Suspected Thiamine Deficiency Secondary to Chronic Gastrointestinal Illness: A Case Report.

Introduction: Thiamine deficiency, also known as beriberi, is a nutritional disorder caused by a lack of thiamine (vitamin B1) in the diet. It can occur in 2 forms: dry beriberi, which affects the nervous system, and wet beriberi, which affects the cardiovascular system. Gastrointestinal beriberi is a subtype that affects the digestive system and can lead to multisystem involvement. In the United States (US), thiamine deficiency often arises from chronic malnutrition secondary to alcoholism, known as Wernicke-Korsakoff Syndrome. Case Presentation: A 45-year-old female with no known past medical history or alcohol use disorder came to the emergency department with an altered mental status and with a history of intractable nausea and vomiting for several months prior to presentation. During intake, the medical team discovered she had bilateral lower extremity weakness and an anion gap metabolic acidosis. Her inpatient workup ruled out meningitis, encephalitis, peritonitis, diabetic ketoacidosis, and cerebrovascular accident. A thiamine deficiency was the most probable cause of her presentation, secondary to her protracted history of vomiting and poor oral medication intake. Refeeding syndrome complicated her hospitalization. After replenishing thiamine, the patient experienced significant improvement in mental status and lower extremity weakness. The healthcare team later discharged her with home physical therapy rehabilitation and nutritional counseling. Conclusion: Thiamine deficiency is not common in the US. However, this case highlights the importance of including this deficiency in the differential when a patient arrives with a history of malnourishment secondary to a gastrointestinal illness with signs of altered mental status and neurological symptoms.

The Weight of Bariatric Surgery: Wernicke-Korsakoff Syndrome after Vertical Sleeve Gastrectomy-A Case Series.

In this case series, the simultaneous occurrence of Wernicke's encephalopathy (WE) and dry beriberi was reported in three patients who underwent vertical sleeve gastrectomy (VSG) between May 2021 and May 2023. All patients were obese women who underwent vertical sleeve gastrectomy (VSG) without immediate postoperative complications, but two weeks later, hyperemesis and subsequent encephalopathy with ocular movement abnormalities and weakness were observed over the following thirty days. Patients were referred to neurology, where due to the high suspicion of WE, thiamine replacement therapy was initiated; meanwhile, diagnostic neuroimaging and blood tests were conducted. Neurological and psychiatric evaluations and neuroconduction studies were performed to assess the clinical evolution and present sequelae. One year after diagnosis, all patients exhibited affective and behavioral sequelae, anterograde memory impairment, and executive functioning deficits. Two patients met the criteria for Korsakoff syndrome. Additionally, peripheral nervous system sequelae were observed, with all patients presenting with sensorimotor polyneuropathy. In conclusion, Wernicke's encephalopathy requires a high diagnostic suspicion for timely intervention and prevention of irreversible sequelae, which can be devastating. Therefore, raising awareness among medical professionals regarding the significance of this disease is essential.

Rehabilitation Strategies for Wernicke-Korsakoff Syndrome: Physiotherapy Interventions and Management Approaches.

Korsakoff syndrome and Wernicke's encephalopathy (WE) show neurological and cognitive deficits. Wernicke-Korsakoff syndrome (WKS) is a compound neurological condition. The cause of this neurological condition could be the consumption of alcohol regularly for a chronic duration. A tailored rehabilitation protocol that focuses on cognitive and physical deficiencies was implemented along with thiamine supplementation for managing a case of a 49-year-old male patient who had a history of high alcohol consumption and was exhibiting typical signs of WKS. After planning a proper physiotherapy plan, it is necessary to look after the patient's progress along with re-evaluation, which reveals notable gains in cognitive function, memory, and functional independence. There is a dearth of research on the impact of physical therapy in managing WKS. The above case report reflects the benefits of combining physiotherapy, cognitive rehabilitation, and balance training to improve patient functionality and independence. Tailored rehabilitation interventions like the Benson relaxation method (BRM), brain gym exercises, Frenkel's exercise, electrical stimulation, sensorimotor training, basic body awareness therapy (BBAT), and gait training can be used to enhance a patient's quality of life. Addressing individual needs is essential in managing WKS, focusing on the importance of comprehensive care beyond cognitive rehabilitation alone.

