Paralytic pontine exotropia in subarachnoid hemorrhage. A clinicopathological correlation

269

PARALYTIC PONTINE EXOTROPIA IN SUBARACHNOID HEMORRHAGE. A CLINICOPATHOLOGICAL CORRELATION L. Crevits, J. de Reuck and H. vander Eecken”

SUMMARY A syndrome of combined right lateral gaze palsy and right internuclear ophthalmoplegia, followed by a left exotropia in a case of subarachnoid hemorrhage is presented. At necropsy a single small pontine end-zone infarction was found, involving the medial part of the right paramedian pontine reticular formation, the tectospinal tract and the ventral part of the right medial longitudinal fasciculus. The fila radicularia of the right abducens nerve passed through the necrotic area. The mechanism of these characteristic ocular motor disturbances in relation to the post mortem are discussed.

findings

and the topopathogenesis

of the pontine

infarction

INTRODUCTION

The term ‘ophthalmoplegia internuclearis’ was first used by LHERMITTE in 1922 (cited by SMITH and COGAN, 1959) to describe a clinical syndrome, characterized by a paresis of a medial rectus ocular muscle on attempted conjugate lateral gaze, with nystagmus predominantly of the abducting eye and caused by a lesion of the medial longitudinal fasciculus ipsilateral to the paresis of adduction. This syndrome may be transient or permanent (HARRINGTON, HOLLENHORST and SAYRE, 1966). COGAN (1956) subdivided the internuclear OphthaImoplegia into an anterior mesencephalic and a posterior pontine type according to whether convergence was impaired or not. Although it has been described in brainstem tumors, encephalitis, Arnold-Chiari malformation, syringobulbia, neurosyphilis, myasthenia gravis, Wernicke encephalopathy, subacute necrotizing encephalomyelopathy and head injury, the most common causes are multiple sclerosis in case of bilateral internuclear OphthaImoplegia, and vascular disease of the basilar artery due to occlusion of one of the perforating branches in case of unilateral internuclear ophthalmoplegia (COGAN, 1956; SMITH and COGAN, 1959; KUPFER and COGAN, 1966; WALSH and HOYT, 1969; COGAN and WRAY, 1970; MONTPETIT, ANDERMANN, CARPENTER, FAWCETT, ZBOROWSKA-SLUIS and GIBERSON, 1971: CAMBIER, MASSON and LECHEVALIER, 1972; SATO, SUGITA, OOKOCHI, SUZUKI and UMEI, 1974). In a simplified way it can be stated (PENFIELD and JASPER, 1954; TRUEX and CARPENTIER, 1969; SACHSBNWEGER, 1969; ASTRUC, 1971; DE RECONDO, 1971; ” Department of Neurology, University of Ghent, Belgium. Clin. Neurol. Neurosurg. 1975-4

270 %EE, ~~IE~~LlcH

l973a; ZEE, GRIFFIN ZiIlCi PKKE. 1974b) th:tt gaze arise from the frontal gaze center and those fol

and ROBINSON,

impulses for voluntary

reflex i’ixation mechanism from the occipital gaze center. Corticofugal mediating conjugate horizontal eye nl~}venlents, traverse the midbrain

pathwqh. tegillent~i~l

and descend to the ‘pontine gaze center’. The latter has been situated in the vestibular nucleus, in the pontine reticular substance and in or near the abducenx

nucleus (para-abducens center of CROSBY, 19.53). Each pontine center transmits impulses to the ipsilateral abducens nucleus and by way of the medial longitudinal fasciculus to the nucleus of the contralateral medial recuts muscle. Despite the important role of the medial longitudinal fasciculus and of the paraand median pontine reticular formation (CHRISTOFF, ANDERSON, NATHANSON BENDER, 3960) there is little detailed information about the anatoi~ical changes associated with pontine lesions which produce conjugate ocular motor disturbances in man. In most instances, the lesions are so extensive that a dinicopathoIogica1 correlation can not reliably be made and most deductions are influenced by experimental observations in animal (COHEN, KOMATSUZAKI and BENDER, 1968; GOEBEL, ~OMATSUZAKI, BENDER and COHEN, 1971; COHEN and HENN, 1972: COHEN and KOMATSUZAKI, 1972). The present study attempts to correlate the combined lateral gaze palsy, the internuclear ophthalmopiegia and the exotropia with the pontine infarction observed in a case of subarachnoid hemorrhage and the responsible mechanism is briefly discussed.

