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Internuclear ophthalmoplegia in tuberculous meningitis
0041-3879/89/0070-0061/$10.00
Tuberc/e(1989)70,61-64 0
Longman
Group
UK
Ltd 1989
INTERNUCLEAR
OPHTHALMOPLEGIA
R. Teoh,” M. J. Humphries,S Departments
IN TUBERCULOUS
MENINGITIS
J. C. N. Ghan,* H. K. Ng,t G. O’MahonyS
of Medicine* and Morbid Anatomy, t Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong and the Ruttonjee Sanatorium,S Hong Kong
Summary Two patients with tuberculous meningitis and internuclear ophthalmoplegia are described. Despite treatment with anti-tuberculosis chemotherapy and corticosteroids, both patients died. In one case autopsy showed severe basal meningitis with diffuse brain stem infarction secondary to widespread vasculitis.
L’auteur decrit le cas de deux d’ophtalmoplegie internucleaire. chimiotherapie antituberculeuse des cas, I’autopsie a montre une tronc cerebral, consecutif a une
malades atteints de meningite tuberculeuse et Les deux patients sont decedes malgre une et I’administration de corticosteroides. Dans un meningite basale severe avec infarcissement du vasculite largement repandue. Resumen
Se describe el case de 2 enfermos de meningitis tuberculosa y oftalmoplegia internuclear. Los 2 pacientes fallecieron a pesarde una quimioterapia antituberculosa y la administration de corticoesteroides. En uno de 10s cases la autopsia demostro una meningitis basal severa con infattacion difusa del tronco cerebral, secundaria a una vasculitis ampliamente extendida. Introduction The prognosis of tuberculous (TB) meningitis is closely related to the clinical stage at which appropriate chemotherapy is started [I, 21. Unfortunately, there are few other helpful features which can alert the clinician to the possibility of a poor outcome 121. Internuclear ophthalmoplegia is caused by dysfunction of the medial longitudinal bundle and results in failure of adduction of the eye ipsilateral to the lesion, with nystagmus in the abducting eye [3]. When these signs are present on horizontal gaze in both directionsbilateral internuclear ophthalmoplegia-it is most frequently due to multiple sclerosis 13, 4, 51. Unilateral internuclear ophthalmoplegia is usually vascular in origin [3], but cryptococcal meningitis [6], encephalitis and brain stem gliomas 171 have all been implicated. The association of TB meningitis and internuclear ophthalmoplegia has not been described previously; furthermore, unlike ocular nerve palsies, the appearance of internuclear ophthalmoplegia indicates intrinsic brain stem damage and a poor prognosis.
Case 1.
Case histories
A 45-year-old Chinese cook from New York City, while on holiday in Hong Kong in January
62
Teoh and others
1987, consulted his doctor because of a 6-week history of progressive unsteadiness on walking and impaired vision, but there was no headache. On examination, he was fully orientated and afebrile but with marked neck stiffness, dysarthria and an ataxic gait. The optic discs were normal but the visual acuity on the right was impaired at 6/36 and the left 6/18. Bilateral internuclear ophthalmoplegia was present: adduction of both eyes was slow and incomplete, with nystagmus in the abducting eyes. The deep tendon reflexes were preserved and both plantar responses were extensor. A CT scan showed multiple contrast enhancing lesions. On transfer to this hospital he was found to be drowsy but fully orientated. Routine blood tests and chest X-ray were normal. Cerebrospinal fluid (CSF) examination showed an opening pressure of 8 cm H20, protein 1.95 g/l, glucose 2.4 mmol/l (concurrent blood glucose 5.8 mmol/l), 292 white cells/ml (99% lymphocytes). Ziehl Neelsen staining of CSF was positive for acid-fast bacilli. Cryptococcal antigen was absent in CSF. Antibody to human immunodeficiency virus was negative. A diagnosis of TB meningitis and intracranial tuberculoma was made and daily chemotherapy was started: streptomycin 1 G, isoniazid 600 mg, rifampicin 600 mg, pyrazinamide 1.5 G, and prednisone 20 mg. After 2 weeks of treatment he became disorientated in time and place and developed hiccups, increasing neck stiffness and a left VII nerve palsy. A repeat CT scan revealed similar changes to the first study. The dose of steroids was increased to dexamethasone 4 mg qid. After 1 month of treatment he had improved so that he could obey commands. Two weeks later, diabetes insipidus developed which required intramuscular desmopressin to control the polyuria. Despite careful electrolyte monitoring and continued treatment with anti-tuberculosis drugs and steroids the clinical