A Case Report of Nonalcoholic Gayet-Wernicke Encephalopathy: Don't Miss Thiamine.

Gayet-Wernicke encephalopathy (WE) is an acute neurological disorder resulting from deficiency of thiamine, commonly related to chronic abuse of alcohol, but frequently missed or overlooked as a diagnosis when a nonalcoholic patient presents with atypical signs and symptoms of the disease. The diagnosis of the disease is clinical, and confirmation is done by magnetic resonance imaging. We aim to highlight a case of WE in a nonalcoholic postoperative surgical patient receiving total parental nutrition where high-dose intravenous administration of thiamine in time mitigated the symptoms of disease and prevented permanent neurological sequelae. We spotlight the significance of adequate thiamine for postoperative malnourished surgical patients.

Missing the early signs of thiamine deficiency. A case associated with a liquid-only diet.

BACKGROUND: Wernicke encephalopathy (WE) predominantly occurs in alcoholic patients. Few case reports have described this diagnosis as a result of dieting. The diagnosis is often missed or delayed resulting in permanent and severe neurologic sequelae and even death. The typical neurological signs may be absent or missed during the early stages of thiamine deficiency. CASE REPORT: A 23-year-old female presented to the hospital with confusion, bilateral lateral rectus palsy, and ataxia. Based on the typical neurological triad, WE was suspected. The brain MRI was also typical for WE. Prompt clinical improvement was seen within days after intravenous thiamine supplementation. A detailed medical history revealed that during the past 3 months she had been following a liquid-only diet and had lost about 30 kg. During that time, she had visited the emergency department on multiple occasions due to fatigue, nausea, and vomiting. CONCLUSION: A high level of suspicion is required by physicians to recognize that fatigue, nausea, and vomiting may represent early signs of thiamine deficiency in patients at risk for nutritional deficiencies. Empirical thiamine supplementation may be reasonable in such cases.

An autopsied case of MM1-type sporadic Creutzfeldt-Jakob disease with pathology of Wernicke encephalopathy.

An 83-year-old Japanese man presented with gait disturbance followed by rapidly-progressive cognitive impairment. Magnetic resonance diffusion-weighted images showed extensive hyperintense regions in the cerebral cortex. Four weeks after symptom onset, myoclonus appeared, and the patient developed difficulty swallowing; intravenous peripheral continuous infusions without vitamin supplementation were administered during the last two months of the patient's life. The patient reached the akinetic mutism state and died 12 weeks after symptom onset due to sepsis. The brain weighed 940 g and showed general cerebral atrophy. Extensive spongiform change were observed in the cerebral cortex, striatum, thalamus, and cerebellar cortex, but gliosis was generally mild. Numerous newly-developed hemorrhage foci were observed in the mammillary body, the areas adjacent to the third and fourth ventricles, and the periaqueduct of the midbrain; however, proliferation of capillaries and endothelium and collections of macrophages were relatively inconspicuous. These findings suggested comorbidity with the acute stage of Wernicke encephalopathy (WE). Immunostaining showed extensive diffuse synaptic-type prion protein deposition in the gray matter. According to the neuropathological, genetic, and molecular findings, the present case was finally diagnosed as MM1-type sporadic Creutzfeldt-Jakob disease (CJD) with WE. We should remain alert to the diagnosis of WE when CJD is suspected, and it is necessary to consider the complications of both diseases. This report emphasizes the importance of pathological investigations for the diagnosis of CJD, WE, and the coexistence of both.

Recurrent Wernicke's encephalopathy in pregnancy: A case report.

INTRODUCTION: Wernicke's encephalopathy (WE) is an acute neurologic syndrome resulting from a deficiency in thiamine, also known as Vitamin B1. Thiamine stores can be depleted rapidly in patients with severe hyperemesis. Treatment with thiamine typically results in complete resolution of the neurological abnormalities. CASE REPORT: A 15-year-old G2P0010 at 13.2 weeks gestation presented with altered mental status and transaminitis. She had a medical termination in her previous pregnancy following an admission for a similar clinical scenario. She was initially thought to have a postoperative surgical complication due to recent cholecystectomy, but further evaluation revealed thiamine depletion. Magnetic resonance imaging confirmed the diagnosis of WE. Repletion of thiamine and folic acid resulted in rapid clinical improvement. CONCLUSION: WE should be considered in the differential diagnosis of pregnant patients with hyperemesis and altered mental status. A prior history of WE increases the risk of recurrence during pregnancy. Severe hyperemesis during pregnancy increases the risk of thiamine deficiency and WE. Early thiamine supplementation may reduce the risk of WE in patients with a prior clinical history or in patients with severe hyperemesis gravidarum.

