Gastrointestinal beriberi: a forme fruste of Wernicke's encephalopathy?

Gastrointestinal symptoms, such as anorexia, nausea, vomiting and abdominal pain, are very common in patients with Wernicke's encephalopathy (WE). Mild thiamine deficiency may have only gastrointestinal symptoms. We are reporting two patients with thiamine deficiency who predominantly had gastrointestinal symptoms. Case 1: a 38-year-old man had gastrointestinal problems for about 2-3 years. It gradually became severe. The patient came to the neurology outpatient department for his recent-onset vertigo and headache. Clinical examinations fulfilled Caine's criteria of WE. Gastrointestinal symptoms responded dramatically to intravenous thiamine. Case 2: a 21-year-old woman developed drug-induced hepatitis and gastritis. Associated nausea, vomiting and abdominal pain progressively increased over the weeks. The patient responded only to intravenous thiamine administration.We suggest that a suspicion for gastrointestinal beriberi should arise if gastrointestinal symptoms (anorexia, nausea, vomiting and abdominal pain) are refractory to the usual therapies.

Wernicke Encephalopathy in Adolescents After Bariatric Surgery: Case Report and Review.

Roughly 1% of all weight loss surgery is performed in adolescents. There is strong evidence demonstrating significant postsurgical weight loss, improvement in quality of life, and reduction in comorbidities such as hypertension and diabetes. Reports of postoperative complications in adolescents are few because of the small sample size in most series. Despite vitamin supplementation, nutritional deficiencies requiring hospitalization occur occasionally after Roux-en-Y gastric bypass. Wernicke encephalopathy, a triad of ophthalmoplegia, ataxia, and altered mental status, is a serious consequence of thiamine (vitamin B1) deficiency. Few cases of Wernicke encephalopathy after weight loss surgery have been reported in the literature and even fewer in the pediatric population. Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. The clinical presentation, diagnosis, and treatment of Wernicke encephalopathy in adolescents after bariatric surgery are discussed.

Clinical awareness for health care professionals: Fatal encephalopathy complicating persistent vomiting in pregnancy.

Women with persistent vomiting during pregnancy need early referral to appropriate health facilities. Delayed referral and inappropriate management may lead to metabolic encephalopathy from a variety of causes, including electrolyte derangements or thiamine deficiency (Wernicke's encephalopathy) (WE). We present a case of persistent vomiting in pregnancy in which there was delayed referral, inappropriate treatment and failure to associate neurological signs such as terminal neck stiffness with WE, resulting in poor fetomaternal outcomes. In this report, we discuss the following lessons: (i) the need for early transfer of a patient with persistent vomiting and enigmatic clinical features to a higher healthcare facility; (ii) failure to associate neurological signs with complications of hyperemesis gravidarum/WE; (iii) lack of thiamine supplementation; and (iv) the advantages of magnetic resonance imaging over a computed tomography scan in the diagnosis of WE.

Consecuencia del abuso de alcohol / A consequence of alcohol abuse

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Evolution of abnormal eye movements in Wernicke's encephalopathy: correlation with serial MRI findings.

A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.

Restoration of mammillothalamic functional connectivity through thiamine replacement therapy in Wernicke's encephalopathy.

Resting-state functional MRI (fMRI) is now providing further understanding of neuropsychiatric illnesses. However, its practical applicability in the clinical realms is still questionable. Here we report three consecutive followed-up resting-state fMRI data in a single case with Wernicke encephalopathy before and after high-dose thiamine replacement therapy ranging over 20 months. We measured the mammillothalamic functional connectivity strength between the first ROI (mammillary body) and a voxel which showed the highest co-activation among voxels within the anterior thalamus (the second ROI) to enhance the specificity of the functional connectivity data. We found that the time-series changes in the mammillothalamic functional connectivity generally paralleled to the changes in delayed verbal and nonverbal recall memory scores in the left and right hemisphere, respectively. Among these, the left-side connectivity and delayed verbal recall score seemed to be related to the overall clinical status change. Modified directed transfer function (dDTF) analysis also identified significant information flows with mammillary-to-thalamic direction except at the acute illness state. Our findings, though preliminary in nature, suggest the practical applicability of resting-state fMRI to trace an effect of thiamine replacement therapy on the memory tract function in Wernicke encephalopathy at single-patient level.

Loss of astrocytic glutamate transporters in Wernicke encephalopathy.

