The production, maintenance, and relief of spasticity in the cat

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NAME AND ADDRESS

DATE

NORTHWESTERN UNIVERSITY

THE PRODUCTION, MAINTENANCE, AND RELIEF OF SPASTICITY IN THE CAT

A DISSERTATION SUBMITTED TO THE GRADUATE SCHOOL IN PARTIAL FULFILLMENT OF THE REQUIREMENTS for the degree DOCTOR OF PHILOSOPHY

DEPARTMENT OF ANATOMY

By LEON H. SCHREINER CHICAGO, ILLINOIS

HAY, I960

ProQuest Number: 10101933

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I REVIEW OF PERTINENT LITERATURE............................... Page 3. MATERIALS ANDMETHODS . ! OBSERVATIONS

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INTROD0CTXOH* The basic feature underlying spasticity has recently been shown to be attributed to over-activity or exaggeration of spinal stretch reflexes* Such abnormal reflex activity is manifested experimentally and clinically by muscular hypertonus, hyperreflexia, and clonus, which together constitute the spastic state*

Spasticity has further been shown to be precipitated by

withdrawal of neural influences, of cortical and sub-cortical origin, which normally act to suppress spinal stretch reflexes* Although the initiation of the spastic state depends upon release from suppresor influences upon the myotatic reflex, its maintenance is directly attributed to the unopposed Influx to the cord of motor faeilitatory mech­ anisms originating within the brain stem*

These influences are conducted to

the final common pathway by retioulo-spinal and vestlbulo-spinal tracts coursing chiefly in the ventral half of the spinal cord* Of these two known brain stem faeilitatory mechanisms, the vestibulo­ spinal system has been thought to be of major importance in the maintenance of spasticity*

However, recent investigations indicate that the reticulo­

spinal system, although less well known, might be of equal or greater sig­ nificance*

The present series of experiments were undertaken in an attempt

to clarify this problem by destroying these systems individually and in combination, thus evaluating the importance of each in the maintenance of spasticity# Since electromyography serves so adequately as an objective method of recording alterations in stretch reflex activity in man, this quantitative method was employed by us in our experiments on the production, maintenance,

2*

and subsequent relief of spasticity In the eat* The results of this work have already been published* It Is our purpose < here to record the observations in more detail along with protocols, diagrams of lesions* and serial electromyographic recordings of each experiment* thus bringing all the available information together for correlation with the findings of other workers on this general subject*

5*

REVIEW OF PBRTIMBNT LITERATURE* A m l e w of the literature leading up to our present knowledge of the neural mechanisms underlying spasticity involves the recordings of obser­ vations of a great many workers*

Their experiments were made upon widely

scattered parts of the nervous system* extending from the cerebral cortex to the spinal nerves*

For this reason* it seemed convenient to record

these earlier works in three sections* beginning with the spinal stretch reflex arc# followed by a recording of experimental evidence for the exist­ ence of motor faoilitatory and inhibitory mechanisms of central origin* and finally* the location of these pathways as they descend within the cord to exert their Influence upon the stretch reflex# THE STRETCH REFLEX Although the basic anatomical structures constituting the reflex arc* namely dorsal and ventral roots of spinal nerves* were described by Galen (131 - 201), one of the earliest recordings of investigations on the nervous system in an attempt to establish its physiological significance was carried out by Robert $hytt (1714 - 1766)*

In 1761* he wrote*

*A certain power or influence lodged in the brain* spinal marrow and nerves# is either the immediate cause of the contraction of the muscles of animals* or at least necessary to it* The truth of this appears from the convulsive motions and palsies affecting the muscles when the medulla cerebri* medulla obiongota and spinalis are pricked* or any other ways irritated or compresseds as well as from observing that animals lose the power of moving their muscles as soon as the nerve or nerves belonging to them are strongly compressed* cut through * or otherwise destroyed*" Whytt thus attributed great significance to the nervous system as a regulator of muscle activity In animals*

In these same writings* the author

cited the work of Kedi* who observed that turtles were able to sustain them-

4*

salves and move about for several months after decerebration*

This then

Indicated to Shytt that* although the upper portion of the brain had great functional significance* its absence was compatible with life and that the spinal cord and its segmental nerves must remain intact for muscular activity to exist*

His writings also gave us one of the first descriptions of the

aayotatio reflex* the existence of which was substantiated by experimental investigation at a much later date* "Whatever stretches the fibers of any muscle* so as to extend themselves beyond their usual length* excites them Into contraction almost in the same manner as if they had been Irritated by any sharp instrument* or acrid liquor*" Although the efforts of these early investigators indicated that muscular activity could oeour in the absence of influences of higher origin acting upon the cord and spinal nerves* It remained for Marshall Hall (1790 - 1807) to give us the first accurate description of the spinal reflex arc*

He observed that* after transversely dividing tie body of a frog* ir­

ritation of the skin of a lower extremity caused that extremity to be thrown into violent convulsive activity as long a® the gray matter of the cord was intact*

This was confirmed later in warm-blooded animals by other

workers* With these early observations* the foundation was laid for intensive investigations on the functional significance of the nervous system*

The

existence of sensory and motor components of spinal nerves was firmly es­ tablished by Bell in 1610* when on studying spinal nerves* he observed a decided difference in the anatomical appearance of the dorsal and ventral roots* and on this basis alone* he oonoluded that each root had a separate function*

