Homolateral reflex exaggeration after brain-stem lesion

HOMOLATERAL REFLEX EXAGGERATION ,4FTER BRAIN-STEM LESION

FRED A. METTLER AND FREDERICK T. ZIMMERMAN Department of Neurology, Chlege of Physicians and Surgeons,

Columbia University, New Pork

FIVE FIQURES

In the course of a previous investigation (Mettler and Lubin, '42) it was observed that, while exaggeration of the ipsilateral knee-jerk occurred after lesion of the brachium pontis, this result was not restricted to lesion of this structure. It was further remarked that tegmental injury might produce such a result and that lesions of the brachium pontis are not infrequently accompanied by damage of the vasculature sup- plying the tegmentum. I n an effort to obtain further in- formation on the subject of changes in reflexes after lesion of structures other than the cortico-spinal system stereotaxic lesions were placed in the brain-stem of several cats from which the six animals now reported were chosen. Of these, two showed contralateral and two ipsilateral hyperreflexia, while two exhibited no consistently unequal reflexes. The lesions produced are shown in the accompanying schema

Cat 272 Lesion. The most rostral portion of the lesion in this animal extends

to the level of the rostral part of the medial geniculate body where it is represented by three nearly confluent needle tracts lying in the area indicated in figure 1 A. From this point caudally it occupies the lateral half of the tegmentum as indicated in figure 1 B-F. It does not involve the substantia nigra except at the level of the interpeduncular nucleus, where the lesion infringes upon the dorsolateral edge of the cerebral peduncle. Its most caudal extent is at the level of the superior olive.

(fig. 1).

113

114 F. A. METTLER AND F. T. ZIMMERMAR

Fig. 1 Diagrams of lesions in the six eats discussed in the text. In animals 272 and 273 the side of the lesion and reflex exaggeration were identical. I n 277 and 279 the side of reflex exaggeration was the opposite of that containing thc lesion. In 280 and 312 no consistent reflex inequality was observed.

HOMOLATERAL REFLEX EXAGGERATION 115

Physiological. The day after operation this animal was seen to circle toward the side of the lesion and fall toward the opposite side. It was weak on the side of the body homolateral with the lesion and the hind leg was employed with difficulty, the locomotor pattern being grossly ataxic. The opposite side of the body was hypoesthetic and both sides of the face showed a reduced sensitivity to stimulation. The pupils were unequal, that of the opposite side being wider. The knee-jerks were unequal, that of the same side was markedly overactive and that of the opposite side ,was nearly absent.

Three days after operation the animal was more seriously disabled. In addition to an aggravation of the signs noted above, there was now a dystonic head jerk which appeared when movement was attempted.

A week after operation the pupillary inequality noted above was still apparent. The homolateral nictitating membrane was relaxed. Some sensitivity had returned in the opposite side of the face. There was no longer any particular tendency to turn while walking. Locomotion was carried out on a grossly widened base and there was a tendency to shift the weight to the contralateral side. The homolateral hind leg usually collapsed when weight was put upon it and the animal walked on the whole of the metatarsal plantar surface of this leg, instead of merely upon the foot pad. The ipsilateral foreleg was overextended during locomotion.

Sixteen days after operation (killed this day) the animal still displayed the very abnormal locomotor pattern which has been previously described as following section of the brachium pontis (Mettler and Lubin, '42). Thus, the pelvic girdle was carried to the contralateral side of the line of progression. The base was widened, especially posteriorly, and the homolateral hindpaw was the least certain of the four. The homolateral foreleg was overflexed and overextended in walking and was crossed before the contralateral foreleg. A very marked lateral swaying movement, especially in the hind quarters which were swung from side to side, was present during walking. The tail was swung in a normal fashion. The homolateral palpebral fissure and pupil were narrower and the contralateral side of the face was more sensitive. No corneal opacities had developed. The knee jerks were overactive and unequal, that of the homolateral side being more pronounced. Placing reactions were present in both forelimbs but absent in the homolateral hind limb.

Degelzeration. The degenerations resulting from the above and following lesions are shown for purposes of brevity and comparison in tabular form (table 1) ; see also figures 2 to 4.