Putamina involvement in Wernicke encephalopathy induced by Janus Kinase 2 inhibitor.

OBJECTIVE: The aim of the study was to report a case of Wernicke encephalopathy (WE) due to fedratinib (Janus Kinase 2 inhibitor) treatment with atypical neuroimaging findings. METHODS: We present a detailed report of the case and literature review. RESULTS: A 68-year-old woman under treatment with fedratinib (investigational JAK2 inhibitor) developed memory impairment, diplopia, and ataxia compatible with WE. Brain magnetic resonance imaging showed extensive lesions involving medial thalami, periaqueductal gray, caudate nuclei, and putamina. Thiamine supplementation provided clinical recovery and radiological improvement of the lesions described. Basal ganglia lesions have been previously described in children with this disease, but this is rarely found in adults. Clinical trials including fedratinib have been recently discontinued, and its involvement in pathogenesis of WE may be related to thiamine-transporter inhibition. CONCLUSIONS: Our case represents an example of drug-related WE, with a rare radiological pattern. Precocious diagnosis and treatment are essential to prevent irreversible brain injury.

Pyrithiamine-induced thiamine deficiency alters proliferation and neurogenesis in both neurogenic and vulnerable areas of the rat brain.

Thiamine deficiency (TD) leads to Wernicke's encephalopathy (WE), in which focal histological lesions occur in periventricular areas of the brain. Recently, impaired neurogenesis has been reported in the hippocampus during the dietary form of TD, and in pyrithiamine-induced TD (PTD), a well-characterized model of WE. To further characterize the consequences of PTD on neural stem/progenitor cell (NSPC) activity, we have examined the effect of this treatment in the rat on both the subventricular zone (SVZ) of the rostral lateral ventricle and subgranular layer (SGL) of the hippocampus, and in the thalamus and inferior colliculus, two vulnerable brain regions in this disorder. In both the SVZ and SGL, PTD led to a decrease in the numbers of bromodeoxyuridine-stained cells, indicating that proliferation of NSPCs destined for neurogenesis in these areas was reduced. Doublecortin (DCX) immunostaining in the SGL was decreased, indicating a reduction in neuroblast formation, consistent with impaired NSPC activity. DCX labeling was not apparent in focal areas of vulnerability. In the thalamus, proliferation of cells was absent while in the inferior colliculus, numerous actively dividing cells were apparent, indicative of a differential response between these two brain regions. Exposure of cultured neurospheres to PTD resulted in decreased proliferation of NSPCs, consistent with our in vivo findings. Together, these results indicate that PTD considerably affects cell proliferation and neurogenesis activity in both neurogenic areas and parts of the brain known to display structural and functional vulnerability, confirming and extending recent findings on the effects of TD on neurogenesis. Future use of NSPCs in vitro may allow a closer and more detailed examination of the mechanism(s) underlying inhibition of these cells during TD.

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.

Wernicke encephalopathy with atypical magnetic resonance imaging.

Wernicke encephalopathy (WE) is a medical emergency caused by thiamine (vitamin B1) deficiency. Typical clinical manifestations are mental change, ataxia, and ocular abnormalities. Wernicke encephalopathy is an important differential diagnosis in all patients with acute mental change. However, the disorder is greatly underdiagnosed. Clinical suspicion, detailed history taking, and neurologic evaluations are important for early diagnosis. Magnetic resonance imaging (MRI) is currently considered the diagnostic method of choice. Typical MRI findings of WE are symmetrical involvement of medial thalamus, mammillary body, and periaqueductal gray matter. Prompt thiamine supplement is important in avoiding unfavorable outcomes. Here, we report a case of alcoholic WE with typical clinical presentation but with atypical MRI. Axial fluid-attenuated inversion recovery images showing symmetrical hyperintensity lesions in dentate nuclei of cerebellum, olivary bodies, and dorsal pons. Although atypical MRI findings are more common in nonalcoholic WE, it can also occur in alcoholic WE. This article is aimed to highlight the potential pitfalls in diagnosing acute mental change, the importance of clinical suspicion, and early treatment in WE.

Neurological complications in hyperemesis gravidarum.

