J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.32.2.134 on 1 April 1969. Downloaded from

J. Neurol. Neurosurg. Psychiat., 1969, 32, 134-139

Vestibular paresis: a clinical feature of Wernicke's disease

CLAUDE GHEZ From the Division ofNeurology, Cleveland Metropolitan General Hospital, and Case Western Reserve University School ofMedicine, Cleveland, Ohio, U.S.A.

Wernicke's disease is a well-defined clinical and with unequivocal signs of Wernicke's disease. All showed pathological entity, and its aetiology has been an initial global confusional state and variable degrees of conclusively traced to deficiency (Phillips, memory loss as a persistent finding. All patients had Victor, Adams, and Davidson, 1952). Its essential and severe of gait as well as signs of features are the subacute onset of , mild polyneuropathy. Ophthalmoplegia was seen in 12 ophthalmoplegia and/or nystagmus, and ataxia patients (bilateral abducens palsies in 11 and total of external in stance and gait. It invariably occurs against a ophthalmoplegia one) and lasted from one to background of seven days. Mild cerebellar signs of the lower extremities and often chronic could be elicited in nine and of the . and the upper extremities in Ophthalmoplegia, ataxia, global two. Vertigo was not a complaint in any. Thiamine confusion respond readily to thiamine admin- was hydrochloride (100 mg) administered intramuscularlyProtected by copyright. istration, but the patient is often left with a upon admission to all patients and orally for several days conspicuous disorder in memory (Korsakoff's thereafter. All patients were examined neurologically in psychosis), and not infrequently some degree of a serial fashion. Head injuries were not a factor in any of ataxia when attempting to walk on a narrow base the patients and routine skull films were normal. All (heel to toe). patients had been hospitalized throughout the course of In the acute stages of the disease there is this study during which time they received an adequate frequently diet and no . a striking discrepancy between the patient's ability Control to stand and subjects were 12 chronic alcoholic patients, walk and his ability to perform tests seven with and five with alcoholic designed to assess cerebellar function-that is, cerebellar degeneration (Victor et al., 1959). The latter heel-to-shin, finger-to-nose, etc. The patient may group had no impairment in mental function or literally be unable to take even a few steps without ophthalmoplegia. Their neurological deficit consisted of support; his legs are rigidly held wide apart, the mild ataxia of stance and gait with an associated sym- body pitched forward as he clutches the nearest metrical ataxia of legs and to a lesser extent of the arms. solid The object for fear of falling. In a study of 245 patients onset of the disturbance had been gradual and no with Wernicke's disease by Victor, discernible episode of Wernicke's disease had occurred. Adams, Collins, No significant change in the of their severity ataxia was http://jnnp.bmj.com/ and Silby (to be published), it was found that ataxia noted of stance during the course of their hospital stay. and gait occurs in 87 %, whereas ataxia of Vestibular function was assessed the lower extremities in by means of a only 20 %. standard ice water caloric test. The ears were irrigated for One interpretation of this finding attributes the 30 seconds with 5 ml. ice water with at least a five minute ataxia of stance and gait to lesions in the midline interval between the testing of each ear. The patient was , and the ataxia of the lower instructed to fix his gaze on a point straight ahead and the extremities to an extension of the lesion into more time elapsing between the time of injection and end of the lateral areas of the anterior lobes ensuing nystagmus was determined. Past pointing with (Victor, Adams, eyes closed and Mancall, 1959). Vestibular before and after stimulation was evaluated. on September 28, 2021 by guest. function, which is Tests were known to be of paramount in the performed on more than one occasion in importance regula- 14 patients. Four were tion of postural adjustments, has not heretofore patients tested only twice; the been other 10 were tested on multiple occasions, on alternate determined. This study was undertaken to evaluate days at the beginning and at weekly and monthly intervals vestibular function in the acute and chronic stages later in the course of their illness. of Wemicke's disease. Five patients were tested for directional preponderance by means of a modification of the method of Fitzgerald MATERIAL AND METHODS and Hallpike (1942) in which the ears were alternately irrigated with 75 ml. water at 30 and 44°C. The subjects were 17 chronically malnourished patients With one none of our admitted to Cleveland exception, patients had any Metropolitan General Hospital hearing deficit by history or on routine clinical testing 134 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.32.2.134 on 1 April 1969. Downloaded from

