Brain stem auditory evoked responses in chronic alcoholics.

Brain stem auditory evoked responses (BAERs) were performed on 25 alcoholic patients with Wernicke-Korsakoff syndrome, 56 alcoholic patients without Wernicke-Korsakoff syndrome, 24 of whom had cerebellar ataxia, and 37 control subjects. Abnormal BAERs were found in 48% of patients with Wernicke-Korsakoff syndrome, in 25% of alcoholic patients without Wernicke-Korsakoff syndrome but with cerebellar ataxia, and in 13% of alcoholic patients without Wernicke-Korsakoff syndrome or ataxia. The mean value of the I-V interval was prolonged in all patient groups. There were more patients with prolonged I-V and I-III intervals in the Wernicke-Korsakoff syndrome group than in the group without the syndrome. The I-III interval was prolonged in 32% of those with Wernicke-Korsakoff syndrome but in only 6% of alcoholics without the syndrome. These abnormalities improved following thiamine treatment and abstinence from alcohol. The presence of prolonged I-III interval in an alcoholic should raise the possibility of Wernicke's encephalopathy.     

Severe dysphagia as the presenting symptom of Wernicke-Korsakoff syndrome in a non-alcoholic man

We present the case of a non-alcoholic man, who, following severe malnutrition, presented with dysphagia that necessitated gastrostomy tube placement. The patient subsequently developed encephalopathy, at which point thiamine deficiency was suspected and thiamine supplementation initiated. The encephalopathy and the dysphagia resolved, but the patient was left with a dense amnestic deficit consistent with Korsakoff syndrome. MRI at the time of the encephalopathy revealed lesions consistent with Wernicke-Korsakoff syndrome. This case represents a remarkable example of Wernicke-Korsakoff syndrome that for a prolonged time period had as its sole manifestation severe dysphagia. To our knowledge, there is only one similar case reported in the literature. This case serves to alert neurologists that isolated dysphagia may be the presenting symptom of this classic neurological syndrome even in the absence of alcoholism.     

Delayed matching to sample and concurrent learning in nonamnesic humans with alcohol dependence.

Small samples of alcohol-dependent subjects who showed no clinical signs of Wernicke-Korsakoff syndrome were compared with nonalcohol-dependent controls on two animal memory tests which are performed poorly by human amnesics. Compared to the control subjects, the alcohol-dependent subjects' performance was impaired on a version of the delayed matching to sample task. On concurrent discrimination learning the overall group difference just failed to reach significance. The results are interpreted as suggesting that behavioural impairment may occur in alcohol-dependent subjects who are not clinically amnesic, and that the impairment is similar in type to that observed in cases of severe Wernicke-Korsakoff syndrome.     

Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy

The determination of blood transketolase before and serially after thiamine administration, and the response of clinical symptomatology after thiamine are reported in two normomagnesaemic patients and one hypomagnesaemic patient with acute Wernicke-Korsakoff encephalopathy. The response of the depressed blood transketolase and the clinical symptoms was retarded in the hypomagnesaemic patient. Correction of hypomagnesaemia was accompanied by the recovery of blood transketolase activity and total clearing of the ophthalmoplegia in this patient, suggesting that hypomagnesaemia may be a cause of the occasional thiamine refractoriness of these patients.     

Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions

Rhesus monkeys were subjected to one, two, or four periods of thiamine deficiency to determine how the number of deprivation episodes affects the development and progression of neurological and neuropathological changes. Recrurent thiamine deprivation produced all major neurological signs and most of the anatomical lesions found in Wernicke-Korsakoff syndrome. Neither the number and gravity of neurological symptoms nor the extent or location of lesions was related to the number of deprivation periods in a simple way. Thus, some structures, such as the inferior colliculus and medial vestibular nuclei, were affected after only one period of deficiency. Other structures, such as the parafascicular nucleus of the thalamus, were more resistant and exhibited degeneration only after four periods of thiamine deprivation. Severe damage in the basal ganglia was infrequent and was associated with prolonged rather than multiple periods of deprivation. No parenchymal damage was found in the mammillary bodies or mediodorsal nucleus of the thalamus, suggesting that lesions in these prominent sites of damage in Wernicke-Korsakoff disease develop only in the most advanced stages of thiamine deprivation. As a consequence of individual differences in susceptibility to thiamine deficiency, neurological symptoms and signs were more related to the profile of neural damage than to the number or duration of deprivation episodes.     

