.31 4.7.2.1  C  entral Patterns of Head-shaking and Periodic Alternating Nystagmus (PAN) Case:  A 35-year-old man suffered a gunshot wound to the cerebellum. When he regained consciousness days later, he experienced oscillopsia due to periodic alternating nystagmus (PAN). He was started on baclofen 10 mg bid, and there was a transition to a persistent, mild spontaneous left-beating nystagmus (without PAN). The dose was increased to 20  mg 4 times/day, at which time nystagmus and oscillopsia resolved completely (without side effects). However, following 10–15 seconds of 2–3 Hz horizontal head-shaking, there was robust left-beating nystagmus despite the absence of right ­unilateral vestibular loss. This could be explained by injury to the nodulus, a localization that explains both PAN and certain central patterns of head-shaking nystagmus (HSN) such as this (i.e., robust horizontal HSN in the absence of unilateral vestibular loss). Neuronal circuits responsible for velocity storage are

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4  Motility and Ocular Motor Disorders

mainly located in the vestibular nucleus and nodulus. The main purpose of velocity storage is to prolong vestibular responses beyond the mechanical constraints of the semicircular canal, which improves VOR performance during low-frequency rotations. Disinhibition of velocity storage due to nodulus injury can therefore contribute to an overactive vestibular response, which can result in PAN or central HSN. Other “central” HSN patterns include a reversal from spontaneous nystagmus (e.g., contralesional (right-beating) horizontal nystagmus due to left medullary stroke and ipsilesional (left-beating) HSN) or vertical HSN following horizontal head-shaking (so-called “cross coupling”). Video 4.44: Spontaneous downbeat nystagmus may also result from a nodulus/uvula lesion.

4.7.2.2  Positional Nystagmus Be concerned about a lesion of the nodulus/uvula in a patient with apogeotropic positional nystagmus that is associated with neurologic or ocular motor abnormalities, or which persists despite repeated, properly performed repositioning maneuvers. One theory for apogeotropic central positional nystagmus is that there may be a mismatch between gravity signals derived from the otolith organs and the velocity storage system.

4.7.3 Syndrome of the Dorsal Vermis and Posterior Fastigial Nucleus (Figs. 4.7 and 4.8) 4.7.3.1  OMV • Unilateral lesion—ipsiversive hypometric and contraversive hypermetric saccades • Bilateral lesions—bilaterally hypometric saccades • Bilateral lesions—divergency insufficiency (flocculus may also contribute). Example of a patient with divergence insufficiency who has a cerebellopathy and features of sagging eye syndrome—Video 4.4

References

189

4.7.3.2  FOR • Unilateral lesion—ipsiversive hypermetric and contraversive hypometric saccades. However, since each fastigial nucleus sends fibers through the contralateral fastigial nucleus, a unilateral structural lesion is effectively a bilateral lesion, resulting in bilaterally hypermetric saccades. Video 4.45: bilaterally hypermetric saccades • Bilateral lesions—bilaterally hypermetric saccades; macrosaccadic oscillations and saccadic intrusions (square wave jerks); exophoria.

Read These Books!  [13–15, 16–18] References 1. Brazis PW. Ocular motor abnormalities in Wallenberg’s lateral medullary syndrome. Mayo Clin Proc. 1992;67(4):365–8. 2. Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revisited. Surv Ophthalmol. 2006;51(2):105–28. 3. Frohman TC, Galetta S, Fox R, Solomon D, Straumann D, Filippi M, et  al. Pearls & Oy-sters: the medial longitudinal fasciculus in ocular motor physiology. Neurology. 2008;70(17):e57–67. 4. Tamhankar MA, Biousse V, Ying GS, Prasad S, Subramanian PS, Lee MS, et al. Isolated third, fourth, and sixth cranial nerve palsies from presumed microvascular versus other causes: a prospective study. Ophthalmology. 2013;120(11):2264–9. 5. Zwergal A, Rettinger N, Frenzel C, Dieterich M, Brandt T, Strupp M. A bucket of static vestibular function. Neurology. 2009;72(19):1689–92. 6. Wong AM, Colpa L, Chandrakumar M. Ability of an upright-supine test to differentiate skew deviation from other vertical strabismus causes. Arch Ophthalmol. 2011;129(12):1570–5. 7. Ivanir Y, Trobe JD. Comparing hypertropia in upgaze and downgaze distinguishes congenital from acquired fourth nerve palsies. J Neuroophthalmol. 2017;37(4):365–8. 8. Strupp M, Kremmyda O, Adamczyk C, Bottcher N, Muth C, Yip CW, et  al. Central ocular motor disorders, including gaze palsy and nystagmus. J Neurol. 2014;261(Suppl 2):S542–58. 9. Fearon C, Field R, Donlon E, Murphy OC, Cronin S, Buckley C, et al. The “round the houses” sign and “zig-zag” sign in progressive supranu-

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clear palsy and other conditions. Parkinsonism & related disorders. 2020;81:94–5. 10. Rivaud-Pechoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B, Pierrot-Deseilligny C.  Longitudinal ocular motor study in corticobasal degeneration and progressive supranuclear palsy. Neurology. 2000;54(5):1029–32. 11. Hoglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32(6):853–64. 12. Shemesh AA, Zee DS.  Eye movement disorders and the cerebellum. J Clin Neurophysiol. 2019;36(6):405–14. 13. Biousse V, Newman NJ.  Neuro-ophthalmology illustrated. 3rd ed. New York: Thieme; 2020. 14. Liu GT, Volpe NJ, Galetta SL.  Neuro-ophthalmology: diagnosis and management. 3rd ed. Philadelphia: Elsevier; 2019. 15. Miller NR, Subramanian PS, Patel VR. Walsh & Hoyt’s clinical neuro-­ ophthalmology: the essentials. 4th ed. Philadelphia: Wolters Kluwer; 2021. 16. Brodsky MC.  Pediatric neuro-ophthalmology. 3rd ed. New  York: Springer; 2016. 17. Leigh RJ, Zee DS. The neurology of eye movements. 5th ed. New York: Oxford University Press; 2015. 18. Wong AM.  Eye movement disorders. New  York: Oxford University Press; 2008.

5

Oscillopsia, Nystagmus, and Other Abnormal Movements

5.1

 he History—How to Approach T Oscillopsia and Nystagmus

Patients with nystagmus or saccadic intrusions/oscillations often complain of oscillopsia, or the visual illusion of movement of a stationary object. When a patient complains of “sitting” oscillopsia (i.e., oscillopsia that is independent of head movement, Video 5.1), it is important to understand whether there are associated symptoms to indicate a vestibular disorder or a neuro-ophthalmic disorder. If the oscillopsia is vestibular in origin, dizziness, vertigo, or imbalance should also be experienced, and these balance sensations persist despite eye closure. Ask if the patient is experiencing simultaneous migrainous symptoms to suggest vestibular migraine; aural symptoms that might indicate vestibular paroxysmia, superior canal dehiscence syndrome (SCDS, sound and/or pressure are triggers in these cases), or Meniere’s attacks; or neurologic symptoms that might indicate vascular events. If “sitting” oscillopsia resolves completely with eye closure, then a vestibular disorder is unlikely. Instead, consider non-vestibular disorders such as acquired pendular nystagmus (e.g., due to multiple sclerosis), sacSupplementary Information The online version of this chapter (https://doi. org/10.1007/978-­3-­030-­76875-­1_5) contains supplementary material, which is available to authorized users.

© Springer Nature Switzerland AG 2021 D. Gold, Neuro-Ophthalmology and Neuro-Otology, https://doi.org/10.1007/978-3-030-76875-1_5

191

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5  Oscillopsia, Nystagmus, and Other Abnormal Movements

cadic intrusions (e.g., macrosaccadic oscillations), and superior oblique myokymia (especially with monocular oscillopsia). Note that oscillopsia is rarely experienced with infantile nystagmus, although there are some situations that can cause decompensation and the experience of occasional oscillopsia, usually later in life (e.g., change in strabismus or vision [refractive error or new ocular disease], new neurologic diseases or certain centrally-acting medications). A patient with pendular nystagmus due to MS with severe vision loss due to optic nerve disease may experience minimal or no oscillopsia due to poor visual function.

5.2

 he Exam—Does My Patient Have T Nystagmus or Something Else? [1]

Not everything that jiggles is nystagmus! Fig. 5.1 Nystagmus is a rhythmic involuntary movement of the eyes, where the slow phase is the pathologic phase, and is classified as (1) jerk—each slow phase is followed by a fast phase (position reset mechanism) (Video 5.2), or (2) pendular—back to back slow phases, resembling a pendulum. (Video 5.3). Square wave jerks are one saccadic intrusion that become more frequent with aging, but are especially common in neurodegenerative disorders that affect the cerebellum (progressive ataxia) or basal ganglia (parkinsonism). These intrusions are initiated by saccades (not a slow phase), and are therefore distinct from nystagmus (Video 5.4). If a patient has continuous “sitting” oscillopsia, nystagmus or intrusions/oscillations can usually be observed and the diagnosis can be made (e.g., vertical oscillopsia in downbeat nystagmus). In contrast, “walking” (head-movement-dependent) oscillopsia is almost always due to a vestibulo-ocular reflex (VOR) deficit (Video 5.5) (the concept of “sitting” vs “walking” oscillopsia is courtesy of Dr. David Newman-Toker). Oftentimes, the oscillopsia is episodic (especially when vestibular), and so the examiner should try to provoke nystagmus and typical symptoms (e.g., Dix–Hallpike in benign paroxysmal positional vertigo, Valsalva and pinched-nose Valsalva in SCDS, having the patient look down and contralaterally when superior

The Exam—Does My Patient Have Nystagmus or Something Else?

193

NYSTAGMUS (slow phase is the culprit) Pendular

Jerk Linear (constant)

(slow phase velocities) Decreasing

Increasing

INTRUSIONS/OSCILLATIONS (saccade is the culprit) Square Wave Jerks

Macrosaccadic Oscillations

Opsoclonus & Flutter

Fig. 5.1  Is it nystagmus or a saccadic intrusion/oscillation? Nystagmus can be classified into pendular and jerk waveforms (which are typically generated with video-oculography, video-nystagmography, or electro-nystagmography), where both are generated by a slow, pathologic phase. In pendular nystagmus, the characteristic appearance is the result of back-to-back slow phases. Jerk nystagmus can have constant, increasing or decreasing slow phase velocity: vestibular nystagmus has a linear slow phase velocity due to vestibulo-­ocular reflex imbalance; gaze-evoked nystagmus has a decreasing slow phase velocity due to a leaky neural integrator (i.e., a problem with the gaze-holding machinery); congenital nystagmus and certain posterior fossa disorders can cause an increasing slow phase velocity due to an unstable neural integrator. In jerk nystagmus, the slow (pathologic) phase is followed by the fast (named) phase. Nystagmus should be distinguished from oscillations and intrusions, particularly given disparate localizations and etiologies. These include saccadic intrusions (e.g., square wave jerks) and saccadic oscillations (e.g., ocular flutter and opsoclonus). Saccadic intrusions consist of saccades with an intersaccadic interval (i.e., a brief pause between movements), while saccadic oscillations lack this interval. Square wave jerks are small saccades that move the line of sight away from the target and then return to fixation 200 ms later, and the name derives from the fact that the waveforms have a squarelike appearance. Macrosaccadic oscillations are saccades that take the eye off target and oscillate the line of sight about the object of regard—these movements straddle fixation, and are often seen in association with hypermetric saccades. Ocular flutter is confined to the horizontal vector whereas opsoclonus has horizontal, vertical and torsional components, and occurs in bursts; however, the differential diagnosis, implications, and treatment of flutter and opsoclonus are essentially the same

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oblique myokymia is suspected). If oscillopsia is only brought on with convergence and associated with spasm of the near triad, this is suggestive of voluntary nystagmus/flutter. While some nystagmus or intrusions (latent/infantile nystagmus or square wave jerks, respectively) are benign, others can suggest a potentially dangerous condition (spontaneous upbeat nystagmus and/or direction-changing nystagmus in Wernicke’s or stroke; flutter/opsoclonus in paraneoplastic disorders). Recognizing the pattern of nystagmus or oscillation/intrusion assists in diagnosis and localization. Occasionally, nystagmus is just too subtle to appreciate without using the magnification of the ophthalmoscope or slit lamp (e.g., observing the conjunctival vessels helps with the evaluation of torsional nystagmus). Observation of the fundus can assist in determining the vector (horizontal or elliptical in pendular? Conjugate or dissociated between the eyes?), and appearance (is this nystagmus or is this an intrusion, or is there nystagmus AND intrusions—for example, a patient with downbeat nystagmus AND square wave jerks?). Ocular microflutter is a benign condition that is usually chronic and associated with a migraine history, and does not generally require an extensive workup. In this disorder, there are short bouts of (horizontal) flutter causing oscillopsia that are so subtle that they are typically missed without the aid of eye movement recordings or an ophthalmoscope. In contrast, the acute/subacute onset of ocular flutter (which is clearly visible at the bedside) can suggest an underlying neoplastic condition. The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1

5.3

Nystagmus

5.3.1 Horizontal Nystagmus (Bruns Nystagmus) Case:  A 15-year-old girl presented to clinic with headaches, imbalance, left-sided hearing loss, and “jumping” of the vision in lateral gaze. Her balance difficulties had been progressive over the last 2 years, and she had experienced an increase in headache frequency

Central vestibular nystagmus in the acute vestibular syndrome

Peripheral vestibular nystagmus in the acute vestibular syndrome

Horizontal, Jerk torsional, horizontaltorsional (each can be ipsilesional or contralesional), vertical or vertical-torsional

Appearance Spontaneous horizontaltorsional slow phase (toward the affected ear)

Brainstem or cerebellum

Type of nystagmus or oscillation Localization Jerk Semicircular canal or CN8 A few etiologies to consider Vestibular neuritis (no hearing loss); labyrinthitis (hearing loss—don’t forget labyrinthine stroke) Stroke, demyelination None—usually short-lived

Medication None—usually short-lived

(continued)

Distinguishing feature(s) Unidirectional and contralesional (fast phase); follows Alexander’s law; often mixed horizontal-­torsional; suppression with fixation; associated with ipsilesional abnormal head impulse test (HIT); negative test of skew Can be unidirectional or bidirectional (gaze-­evoked); can follow Alexander’s law; often doesn’t suppress with fixation; HIT is usually normal, and when a vertical ocular misalignment is seen, skew deviation should be assumed until proven otherwise

Table 5.1  Help me now with nystagmus & intrusions/oscillations: Is it urgent and what should I look for?