CLlNlCOPATHOLOGICALOBSERVATION

4.5year-old woman was admitted to the neurological department because of sudden coma with generalized convulsions and vomiting. The previous history included only hype~ension. The neurological examination revealed a deeply comatose woman with signs of meningeal irritation. Both pupils reacted to light. The eyes could be moved in al1 directions by the doll’s head manoeuvres. There was flexion hypertonia of the upper and extension hypertonia of the lower limbs. The tendon reflexes were brisk with bilateral ankle clonus, however, without Babinski’s responses. On painful stimuli the patient moved inconstantly arms and legs. The fundoscopic examination showed retinal hemorrhages on both sides. Except for the high blood pressure (200/~45), the physical examination was unremarkable. There were no signs of hemorrhagic diathesis. Bilateral carotid and right vertebra1 arteriographies, immediately performed, did not reveal any abnormality, apart from an important slowdown of the cerebral blood flow, On lumbar puncture a grossly bloody fluid under an extremely high pressure was found. (520.000 Rbc/mm3, p > 600). The electroencephalogram showed a generalized irritative dysrhythmia. Intravenous hypertonic fluid, antihypertensive drugs and steroids were given. A

271 The dilatation

next

day

the

patient

of the left pupil,

alert, some ocular

motor

was

less comatose

still reacting disturbances

and

presented

an interm:ttent

to light. Two days later, when she became could

be evaluated:

during

attempted

left-

ward gaze, although both eyes had a midline position at rest, the right eye by no way did adduct. During attempted rightward gaze neither of the eyes could move beyond the midline. Nystagmus was absent. Vertical gaze, eyelid function, pupiliary reactivity to light and to convergence were normal. No other neurological deficits were present. Three days later the ocular motor findings were changed by the development of a left exotropia of about 25 degrees (fig. I). During attempted Ieftward gaze, the right eye did not adduct but the left eye abducted fully without nystagmus. The right eye could not abduct, but the left eye adducted very slowly up to the midline position on refixation and persuit attempts to the right. Horizontal weak-

Fig. 1: Left exotropia (top); adduction of the exotropic eye to the midline during attempted rightward gaze; full abduction of the exotropic eye during attempted Ieftward gaze. The right eye does not move horizontally. Conjugate gaze in the vertical plane is preserved.