To establish the exact function of spinal nerve roots* he turned

Bm

to investigations of a physiological nature* after which he wrotet * I said* if the endowment of a nerve depend on the relation of its roots to the columns of the spinal marrow and base of the brain* then must the observation of their roots indicate to us their true distinctions and their different uses* It was necessary to know in the first place, whether the phenomenon exhibited on injuring the separate roots of the spinal nerves corresponded with what was sug­ gested by their anatomy* After delaying long on account of the un­ pleasant nature of the operation* I opened the spinal canal of a rabbit and out the posterior roots of the nerves of the lower ex­ tremity j the creature crawled* but I was deterred from repeating the experiment by the protracted cruelty of the dissection* I re­ flected that an experiment would be satisfactory if done on an ani­ mal recently knocked down and insensible; that whilst X experi­ mented on a living animal* there might be trembling of action ex­ erted In the muscles by touching In a sensitive nerve* which motion it would be difficult to distinguish from that produced more im­ mediately through the Influence of motor nerves* I therefore struck a rabbit behind the ear so as to deprive it of its sensibility by the concussion* and then exposed the spinal marrow* On irritating the posterior roots* 1 could perceive no motion consequent on any part of the muscular frame; but on Irritating the anterior roots of the nerve* at each touch of the forceps* there was a corresponding motion of the muscles to which the nerve was distributed* these ex­ periments satisfied me that the different roots and different columns from whence these roots arise* were devoted to distinct offices*

On finding this confirmation of the opinion that the anterior column of the spinal marrow and the anterior roots of the spinal nerves were for motion* the conclusion presented itself that the posterior column and posterior roots were for sensibility* Buthere a difficulty arose* An opinion has prevailed that ganglia were intended to cut off sensation; while everyone of the nerves which X supposed were the in­ struments of sensation* had ganglia on their roots* Some very decided experiment was necessary to overturn this dogma* I selected two nerves of the encephalon; the fifth* which had a ganglion* and the seventh* which had no ganglion# On cutting across the nerve of the fifth pair on the face of an ass* it was found that the sensibility of the parts to which it was distributed was entirely destroyed* By pursuing the enquiry* it was found that a ganglion nerve is the sole origin of sensation in the head and face* and thus my opinion was con­ firmed* that the ganglionic roots of the spinal nerves* were the fooul or funiculi of sensation*** These observations thus led to the establishment of the Bell-Magendie law*

The exact contribution by A&gendle is somewhat obscure; however* his

.

6

work, which led to the same conclusions as that of Bell, was carried out and published at a somewhat later time, and there exists in the literature of that era some indication of ill-feeling between these two great in­ vestigators* With this baekground of information concerning reflex activity, the early vague description of the niyotatio reflex by Whytt was definitely crystallised by the work of Sachs (1873)*

To him is given the credit for

the first conclusive histological demonstration of the sensory nerve supply to muscles*

He showed further that they are derived from the posterior roots

of the spinal nerves and have a course and distribution distinctly separate from those of the motor nerves*

The existence in muscles of certain nerve

endings which did not end in motor end plates were first mentioned by Kftlliker (i860 - 1868)*

Kuhne (1383), in studying the histologic make-up of adult

muscle, described atypical, fusiform muscle fibers surrounded by a capsule into which nerve fibers enter to disperse themselves throughout the enclosed muscle cells#

By virtue of the shape of these encapsulated neuro-muscular

bodies, he designated them as wiauskel-splndeln"* Huffini assumed that these spindles had a sensory function.

In 1893, he wrotei

"I cannot today say

other than 1 said in my communication already published, namely, that the muscle spindles may be special nerve organs entrusted with some peculiar sensorial function, but in saying so, I look forward to an experiment for the final word upon the matter." Sherrington performed the experiment suggested by Buffini*

In 1894, he

wroteI m %■ own experiments have been suitable for examining the effect

7*

of degeneration of the motor spinal roots upon the nerve fibers sup­ plying muscle spindlesi they demonstrate that the muscle spindle is supplied with nerve fibers arising in the cells of the spinal gang­ lion* In muscles from which all motor fibers have been entirely re­ moved by degeneration* 1 have never In a single instance failed to find every spindle met with in the muscle still possessed of perfectly sound myelinated nerve fibers* These myelinated nerve fibers are traceable from the sensory roots* penetrate into the spindles* and terminate within them* The muscle spindle therefore proves to be a sensorial organ*1* Up to 1934* many hypotheses existed concerning the underlying cause for exaggeration of muscle tone in various diseases of the nervous system*

Ho

doubt* all workers in this field of research realised that abnormal tone in striated muscles was dependent Upon an alteration in the neuronal influences conveyed to them by the anterior horn cell*

However* a true understanding

of muscle tone came only after the brilliant researches of Sherrington*

He

showed that tonus of the striated musculature was dependent primarily upon sensory impulses originating from the muscles themselves*

Thus* the stretching

of a muscle causes stimulation of sensory nerve endings lying within it* followed by transmission of the Impulse to the anterior horn cell* which in turn causes reflex contraction of that muscle*

Be concluded that tonus was

fundamentally a stretch reflex and that this reflex activity accounts for the substratum of muscular tension which underlies posture*

He referred to

this as *myotatic reflex1* activity* which phrase has continued in use up to the present time*

With the introduction of these fundamental observations

concerning muscle activity* many of the previously described hypotheses were altered somewhat* and subsequent investigations concerning muscle tone stemmed from these Important findings* Hecent investigations by Lloyd (1944) have shown that the spinal stretch reflex are of Sherrington in composed of but two neurones*

The electrical

6#

Impulses, set up by derangement of sensory spindles within the muscle proper, are conveyed through the dorsal spinal root to the gray matter of the oord to stimulate anterior horn cells by direct synapse*

The anterior horn cell,

together with its processes, constitute the second component along which the efferent Impulses are conveyed to the muscle exciting it into contraction* From the above review of the literature concerning anatomical components and physiological characteristics of the myotatie reflex, it is apparent that altered function of this neural unit is responsible for spasticity* CBNTHAh IHHIB1TI0K