116 F. A. METTLER AND F. T. ZIMMERMAN

~~~ __ ~

Vent. limb brach. 1

Remainder of braeh. con j . I++++ conj. I

Med. lemn. ++++ Lat. lemn. ++++ Spinothal. tr. ++++ Quintothal. tr. ++++

TABLE 1

Tabular representation of amount of degeneration in various long fiber systems

i s separated f r o m the rest of t h i s system f o r , in $73 and 273, it represented the only par t of th i s bundle which was degenerated.

in animals presented. T h e ventral part of the brachium conjunct ivnm

279 1 280 312 I 277 ~ - -

I i 272 I 2 7 3 -

~

Ascending

++++ + ++++ ++++ ++++ ++++

i +++ + + +++

~ ++

++++ +++

I + + + +++ ++++++++ +i++ ++++ 1

Descending

-

Dese. lillllJ. brarh. conj.

Mes. V. Spinal V. T'iicrossed rrticulosp. Rubrosp. Pyramid Lat. restibsp. Med. vestibsp. Tectosp. tr. Cerebral ned.

~~ ~

I

+++ it:+ ++ I + + ++++ ++++ +++ '+

I /++ I + + + + + + + I + + +

~ ++++, I

++ I

i +++ ++++ ++++ I ++ I ++++ ++

Cat 27'3

Lesion. The most rostra1 extent of the lesion is encountered at the level of the medial geniculate where two fused needle tracks, lying in dorsoventral relation, form a fused lesion the most ventral part of which is the most extensive and lies squarely in the substantia nigra (fig. 1 A ) . The most dorsal part lay medial to the middle of the medial geniculate and in the area occupied by the spino-thalamic tract. At the level of the red nuclei (fig. 1 B ) the lesion destroys the lateral part of the substantia nigra and the area of the strio- pednncular tract, as given by Papez ( '29, fig. 164). The dorsolateral ctlpc of the cerebra! peduncle is involved. At levels through the


inferior colliculi (fig. 1 D-E) the lesion is almost identical with what was seen in cat 272 but, jtst caudal to the inferior colliculus, the lesion is less wide and extends farther dorsomedially than that in 272 (fig. 1 F). At levels through the exit of the facial nerve the most caudal part of the lesion ends in two tails one of which terminates between the superior olive and pyramid while the other lies just dorsomedial to the nucleus of the spinal root of the trigeminus and encroaches slightly upon this, destroying the area traversed by the facial nerve and tract of Probst.

Physiological. The day after operation the head was rotated over the homolateral shoulder. The vertebral column displayed a slight sigmoid curvature in which the anterior convexity was toward the contralateral and the posterior to the homolateral side. There was moderate exaggeration o€ extensor tonus in all four extremities, more particularly in those of the contralateral side. The animal engaged in spontaneous, tremulous, treading movements in which the tremor was marked during flexion. There was also some tremor in the hind limbs while the animal was a t rest. There was no nystagmus. The pupils were equal.

On the following day the appearance of the animal was quite otherwise. I ts head was now rotated over the contralateral shoulder. There was extreme extension of the homolateral foreleg which exhibited a definite clasp-knife reflex. The cat had a tendency to turn toward the contralateral side and, like many animals with vestibular damage, showed periodic backing movements. There was no obvious tremor and the treading movements had ceased. The homolateral pupil had become slit-like, the contralateral was normal. There was some enophthalmos and the homolateral eye was developing an opacity.

Four days after operation the animal still maintained the position noted above in which the sigmoid curve of the vertebral column was the reverse of that originally described. The cat would not lie on the contralateral side. Placing reactions were obscured by tonic twisting. If suspended horizontally, a pronounced extensor thrust appeared in the contralateral hindlimb. When held up by the scruff of the neck the tail was swung round and round in clockwise direction with regard to the anus (lesion on left side). There was no tremor and no nystagmus unless the head was forced toward the homolateral side. When the animal lay on the homolateral side it exhibited moderate emprosthotonos and kept its homolateral forelimb stiffly extended. In \Talking it turned toward the contralateral side.

Eight days after operation the situation was substantially the same as that described on the fourth. The knee-jerks were unequal, being more pronounced on the homolateral side. The findings remained the same until the animal was killed on the fourteenth postoperative


