Nonalcoholic Wernicke-Korsakoff Syndrome Resulting From Psychosis.

ABSTRACT: Wernicke encephalopathy (WE) results from thiamine deficiency. If undiagnosed or inadequately treated, WE evolves into Korsakoff syndrome (KS). We herein report a case of nonalcoholic Wernicke-Korsakoff syndrome (WKS) that resulted from malnutrition due to psychosis in a 42-years-old male patient. Thiamine deficiency was secondary to severe malnourishment due to poisoning delusions and daily life disorganization in a patient with previously unrecognized schizophrenia. Besides the presence of WE's classic triad of signs, brain magnetic resonance imaging showed also typical thalamic lesions. Furthermore, the patient also presented anterograde and retrograde amnesia, executive dysfunction, and confabulations, compatible with KS being already present. Intravenous treatment with thiamine was given for 37 days. Improvement in cognitive functions and brain imaging alterations was evident. Nevertheless, persistent WKS deficits were present. This case highlights the multiplicity of etiologies of WKS, namely, psychiatric, and its debilitating consequences if not promptly recognized and treated.

From psychosis to Wernicke encephalopathy: a case of hunger strike in prison.

Wernicke encephalopathy (WE) is a neuropsychiatric condition associated with  thiamine deficiency that includes a triad of mental status changes, ophthalmoplegia, and ataxia. Worsening WE may lead to Korsakoff syndrome(KS), in which cognitive impairments such as confabulation and memory deficits and also psychiatric symptoms may occur. Diagnosis of Wernicke-Korsakoff syndrome can be complicated in many cases. We present the case of a prisoner who commenced a hunger strike and developed WE. The preceding factors were associated with his oral intake refusal, which originated from his mental disorder with psychotic content. We discuss the clinical and treatment concerns for this complicated condition.

[The knowledge of resident doctors on diagnostics, etiology and treatment of Wernicke encephalopathy]. / De kennis van a(n)iossen over diagnostiek, etiologie en behandeling van wernicke-encefalopathie.

BACKGROUND: Wernicke encephalopathy (we) is a severe, acute neuropsychiatric disorder caused by a deficiency in thiamine. There have been indications that we is undertreated, which can lead to the Korsakoff syndrome, delirium or death. Treatment according to protocol is simple and effective. The knowledge of physicians about we has not been researched before.
AIM: To test the knowledge of resident doctors on diagnosis, etiology and treatment of we.
METHOD: The knowledge of 70 resident doctors in different medical specialties was examined through two clinical cases: the first with we due to hyperemesis gravidarum and the second due to alcohol abuse. Both open and multiple-choice questions were asked. Cues of the classical triad of we (cognitive disorder, eye movement disorder and gait disorder) were given accumulatively.
RESULTS: The classical triad of we was not recognized by 73% of the resident doctors in the case of hyperemesis gravidarum and they missed we in the case of alcohol abuse. Many of the resident doctors were not able to name the thiamin deficiency, the triad of we, more than three causes of we or the correct treatment with thiamine sufficiently. 67% of resident doctors indicated that their knowledge of we was insufficient and 76% expressed a need for more information about we.
CONCLUSION: The knowledge of resident doctors about the diagnostics, etiology and management of we is insufficient. Moreover, the resident doctors evaluate their knowledge about we to be insufficient. Medical school and postgraduate specialization have to focus more on this common and severe syndrome, which can appear in different medical areas.

Thiamine Substitution in Alcohol Use Disorder: A Narrative Review of Medical Guidelines.