Nystagmus 195

Horizontal slow Jerk phase to the right transitioning to the left and back to the right (every 90–120 seconds)

Periodic alternating nystagmus

Jerk

Downward slow phase

Upbeat nystagmus (UBN)

Jerk

Upward slow phase

Type of nystagmus or oscillation

Downbeat nystagmus (DBN)

Appearance

Table 5.1 (continued)

A few etiologies to consider

Neurodegenerative cerebellar ataxia, Chiari, paraneoplastic, medication (lithium) Dorsal medulla Stroke, or pontodemyelination, mesencephalic encephalitis, regions Wernicke’s Lesion of the Stroke, medication cerebellar toxicity, nodulus/ventral neurouvula degenerative disorder

Usually cerebellar flocculus/ paraflocculus

Localization

Baclofen, memantine

4-aminopyridine, memantine, baclofen

4-aminopyridine, baclofen, clonazepam, chlorzoxazone

Medication

Will be right-beating (RBN) for 90–120 seconds, will slow and then have a null phase (at which time, sometimes downbeat or other nystagmus or saccadic intrusions can be seen), followed by left-beating nystagmus (LBN), null phase, RBN, etc.

Increases with convergence and in lateral gaze; gaze-evoked nystagmus and impaired pursuit are often present; increased with prone, straight head-hanging or other positional maneuvers, in addition to head-shaking, hyperventilation Follows Alexander’s law (more UBN in up gaze); in Wernicke’s, UBN may transition to DBN with convergence

Distinguishing feature(s)

196 5  Oscillopsia, Nystagmus, and Other Abnormal Movements

Gaze-evoked nystagmus (GEN)

Slow phase drifting back to center (due to orbital elastic forces) initiates the movement, fast phase beating in the direction of gaze (e.g., RBN in right; LBN in left)

Jerk

Lesion involving the neural integrator (nucleus prepositus hypoglossi horizontally; interstitial nucleus of Cajal vertically; flocculus/ paraflocculus horizontally and vertically

Stroke, medication None toxicity, neurodegenerative disorder

If direction-changing horizontal nystagmus in far lateral gaze, it is likely to be physiologic end point nystagmus if low amplitude, it fatigues after several seconds, and if bringing the visual target back to a three-quarters gaze position (so that the target can be seen by the adducting eye as well) mitigates the nystagmus; think GEN when the amplitude is larger, nystagmus persists even in three-quarters position, and if when returning to primary gaze, the nystagmus changes direction—e.g., RBN in right followed by LBN when the eyes are brought back to primary (continued)

Nystagmus 197

Oculopalatal Often vertical tremor (OPT) and/or torsional slow phases, can have horizontal component as well, can be disjunctive

Appearance

Table 5.1 (continued)

Pendular

Type of nystagmus or oscillation

Mollaret’s triangle (inferior olive [IO] to contralateral dentate nucleus, decussates and wraps around contra- red nucleus and descends to ipsi- IO)

Localization

Medication

Dorsal pontine Gabapentin, hemorrhage memantine, involving central trihexyphenidyl tegmental tract is common; consider progressive ataxia and palatal tremor (PAPT) when structural lesion is absent

A few etiologies to consider

When OPT is due to a pontine lesion of the central tegmental tract, the following signs are commonly also seen: lower motor neuron facial palsy, fascicular 6th nerve palsy, nuclear 6th causing horizontal gaze palsy, internuclear ophthalmoparesis (INO), one-and-a-half syndrome; when pendular nystagmus is seen, always look at the resting palate; inferior olivary hypertrophy (T2/FLAIR hyperintensity) on MRI is characteristic; OPT due to a lesion in Mollaret’s triangle develops weeks to months after the injury, not acutely

Distinguishing feature(s)

198 5  Oscillopsia, Nystagmus, and Other Abnormal Movements

Square wave jerks (SWJ)

Other acquired pendular nystagmus (APN)

Usually horizontal or elliptical slow phases in multiple sclerosis (MS) (and can be dissociated/ disconjugate); divergentconvergent slow phases in Whipple disease Small horizontal back-and-forth saccades

Instability of neural integrators (in MS); associated with afferent dysfunction (e.g., cataract causing HeimannBielschowsky phenomenon) Saccadic Cerebral intrusion cortical, basal with ganglia, intersaccadic cerebellar, interval increase with normal aging

Pendular

Parkinson’s disease, progressive supranuclear palsy, cerebellar ataxia

Usually visually asymptomatic, no strong evidence for any medication

MS (common); Gabapentin, medication/ memantine toxicity (toluene)-induced, stroke, neurodegenerative disease (rare)

SWJ can become more frequent with normal aging especially when asymptomatic and in isolation; if SWJ are >15/ minute and associated with gaze-evoked nystagmus, saccadic pursuit or other central ocular motor findings, they are likely to be pathologic (continued)

APN in MS is commonly seen with other ocular motor disorders localizing to the posterior fossa including gaze-evoked nystagmus, saccadic pursuit, INO, hypermetric saccades; APN is usually more prominent in the worse-seeing eye in MS; occasionally, an MS patient may have APN and normal afferent function

Nystagmus 199

Ocular flutter / opsoclonus

Rapid back-toback saccades horizontally (flutter) or horizontally and vertically (opsoclonus)

Appearance

Table 5.1 (continued)

Saccadic intrusion without intersaccadic interval

Type of nystagmus or oscillation

Brainstem (omnipause cells in nucleus raphe interpositus) or cerebellum (fastigial pathways)

Localization Reported in many infectious (and postinfectious), paraneoplastic (neuroblastoma in the very young, lung and gynecological among others in older), medication-related conditions

A few etiologies to consider Distinguishing feature(s)

Acute—steroids, Often associated with myoclonic intravenous jerks involving arms, legs, truncal immunoglobulin, muscles; exaggerated startle response plasma exchange; acute or chronic— rituximab, clonazepam, gabapentin, memantine, others (mainly case reports/ series)

Medication

200 5  Oscillopsia, Nystagmus, and Other Abnormal Movements

Nystagmus

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during the same period of time. She did have a history of migraines, but her recent headaches felt different. Neurologic examination was normal with the exception of an inability to tandem walk for more than a few steps, nor could she stand in tandem. Neuro-ophthalmic examination was normal including afferent function and motility/ ocular alignment. There was very mild spontaneous right-beating nystagmus (RBN), which was unchanged in up- and downgaze, and her RBN was more prominent in right gaze where she experienced mild oscillopsia. In left gaze, there was a larger amplitude left-beating nystagmus (LBN) and more oscillopsia. Saccades were normal. Smooth pursuit appeared mildly saccadic in all directions (especially to the right in the direction of the slow phase), while vestibuloocular reflex suppression (VORS) appeared saccadic in all directions except to the left, where it appeared normal. Head impulse test (HIT) was normal to the right and abnormal to the left. With fixationremoved while wearing Frenzel goggles, RBN was more noticeable, and RBN increased slightly with mastoid and vertex vibration and horizontal head-­shaking. Following 40  seconds hyperventilation, there was robust LBN. Otoscopic examination was normal, although finger rub was diminished on the left side, Rinne demonstrated that air conduction was greater than bone conduction AU, and Weber lateralized to the right ear (consistent with a left sensorineural hearing loss). Contrast-enhanced MRI demonstrated a large left cerebellopontine angle tumor thought to be due to vestibular schwannoma, which was resected and pathology was found to be consistent with this diagnosis. Video/figure:  Video 5.6 and Fig. 5.2 Key questions to ask:  • Are there episodes of dizziness or vertigo (i.e., less likely to be a vestibular schwannoma) or just a progressive balance disorder? • Is there head-­movement-­dependent (“walking”) oscillopsia to suggest severe bilateral (or poorly compensated) vestibular loss?. The combination of progressive headaches, left sided hearing loss, and imbalance is highly suspicious for a left cerebellopontine angle (CPA) mass lesion causing CN8 dysfunction.

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a

d

b

UBN

OPT

e

c

Torsional

Bruns

DBN/GEN

f

PAN/CPPN

Fig. 5.2  Common lesions and localizations for nystagmus as seen on MRI: (a) Upbeat nystagmus (UBN)—typically associated with midline brainstem lesions, especially involving the dorsal medulla (nucleus of Roller, nucleus intercalatus). Seen here are bilateral dorsal medullary (axial) FLAIR hyperintensities (arrow) in a patient with pure UBN due to multiple sclerosis. (b) Torsional nystagmus—this is usually the result of a brainstem lesion affecting the central utriculo-ocular motor or vertical semicircular canal pathways (pure torsional nystagmus with symmetric injury to the anterior and posterior pathways, and vertical-torsional nystagmus typically results from asymmetric injury). This patient suffered a right interstitial nucleus of Cajal stroke seen on axial MR diffusion-weighted imaging (DWI, arrow) causing torsional nystagmus with the top poles of both eyes beating toward the right ear (accompanied by a contraversive ocular tilt reaction, which is another common feature). (c) Downbeat (DBN) and gaze-evoked nystagmus (GEN)—while a discrete flocculus/paraflocculus lesion may be seen, diffuse cerebellar atrophy (on sagittal T1) is commonly seen as in this patient with a cerebellar degeneration causing DBN, GEN, saccadic pursuit and limb/gait ataxia. (d) Oculopalatal tremor (OPT)—a dorsal pontine hemorrhage involving the descending inhibitory central tegmental tract is a common cause of OPT, seen here as a hypointensity in the dorsal pons (arrow) on axial gradient echo sequence (note that inferior olivary hypertrophy/hyperintensity is commonly seen on FLAIR/T2, but this represents physiologic changes that have occurred within Mollaret’s triangle rather than representing the insult itself - see Fig. 5.7). (e) Bruns nystagmus—seeing vestibular nystagmus in left gaze and gaze-evoked nystagmus in right gaze should alert the clinician to a large right cerebellopontine angle tumor, such as a vestibular schwannoma (axial T1 contrast, arrow, image courtesy of Dr. Jeffrey Sharon). (f) Periodic alternating nystagmus (PAN)—this localizes well to the nodulus (arrow) and ventral uvula, as seen on this axial diffusion-weighted image in a patient with PAN due to an acute stroke. Central paroxysmal positional nystagmus (CPPN)—commonly downbeat in straight head hanging or prone and apogeotropic in Dix-Hallpike and supine roll—is commonly seen with nodulus lesions as well