212 ness of eye movements was not overcome by oculocephalic manoeuvres. Vertical gaze was normal except for the persistence of the left exotropia. Pupillary reactivity and convergence remained intact. Ptosis of the eyelids was absent. The further neurological examination was characterized by nuchal rigidity, bilateral papiliedema with fresh retinal hemorrhages, generalized hyporeflexia and hypotonia with brisk movements on pain stimulation. The electroencephalogram showed a more severe generalized dysrhythmia. Although the clinical picture was suspect for an arachnoid hemorrhage from an anterior communicatin,g artery aneurysm, the btai-nscanning and repeated bilateral carotid as well as bilateral vertebral angiographies were normal. One week later the patient needed assisted respiration for a few hours because of a sudden apnea. She was again more stuporous and presented vitreous hemorrhages in both eyes. A new lumbar puncture revealed an uniformly bloody cerebrospinal fluid under increased pressure (520.000 Rbcimm”, p = 5401, indicating a recurrence of the subarachnoid hemorrhage. The patient became progressively more comatose in the next few days. Repeated lumbar punctures revealed each time bloody cerebrospinal fluid under increased pressure although high quantities of fluid were evacuated. The ocular motor disturbances were unchanged. The further evolution was characterized by the occurrence of a gastro-intestinal bleeding and autonomous dysfunctions leading to death three weeks after admission. The brain was removed 24 h. after death and weighed 1430 g. The skuli and dural sinuses appeared normal. A fresh flat subdural hemorrhage was present over the convex face of the left cerebral hemisphere. There was marked atherosclerosis of the arteries of the circle of Willis. No occluded vessel nor aneurysmal dilatation could be observed. Clotted blood was mainly present at the base of the frontal lobes, around the optic chiasm and the olfactory nerves, and in the longitudinal cerebral fissure. The external surface of the cerebral hemispheres was normai, without softening or asymmetry. Coronal sections were unremarkable except for the presence of the subarachnoid hemorrhage on the ventro-medial surface of both frontal lobes. The ventricular system was filled with liquid blood. Horizontal sections through the brainstem and the cerebellum did not reveal any macroscopically visible lesion. Serial sections were made of the frontal cortex and white matter, bordering the longitudinal cerebral fissure, and of the brainstem. They were stained with hematoxylin-eosin and phosphotungstic acid hematoxylin for light microscopic examination. The leptomeninges around the frontal lobes and in the longitudinal cerebral fissure were invaded by a large number of fresh red blood cells but also by many macrophages loaded with hemoside~n pigments. Some leptomeningeal arteries were narrowed by atheromatous plates and showed a variable degree of degeneration of the media and the elastica. No thrombosis nor dilatation of these vessels, and in particular of the anterior communicating and anterior cerebral

273 arteries were observed. Most neurons of the cerebral cortex of the straight and orbital gyri were pyknotic and the neuropile had a spongy appearance. There was a mild proliferation of fibrous astrocytes, more pronounced in the superficial layers of the cerebral cortex. The other regions at some distance from the major subarachnoid hemorrhage had a normal appearance. On serial sections of the brainstem a small necrotic area was observed in the right paramedian dorsal part of the pons, extending from the level of the facial coiliculus to the level of the caudal border of the pons. This softened area had a rectangular shape of 3 mm. length in ventro-dorsal direction and 2 mm. width. it contained many fatty macrophages and was surrounded by a small band of fibrillary astrocytes. The lesion was sharply bounded. No occlusion of the deep perforating arteries could be demonstrated. In its upper part it involved the medial part of the right paramedian reticular formation and of the tectospinal tract and the ventral part of the right medial longitudinal fasciculus. At its lowest level the infarction involved only partly the right tectospinal tract and the medial part of the paramedian reticular formation. The lowest fila radicularia of the right abducens nerve passed through the infarcted area. The nucleus of the abducens nerve, the germ of the facial nerve, the thalamo-olivary tract and the lemniscus rnedialis were spared. The other nuclei and tracts also were unaffected; especially the nuclei of the trochlear and oculomotor nerves, the medial nucleus of Perlia and the medial longitudinal fasciculi in the upper pons and mesencephalon were well preserved (Fig. 2).

IXSCUSSION

Three days after the onset of the subarachnoid hemorrhage, some distinctive ocular motor disturbances appeared when the patient became alert: conjugate movements of both eyes to the right and of the right eye to the left were lost, as well on voluntary efforts, on pursuit attempts as on oculovestibular stimulations. Nystagmus was absent. Both eyes, however, had a midline position at rest and the convergence was not disturbed. The preserved eyelid function, pupihary reactivity and vertical gaze also argued for the integrity of mesencephalic ocular motor functions. Clinical differentiation between bilateral internuclear ophthalmopleg~a with concomitant right abducens palsy, and right posterior internuclear ophthalmoplegia with concomitant right lateral gaze paralysis was difficult. The absence of convergent strabismus in the primary position rather pointed to an unilateral lesion. In addition, three days later the patient developed a left exotropia of about 25 degrees, while the mesencephalic ocular motor functions remained intact. The preserved adduction of the exotropic eye just to the midline on refixation or pursuit attempts suggested that the medial longitudinal fasciculus projecting to the nucleus of the left medial rectus muscle probably was spared. At necropsy, a single small infarction of about three weeks old was found in the right paramedian dorsal part of the pons, extending from the level of the facial colliculus to the

