Integrated Neuroscience: a Clinical Problem Solving Approach 9781461353836, 9781461510772, 1461353831, 1461510775

Citation preview

INTEGRATED NEUROSCIENCE A Clinical Problem Solving Approach

INTEGRATED NEUROSCIENCE A Clinical Problem Solving Approach by

Elliott M. Marcus, M.D. Professor Emeritus of Neurology, University of Massachusetts School of Medicine; Lecturer in Neurology, Tufts University School of Medicine; Chairman Emeritus, Dept. of Neurology, St. Vincent Hospital and Fallon Clinic and

Stanley Jacobson, Ph.D. Professor of Anatomy & Cellular Biology Tufts University Health Science Campus, Boston, M A

With Contributions by Brian Curtis, Ph.D. University of Illinois School of Medicine at Peoria Illustrations by Mary Gauthier Delaplane Boston University School of Medicine

SPRINGER SCIENCE+BUSDSfESS MEDIA, L L C

Library of Congress Cataloging-in-Publication Data Marcus, Elliott M , 1932Integrated neuroscience : a clinical problem solving approach / by Elliott M . Marcus and Stanley Jacobson ; with contributions by Brian Curtis ; illustrations by Mary Gauthier Delaplane. p.; cm. Includes bibliographical references and index. Additional material to this book can be downloaded from http://extras.springer.com ISBN 978-1-4613-5383-6 I S B N 978-1-4615-1077-2 (eBook) D O I 10.1007/978-1-4615-1077-2 1. Neurosciences. 2. Nervous system—Diseases. I. Jacobson, Stanley, 1937-11. Title. [DNLM: 1. Nervous System Diseases—diagnosis. 2. Nervous System Diseases—therapy. 3. Nervous System—anatomy & histology. 4. Nervous System Physiology. W L 140 M322i 2002] RC341 .M29 2002 612.8—N

'I.e ErE OPENING

c-o

ErE CLOSURE

l8C

L

t~WNI(~""''''lh~.,\wtW,~f~W'-~JNW/

R

~~II\W~~~W~~"""!{:fi·""'rNN"""~l;~ifti..~

L

fr-,WI""I~""\~~~U,~~

R

~""\~~~M'MW.

T-O

I ~"V

lue.

Figure 2-18. A) The International Fetkrlltion Ten-Twenty Ele&trode Pltuement System. Frontal superior lind posterior views; lind II single plllne projection of the hetld tIemonstrR.ting the standllrd positions lind the rolllndic lind sylvian fissures. The mom ten-twenty is blUed on the pltuement ofelectrodes lit ptlrticulllr percentages of the distanu between nIIsion lind inion. From JIUj1er, RH.: Electroeneepb. Clin. NeuroPlrPsiol.10: 374, 1958 (Elsnier). B) The not"mlll tldult e/earoencepbtdogmm. The ptltient is IIWllke but in II resting state, recumbent with eyes closed. F =fronta~ T =tempor~ C =centrlllllnd 0 .. occipital. (Bipolllr recordings) These abbrePilltions will be utilized in subseiJ.uent ill14Strlltlons. C) EjfraJ of Eye Opening lind Closure. Opening is lISSOCillteil with II blocking or suppression of the alpbll rhythm of 10 cps lind with the IIppellrllnu of II low voltage fost-lUtivity of20 cps (beta rhythm). With eye closure, there is II return of the alpbll rhythm. severe anoxic encephalopathy or the vegetative state. This total suppression of activity accompanied by an absence of brain stem reflex activity and an absence of spontaneous respiration occurs in brain death. Similar findings of total suppression of activity both electrical and reflex may also occur under condition of deep anesthesia. b. Specialized Techniques Employing Electroencephalography: 1. Sphenoidal electrodes - these are small needle electrodes placed in the sphenoidal sinus area to record from the medial aspects of the temporal lobe. 2. Video EEG monitoring: The recording of EEG and behavior onto single videotape allows correlation of electrical activity and of clinical seizure activity. This is usually a prerequisite study prior to epilepsy surgery and is also uti-

ANT. t - MID. "[

R_

Moo. t-l'OStt

PAR. - OCC.

Figure 2-22. Foc1I12-3 Hz slow wllve IUtivity in the e/ectroeneepblllogrllm: /eft tempomlilrell indiclJting foclll tiamllge in this llrell. Brllin abscess, /eft temporal lobe in II 14-yellr-oltl fomaIe secondary to lin acute S lIureus mastoiditis extending into the petrous ridge. Electroeneepblllogrilm. Bipolllr recording. (LAT. F. IIIteral frontal; ANT- T- .. IInterior temporal; MID. T. .. mid- temporll~ POST. T- =posterior temporll~ PAR. .. Pllrieta~ occ. .. occipital). (Listed in text lind CD ROM as Figure 27-22).