BXCXTATIOH OF THIS STB8TCB REFLEX

Cortical Suppressor Areas and Projections After the neural components making up the myotatic reflex arc were identified, the Influences upon this arc, whose origins are high in the oerebro-apin&l axis, were shown to exist following the experiments of Fritsoh and Kitsig*

In 1870, in a series of experiments on dogs, they

found that the direct application of galvanic current to the exposed cerebral hemispheres in certain regions caused movements and also, the more important observation, that definite muscular contractions were associated with irritation of certain circumscribed cortical areas*

Thus, they localised

cerebral centers for movement of the adductors, flexors, and extensors of the opposite limbs and also the centers in relation to certain facial, head, and neck muscles* Ferrier and Ye© (1871 «* 1884) not only confirmed the findings of Fritsoh and Hitsig but also demonstrated that ablation of the eortlo&l motor areas resulted in profound alterations in motor activity in cats and monkeys* Following such lesions, the authors were able to follow degenerated neuronal

pathways from the internal capsule to the lower level of the pons# Experimental confirmation of the presence of cerebral motor areas in the human was carried out by Bartholow.

In 1874, he reported the results

of direct application of an electrical current to the surface of the brain in the case of a patient whose brain was partially exposed by a cancerous ulceration of the skull#

He found that insertion of needle electrodes, in

connection with an induction coil, into the gray matter of the hemisphere in the region of the parieto-occipital lobes caused convulsive movements of the arm and leg on the opposite side#

Following these observations, it was

soon determined that neurons originating in this cortical motor area initiate and conduct impulses to the anterior horns of the spinal cord, whose oells give origin to the final motor pathways# Neural influences upon muscle activity, which have a central origin and are distinct from the now well known pyramidal pathways, were first described by Hughlings Jackson#

His early views concerning the origin of muscle rigidity

in hemiplegia and other syndromes were purely hypothetical and were based entirely upon clinical observations, post-mortem examination, and evolution of Darwinian variety as regards the nervous system#

In 1887, he wrote*

"It is not possible at this stage to do more than state in incomplete outline the evolutionary hierarchy of the nervous centers*

However, the

periphery is the real lowest most level of neural activity

consisting

of the anterior and posterior hornsof

the spinal cord — and represents

all parts of the body most nearly directly#

The middle part consists of

Ferrier,s motor and sensory regionsof

the cerebral hemispheres and corpus

striatum, which represent all parts of

the body doubly indirectly#

The highest

level consists of the highest motor centers (prae-frental lobes), highest sensory centers (occipital lobes), and the "mental centers*• They represent all parts of the body triply indirectly*

These highest centers make up the

*organ of mind", or physical basis of consciousness and are evolved out of the middle, as the middle are out of the lowest and as the lowest out of the periphery; thus the highest centers re- re- represent the body — represent it triply indirectly**

that is

He thus concluded that the derangement of

any neural-functional level by disease was followed by a "release" of the next lowest level, resulting in its increased functional activity* At a later time, Jackson added his "influx theory* to motor activity, in which he ocnoelved of impulses arising at higher levels which antagonise or inhibit one another and do so in different degrees upon different lowest motor centers*

In accordance with this hypothesis, he stated that the muscle

rigidity and hyperreflexia in hemiplegia were due to release of lowest motor centers from cerebral (inhibitory?) influences, thus allowing cerebellar influx (of a faeilitatory nature?) to act unopposed upon these lower motor centers*

Such brilliant conclusions, arrived at by methods other than animal

experiments, had a profound influence on subsequent workers on this general subject* In 1096, Sherrington first reported that, after transection of the brain (oat or dog) through the cephalic portion of the mesencephalon, a tonic con­ traction of the extensor musculature ensued*

the extremities were stiffly ex­

tended; the neck, was retracted; and the tail was dorsi-flexed#

He pointed out

that this extensor hypertonus was present in those muscles that normally coun­ teract the force of gravityj the operation freed the anti-gravity muscles from

some inhibitory control lying above this plane of injury#

Sherrington re­

ferred to this tonic contraction of extensor musculatne as "decerebrate rigidity*• Weed (1914) endeavored to identify the inhibitory tract whose severance resulted in decerebrate rigidity or extensor hypertonus as described by Sherrington#

The cut surface of the brain stem in a decerebrate preparation

was explored with an eleotrio current; the area stimulated was that ordinarily exposed in the technique of deoerebration#

tlci ac

The a r e a a b o v e , i n r e d , c irc u m s c rib e s th e le s io n p la c e d i n th e s u b -th a la m u s and c a u d a l hyp o th alam u s o f o a t 6 . These s tr u c t­ u r e s , as tr a c e d i n s e r i a l s e c tio n s th ro u g h th e e n t ir e e x te n t o f th e le s io n , w ere c o m p le te ly d e s tro y e d . A t t h is l e v e l , th e c e r ­ e b r a l p e d u n c le s w e re a ls o in t e r r u p t e d .

82. n M C f e m m x m p m o asPHESsmtioi? of spasticity m r

oat

6#

s

CAT 6 2.

nHfrWb'

PERICRUCIATE AREA BILATERALLY 3 2 ND RO. DAY

.-* • .* ..

