Journal of Neuro-Ophthalmology, June 1992, Volume 12, Issue 2

Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy.

The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy.

jOllrnal 0/ Clime" l Nellro- 0l'htlwllll" loSY 12( 2): 116-- 12[ 1, 1992. Bilateral Internuclear Ophthalmoplegia in a Patient with Wernicke's Encephalopathy Monica A. De La Paz, M. D., Sophia M. Chung, M. D., and John A. McCrary III, M. D. 1;; 1992 Raven Press, Ltd., New York The most common cause of bilateral internuclear oph­thalmoplegia is multiple sclerosis, Wernicke's encepha­lopathy has been reported as a cause of unilateral inter­nuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia, In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy, Key Words: Internuclear ophthalmoplegia- Wernicke's encephalopathy- Alcoholism From the Department of Ophthalmology ( M. A. D.), Massa­chusetts Eye and Ear Infirmary. Department of Ophthalmol­ogy, Boston. Massachusetts; Bethesda Eye Institute ( S. M. C.), Saint Louis University Medical Center, Saint Louis. Missouri; and Cullen Eye Institute a. A. M.), Baylor College of Medicine, Houston. Texas. U. s. A. Address correspondence and reprint requests to Dr. Sophia M. Chung. Bethesda Eye Institute. Saint Louis University Med­ic~ 1 C.' nlt'f, 3ASS Vi<; la A\' enut', Saint LouIs. 11.1063110. U. S. A. Internuclear ophthalmoplegia is caused by a le­sion of the medial longitudinal fasciculus and man­ifests as impaired adduction of the eye ipsilateral to the side of the lesion, with jerk nystagmus of the abducting eye. Vertical nystagmus usually evoked by upgaze is a frequent finding. The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis ( 1,2). Other causes include isch­emia from basilar arterial disease, vasculitides, brainstem malignancies, syphilis, Arnold- Chiari malformation, trauma, and overdose of exogenous agents, such as narcotics ( 3- 8). An ocular motor pattern resembling internuclear ophthalmoplegia has been described in myasthenia gravis ( 9). Uni­lateral internuclear ophthalmoplegia has been well described in association with Wernicke's encepha­lopathy ( 1, 10). The association of Wernicke's en­cephalopathy with bilateral internuclear ophthal­moplegia has, to the best of our knowledge, not been described. In this report, we describe the case of a patient with bilateral internuclear ophthal­moplegia whose clinical presentation and diagnos­tic studies are most consistent with a diagnosis of Wernicke's encephalopathy. CASE REPORT A 29- year- old white man with a long history of alcohol abuse was in his usual state of health until 2 weeks before presentation, when he noted the onset of horizontal diplopia. The episode occurred after a drinking binge, at which time the patient lost consciousness and awoke with horizontal dip­lopia and divergent gaze. Prior ocular history was unremarkable, and there were no complaints re­lated to other neurological findings. The past med­ical history was remarkable for gastritis. There was a history of intravenous cocaine abuse. The last use of cocaine was several days before the onset of diplopia. 116 DIVERGENT GAZE IN WERNICKE'S ENCEPHALOGRAPHY 117 On examination, the patient was a slightly drowsy, thin white man. Visual acuity of both eyes was 20/ 20. There was mild ptosis of both eyes, with normal function of both levator palpebrae. The pupils were sluggishly reactive to light. There was no light- near dissociation or afferent pupillary defect. A variable angle alternating exotropia from 30 to 90 prism diopters ( PO) was present. Down­beat nystagmus was present in primary gaze. There was evidence of a bilateral internuclear oph­thalmoplegia ( Fig. 1), with horizontal nystagmus in abduction and marked impairment of adduction of both eyes. Adduction was improved with con­vergence. Lateral rectus function was full in both eyes. Upbeat nystagmus occurred with elevation and downbeat nystagmus with downgaze. Con­frontation visual fields were normal. Funduscopic examination was remarkable for bilateral juxtapap­illary myelinated nerve fibers. The remainder of the ocular examination was normal. The patient was not oriented to place, person, or time. There was impairment of short- term mem­ory, and he confabulated. The other cranial nerves were normal. The motor and sensory examination and deep tendon reflexes were normal. No Babin­ski sign was present. Cerebellar examination re­vealed decreased rapid alternating movements and a wide- based ataxic gait. The remainder of the physical examination was within normal limits. Hematological studies revealed a macrocytosis without anemia. The erythrocyte sedimentation rate was 15 mm/ h. Serum chemistries showed ev­idence of abnormal liver function consistent with the chronic abuse of alcohol. The ANA was nega­tive. The rheumatoid factor was 28 IU/ mI. and the RPR was nonreactive. The patient was admitted for further evaluation. Intravenous thiamine followed by intramuscular supplementation was administered, in addition