2-24

CHAPTER 2

L~"fIr~

F -

C

C -

0

.~_,,~

POS"t f - PAR.

L

",\"'/.I~'frfrt¥'AJt~~~~4r(

.~~ PAR. -OCC.

50"N1~~

_______________________

, 68Il.

~ I ....

Figure 2-23. Focal suppression of EEG activity right temporal area and focal slow wave activity right frontal. Total right middle cerebral artery occlusion in a 61-year-old female with hypertension. Case 26-4. ANT.F. = Anterior frontal parasagittal; POST.F. = Posterior frontal (parasagittal); PAR. = parietal; OCc. = occipital; ANT.T. = anterior temporal; MID.T. =mid temporal; POST.T. =Posterior temporal. (Listed in text and CD ROM as Figure 26-14). c

5OmVII ...

AGE 4 yr.

EEG N040998

3-SO-69

Figure 2-24 Generalized delta 1-2 Hz slow wave activity that persisted despite attempts at arousal this 4-year-old male had acute viral encephalitis.

lized in the analysis of pseudoseizures or other unresolved "spells". c. Depth electrode recording: from medial temporal and other structures may be performed prior to epilepsy surgery often in combination with video monitoring. d. Subdural surface grids of electrodes: may be placed on the cortical surface for better correlation of seizure discharges arising in the frontal or other neocortical areas,

Figure 2-25. Generalized theta 5 Hz slow wave activity. This 67-year-old female had a metabolic encephalopathy due to impaired hepatic Junction secondary to cirrhosis and at this point was semicomatose in a stuporous state. When the patient was more deeply comatose, the awake activity was even slower at 4 Hz. When the patient was alert during intervening periods of recovery, the dominant activity was in alpha range.

e. Electrocorticography: recording directly from the pial surface may be utilized during epilepsy surgery. f Polysomnography(PSG): this technique is utilized in the evaluation of sleep disorders such as narcolepsy and sleep apnea. EEG activity from the parietal occipital or vertex areas of the scalp is correlated with (I) Cardiac activity (EKG) rate and rhythm (2) Respiratory activity rate and rhythm (3) Oxygen (02) saturation (4) Extraocular movements (5) EMG activity chins and or limb The use of the PSG and the multiple sleep latency study will be discussed in chapter 29 c. Evoked Potentials: ( I) Visual (VER or pattern reversal visual evoked potential: PVER): The time of conduction over the entire visual pathway - to cerebral cortex is measured. Pattern reversal generates a prominent very stable wave at approximately lOOms, the PIOO wave (Fig.2-26). (2) Somatosensory evoked potentials: As discussed above, these studies may provide information regarding delays in conduction in the thalamocortical system. 3. Neuropsychological tests: A variety of tests have been developed, These include the Wechsler Adult Intelligent Score (WAIS) for-

2-25

LOCALIZATION OF FUNCTION, AND NEUROLOGICAL DIAGNOSIS

merly termed the Wechsler Bellevue Test of Adult Intelligence. This has a series of separate subtests covering multiple areas of verbal and performance functions. A total, verbal and performance intelligence quotients are derived. A series of tests have been developed to study aphasia and frontal lobe function and are discussed in those chapters. The Wisconsin Card Sorting Test is utilized to study cognitive perseveration. The Wechsler Memory Score provides a quantitative measure of memory function. The Minnesota Multiphasic Personality index, provides information regarding personality, affect, depression etc. Projection tests have also been developed to study personality function the Rorshark and the Thematic Apperception Test. The answers to the pictures provided unless very bizarre may be difficult to score and the results are open to several interpretations. 3. Techniques for the study of the cerebral circulation a. Magnetic Resonance Angiography (MRA) - Normally in MRI scans, rapidly moving blood is not clearly imaged. However with special software programs, a non-invasive visualization of flow through vessels can be achieved. (Fig 2-27, 2-28). At present, resolution in the range of 2-3 mm can be achieved, allowing visualization of significant aneurysms. This procedure allows imaging of the carotid and other arteries prior to carotid endarterectomy* . b. In contrast, cerebral angiography (or arteriography) is invasive. A catheter must be placed in the femoral artery and advanced into the aorta and then into the carotid or vertebral arteries. Radiopaque dye is then injected to directly image the cerebral vessels. This is the best technique when detailed study of the cerebral vascular is required, e.g., prior to aneurysm surgery. With the increase resolution of MRA and of CT scan angiography, direct arteriography may be replaced by these non-invasive techniques. Under special circumstances, spinal angiography employing selective catheterization of

26A

26B

'''"l.~ tHin VI,UAL POlitO IIUIIONIU ANALYStS P21"OO, AT CMECK SIlt:" I, ... HI.. 102"

"'*' (CIACL.IE)

LATE:NcY {WSI!C) AS fUNCTION Of' CH[CJ(. SIZE TOTAL. eMECICS PlA MONITOR SCREEN (VISUAl AHGLG OF ARC rOAI EACH CHlCK AT I M£lERI S~

CoNI"Oi'.H . .. 2 l.,-

U'" 'I ...... CYHA'lOfJ

......