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Key findings to elicit:  When a CPA angle tumor is suspected: (1) Evaluate for unilateral hearing loss with finger rub, Rinne/ Weber and perform otoscopy (referrals to audiology and ENT are also warranted), (2) Evaluate for unilateral vestibular loss with removal of fixation and provocative maneuvers such as vibration and headshaking (which often increase contralesional vestibular nystagmus), HIT (HIT can appear normal if compensation has occurred given the chronicity of the lesion, so video HIT and calorics are often helpful), (3) Hyperventilate the patient and look for ipsilesional (excitatory) nystagmus, (4) Evaluate for neurologic (e.g., gait or limb ataxia) or ocular motor (e.g., saccadic dysmetria, saccadic pursuit/VORS, gaze-evoked nystagmus) abnormalities to suggest cerebellar or brainstem compression, (5) Evaluate for Bruns nystagmus—because of involvement of the left brainstem/cerebellum (e.g., dysfunction of the neural integrator/gaze holding apparatus, especially compression of the flocculus in this case) by the CPA mass, left-beating (ipsilesional) “gaze-evoked” nystagmus will be seen in left gaze (a larger amplitude and lower frequency nystagmus). Because of involvement of the left 8th cranial nerve, right-beating (contralesional) “vestibular” nystagmus will be seen in right gaze (increased RBN in the direction of the fast phase, in accordance with Alexander’s law, a smaller amplitude and higher frequency nystagmus). The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  If the schwannoma is small, it can be missed on a noncontrast MRI that lacks high resolution/thin cuts through the internal auditory canal (IAC). Because the unilateral vestibular loss (UVL, due to CN8 compression) occurs over months to years, the UVL may be very well compensated for and can be missed with bedside HIT. This is why removal of fixation and utilization of provocative maneuvers (described above) is particularly impor-

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tant. In a patient with horizontal nystagmus, also consider the possibility of latent nystagmus, which is typically associated with a known childhood history of strabismus (infantile esotropia). Latent nystagmus will change direction depending on the viewing eye—for example, right-beating with the right eye viewing and left-beating with the left eye viewing (Video 5.7). This nystagmus will make interpretation of bedside and laboratory vestibular testing particularly challenging even when the vestibular system is intact. Infantile nystagmus should also be considered, but usually patients are aware of this history (and their nystagmus) while patients with latent nystagmus may be unaware. Do not miss this!  Rarely, a vestibular schwannoma can cause, or present with, vertigo attacks, although progressive hearing loss and imbalance is a far more typical symptom complex. Consider neurofibromatosis type 2 when bilateral vestibular schwannomas are present. In patients with unilateral or bilateral hearing loss, consider first whether the onset is gradual (symmetric or asymmetric?) or sudden in onset (with or without vertigo?). What is next?  Contrast-enhanced IAC protocol MRI. Treatment options:  Depending on the symptoms, exact location and extent of the vestibular schwannoma, surgery may be indicated with ENT and/or neurosurgery, although gamma knife and similar therapies may be favored in some, versus watchful waiting in others. If you can only remember one thing…  Bruns nystagmus, characterized by ipsilesional gaze-evoked and contralesional vestibular nystagmus, is highly localizing to the CP angle. However, another localization for Bruns nystagmus when hearing loss is absent could be the (left) medulla—e.g., contralesional (right-beating) vestibular nystagmus due to involvement of central semicircular canal pathways, and ipsilesional (left-beating) gaze-evoked nystagmus due to involvement of nuclei involved in horizontal gaze-holding (nucleus prepositus hypoglossi and medial vestibular nucleus). Want to know more?  [2]

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5.3.2 Periodic Alternating Nystagmus Case:  A 60-year-old woman presented with complaints of several years of worsening imbalance and oscillopsia. Examination demonstrated gait and limb ataxia, hypermetric saccades, saccadic smooth pursuit and vestibulo-ocular reflex suppression (VORS), and gaze-evoked nystagmus (GEN). She had spontaneous horizontal nystagmus that alternated between right-beating and left-beating every ~100 seconds (with a null or quiet period in between), consistent with periodic alternating nystagmus (PAN). Reversible/treatable causes of a cerebellar disorder were unrevealing including contrast-enhanced MRI, and a progressive cerebellar ataxia (due to spinocerebellar ataxia type 6 or similar) was suspected. Video/Figure:  Video 5.8 and Fig. 5.2 Key questions to ask:  If the onset is abrupt and/or vascular risk factors are present, consider stroke and ask about other posterior circulation symptoms. Ask about headaches (e.g., Chiari, midline cerebellar tumor), associated neurologic symptoms, and family history of balance disorders (e.g., spinocerebellar ataxia). Key findings to elicit:  Evaluate for truncal/gait and limb ataxia. Examine all classes of eye movements for a better understanding of localization, which can help with the differential diagnosis. In this case, she had evidence of diffuse cerebellar involvement which was supported by limb and gait ataxia, saccadic pursuit and GEN (­flocculus/paraflocculus), saccadic hypermetria (fastigial nucleus), as well as PAN and cross-coupling with head-shaking (nodulus/uvula). The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  In any patient with spontaneous horizontal nystagmus (that is not obviously related to acute vestibular neuritis/peripheral vestibulopathy), observe the nystagmus for at least 120 seconds to specifically evaluate for PAN.

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Do not miss this!  If the onset of PAN is abrupt, stroke is most likely. If progressive, consider a degenerative cerebellar condition (e.g., SCA 6, see example—Video 5.9), or structural lesion (e.g., Chiari malformation). In children, consider congenital PAN once a structural lesion has been excluded. What is next?  Contrast-enhanced MRI, and depending on the result and chronicity, consideration of cerebellar labs and testing (inflammatory, infectious, nutritional, paraneoplastic, genetic). Treatment options:  Baclofen has been shown to be beneficial for patients with PAN. Memantine may help in some cases. Want to know more?  [3, 4]

5.3.3 Downbeat Nystagmus Case:  A 60-year-old woman presented with the subacute onset over several weeks of a gait disorder, dizziness, and oscillopsia. Examination demonstrated spontaneous DBN with side pocket nystagmus in lateral gaze (a combination of horizontal gaze-­evoked and downbeat nystagmus, giving an oblique [downward and lateral] appearance), in addition to hypermetric saccades, saccadic smooth pursuit and VOR suppression. Contrast-enhanced MRI was normal, and lumbar puncture demonstrated a mild cerebrospinal fluid pleocytosis with normal protein, glucose, cytology, and flow cytometry. CT of the chest/abdomen/pelvis revealed a left hilar mass with extension into the bronchus, and biopsy revealed small cell carcinoma of the lung. It was thought that a paraneoplastic cerebellopathy was the most likely culprit despite a negative serum paraneoplastic panel. There was significant subjective improvement in vertical oscillopsia and objective improvement in her downbeat nystagmus with intravenous immunoglobulin in addition to treating the malignancy with resection and chemotherapy.

Nystagmus

a

SS

207

b.

MSA (early)

Chiari

c.

MSA (advanced)

Fig. 5.3  Disorders and localizations to consider in patients presenting with chronic imbalance and downbeat nystagmus (DBN): All patients with evidence of cerebellar dysfunction require an MRI of the brain, preferably with contrast and susceptibility weighted imaging (SWI). (a) In this patient with superficial siderosis (SS), SWI demonstrates hypointense signal (arrows) involving the brainstem, cerebellum, as well as the vestibulocochlear nerves (this patient also had bilateral vestibular and hearing loss), that is indicative of hemosiderin deposition lining these structures. The source of the hemosiderin could not be elucidated in his case. (b) In this patient with multiple system atrophy (MSA), there was mild DBN (in addition to gaze-evoked nystagmus) when upright and a significant increase in DBN when supine. On exam, there were parkinsonian symptoms including bradykinesia and rigidity, and axial T2 demonstrated pontine atrophy with a cross-shaped (arrows) hyperintensity within the pons (an early “hot cross bun sign”). The bottom image demonstrates a more prominent “hot cross bun sign” (hyperintense on FLAIR) in advanced MSA (Image courtesy of Dr. David Zee). (c) A young woman presented with occipital headaches (worse with coughing), DBN and imbalance, and MRI demonstrated a Chiari malformation causing tonsillar (paraflocculus) herniation, with a peg-like appearance of the tonsils (arrow). Her severe imbalance was due to both cerebellopathy and a myelopathy (hyperreflexia, ankle clonus, + Babinski) from an associated syrinx

Video:  This patient: Video 5.10; prominent DBN in a cerebellar degeneration Video 5.11, Figs. 5.2 and 5.3. Key questions to ask:  In patients with DBN, the time course is most important: (1) if acute, think about a stroke (rare but consider bilateral vestibulocerebellar ischemia or a lesion of the brainstem paramedian tracts), infection (cerebellitis), medication (e.g., anti-

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convulsants), or other toxicities; (2) if subacute, think about a paraneoplastic etiology (in an older person) or rarely Creutzfeldt–Jacob disease; (3) if chronic, think about a structural (e.g., Chiari), hereditary (e.g., spinocerebellar ataxia), neurodegenerative (e.g., multiple system atrophy), medication-­induced (e.g., lithium—may be acute/ subacute as well), or nutritional disorder. If there is associated headmovement-dependent “walking” oscillopsia (due to bilateral vestibular loss) and/or distal limb numbness/tingling (due to neuropathy), consider cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS—a chronic unexplained dry cough is another common symptom of this disorder, in addition to a saccadic visually enhanced vestibulo-ocular reflex [vVOR]—Video 5.12) [5]. Key findings to elicit:  If accompanied by gaze-evoked nystagmus, impaired pursuit/vestibulo-ocular reflex (VOR) suppression, normal saccades, think about a flocculus/paraflocculus ­localization (consider spinocerebellar ataxia type 6 or similar in chronic conditions). If there is DBN without impaired pursuit/VOR suppression or gaze-evoked nystagmus, also consider a nodulus/uvula localization. DBN typically increases in lateral gaze and downgaze (another reason why these patients should avoid ­progressives, bi- and trifocals), and decreases in up gaze. Evaluate the VOR (head impulse test, dynamic visual acuity, etc.) given the possibility of CANVAS, multiple system atrophy, spinocerebellar ataxia type 3, superficial siderosis, among others that can affect cerebellar and vestibular function. Evaluate for a neuropathy given the possibility of CANVAS or a nutritional disorder (B12 deficiency). Evaluate saccades (especially accuracy and velocity) to better understand the extent of brainstem/cerebellar involvement. A complete neurologic (including cognitive) and neuro-ophthalmic (e.g., optic neuropathy in B12 deficiency or maculopathy in SCA 7) examination is essential in these patients. The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  A patient may have mild “central” ocular motor examination findings (such as mild gaze-evoked nystagmus) with little

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to no DBN. DBN can be provoked or accentuated by a variety of maneuvers such as convergence, hyperventilation, horizontal head-shaking (cross-coupling), prone positioning (or simply leaning forward so the head is between the legs), straight head-hanging or Dix–Hallpike (Video 5.13). Provocation of DBN is a strong indication of cerebellar dysfunction, especially useful in the evaluation of patients with undiagnosed balance disorders. Do not miss this!  Any older patient presenting with the subacute onset of a DBN/cerebellar syndrome should be worked up expeditiously for a paraneoplastic disorder. The vast majority of the time, pure DBN does not present acutely and does represent a neurologic emergency. When it does, think about bilateral strokes (cerebellar flocculus/paraflocculus or midline brainstem paramedian tracts), infection (cerebellitis), or medication toxicity. Acute Wernicke’s encephalopathy can present with vertical nystagmus, although this is often upbeat nystagmus (UBN). However, UBN can transition to DBN with convergence, and a gradual evolution to spontaneous DBN often occurs subacutely/chronically in Wernicke’s. What is next?  All patients require contrast-enhanced MRI to evaluate for a structural lesion (especially a cervicomedullary lesion such as Chiari malformation). If normal, focus the workup based on the onset/timing of symptoms and the presence or absence of other neurologic signs. Treatment options:  As long as there is no seizure history, trial of 4-aminopyridine (available as dalfampridine in the United States, but only indicated to improve gait in multiple sclerosis; a compounded formulation is another option) is warranted in patients with oscillopsia due to DBN (some patients can have a dramatic response). Other medications which may be effective in select patients include clonazepam, chlorzoxazone, and baclofen. Unfortunately, large-scale randomized controlled trials are lacking in support of these medications. Advanced:  DBN is usually due to pathology involving the flocculus/paraflocculus and less commonly the nodulus/uvula

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(rarely the paramedian tracts). Theories for its genesis include: (1) vertical smooth pursuit asymmetry (due to an inherit upward-­ downward asymmetry); (2) otolith pathway asymmetry; (3) loss of inhibition of anterior canal pathways, causing an upward drift (slow phase) and a downward reset movement (DBN), an ocular motor finding that is usually associated with flocculus/paraflocculus dysfunction, which causes overaction of the anterior canal (upward or antigravity) pathways relative to posterior canal (downward or gravity) pathways. This results in a continuous slow upward phase and subsequent fast downward phase, causing the DBN. Want to know more?  [6]

5.3.4 Upbeat Nystagmus Case:  A 40-year-old woman presented to the hospital with imbalance, dizziness, confusion, and oscillopsia. In the months leading up to presentation, she had lost 50 pounds due to poor oral intake in the setting of a severe depressive episode, in addition to intractable vomiting in the days leading up to hospitalization. Exam demonstrated upbeat nystagmus (UBN) in primary gaze, and her nystagmus followed Alexander’s law as UBN typically does—that is, when looking in the direction of the fast phase (up), her UBN increased in intensity. There was no gaze-­evoked nystagmus, and head impulse test in the planes of the horizontal canals was normal (although IV thiamine had already been given). She had severe gait ataxia. Poor nutrition and vomiting caused thiamine deficiency which led to Wernicke’s encephalopathy. She was given IV thiamine upon presentation to the hospital, with gradual improvement in dizziness, imbalance, and UBN.