condition continued to deteriorate: the fever recurred, there was now conjugate deviation of the eyes to the right, and the dysarthria was so severe that speech was virtually unintelligible. Seven weeks after the start of chemotherapy, cardiac arrest occurred. He was successfully resuscitated and maintained on intensive respiratory and cardiovascular support, but died 10 days later. Post-mortem examination was limited to the brain, which on external examination was diffusely soft with thick green exudate in the basal cisterns and over the cerebral convexities. Dense dural adhesions were present between the inferior surfaces of the temporal lobes and dura. The exuberant exudate had completely obliterated both cerebellopontine angles, The basilar artery was thrombosed along its entire length. Cut sections of the brain showed diffuse areas of softening and swelling. Scattered foci of haemorrhagic necrosis were present throughout the pons, tectum, and medulla. Extensive exudate in the left cerebella-pontine angle had eroded into the pons and left middle cerebellar peduncle. Microscopy showed extensive necrosis of pontine and tectal structures; the thrombosed basilar artery as well as its smaller pontine branches were cuffed with acute on chronic inflammatory infiltrate. A smear of the fibrinous exudate demonstrated the presence of acid fast bacilli. Gram stain revealed no bacteria. No granuloma could be identified in the parenchyma. Case 2. A 23-year-old mahjong tile carver was in good health until May 1987 when fever developed with anorexia, non-productive cough, intermittent headache and nausea. He was able to continue work but after 10 days the headache became more severe and he was admitted to hospital. Three days later, he became confused, was unable to recognise his family or feed himself and was incontinent of urine. There was a low grade fever and mild neck stiffness but no focal neurological signs.
Tuberculous
meningitis
63
Chest radiograph showed miliary shadowing; CSF examination revealed an opening pressure of 38 cmHpO , white cell count 120/ml (68% lymphocytes), protein 0.8 g/l, glucose 2.5 mmol/l; acid fast bacilli were seen on Ziehl Neelsen stain of CSF. Treatment was started with daily streptomycin 1 G, isoniazid 600 mg, rifampicin 600 mg, pyrazinamide 2 G. Streptomycin was stopped after 10 days because of dizziness but the other anti-tuberculosis drugs continued. His condition improved, the fever subsided and he was able to recognise his relatives, feed himself, walk and was continent of urine. Mycobacterium tuberculosis was subsequently cultured from CSF and early morning urine and was fully sensitive to the drugs prescribed. However after 3 weeks of treatment the fever, headache and vomiting recurred and he was again drowsy. The right optic disc margin was blurred, the deep tendon reflexes brisk and the plantar responses equivocal. Urgent CT brain scan showed mild hydrocephalus with basal meningeal enhancement but no tuberculoma. Streptomycin was restarted and dexamethasone 2 mg qid added. Serum electrolytes showed severe hyponatraemia (serum sodium between 116 and 120 mmol/l) due to inappropriate anti-diuretic hormone secretion. Despite improvement in the hyponatraemia with fluid restriction, the neurological condition continued to deteriorate. A repeat CT brain scan showed further hydrocephalus with enlargement of the third and both lateral ventricles and an urgent ventriculo-peritoneal shunt was performed. Ventricular CSF examination showed a white cell count of 37/ml (80 % lymphocytes), protein 0.75 g/l and glucose I.6 mmol/l. Post-operatively there was radiological improvement of the hydrocephalus on CT scanning, however, the hyponatraemia (120 mmol/l) persisted and there was no clinical improvement. Six weeks after the start of chemotherapy a left internuclear ophthalmoplegia developed: on looking to the right, there was failure of adduction of the left eye, with nystagmus in the right eye. There was also a right hemiparesis and bilateral extensor plantar responses. Despite increasing the dose of dexamethasone to 4 mg qid the level of consciousness deteriorated further; he was unable to obey verbal commands and was incontinent of faeces. He died 4 days after the appearance of the internuclear ophthalmoplegia. Permission for autopsy was refused. Discussion It is now well recognised that prognosis in TB meningitis is closely related to the clinical stage at which chemotherapy is started [I, 21. Whereas a good outcome can be predicted for patients with no disturbance of consciousness or focal neurological