to supplemental folate and overall nutritional sup­port. A lumbar puncture was performed. The opening pressure was normal, and the cerebrospi­nal fluid was clear and colorless, with 2 WBClmm3 . The glucose level was 67 mgldt and the protein was 61 mgldl. The spinal fluid electrophoretic study was normal. Specifically, no oligoclonal bands were detected. Special stains revealed no organisms, and cultures were sterile. Cerebrospi­nal fluid cytology showed no evidence of malig­nant cells. An HIV antibody test was negative. A Tensilon test was performed with no improvement in the ocular motility. A computed tomography ( CT) scan of the brain with contrast showed no lesions. Subsequently, magnetic resonance imag­ing ( MRI) of the brain was performed. High­intensity signals on both spin density and T2­weighted scans were present in the mesencepha­lon anterior to the aqueduct extending along both medial longitudinal fasciculi ( Figs. 2 and 3). There was no mass effect, and no other lesions were noted. Thiamine supplementation was begun at the time of admission. Orientation and drowsiness im­proved significantly within the first 24 hours; the ataxia improved within the second 24 hours of the hospitalization. Symptoms of alcohol withdrawal were treated with oral chlordiazepoxide. Over the next 2 weeks, the ocular motility exam­ination of the patient improved. The amplitude and frequency of the vertical nystagmus dimin­ished. There was improvement in the intermittent exotropia, which ranged from 10 to 60 PD. The adduction weakness was unchanged. The patient was discharged from the hospital after 2 weeks; he FIG. 1. Motility series of patient demonstrating bilateral internuclear ophthalmople­gia. There is exotropia in all positions of gaze and marked adduction deficit of both eyes. I Clin Neuro- ophthalmol. Vol. 12. No. 2. 1992 118 M. A. DE LA PAZ ET AL. FIG. 2. This T2- weighted MR scan taken at the level of the mesencephalon demonstrates the periaqueductal gray matter lesion ( arrow). failed to return for follow- up, although an emer­gency room physician noted divergent gaze 3 months after hospitalization. DISCUSSION We present a patient with a history of alcoholism who developed acute onset of diplopia secondary to bilateral internuclear ophthalmoplegia, with ad­ditional features of downbeat nystagmus in pri­mary gaze, vertical nystagmus, and cerebellar dys­function. The MRI findings correlate the clinical features with bilateral lesions of the medial longi­tudinal fasciculi. Bilateral internuclear ophthalmoplegia is the most common ocular motor manifestation of mul­tiple sclerosis ( 1). In the patient under discussion, numerous features of the case make the diagnosis of multiple sclerosis less likely. By history, there are no prior episodes of neurological symptoms, although it is possible that this may be a primary event. The cerebrospinal fluid has been shown to be abnormal in 90% of clinically definite cases of multiple sclerosis ( 11, 12). In the case under discus­sion, no oligoclonal bands were present. Further­more, downbeat nystagmus in the primary posi­tion is only rarely associated with multiple sclero­sis ( 13,14). FIG. 3. This spin- density MR scan demonstrates ex­tension of the disease process into the medial longi­tudinal fasciculi ( arrow indicates right fasciculUS). MRI has been shown to be superior to CT in the diagnosis of multiple sclerosis ( 15,16). White mat­ter lesions adjacent to the lateral ventricles are the most common finding on MRI in patients with multiple sclerosis ( 17,18). The plaques are best seen on the T2- weighted scans ( 16,19). Our patient did not reveal periventricular changes on MRI. De­spite clinical evidence of brainstem and cerebellar pathology, lesions in these areas are not often demonstrated with MRI ( 17). One study, however, found that three patients with ocular motor distur­bances secondary to multiple sclerosis had MRI studies demonstrating lesions of the brainstem with areas of prolonged T1 and/ or T2 ( 20). These patients had at least one additional periventricular white matter lesion. The history and clinical eval­uation reasonably excluded other etiologies of bi­lateral internuclear ophthalmoplegia, including Arnold- Chiari malformation, basilar arterial dis­ease, meningitis, vasculitides, brainstem malig­nancies, syphilis, and narcotic overdose. Wernicke's encephalopathy is a metabolic dis­ease of the central nervous system caused by a nutritional deficiency of thiamine, which usually occurs in malnourished alcoholic patients ( 21). The most common neurological features associated with Wernicke's encephalopathy are disturbance of mentation and consciousness, paralysis of eye DIVERGENT GAZE IN WERNICKE'S ENCEPHALOGRAPHY 119 movements, and ataxic gait as demonstrated by our patient. Eye movement disorders include weakness of abduction, gaze- evoked nystagmus, horizontal and vertical gaze palsies, primary posi­tion upbeat and downbeat nystagmus, and inter­nuclear