274 Fig. 2: Horizontal scct~on through the mesencephalon. The nuclei of the oculomotor nerves (III), the medial nucleus of Perlia (P) and the medial longitudinal fasciculi (MLF) are preserved (HEX. 30 x). B Horizontal section through the lower pons. A small infarction is observed involving the tectospinal tract (TST), the paramedian pontine reticular formation (PPRF) and the fila radicularia of the abducens nerve (VI) on the right Gde (HEX, 30 x ).

level of the caudal border of the pans; rostrally the medial part of the tectospinal tract, the medial part of the paramedian pontine reticular formation and the ventral part of the right medial longitudinal fasciculus were involved; caudally there was a lesion of a part of the tectospinal tract and of the param~dia~ reticular formation. From the latter, according to the classification of OLSZEWSKI and BAXTER (1954), the nuclei gigantocellularis and pontis caudalis were partly destroyed. The left paramedian pontine reticular formation, the left medial longitudinal fasciculus as well as both facial colliculi were preserved. The fila radicularia of the right ahducens nerve passed through the necrotic area. FISHER (1967) termed the combination of a lateral gaze palsy in one direction and an internuclear ophthalmoplegia in the other direction the ‘one-anda-half syndrome’ and pointed it to an unilateral pontine lesion. Exotropia was

275 described exotropia

as an inherent feature. GONYEA and COLLINS (1974) considered the as indicative of contralateral involvement whereas SCHARPE, ROSENBERG, HOYT and DAROFF (1974) owed it to tonic horizontal ocular deviation in the acute phase. They introduced the term ‘paralytic pontine exotropia’. In the present case the lesion of the right paramedian pontine reticular formation is held responsible for the ipsilateral gaze palsy, and the involvement of the right medial longitudinal fasciculus for the ipsilateral internuclear ophthalmoplegia. If the left exotropia is due to tonic activity of the left paramedian pontine reticular formation, the failure of the right eye to deviate could be explained by the right internuclear ophthalmoplegia. It is noteworthy that exotropia only occurred a few days after the onset of the combined contralateral internuclear ophthalmoplegia and horizontal gaze palsy and that it remained constant for about two weeks until death occurred. It must be stated that fibres arising from the paramedian pontine reticular formation project into the ipsilateral abducens nucleus before they pass through the facial colliculus, crossing the midline to the contralateral medial longitudinal fasciculus. This distinctive syndrome of pontine paralytic exotropia, mainly characterized by horizontal immobility of one eye and paralytic lateral deviation of the other eye, indicates a lesion of the pontine tegmentum contralateral to the deviated eye, involving the paramedian pontine reticular formation and the medial longitudinal fasciculus. In this case of subarachnoid hemorrhage the syndrome is caused by an infarction. The invasion of the leptomeninges by fresh red blood cells as well as by macrophages indicates relapsing bleedings. Previous authors mentioned ischemic changes in subarachnoid hemorrhage (SMITH, 1963). In this case the clinical signs, such as papilledema, vitreous bleedings, intermittent anisocoria, the findings on lumbar puncture and the post mortem observations such as the fresh subdural hemorrhage, the ischemic lesions in the frontal cortex and the presence of bIood in the ventricular system, prove the existence of intracranial hypertension which can account for compression of arteries (LINDENBERG, 1963), one of the preferential sites being the pontine paramedian branches of the basilar artery (LINDENBERG, 1959). The location of the infarction near the ventricular wall corresponds to an end-zone distribution (DE REUCK, 1971) of these branches, which is one of the most vulnerable sites to ischemia.

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