Neurologic complications after gastric restriction surgery for morbid obesity

We report the occurrence of neurologic complications in 23 patients who underwent gastric restriction surgery for the treatment of morbid obesity. Complications occurred 3 to 20 months after surgery. All the patients had had protracted vomiting for the first 3 months after the operation. The following syndromes were found: chronic or subacute symmetric polyneuropathy (12 patients), acute severe polyneuropathy (1 patient), burning feet syndrome (2 patients), meralgia paresthetica (3 patients), myotonic syndrome (1 patient), posterolateral myelopathy (2 patients), and Wernicke-Korsakoff encephalopathy (2 patients). The patients suffering from burning feet syndrome and those with Wernicke-Korsakoff encephalopathy showed a clear improvement after parenteral thiamine treatment. As to the rest of the patients, the occurrence of the complications seems to be linked to nutritional causes, although no such deficiencies were detected.     

Computed tomographic findings in Wernicke-Korsakoff syndrome

An unconscious patient had a differential diagnosis of coma. Traumatic, metabolic, and infectious origins were considered, but none explained her condition satisfactorily. Clinical features on examination were compatible with Wernicke-Korsakoff syndrome. Her condition improved with supportive treatment and thiamine hydrochloride administration. A computed tomographic scan showed large, symmetric, low-density thalamic lesions, the condition of which improved after three months.     

Visual evoked responses in chronic alcoholics.

Visual evoked responses (VERs) were recorded on 52 chronic alcoholics patients without Wernicke-Korsakoff syndrome, 22 of whom had cerebellar ataxia, and eight chronic alcoholics with Wernicke-Korsakoff syndrome. Abnormal VERs were found in 23% of patients without and 37% of patients with Wernicke-Korsakoff syndrome. The main VER abnormalities of all the alcoholic groups were prolonged latency and reduced amplitude of the P100 component. Improvement followed a six month period of abstinence. VERs may be useful in the early detection of alcohol induced brain damage, and in following the progress of patients with the condition.     

The Spectrum of Vestibular and Ocular Motor Abnormalities in Thiamine Deficiency

Purpose

The first aim of this review is to summarize recent ocular motor signs in pre-encephalopathy patients with nutritional deficiency at risk of thiamine deficiency. Timely recognition of thiamine depletion in these patients, who may have a normal brain MRI, could lead to appropriate management and prevention of Wernicke’s encephalopathy (WE) with full recovery. The second aim is to incorporate recent diagnostic testing on the revised WE diagnostic criteria and the identification of patients who may show slow, partial, or no response to treatment.

Recent Findings

Selective vulnerability of periventricular gray neurons in thiamine deficiency is well known. Involvement of the vestibular and abducens nuclei may precede encephalopathy. Studies have shown mild ophthalmoparesis and bilateral symmetric vestibular loss in thiamine deficiency. Moreover, quantitative data has shown decreased horizontal vestibulo-ocular reflex (VOR) gain and nystagmus, with a favorable response to timely treatment.

Summary

Ophthalmoparesis, horizontal nystagmus, and decreased gain of the horizontal VOR, sparing the vertical VOR, may be present in the early pre-encephalopathy stage of thiamine deficiency. Rapid response to a loading dose of parenteral thiamine might be seen in some cases and normalization, albeit slower in others. In contrast, analogous to the Korsakoff’s syndrome, ocular motor and vestibular abnormalities may show only partial improvement. Future studies in larger populations at risk are needed to confirm the results of these preliminary observations.

     

Coma and death in unrecognized Wernicke's encephalopathy. An autopsy study.

Eleven out of 36 autopsied cases of Wernicke's encephalopathy had developed coma. None of these patients had the diagnosis during life. There were six men and five women with ages ranging from 26 to 50 years (mean 36.6). Seven of these patients were heavy drinkers, three exhibited signs of severe malnutrition, whereas one was being evaluated for a disseminated gastric cancer and one was in treatment of hyperemesis gravidarum. Two patients were brought to the hospital after found unconscious at home. Neuropathological examination disclosed gross changes in the mammillary bodies in eight cases and microscopic changes in all cases. In one case there was atrophy of the anterior superior part of the vermis. Petechial hemorrhages were observed particularly in the walls of the third ventricle. Microscopically there were in addition to hemorrhages, glial proliferation, endothelial hypertrophy and necrosis of nerve cells and myelin. Central pontine myelinolysis was observed in one case. Wernicke's encephalopathy is a clinically underdiagnosed condition. Coma may mask its classical clinical picture or even be the sole manifestation. Although coma points to a poor outlook it may be reversed by thiamine administration. Any patient with coma of unknown etiology should be given parenteral thiamine.     