Silent Echoes: A Case Report of Wernicke Encephalopathy's Unheard Voice.

Wernicke encephalopathy (WE) is an acute neuropsychiatric emergency that is caused by a deficiency in vitamin B1 (thiamine). This condition is most commonly seen in patients with alcohol use disorder; however, patients with other disorders of severe malnourishment are also at increased risk. In severe cases, this disease may be followed by Korsakoff's psychosis and even death.  We present a case of a 64-year-old African American female with a history of alcohol use disorder who presented to the emergency department on account of an acute confusional state. Neurological examination revealed right beating nystagmus on the left gaze and a wide-based gait. Initial laboratory work-up was unrevealing; however, magnetic resonance imaging (MRI) of the brain demonstrated an abnormal T2 fluid-attenuated inversion recovery (FLAIR) signal involving the bilateral mammillary bodies and surrounding lateral ventricles that extended into the periaqueductal parenchyma. The patient was admitted to the neurology unit, and high-dose intravenous thiamine was commenced. During hospitalization, the patient's confusion improved and they were subsequently discharged with oral thiamine. The spectrum of severity of WE is wide, ranging from fatal disease and can lead to permanent brain damage or even Korsakoff syndrome, characterized by severe memory loss and confabulation. The diagnosis is mainly clinical and based on the presence of symptoms in the classic triad of mental status change, oculomotor abnormality, and ataxia. This triad is only present in about 10% of cases, making the diagnosis very challenging. Laboratory testing can assist in making the diagnosis, but it is not always reliable or available. In situations of clinical uncertainty, imaging may also be used to support diagnosis or rule out other differentials. The mainstay of treatment is with high-dose parenteral thiamine.

Over a Century of Study and Still Misunderstood: Recognizing the Spectrum of Acute and Chronic Wernicke-Korsakoff Syndrome.

The aim of this study was to objectively evaluate the hypothesis that the neuropsychological presentation of Korsakoff's syndrome, the chronic phase of Wernicke-Korsakoff syndrome (WKS), is invariably a severe, selective amnesia against a background of relatively preserved general intellectual functions in a consecutive clinical sample. An analysis of the neuropsychological profiles of nine cases with a recorded history of WKS was undertaken. All cases were adult males (ages 32 to 70) with a long history of alcohol use disorder. Eight cases were chosen retrospectively on a consecutive basis from patient referrals. One additional case was recruited prospectively. Conventional understanding and some current opinion of Korsakoff's syndrome predicts anterograde memory to be consistently more impaired than other cognitive abilities, but this was not found in this case series. The Mean Wechsler Delayed Memory Index was not significantly different from the Wechsler Full-Scale IQ (FSIQ), p = 0.130. Regression of Delayed Memory on FSIQ produced a non-significant intercept, p = 0.213. The 'hallmark' criterion of anterograde memory score at least 20 points less than intelligence score was observed in four of eight cases with available data, equating to a 'sensitivity' of 50%. Three of eight cases with available data had an FSIQ less than the memory score. Contrary to a common view, general intellectual function was not consistently preserved in Korsakoff's syndrome relative to memory function. This study illustrates one of the specific merits of case series, namely, to critique an established view. Clinicians and researchers should expand their diagnostic criteria for Korsakoff's syndrome to include more variable cognitive phenotypes, including a potentially reversible dementia-like impairment of variable severity, and focus on potential treatment opportunities.

Wernicke-Korsakoff Syndrome as a Consequence of Hyperemesis Gravidarum: A Case Report.

Wernicke-Korsakoff syndrome (WKS) is caused by severe thiamine (vitamin B1) deficiency and can lead to chronic deficits. In this case, a 22-year-old pregnant patient at 10 1/7 weeks of gestation presented to the emergency department with malaise, asthenia, headache, weakness, vomiting, and weight loss of 12 kg. Pancreatitis and hepatic steatosis were considered but ruled out, and cholecystolithiasis was confirmed by ultrasound. After significant neurological deterioration, the patient underwent a cranial MRI that revealed suggestive findings in the thalamus consistent with WKS. WKS is a rare complication of hyperemesis gravidarum and should be included in the differential diagnosis of persistent vomiting in order to initiate early and appropriate treatment.