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Video:  Video 5.14, Figs. 5.2, 5.4, and 5.5 Key questions to ask:  When UBN is present and acute/subacute in onset, consider brainstem syndromes caused by ischemia, infection (encephalitis), paraneoplastic and demyelination and ask about vascular risk factors and history of previous neurologic and visual (e.g., optic neuritis) symptoms, respectively. If suspicion is high for Wernicke’s encephalopathy, inquire about gastric bypass surgery, malnutrition and/or alcoholism, hyperemesis gravidarum or other causes of frequent vomiting (e.g., chemotherapy). Key findings to elicit:  Because upbeat nystagmus typically localizes to the brainstem, evaluate for other posterior circulation (e.g., homonymous visual field defect) and posterior fossa (e.g., skew deviation, ocular lateropulsion, hemi-ataxia) signs. In Wernicke’s encephalopathy, patients may have an encephalopathy or confabulate, and oftentimes ataxia and severe gait imbalance

Axial FLAIR

Fig. 5.4  MRI in Wernicke’s encephalopathy: These two images demonstrate FLAIR hyperintensities involving the periventricular region anterior to the fourth ventricle (white arrow), and periaqueductal area (dashed arrow), which are common MRI findings in Wernicke’s. Also look for lesions affecting the mammillary bodies and bilateral thalami

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Ventral Inferior olive

Anterior Spinal A

Inferior olive Vertebral A

Nucleus of roller Nucleus intercalatus

Nucleus of roller Nucleus intercalatus

PICA

IC

IC

P MVN

P MVN

Dorsal

Fig. 5.5  Vascular distribution and anatomy relevant to the medial medullary syndrome: This axial section of the medulla highlights those structures that, when damaged, are often responsible for spontaneous upbeat nystagmus (UBN). The nucleus of Roller and nucleus intercalatus normally have an inhibitory influence over the cerebellar flocculus, and when there is a lesion of Roller/intercalatus, there is less inhibition of the flocculus. The Purkinje cells of the flocculus normally inhibit the antigravity or upward anterior semicircular canal (SCC) pathways. With a lesion of Roller/intercalatus, the flocculus will over-inhibit the anterior SCC pathways, causing relative over-activation of the posterior SCC pathways which will generate a downward slow phase. The fast/position-reset phase will be upward, and these alternating slow (downward) and fast (upward) phases are responsible for UBN

with associated dizziness or vertigo is present. In Wernicke’s, the following ocular motor/vestibular signs should be sought: spontaneous UBN (due to dorsal medullary involvement (Fig. 5.5)), which may transition to downbeat nystagmus (DBN) with convergence (see an example with discussion of mechanism, Video 5.15); horizontal gaze-evoked nystagmus (GEN) is common; ophthalmoparesis (especially 6th nerve palsy/palsies) may or may not be present; UBN may occasionally increase in downgaze (i.e., socalled anti-Alexander’s law) instead of upgaze in Wernicke’s; loss of the horizontal vestibulo-­ocular reflex (VOR) with relative sparing of the vertical VOR (which can correct within minutes of IV thiamine administration). Chronically, patients may develop spontaneous DBN.

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The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  Spontaneous UBN, GEN, and bilateral VOR loss due to Wernicke’s can occur without ophthalmoparesis. If there is any suspicion for Wernicke’s encephalopathy, IV thiamine should be given without delay. The classic triad of confusion, ophthalmoplegia, and ataxia is often absent. Do not miss this!  The acute onset of UBN is concerning for a variety of dangerous disorders including brainstem ischemia, encephalitis, and Wernicke’s encephalopathy. Consider demyelination as well, including multiple sclerosis (Video 5.16), neuromyelitis optica (NMO), as well as anti-myelin oligodendrocyte glycoprotein (MOG) syndromes. In a young patient with UBN and new head or neck pain, rule out vertebral artery dissection. If spontaneous upbeat-torsional nystagmus is seen, this is often due to involvement of the anterior semicircular canal pathway, as it travels through the lateral pontine superior vestibular nucleus (Video 5.17), medial longitudinal fasciculus (Video 4.24), ventral tegmental tract, or brachium conjunctivum/superior cerebellar peduncle. What is next?  Urgent brain MRI to evaluate for ischemia, with the addition of contrast when there is uncertainty. Vascular imaging of the head and neck when ischemia or vertebral artery dissection are suspected. Treatment options:  Rapid administration of IV thiamine when Wernicke’s is suspected. If patients experience oscillopsia from persistent UBN (relatively rare), consider 4-aminopyridine (available as dalfampridine in the United States, but only indicated to improve gait in multiple sclerosis; a compounded formulation is another option) or memantine. Want to know more?  [7, 8]

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5.3.5 Torsional Nystagmus The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. A few pearls: • Usually, spontaneous pure jerk torsional nystagmus localizes to the medulla/pontomedullary junction (e.g., medullary tumor Video 5.18) or pontomesencephalic (interstitial nucleus of Cajal/rostral interstitial nucleus of medial longitudinal fasciculus, Video 4.35) regions and is often due to a brainstem lesion (e.g., ischemia, demyelination, encephalitis). Pendular torsional nystagmus is often due to oculopalatal tremor (covered in the next section—Video 5.19). • Jerk torsional nystagmus is commonly seen in a mixed pattern, in conjunction with horizontal nystagmus (e.g., mixed horizontal-­torsional nystagmus in vestibular neuritis—Video 5.20), or with vertical nystagmus. Vertical-torsional nystagmus can be “peripheral,” as in posterior canal benign paroxysmal positional vertigo (triggered UB-torsional due to stimulation of a single posterior canal), or “central” as in an acute medial longitudinal fasciculus stroke (persistent UB-torsional nystagmus resulting from involvement of the central anterior semicircular canal pathway). • Because central (usually brainstem) anterior/posterior semicircular canal and/or utriculo-ocular motor pathway injury is thought to be responsible for pure spontaneous jerk torsional nystagmus, skew deviation or other features of the ocular tilt reaction (ocular counterroll, head tilt) are commonly seen as well—Video 5.21. It is possible to have pure torsional nystagmus on a peripheral basis, but this would require strategically damaging a posterior canal along with the ipsilateral anterior canal, which is an uncommon occurrence (Fig. 5.6).

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MR

SR LR

MR

IO

L PC

IO

IR

R AC

SO

SO

LR IR

R HC

SR

R PC

L HC L AC

MUSCLE

PRIMARY ACTION

SECONDARY ACTION

Superior Rectus (SR)

Supraduction

Incycloduction

Inferior Rectus (IR)

Infraduction

Excycloduction

Superior Oblique (SO)

Incycloduction

Infraduction

Inferior Oblique (IO)

Excycloduction

Supraduction

Fig. 5.6  The cyclovertical extraocular muscles and their semicircular canal innervation: When stimulated, each of the 6 angular acceleration detecting semicircular canals (3 on the right and 3 on the left) responds with a conjugate eye movement, with the vector(s) indicated above. PC, posterior canal; HC, horizontal (also known as lateral) canal; AC=anterior (also known as superior) canal. (1) When the right AC (red) is stimulated as in exposure to a loud noise in superior (or anterior) canal dehiscence syndrome, excitatory slow phases that are upward and torsional (towards left ear) are generated. This is due to contraction of the right superior rectus (up and incycloduction OD) and left inferior oblique (up and excycloduction OS) muscles (both also in red). Fast phases are in the opposite direction—downbeat and torsional toward the right (ipsilateral) ear—are then seen clinically. (2) When the right HC (green) is stimulated as in a rapid rightward head turn, the vestibulo-ocular reflex (VOR) results in a conjugate eye movement to the left via contraction of the right medial rectus and left lateral rectus muscles (also in green). (3) When the right PC (blue) is stimulated as in right PC benign paroxysmal positional vertigo (BPPV), excitatory slow phases that are downward and torsional (towards left ear) are generated. This is due to contraction of the right superior oblique (down and incycloduction OD) and left inferior rectus (down and excycloduction OS) muscles (both also in blue). Fast phases are in the opposite direction upbeat and torsional towards the right (ipsilateral) ear—are then seen clinically

A few practical points for recognizing and naming torsional nystagmus: • Sometimes torsional nystagmus can be difficult to appreciate and to characterize. Viewing a conjunctival blood vessel can assist in the evaluation of direction, and the nystagmus should be named by the direction to which the top poles of the eyes beat—to the right ear or to the left ear. When performing

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direct ophthalmoscopy, since the examiner’s line of sight is parallel to the axis of rotation, the torsional nystagmus will be in the same direction as the nystagmus viewed without the ophthalmoscope. Compare this to horizontal or vertical nystagmus, where the axis of rotation is different and the examiner views the optic nerve (which is posterior to the axis of rotation); therefore, the nystagmus viewed with the direct ophthalmoscope will be opposite to that viewed without it (e.g., downbeat nystagmus will appear to be upbeat nystagmus with the ophthalmoscope). Treatment options:  There is no strong evidence for any one particular medication, and torsional nystagmus usually resolves quickly after a stroke or demyelinating lesion; therefore, medications are usually not necessary, although gabapentin may help some patients. Want to know more?  [9, 10]

5.3.6 Oculopalatal Tremor Case:  Five years prior to presentation, a 50-year-old woman experienced the acute onset of right sixth and seventh nerve palsies and left hemiparesis. Two cavernomas within the right pons (one in the region of the facial colliculus) were demonstrated by MRI. She then experienced a second episode of right facial palsy and dysphagia. Imaging revealed acute pontine hemorrhage and she underwent surgical resection of the cavernoma. Postoperatively, she had facial diplegia and bilateral horizontal gaze palsies. Several months later, she experienced vertical oscillopsia. On examination at that time, she had continuous large amplitude vertical pendular nystagmus and symmetric palatal tremor. She had bilateral horizontal gaze palsies with intact vertical movements. Convergence increased her ability to adduct OU slightly. Review of her MRI 2 months postop-

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eratively revealed surgical changes to the floor of the fourth ventricle as well as marked hyperintensities of the bilateral inferior olivary nuclei. This patient presented with classic features of oculopalatal tremor (OPT), including vertical pendular nystagmus, palatal tremor, and MRI evidence of inferior (medullary) olivary hypertrophy. Given the proximity of the central tegmental tract (CTT) to the abducens nuclei and facial nerve fascicles, she also had horizontal gaze palsy and facial diplegia. Unfortunately, neither memantine nor gabapentin resulted in improvement with regard to (subjective) oscillopsia or (objective) pendular nystagmus. Video:  Video 5.22. Figure:  Figs. 5.2 and 5.7. Key questions to ask:  OPT often develops months (but can be weeks or years) after a clear inciting event, usually a hemorrhage (commonly affecting the CTT, but also the dentate nucleus or other structures that make up Mollaret’s triangle), trauma or less commonly, an ischemic stroke or another brainstem syndrome (e.g., NMO, sarcoidosis). If there was no inciting event, and symptoms are progressive over years, consider Alexander disease (a leukodystrophy) or progressive ataxia with palatal tremor (PAPT). Key findings to elicit:  The pendular nystagmus associated with OPT often has mixed vertical and torsional components (see example—Video 5.19). However, pure vertical or pure torsional pendular nystagmus can be seen, as well as a horizontal or convergent-­divergent (also consider Whipple’s disease with this pattern, usually patients have gastrointestinal symptoms as well) component. Nystagmus can be disjunctive (different in each eye, see example—Video 5.23), or very subtle and best seen with ophthalmoscopy (see example—Video 5.24). The ocular oscillations are often accentuated by gentle eyelid closure (referred to as ocular synchrony), even in a patient where nystagmus is not apparent with eyes open (see example—Video 5.25). When OPT is sus-

5  Oscillopsia, Nystagmus, and Other Abnormal Movements

218

Central Tegmental Tract

IN MIDBRA

Red N.