signs (Stage I), the outcome for Stage III disease remains poor [I, 21. In a recent series of 180 patients, 73 % of patients presenting with Stage III disease died while 9 % of those with Stage I succumbed [II. Internuclear ophthalmoplegia, resulting from disturbance of the medial longitudinal fasciculus ipsilateral to the eye which fails to adduct [71, has not previously been reported in TB meningitis. Disturbances of eye movements are usually the result of Ill or VI nerve palsies which are present in 5-14 % of all patients 12, 31 and may be present at the time of diagnosis or develop during treatment 121. The nerves are compromised as they emerge from the brain stem by the basal meningitis and function is disturbed by the exudate directly, or by involvement of the vasa nervorum [2,81. Other eye movement disorders in TB meningitis’are exceedingly rare: conjugate deviation of the eyes was described in the era before effective anti-TB chemotherapy was available and was attributed to tuberculous involvement of the cerebral convexity or midbrain [9]. The diagnosis of TB meningitis was confirmed in both our patients by the identification of acid-fast bacilli on Ziehl Neelsen staining of CSF. In one patient; both medial longitudinal
64
Teoh and others
fasciculi were involved at presentation; in the other, the internuclear ophthalmoplegia was unilateral and developed after 6 weeks of chemotherapy. Involvement of the medial longitudinal fasciculus in TB meningitis was the result of ischaemic necrosis rather than to a brain stem tuberculoma, as autopsy in one patient revealed extensive occlusion of the vessels in the brain stem and in neither patient was there evidence of tuberculomata on CT scanning. However, when occlusive vascular disease causes internuclear ophthalmoplegia, it is usually unilateral [3,4,5,7] as the medial longitudinal fasiculi are supplied by paired vessels arising independently from the basilar artery. Though bilateral internuclear ophthalmoplegias are usually the result of multiple sclerosis 13, 71,vascular disease has also been reported as a cause. In a combined series of 167 cases of internuclear ophthalmoplegia [4, 51, 85 were bilateral and of these, 15 were the result of occlusive vascular disease; pathological confirmation was obtained in two patients 151. In TB meningitis, the vessels around the base of the brain are most prone to develop inflammatory occlusion as this is where the meningeal inflammation is most intense [2, 81. Thus, it is the very vessels arising from the basilar artery, and supplying the medial longitudinal fasciculi which are most likely to become involved. The poor outcome in our two patients probably reflects spread of the ischaemic damage to neighbouring vital structures either directly or by involvement of adjacent vessels by the basal meningitis. In conclusion, while ocular nerve palsies are common in TB meningitis and do not suggest a poor outcome, the appearance of internuclear ophthalmoplegia is indicative of intrinsic brain stem damage from thrombotic endartiritis and thereby a poor prognosis. It is possible that earlier recognition of internuclear ophthalmoplegia in TB meningitis with prompt institution of corticosteroids may control the inflammatory vasculopathy and reduce the risk of ischaemic damage. But in both our patients, corticosteroids were of no benefit in this aggressive vasculitis. References 1 Ramachandran
2 3 4 5 6 7
8 9
P, Duraipandian M, Nagarajan M, Prabhakar Ft. Ramakrishnan CV, Tripathy SP. Three chemotherapy studies of tuberculous meningitis in children. Tubercle 1986; 67: 17-29. Tandon PN. Tuberculous meningitis (cranial and spinal). In: Vinken PJ, Bruyn GW, eds. Handbook of clinical vol 33. Amsterdam: North Holland, 1978: 195-262. neurology, ,WalshFe, Hoyt WF. ClinicalNeuro-ophthalmology. 3rd. ed. Baltimore: Williams and Wilkins 1969; I: 239. Cogan DG. Internuclear ophthalmoplegia, typical and atypical. Arch Ophthalmol 1970; 84: 583-9. Gonyea EF. Bilateral internuclear ophthalmoplegia. Arch Neural 1974; 31: 168-73. Gonyea EF, Heilman KM. Neuro-ophthalmic aspect of central nervous system cryptococcosis. Arch Ophthalrnol 1972; 87: 164-8. Leigh RJ, Zee DS. The neurology of eye movements. Philadelphia: FA Davis 1983. Smith HV, Daniel P. Some clinical and pathological aspects of tuberculosis of CNS. Tubercle 1947; 28: 64-80. Kyrieleis W. Augenveranderungen bei den entzundlichen Erkrankungen des Zentralnervensystems. Die geschwulstbildende Tuberkulose. In: Schieck F, Bruckner A, eds. Kurzes Handbuch der Ophthalmologic, vol 6. Berlin: J Springer, 1931: 701-2.