■~-(Uv

FASTIGIAL NUCLEUS BILATERALLY 6 2 ND RO. DAY

----t

SUBTHALAMUS AND CAUDAL HYPOTHALAMUS 4 T H RO. DAY

The effect upon stretch reflexes resulting from placement of serial lesions In cat 6 is represented by the electromyographic tracings as shown above* The sequence of lesions is designated by nxm ■,'ls in the upper left comer of each postoperative recording block* Each block con­ sists of tracings from the left quadriceps, hamstrings, gastrocnemius, and tibl&lie anterior muscles which are arranged in this order when read from top to bottom* In each case, stretch was applied to the designated muscle In the interval between the plus and minus signs. Records of tendon re­ flexes may be seen immediately to the right of the corresponding stretch reflex tracings. In some cases, elicitation of tendon reflexes was fol­ lowed by clonus*

P re o p e ra tiv e exam ination*

No increased resistance to muscle stretch was encountered in any of the extremities*

Both knee jerks were of moderate threshold* brisk* and

of moderate excursion*

The patellar reflexes wers> present bilaterally*

The

tibialis anterior reflexes were present and minimal* as was the left aohilles jerk*

The right aohilles jerk was absent*

The right trioeps response was

brisk* of moderate threshold and excursion* and was followed by a repetitive element of three to four cycles*

This sometimes appeared to be a true olonus*

No other reflexes were elicitable* due to resistance given by the oat* Operation J* The pericruciate area of the cerebral cortex was aspirated bi­ laterally on January 27* 1948* First postoperative day* The cat was still under the influence of nembutal, though awake and vocalising*

It was able to walk but frequently fell to the right side

and had poor to no placing reactions* Moderate to extreme resistance was observed on flexing the hind­ legs* which tended to remain in extension*

The forearms offered moderate

resistance to both flexical and extension at the elbows* Both knee jerks had low thresholds* were brisk, tight, and followed by a repetitive element of three to four cycles duration* elicitable from the tendons only*

These reflexes were

Both tibialis responses were active*

First postoperative day JP»M. The animal was able to stand and walk slowly without falling to

the right side* as was done earlier in the day* limbs and moved with slow deliberate steps* ! ^ j.

feet were lost*

The oat stood high on its

All placing reactions of the

The animal vocalised and was able to drink milk*

When the animal was held* belly up, in the examiner’s lap, its hindlimbs assumed a position of extreme extension*

Saoh hindleg oould be

! collapsed by the use of moderate to extreme force* that necessary to collapse i: the left leg was greater than for the right* The gastrocnemius muscles rei.

slated stretch to an extreme degree bilaterally*

Neither the tibialis anterior

I! nor the hamstrings muscles offered resistance to manipulation*

The forelegs

were held in a semi-flexed position and periodically and rhythmically slowly i ; extended alternately in kneading movements* Both biceps muscles moderately I resisted stretch and the triceps resisted minimally* The knee jerks were of low threshold* elicited best and more actively on the left side of the tendon* the reflexogenic sones extending down to the ankles*

These reflexes were brisk* somewhat pendular* of moderate excursion*

and followed by a repetitive element of two or three cycles duration*

Both

tibialis anterior reflexes were present* of low threshold, brisk, of large excursion, and equal in quality bilaterally* were obtainable on either side*

Occasionally* the aohilles jerks

Examination of the arms revealed the biceps

jerks to be present bilaterally, having moderate threshold* being neither brisk nor tight and best elicited by tapping the front of the forearm* reflex on the right side was less active than on the left*

The

Occasionally, the

triceps responses could be obtained bilaterally but showed no undue hyper­ activity, since the biceps jerks fired at the same instant* reflexes were brisk* tigjht, and of low threshold*

Forearm extensor

SummaryJ

The animal was moderately spastic, more pronounced

in the extremities of the left side* Seventh postoperative day* The animal was able to move about in the cage*

When held in the

examiner’s lap, the cat carried out kneading or stepping siovements wxth its upper extremities# When the animal was held on its back* the hindlimbs were In semiextension! forelimbs In flexion*

Moderate resistance* equal bilaterally, was

encountered upon stretching the quadriceps and gastrocnemius muscles*

The

tibialis anterior muscles opposed stretch to a slight degree on both sides* Both arms offered moderate resistance to both flexion and extension at the elbows; however, this latter resistance appeared to be partly voluntary* Both knee jerks had moderate thresholds* were brisk but somewhat loose* and each was followed by a repetitive element of one or two cycles duration*

The response on the left side was slightly more active*

Both

tibialis reflexes had low thresholds* were brisk but pendular and of wide ex­ cursion* had reflexogenic zones extending from the toes up to the knees* and were followed by one or two cycles of repetitive activity* reflex was slightly more active* and of wide excursion* hyperactivity#

Again, the left

The aohilles responses were minimal* sluggish,

The biceps jerks were present and minimal* showing no

No other reflexes were elicited*

Summary!

The cat was moderately spastic bilaterally; however* the

spastioity was slightly more pronounced on the left side# Sixteenth postoperative day* Both quadriceps muscles resisted stretch from a moderate to an

extreme degree* equal on the two sidea*

The hamstrings muscles opposed

stretch moderately and equally* as did the gastrocnemius muscles bilaterally. No resistance to manipulation was offered by the tibialis anterior muscles* | Both biceps muscles resisted stretching moderately and equally on the two ]| j; sides; whereas* the triceps muscles resisted to an extreme degree* espe­ cially after the ninety degree angle was approached at the elbows* Both knee jerks were of low threshold, brisk* fairly tight, and followed by a clonus of two to four cycles duration* was the more active#

The right knee jerk

The tibial reflexes had moderate thresholds* were

brisk* tight, and equal in degree on the two sides*

Hie triceps responses

had low thresholds, wide reflexogenic zones* were brisk* tight* and somewhat more active on the right aide*

Hie biceps reflexes had moderate thresholds

and were brisk and somewhat pendular*

Forearm extensor reactions were pre­

sent bilaterally and were moderately hyperactive* Summary*

The animal showed moderate spastioity as characterized

by hypertonus* which was equal bilaterally* and hyperreflexia* which was slightly more pronounced on the right side*

Clonus was present following

percussion of either patellar tendon, and irradiation of reflex activity was observed* Thirty-sixth postoperative day* The cat walked with apparent ease* standing high on Its legs and walking stiff-legged*