Antipsychotic Use and Mortality in Persons with Alcohol-Related Dementia or Wernicke-Korsakoff Syndrome: A Nationwide Register Study in Finland.

BACKGROUND: Research on the use of psychotropic drugs in people with alcohol-related neurocognitive disorders is virtually nonexistent. We examined the prevalence of antipsychotic drug use and its effect on mortality among patients with Wernicke-Korsakoff syndrome (WKS) or alcohol-related dementia (ARD). METHODS: In this nationwide register study, we collected data on the medication use and mortality of all persons aged ≥40 diagnosed with WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the prevalence of antipsychotic use within one year of diagnosis and the adjusted cumulative mortality of antipsychotic users versus non-users in relation to the age-, sex-, and calendar year-matched general population. RESULTS: Of the WKS and ARD patients, 35.9% and 38.5%, respectively, purchased one or more antipsychotic drugs in the year following diagnosis. The adjusted cumulative mortality of the antipsychotic users was significantly lower than that of non-users in both the WKS and ARD groups, where the adjusted hazard ratios (95% CI) were 0.85 (0.72-0.99) and 0.73 (0.65-0.81), respectively. WKS and ARD patients using antipsychotics were less likely to die of alcohol-related causes than antipsychotic non-users, but the difference was significant only in the ARD group. CONCLUSIONS: This population-based study shows that antipsychotic use is common in patients with WKS or ARD. In contrast to other dementia studies, our results indicate that the mortality of antipsychotic users is significantly lower than that of non-users. The lower mortality could be explained by decreased alcohol use and better healthcare coverage in antipsychotic users.

When time is brain: a systematic review about Wernicke encephalopathy as a dramatic consequence of thiamin deficiency in hyperemesis gravidarum.

Nausea and vomiting affect up to 80% of all pregnancies, sometimes so severely that the condition of hyperemesis gravidarum (HG) is established. HG may in addition be a predisposing factor for Wernicke encephalopathy (WE), a severe and life-threatening condition due to vitamin B1 (thiamin) deficiency. If untreated, WE may progress to Korsakoff's syndrome, an irreversible cognitive disorder. We reported a case that recently occurred at our clinic and performed a systematic review of the literature to investigate the clinical presentation, maternal and perinatal outcomes and treatment of WE in women with HG. METHODS: We performed a systematic review of case series and case reports searching the Medline database on Pubmed from inception until December 2021. We used as search terms (Wernicke encephalopathy) OR (Wernicke-Korsakoff syndrome) AND (hyperemesis gravidarum) AND (pregnancy) AND (thiamin deficiency). Articles were considered eligible for inclusion in our review if they described at least one case of WE due to thiamin deficiency in relation to HG. An overall of 82 cases of WE due to HG in pregnancy from 66 manuscripts, including our own, were selected. RESULTS: The maternal mean age was 26.38 ± 5.23 years, while mean gestational week at hospitalization was 14.57 ± 4.12 after a mean of 6.6 ± 3.14 weeks of vomiting duration. WE manifestation occurred at a mean gestational age of 16.54 ± 3.06 weeks. Regarding clinical presentation, ocular signs and symptoms were reported by 77/82 (93.9%) women, 61/82 (74.4%) presented with ataxia and 63/82 (76.8%) with confusion. Dysarthria affected 15/82 women (18,3%), while muscular weakness was present in 36/82 (43.9%) and impaired reflexes in 42/82 (51.2%). Memory impairment involved 25/82 (30.5%) of the study population. Almost all cases reported a thiamin administration treatment, however data regarding the clinical course of the neurological condition and the perinatal outcomes were often missing and showed a great heterogeneity when reported. CONCLUSION: WE is a challenging diagnosis, as its clinical presentation is nonspecific. A high clinical suspicion and the awareness of its possible predisposing conditions such as HG may help clinicians to get a prompt diagnosis and starting treatment, which are vital to prevent possible life-impairing neurological sequelae.