Wernicke encephalopathy (WE), a neurological disorder caused by thiamine deficiency (TD), is characterized by structural damage in brain regions that include the thalamus and cerebral cortex. The basis for these lesions is unclear, but may involve a disturbance of glutamatergic neurotransmission. We have therefore investigated levels of the astrocytic glutamate transporters EAAT1 and EAAT2 in order to evaluate their role in the pathophysiology of this disorder. Histological assessment of the frontal cortex revealed a significant loss of neurons in neuropathologically confirmed cases of WE compared with age-matched controls, concomitant with decreases in alpha-internexin and synaptophysin protein content of 67 and 52% by immunoblotting. EAAT2 levels were diminished by 71% in WE, with levels of EAAT1 also reduced by 62%. Loss of both transporter sites was confirmed by immunohistochemical methods. Development of TD in rats caused a profound loss of EAAT1 and EAAT2 in the thalamus accompanied by decreases in other astrocyte-specific proteins. Treatment of TD rats with N-acetylcysteine prevented the downregulation of EAAT2 in the medial thalamus, and ameliorated the loss of several other astrocyte proteins, concomitant with increased neuronal survival. Our results suggest that (1) loss of EAAT1 and EAAT2 glutamate transporters is associated with structural damage to the frontal cortex in patients with WE, (2) oxidative stress plays an important role in this process, and (3) TD has a profound effect on the functional integrity of astrocytes. Based on these findings, we recommend that early treatment using a combination of thiamine AND antioxidant approaches should be an important consideration in cases of WE.

Thiamine deficiency-related brain dysfunction in chronic liver failure.

End-stage chronic liver failure results in thiamine deficiency caused principally by depletion of liver thiamine stores. Chronic liver failure also leads to increased brain ammonia concentrations. Both ammonia and thiamine deficiency result in decreased activity of alpha-ketoglutarate dehydrogenase, a rate-limiting tricarboxylic acid cycle enzyme. Loss of enzyme activity results in a mitochondrial oxidative deficit in brain and consequent increases in brain lactate, oxidative/nitrosative stress, cellular energy impairment and release of proinflammatory cytokines, all of which have been described in brain in end-stage chronic liver failure. Synergistic effects of ammonia exposure and thiamine deficiency could explain the diencephalic and cerebellar symptomatology described in patients with "hepatic encephalopathy". Unsuspected brain lesions due to thiamine deficiency could explain the incomplete resolution of neuropsychiatric symptoms following the use of ammonia-lowering agents or liver transplantation in patients with end-stage chronic liver failure. These findings underscore the need for prompt, effective thiamine supplementation in all patients with chronic liver failure.

Neurologic complications of gastric bypass surgery for morbid obesity.

BACKGROUND: The number of bariatric procedures is rapidly growing as the prevalence of obesity in the USA is increasing. Such procedures are not without complications, and those affecting the nervous system are often disabling and irreversible. We now describe our experience with these complications and review the pertinent literature. METHODS: We describe 26 patients with major neurologic conditions that seemed causally related to bariatric surgery encountered in the neurology service of a tertiary referral university medical center over a decade. RESULTS: The neurologic complications affected most regions of the nervous system: encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. Myelopathy was the most frequent and disabling problem; symptoms began about a decade after surgery. Encephalopathy and polyradiculoneuropathy were acute and early complications. Except for vitamin B(12) and copper deficiencies in patients with myelopathy, we could not correlate specific nutritional deficiencies to the neurologic complications. All patients had multiple nutritional deficiencies, but their correction did not often yield dramatic results. The best result was achieved in one patient after surgical revision to reduce the bypassed jejunum. CONCLUSIONS: A wide spectrum of serious neurologic conditions may follow bariatric surgery. These complications may occur acutely or decades later.

Argumentation with restricted linguistic ability: performing a role play with aphasia or in a second language.

The main objective of this study is to illustrate how adaptation to linguistic limitations takes place in a specific activity and is affected by factors pertaining to the social activity or the individuals. A man with aphasia is compared to an adult immigrant L2 learner. An argumentative role play was video-recorded, transcribed and analysed. Both subjects have a very limited vocabulary and produce short utterances. The L2 learner often uses words that are semantically related to the target word, while the subject with aphasia uses more general and vague words, like pronouns, in combination with adverbs and set phrases. Both subjects use gesturing as strategy, and it is suggested that the semantic specificity of words as well as gestures is important in determining the role of gesture. Apart from gesture, he L2 learner uses mainly simplification and appeal strategies, while the subject with aphasia uses mainly fluency and sociolinguistic strategies.

Downregulation of complexin I and complexin II in the medial thalamus is blocked by N-acetylcysteine in experimental Wernicke's encephalopathy.

Metabolic dysfunction as a consequence of thiamine (vitamin B1) deficiency (TD), a model of Wernicke's encephalopathy, leads to elevation of extracellular glutamate concentration in vulnerable brain regions consistent with the development of excitotoxicity. Complexin I and complexin II are two genes labeling principally inhibitory and excitatory synapses, respectively. Because current evidence supports an important role for complexins in the modulation of neurotransmitter release, we examined the involvement of both proteins in the pathology of the medial thalamus and inferior colliculus in TD rats by immunoblotting. At the symptomatic stage, complexin I and complexin II levels in the medial thalamus were decreased by 63% and 45%, respectively, compared to control animals, but were unchanged in the inferior colliculus. These changes in thalamus were also observed using immunohistochemical methods, and seemed to be due to downregulation of both proteins because synaptophysin levels were unaffected in this brain region. In addition, cotreatment with the antioxidant N- acetylcysteine prevented both neuronal loss and downregulation of complexins. Our findings suggest dysregulation of excitatory and inhibitory neurotransmitter release in the medial thalamus, which is not present in the inferior colliculus. Furthermore, loss of complexin I and II in the thalamus may be mediated by processes that involve oxidative stress. Such changes in complexin levels may contribute to the pathophysiology of thalamic damage in TD, and offer a potential basis for the well-known differences in pathology between this structure and the inferior colliculus in this disorder.