Persistence of disturbed thalamic glucose metabolism in a case of Wernicke-Korsakoff syndrome

We report the case of a 40-year-old alcoholic male patient, hospitalized with an acute ataxia of stance and gait, ocular muscle weakness with nystagmus and a global apathetic-confusional state. After admission, an amnestic syndrome with confabulation was also observed and diagnosis of Wernicke-Korsakoff syndrome was made. Under treatment with intravenous thiamine, the patient recovered completely from gaze weakness and ataxia, whereas a severe amnestic syndrome persisted. Fluorodeoxyglucose (FDG) positron emission tomography (PET) showed bilateral thalamic and severe bilateral temporal-parietal hypometabolism resembling a pattern typical for Alzheimer's disease. Longitudinal assessment of the alcohol-abstinent and thiamine-substituted patient revealed improvements of clinical state and neuropsychological performance that were paralleled by recovered cerebral glucose metabolism. In contrast to metabolic rates that increased between 7.1% (anterior cingulate, left) and 23.5% (parietal, left) in cortical areas during a 9-month remission period, thalamic glucose metabolism remained severely disturbed over time (change: left +0.2%, right +0.3%).     

The locus coeruleus and memory: a study of chronic alcoholics with and without the memory impairment of Korsakoff's psychosis.

The loss of noradrenergic locus coeruleus neurons has been identified as the possible critical lesion inducing amnesia in alcoholic patients with the Wernicke-Korsakoff syndrome. The present study aims to test this hypothesis by quantifying the number of pigmented locus coeruleus neurons in 4 alcoholics with the Wernicke-Korsakoff syndrome, 5 alcoholics with Wernicke's encephalopathy alone but no amnesia, and 1 alcoholic and 5 age-matched controls with no neurological disorders. Apart from an increased vascularity in the locus coeruleus of alcoholics, no significant differences in the number, morphology or distribution of pigmented locus coeruleus neurons was noted between any of the groups analysed. There was a significant correlation between the number of locus coeruleus neurons and brain weight. These data demonstrate that neither alcohol neurotoxicity nor thiamine deficiency result in a reduction in the number of pigmented cells in the locus coeruleus and refute the hypothesis that locus coeruleus cell loss is critical for the amnesia in the Wernicke-Korsakoff syndrome.     

Characteristics of the memory loss of a patient with Wernicke-Korsakoff's syndrome without alcoholism

The memory loss in alcoholic Wernicke-Korsakoff syndrome has been well characterized. However, it has been suggested that some of the neuropsychological defects seen in these patients are due to frontal lobe dysfunction resulting from chronic alcohol abuse. The present report details the nature and extent of the amnesia in a Wernicke-Korsakoff patient who did not have a history of alcoholism. In spite of her normal performance on measures of frontal lobe function, this patient showed many characteristics similar to those seen in alcoholic Wernicke-Korsakoff syndrome including a graded loss of remote memories and abnormal semantic information processing. Thus, the extent of the "core" features of this amnesic syndrome may be greater than was previously thought.     

Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy

We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.     

Persistence of habituation deficits after neurological recovery from severe thiamine deprivation

Rats were fed a thiamine-deficient diet for 4 weeks and injected daily with pyrithiamine during the last two weeks of the diet. This regime induced severe neurological anomalies such as ataxia, loss of righting reflex and visual place reflex, and finally full tonic-clonic seizures. These symptoms are reminiscent of the clinical Wernicke-Korsakoff syndrome. Injection of thiamine dramatically reversed these symptoms within one or two hours as seen in Wernicke patients. Six weeks later these rats showed a marked deficit in habituation of exploratory behavior and of the auditory orienting response. To what extent this chronic deficit in habituation contributes to the cognitive dysfunctions seen in Wernicke-Korsakoff patients is discussed. Histological examination of the brains of 6 of the rats revealed a heterogeneous pattern of damage to the brainstem, including mamillary bodies and several thalamic nuclei, reminiscent of that seen in Korsakoff patients. In addition there were many dark abnormal cells in limited fields of hippocampus neocortex and thalamus in almost all animals.     