A mild bilateral conjunctivitis was present*

$h©n the animal was held on its back in the examiner’s lap* its hindlimbs were in complete extension, and the forelimbs were semi-extended* Both quadriceps and gastrocnemius muscles resisted stretching from a

moderate to an extreme degree* which was equal on the two sides*

The ham­

strings and tibialis anterior muscles offered little or no opposition to manipulation#

Both triceps muscles resisted stretch from a moderate to

an extreme degree* which was equal bilaterally; whereas* the bleeps re­ sisted only minimally* The patellar reflexes had moderate thresholds* fairly large reflexogenic zones* and were extremely brisk and tight*

Each reflex was

followed by a repetitive element of two to four cycles duration* and by crossed patellar and ipsil&teral tibialis anterior reflexes#

This re­

petitive activity sometimes amounted to a clonus* which was slightly more prolonged on the right side*

The tlbial reflexes had small reflexogenic

zones* were brisk* tight* and followed by a repetitive element of two or three cycles duration* the repetition in the right foot sometimes appearing to be clonus* side*

These reflexes were slightly more pronounced on the right

The aohilles jerks had low thresholds* were brisk* somewhat loose*

and equal on both sides* active*

The hamstrings responses were minimally hyper­

The biceps reflexes were elioitable bilaterally* having high

thresholds and being sluggish* pendular* and equal on the two sides*

The

triceps jerks were not obtained* Summaryt

The animal was moderately spastic bilaterally* the

spastioity being slightly more pronounced on the right side*

The clonus*

present on previous examination* was diminished somewhat* Operation IX* Lesions designed to destroy the caudate nucleus were placed

bilaterally on March 6* 1948*

Fo u rth p o sto p e ra tiv e day,

The oat was able to move about, though it stood hi$i on its legs, moved very slowly, and tended to overstep with its forelin&s*

It usually

kept its head near the floor* When held on its baek in the examiner’s lap, the animal carried out running movements with its forelimbs*

Both quadriceps and gastrocnemius

muscles resisted stretch fro® a moderate to an extreme degree, which was slightly more pronounced on the right side*

The hamstrings opposed stretch

to a moderate degree bilaterally; whereas, the tibialis anterior muscles re­ sisted only minimally*

Both triceps muscles offered moderate resistance to

stretch after the elbow reached ninety degrees flexion, and only minimal re­ sistance to stretch was offered by the biceps muscles* Both knee jerks had low thresholds, wide reflexogenic zones, and were very brisk and tight*

Each reflex gave crossed patellar and tiblal and

ipsilateral tibialis anterior reflex responses and was followed by a repetitive element of five to seven cycles duration*

This repetitive activity many times

amounted to a frank clonus, and a crossed clonus was occasionally observed* Both tibialis responses had low thresholds, wide reflexogenic zones, were brisk, very tight, and were followed by clonus of several cycles duration* The reflex on the right side was slightly more pronounced*

The aohilles

jerks had low thresholds and were brisk and moderately pendular* reflex on the right side was slightly more pronounced*

Again, the

So triceps reflexes

were elicitable* Summary*

The animal was moderately to extremely spastic before

the recent operation*

However, the spasticity seemed to be augmented to

$9*

some degree by the caudate lesion*

the eat sheered moderate to extreme

spasticity, which was slightly more pronounced on the right side* fhlrty-elgfrth postoperative day* On it® back in the examiner’s lap, the animal held both its hind­

limbs in complete extension and forelimb® in semi-flexion* ments were constantly being carried out by the forelimbs*

Stepping move­ Both quadriceps

and gastrocnemius muscles resisted stretch to an extreme degree on either side, while the hamstrings and tibialis anterior resisted to a minimal de­ gree only*

Both bleeps and triceps muscles opposed stretching moderately* the knee jerks had moderate thresholds with fairly large reflexogenic

cones, were brisk, of rather large excursion, and followed by repetitive acti­ vity which sometimes amounted to clonus*

Both tibialis anterior reflexes had

moderate thresholds, and were brisk and tight* the aohilles jerks were pre­ sent bilaterally and moderately hyperactive*

the biceps reactions had wide

reflexogenic cones and were brisk and somewhat pendular on both sides* Summary*

the animal was moderately to extremely spastic bilaterally§

demonstrating the three elements of spasticity to a pronounced degree* Operation III* Deiter’s Huoleus was destroyed bilaterally on May 12, 1948* First postoperative day* The animal was found dead in its cage.

Some slight hemorrhage

had occurred in the brain, and it was possible that the animal hadbeen over­ heated*

The brain was removed and fixed in formalin*

GROSS AND MICROSCOPIC DESCRIPTION OF LESIONS IN CAT 8*

The extent of injury within the cerebral cortex of cat 8 is seen in the above diagram. The lesion in the right cerebral hemi­ sphere, in red, destroyed the anterior portion of the lateral and coronal gyri, the entire perioruciate area, the frontal gyrus, the gyrus proreus, and a portion of the olfactory tract* The lesion in the left cerebral hemisphere, in green, resulted in cortical destruction equal in extent to that on the opposite side*

91*

Sec, 131

X7

lU8

The areas above, In red, circumscribe lesions placed in the caudate nuclei of oat 8* At this level, the posterior portion of the head of the left oaudate nucleus was completely destroyed! whereas, on the right side, only the dorso-aedial one-third of the head of the nucleus was Injured, The lesions, as traced In serial sections, extended c&udslly to destroy the rostral portion of the body of each nucleus. Placement of lesions resulted In production of hydrocephalus.