Vestibular paresis: a clinicalfeature of Wernicke's disease 135 (Weber, Rinne, and Schwabach). Pure tone audiograms Three patients showed past pointing towards the were obtained in six patients and the more sensitive side of the ice water irrigation, even though nystag- Von Bekesy audiograms, tone decay, and Short mus was completely absent. Vertigo, however, never Increment Sensitivity index were done in three cases. occurred without nystagmus. In contrast, the responses of all control subjects RESULTS were within normal limits. In 10, contralateral nystagmus developed on calorization and lasted . RESPONSES TO ICE WATER IRRIGATION (a) Ab- between two and three minutes. Asymmetries normalities on initial testing (Table I) Despite some between ears greater than 20 seconds were not seen. variation in the time at which the first test was Two patients suffering from delirium tremens who carried out, all 17 patients showed profound were heavily sedated with paraldehyde and chlor- abnormalities in vestibulo-ocular responses. In 11 diazepoxide showed ipsilateral tonic-ocular deviation patients the responses were absent bilaterally and in about two minutes six patients unilateral unresponsiveness was seen lasting following irrigation. (even in the first few days following hospitalization). (b) Mode ofrecovery Some degree of recovery of The presence of abducens palsies did not interfere vestibular function was ascertained by serial caloric with the reflex which could be recognized in the testing in 10 patients. The onset of recovery varied adducting eye. from six to 60 days, and in seven patients it began in the second week following thiamine administration (Table I). TABLE I In seven patients, the tests were carried out at INITIAL RESPONSES AND ONSET OF RECOVERY intervals sufficiently short so that the manner of evolution of the caloric responses could be assessed. Patients Protected by copyright. Absent response on initial These data are illustrated by five representative cases examination (no.) (Y%) in Fig. 1 and indicate that recovery occurs in a (17 patients) 17 100 gradual, often asymmetrical, fashion and can be Bilateral 11 64 7 prolonged and incomplete. On occasion, the Unilateral 6 35-3 duration of nystagmus was longer than normal, Onset ofrecovery (10 patients) although not necessarily in relation to directional Range 6 days-2 months preponderance (Fig. 3). In the early phases of 7 patients 6-16 days recovery, marked irregularity and a reduced

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136 Claude Ghez amplitude of the nystagmic movements were com- monly observed and could be easily appreciated by visual inspection alone. The cumulative data from all patients are presented graphically in Figure 2. It was found that .-j after the tenth day following therapy the proportion of patients showing abnormal caloric responses started to decline. At eight months, 20 % were -i abnormal. It must be stat-ed that this latter figure represents an approximation of what is to be z expected in the chronic phase of Wernicke's disease co in view of the fact that at eight months a smaller number of patients were available for testing than in the acute stages of the disease. Caloric responses were deemed abnormal either if the duration of nystagmus was less than 1 minutes or if an asymmetry greater than 30 seconds between sides was found. Abnormal responses consisted in the TIME complete absence of vestibulo-ocular response on one or both sides, with the exception of six patients FIG. 2. Evolution of caloric responses-cumulative data. at 10 days, one at 20 days, and one at four months. Caloric responses were deemed abnormal if the duration of nystagmus was less than 1 min 30 sec or if the difference between the two sides was 2. DIFFERENTIAL CALORIC RESPONSES. DIRECTIONAL greater than 30 sec. PREPONDERANCE (Fig. 3) Significant directional Protected by copyright. preponderance was found in only one of five patients in whorn it was specifically sought during 300