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

Increased mast cell degranulation within thalamus in early pre-lesion stages of an experimental model of Wernicke's encephalopathy.

A large increase in the number and percentage of degranulating mast cells was observed within thalamus of rats after 6-7 days of thiamine deficiency (TD). No mast cells were detected in the inferior olivary and lateral vestibular nuclei, which are also severely damaged by TD. After 11-12 days of TD, the number of ED2 immunopositive macrophages increased in thalamus. In the brainstem nuclei, an increase in the number of macrophages occurred much earlier in treatment (i.e. day 6). An increase in GFAP-positive astrocytes within thalamus occurred after the changes in mast cells and prior to the increase in macrophages. In brainstem, reactive astrocytes appeared along with the increase in macrophages. These data suggest that mast cell degranulation is a very early response induced by TD, and the resultant release of cytokines and other chemical mediators may play critical roles in both the early vascular damage and eventual tissue destruction within thalamus, but not within brainstem. These results also suggest that macrophages and reactive astrocytes may play more direct roles in the pathogenesis of brainstem lesions.

Receptor binding sites and uptake activities mediating GABA neurotransmission in chronic alcoholics with Wernicke encephalopathy.

Superior frontal cortex (SFC) and primary motor cortex tissue was obtained at autopsy from thirteen severe chronic alcoholics with neuropathologically confirmed Wernicke Encephalopathy (WE) and 22 controls. Cases with both WE and cirrhosis showed markedly fewer neurones in SFC than did WE cases without cirrhosis. The extent of the apparent neuronal loss corresponded to an increase in post-synaptic GABAA receptor sites, as assessed by the binding of [3H]muscimol to synaptic membranes. Increased [3H]muscimol binding was not accompanied by an increase in 'central-type' benzodiazepine binding sites: as assessed by [3H]flunitrazepam binding, these sites were apparently unaltered, while as assessed by [3H]diazepam binding, they were decreased. The affinities of the two benzodiazepine ligands varied differently with disease. These discrepancies between [3H]flunitrazepam and [3H]diazepam binding could not be accounted for, either by the presence of a second, diazepam-preferring, 'central-type' benzodiazepine binding site, or by loss of 'peripheral-type' sites. The changes in the post-synaptic GABAA-benzodiazepine receptor sites did not reflect any regional, disease-related deficit of afferent GABAergic terminals, as assessed by synaptosomal high-affinity [3H]GABA uptake. On a number of indices, it appears most likely that the data reflect both a loss of receptor sites, and a change in the population of receptor sub-types.

Radio-frequency lesions of the thalamus produce delayed-nonmatching-to-sample impairments comparable to pyrithiamine-induced encephalopathy in rats.

Rats were trained and matched on a delayed-nonmatching-to-sample (DNMTS) task and randomly assigned to treatment. In Experiment 1, radio-frequency (RF) lesions were aimed at lateral portions of the internal medullary lamina (L-IML), midline thalamus (MT), mammillary bodies (MB), and the combination of MT and MB. In Experiment 2, RF lesions were aimed at the fornix. After recovery, DNMTS was retrained at retention intervals retention interval of 3.0-18.0 s, the critical retention interval for 75% DNMTS accuracy was determined by a staircase procedure, and spontaneous exploration was observed in an open field. L-IML lesions produced significant deficits on DNMTS and exploratory behavior that were comparable to deficits on the same tasks in rats recovered from pyrithiamine-induced thiamine deficiency. Fornix lesions produced significant DNMTS deficits that were substantially smaller than for the L-IML group. The MT, MB, and MT+MB treatments had no significant effect on DNMTS.

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to one of four treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to 15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment.

The value of brainstem auditory evoked potentials in early diagnosis of Wernicke's encephalopathy.

Statistical analysis of the interpeak latencies of brainstem auditory evoked potentials (BAEP) shows that a delayed IPL I-V is a very sensitive indicator for an early diagnosis of Wernicke's encephalopathy. In cases of uncomplicated delirium tremens no significant deviations of BAEP were found.

Wernicke's encephalopathy.

Wernicke's encephalopathy should be considered as a possible diagnosis in comatose and hypothermic patients. The classic triad of confusion, ophthalmoplegia (or nystagmus) and ataxia may be absent, and the history of alcohol abuse or other causes of thiamine deficiency may be unknown. Left untreated, acute Wernicke's encephalopathy has a 17 percent mortality rate. Since the morbidity from Wernicke's encephalopathy is potentially reversible with parenteral thiamine, and large doses of thiamine can be given without documented ill effects, it is recommended that all comatose or hypothermic patients, as well as those with more classic presentations of Wernicke's encephalopathy, be given parenteral thiamine before administration of glucose.