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Figure 1* Effect of removal of the perlcruclate cortex on stretch reflexes of the quadriceps, Ay hamstrings, Of tibialis, Of and gastrocnemius, Q? stretch being applied between plus and minus signs* Corresponding records of the knee jerk, By tibialis Jerk, Ey and Achilles jerk, F, are included* Legions of the caudate nucleus Injury to the caudate nuclei, in animals whose brain was otherwise intact, was followed by signs of spasticity which were moderate in degree and transient in nature*

Such were the findings in oats 13 and 14 of our series*

Rleotroajyogyaphlo recordings during passive stretch of the quadriceps (Fig* 2 F# 1) and gastrocnemius (Fig# 2 0# 1)* obtained preoperatlvely# were augmented

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Figure 2# Effect of lesions of cerebellar cortex on stretch reflexes of quadriceps# A# and gastrocnemius# B* Records obtained preoperatlvely# 1# one month postoperatively# 2# end three dare after adding lesion of f&stiglal nuclei# S# Effect of primary lesion of fastlgial nuclei on stretch reflexes of quadriceps# 0# and gastrocnemius# D. Records obtained preoperatlvely 1# two weeks postoperative^# 2# and one month postoperatively# 5# Stutz reaction# ®# was obtained one month postoperatively. Effect of primary lesion of caudate nuclei on stretch reflexes of quadriceps# F# and gastrocnemius# Q« Records obtained preoperatlvely# 1# one week postoperatively# 2# and three weeks postoperatively# 3* within one week following placement of the lesions (Fig* 2F# 2 and 0# ?)• After three weeks# the muscle tone subsided to a near normal level (Fig* 2

F# 5

G# 5}#

Caudate lesions# In animals made spastic by previous destruo-

tlon of the perlcruclate cortex or injury to cerebellar suppressor systems# also resulted In transient augmentation of the pre-existing spasticity* Cerebellar cortex and nuclei A suppressor system having cortical and sub-cortical components is known to exist within the cerebellum*

The cortical origin of this neural

eyetea appears to lie almost entirely within the anterior lobe*

pathways

from this area apparently project to the underlying fastigial nuclei before descending inferlorly to the brain stem*

We have found that destruction of

the cortex of the anterior lobs of the cerebellum (oat ?} resulted in spas* tlcity which was moderate in degree and transient In nature*

Within one

month after placing the lesion# extensor stretch reflex activity had subsided to a near normal level (Fig* 2 A# B# 2)*

In the same animal# bilateral ablat­

ion of the fastigial nuclei 40 days after the cerebellar cortical lesion# resulted in transient reappearance of hyperactive stretch reflexes (Fig* 2 A# B# 3}#

In other animals# destruction of the fastigial nuclei# leaving the

overlying cerebellar cortex Intact# was followed by spasticity similar in degree and duration to that observed following initial destruction of the cerebellar cortex*

Stretch reflexes of the antigravity muscles became ex­

aggerated early in the postoperative period (Fig- % 0, D, 2)5 however# within one month# such muscle fcyperbonus had declined markedly (Fig* 2 0# D# 5). In all animals which sustained injury to the cerebellum# abnormal features of motion such as ataxia# hypermetria# and tremor# were associated with the signs of spasticity* •i

Com bined s u p p re s s o r le s io n s

Simultaneous destruction of suppressor systems in both the cerebrum and cerebellum resulted in the appearance of extreme spasticity which was rel-

ativoly unchanged with the passage of time*

Two animals in our aeries (cats

IT and 18), which sustained bilateral destruction of the perlcruclate cortex, caudate nuclei, and fastigial nuclei, survived for periods of one and two months respectively*

During the first 15 days of their postoperative course,

these animals were unable to sit or stand and their extremities remained in marked extension at a H times*

All muscles of the extremities and trunk were

extremely rigid and any attempt to stretch them caused vocalisation of a pain* ful nature*

Tendon reflexes were virtually impossible to detect olinically

because of the extreme hypertonus in both agonistic and antagonistic muscles of the extremities* Composite eleetromyograms obtained from these animals at various postop­ erative periods are shown in Figure 3*

The preoperative minimal stretch re­

flexes (Fig* 3 A-G, 1) became markedly augmented four days after operation (Fig* 3 A-Q, 2)*

Again, the antlgrsvity quadriceps (Fig* 3 A, 2) and gastroc­

nemius (Fig* 5 Q, 2) demonstrated the greatest degree of stretch reflex en­ hancement* 3, 0*

A representation of maximal muscle hypertonus is seen in Figure

This record was obtained during forceful stretch of the gastrocnemius

by gradual, but complete, dorsi-flexion of the foot at the ankle*

As seen,

maximal discharge continued throughout the stretch and, after its cessation, activity within the muscle slowly subsided. The constant discharge in antigravity muscles of the extended extremity is seen in Figure 3 H, I, 1 and 3*

However, when the limbs were placed In

a position of complete rest, discharge was at a minimum (Fig* 3 H, I, 2 and 4).

Tendon reflexes were enhanced and repetitive (Fig* 5 B, 2S, F}*

Clonus

frequently followed elicitation of the patellar and Achilles reflexes and occasionally occurred spontaneously (Fig* 3 J and K). With the passage of time, the signs of spasticity became less pronounced.

During the second postoperative month, the animals were able to stand and walkf although ataxia, hypermetria and tremor during movement continued to be present. At this time, stretch reflexes of the flexor muscles had returned to normal (Fig. 3 0, D, 3), and those of the quadriceps were diminished (Fig* 3 A, 3). Stretch reflex activity of the gastrocnemius, on the other hand, remained at Its early augmented level (Fig. 3 G, S).

