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Show Journal of Neuro- Ophthalmology 19( 2): 131- 135, 1999. © 1999 Lippincott Williams & Wilkins, Inc., Philadelphia Wall- Eyed Bilateral Internuclear Ophthalmoplegia in Central Nervous System Cryptococcosis Peter M. Fay, M. D., and Mitchell B. Strominger, M. D. Only one case of wall- eyed bilateral internuclear ophthalmoplegia ( WEBINO) has been described in central nervous system cryptococcosis. The disorder was initially unilateral, then became bilateral with skew deviation and vertical upgaze deficit. We report a case of WEBINO in central nervous system cryptococcosis in a patient with acquired immune deficiency syndrome. Magnetic resonance imaging revealed high signal on T2 images in the right midbrain, left frontal vertex, left sple-nium, and cerebellum. With treatment, the internuclear ophthalmoplegia improved; however, the convergence insufficiency remained. Disruption of input from cortical supranuclear locations or the region of the rostral interstitial nucleus of the medial longitudinal fasciculus has been proposed as a mechanism in the absence of convergence. This correlates in our patient with the lesions seen on magnetic resonance images. Key Words: acquired immune deficiency syndrome, convergence cryptococcosis, wall- eyed bilateral internuclear ophthalmoplegia. Wall- eyed bilateral internuclear ophthalmoplegia ( WEBINO) is characterized by bilateral internuclear ophthalmoplegia ( INO) with absence of convergence and exotropia in primary position ( 1). The most common causes of WEBINO are multiple sclerosis ( MS) and cerebrovascular disease ( 2). Both WEBINO and unilateral INO secondary to cryptococcal meningitis are unusual. Gonyea and Heilman ( 3) reported two cases of internuclear ophthalmoplegia from cryptococcal meningitis with one patient progressing to bilateral INO. Sung et al. ( 4) described a similar case of unilateral INO. To the best of our knowledge, we are reporting the first case of WEBINO secondary to central nervous system cryptococcosis present at the time of diagnosis. Our patient's case is also interesting, in that despite treatment and improvement in medial rectus function, convergence remained absent. Manuscript received December 28, 1998; accepted February 10, 1999. From the Department of Ophthalmology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York, U. S. A. Presented in poster format at the North American Neuro- Ophthalmology Society ( NANOS) meeting, Orlando, Florida, March 21- 26, 1998. Address correspondence and reprint requests to Mitchell B. Strominger, MD, Department of Ophthalmology, SUNY- HSC at Brooklyn, Box 58,450 Clarkson Avenue, Brooklyn, NY 11203, U. S. A. CASE REPORT A 33- year- old man with acquired immune deficiency syndrome ( AIDS) sought medical attention at an outlying hospital and reported symptoms including diplopia, headache, right arm weakness, and left leg weakness. Cerebral spinal fluid examination revealed leukocyte count 115 cells/ mm3, with 85% lymphocytes and an opening pressure of 38 cm H20. India ink stain and cryptococcal antigen were positive. Treatment with 42 mg/ day intravenous amphotericin B was initiated, and the patient was transferred to our institution. Amphotericin B was continued for 5 days and replaced by 400 mg/ day oral fluconazole. On neuro- ophthalmic examination the patient's vision was 20/ 30 OU. Pupils were equal and reactive without an afferent pupillary defect. Color vision was full, and the optic nerves were normal. Motility examination showed exotropia in primary position, limitation of both eyes past the midline on horizontal gaze, and absence of convergence ( Fig. 1). On right and left lateral gazes there was a horizontal jerk nystagmus in the abducting eye. Magnetic resonance imaging ( MRI) revealed increased signal on T2- weighted images in the right midbrain, left frontal vertex, left splenium, left parietal lobe, and both right and left cerebellum ( Figs. 2- 5). The parietal and cerebellar lesions enhanced with gadolinium on Tl- weighted images. An incidental pineal cyst was noted ( Fig. 6). After 6 weeks of continued treatment with oral fluconazole, a second lumber puncture showed a decrease in leukocytes to 5/ mm3 ( 94% lymphocytes and 6% monocytes) and a cryptococcal antigen titer of 1: 8. On motility examination 1 month later, the adduction deficit of the left eye had improved. However, convergence remained absent ( Fig. 7). DISCUSSION The term wall- eyed bilateral internuclear ophthalmoplegia was introduced by Dr. Martin Lubow to describe patients with bilateral internuclear ophthalmoplegia associated with exotropia and absence of convergence ( 1). Lutz ( 5) characterized anterior and posterior types of unilateral INO, with paresis of ocular abduction 131 132 P. M. FAY AND M. B. STROMINGER FIG. 1. Pretreatment extraocular movements demonstrating bilateral adduction deficits with exotropia in primary position. Bottom right picture shows absence of convergence. in the latter. Cogan ( 6) modified this classification such that both anterior and posterior types displayed paresis of adduction past the midline, together with nystagmus in the abducting eye. The two are differentiated by the absence of convergence in the anterior variety. The causes of unilateral INO are numerous and have been extensively reported in the literature. However, the list of causes of bilateral INO is much shorter. Cogan ( 2) found that multiple sclerosis was the major cause of bilateral INO in his patients. Other causes include occlusive vascular disease, syphilis, and the Arnold- Chiari malformation. Gonyea ( 7) verified Cogan's findings. In 41 patients with bilateral INO, MS was the cause in 63% of cases and vascular events in 29% of cases. After these reports, there have been published cases of WEBINO secondary to head trauma ( 8), tuberculous granulomas ( 9), mesencephalic clefts ( 10), and carcinomatous meningitis ( 11). To the best of our knowledge there have been only two reports of cases of INO in cryptococcosis. Sung et al. ( 