day. The homolateral pupil retained its slit-like shape until opacity and proptosis obscured further opportunity to observe it. As the animal’s locomotor capacity improved, it became apparent that the homolateral forelimb exhibited oversteppage. The tendency to keep the vertebral column hunched also endured although the backing movements disappeared. The homolateral knee-jerk remained more pronounced than the contralateral.

Cat 277

Lesioiz. The lesion entered the mesencephalon at the side of the superior colliculus and swept beneath this (fig. 1 A-C), effectively disconnecting this structure from the rest of the mesencephalon. It terminated just rostral to the inferior colliculus. At the level of the red nuclei the central gray was involved. After passing out of the brain-stem the lesion cut off the brachium pontis of the same side.

Physiological. The day after operation and for 19 days thereafter this animal was found to walk well and was able to traverse a bar. There was some tendency to walk in wide circles to the contralateral side. The contralat3ral extremities showed awkwardness in scratching or in “polishing up’’ and some impairment of placing reactions. The contralateral extremities also showed some slight overextension in walking and, when held upside down, these were held in marked extension. The pupils were equal. Both knee-jerks were very overactive, the contralateral more so. This cat preferred to lie on its cwntralateral side.

Cat 279

Lesioiz. The most rostral part of the lesion is seen at the level of the medial geniculate body where it appears as a curved wedge lying between the lateral edge of the superior colliculus and medial d g e of the medial peniculate. The apex of the lesion infringes upon the central gray (fig. 1 A ) . At the level of the red nucleus the lesion occupies a wedge-shaped area which begins just ventral to the superior colliculus and extends dorsal to the cerebral peduncle. Its apex still is plunged into the central gray (fig. 1 B) . Farther caudally (fig. 1 C-F) the lesion occupies a position which destroys the lateral portion of the tegmentum and it finally ends (fig. 1 G) as a narrow, oblique, necrotic area which lies just lateral to the dorsal half of the lateral course of the facial nerve.

Physiological. On the day after operation the animal was found to have unequal pupils the homolateral being the smaller. There was a homolateral facial paresis and anesthesia. The gait was very ataxic,


especially in the hind-quarters. Two days after operation it was obvious that the animal was weak on the homolateral side. The contralateral forefoot was abducted and externally rotated and the weight was shifted toward this side.

Three days after operation the homolateral hindleg was found particularly weak, collapsing when weight was put upon it. The extensor tone of the homolateral forepaw was exaggerated and this limb was kept extended, no matter in what position the animal was placed. The cat lay on the contralateral in preference to the honio- la1 era1 side. Placing reactions were deficient homolaterally. The knee-jerks were unequal, the contralateral being the greater.

On the day the animal was dispatched (nineteenth postoperative) the situation was essentially the same except that the contralateral as well as the homolateral hindleg had developed a tendency to collapse and the animal could no longer walk about. The homolateral eye had become opaque and proptosed.

Degeneration. The degeneration resulting from lesions 277 and 279 is shown in tabular form in table 1. I n comparison with that encountered in cases 272 and 273 it is apparent that, since the brachium pontis was involved in all four animals two of which exhibited the greatest knee-jerk contralaterally and two homolaterally, it is impos- sible for this alone to be the determining factor. In both cases 272 and 273 the brachium conjunctivum was involved, particularly its descending limb. Although in case 279 the animal also suffered some damage to this efferent cerebellar system, it may be well to examine what happens when the brachium conjunctivum is extensively damaged with a minimum of injury to other structures.

Cat 280