Hyperemesis gravidarum can impair correct absorption of an adequate amount of thiamine and can cause electrolyte imbalance. This study investigated the neurological complications in a pregnant woman with hyperemesis gravidarum. A 29-year-old pregnant woman was admitted for hyperemesis gravidarum. Besides undernutrition, a neurological examination disclosed weakness with hyporeflexia, ophthalmoparesis, multidirectional nystagmus and optic disks swelling; the patient became rapidly comatose. Brain MRI showed symmetric signal hyperintensity and swelling of periaqueductal area, hypothalamus and mammillary bodies, medial and posterior portions of the thalamus and columns of fornix, consistent with Wernicke encephalopathy (WE). Neurophysiological studies revealed an axonal sensory-motor polyneuropathy, likely due to thiamine deficiency or critical illness polyneuropathy. Sodium and potassium supplementation and parenteral thiamine were administered with improvement of consciousness state in a few days. WE evolved in Korsakoff syndrome. A repeat MRI showed a marked improvement of WE-related alterations and a new hyperintense lesion in the pons, suggestive of central pontine myelinolysis. No sign or symptom due to involvement of the pons was present.

Atypical Wernicke's encephalopathy showing involvement of substantia nigra.

CASE HISTORY: Wernicke's encephalopathy is a metabolic disorder caused by deficiency of thiamine (vitamin B1) seen in alcoholics and even in nonalcoholic patients, classically presenting with a triad of ataxia, ophthalmoplegia, and altered mental status. Typical findings in magnetic resonance imaging are represented by symmetric signal alterations in medial thalami, mamillary bodies, tectal plate, and periaqueductal area and atypical findings involve lesions in cerebellum, midline vermis, red nuclei, dentate, caudate, cranial nerve nuclei, splenium and cerebral cortex. We report here a case of nonalcoholic starvation induced atypical WE showing symmetrical lesions in substantia nigra in addition to the classical neuroradiological findings.

[Wernicke's encephalopathy in chronic alcoholics]. / Wernicke-sjúkdómur medal áfengissjúkra.

Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition. Clinically, its key features are mental status disorders and oculomotor abnormalities as well as stance and gait ataxia. The diagnosis of WE is frequently missed although delay of appropriate treatment can lead to death or Korsakoff's amnestic syndrome. It is therefore crucial in suspected cases of WE, not to await confirmation of diagnosis, but immediately administer high-dose intravenous thiamine and simultaneously treat magnesium deficiency. Alcoholics at risk of WE should on admission receive immediate prophylactic therapy with parenteral thiamine.

A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations.

BACKGROUND: SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases. METHODS: We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions. RESULTS: Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient. CONCLUSION: Our cases broaden the phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.

Neuroimaging findings in pediatric Wernicke encephalopathy: a review.

Wernicke encephalopathy (WE) is an acute neurological disease resulting from dietary thiamine (vitamin B1) deficiency. WE is characterized by changes in consciousness, ocular dysfunction, and ataxia. Neuroradiologic findings usually show symmetric signal intensity alterations in the mammillary bodies, medial thalami, tectal plate, and periaqueductal area. Selective involvement of the cranial nerve nuclei, cerebellum, red nuclei, dentate nuclei, fornix, splenium, cerebral cortex, and basal ganglia characterize nonalcoholic WE patients. Furthermore, symmetric basal ganglia alterations with involvement of the putamen have only been observed in children. The incidence of WE is underestimated in both adult and pediatric patients. Interestingly, the frequency of WE in children appears to be similar to that observed in adults. The prognosis of the disease largely depends on the time from diagnosis to thiamine supplementation. The aim of this pediatric literature review is to provide an update on neuroradiologic findings in children affected by WE in an effort to determine pertinent clinical and imaging findings that can improve the detection and early identification of the disease. A thorough knowledge of the MRI findings of WE will assist in arriving at an early diagnosis, thereby reducing the morbidity and mortality associated with this disease in children.

Wernicke's encephalopathy induced by total parental nutrition.

Wernicke's encephalopathy is an acute neurological syndrome due to thiamine deficiency, which is characterized by a typical triad of mental status changes, oculomotor dysfunction and ataxia. Despite the fact that Wernicke's encephalopathy, in developed countries, is frequently associated with chronic alcoholism, there have been a number of published cases associating this encephalopathy with parenteral feeding without vitamin supplementation. Diagnosis is primarily a clinical one, and can be supported by laboratory tests and imaging studies; treatment should start as soon as possible, for the morbidity and mortality (almost 20%) associated with this syndrome is high. Thiamine supplementation, along with other vitamins, is recommended for patients in risk of developing this syndrome.

[Familial Wernicke's-like encephalopathy].