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Figure 3* JSffbet of combined lesions of suppressor areas (pericruciate cortex, caudate nuclei and fastigial nuclei) on stretch re­ flexes of the quadriceps, A) hamstrings, Gy tibialis, D; and gastroc­ nemius, 0. Records obtained preoperatlvely, 1; four days postoperat­ ively, and one month postoperatively, 3. Corresponding records of knee, By tibialis, 2f and Achilles, F; jerks are shown.

Its summary# injury to cerebral and cerebellar suppressor systems* In the cab# results in the production of spasticity*

Among the specific areas which

jhave an inhibitory effect upon peripheral motor activity are the cerebral perlcruclate cortex and the caudate nucleus*

Components making up the cer­

ebellar system are the cortex of the anterior lobe# the paramedian lobules* the fastigial nuclei*

C

Both cerebral and cerebellar systems appear to

jeet inferiority and eaudally to the bulbar reticular formation*

Proa

this common pool* the suppressor influences are conveyed via the reticulo­ spinal pathways through the cord to effect muscle stretch reflex activity at

the spinal level* The bulbar Inhibitory center* into which cerebral and cerebellar suppressor influences project* is apparently incapable of intrinsic function for* after cerebral and cerebellar lesions* suppression of peripheral motor activity is in abeyance and spinal stretch reflexes become augmented*

Release from sup­

pression is thus a primary qualification for the production of the spastic state* Ablation of single suppressor areas is followed by the appearance of spasticity which is moderate in severity and transient in nature*

The most

effective and prolonged spasticity following injury to single suppressor sys­ tems was observed following ablation of the perlcruclate cortex* i

The caudate

|nuclei* when destroyed* precipitated pronounced muscle hypertonus and hyperI reflexiaj however* such signs of spasticity diminished markedly in the early postoperative period*

The cerebellar suppressor system# when destroyed* was

the least effective in the production of spasticity*

Following these lesions,

associated abnormalities of motion such as ataxia, hypermetria, and tremor* were outstanding#

j

The gradually diminishing initial spasticity following Injury to any single suppressor area could be augmented to or above its previous high level by sub-

II

|j sequent destruction of other suppressor systems*

Spasticity resulting from

cerebellar or caudate lesions is markedly augmented by subsequent destruction of the perlcruclate cortex* whereas* caudate and cerebellar lesions enhance to a less degree the spasticity resulting from initial cerebral cortical ablat­ ion* Simultaneous destruction of both cerebral and cerebellar suppressor sys­ tems results in spasticity which is more pronounced and enduring than that following single lesions or destruction of single suppressor systems in ser­ iatim*

Sven with such massive destruction of suppressor systems# the signs

of spasticity tend to diminish with the passage of time* It would seem* therefore* that reorganisation must occur in the known suppressor systems which have escaped complete destruction*

Alternative

explanations are that functionally important suppressor systems, of unknown location# exist within the brain of the cat* or that the bulbar inhibitory center# though at present is not thought to have intrinsic function# may become spontan­ eously ingrained with suppressor activity when a sufficient number of influences j to It from higher centers are withdrawn* igatlon.

Such hypotheses deserve further invest-

|

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| Utilising as a baokgraund the spastiolty resulting froa single or ooar *! jblmed destruction of suppressor systems, motor faollltatory mechanisms known |to exist within the cat»s brain were investigated in an attest to establish |the exact role of each in the maintenance of the spastic state.

That such

centrally located faoilitatory systems exist, was established by transecting the cord of a spastic animal at the mid-dorsal level.

In such a preparation!

the previously hyperactive stretch reflexes of the quadriceps (Fig, 4 A, 1) i |and gastrocnemius (Fig, 4 B, 1), following the lesion, became hypoaetive. In Icontrast, hypertonus of the triceps (Fig, 4 0) and ventro-flexors of the forei

|arm (Fig, 4, D), the reflex arcs of which are situated above the level of the j! Icord transection and therefore remaining connected to the brain, remained at I their originally exaggerated level.

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Figure 4, Effect upon spasticity In the lower extremity fol­ lowing transection of the spinal cord at the mid-thoraolc level.

In the light of these results, It Is apparent that hyperactive stretch reflexes present in the spastic state are dependent upon excltor influences originating at more rostral levels.

Two such eystems are known to exist,

one

of these, the vestlbulo-splnal pathway which takes its origin from Baiter's nucleus, has long been known to convey excltor influences to the eord.

The

other, the reticulo-spinal system, has only recently been shown to be im­ plicated in the maintenance of the spastic state.

The relative importance

of these two systems in the maintenance of stretch hyperreflexla, precipitated by destruction of motor inhibitory systems, is as yet unknown. To evaluate their relative importance, these systems were interrupted in spastic animals by placing selective lesions within the dlenoephalon, basal ganglia, and the brain stem at various levels*

Results obtained following

placement of such lesions have been organised with regard to the portion of the brain under consideration.

We may begin, therefore, with the basal ganglia

and proceed caudally. Basal gamlla and dlenoephalon The intensity of spasticity following injury to motor suppressor systems is, for the most part, unchanged by subsequent destruction of the basal ganglia, ventral dlenoephalon, or connections descending from these structures to the brain stem.

Stretch reflex activity following such lesions seemed to

be quite variable in intensity as observed from day to day; however, mild enhancement of hypertonus occurred in certain muscle groups. |

We have found that massive bilateral lesions in the putamen, following

destruction of the perlcruclate cortex and caudate nucleus (cat 16), had no i

definite effect on the pre-existing spasticity.

In this animal, separate

©lectromyograms taken on the same day gave conflicting results. Those recorded I in the observations section (cat 16) show a definite reduction of stretch

reflex activity in all muscle groups following destruction of the putamen.