Lesion. The most rostra1 portion of the lesion entered the medial part of the superior colliculus a t the level of the medial geniculate (fig, 1 A ) . It then passed caudally, lateral to the central gray and medial to the innominate nucleus and terminated at the level of the middle of the inferior colliculus where it destroyed most, if not all, of the brachium conjunctivum.

Physiological. On the day following operation, and thereafter until killed (17 days after operation), the animal was found to stand and walk well though slowly. There was no evidence of ataxia nor of any abnormal movements. The homolateral pupil was larger than the contralateral. There was some impairment in the placing reaction of the contralateral forepaw and this showed a barely perceptible increase in extensor tone. The animal preferred to lie on the homolateral side. There was no consistent inequality in the knee-jerks but,


when such inequality was found, the contralateral jerk was the more pronounced.

Degeneration. Aside from some local degeneration the only fibers taking the Marchi stain are the main ascending part of the brachium conjunctivum and its descending limb. There was no notable involve- ment of the ventral limb of the brachium. The possibility that the cerebral peduncle or substantia nigra are solely responsible for reflex alteration can be discarded from a consideration of the following case.

Cat 312

Lesion. The most rostra1 portion of the lesion destroys the medial half of the substantia nigra and cerebral peduncle at the level of the medial geniculate. From this point the lesion progresses caudally, retaining its position in the substantia nigra and cerebral peduncle until its end which lay at the upper border of the pons and which is very slightly involved in the lesion.

Physiological. During the two postoperative weeks this animal was allowed to live it never showed detectable alteration in behavior. The' knee-jerks were equal and not exaggerated.

SUMMARY

The physiological evidence presented above supports 'the belief that the cortico-spinal pathway is unrelated to the decp reflexes in cats. Thus, in case 272, in which the pyramid was hemisected, the side on which the reflexes were exaggerated was homolateral with the lesion and, in case 312, in which the cerebral peduncle was fulgurated and both cortico-pontal and cortico-spinal fibers could be seen to be degenerated, no reflex inequality was encountered. The brachium pontis was severed in cases 272, 273 and 279. I n two of these, the lesion was homolateral with the extremities in which the reflexes were exaggerated. In one (279) the situation was reversed. Ap- parently damage to the cortico-pontine > ponto-cerebellar circuit cannot be solely responsible f o r the alteration of reflexes.

- .- . - .~ - -

Fig. 2 Degeneration emanating from ventral limb of brachium conjunctivum. IP, interpeduncular nucleus. A, animal 273, level of D, figure 1; arrows indicate course of fibers from ventral limb. B, animal 272, level of E, figure 1; arrows indicate degeneration in descending component of ventral limb ending in opposite reticulo-tegmental nucleus. C, same animal, level of D ; arrow shows degeneration in descending component of ventral limb, after crossing. D, same animal, level of C; both the decussation and the descending component of the ventral limb (arrows) are shown.

HOMOLATERAL B E F L E X EXAGGERATION 121

122 F. A. METTLER AKiL) F. T. ZIILIMEI;I17AS

This conclusion is fnrtllcr fortiiicd by a consideration of case 280 in which, although tlic brachium corijunctivum was damaged, no consistent inequality appeared. I n cii ses 272 ; ~ n d 273 the sides of tlic lesion a i d cswggcration of reflcxcs u ~ r c identical. Rotli of these animals suffered cstciisivc

Fig. 3 A. Re1:itiw liositions of t,lic rub~-spi~i : r l , direct rcticulo-spiii:il :I tic1 cortico-spinal systciiis :it the level of the pyr:miidal dconss:it,ioii (c:i.t “2) ; PVR., eortico~sliinnl fibcis; RETIC’S l’., i,iiertrxsed ~ ~ , t . i ( ~ ~ i l ~ - s p i ~ i : ~ I fi t i n s , RH., mlmi- spinal t ract . R. 1oc;itioii of comniissiirnl fibers in anterior i i ltdii l l:~ry reliini (eat 272) .

damage of the tegineiiturn a id if tlic path responsible for exaggeration does not travel in tlic pyramids o r through tlic cortico-pontine >poiit()-cerebellar circuit, as appears from tlic above, it is scawely surprising to find it in the tegmentum. That it should have already crossed at such levels as arc indicated by the lesions in 272 and 273 indicates that the shift