Wernicke's encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, and confusion with thiamine deficiency. We reported on two Japanese brothers with a newly discovered recessively inherited syndrome similar to Wernicke's encephalopathy that developed in the second decade of life; this syndrome was manifested clinically as thiamine-responsive diplopia, ataxia and confusion without serum thiamine deficiency. The patients had complex partial seizure. The administration of high-dose thiamine improved these symptoms. MRI of the brain showed high-intensity signals in the bilateral medial thalamus and periaqueductal region on fluid-attenuated inversion recovery images; these signals were characteristic of findings in Wernicke's encephalopathy. There was no history of chronic alcoholism. The clinical and images features resembling Wernicke's encephalopathy in these patients suggested that the syndrome was caused by a genetic disorder of thiamine metabolism. Genomic analysis of SLC10A3 encoding human thiamine transporter 2 revealed that the patients were compound heterozygotes for the K44E and E320Q mutations. Gene-expression analyses of mammalian culture cells showed that intracellular thiamine uptake activities were decreased significantly. High expression of SLC19A3 RNA in the thalamus may explain the selective thalamic lesions on MRI. The identification of this syndrome proves insight into the thiamine metabolism associated with Wernicke's encephalopathy in humans.

Hyperemesis-gravidarum-induced Wernicke's encephalopathy: serial clinical, electrophysiological and MR imaging observations.

Wernicke's encephalopathy (W.E.), a potentially reversible condition caused by thiamine deficiency, is usually suspected in the setting of chronic alcoholism and might not be recognized when associated with other conditions. We describe a young pregnant woman who presented with rapidly evolving ataxia, diplopia and irrelevant speech following repeated vomiting. Characteristic brain MRI and rapid response to thiamine suggested that she had W.E. possibly due to hyperemesis gravidarum. A high index of suspicion is required, since delayed or lack of treatment may lead to high morbidity and mortality.

MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics.

BACKGROUND AND PURPOSE: Wernicke encephalopathy (WE) is a severe neurologic disorder resulting from dietary vitamin B(1) deficiency. This study was undertaken to analyze and compare MR imaging findings and neurologic manifestations at clinical presentations of patients with WE with and without a history of alcohol abuse. MATERIALS AND METHODS: WE patients were identified using diagnostic neurologic data bases. Fifty-six patients (29 females, 27 males) diagnosed between 1999 and 2008 with WE who improved within 1 month from the onset of thiamine administration were included in the analysis. Patients' records were reviewed for clinical manifestations and imaging studies' findings. MR imaging was performed in the acute phase of the disease at a field strength of 1T (16 patients) and 1.5T (40 patients). All MR images were of acceptable to good quality and were retrospectively reviewed. We compared imaging findings and clinical presentation in the alcoholic (AL) group versus the non-alcoholic (NA) group using the 2-tailed Fisher exact test and the Phi coefficient as appropriate. RESULTS: Forty-three percent of the patients were in the AL group, whereas 57% were in the NA group. Eighty-nine percent showed changes in consciousness, 75% had ocular manifestations, and 54% had ataxia. On MR imaging, 80% of the patients had evidence of symmetric lesions in the medial thalami and in the periventricular region of the third ventricle; 59%, in the periaqueductal area; 45%, in the mamillary bodies; 36%, in the tectal plate; and 7%, in the periventricular gray matter located anteriorly to the fourth ventricle. Signal-intensity alterations in areas considered atypical for the disease were noted only in the NA group and always in association with the typical findings. Contrast enhancement of the thalamus and mamillary bodies was significantly associated with alcohol abuse. CONCLUSIONS: Contrast enhancement in the mamillary bodies and thalamus is a typical finding of the disease in AL patients. Atypical MR imaging findings characterize NA patients.

[Wernicke encephalopathy after subtotal gastrectomy for morbid obesity]. / Encéphalopathie de Gayet-Wernicke après gastrectomie partielle pour obésité morbide.

Wernicke's encephalopathy (WE) is one of the potential complications of obesity surgery. It is an acute neuropsychiatric syndrome resulting from thiamine deficiency often associated with repeated vomiting. The classic triad is frequently reported in these patients (optic neuropathy, ataxia and confusion), associated with uncommon features. Cerebral impairment affects the dorsal medial nucleus of the thalamus and the periaqueductal grey area, appearing on MRI, as hyperintense signals on T2, Flair and Diffusion weighted imaging. Early diagnosis and parenteral thiamine are required to decrease morbidity and mortality. We report a case of WE and Korsakoff's syndrome in a young obese patient after subtotal gastrectomy, who still has substantial sequelae. The contribution of MRI with diffusion-weighted imaging is illustrated. The interest of nutritional supervision in the first weeks and preventive thiamine supplementation in case of repeated vomiting are of particular importance in these risky situations.

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.