M

B RE

MEDULLA

Denta te

CE

PONS

LU EL

Inferior Olive

Superior Cerebellar Peduncle Purkinje Cell (Cortex)

Inferior Cerebellar Peduncle (Climbing Fibers)

Fig. 5.7  The Guillain-Mollaret triangle, and its role in oculopalatal tremor (OPT): Also referred to as the dentato-olivary pathway, reflecting the three points of this imaginary triangle: (1) dentate nucleus, (2) red nucleus, and (3) inferior olivary nucleus. The olive sends decussating climbing fibers through the contralateral inferior cerebellar peduncle that travel from the Purkinje cells of the cerebellar cortex to the dentate nucleus; the dentate sends decussating fibers (via the superior cerebellar peduncle) that wrap around the contralateral red nucleus; these fibers descend from red nucleus to the ipsilateral inferior olive via the central tegmental tract (CTT). Injury to any of these structures may result in oculopalatal tremor (OPT). Since the CTT normally inhibits the ipsilateral inferior olive, damage to the CTT results in decreased inhibition of the ipsilateral olive resulting from transsynaptic degeneration. Hypertrophic inferior olivary degeneration occurs as swollen and vacuolated neurons come into contact with each other and corresponds to MRI T2/ FLAIR hyperintensity (on the right)

pected, the palate must be viewed at rest, or else the tremor can be easily overlooked. Subtle facial muscle contraction is often seen, which is synchronous with palatal tremor. Finally, when OPT is due to a CTT lesion, lower motor neuron facial palsies, 6th nerve palsy, internuclear ophthalmoplegia (INO), one-and-a-half syndrome, and horizontal gaze palsies are often seen. The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  Because OPT begins months following an event (usually pontine hemorrhage), new oscillopsia (due to pendular nys-

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tagmus) and gait imbalance may prompt an expensive and unnecessary workup. When the suspicion is high, OPT can be quickly recognized at the bedside and unilateral or bilateral medullary inferior olivary hypertrophy appreciated on MRI. Notably, the development of OPT does not represent a new hemorrhagic event or seizure activity. Do not miss this!  OPT may present with palatal tremor and little to no nystagmus or nystagmus with little to no palatal tremor. The clinician must have a high suspicion for OPT in these cases. What is next?  If a patient suffered a known hemorrhagic, surgical or traumatic event and MRI demonstrates hypertrophic olivary degeneration, no additional workup is needed. Otherwise, contrast-­enhanced brain MRI is necessary, and PAPT and other degenerative conditions should be considered in the differential. Treatment options:  Like acquired pendular nystagmus in MS, gabapentin and memantine are the two medications that have the most evidence for their use. Want to know more?  [11, 12]

5.3.7 M  ultiple Sclerosis Acquired Pendular Nystagmus Case:  A 30-year-old man with a 15-year history of multiple sclerosis (MS) presented with “shaking” of vision for the last 12  months. The visual motion of the environment (oscillopsia) was independent of head movements, and the onset was initially intermittent, but then gradually became constant over months. He did not complain of double vision. He did have a history of bilateral attacks of optic neuritis 10+ years ago, and accordingly, his visual acuity was 20/100 OU with severe dyschromatopsia and

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optic nerve pallor OU. On examination, there were ocular motor abnormalities including gaze-evoked nystagmus, saccadic smooth pursuit, and hypermetric saccades, signs that were compatible with demyelinating plaques in the posterior fossa. His oscillopsia was horizontal and due to horizontal pendular nystagmus, which suppressed briefly following the termination of saccades and blinking, which are typical features of acquired pendular nystagmus (APN) due to MS. Video:  Video 5.26. Key questions to ask:  Usually, patients with acquired pendular nystagmus (APN) due to MS have a known history of MS for years—that is, APN is not a common presenting sign of MS. Because acute/subacute APN can (rarely) result from a posterior fossa stroke, infection (Whipple’s disease, usually with a convergent-divergent component—oculomasticatory myorhythmia—often with prominent GI symptoms), toxicities (toluene), and chronic APN can be due to spinocerebellar ataxia or metabolic disorders (see below), a focused history is essential in the absence of known MS or a known posterior fossa insult (e.g., pontine hemorrhage causing oculopalatal tremor, OPT). Key findings to elicit:  While APN due to MS is usually horizontal, it can also be vertical or have a convergent-divergent appearance. If horizontal and vertical components are present, the appearance can be circular or elliptical (see example—Video 5.27). Typically APN due to MS will be suppressed by blinks and saccades (see example in a patient without MS—Video 5.28). In MS patients with APN, a variety of other ocular motor abnormalities are often seen including gaze-evoked nystagmus, INOs, saccadic smooth pursuit, and saccadic dysmetria. APN is often dissociated/disconjugate (more intense in one eye) and may also be monocular, and when this is the case, it is typically worse or present in the eye with poorer vision (see examples—Video 5.29). The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1.

Nystagmus

221

Pitfalls:  When monocular vertical pendular nystagmus in an eye with poor vision (due to optic nerve disease, but also ophthalmic conditions such as amblyopia, cataracts, severe refractive error, etc.) is seen, consider the Heimann–Bielschowsky phenomenon (HBP), which is benign and of no neurologic consequence. It is also important to recognize, because correcting the ophthalmic disorder (e.g., cataract surgery) may lead to resolution. Recognition of the HBP will also prevent expensive and unnecessary neurologic testing. Patients with vision loss due to other etiologies (e.g., retinitis pigmentosa) may develop binocular conjugate pendular nystagmus, perhaps related to poor calibration of eye position. Do not miss this!  APN due to MS and OPT are most common. Although rare, other reported causes of pendular nystagmus include peroxisomal assembly disorders, toluene abuse, Whipple’s disease, acute brainstem stroke, spinocerebellar ataxia (SCA), hereditary spastic paraplegia (SPG7 mutation), celiac disease, disorders of vitamin E, and coenzyme q10 metabolism. Remember that infantile nystagmus has mixed waveforms including both pendular and jerk nystagmus (Video 5.30). What is next?  If APN is diagnosed in a patient with known MS, aside from obtaining contrast-enhanced MRI to monitor for disease progression, no additional workup is typically needed. If there is diagnostic uncertainty, testing should focus on the aforementioned etiologies. Treatment options:  Like OPT, gabapentin and memantine are the two medications that have the most evidence for their use. Want to know more?  [13–15]

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5.4

5  Oscillopsia, Nystagmus, and Other Abnormal Movements

 accadic Intrusions, Oscillations, S and Other Nystagmoid Movements (Fig. 5.1)

5.4.1 S  quare Wave Jerks (SWJ) and Related Saccadic Intrusions The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. A few pearls • SWJ are the most common form of saccadic intrusion, common with aging, but especially frequent in neurodegenerative disorders. • Oftentimes, SWJ are misinterpreted as nystagmus, although saccades are the culprit (saccades initiate the movements) in intrusions/oscillations, while a slow phase initiates the movement with jerk or pendular nystagmus. • When SWJ are particularly frequent (>15/minute), suspicion should be high for a cerebellar or a parkinsonian syndrome. The history should focus on symptoms that may occur with cerebellar ataxia (e.g., oscillopsia, imbalance, dysarthria, incoordination), Parkinson’s disease (PD, e.g., tremor, slowness, postural instability, stiffness), and progressive supranuclear palsy (PSP, SWJ are more prominent than in PD, see section above and see example of SWJ and other typical features of PSP Video 5.31). A few practical points • With SWJ, macro-SWJ (SWJ that are larger in amplitude up to about 50 degrees), and macrosaccadic oscillations (movements that straddle fixation, usually associated with hypermetric saccades and cerebellar disease), there should be an intersaccadic interval (i.e., there is a short pause between saccades, usually apparent at the bedside, but occasionally eye

Saccadic Intrusions, Oscillations…

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movement recordings are needed—see examples of these saccadic intrusions/oscillations in Video 5.32). If there is no intersaccadic interval, this is due to ocular flutter or opsoclonus (see section below). • Because patients with cerebellar disease can have both intrusions (e.g., SWJ) and nystagmus (e.g., downbeat or periodic alternating nystagmus), eye movement recordings can be helpful as well as performing ophthalmoscopy. When viewing the optic nerve with the magnification of the ophthalmoscope, it can be easier to identify the upward slow and downward fast phases associated with DBN and the simultaneous horizontal back and forth saccadic movements of the SWJ. • SWJ are usually of no visual consequence and do not require medication. Occasionally they can cause oscillopsia, and anecdotally, benzodiazepines and other medications may be beneficial in a subset of patients. • There are a variety of spontaneous abnormal eye movements that can be seen in comatose patients, which can be classified as “saccadic disorders”, although their exact pathogenesis remains uncertain (e.g., ocular bobbing—Video 5.33).

5.4.2 Opsoclonus/Ocular Flutter Case:  A 35-year-old woman presented with oscillopsia several weeks following a flu-like illness. She described being easily startled, with “shakiness” of the head/neck and body. Aside from mild unsteadiness on her feet, she denied any other neurologic symptoms. Examination demonstrated periodic myoclonic jerks involving the trunk, arms, legs, and neck in addition to frequent horizontal back-to-back saccadic oscillations with the appearance of ocular flutter. In fact, with eye movement recordings, there was no intersaccadic interval seen (in between each saccadic movement), which was compatible with a diagnosis of ocular flutter (oscillations were only horizontal). Flutter was most prominent

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5  Oscillopsia, Nystagmus, and Other Abnormal Movements

and frequent with convergence or immediately following termination of saccades in all planes. Workup to evaluate for infectious or paraneoplastic etiologies was unremarkable (including cerebrospinal fluid analysis), she was treated conservatively with gabapentin alone given the fairly mild nature of her symptoms, and her flutter-myoclonus syndrome resolved over the subsequent weeks. She recovered completely from this monophasic disorder, which was thought to be post-infectious in etiology. Video:  Video 5.34. Key questions to ask:  In a young person, ask about preceding infections. In older patients, the biggest concern is a paraneoplastic disorder (associated with a variety of cancers and antibodies) so ask about smoking history and other risk factors. However, a young person can also have a paraneoplastic disorder (e.g., anti-­ NMDA antibody-mediated opsoclonus associated with a teratoma), while an older person can have opsoclonus due to acute or resolving infection (see example of opsoclonus—Video 5.35). Key findings to elicit:  In a baby or young child, flutter/opsoclonus can be the initial manifestation of neuroblastoma (see Chap. 7: Pediatric Clinical Pearls). Episodes of flutter/opsoclonus can be frequent and striking, or intermittent and/or mild in other cases. In addition to provoking these oscillations by convergence and with saccades, the examiner should also observe the corneal bulges under closed eyelids. Myoclonic jerks (probably related to reticular formation involvement) may involve the trunk/neck and head, arms, legs, and truncal, gait and appendicular ataxia may also be seen. The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  Occasionally, a high frequency nystagmus can be mistaken for opsoclonus/flutter. In these situations, distinguishing nystagmus from a saccadic oscillation is essential as the localizations and etiologies vary widely. Eye movement recordings— used first to distinguish nystagmus from an intrusion/oscillation

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225

(which is the culprit - slow phase or saccade?), and second to decide whether the intrusion/oscillation has an inter-saccadic interval or not (opsoclonus/flutter will have no interval)—can be very helpful in this setting. Do not miss this!  There are many dangerous etiologies of opsoclonus/flutter which should be entertained. In the very young, neuroblastoma should be considered first, although occasionally it can be a transient phenomenon in healthy neonates. Ocular micro-flutter (i.e., only seen with the ophthalmoscope) is a rare but benign chronic cause of oscillopsia, and is often associated with migraine. Occasionally, oscillations can be generated volitionally and can mimic pathologic ocular flutter, so-called “voluntary flutter.” This can only be sustained for a short time, and is almost always associated with convergence and other features of activation of the near triad, including miosis (see example— Video 5.36). Reported autoimmune causes of opsoclonus/flutter include multiple sclerosis and neuromyelitis optica; many infections (especially viral) have been implicated in its pathogenesis (during or following the infection); structural lesions include brainstem stroke, hemorrhage, trauma; toxicity (toluene, phenytoin, amitriptyline, diphenhydramine, lithium); neurodegenerative disorders (Friedreich’s ataxia) among many others. What is next?  Neuroblastoma should be excluded in the young (see Chap. 7). If there was a preceding infection, viral (e.g., HIV) and bacterial (e.g., Lyme) etiologies should be considered, and contrast-enhanced brain MRI should be obtained. If there was no preceding infection, paraneoplastic workup should include contrast-enhanced brain MRI, body CT (preferably PET/CT), thorough medical examination, consider mammography and pelvis ultrasound in women and testicular ultrasound in men, paraneoplastic panels in serum and CSF.  Autoimmune/ inflammatory disorders should be considered as well depending on CSF analysis and MRI findings (or lack thereof). Treatment options:  To treat the underlying autoimmune/ immune-mediated or inflammatory etiology, intravenous immunoglobulin, plasma exchange, rituximab, or steroids may be

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5  Oscillopsia, Nystagmus, and Other Abnormal Movements

beneficial and diminish the ocular oscillations. Other medications have been reported to reduce oscillations (and oscillopsia) including clonazepam, gabapentin, propranolol, memantine, among others. Want to know more?  [16–20]