.....,... 'SO

u...,.

417- ,

114~·J

1oth9

IQI!, '11

...... .,. .

13·llo.

·lSOIP

.."

Il"

wK( YIID.

"C." I

.... ,,' I SD

......

0-"

Ilk,a ... ' 3501P

T

01)31

,.1

rJ'1:1- ' ... 'l - .. /1.. .. •. ,...

!4 LU

.....

n.

"fZ~· '

101 I !'I

... '

fl ·""

..

Z'1l1

...'

+. +... .... .. ...... '.

HI

,as',

•.

l006.! 6

,..

10;1011:10'1

"*

i l~' 1

9thlS

1D'3',!o

,'.'09

.s·I11

11.,

IUJ

,.;,r

ahllJ

lh1'

':WI

C>-I

n.

.... ,.

" "11'\:

..

...,

. I"

......•....•... . ; ..... ···1··· ~G I 9,

.. .........:.. ~ ... "f-l-- ~ :I':" ....... . , .............. : .. '5' " ... '" .. !"'\o:\ilill +· .. ·-f···· ....... '.. ~' . ~.

~ :~: ... :~::;~ ~ I · ~;~ :·::~:"::.· "·:.:·iJ: ~+';.:(~.; ' ~

...... +....... f-V' ~

: ... '_ ~ 'J ~'ff9Z ~:. , ",::.

,·1 .

.......,......~ ro'"'

!i

. ~ ~;..

: :..". . .: :::: r ... ,... .' ~

~ ~i

",-iJ" '" i'\.rI.J..

\fit,

II--c C

Fig 5-24. The inner surface of the channel is exposed to an artificial cytoplasm; the site is tlephosphorylated and channel tutillity cease. Channel tutillity is regained when the phosphorylation enzyme system is added. (From Armstrong and Eckert, Proc.Natl. Acad. Sci. USA. 84: 2518-2522, 1987)

CHAPTER 6

Skeletal Muscle and Nerve-Muscle Junction GROSS STRUCfURE AND FUNCTION. Skeletal muscles are the major ending of the efferent branch of the central nervous system. We work our will upon the outside world through these muscles. Skeletal muscles occupy about 80 %of the total weight of the body. They use about 6 %of the resting oxygen consumption to maintain ionic gradients; after strenuous exercise they may use as much as 70 %of the oxygen consumption. Each anatomic muscle is delimited by strong fascial sheets and has a characteristic origin and insertion. The basic unit of the muscle is the muscle fiber or cell that runs from one end of the muscle to the other end and has a diameter of 50 to 100 pm. Motor Units. Anatomic muscles are subdivided into bundles of many fibers (Fig. 6-1). Each muscle fiber is innervated by only one motor nerve fiber. Groups of muscle fibers are delimited functionally by their nervous innervation. As the Fig. 6-1 shows, the motor nerve branches and innervates a number of muscle fibers. The muscle fibers that are innervated by a single motor nerve are called a motor unit or group. All these fibers act in the same manner since a single nerve controls them. The number of muscle fibers in a motor unit varies from 300 to 400 in the gastrocnemius (calf) muscle to 4 to 6 in the extraocular muscles. In general, the size of the muscle group is proportioned to the delicacy of the required movement. The extraocular muscles make very small, fine adjustments; the gastrocnemius muscle, coarse, powerful movements. When the motor nerve is stimulated, an action potential travels down the axon until it reaches the end-plate region, where it releases a chemical transmitter, acetylcholine. The acetylcholine diffuses to a specialized portion of the muscle surface, the motor end plate, and initiates a second action potential on the surface membrane of the muscle fiber. We will discuss the motor endplate in greater detail later in the chapter.

Figure 6-1. The organization of muscle fibers into structural units, muscle bundles and functional units, motorgroups.