Chronic Alcohol Use Associated Encephalopathy With a Nearly Identical Presentation to Normal Pressure Hydrocephalus.

We present the case of a 52-year-old male who arrived at the Emergency Department after several ground-level falls in the past month. He complained of urinary incontinence, mild confusion, headaches, and appetite loss in the past month as well. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed, which showed enlarged ventricles with moderately prominent cortical atrophy and no acute abnormalities. It was decided to conduct a cisternogram study with serial scans. The study showed a type IIIa cerebrospinal fluid (CSF) flow pattern at 24 hours. At the 48- and 72-hour marks, the study displayed an absence of radiotracer activity within the ventricles, while all the activity was concentrated within the cerebral cortices. These findings successfully ruled out normal pressure hydrocephalus (NPH) due to the highly specific indication of normal CSF circulation pattern. The patient was treated with thiamine and advised to quit drinking, as well as return for follow-up in one month as an outpatient for a repeat brain CT.

Fetal demise and Wernicke-Korsakoff syndrome in a patient with hyperemesis gravidarum: a case report.

BACKGROUND: Wernicke-Korsakoff syndrome is a neuropsychiatric disorder caused by thiamine deficiency composed of two related disorders accounting for an acute presentation and chronic progression. Hyperemesis gravidarum presents a significant risk factor for Wernicke-Korsakoff syndrome as symptoms may rapidly progress in the setting of pregnancy. We present the first-reported case of hyperemesis-gravidarum-associated Wernicke encephalopathy in a patient in the first half of pregnancy in which a missed diagnosis led to septic shock, fetal demise, and eventual profound Korsakoff syndrome. CASE PRESENTATION: We present the case of a 33-year-old primigravid African American woman at 15 weeks gestational age who initially presented at a community emergency department with nausea and vomiting that ultimately progressed to severe hyperemesis-gravidarum-associated Wernicke-Korsakoff syndrome, fetal demise, and septic shock. The patient received a total of 6 weeks of high-dose parenteral thiamine. Magnetic resonance imaging of the head and formal neuropsychological assessment following treatment plateau confirmed the diagnosis of Wernicke-Korsakoff syndrome. CONCLUSIONS: The multisystem complications seen in severe thiamine deficiency can delay timely administration of high-dose thiamine, particularly in pregnancy, in which the classic triad of Wernicke-Korsakoff syndrome may not raise clinical suspicion due to rapid progression of neurological sequelae in this population. We advise a low threshold for parenteral thiamine repletion in pregnant women with persistent vomiting as hyperemesis gravidarum-induced severe thiamine deficiency can result in Wernicke-Korsakoff syndrome, sepsis, and fetal demise.

Protocatechuic Acid Prevents Some of the Memory-Related Behavioural and Neurotransmitter Changes in a Pyrithiamine-Induced Thiamine Deficiency Model of Wernicke-Korsakoff Syndrome in Rats.

The purpose of this research was to investigate the effects of protocatechuic acid (PCA) at doses of 50 and 100 mg/kg on the development of unfavourable changes in cognitive processes in a pyrithiamine-induced thiamine deficiency (PTD) model of the Wernicke-Korsakoff syndrome (WKS) in rats. The effects of PCA were assessed at the behavioural and biochemical levels. Behavioural analysis was conducted using the Foot Fault test (FF), Bar test, Open Field test, Novel Object Recognition test (NOR), Hole-Board test and Morris Water Maze test (MWM). Biochemical analysis consisting of determination of concentration and turnover of neurotransmitters in selected structures of the rat CNS was carried out using high-performance liquid chromatography. PTD caused catalepsy (Bar test) and significantly impaired motor functions, leading to increased ladder crossing time and multiplied errors due to foot misplacement (FF). Rats with experimentally induced WKS showed impaired consolidation and recall of spatial reference memory in the MWM test, while episodic memory related to object recognition in the NOR was unimpaired. Compared to the control group, rats with WKS showed reduced serotonin levels in the prefrontal cortex and changes in dopamine and/or norepinephrine metabolites in the prefrontal cortex, medulla oblongata and spinal cord. PTD was also found to affect alanine, serine, glutamate, and threonine levels in certain areas of the rat brain. PCA alleviated PTD-induced cataleptic symptoms in rats, also improving their performance in the Foot Fault test. In the MWM, PCA at 50 and 100 mg/kg b.w. improved memory consolidation and the ability to retrieve acquired information in rats, thereby preventing unfavourable changes caused by PTD. PCA at both tested doses was also shown to have a beneficial effect on normalising PTD-disrupted alanine and glutamate concentrations in the medulla oblongata. These findings demonstrate that certain cognitive deficits in spatial memory and abnormalities in neurotransmitter levels persist in rats that have experienced an acute episode of PTD, despite restoration of thiamine supply and long-term recovery. PCA supplementation largely had a preventive effect on the development of these deficits, to some extent also normalising neurotransmitter concentrations in the brain.