Vestibular paresis: a clinicalfeature of Wernicke's disease 137 cerebellar degeneration. It should, however, be not intoxicated and control subjects in delirium did stated that one of our patients showed complete not show this abnormality. Hepatic , recovery of gait while his vestibular responses had another common metabolic complication of chronic only partially recovered. alcoholism, does not interfere with vestibulo-ocular responses (Conomy and Swash, 1968), nor was it DISCUSSION present in our cases. The absence of vertigo and/or deafness suggests Neither single case reports of Wernicke's disease nor that pathological changes in end-organ or vestibular large series of cases (Campbell and Russell, 1941; nerve are unlikely to account for our observations Jolliffe, Wortis, and Fein, 1941; Riggs and Boles, (Aschan, 1967). The relatively rapid rate of improve- 1944; Cruikshank, 1950; Malamud and Skillicom, ment, in contrast with the slow evolution of 1956) have previously called attention to the exist- nutritional polyneuropathy, and the absence of skull ence ofvestibular abnormalities. A possible exception fractures, are further arguments against the exist- to this statement is the case of Chavany, Messimy, ence of a nutritional or traumatic insult to these and Lefranc (1958), which was probably a case of structures. Wernicke's disease in which bilateral caloric The pathological findings in Wernicke's disease hyporesponsiveness is merely recorded. The cases may indicate the site and nature of the lesions presented here indicate that such an abnormality is responsible for the vestibular dysfunction. In a an extremely common if not a constant sign of acute detailed and extensive study, Victor et al. (to be Wernicke's encephalopathy. published) found that among 38 cases in whom An ice water test was used because the more specific brain-stem nuclei were examined 71-1 % elaborate techniques of bithermal stimulation do not showed definite lesions of the medial vestibular appear to be necessary for the clinical demonstration nucleus. The lateral, superior and spinal nuclei were of the disturbance, and because of the ease with involved in 500, 35 7, and 29-7 % respectively. It Protected by copyright. which it can be performed at the bedside. Differ- should be emphasized that, while the histological ential caloric tests at 30 and 440 do provide features of Wernicke's disease may be in the nature information regarding 'directional preponderance' of frank necrosis and demyelination in nuclear areas, and are said to be more precise (Cawthorn, Dix, the vestibular lesion is of a relatively milder degree. Hallpike, and Hood, 1956) and to cause less dis- It consists primarily in relatively symmetrical comfort than ice water. Furthermore, the latter is affection of a triangular zone which may include the said to occasionally cause a reduction in vestibular dorsal motor nucleus of the vagus and extends afferent input by direct action upon the vestibular laterally into the vestibular complex. Mild nerve cell nerve (Gernandt, 1949). In addition, there is a and loss associated with a conspicuous theoretical advantage in using warm and cold increase in microglia and are seen. This stimuli, since the former has been found to cause an change is similar to that seen in the abducens increase while the latter a decrease in frequency of nucleus. In so far as the vestibulospinal tract discharge recorded in the ampullar nerves from the originates from the lateral vestibular nucleus horizontal semi-circular canals (Gernandt, 1949). (Brodal, Pompeiano, and Walberg, 1962), the Nevertheless, it has been shown that the effective- occasional preservation of past pointing may bear http://jnnp.bmj.com/ ness of ice water is only slightly greater than that of some relation to the lower incidence of involvement water at 300, and that the amount of water is of of this structure. relatively little consequence in relation to the Following the historic studies of Prickett (1934), duration of the ensuing nystagmus (Jonkees, 1949). Alexander, Pijoan, and Meyerson (1938) pointed In our experience the difference between the duration out the similarity between the histopathological of nystagmus or the discomfort resulting from the changes of Wernicke's disease and those resulting two cold stimuli (ice water and water at 30°C) was from in the experimental animal, never significant. Finally, had direct effect of ice Phillips et al. (1952) demonstrated that the human on September 28, 2021 by guest. water on the vestibular nerve actually occurred, it condition responded specifically to thiamine would have produced the same effect as that resulting administration. from labyrinthine stimulation itself-that is, inhibi- Although the affection of vestibular nuclei has long tion of vestibular discharges. been known (Prickett, 1934; Zimmerman, 1939; Despite the common occurrence of nystagmus Swank and Prados, 1942), the only experimental during (Bernhard and Goldberg, studies of vestibular function per se in athiaminotic 1934; Aschan, 1958) and withdrawal (Goldberg, animals are those of Church (1933, 1935). Rats, 1961), these conditions do not appear to contribute given an autoclaved yeast diet deficient in thermo- to the vestibular disorder, since our subjects were labile thiamine, lost their labyrinthine-righting J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.32.2.134 on 1 April 1969. Downloaded from