HOMOLATERAL REFLEX EXAGGERATIOX 123

in sides must occur a t riieseiiceplinlic levels o r higher. In both 277 and 279, which showed coiitralateral reflex exaggeration, the lesion traversed the area occupied by the fibers of passage between teleiiceplialic extrapyramidal mechanisms arid those situated at more caudal levels. It is difficult to say precisely which tracts are respoiisible for the alteration of the 1-eflcxes. Tlie common, ipsilateral long system damage in cases

Fig. 4 A. Relative positions of rubro-spinal, direct reticulo-spinal and cortico- spinal systems at cord levels (cat 272) ; PYR., rortico-spinal fihers, RETICS., uncrossed retieulo-spinal fibers, RS., ruhro-spinal tract. B. Position of descending limb of brachiurn conjunetivurn (cat 280) ; DLBC, descending limb of brachiurn eonjunetivum after drcussation, SCN, superior central nucleus.

124 F. A. METTLEB AND F. T. ZIMMERXAN

2T2 and 273 wras tlic direct reticulo-spinal arid tlte rubiw-spinal tract. ITowevcr, the rubro-spinal system w a s also soniewltat damaged in 279 in which the side o i i whiclt the i d e x e s TVCIT

most active was contralatwal to the lesion. Tn cases 277 and 279 which both showed contralateral hyperreflexiw tlie conirnori factor was yrerubral damage. While the evidence secnis to point to disturlnance of the outflow from the red nuc~lcus as tlie factor responsible for enhancement of tlic reflexes, it i. rieccssary to assumc (case 279) that slight rubro-spinal darn;igc is ineffective. Certwiiilp intcriwption of tlic i.eticulO-si)iitiil system caiiiiot be excluded as the causative factor.

Although the superior colliculus was disconnected iit ca scs 377 and 270, no evidence of a lateral or uncrossed tccto-spinal tract could be discovered. I n none of the preceding experi- ments could the csistence of desccnding fibers in the position of the so-called central tegmental tract be substantiated. Neither could a specific system be found passing from the substantia nig1.a to the striaturn. The organization of tltc vestibulo-mc~ericcphalic arid vcstibulo-spinal tracts, as give11 by Papcz, caoulcl bc easily verified and his plan of thc reticulo- spinal apparatus, though we have only fi-agmentsry data upon it, appears to be substantially correct. In the region of the Slccussation of the pyramids the reticulo-spinal tract slips ventrally, lateral to the cortico-spinal (fig. 3 A ) . Thc rubro-spinal occupies the latcroventral concavity of tlic central gray colunin. The relative positions of these tracts in tlic cord are shown in figure 4 A.

I n anirnal 272, in sections just caudal to the inferior colliculus, the area just rostra1 to the masticator iiuclei was interconnected by coriimissural fibers which passed through the substance of the anterior nicdullary velum (fig. 3 R) . Some of these fibers cut through the medial edge of the brachiuni conjunctivum. They lic lateral to Probst’s tract. Such fibers a re not seen after complete clegenci*ation of tlic bracliium conjunctivum. ITe do not lriiowr precisely w1ier.c they originate.

HORIOLATERAL REFLEX EXAGGERATION 125

The organization of the feline brachium conjunctivum is more complex than is indicated by conventional descriptions. Thus, in levels through the superior central nucleus (central reticular nucleus), a significant number of its fibers have already filtered ventrally from the main body and lie loosely arranged along the dorsolateral edge of the medial lemniscus. The cxtreme lateral position of these fibers, which constitute the homologue of thc vcntral limb of the primate brachium conjunctivum, is surprising and it is possible for them to be destroyed without interfercrice with the main body of the structure. As onc proceeds rostrally they course mediallp and, encountering the interpeduncular nucleus, clamber up over its dorsal surface (fig. 2 A). After reaching the opposite side, some of them turn caudally and terminate in the reticulo- tegmental nucleus (ventral reticular nucleus, nucleus reticularis of Bechterew) as indicated in figure 2B. Noric run caudal to this point. Retracing these fibers (fig. 2 C-D), they are observed to lie in the position wliich Papez indicates as the descending limb of the brachiurn conjunctivum (Papez, '29, figs. 162, 163, dbc). Not all of the fibers wliich cross over the dorsal aspect of the intcrpeduncular iiucleus descend. Many contiiiuc rostrally and have the same oral distribution as the remainder of tlic brachiurn conjunctivum.