Case report: Wernicke-Korsakoff syndrome after bariatric surgery.

Vitamin and mineral deficiencies are prevalent nutritional disorders following bariatric surgery. Although they are more prevalent after malabsorptive procedures such as bypass, they also occur in restrictive procedures such as gastric sleeve. The mechanisms that lead to the occurrence of these deficits are related to the presence of poor nutritional intake or poor adherence to multivitamins and multimineral supplementation. Wernicke-Korsakoff syndrome (WKS) is an acute neurological disorder resulting from thiamine deficiency. This syndrome is composed of two distinct phases: first, Wernicke Encephalopathy (WE), the acute phase of this syndrome, which is characterized by a triad of mental confusion, ocular signs, and ataxia, followed by the chronic phase of WKS, called Korsakoff's syndrome (KS), which is known for the presence of anterograde amnesia and confabulation. We aimed to report a case of a patient with WKS after bariatric surgery. The patient's retrospective chart review was performed in order to retrieve the relevant clinical data. The patient was a 24-year-old female student with a BMI of 48 kg/m2 who underwent sleeve gastrectomy surgery for morbid obesity. Over the following 2 months, recovery from surgery was complicated by non-specific symptoms such as nausea, recurrent vomiting, and a significant reduction in food intake, which led the patient to visit the emergency department six times with hospitalization on the last occasion for a definitive diagnosis. During the 15 days of hospitalization, the patient developed ocular diplopia, nystagmus, complaints of rotatory vertigo, and gait abnormalities. A magnetic resonance imaging of the head was performed but revealed no significant changes. After a formal neurological assessment, treatment with parenteral thiamine (100 mg, three times a day) was started without prior dosing. The observed clinical improvement confirmed the diagnosis of WKS. Bariatric surgery may contribute to thiamine deficiency and, consequently, to WKS. Education about the adverse consequences of malnourishment is mandatory before and after the surgery. Investigation of nutritional deficiencies both pre- and post-operatively is crucial in order to prevent complications such as WKS.

Hemosiderin Detection inside the Mammillary Bodies Using Quantitative Susceptibility Mapping on Patients with Wernicke-Korsakoff Syndrome.

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS.

Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke's encephalopathy: Findings in preclinical models and in a postmortem human case.

Wernicke's encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder its main risk factor. WE patients present limiting motor, cognitive, and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed to be one of the phenomena that contribute to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR)4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet [TDD] and receiving pyrithiamine). Nevertheless, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. In addition, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or combined treatment (CA + TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its coreceptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFκB p65 and IκBα, in the postmortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer's disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NF-ĸB and IĸBα in the CA + TDD animal model. In the patient diagnosed with alcohol-induced WE, we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Hence, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in alcohol consumption-related WE.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Incidence and mortality of alcohol-related dementia and Wernicke-Korsakoff syndrome: A nationwide register study.