Contraction. The action potential travels along the muscle surface from the end-plate region with a conduction velocity of about 1meter/sec. The response to a single stimulus, either to the motor nerve or to the muscle surface, is called a twitch. Muscle activity usually occurs in response to a series of action potentials, a partial or complete tetanus as illustrated in Figure 6-2B,C, and D. It can be seen that increasing the frequency of stimulation to a muscle increases the tension generated. Since motor units are in parallel, their tension is additive. The total tension a muscle produces is primarily a function of the number of motor units activated. Sarcomeres and Filaments. When we study the structure of the muscle fiber, the mechanism of contraction becomes clearer. Figure 6-3, A-D shows the structure of a lOO-pm diameter muscle fiber and its component 1 pm myofibrils. The banded pattern (D) is clearly seen in the light microscope in either single living fibers or fixed and stained material. A dark A band alternates with a light I band. The I band is bisected by a thin, dark Z disk. The basic contractile unit is a length of myofibril from Z line to Z line

6-2

CHAPTER 6

II SEC.

A

IO/SEC.

B

12/SEC.

c

30/SEC.

o I I SEC.

...

"I

Figure 6-2 Isometric tension in response to stimuli of constant voltage and a varying frequency. Note that the total tension isgreater when the frequency ofstimulation is increased until a maximum (tetanus) tension is reached. Record from a human flexor carpi radialis muscle in situ. The subject's arm was held to a table with adhesive tape; stimulation was via a carbon electrode over the muscle mass in the upper forearm and a laflJe EGG electrode at the wrist. The tension transducer was in contact with the styloid process on the wrist below the base of the thumb. Both wrist and finger flexors can be stimulated by this method.

called a sarcomere. After isolation, this unit, 1 pm in diameter and 2.5 pm long, will still con-

tract. At higher magnification, in the electron microscope (Fig 6-3E), it is clear that the bulk of the muscle structure is made up of two types of filaments. The larger of these filaments, the thick filament, is 10 nm in diameter and 1.5 pm long and is located entirely within the A band. Indeed, all of the properties of the A band can be attributed to these filaments. The thin filaments are 4 nm in diameter and 1.0 pm long and run from the Z line various distances into the A band. During contraction the thin filaments are pulled past the thick filaments to reduce sarcomere length.

Excitation Contraction Coupling Muscle activation begins when an action potential spreads over the surface and then into the depth of each fiber. Calcium released from intracellular structures allows the thick and thin filaments to interact, produce tension, and shorten. Contraction ceases when CA++ is transported into the same intracellular structures. Reticular Structures. Skeletal muscle has an enlarged and specialized reticular network that is shown in Figure 6-4. It can be subdivided into two portions: the transverse tubules or T system and sarcoplasmic reticulum (SR). The T system is a tubular network that is continuous across the whole fiber and contains extracellular fluid. If a perfect cross section were cut across the fiber, the T system would look like a chicken wire fence with the fibrils running through the holes in the wire. The sarcoplasmic reticulum wraps around the myofibrils like the bun around a hot dog. The (T) system conducts the surface action potential rapidly inward to initiate contraction. When small patches of the surface membrane are stimulated to induce local contraction, the sensitivity of an area depends on its location with respect to the T system. The most sensitive location varies; it is at the Z line in the frog and at the A-I junction in the lizard and many mammals (arrows, Fig. 6-4). Inward conduction is an active, Na+ dependent process in the tubular wall, probably much like the surface action potential. Depolarization of the transverse tubular system generates a charge = movement signal which precedes Ca++ release from the SR. This charge = movement signal has many similarities to the gating current of the axon. The basic ionic mechanisms underlying the muscle action potential are quite similar to those in nerve, a regenerative increase in sodium permeability (to depolarize) which quickly inactivates' followed by an increase in potassium permeability (to repolarize). In skeletal muscle there is also a large, but unchanging, chloride permeability which participates in the repolarization phase. Chloride is in equilibrium across the membrane at a resting potential of -90 mV. The surface area of the T system gives the 'surface' action potential a slow velocity (1 m/sec). Most of the potassium channels are in the T = tubule membrane so the potassium efflux

6-3

SKELETAL MUSCLE AND NERVE-MUSCLE JUNCTION

during the falling phase of the action potential is into the lumen of the T system. After several action potentials, K+ builds up in the T lumen and begins to depolarize the fiber. In normal muscles this depolarization is not large and is buffered by the chloride conductance in the sur-

face membrane. Myotonia. In muscle fibers from myotonic goats the potassium buildup in the T tubules causes a significant depolarization and action potentials continue to fire after stimulation ceases. Much the same result is obtained when nor-

SKELETAL MUSCLE

Muscle Fasciculus

G-Ac:tln Molecu III

ooog 00

J

K

l

F

••••• •••• •••

..• •.•..• ~

......

.:;:;:~:.

-:-:.:.

c:==:::;j~