In lesion 272 the reticulo-tegmental iiucleus on the side opposite the lesion also received degenerated fibers from the lesion. Control preparations show that these fibers do not originate from the cerebellum. They pass into the nucleus at lower levels than those from the latter structure and pass directly across the midline through the area which Papez ( '29, fig. 162, re) indicates is occupied by the reticnlo-cerebellar fibers which he believes originate in the reticulo-tegmental nucleus. Beyond the fact that they traverse some area con- tained within lesion 272 (see fig. 1 F) we do not know what their origin is.

The main body of the brachiurn conjunctivum also sends fibers to the reticulo-tegmental nucleus. Since this descending limb of the brachium conjunctivum is larger and contains

1% F. A . METTLER A N D F T. ZIMMEKMAN

VENT. 6 ARC.

R E T I C T E ~

UNCROSSED

DESC LIMB

Fig. 5 Sclicnia of distribution of some of the components of the brachium conjunctivum. The following abbrevntions are not obvious : PONTEG., pontal tegmental nucleus ; RETICTEG., reticulo-tegmental nuc. (ventral reticular nuc., nuc. reticularis Bechterew) ; S.C.N., superior central nuc. ; 272, degenerated fibers peculiar to lesion 272.

H O M O L A T E R A L R E F L E X EXAGGERATION 127

more diversely distributed fibers than those which arise from the ventral limb alone it is indicated in table 1 as the descending limb of the brachium conjunctivum. Thus in case 280, where the ventral limb was undegenerated, an abundance of black fibers passed medially to the opposite side through the decussation of the brachium conjunctivum. Once across the midline, many of these fibers turned caudally and passed downward just lateral to the superior central reticular nucleus (fig. 4 B ) . They occupied the entire area between the deep tegmental and reticulo-tegmental nuclei. It is remotely possible that these fibers constitute the group sometimes called lateral tecto-spinal tract but they have a crossed course and what is usually considered the medial part of the tecto-spinal system was undegenerated. Some degenerated fibers passed from the ventral part of this group to the reticulo-tegmental nucleus. Others ran from the dorsal part to the deep tegmental nucleus while still others made their way into the pontal tegmental nucleus. Many con- tinued caudal to the pontal tegmental nucleus and, pursuing a direct course, became fewer in number. The remainder passed the dorsomedial edge of the inferior olive and the level of the decussation of the pyramids, from which they lay lateral. Some could be traced into the medial part of the ventral column of the cord, one or two traveling as far as the lumbar enlargement.

CONCLUSIONS

1. Exaggeration of the knee-jerk in the cat is not related to damage of the pyramid o r substantia nigra nor to injury of the brachium pontis or brachium conjunctivum.

2. Lesions of the tegmentum are sufficient to evoke inequality of the knee-jerk. If the lesion is below the level of the red nuclei the more active reflex is on the side of injury. If the lesion involves prerubral areas, that is, areas of passage of fibers from telencephalic extrapyramidal mechanisms, the greater reflex is on the contralateral side.


3. It is not clear which pathways must be duuiaged to produce exaggeration of reflexes. Present evidence indicates that iriterfercnce with the normal function of the uricrossed rcticulo-spinal or rubro-spinal systems or both may be responsible. 4. Tlie data at hand do not support the existence of a feline

lateral uncrossed tccto-spinal tract, a significant ascending nigro-striatal tract, cerebellar afferents in the brachiurn conjunctivum, nor a definite descending central tegmental tract, apart fi-orn fibers to tlic inferior olive.

LITERATCRE CITED

MBTTLER, FRED A,, AND A. J. LIJBIN 1940 Tcrniination of the brnchium pontis.

PAPEZ, J. W. 1929 Compnrntivc neurology, Thomas Y . Crowcll Co., N. Y., .J. Comp. Neur., vol. 77, pp. 391-307.

pp. 518; see iiidicatcd pages and figures.

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Homolateral reflex exaggeration after brain-stem lesion