5.4.3 Superior Oblique Myokymia Case:  A 40-year-old man presented with complaints of jumping vision in the right eye, associated with vertical double vision. He experienced many typical episodes in the office, where simultaneous incycloduction and depression could be observed in the right eye, causing oscillopsia and vertical diplopia, respectively. In between attacks, vertical ocular alignment was normal. During attacks, there was a measurable left hypertropia which correlated with his diplopia. He was diagnosed with right superior oblique myokymia (SOM). Routine MRI was normal, and unfortunately high resolution heavily T2-weighted CISS/FIESTA images to evaluate for neurovascular compression could not be performed. Symptoms did not respond to timolol ophthalmic drops OD, but diminished with gabapentin. Video:  Video 5.37. Key questions to ask:  The key with SOM is monocular oscillopsia. The typical causes of spontaneous oscillopsia—nystagmus and saccadic intrusions—are almost always bilateral and conjugate, with some exceptions (e.g., monocular pendular nystagmus in multiple sclerosis—Video 5.38, or the Heimann–Bielschowsky phenomenon with unilateral visual deprivation). Key findings to elicit:  To appreciate the sometimes very subtle incycloduction and/or depression associated with SOM (Video

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227

5.39), the magnification of an ophthalmoscope (focus on a retinal vessel where torsion can be best appreciated), slit lamp or Frenzel goggles may be necessary. To trigger an attack, ask the patient to look in the direction of the action of the superior oblique muscle— for example, in right SOM, symptoms/signs may be triggered by looking left, down, left/down, or by tilting the head to the right. Remember the actions of the SO muscle—the primary action is incycloduction (which initiates the SOM, and is followed by a slow drift back to a normal position—this explains monocular oscillopsia) and the secondary action is depression, which explains the vertical diplopia that is experienced by many during attacks. The approach (history and exam) to the patient with nystagmus or oscillations:  Table 5.1 and ESM 5.1. Pitfalls:  When symptoms are non-specific (e.g., an episodic blurriness), the examiner must have a high suspicion for SOM to understand whether the visual symptom is monocular, whether oscillopsia is present, and if so, in what plane (patients usually notice a torsional/rotary component)? Do not miss this!  Aside from other rare causes of monocular oscillopsia (see above), also consider ocular conditions such as iridodonesis (excessive movement of the iris as in a lens subluxation) or pseudophakodonesis (excessive movement of a lens implant), which can both be appreciated with slit lamp exam and may be monocular. Consider ocular neuromyotonia, where patients experience transient diplopia (usually demyelinating disease (~20% of AVS) or vestibular neuritis (~80% of AVS). 2. Triggers: • Positional—triggered by movement. –– BPPV—lying to seated, seated to lying, rolling over in bed, looking up or down, brought on by head movement. –– Orthostatic hypotension—arising from lying or seated position (should not come on from sitting to lying, which can differentiate from BPPV). • Head movement—occurs during or time-locked to movement. –– Bilateral vestibular loss—most common. –– Unilateral vestibular loss—acute phase prior to compensation, or chronic and uncompensated. • Sound—Tullio’s phenomenon. –– Superior canal dehiscence syndrome—SCDS). • Valsalva—against closed glottis and/or pinched nose. –– SCDS. –– Cervicomedullary junction lesion (Chiari malformation). • Complex visual stimulation—e.g., grocery store, crowded environments. –– Vestibular migraine—also may be triggered by sleep deprivation, skipping meals, certain foods, menstrualrelated, barometric pressure changes. –– Persistent postural perceptual dizziness (PPPD). 3. Targeted Exam: • HINTS “Plus” (Head Impulse, Nystagmus, Test of Skew, “Plus” = bedside assessment of auditory function using finger rub) for AVS. –– Do not forget about associated symptoms common in posterior fossa disease including diplopia, dysarthria, dysphagia, dysphonia, loss of sensation, weakness, room tilt illusion, incoordination, drop attacks, abrupt loss of hearing (remember that the internal auditory artery usually comes off the anterior inferior cerebellar artery).

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233

• Dix-Hallpike (DH) and supine roll test for BPPV. • In more chronic balance/vestibular conditions, particular attention to the general neurologic exam is essential look for evidence of parkinsonism; cerebellar disease (e.g., gazeevoked nystagmus, saccadic smooth pursuit, spontaneous downbeat nystagmus); myelopathy; neuropathy; vestibular exam looking for unilateral or bilateral vestibular loss.

6.1.3 Test (Table 6.1) • A few common examples: –– Audiogram with hearing loss/changes or any aural symptoms (tinnitus, pain, fullness, popping) or when Meniere’s disease is suspected (ESM 6.1). –– Vestibular function testing when unilateral or bilateral vestibular loss is suspected and in other special situations (ESM 6.2, 6.3, 6.4, 6.5, and 6.6). –– MR with diffusion-weighted imaging (DWI) with attention to the brainstem/cerebellum when stroke is suspected in AVS. –– Contrast-enhanced MRI with internal auditory canal protocol to evaluate for vestibular schwannoma and vestibular paroxysmia (neurovascular contact with CN8 - should include heavily T2-weighted CISS or FIESTA images). –– CT temporal bones when SCDS is suspected.

6.2

The Vestibular Examination

The vestibular examination The rotational vestibulo-ocular reflex (VOR) allows for retinal stability during angular movements of the head, both horizontally (horizontal semicircular canals) and vertically (posterior and anterior semicircular canals) (Fig. 4.9). For example: a person with a normal VOR can walk down the street and clearly read a sign in front of them as the VOR constantly adjusts the eye position to keep retinal images stable when the head is in motion. A person with bilateral vestibular loss will walk down the street and the sign will appear to jump or bounce—that is, the retinal images

++a

+c ++ +e −

− +d − ++

+c − − +

+ − ++ + +

+ − − ++ ++

++b − − − −

++b − − − ++

++b ++ ++ + +

− − − − −

−

VN VM Menière’s SCDS BPPV VP BVL PPPD + + ++ ++ + ++ − − ++ − + + ++ − − −

++a

TIA/ stroke + +

− − − ++

+

Cerebellar syndrome − +

+ ++ − ++

++b

Vestibular schwannoma ++ ++

VN vestibular neuritis, VM vestibular migraine, VP vestibular paroxysmia, vHIT video head impulse test, VNG video-nystagmography, ENG electronystagmography, VOG video-oculography, VEMPs vestibular evoked myogenic potentials, SCDS superior canal dehiscence syndrome, BPPV benign paroxysmal positional vertigo, BVL bilateral vestibular loss, PPPD persistent postural perceptual dizziness (no specific test is helpful to make this diagnosis, but patients often develop PPPD as the result of another poorly treated or anxiety-provoking vestibular disorder—e.g., vestibular migraine, BPPV or vestibular neuritis) – Not usually helpful + May be helpful ++ Very helpful a In the acute setting when spontaneous nystagmus is present b During provocative maneuvers (including Valsalva, pinched-nose Valsalva, tragal compression, loud sounds, Dix-Hallpike/supine roll test, hyperventilation)

Test Audiogram vHIT VNG, ENG or VOG Rotary chair Calorics VEMPs Imagingf

Table 6.1  Common audiovestibular lab tests

234 6  Vestibular Disorders

Rotary chair may show slightly low time constants and gains with unilateral vestibular loss, and may show prolonged time constants in migraine d Depending on the posterior fossa localization, there may be caloric weakness with some strokes e VEMPs may assist in the localization of inferior versus superior division vestibular neuritis f Neuroimaging is needed (MRI internal auditory canal [IAC]) protocol w/wo) in migraine and Menière’s cases where there is diagnostic uncertainty or atypical features. In SCDS, CT temporal bones is the test of choice. For vestibular paroxysmia, heavily T2-weighted CISS or FIESTA imaging. In BVL, if the cause is clearly ototoxicity from gentamicin for instance, neuroimaging will not be helpful. Otherwise, neuroimaging is essential

c

The Vestibular Examination 235

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6  Vestibular Disorders

are unstable due to an impaired VOR, so the stationary image will appear to be moving (so-called “walking” oscillopsia Video 5.5). The following are ways to evaluate VOR function at the bedside. • Dynamic visual acuity (Video 6.1): Passive rotation of head (horizontally to evaluate the horizontal SCC and vertically to evaluate the anterior and posterior SCC function) at 2 Hz while viewing a distance (preferred) or near eye chart. A decrease in best-corrected vision of two lines or more from baseline is considered abnormal—patients with unilateral vestibular may lose two to three lines prior to compensation, while patients with bilateral vestibular loss will lose four or more lines. • Visually enhanced VOR (vVOR): Passive rotation through the entire horizontal or vertical ocular motor range at 0.5 Hz while fixating on the examiner’s nose. This combines smooth pursuit and VOR. If pursuit is impaired and the VOR is hypoactive (e.g., cerebellopathy and bilateral vestibular loss due to cerebellar ataxia, neuropathy, vestibular areflexia syndrome, CANVAS), the vVOR will be impaired and will look choppy or saccadic (Video 5.12). If either system is functional, this will be smooth. • Head impulse test (HIT, Video 6.2): When vVOR is assessed in a patient with unilateral vestibular loss, the good ear can drive the response; however, when a rapid HIT is applied, the good ear can no longer compensate and the VOR deficit will be apparent at the bedside. With the patient fixating on the examiner’s nose, perform a brief, rapid head rotation of 15–20° (the novice should start by performing the HIT from right to center or from left to center - this will ensure that the head movement doesn’t go too far). In a “normal” HIT, the eyes will stay on the visual target (usually the examiner’s nose) with each impulse. In the case of an acute right peripheral vestibulopathy due to vestibular neuritis, a rightward HIT will result in the eyes moving to the right with the head initially, so that a corrective re-fixation saccade will be needed to move the eyes back to the target, or to the left. When this corrective saccade is seen, the HIT is “abnormal” or “positive” which usually suggests a peripheral process (see

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example of a patient with Ramsay Hunt syndrome causing severe unilateral vestibular loss causing abnormal HIT in the planes of horizontal, anterior and posterior canals—Video 6.3). The HIT will be bilaterally abnormal with bilateral vestibular loss (see example—Video 6.4) [3]. The video HIT (vHIT, see ESM 6.2) is a rapid, noninvasive test that can quantify the gain of the VOR in addition to demonstrating both overt corrective saccades (those that are visible to the examiner at the bedside that occur after the head movements) and covert corrective saccades (those that are invisible to the examiner at the bedside that occur with head movements). These can be particularly helpful weeks, months, or years after a vestibular injury (e.g., vestibular neuritis), since effective covert saccades can make the bedside HIT appear normal. Being less predictable by varying the velocity and amplitude of the bedside HIT can help to unmask these covert saccades to assist in the diagnosis of peripheral vestibular loss [4, 5]. • Vibration (Video 6.5): Vibration of the mastoids and vertex will induce an ipsilesional slow phase with unilateral vestibular loss, more so acutely than chronically. With peripheral lesions, the slow phase is toward the affected ear as seen in this patient with vestibular neuritis—Video 6.6 [6]. • Head-shaking (Video 6.5): Sustained, rapid, back and forth, horizontal head shaking for ~15 secs may produce a spontaneous nystagmus that slowly abates. With peripheral lesions, the slow phase is toward the affected ear as in this patient with Ramsay Hunt syndrome— Video 6.7. With central lesions, the slow phase may be vertical or the nystagmus may change direction from the baseline spontaneous nystagmus. If there is strong HSN without clear unilateral vestibular loss (Video 6.8) or a cross-coupled response (e.g., horizontal head-shaking causes downbeat nystagmus—Video 6.9), consider a central process [7, 8]. • Pressure-induced (Video 6.10): Evaluate for nystagmus during Valsalva against a closed glottis, pinched-nose Valsalva, and with tragal compression (pressure in the external auditory canal causing nystagmus,

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6  Vestibular Disorders

Hennebert’s sign), which may be seen in SCDS (Video 6.11); look for Valsalva-induced symptoms and signs with cervicomedullary lesions such as a Chiari; sound-induced nystagmus (Tullio’s phenomenon) mainly in SCDS. • Hyperventilation (Video 6.12): Alkalosis and changes in ionized calcium from 30–60 seconds of hyperventilation may improve conduction through an affected segment of eighth cranial nerve due to vestibular schwannoma (Video 6.13) or neurovascular compression, usually causing excitatory nystagmus with a contralesionaldirected slow phase. When a chronic vestibular imbalance has been compensated for by central mechanisms, hyperventilation can cause a transient decompensation and bring out nystagmus with an ipsilesional slow phase. Hyperventilation can enhance/produce downbeat nystagmus in cerebellar disease (perhaps related to a sensitivity of cerebellar calcium channels, Video 6.14) [9]. • Positional maneuvers: –– Dix-Hallpike maneuver; Used to test for posterior canal (PC) BPPV. For example: in a patient with right PC BPPV, turn the head 45° to the right, and rapidly move en bloc straight back so that the head is slightly hyperextended (~20°) and hanging over the edge of the examination table with the head still turned 45° to the right. This maximally stimulates the right PC SCC. In right PC-BPPV, the right Dix-Hallpike will provoke upbeat-torsional nystagmus towards the right (lowermost) ear, which is due to otoconial debris falling through the right posterior canal (causing endolymph movement and cupular deflection in an excitatory direction). The nystagmus (a) typically begins with a short latency (sometimes as long as 30-60 seconds) after change in head position, (b) lasts less than 1 min, (c) fatigues with repeated testing, and (d) often reverses direction (downbeat-torsional towards the left ear with right PCBPPV) when the patient sits up again. –– Supine roll test: Used to test for horizontal canal (HC) BPPV.  For example: in a patient with right geotropic HC BPPV, have the patient lay down with the head flexed 20–30° (to bring the HC into a position perpendicular to the

Bedside Auditory Testing

239

ground) and then turn the head (or body and head en bloc if the cervical range of motion is poor) 90° to the right. This will induce a geotropic (i.e., beating toward the ground) right-beating nystagmus along with prominent vertigo. Similar to PC BPPV, a latency and crescendo-decrescendo appearance will be observed. Then come back to neutral and roll the head 90° to the left. This will induce a geotropic left-beating nystagmus, although the nystagmus and vertigo in this position will be less robust as compared to the right supine roll position (the opposite will be true for apogeotropic HC BPPV—see BPPV section below) [10]. • The virtual (telemedicine) vestibular examination (Video 6.15).