AIMS: Patients with alcohol use disorder (AUD) frequently suffer from cognitive deficits ranging from mild symptoms to most severe forms. Wernicke encephalopathy (WE), caused by thiamine deficiency, is a potentially fatal syndrome characterized by the clinical triad of ophthalmoplegia, ataxia, and confusion. WE frequently presents in patients with AUD and, if left untreated, can progress to Wernicke-Korsakoff syndrome, which constitutes severe anterograde amnesia, confabulation, and behavioral abnormalities. Due to oftentimes indistinct clinical presentation, WE remains undiagnosed in up to 80% of cases. We conducted a review of current treatment guidelines for AUD in order to identify recommendations for the use of thiamine. METHODS: Three different keyword combinations ("alcohol treatment guideline," "alcohol withdrawal guideline," and "alcohol treatment recommendation") were entered in PubMed and Scopus, additional guidelines were searched screening the online sites of the respective agencies or societies. In total, 14 guidelines were included. RESULTS: Thiamine was mentioned in all but one of the reviewed publications. Specifications on application modalities and indications varied considerably. While the majority of reviewed guidelines recommended parenteral thiamine only for patients at high risk for WE, some gave no information regarding the application form or dosage. CONCLUSION: Substitution of parenteral thiamine in individuals with suspected WE is a well-established treatment regimen. However, suggestions according to guidelines vary widely. Furthermore, hardly any evidence-based recommendations exist on a more general use of thiamine as a preventative intervention in individuals with AUD. Further research is of utmost importance to raise awareness for this potentially undervalued problem.

Hyperemesis gravidarum causing Wernicke-Korsakoff syndrome: A rare complication.

Wernicke-Korsakoff syndrome (WKS) is a rare neurological disorder due to severe thiamine deficiency. It is most prevalent among alcoholics. However in nonalcoholics the prevalence varies from 0.04% to 0.13%. We report a case of WKS due to hyperemesis gravidarum. Primigravida patient with 16 weeks pregnancy with continuous vomiting for 1 month developed Wernicke's encephalopathy which progressed to Korsakoff psychosis. Patient was conservatively managed till term with appropriate thiamine replacement and antipsychotics. She developed oligohydramnios with late intrauterine growth retardation. Elective cesarean was done at 36 weeks. Female child with birth weight of 2.2 kg was born. Hyperemesis is a rare cause of WKS. This patient was inappropriately treated with dextrose and antiemetic without proper thiamine replacement. This case report highlights the importance of thiamine replacement and proper management of hyperemesis gravidarum with a scientific approach to prevent fatal complications like WKS.

Wernicke-Korsakoff syndrome in patients with cancer: a systematic review.

Wernicke-Korsakoff syndrome in patients with cancer is understudied. Much of what is known-that significant under-recognition and delays in treatment exist-comes from studies of alcohol misuse disorders or non-alcohol-related Wernicke-Korsakoff syndrome in patients. We investigated the frequency and associated features of cancer-related Wernicke-Korsakoff syndrome in the published literature. We included 90 articles reporting on 129 patients. Only 38 (30%) of 128 patients with data available exhibited the entire triad of classic features of Wernicke-Korsakoff syndrome: confusion, ataxia, and ophthalmoplegia or nystagmus. Diagnosis during life was missed altogether in 22 (17%) of 128 patients. The operational diagnostic criteria (at least two of the following: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment), which are considered more reliable than the classical triad, were used in only nine (7%) cases, yet 120 (94%) met the operational criteria for diagnosis at the time of presentation when applied retroactively. Complete recovery was reported in only 47 (36%) cases. Given that oncologists or haematologists accounted for only 17 (19%) first authors among the articles included, it is important that oncologists are aware of the risk factors for cancer-related Wernicke-Korsakoff syndrome, and that they are vigilant about diagnosing and treating the disease especially in the absence of alcohol misuse disorders.

Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review.