ophthalmoplegia ( 10,22,23). Bilateral internuclear ophthalmoplegia has not been described in association with Wernicke's en­cephalopathy. Four patients reported by Schiffter ( 24) to have bilateral internuclear ophthalmoplegia caused by Wernicke's encephalopathy are not compatible with our patient as they had bilateral failure of abduction of the eyes, not adduction fail­ure. Thiamine deficiency in Leigh's disease, a nec­rotizing hemorrhagic encephalomyelopathy in patients without a history of alcoholism or malnu­trition, has been shown to cause bilateral internu­clear ophthalmoplegia ( 25). The presence of the classic triad of impaired oc­ular motility, ataxia, and disturbance of mentation followed by prompt improvement in the clinical findings after thiamine supplementation is diag­nostic of Wernicke's encephalopathy. It is well documented that improvement in abducens pare­sis may occur within hours after administration of thiamine and is usually complete within days ( 6,23), whereas nystagmus may persist for years despite adequate thiamine replacement ( 10). What remains unclear is the rate of response of internu­clear ophthalmoplegia to thiamine. Postmortem studies describe destructive changes adjacent to the third and fourth ventricles and the aqueduct of Sylvius ( 26,27). Histopatho­logical features of lesions in Wernicke's encepha­lopathy include varying degrees of parenchymal necrosis with neuron loss and astrocytic prolifera­tion and, in some cases petechial hemorrhages. These pathological findings, however, do not ex­plain the rapid reversal of ocular palsies in re­sponse to thiamine administration; instead, a bio­chemical deficit is implied, rather than a structural lesion. Pathological studies support this interpre­tation by the lack of significant damage of the oc­ular motor nuclei seen at autopsy in patients with Wernicke's disease ( 27). The destructive changes seen may also explain the slow and incomplete recovery of the nystagmus, ataxia, and memory. In the patient we have presented, the primary position downbeat nystagmus, mild confusional state, and ataxic gait followed by the improvement in the clinical findings after thiamine supplemen­tation are highly suggestive of a diagnosis of Wer­nicke's encephalopathy. The incomplete resolu­tion of the bilateral internuclear ophthalmoplegia upon thiamine supplementation, although not typical of Wernicke's encephalopathy, may be ex­plained on the basis of destructive lesions involv­ing both medial longitudinal fasciculi, as sug­gested by the MRI findings. There are only a few reports in the literature that describe the neuroimaging findings of patients with Wernicke's encephalopathy. CT scanning has revealed bilateral low- density thalamic lesions ( 28); nonenhancing hypodense areas around the cere­bral aqueduct were noted in one patient who pre­sented in a stuporous state with absent oculoceph­alic responses, with minimal improvement after thiamine and nutritional supplementation ( 29). MRI findings include increased signal in the dorsal medial nuclei of the thalami on T2- weighted im­ages. Another study found that MRI scans on three of five patients demonstrated signal hyper­intensities surrounding the third ventricle and aq­ueduct on T2- weighted images ( 30). These hyper­intensities showed a " double wing" configuration that resembled that of the patient under discus­sion. In addition, the intensity of these regions was noted to decrease on follow- up studies, with consequent third ventricular and aqueductal dila­tion. However, exact correlation between the type of ocular motor deficit and MRl abnormality was not indicated in the article. MRl is considered to be superior to CT scanning in Wernicke's encepha­lopathy because of improved clarity of lesions ( 31,32). In summary, we believe that the clinical course of this patient with bilateral internuclear ophthal­moplegia and a history of alcoholism is most con­sistent with a diagnosis of Wernicke's encephalop­athy. The case is of interest because we have not found previous reports of bilateral internuclear ophthalmoplegia in association with Wernicke's encephalopathy. In addition, the acute MRl find­ings in a patient with Wernicke's encephalopathy are readily demonstrated, indicating that MRI scanning can play a valuable role in establishing the diagnosis of this potentially fatal disease. The possibility that alcohol abuse resulting in nutritional compromise and Wernicke's encepha­lopathy may be the cause of bilateral internuclear ophthalmoplegia must be recognized. Prompt, ap­propriate replacement of depleted thiamine by parenteral administration is essential for the best neurologic outcome as Wernicke's encephalopathy represents a neurologic emergency. REFERENCES 1. Smith JL, Cogan DC. Internuclear ophthalmoplegia. Are · view of 58 cases. Arch OphthalmoI1959; 61: 687. JClin Neuro- ophthalmol. Vol. 12, No. 2. 1992 120 M. A. DE LA PAZ ET AL. 2. Cogan DG. 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