BACKGROUND: Epidemiological data on alcohol-related cognitive disorders are scarce. Up-to-date population-based incidence and mortality rates for Wernicke-Korsakoff syndrome (WKS) and alcohol-related dementia (ARD) are necessary to understand the burden of these diseases. METHODS: We collected diagnostic data from the Finnish Hospital Discharge Register and mortality data from Statistics Finland for all persons aged ≥40 years who had received a diagnosis of WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the incidences and mortality in relation to the age-, sex- and calendar year-matched general population. Causes of death were ascertained from death certificates. RESULTS: For WKS, the incidence per 100,000 person-years (95% confidence interval (CI)) was 3.7 (3.4-3.9) in men and 1.2 (1.1-1.3) in women. For ARD, the incidence was 8.2 (7.9-8.6) in men and 2.1 (1.9-2.3) in women. The incidence of WKS peaked in people aged 50-59 years and the incidence of ARD in people aged 70-79 years. The standardized mortality ratio (95% CI) was 5.67 (5.25-6.13) in WKS patients and 5.41 (5.14-5.70) in ARD patients. Most of the excess mortality resulted from alcohol-related causes. CONCLUSIONS: To our knowledge, this is the first study describing population-based incidence and mortality rates, sex-segregated data and causes of death in patients with WKS or ARD. Our results establish a point of reference for the incidence of WKS and ARD and show the high mortality and poor prognosis of these disorders.

What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.

BACKGROUND: The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose. METHODS: Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but "at-risk" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up. RESULTS: No significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings. CONCLUSIONS: The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.

Genetic Creutzfeldt-Jakob disease shows fatal family insomnia phenotype.

We report a case of genetic Creutzfeldt-Jakob disease (gCJD), which has a clinical phenotype that is highly similar to Fatal Family Insomnia (FFI) and has a triad of Wernicke-Korsakoff syndrome (WKs) at the developmental stage of the disease. The 51-year-old male complained of sleep disorder and imbalance who had visited five different hospitals before diagnosed. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk, and memory disturbances. The disturbances increased during the course of the disease, which led to the death of the patient 18 months after the appearance of the signs. Although the patient show negative in brain magnetic resonance imaging (MRI) and 14-3-3 protein of cerebrospinal fluid (CSF), he was finally diagnosed with gCJD disease by the human prion protein (PRNP) gene mutations.

Case Report: Intensive Inpatient Neurorehabilitation Achieves Sustained Real-World Benefits in Severe Alcohol-Related Wernicke-Korsakoff Syndrome: A Case Study With 7-Years Follow-Up.

About 85% of survivors of acute Wernicke's Encephalopathy (WE), a frequent and serious consequence of thiamine deficiency and alcohol misuse, sustain chronic neurocognitive deficits also known as chronic Wernicke-Korsakoff syndrome (WKS). If alcoholism is combined with smoking, tobacco alcohol optic neuropathy (TAON) may occur which leads to visual impairment. In contrast to WKS, TAON may be treated successfully by early vitamin substitution and detoxification. Little research has been conducted on WKS longterm outcomes. Existing literature suggests poor prognosis. Symptoms remaining beyond the acute treatment with thiamine are thought to be irreversible. Whether neurorehabilitation may be an effective route to help recovery of those persistent symptoms is an open question. At our neurorehabilitation center, which specializes in the treatment of severe chronic deficits after brain injury, the opportunity arose to treat a 35 year old male with WKS, and to conduct follow-up assessments 3- and 7-years post discharge, respectively. Initially MK was admitted to emergency care with suspected postconcussive syndrome, alcohol-related thiamine deficiency, and TAON. Thiamin, cobalamin, and folate substituion improved TAON but major cognitive deficits remained. When admitted to our center 4 months later, he was fully reliant on care staff for all activities of daily living (ADL). Through intensive neurocognive training and psychological treatment he improved gradually and, after 26 months, was well enough to be discharged into the community and pursue work in a sheltered setting. Neuropsychological tests, as well as patient reports obtained at the follow-ups showed that the benefits apparent at discharge had been sustained, and for some scores, improved further. This was particularly evident in the Rey-Osterrieth Complex Figure Test which improved from percentage ranges <1 for immediate recognition and recall at discharge to rank 16 for immediate recognition and rank 5 for recall at the 7-year follow-up. This case study illustrates the immense benefits neurorehabilitation can have for WKS induced by alcohol misuse. It further demonstrates how skills and strategies, learned in the inpatient setting, translate into living well and independently, and how the latter promotes further improvement long after discharge.