4) reported a case of unilateral INO in cryptococcal meningitis. Gonyea and Heilman ( 3) reported two cases of unilateral INO in cryptococcal meningitis, one of which progressed to WEBINO. Our case is therefore unusual in that the WEBINO syndrome was present when the patient sought treatment for central nervous system cryptococcosis. Cryptococcus neoformans is an encapsulated, yeastlike fungus that reproduces by budding. Although high concentrations of the fungus are found in pigeon droppings, occupational predisposition and histories of exposure to pigeons are not helpful in the diagnosis. Because the organism is ubiquitous and exposure is thought to be common, there must be a high natural resistance to infection, because new cases were relatively rare before the advent of AIDS. Currently, AIDS is the predisposing factor in 80% to 90% of cryptococcal infections, which usually appear when CD4+ T- lymphocyte counts are reduced below 200/ mm3 ( 12). Although the onset of central nervous system crypto- FIG. 2. Axial T2- weighted magnetic resonance image showing high- signal lesion ( arrow) in the right midbrain. J Neuro- Ophthalmol, Vol. 19, No. 2, 1999 BILATERAL OPHTHALMOPLEGIA IN CNS CRYPTOCOCCOSIS 133 Hi 10 ft V FIG. 3. Axial T2- weighted magnetic resonance image showing high- signal lesions ( arrows) in the cerebellum. FIG. 5. Axial T2- weighted magnetic resonance image showing high- signal lesion ( arrow) in the left parietal region. coccosis may be insidious, acute manifestations are more common in immunosuppressed patients. Patients are often afebrile or have a mildly elevated temperature. Most patients have no nuchal rigidity. Papilledema is noted in approximately one third of cases and cranial nerve palsies in approximately one fifth. Abnormal cerebrospinal fluid findings are almost always seen with central nervous system involvement. The opening pressure is often FIG. 4. Axial T2- weighted magnetic resonance image showing high- signal lesion ( arrow) in the left frontal vertex. FIG. 6. Sagittal T1- weighted magnetic resonance image showing the pineal cyst. J Neuro- Ophthalmol, Vol. 19, No. 2, 1999 134 P. M. FAY AND M. B. STROMINGER >- isa FIG. 7. Posttreatment extraocular movements showing the ability of the left eye to adduct past the midline ( middle left). Absence of convergence continued { bottom right). elevated, glucose is depressed, protein concentration is usually increased, and leukocyte counts are usually 20/ mm3 or higher, with a predominance of lymphocytes. The characteristic lesions within the brain consist of cystic clusters of fungi with no inflammatory response, although large focal collections of organisms with some inflammatory response may occur in the brain. The basal ganglia and cortical gray matter are usually involved ( 13). The distinguishing features of the WEBINO syndrome are exotropia and the absence of convergence. Many investigators have speculated about the anatomic site that could cause such a condition. It is thought by many that absence of convergence may be caused by lesions involving the medial rectus subnuclei of the oculomotor complex. Strominger et al., ( 14) however, reported a case of WEBINO with autopsy confirmation that showed an intact oculomotor complex with both cystic and demye-linating lesions in the internal capsule. They speculated that the lesions of the internal capsule interrupted fibers from the frontal eye fields or other cortical areas and abolished the ability to converge. Stimulation of the frontal and occipital eye fields in monkeys has produced convergence movements, and it may be that higher cortical functions play a significant role in these volitional, self- initiated movements ( 15). The cerebellum has also been implicated in the control of vergence. Acute cerebellar lesions have been shown to cause weakness of convergence ( 16). Although the specific part of the cerebellum that participates in convergence is unknown, the cerebellar flocculus is known to have neurons that discharge proportionally with the amount of convergence ( 17). Therefore, the high- intensity signals seen in the cerebellum, left frontal lobe, and left parietal region of our patient may help explain the absence of convergence, despite improvement in medial rectus function. Another area involved in the control of vergence is the mesencephalic reticular formation. Mays ( 18) localized vergence neurons to 1 to 2 mm dorsal and dorsolateral to the oculomotor complex. Three classes of neurons were identified: vergence tonic cells, vergence burst neurons, and vergence burst- tonic cells. Each may have separate roles in vergence movements, with the vergence tonic cells discharging in relation to vergence angle and vergence burst neurons discharging in relationship to vergence velocity. Our patient may have been predisposed to difficulty with convergence because of the presence of the incidental pineal cyst located in this region. This case has two unusual aspects. First is the presence of WEBINO in central nervous system cryptococcosis. Second is that convergence remained absent despite treatment and improvement of medial rectus function on horizontal gaze. By disrupting input into the oculomotor complex, lesions in the cerebral cortex, cerebellum, and pineal region may be the mechanism by which convergence failed to recover. REFERENCES 1. Daroff RB, Hoyt WF. Supranuclear disorders of ocular control systems in man. In: Bach Y, Rita P, Colins C, Hyde J, eds. The Control of eye movements. New York: Academic Press, 1971: 223- 6. 2. Cogan DG. Internuclear ophthalmoplegia, typical and atypical. Arch Ophthalmol 1970; 84: 583- 9. 3. Gonyea EF, Heilman KM. Neuro- ophthalmic aspects of central nervous system cryptococcosis: Internuclear ophthalmoplegia and supranuclear ophthalmoplegia. Arch Ophthalmol 1972; 87: 164- 8. J Neuro- Ophthalmol, Vol. 19, No. 2, 1999 BILATERAL OPHTHALMOPLEGIA IN CNS CRYPTOCOCCOSIS 135 4. Sung YJ, Cheng PN, Lai KN. Intemuclear ophthalmoplegia in cryptococcal meningitis. 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