6.3

Bedside Auditory Testing

• Finger rub: It has been shown that bedside hearing tests including finger rub, whispered speech, watch tick, and the Rinne and Weber tuning fork tests have poor sensitivity to detect hearing loss in older adults, although their specificity is good. A combination of bedside tests including Rinne, Weber, and finger rub (especially the calibrated finger rub auditory screening test or CALFRAST), will achieve the highest sensitivity, although this is still below acceptable levels and not a substitute for audiometry. To perform the CALFRAST test, the patient should close the eyes and the examiner will stand nose to nose, 6–10 inches in front of the patient. The examiner will extend both arms straight outward so that the examiner’s fingers are equidistant from the examiner’s and subject’s ears, at a distance of approximately 70  cm. First the “CALFRAST-Strong 70” is performed, where the examiner rubs the thumb and distal fingers together vigorously (but without snapping), one ear at a time (repeated 3 times in its initial description). If the patient hears the rubbing, next is the “CALFRAST–Faint 70,” where hearing is assessed using the faintest rub/sounds the examiner can still hear (at 70 cm). If the patient hears “Faint 70” in both ears, testing is complete. If “Strong 70” was not heard then the same strong stimulus is repeated at 35 cm, then 10 cm, then 2 cm— that is, until the stimulus is heard [11, 12].

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• Rinne and Weber (Video 6.16): The Rinne test is an assessment of auditory thresholds to air and bone conduction of sound. The Weber test is a comparison of bone conducted sound of either ear. Conductive hearing loss results in a loss of air conducted greater than bone conducted sound, whereas sensorineural hearing loss results in the loss of both air and bone conducted sound. Peripheral vestibular disease affecting the labyrinth or the eighth cranial nerve can be associated with sensorineural hearing loss. In these cases, the sensitivity to air conduction will remain greater than to bone conduction. Weber will lateralize away from the side of sensorineural hearing loss. As an example, destruction of the right labyrinth (e.g., bacterial labyrinthitis) will cause decreased hearing in the right ear, and air conduction will be greater than bone conduction in the right (affected) and left (unaffected) ears. Weber will lateralize to the left (unaffected) ear. In the case of superior semicircular canal dehiscence (SCDS), there may be increased sensitivity to bony transmission of sound through a (third mobile window) as well as conductive hearing loss, with bone conduction greater than air conduction and Weber lateralizing to the side of the dehiscence. • Otoscopy: Evaluate for (herpetic) vesicles, abnormalities of or behind the eardrum to suggest infection, glomus tumor, or carotid aneurysm.

6.4

 aboratory Testing of Audiovestibular L Disorders (Fig. 6.1, Table 6.1, ESM 6.1, 6.3, 6.4, 6.5, and 6.6)

6.5

Vestibular Syndromes

6.5.1 Acute Vestibular Syndrome (ESM 6.7) 6.5.1.1  The HINTS History The acute vestibular syndrome (AVS) is characterized by the acute onset of continuous vestibular symptoms (usually a sensation of environmental motion/movement or vertigo which persists

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a

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Fig. 6.1  Audiometry: what does it look like and how do I interpret it? An audiogram measures a patient’s auditory threshold responses with pure-tone stimuli across a range of sound frequencies that are important for human communication, typically  250 Hz – 8000  Hz. The threshold is the sound intensity level at which an individual detects the tone 50% of the time. Hearing loss severity is referenced to a healthy population (a). An audiologist generally assesses both air-conducted (circles) and bone-conducted sound (brackets). Both results are graphed with frequency on the x-axis, measured in Hertz (Hz), and the threshold for sound intensity on the y-axis, measured in decibels hearing level (dB HL). (b) Sensorineural hearing loss can be differentiated from (c) conductive hearing loss by the presence of an air-bone gap in which a difference exists between air-conduction and bone-conduction thresholds. Some patients with both conductive and sensorineural components of hearing loss in the same ear are said to have mixed hearing loss (d). In patients with age-related hearing loss (b), an audiogram typically displays symmetric hearing loss primarily at higher frequencies between 2000 and 8000  Hz. Only right ear data are graphed for simplicity. (Courtesy of Drs. Carrie Nieman and Bryan Ward) [17]

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with head still and eyes closed), head motion intolerance (symptoms are aggravated when moving the head), nausea/vomiting, imbalance and spontaneous nystagmus (often causing oscillopsia in addition to vertigo, although the oscillopsia [a visual symptom] will resolve with eyes closed). About 80% of the time, the AVS is due to vestibular neuritis, and about 15–20% of the time, it is due to a central lesion (usually posterior fossa stroke).

6.5.1.2  The HINTS Exam A three-step bedside ocular motor exam known as HINTS has a higher sensitivity (96.8%) and specificity (98.5%) to detect a central cause of the AVS as compared to MR with diffusion weighted-­ imaging (which may miss up to 20% of small posterior fossa strokes causing isolated vertigo in the first 24–48 hours) in the hands of subspecialists [13–16]. When evaluating a patient in the ED, sometimes it can be challenging to determine whether a patient’s continuous dizziness or vertigo is “vestibular” in origin (as opposed to a cardiac or pharmacologic etiology). If associated symptoms include internal or external vertigo, nausea, head motion intolerance and imbalance, it is likely that a “vestibular” etiology is to blame. However, when present, these features do not help differentiate a “central” vestibular from a “peripheral” vestibular etiology. 6.5.1.3  Vestibular Neuritis Case:  A 50-year-old woman with hypertension, dyslipidemia and pre-diabetes suddenly developed continuous vertigo that gradually worsened over 60  minutes and she presented to the emergency department (ED) within hours of onset. Associated symptoms included nausea and vomiting, head motion intolerance and unsteadiness. There was no diplopia, dysarthria, weakness or sensory symptoms. Examination demonstrated horizontal-torsional left-beating nystagmus (LBN) in primary position and the nystagmus remained left beating-torsional when she looked laterally or vertically. When looking to the right, the LBN decreased and when looking to the left, the LBN increased in intensity, in keeping with Alexander’s law. With alternate cover testing, there was no vertical ocular misalignment suggestive of skew deviation. With head impulse test (HIT) to the right, there was a corrective refixation saccade (a positive or abnormal HIT) and no corrective saccade when her head was turned

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243

quickly to the left. There were no focal findings on neurologic exam, although she required some assistance to ambulate. Saccades and smooth pursuit appeared to be normal when taking the spontaneous nystagmus into account. There was no hearing loss or other aural symptoms, and otoscopy was n­ ormal. She was diagnosed with rightsided vestibular neuritis based on a peripheral pattern of the HINTS “Plus” (Head Impulse [abnormal—to the right], Nystagmus [unidirectional—LBN], Test of Skew [no vertical refixation saccade], Plus [no hearing loss]) exam, and was discharged from the ED with a short course of steroids. At follow-up several days later, there was significant subjective (vertigo) and objective (nystagmus and balance) improvement (Figs. 6.2, 6.3 and 6.4). Video of patient’s exam in the ED:  Video 6.17. Key questions to ask:  Is the vertigo or dizziness of sudden onset, continuous (even with eyes closed and head still) and associated with spontaneous nystagmus, nausea/vomiting, head motion intolerance, imbalance? If so, this is the acute vestibular syndrome (AVS) and main concerns include stroke (dangerous) or vestibular neuritis (benign).

Hearing Loss

Gradual Onset Months to Years

Sudden Onset Hours to Days

Symmetric

Asymmetric

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Otosclerosis

Cholesteatoma

Ossicular Chain Discontinuity

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+ vertigo

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Brainstem Stroke

Meniere’s Disease Temporal bone fracture

Cerumen impaction

Generally symmetric but can be asymmetric

Labyrinthine concussion

Acute otitis externa Pathologies in Neurology Practice

Less Concerning Pathologies Acute otitis media

Post-concussion syndrome

Otitis media with effusion

Meningitis

Fig. 6.2  What is the cause of my patient’s hearing loss? This is a flowsheet that can be used to differentiate multiple causes of hearing loss. The onset and chronicity of hearing loss is a critical starting point in understanding whether urgent action is needed, such as in the setting of suspected stroke or sudden sensorineural hearing loss. For hearing loss that has been present for months to years, differentiating whether the loss is primarily symmetric or asymmetric is another point that should prompt consideration of referral and further evaluation. Regardless of the underlying cause of hearing loss, including agerelated hearing loss, assessment and interventions can and should be offered. (Courtesy of Drs. Carrie Nieman and Bryan Ward) [17]

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Anterior Inferior Cerebellar A.

Basilar A.

AC Internal Auditory A. Anterior Vestibular A.

U C

HC S PC

Posterior Vestibular A.

Main Cochlear A.

Fig. 6.3  Vascular supply of the labyrinth: In the HINTS “Plus” examination (Head Impulse, Nystagmus, Test of Skew, “Plus” is a bedside test of auditory function using finger rub), loss of hearing is seen as a red flag or dangerous finding in the acute vestibular syndrome. As seen above, the basilar artery supplies the anterior inferior cerebellar artery, which supplies the internal auditory artery so that an acute vestibulopathy accompanied by partial or complete sensorineural hearing loss can be not only “peripheral” but also dangerous (e.g., due to labyrinthine stroke)

Key findings to elicit:  In a patient with the AVS, the HINTS Plus exam should be applied to distinguish if the vertigo is central or peripheral (to remember this, think of it as the AVS-HINTS exam—that is, it should not be applied in patients without spontaneous nystagmus and ongoing vestibular symptoms). Videooculography and video HIT, when performed acutely in the emergency department, can augment the evaluation by quantifying the nystagmus and vestibulo-ocular reflex function (see example— Video 5.20). When possible, also look for central patterns of headshaking nystagmus, and evaluate saccades (e.g., saccadic dysmetria in lateral medullary stroke) and smooth pursuit (e.g., impaired

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Fig. 6.4  Innervation of the labyrinth: When a patient experiences a bout of vestibular neuritis, typically the superior division or the superior and inferior divisions are involved and rarely is the inferior division involved in isolation. Knowledge of the specific innervation patterns of the semicircular canals and otoliths allows for accurate localization and insight into etiology. The superior division innervates the anterior and horizontal canals, utricle, as well as some innervation to the saccule. The inferior division innervates the posterior canal and provides most of the saccular innervation. Cervical vestibular evoked myogenic potentials (c-VEMPs) can help to elucidate inferior division involvement with damage to the saccule, while ocular-VEMPs can help to elucidate superior division involvement with damage to the utricle. As another example, if the horizontal (HC) and anterior canals (AC) are the only canals affected in a patient with the acute vestibular syndrome, the localization is usually vestibular neuritis with involvement of the superior division of the vestibular nerve. However, if the HC and posterior canals (PC) are the only canals affected, since these canals only synapse in the medial vestibular nucleus (MVN, whereas the AC sends afferents to both MVN and superior vestibular nucleus), the possibility of a brainstem disorder should be considered (e.g., ischemia of the vestibular nucleus). While a HIT performed in the plane of the HC can easily be interpreted at the bedside, assessment in the planes of the AC and PC is technically challenging. Therefore, the function of the AC and PC is best evaluated by the video head impulse test; U, utricle; S, saccule; C, cochlea

with paraflocculus or middle cerebellar peduncle stroke, see example—Video 4.10). The approach to the patient with acute onset prolonged vertigo or dizziness:  Table 6.2.