OBJECTIVE: Although Wernicke-Korsakoff syndrome (WKS) is a common condition, diagnosis remains difficult. WKS not associated with alcohol is rare and thought to present differently to alcohol-related WKS. We conducted a systematic review of WKS not related to alcohol to enhance understanding of WKS not related to alcohol and WKS in general. METHODS: A systematic review was conducted of case reports, published in English, of Wernicke's encephalopathy and WKS in patients without a history of alcohol-use disorder. Main data sources: MEDLINE, Index Medicus. Eligible cases totaled 623. Publication dates ranged from 1867 to 2014. Comparisons of clinical presentation were made with published data on samples comprising, almost exclusively, alcohol-related WKS. RESULTS: A wide array of illnesses precipitated WKS. When diagnosis of WKS was performed postmortem, non-alcohol-related cases presented a similar number of signs of the classic triad as alcohol-related cases (p=0.662, Cohen's w=0.12) but more signs when diagnosed antemortem (p<0.001, Cohen's w=0.46). The most common sign was altered mental state. Korsakoff syndrome or ongoing memory impairment was reported in 25% of non-alcohol-related WKS, although cognitive status was not explicitly reported in many cases. When duration of memory impairment was reported, 56% had clinically obvious memory impairment lasting beyond the period of acute presentation. Non-alcohol-related WKS was more often associated with female gender, younger age, shorter duration of precipitating illness and better survival rate compared to alcohol-related WKS. CONCLUSIONS: Thiamine deficiency in the absence of an alcohol-use disorder can cause the full clinical spectrum of WKS, including chronic cognitive impairment and Korsakoff syndrome.

Wernicke-Korsakoff Syndrome as a Consequence of Delusional Food Refusal: A Case Study.

Wernicke-Korsakoff syndrome is caused by thiamine (vitamin B1) deficiency, typically resulting from malnutrition secondary to chronic alcohol abuse. Less often, other conditions can lead to malnutrition and Wernicke-Korsakoff syndrome. We describe a 35-year-old man who developed Wernicke-Korsakoff syndrome with a typical neurologic and neuropsychological presentation after somatic delusions led him to refuse to eat. Cases like his serve to heighten awareness of the interplay between psychiatric and neurologic conditions, their sometimes atypical pathogenesis, and the value to primary care providers of consulting with psychiatrists, neurologists, and neuropsychologists when managing patients with possible Wernicke-Korsakoff syndrome.

Focal thalamic degeneration from ethanol and thiamine deficiency is associated with neuroimmune gene induction, microglial activation, and lack of monocarboxylic acid transporters.

BACKGROUND: Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL). Although TD alone can cause WE, the high incidence in alcoholism suggests that TD and ethanol (EtOH) interact. METHODS: Mice in control, TD, or EtOH groups alone or combined were studied after 5 or 10 days of treatment. THAL and entorhinal cortex (ENT) histochemistry and mRNA were assessed. RESULTS: Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed activated microglia, proinflammatory gene induction and THAL neurodegeneration that was greater than that found with TD alone (TD5), whereas 10 days resulted in marked THAL degeneration and microglial-neuroimmune activation in both groups. In contrast, 10 days of TD did not cause ENT degeneration. Interestingly, in ENT, TD10 activated microglia and astrocytes more than EtOH-TD10. In THAL, multiple astrocytic markers were lost consistent with glial cell loss. TD blocks glucose metabolism more than acetate. Acetate derived from hepatic EtOH metabolism is transported by monocarboxylic acid transporters (MCT) into both neurons and astrocytes that use acetyl-CoA synthetase (AcCoAS) to generate cellular energy from acetate. MCT and AcCoAS expression in THAL is lower than ENT prompting the hypothesis that focal THAL degeneration is related to insufficient MCT and AcCoAS in THAL. To test this hypothesis, we administered glycerin triacetate (GTA) to increase blood acetate and found it protected the THAL from TD-induced degeneration. CONCLUSIONS: Our findings suggest that EtOH potentiates TD-induced THAL degeneration through neuroimmune gene induction. The findings support the hypothesis that TD deficiency inhibits global glucose metabolism and that a reduced ability to process acetate for cellular energy results in THAL focal degeneration in alcoholics contributing to the high incidence of Wernicke-Korsakoff syndrome in alcoholism.

Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy.