Tuberc/e(1989)70,61-64 0
Longman
Group
UK
Ltd 1989
INTERNUCLEAR
OPHTHALMOPLEGIA
R. Teoh,” M. J. Humphries,S Departments
IN TUBERCULOUS
MENINGITIS
J. C. N. Ghan,* H. K. Ng,t G. O’MahonyS
of Medicine* and Morbid Anatomy, t Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong and the Ruttonjee Sanatorium,S Hong Kong
Summary Two patients with tuberculous meningitis and internuclear ophthalmoplegia are described. Despite treatment with anti-tuberculosis chemotherapy and corticosteroids, both patients died. In one case autopsy showed severe basal meningitis with diffuse brain stem infarction secondary to widespread vasculitis.
L’auteur decrit le cas de deux d’ophtalmoplegie internucleaire. chimiotherapie antituberculeuse des cas, I’autopsie a montre une tronc cerebral, consecutif a une
malades atteints de meningite tuberculeuse et Les deux patients sont decedes malgre une et I’administration de corticosteroides. Dans un meningite basale severe avec infarcissement du vasculite largement repandue. Resumen
Se describe el case de 2 enfermos de meningitis tuberculosa y oftalmoplegia internuclear. Los 2 pacientes fallecieron a pesarde una quimioterapia antituberculosa y la administration de corticoesteroides. En uno de 10s cases la autopsia demostro una meningitis basal severa con infattacion difusa del tronco cerebral, secundaria a una vasculitis ampliamente extendida. Introduction The prognosis of tuberculous (TB) meningitis is closely related to the clinical stage at which appropriate chemotherapy is started [I, 21. Unfortunately, there are few other helpful features which can alert the clinician to the possibility of a poor outcome 121. Internuclear ophthalmoplegia is caused by dysfunction of the medial longitudinal bundle and results in failure of adduction of the eye ipsilateral to the lesion, with nystagmus in the abducting eye [3]. When these signs are present on horizontal gaze in both directionsbilateral internuclear ophthalmoplegia-it is most frequently due to multiple sclerosis 13, 4, 51. Unilateral internuclear ophthalmoplegia is usually vascular in origin [3], but cryptococcal meningitis [6], encephalitis and brain stem gliomas 171 have all been implicated. The association of TB meningitis and internuclear ophthalmoplegia has not been described previously; furthermore, unlike ocular nerve palsies, the appearance of internuclear ophthalmoplegia indicates intrinsic brain stem damage and a poor prognosis.
Case 1.
Case histories
A 45-year-old Chinese cook from New York City, while on holiday in Hong Kong in January
62
Teoh and others
1987, consulted his doctor because of a 6-week history of progressive unsteadiness on walking and impaired vision, but there was no headache. On examination, he was fully orientated and afebrile but with marked neck stiffness, dysarthria and an ataxic gait. The optic discs were normal but the visual acuity on the right was impaired at 6/36 and the left 6/18. Bilateral internuclear ophthalmoplegia was present: adduction of both eyes was slow and incomplete, with nystagmus in the abducting eyes. The deep tendon reflexes were preserved and both plantar responses were extensor. A CT scan showed multiple contrast enhancing lesions. On transfer to this hospital he was found to be drowsy but fully orientated. Routine blood tests and chest X-ray were normal. Cerebrospinal fluid (CSF) examination showed an opening pressure of 8 cm H20, protein 1.95 g/l, glucose 2.4 mmol/l (concurrent blood glucose 5.8 mmol/l), 292 white cells/ml (99% lymphocytes). Ziehl Neelsen staining of CSF was positive for acid-fast bacilli. Cryptococcal antigen was absent in CSF. Antibody to human immunodeficiency virus was negative. A diagnosis of TB meningitis and intracranial tuberculoma was made and daily chemotherapy was started: streptomycin 1 G, isoniazid 600 mg, rifampicin 600 mg, pyrazinamide 1.5 G, and prednisone 20 mg. After 2 weeks of treatment he became disorientated in time and place and developed hiccups, increasing neck stiffness and a left VII nerve palsy. A repeat CT scan revealed similar changes to the first study. The dose of steroids was increased to dexamethasone 4 mg qid. After 1 month of treatment he had improved so that he could obey commands. Two weeks later, diabetes insipidus developed which required intramuscular desmopressin to control the polyuria. Despite careful electrolyte monitoring and continued treatment with anti-tuberculosis drugs and steroids the clinical condition continued to deteriorate: the fever recurred, there was now conjugate deviation of