On

Ithe other hand9 similar records* obtained from this cat on the same postop­ erative day* demonstrated a reduction in stretch reflex activity of the quad| (Pig & A $ of* 1 and 2) while those of the gastrocnemius were definitely II augmented (Pig. 5 B, of. 1 and 2)*

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Figure 5* Effect upon spasticity of lesions of basal ganglia and dlenoephalon* A* Bs stretch reflexes of quadriceps (A) and gastrocnem­ ius (B) before (record 1) and 4 days after (record 2) destruction of putamen* G$ Dt stretch reflexes of quadriceps (0) and gastrocnemius (0) before (record 1) and 5 days after (record 2) destruction of globus pallidum* E# Pi preoperative (S) and postoperative (P) records of positive supporting reaction* 0* Hi stretch reflexes of quadriceps (0) and gastrocnemius (H) before (record 1) and 5 days after (record 2} destruction of sub- and hypothalamus* After destruction of the globus pallidus (cat 14)* the moderately hyper-

active stretch reflexes of the quadriceps and gastrocnemius muscles were enhanced to a slight degree (Fig* 5 G and 0, cf. 1 and 2),

Positive sup­

porting reactions were also augmented (Pig. 5 cf. 3 and F).

Lesions of tbs

caudal hypothalamus and sub-thalaaua (cat 6) resulted In a diminution of quad-* rieeps stretch reflex activity (Fig. 5 G* cf. 1 and 2 )5 whereasf that of the gastrocnemius was augmented (Fig. 5 H, of* 1 and 2). In general* the globus pallldua* putamen* sub—thalamus* and caudal hypo­ thalamus, when destroyed* contribute little to the enhancement or maintenance of pre-existing spasticity.

Changes in staretch reflex activity following

such lesions in spastic animals does* however* Indicate that these structures* when intact* do convey motor suppressor influences to muscles of the extrem­ ities. Lesions of the midbrain Injury to the central gray and tegmentum of the midbrain results in augmentation of signs of spasticity produced by previous destruction of sup­ pressor systems located within the cerebrum and cerebellum.

Destruction of

the central grey* in cat 7 of our series* was followed by Increased stretch reflex activity of a H muscle groups of the extremity* particularly that of the quadriceps (Fig. 6 3* of, 1 and 2).

Gastrocnemius hypertonus (Fig. 6 F*

of. 1 and Z) was only slightly augmented postoperatively.

In contrast* poa-

|itlve supporting reactions of the lower extremity diminished in intensity jfbllowing the lesion (Fig. © 0 and H), Massive destruction of the midbrain* including the tegmentum and the great!i

ijer portion of the central gray (cat ©}* was followed by a definite Increase in ij resistance to passive muscle stretch and tendon hyperreflexta. This increase lie shown in records obtained from the quadriceps and gastrocnemius muscles (Fig. 6 & and B* of. 1 and 2).

This animal also frequently exhibited rhythmic

i

s te p p in g w h ic h *

when not in progress* could be induced by ventro-flexion of

ankl« (Klg. 6 0 and D), rsourrlng regularly at a rata of one to tao Uaes |par sacond.

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Figure 6» Effect of mesencephalic lesions upon spasticity* A» B* stretch reflexes of Quadriceps (A) and gastrocnemius (B) before (record 1 ) and 8 days after (record 2) destruction of tegmentum• 0, Dt records of rhythmic stepping during ventroflexion of ankle ; channels are quadriceps (record 1)* hamstrings (record 2 )y gastrocnemius (reoord 3) and tibialis (record 4). lt Ft stretch reflexes of quadrleepe (E) and gastrocnemius (F) before (record 1) and 14 days after (record 2) medial midbrain lesions* 0* H t preoperative (0} and postoperative (H) records of positive supporting reaction.

|

the effect of midbrain lesions upon spasticity is thus similar to that

|i

|following destruction of more rostral structures; namely augmentation, rather than diminution of stretch reflexes*

Such were the findings regardless of the

location of lesions within the midbrain*

It appears then, that the rostral

|brain stem and associated structures $ including the basal ganglia, subserve I suppressor influences to the oond* In some instances however, such lesions resulted in diminution of pre-existing spasticity in certain muscle groups Iof the extremities*

Therefore, portions of the brain stem, particularly

the tegmentum, when intact, may facilitate motor activity at the spinal level. Such were the findings after destruction of more caudal portions of the brain stem as reported in the next section* Melons at the ponto-bulbar level Lesions within the brain stem and located at the junction of the pons and medulla had varying effects upon pre-existing spasticity.

Tran­

section of the tegmentum at this level, without injury to Belter's nuclei, resulted in marked reduction in intensity of stretch reflexes of the quadrioepa and gastrocnemius muscles (Fig* 7 A and B» of* 1 and 2).

The pos­

itive supporting reaction was also markedly reduced (Fig* 7 0 and D)« Pre-existing spasticity was unchanged following lesions limited to Belter* s nucleus*

After operation, the stretch reflexes of the quadriceps

was slightly reduced; whereas, that of the gastrocnemius remained unohanged (Fig. 7 S, Ft of* 1 and 2). Similarly, no change in positive supporting ; |reactions followed placement of the lesions (Fig* 7 I, 1 and 2), and dorms continued to occur following elicitation of the knee jerk (Fig* 7 0 and I). i;

i|

Lesions destroying both the tegmentum and Belter1e nucleus completely

j

|abolished the stretch hyperreflexia of spasticity.

In one animal, the exag­

gerated myotatlo reflexes of the quadriceps and gastrocnemius muscles became ji hypoaotive after operation (Fig. 8 A and B, cf. 1 and 2). Positive supporth ling reactions were also markedly reduced (Fig* 8 e and D), In a second W m a l , similar decrease in stretch hyperreflexia resulted (Fig* 6 3, F, and

210*

It cf. 1 and 2)*

In this aaa©* however, tendon hyperreflexia persisted and