Korsakoff syndrome is a chronic form of amnesia resulting from thiamine deficiency. The syndrome can develop from unrecognized or undertreated Wernicke encephalopathy. The intra-individual course of Wernicke-Korsakoff syndrome has not been studied extensively, nor has the temporal progression of gait disturbances and other symptoms of Wernicke encephalopathy. Here we present the detailed history of a patient whose acute symptoms of Wernicke encephalopathy were far from stable. We follow his mobility changes and the shifts in his mental status from global confusion and impaired consciousness to more selective cognitive deficits. His Wernicke encephalopathy was missed and left untreated, being labeled as "probable" Korsakoff syndrome. Patients with a history of self-neglect and alcohol abuse, at risk of or suffering with Wernicke encephalopathy, should receive immediate and adequate vitamin replacement. Self-neglecting alcoholics who are bedridden may have severe illness and probably active Wernicke encephalopathy. In these patients, mobility changes, delirium, or impaired consciousness can be an expression of Wernicke encephalopathy, and should be treated to prevent further damage from the neurologic complications of thiamine deficiency.

Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders.

Wernicke encephalopathy is an acute, reversible neuropsychiatric emergency due to thiamine deficiency. Urgent and adequate thiamine replacement is necessary to avoid death or progression to Korsakoff syndrome with largely irreversible brain damage. Wernicke Korsakoff syndrome refers to a condition where features of Wernicke encephalopathy are mixed with those of Korsakoff syndrome. Although thiamine is the cornerstone of treatment of Wernicke encephalopathy, there are no universally accepted guidelines with regard to its optimal dose, mode of administration, frequency of administration or duration of treatment. Currently, different dose recommendations are being made. We present recommendations for the assessment and treatment of Wernicke encephalopathy based on literature review and our clinical experience.

Wernicke encephalopathy: limitations in a laboratory and radiological diagnosis.

Wernicke encephalopathy is an emergent neurological disorder caused by vitamin B1 (thiamine) deficiency. Here, we present a case of Wernicke encephalopathy in a male patient in his 70s with normal serum thiamine levels and MRI findings on admission. He had a history of heavy alcohol consumption and a gradual decrease in food intake. On arrival at the hospital, his consciousness was impaired which persisted even after glucose replacement. Moreover, horizontal nystagmus and cerebellar ataxia were observed. Head CT scan and MRI revealed no abnormal findings. Further, his serum thiamine level was within the normal range. The patient was clinically diagnosed with Wernicke encephalopathy, and high-dose thiamine therapy was started. Then, his symptoms improved immediately. Thus, in case of clinical suspicion, treatment for Wernicke encephalopathy must be initiated promptly even in patients with normal serum thiamine levels.

Anterograde episodic memory in Korsakoff syndrome.

A profound anterograde memory deficit for information, regardless of the nature of the material, is the hallmark of Korsakoff syndrome, an amnesic condition resulting from severe thiamine (vitamin B1) deficiency. Since the late nineteenth century when the Russian physician, S. S. Korsakoff, initially described this syndrome associated with "polyneuropathy," the observed global amnesia has been a primary focus of neuroscience and neuropsychology. In this review we highlight the historical studies that examined anterograde episodic memory processes in KS, present a timeline and evidence supporting the myriad theories proffered to account for this memory dysfunction, and summarize what is known about the neuroanatomical correlates and neural systems presumed affected in KS. Rigorous study of KS amnesia and associated memory disorders of other etiologies provide evidence for distinct mnemonic component processes and neural networks imperative for normal declarative and nondeclarative memory abilities and for mnemonic processes spared in KS, from whence emerged the appreciation that memory is not a unitary function. Debate continues regarding the qualitative and quantitative differences between KS and other amnesias and what brain regions and neural pathways are necessary and sufficient to produce KS amnesia.

The evolution and treatment of Korsakoff's syndrome: out of sight, out of mind?