the eyes to the right, and the dysarthria was so severe that speech was virtually unintelligible. Seven weeks after the start of chemotherapy, cardiac arrest occurred. He was successfully resuscitated and maintained on intensive respiratory and cardiovascular support, but died 10 days later. Post-mortem examination was limited to the brain, which on external examination was diffusely soft with thick green exudate in the basal cisterns and over the cerebral convexities. Dense dural adhesions were present between the inferior surfaces of the temporal lobes and dura. The exuberant exudate had completely obliterated both cerebellopontine angles, The basilar artery was thrombosed along its entire length. Cut sections of the brain showed diffuse areas of softening and swelling. Scattered foci of haemorrhagic necrosis were present throughout the pons, tectum, and medulla. Extensive exudate in the left cerebella-pontine angle had eroded into the pons and left middle cerebellar peduncle. Microscopy showed extensive necrosis of pontine and tectal structures; the thrombosed basilar artery as well as its smaller pontine branches were cuffed with acute on chronic inflammatory infiltrate. A smear of the fibrinous exudate demonstrated the presence of acid fast bacilli. Gram stain revealed no bacteria. No granuloma could be identified in the parenchyma. Case 2. A 23-year-old mahjong tile carver was in good health until May 1987 when fever developed with anorexia, non-productive cough, intermittent headache and nausea. He was able to continue work but after 10 days the headache became more severe and he was admitted to hospital. Three days later, he became confused, was unable to recognise his family or feed himself and was incontinent of urine. There was a low grade fever and mild neck stiffness but no focal neurological signs.
Tuberculous
meningitis
63
Chest radiograph showed miliary shadowing; CSF examination revealed an opening pressure of 38 cmHpO , white cell count 120/ml (68% lymphocytes), protein 0.8 g/l, glucose 2.5 mmol/l; acid fast bacilli were seen on Ziehl Neelsen stain of CSF. Treatment was started with daily streptomycin 1 G, isoniazid 600 mg, rifampicin 600 mg, pyrazinamide 2 G. Streptomycin was stopped after 10 days because of dizziness but the other anti-tuberculosis drugs continued. His condition improved, the fever subsided and he was able to recognise his relatives, feed himself, walk and was continent of urine. Mycobacterium tuberculosis was subsequently cultured from CSF and early morning urine and was fully sensitive to the drugs prescribed. However after 3 weeks of treatment the fever, headache and vomiting recurred and he was again drowsy. The right optic disc margin was blurred, the deep tendon reflexes brisk and the plantar responses equivocal. Urgent CT brain scan showed mild hydrocephalus with basal meningeal enhancement but no tuberculoma. Streptomycin was restarted and dexamethasone 2 mg qid added. Serum electrolytes showed severe hyponatraemia (serum sodium between 116 and 120 mmol/l) due to inappropriate anti-diuretic hormone secretion. Despite improvement in the hyponatraemia with fluid restriction, the neurological condition continued to deteriorate. A repeat CT brain scan showed further hydrocephalus with enlargement of the third and both lateral ventricles and an urgent ventriculo-peritoneal shunt was performed. Ventricular CSF examination showed a white cell count of 37/ml (80 % lymphocytes), protein 0.75 g/l and glucose I.6 mmol/l. Post-operatively there was radiological improvement of the hydrocephalus on CT scanning, however, the hyponatraemia (120 mmol/l) persisted and there was no clinical improvement. Six weeks after the start of chemotherapy a left internuclear ophthalmoplegia developed: on looking to the right, there was failure of adduction of the left eye, with nystagmus in the right eye. There was also a right hemiparesis and bilateral extensor plantar responses. Despite increasing the dose of dexamethasone to 4 mg qid the level of consciousness deteriorated further; he was unable to obey verbal commands and was incontinent of faeces. He died 4 days after the appearance of the internuclear ophthalmoplegia. Permission for autopsy was refused. Discussion It is now well recognised that prognosis in TB meningitis is closely related to the clinical stage at which chemotherapy is started [I, 21. Whereas a good outcome can be predicted for patients with no disturbance of consciousness or focal neurological signs (Stage I), the outcome for Stage III