Primary lateral sclerosis. A clinical diagnosis reemerges

Adults with slowly progressive noninherited gait disorders may show no abnormalities on examination other than signs implicating the corticospinal tracts. That is the syndrome of "primary lateral sclerosis" (PLS), a clinical diagnosis that has been avoided because it is a diagnosis of exclusion, proven only at autopsy. Now, modern technology can exclude other disorders that can cause the syndrome with an accuracy of about 95%. That serves to eliminate the following: compressive lesions at the foramen magnum or cervical spinal cord, multiple sclerosis, amyotrophic lateral sclerosis, Chiari malformation, syringomyelia, biochemical abnormality, and persistent infection with human immunodeficiency virus or human T-lymphotrophic virus type I. We studied three autopsy-proved cases of PLS; six living patients in whom PLS was diagnosed clinically after comprehensive evaluations that excluded the alternative diagnoses; and two patients with this syndrome of PLS and antibodies to human immunodeficiency virus seropositivity that clinically resembled PLS. Primary lateral sclerosis is now a respectable and permissible diagnosis.     

Peripheral nerve involvement in pernicious anaemia

Impairment of nervous function and thiamine metabolism were studied in 40 patients suffering from pernicious anaemia, 20 of whom had not been treated and the other 20 were on hydroxocobalamin therapy. Of the untreated patients 13 (65%) showed signs of peripheral nerve dysfunction with reduced conduction velocities, as compared with only 1 (5%) of the treated patients. Reduced blood thiamine levels were found in 16 of the untreated patients (80%), 10 (60%) of whom showed biochemical signs of thiamine deficiency. In the treated group, 7 patients (30%) had reduced blood thiamine levels. Thus, peripheral nerve involvement in pernicious anaemia is much more frequent than would be expected from the literature, and thiamine deficiency was present in the majority of these cases.     

The haematic thiamine level in the course of alcoholic neuropathy

The specific roles of ethanol and malnutrition in the pathogenesis of neurological disorders of chronic alcoholism remain unclear. We measured plasmatic thiamine levels and erythrocyte transketolase activity in 30 alcoholics with peripheral neuropathy and in 4 with a Wernicke-Korsakoff (W-K) syndrome. Thiamine levels in the first group were comparable to those of normal subjects while a significantly lower concentration was found in W-K syndrome. Transketolase activity was lower for both groups in comparison with normal subjects. We suggest that a defect in thiamine utilization is involved in peripheral neuropathy of alcoholics, rather than a lack of thiamine itself.     

Wernicke-korsakoff encephalopathy and polyneuropathy after gastroplasty for morbid obesity: report of a case

BACKGROUND: Gastric partitioning is a surgical procedure for the treatment of morbid obesity that may engender neurological complications, such as Wernicke encephalopathy and polyneuropathy. SETTING: A specialist hospital. PATIENT: A 36-year-old woman developed Wernicke-Korsakoff encephalopathy and polyneuropathy 3 months after gastroplasty for morbid obesity. A magnetic resonance scan documented the diagnosis, and a clear improvement occurred after parenteral thiamine treatment. In our patient and in previously described cases of the literature, postsurgical vomiting is a constant finding that seems to be the precipitating factor of neurological complications of gastric partitioning. CONCLUSION: Persistent vomiting after gastroplasty for morbid obesity should be considered an alarming symptom to treat immediately with appropriate measures.     

Wernicke's encephalopathy associated with hemodialysis: report of two cases and review of the literature.

Two rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients on hemodialysis (HD) are reported. They presented with the clinical triad of WE (ophthalmoplegia, ataxia and disturbance of consciousness) and intravenous administration of thiamine led to complete elimination of these manifestations. Reduced plasma thiamine levels prior to the administration confirmed the diagnosis of WE. Interestingly, a reduction in plasma thiamine levels by about half was seen in one of the patients on HD, suggesting that thiamine, a water-soluble vitamin, can be depleted with HD. In the literature, nine HD-dependent patients have been reported to develop WE, seven of whom were diagnosed postmortem. Their premortem diagnoses included uremic encephalopathy, dysequilibrium syndrome and dialysis dementia, which can often complicate HD and present symptoms similar to those of WE. We therefore emphasize that WE, even though a rare complication, should be suspected in all patients on HD who present with at least one of the clinical triad of WE.