Wernicke's Encephalopathy is an acute neuro-psychiatric condition caused by an insufficient supply of thiamine (Vitamin B1) to the brain. If undiagnosed or inadequately treated, it is likely to proceed to Korsakoff's Syndrome. Wernicke's Encephalopathy can result from dietary deficiency alone and this form is usually successfully treated, with little chance of Korsakoff's Syndrome supervening. On the other hand, thiamine deficiency associated with alcohol misuse/dependence may require up to 1 gram of thiamine IV in the first 24 hours to be treated successfully. The reasons for this difference in treatment will be discussed. Thiamine diphosphate acts as a co-factor for a number of thiamine-dependent enzymes. Thiamine deficiency leads to a reduction in the activity of these enzymes, and this leads to alterations in mitochondrial activity, impairment of oxidative metabolism, decreased energy status and eventually selective neuronal death. The damage caused by the combination of thiamine deficiency and alcohol metabolism probably interferes with adequate thiamine transport at a number of sites in the body, including the blood-brain barrier, as well as causing damage to the apoenzymes which then require higher concentrations of thiamine to work normally. The accumulated damage is likely to render the use of oral thiamine therapeutically inadequate since the body is unable to produce high enough concentrations of thiamine in the blood to traverse the blood-brain barrier. Some individuals are probably genetically predisposed to develop Wernicke's. Long before individuals with alcohol misuse or dependence develop Wernicke's Encephalopathy the neurons and other cells of the body are functioning sub-optimally because of the inadequate supply of thiamine and the neurotoxic effect of alcohol. This relative deficiency initiates a series of pathological changes which accumulate and further interfere with the supply of thiamine and its utilisation at a time when the requirements are increased. The best treatment for Korsakoff's Syndrome is timely recognition of Wernicke's Encephalopathy and appropriate intervention and prevention.

[Clinical application of neuroimaging to alcohol-related dementia].

Alcohol-related dementia (ARD) is one of the most common dementing disorders in middle-aged people and occurs in heavy drinkers who are estimated to be 10 - 15 % of the adult men in a community. While the concept of ARD is multifactorial and includes all cognitive deficits in alcoholics, the central clinical manifestations are exemplified by Korsakoff's syndrome (KS), a persistent neuropsychiatric syndrome, characterized by amnesia and disorientation that is caused by thiamine deficiency along with excessive alcohol consumption. Antemortem detection of intracranial changes has been made possible by MRI and many studies have revealed that alcoholics have atrophic changes in frontal lobe, cerebellum, medial temporal lobe and hippocampus. However, these brain regions are vulnerable to excessive alcohol and seem to be independent of cognitive deficits in alcoholics. This review shows the regional differences in gray matter volumes between cognitively normal alcoholics and patients with KS. By employing a 3-dimensional MRI method for voxel-based morphometry that enables an automated, unbiased, comprehensive assessment, we demonstrate that parahippocampal/hippocampal atrophy is specific to KS and thalamic atrophy and the third ventricle enlargement are more severe in patients with KS than in cognitively normal alcoholics.

[Wernicke-Korsakoff syndrome and other diseases associated with thyamine deficiency]. / Síndrome de Wernicke-Korsakoff y otras patologías asociadas al déficit de tiamina.

Wernicke-Korsakoff syndrome is the best known consequence of thiamine deficiency, frequently associated with patients with chronic and excessive alcohol consumption, but it can be produced by any cause that produces thiamine deficiency. The disease is underdiagnosed so it is essential to have a high clinical suspicion, mainly in patients who do not have alcohol consumption as a risk factor. For this, the diagnosis continues to be eminently clinical, with the difficulty of high clinical variability. Complementary tests are used to support the diagnosis and rule out other causes that can produce similar symptoms, with magnetic resonance imaging being the most cost-effective imaging test. Treatment is based on the administration of thiamine, which should be started early, and parenterally at the appropriate doses, in all patients with compatible symptoms, without waiting to confirm the diagnosis.