138 Claude Ghez reflexes while the neck reflexes remained intact. frequent findings in such patients and undoubtedly Post-rotatory nystagmus was found to increase in exacerbate any functional disturbance brought about proportion to the duration of the deficient state. If by the vestibular defect. the animals were allowed to recover and a second We urge the adoption of the term 'vestibular bout of deficiency was produced the animals failed paresis', which is less anatomically restrictive than completely to develop post-rotatory nystagmus. The 'canal paresis', to indicate a global decrease in changes were considered to be reversible following sensitivity of vestibulo-ocular responses to both treatment with non-autoclaved yeast. warm and cold stimuli. While the work of Swank and Prados (1942) suggested that histological abnormalities occurred SUMMARY in the labyrinthine cristae, vestibular nerves, and nuclei in thiamine deficient pigeons, it has been Caloric responses were evaluated in 17 patients with pointed out (Dreyfus and Victor, 1961) that the Wernicke's disease and in 12 alcoholic controls. All changes described were relatively minor and may patients with Wernicke's disease showed either have been attributable to the well-known ca- unilateral or bilateral unresponsiveness in the first priciousness of the gold and silver stains which week of hospitalization. The course of recovery of were used exclusively. function is outlined. It is felt to contribute to the In the rat, the vestibular complex is selectively severe instability of stance and gait which is present vulnerable to thiamine depletion. The destruction of in these patients. neurones and myelinated fibres is accompanied by These findings are best explained on the basis of an intense glial reaction and macrophage activity. the common lesions in the vestibular nuclei and the The thiamine dependent enzyme has recently reported changes in synaptic terminals and been reported to be depressed selectively in the lateral axons seen in these nuclei in thiamine deficient Protected by copyright. pontine tegmentum at an early stage of deficiency animals. (Dreyfus, 1965). The recent electron microscopic study of the vestibular nuclei in thiamine deficient I am deeply grateful to Professor Maurice Victor for his animals by Tellez and Terry (1968) has direct constant encouragement as well as for his helpful bearing upon our findings. These authors present comments and criticisms of the manuscript. evidence that the earliest affect the pre- changes REFERENCES synaptic endings and axons within the vestibular nuclei. The synaptic boutons were enlarged, their Alexander, L., Pijoan, M., and Meyerson, A. (1938). Beri-beri and . An experimental study. Trans. Amer. Neurol. Ass., 64, membranes thickened, and synaptic vesicles were 135-1 39. either absent or markedly reduced in number. In Aschan, G. (1958). Different types of alcohol nystagmus. Acta were seen to contain unusual oto-laryng. (Stockh.), Suppl. No. 140, 69-78. addition, the endings (1967). Clinical vestibular examinations and their results. (electron-dense) tubular structures with periodic Ibid., Suppl. No. 224, 56-66. darker bands. Degenerative changes in axons were Bernhard, C. G., and Goldberg, L. (1934). Nystagmus spontan6 par suite d'intoxication aigue par l'alcool. Acta med. scand., 84, also reported, although neuronal bodies and 36-44. were unremarkable. It is highly probable that these Brodal, A., Pompeiano, O., and Walberg, F. (1962). The Vestibular

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Vestibular paresis: a clinicalfeature of Wernicke's disease 139

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