disease remains poor [I, 21. In a recent series of 180 patients, 73 % of patients presenting with Stage III disease died while 9 % of those with Stage I succumbed [II. Internuclear ophthalmoplegia, resulting from disturbance of the medial longitudinal fasciculus ipsilateral to the eye which fails to adduct [71, has not previously been reported in TB meningitis. Disturbances of eye movements are usually the result of Ill or VI nerve palsies which are present in 5-14 % of all patients 12, 31 and may be present at the time of diagnosis or develop during treatment 121. The nerves are compromised as they emerge from the brain stem by the basal meningitis and function is disturbed by the exudate directly, or by involvement of the vasa nervorum [2,81. Other eye movement disorders in TB meningitis’are exceedingly rare: conjugate deviation of the eyes was described in the era before effective anti-TB chemotherapy was available and was attributed to tuberculous involvement of the cerebral convexity or midbrain [9]. The diagnosis of TB meningitis was confirmed in both our patients by the identification of acid-fast bacilli on Ziehl Neelsen staining of CSF. In one patient; both medial longitudinal
64
Teoh and others
fasciculi were involved at presentation; in the other, the internuclear ophthalmoplegia was unilateral and developed after 6 weeks of chemotherapy. Involvement of the medial longitudinal fasciculus in TB meningitis was the result of ischaemic necrosis rather than to a brain stem tuberculoma, as autopsy in one patient revealed extensive occlusion of the vessels in the brain stem and in neither patient was there evidence of tuberculomata on CT scanning. However, when occlusive vascular disease causes internuclear ophthalmoplegia, it is usually unilateral [3,4,5,7] as the medial longitudinal fasiculi are supplied by paired vessels arising independently from the basilar artery. Though bilateral internuclear ophthalmoplegias are usually the result of multiple sclerosis 13, 71,vascular disease has also been reported as a cause. In a combined series of 167 cases of internuclear ophthalmoplegia [4, 51, 85 were bilateral and of these, 15 were the result of occlusive vascular disease; pathological confirmation was obtained in two patients 151. In TB meningitis, the vessels around the base of the brain are most prone to develop inflammatory occlusion as this is where the meningeal inflammation is most intense [2, 81. Thus, it is the very vessels arising from the basilar artery, and supplying the medial longitudinal fasciculi which are most likely to become involved. The poor outcome in our two patients probably reflects spread of the ischaemic damage to neighbouring vital structures either directly or by involvement of adjacent vessels by the basal meningitis. In conclusion, while ocular nerve palsies are common in TB meningitis and do not suggest a poor outcome, the appearance of internuclear ophthalmoplegia is indicative of intrinsic brain stem damage from thrombotic endartiritis and thereby a poor prognosis. It is possible that earlier recognition of internuclear ophthalmoplegia in TB meningitis with prompt institution of corticosteroids may control the inflammatory vasculopathy and reduce the risk of ischaemic damage. But in both our patients, corticosteroids were of no benefit in this aggressive vasculitis. References 1 Ramachandran
2 3 4 5 6 7
8 9
P, Duraipandian M, Nagarajan M, Prabhakar Ft. Ramakrishnan CV, Tripathy SP. Three chemotherapy studies of tuberculous meningitis in children. Tubercle 1986; 67: 17-29. Tandon PN. Tuberculous meningitis (cranial and spinal). In: Vinken PJ, Bruyn GW, eds. Handbook of clinical vol 33. Amsterdam: North Holland, 1978: 195-262. neurology, ,WalshFe, Hoyt WF. ClinicalNeuro-ophthalmology. 3rd. ed. Baltimore: Williams and Wilkins 1969; I: 239. Cogan DG. Internuclear ophthalmoplegia, typical and atypical. Arch Ophthalmol 1970; 84: 583-9. Gonyea EF. Bilateral internuclear ophthalmoplegia. Arch Neural 1974; 31: 168-73. Gonyea EF, Heilman KM. Neuro-ophthalmic aspect of central nervous system cryptococcosis. Arch Ophthalrnol 1972; 87: 164-8. Leigh RJ, Zee DS. The neurology of eye movements. Philadelphia: FA Davis 1983. Smith HV, Daniel P. Some clinical and pathological aspects of tuberculosis of CNS. Tubercle 1947; 28: 64-80. Kyrieleis W. Augenveranderungen bei den entzundlichen Erkrankungen des Zentralnervensystems. Die geschwulstbildende Tuberkulose. In: Schieck F, Bruckner A, eds. Kurzes Handbuch der Ophthalmologic, vol 6. Berlin: J Springer, 1931: 701-2.