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Table 6.2  Help me now with acute onset prolonged dizziness & vertigo: What to examine and urgent diagnostic considerations Bedside exam

Head Impulse test (HIT)a

AVS from vestibular neuritis (VN) with spontaneous nystagmus Abnormal Presence of a catch-up saccade—e.g., with right vestibular neuritis, if the patient’s head is quickly turned to the right, the eyes will move with the head to the right which takes the eyes off the target (usually the examiner’s nose)—this is followed by a corrective (overt) saccade to the left to bring the eyes back to the visual target

AVS from stroke with spontaneous nystagmus

Other continuous dizziness or vertigo without spontaneous nystagmusd

Normal Absence of a catch-up saccade—e.g., in a patient with a unilateral cerebellar stroke, if the patient’s head is quickly turned to the right, the eyes will move to the left keeping them on the visual target (examiner’s nose) because the vestibulo-­ ocular reflex is intact; however, the HIT is occasionally abnormal depending on localization (e.g., labyrinthine ischemia, vestibular nucleus)

Acute unilateral vestibular loss due to VN will cause spontaneous nystagmus! If no spontaneous nystagmus is present despite acute, ongoing symptoms, VN is unlikely. Simultaneous (symmetric) bilateral vestibular loss is very rare (e.g., Wernicke’s, ototoxicity due to gentamicin or bilateral labyrinthine strokes). Instead, the history must be relied upon—e.g., vestibular migraine, effects of medication (e.g., anti-seizure, tricyclic antidepressant, benzodiazepines) or other toxicity, medical conditions (abnormalities in blood pressure, glucose levels) (continued)

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Table 6.2 (continued) Nystagmusa Unidirectional horizontal-­ torsional nystagmus Increasing in the direction of the fast phase in accordance with Alexander’s law—e.g., with right VN, there will be left-­beating nystagmus (acutely, a torsional component will be apparent as well, with top poles of the eyes beating toward the left ear) which will decrease (but still be present) in right gaze, increase in left gaze, and remain left-beating in vertical gaze

Direction-­ changing/ gaze-evoked or spontaneous vertical nystagmus E.g., Right-­ beating in right gaze and left-beating in left gaze or vertical gaze-evoked as well; upbeat nystagmus may be unidirectional (increasing in upgaze, following Alexander’s law)

Test of Skewa

Abnormal A vertical refixation with alternate cover test (make sure the patient can see the visual target with both eyes) should be assumed to represent a skew deviation until proven otherwise in the AVS, but is commonly absent with a central etiology.

Normal No vertical refixation movement—note that many normal people have small horizontal phorias (eso- or exophoria), but this is not a skew (which is by definition a vertical ocular misalignment).

Gaze-evoked nystagmus is common with medication toxicity, typically without spontaneous nystagmus. Mild spontaneous nystagmus (usually increased with removal of fixation) can be seen with vestibular migraine, sometimes horizontal, sometimes vertical. Ictal positional nystagmus is also common in VM. A patient with an anterior circulation stroke (especially in temporo-parietal regions of the “vestibular cortex”) may also experience vertigo, oftentimes without spontaneous nystagmus [18]. Expect a normal test of skew unless there is an unrelated strabismus (e.g., congenital fourth NP).

(continued)

6  Vestibular Disorders

248 Table 6.2 (continued) Bedside exam

Auditory functionb

Head-­ shaking nystagmus (HSN)c

AVS from vestibular neuritis (VN) with spontaneous nystagmus Normal Spared in vestibular neuritis; abnormal in labyrinthitis, although otoscopy should also be abnormal

AVS from stroke with spontaneous nystagmus

Abnormal If otoscopy is normal (no vesicles or signs of infection) and the patient has acute unilateral or bilateral hearing loss, consider labyrinthine ischemia (due to redundancy and decussating fibers of the brainstem auditory pathways, hearing loss due to a unilateral [pure] brainstem lesion is rare) Ipsilesional or Contralesional vertical Following E.g., with a right 15 seconds of 2–3 Hz horizontal vestibular nucleus spontaneous head-shaking— left-­beating e.g., with right vestibular neuritis, nystagmus may reverse direction spontaneous to right-beating left-beating HSN; e.g., nystagmus will horizontal intensify with head-shaking in a horizontal patient with head-shaking unilateral flocculus or nodulus stroke may provoke downbeat HSN

Other continuous dizziness or vertigo without spontaneous nystagmusd An isolated cochlear stroke sparing the vestibular apparatus (i.e., no vertigo and no spontaneous nystagmus) would be rare. With symmetric bilateral labyrinthine strokes, there may be minimal or no nystagmus with profound bilateral vestibular and auditory loss.

When dealing with a non-vestibular cause of continuous symptoms, there should be no head motion intolerance or HSN. If there is no unilateral vestibular loss, but strong HSN or with horizontal HS, there’s vertical nystagmus, consider the etiology to be central (e.g., vestibulo-­cerebellar stroke, vestibular migraine) (continued)

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Table 6.2 (continued) Other

Peripheral vestibular nystagmus should suppress with fixation and will intensify with removal of fixation (e.g., penlight cover test, occlusive funduscopy)

Spontaneous nystagmus usually will not suppress with visual fixation, but it can. Look for saccadic hypermetria in one direction and hypometria in the other and ocular lateropulsion (lateral medullary stroke). If smooth pursuit is very saccadic, consider paraflocculus or middle cerebellar peduncle localization

Posterior fossa strokes may present with normal eye movements. In these situations, a thorough general neurologic and gait examination is particularly important. Truncal, gait and/or appendicular ataxia are common in these patients. Also consider thalamic astasia on the differential of acute/ subacute onset of significant imbalance in the absence of clear sensory, motor or cerebellar abnormalities. A “pusher syndrome” can manifest from a unilateral stroke, where a patient will use the non-paretic limbs to “push” toward the paretic side, which often contributes to imbalance and falls. (continued)

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Table 6.2 (continued) Makes up the HINTS exam, which stands for Head Impulse, Nystagmus, Test of Skew. If any of the features of the HINTS exam are in a central pattern, the etiology must be assumed to be central until proven otherwise. Remember that the HINTS exam should only be applied in the acute vestibular syndrome (e.g., spontaneous nystagmus, continuous vestibular symptoms, imbalance, head motion intolerance, nausea, and vomiting) b Along with HINTS, the addition of evaluating auditory function with finger rub makes up the HINTS “Plus” exam c Central/dangerous etiologies may mimic vestibular neuritis, especially with vestibular nucleus or labyrinthine ischemia. Because the anterior inferior cerebellar artery supplies the labyrinth and flocculus, floccular ischemia can result in central HSN (e.g., downbeat nystagmus). Ischemia involving the vestibular nucleus may cause contralesional spontaneous nystagmus that reverses direction (becomes ipsilesional) with head-shaking d The distinction between vestibular and non-vestibular dizziness can at times be a challenge. If the patient has internal or external vertigo, nausea and/or vomiting, imbalance, and head motion intolerance, the etiology is likely to be vestibular (peripheral or central) a

Pitfalls:  The Dix-Hallpike maneuver will aggravate symptoms and spontaneous nystagmus in a patient with the AVS, and as such, may lead to a misdiagnosis of benign paroxysmal positional vertigo (BPPV). Patients with spontaneous nystagmus do not have BPPV, with rare exceptions (e.g., pseudonystagmus in horizontal canal BPPV—see BPPV section). To diagnose vestibular neuritis, ALL 3 features of the HINTS exam must suggest a peripheral pattern (abnormal HIT when the head is turned in the direction of the slow phase of the nystagmus; spontaneous unidirectional horizontal-torsional nystagmus; absence of a vertical ocular misalignment). In vestibular neuritis, there should be no hearing loss although there is hearing loss (by definition) with labyrinthitis. However, otoscopy is often abnormal with the latter condition. Therefore, assume stroke until proven otherwise in a patient with vascular risk factors presenting with the AVS and acute hearing loss with normal otoscopy. Do not miss this!  Stroke (involving brainstem, cerebellum, or labyrinth [hearing loss will almost always be present]); Wernicke’s encephalopathy; demyelinating disease; Ramsay Hunt syndrome (must perform otoscopy, seventh NP is often present as well).

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What is next?  The diagnosis of vestibular neuritis can be confirmed with a very high degree of confidence when the HINTS Plus exam conforms to a peripheral/benign pattern. In such cases, no neuroimaging is necessary unless there are atypical features (e.g., patient is immunosuppressed). Audiogram should be obtained in all patients, especially in those with hearing loss or aural symptoms (ESM 6.1). VNG, ENG or VOG can be helpful in quantifying and recording spontaneous or provoked nystagmus (ESM 6.3). Caloric testing can demonstrate horizontal semicircular canal paresis (ESM 6.5) while vHIT can demonstrate horizontal and vertical semicircular paresis (ESM 6.2). Vestibular evoked myogenic potentials (VEMPs) can assist in the localization by identifying superior division involvement (i.e., abnormal ocular VEMPs from utricle involvement) and/ or inferior division involvement (i.e., abnormal cervical VEMPs from saccule involvement) (ESM 6.6). Treatment options:  For VN, antiemetics and a vestibular suppressant can help with symptomatic relief, but should not be used for more than 3 days from symptom onset as doing so delays normal compensation. Vestibular physical therapy has been shown to expedite recovery, as well as a short course of corticosteroids in some patients. Similar to optic neuritis, steroids may hasten recovery, but have not been shown to impact the ultimate clinical outcome, which in almost all cases is favorable with complete symptomatic recovery over weeks to months. Advanced:  HINTS caveats: (1) head impulse test—this can be abnormal in certain stroke syndromes (or other central etiologies) ipsilaterally due to lesions of the vestibular nucleus, pontine fascicle/ root entry zone of the eighth CN (Video 6.18), labyrinth, or abnormal contralaterally with lesions of the cerebellar flocculus or medullary nucleus prepositus hypoglossi; (2) nystagmus—“central” vestibular nystagmus (e.g., ischemia of the vestibular nucleus) may also be unidirectional and follow Alexander’s law, and may suppress with visual fixation; (3) test of skew—because the superior division of the vestibular nerve carries the utricle afferents, a small skew deviation may be detected with a Maddox rod (not with alternate cover/coveruncover tests) and other features of the ocular tilt reaction can be detected in some (subtle head tilt and ocular counterroll [e.g., appre-

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ciated with fundus photos], associated tilt in the subjective visual vertical [same direction as the head tilt])—however, a skew deviation apparent with “test of skew” that causes vertical diplopia is rare and should be considered central until proven otherwise (a case of a “peripheral” skew deviation in vestibular neuritis: Video 6.19) [19, 20]. A “central” skew deviation is much more common and tends to be larger in amplitude (Video 6.20). If you can only remember two things…  (1) the HINTS exam can ONLY be applied when spontaneous nystagmus is present (think of it as the AVS-HINTS exam - concept from Dr. Stephen Reich). (2) If ANY of the ocular motor findings appear central, you must assume a central etiology until proven otherwise! For example: If a patient with the AVS has an (1) abnormal unilateral HIT, (2) negative test of skew, and (3) gaze-evoked nystagmus (e.g.,— Video 6.21), since (3) is in a “central” pattern, assume that the etiology is central until proven otherwise! This is also why HINTS is a 3-step test and not a 1-step test! Want to know more?  [21]

6.5.2 Episodic Vestibular Syndrome The approach (history and exam) to the patient with episodic vertigo or dizziness:  Table 6.3

6.5.2.1  Triggered, Episodic Vestibular Syndrome Positional Vertigo and Nystagmus The approach (history and exam) to the patient with positional nystagmus, dizziness or vertigo:  Table 6.4 Posterior Canal BPPV

A 65-year-old woman with history of hypertension woke up and rolled over in bed to the right. Several seconds after changing position, she experienced an intense sensation of the room spin-

Vestibular migraine

Vestibular paroxysmia

Benign paroxysmal positional vertigo Superior canal dehiscence syndrome

Can be triggered (head position, hyperventilation) or unprovoked Can be triggered (typical migraine triggers) or unprovoked

Vertigo and nystagmus with sound/pressure; autophony (hearing internal noises that should not normally be perceived) Vertigo and nystagmus, ipsilateral (usually ictal) aural symptoms

Bedside: Valsalva and pinched-­ nose Valsalva, loud sound Lab: Audiogram—supranormal bone conduction with air-bone gap; lowered VEMP threshold Bedside: hyperventilation Seconds (also Imaging: CISS or FIESTA consider cardiac imaging for neurovascular arrhythmia) compression of CN8 Minutes-hours, can Vertigo, dizziness, imbalance, Bedside: no characteristic findings Lab: no characteristic findings be seconds or days motion sickness +/− ictal Be concerned by sudden onset, nystagmus, +/− headache, sustained or severe head/neck pain photophobia, phonophobia, (think dissection) visual aura (continued)

Seconds to minutes, occasional disequilibrium in between

Test Bedside: Dix-Hallpike (PC) Supine roll test (HC)

Yes—pressure or sound (Tulio phenomenon)

Symptomsa/signs Vertigo and nystagmus

Timing 60 years old), blood pressure (1 if SBP > 140 or DBP > 90), clinical features (2 if unilateral weakness, 1 if speech disturbance), diabetes (1 if present), duration (0 if 60 minutes)—if the score is 4 or more, high suspicion for transient ischemic attack (TIA). Even if the score is