Search Results (17)

Background: Wernicke Encephalopathy (WE), a neurological disorder often linked to alcohol use, can also occur under non-alcoholic conditions, including in pediatric populations. Methods: This systematic review examines 88 pediatric WE cases reported over the past 30 years, encompassing diverse etiologies such as cancer (25 cases), gastrointestinal diseases (19), malnutrition (17), psychiatric disorders (13), obesity surgery (5), renal disease (4), COVID-19 (2), PICU complications (1), hyperemesis gravidarum (1), and a genetic mutation (1). Results: Prodromal symptoms included nausea (60%) and vomiting (55%). In total, 37% of the patients received parenteral nutrition without thiamine before WE diagnosis, often progressing to Wernicke–Korsakoff syndrome (WKS). Key findings revealed the classic triad of WKS, eye movement disorders (80%), mental status changes (75%), and ataxia (63%), with MRI demonstrating high diagnostic sensitivity (85%). Treatment varied widely; higher parenteral thiamine doses correlated with faster recovery and better outcomes, while insufficient dosages led to adverse effects. Full remission was achieved in 61% of cases, with improved outcomes in more recent reports due to refined dosing protocols. Conclusions: These findings underscore the importance of early recognition of nausea and vomiting as predictors of pediatric WE and the critical need to incorporate thiamine in parenteral nutrition for children. Optimal dosing remains vital for recovery, particularly in severe cases. Full article

Vitamin B₁ (thiamine) plays an important role in human metabolism. It is essential for the proper growth and development of the body and has a positive effect on the functioning of the digestive, cardiovascular, and nervous systems. Additionally, it stimulates the brain and improves the psycho-emotional state. In vivo, vitamin B₁ occurs in free form as thiamine or as its ester with phosphate residue(s), i.e., as mono-, di-, or triphosphate. It has been proven that supportive therapy with vitamin B₁ can not only provide neuroprotection but also has a positive effect on advanced neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, Wernicke–Korsakoff syndrome, or Huntington’s disease. This paper presents studies on the effect of free thiamine (T) and thiamine pyrophosphate (TPP) on the activity of acetylcholinesterase (AChE), which is an enzyme considered to play an important role in the therapies for neurodegenerative diseases, especially Alzheimer’s disease. The mechanisms of action of these compounds as potential inhibitors of AChE were evaluated using both experimental (enzymatic activity) as well as computational (molecular docking, molecular dynamics simulations, and MM-GBSA calculations) methods. The results of the current study indicate a non-competitive type of enzyme inhibition, in contrast to the previously published works suggesting a competitive one. Full article

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. Full article

Wernicke–Korsakoff Syndrome (WKS) is a severe neurological disorder resulting from thiamine deficiency, commonly associated with alcohol consumption but also stemming from dietary imbalances or other clinical conditions. Cognitive deficits, affecting memory and executive functions, pose a serious concern, with partial recovery often not complete. A 28-year-old woman underwent surgery for acute necrotizing hemorrhagic pancreatitis, leading to admission for post-acute intensive treatment due to prolonged bed rest syndrome. Clinical examinations revealed sensory–motor neuropathy, denervation in the active phase, mammillary body hyperintensity, and cognitive impairment. The patient exhibited poor orientation, lacked awareness of her clinical condition, and experienced impaired nonverbal memory, practical constructive issues, and planning difficulties—consistent with WKS. The patient received high-dose thiamine (300 mg TDS), coupled with daily physiokinesitherapy and occupational therapy. A final neuropsychological evaluation three months later showed substantial remission of executive and memory difficulties, improved spatial–temporal orientation, and enhanced awareness. The complex case required timely multidisciplinary intervention for accurate diagnosis and effective rehabilitation. The patient experienced rapid clinical improvement and cognitive recovery with high-dose thiamine and physiotherapy. Full article

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. Full article

This paper begins with a short case report of florid, spontaneous confabulation in a 61-year-old man with an alcohol-induced Wernicke-Korsakoff syndrome. His confabulation extended across episodic and personal semantic memory, as well as orientation in time and place, as measured on Dalla Barba’s Confabulation Battery. Five other brief case summaries will then be presented, followed by a summary of the clinical, neurological, and background neuropsychological findings in three earlier series of Korsakoff patients. These observations will be considered in light of Wijnia’s recent and my own, earlier reviews of the Korsakoff syndrome. Taken together, they indicate the need for a multi-faceted approach (clinical, neurological, neuropsychological, and neuroimaging) to the assessment and diagnosis of the disorder. Full article

Alcohol-related cognitive disorders have long been an area of study, yet they continue to pose challenges in the diagnosis, treatment, and understanding of underlying neuropsychiatric mechanisms. The present article offers a comprehensive review of Wernicke’s Encephalopathy and Korsakoff’s Syndrome, two conditions often seen on a continuum of alcohol-related brain damage. Drawing on current medical literature, neuroimaging studies, and clinical case reports, we explore the neuropsychiatric and neuropsychological profiles, symptomatology, and differential diagnoses of these disorders. We delve into the biochemical pathways implicated in the development of WE and KS, notably thiamine deficiency and its impact on neurotransmitter systems and neural networks. The article also addresses the challenges in early diagnosis, often complicated by non-specific symptoms and co-occurring psychiatric conditions. Furthermore, we review the current state of treatment protocols, including pharmacological and non-pharmacological interventions. Finally, the article highlights gaps in current knowledge and suggests directions for future research to improve diagnosis, treatment, and patient outcomes. Understanding the nuanced interplay between the neuropsychiatric and neuropsychological aspects of WE and KS is crucial for both clinicians and researchers alike, in order to provide effective treatment and to advance our understanding of these complex conditions. Full article

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. Full article

Wernicke encephalopathy (WE), a neurological emergency commonly associated with alcohol use disorder, results from a severe deficiency of vitamin B1. If left untreated, patients either succumb to the illness or develop chronic Korsakoff’s syndrome (KS). Recently, an increasing number of nonalcoholic WE case studies have been published, highlighting a lack of understanding of malnutrition-related disorders among high-functioning patients. We present the case of a 26 year old female who developed life-threatening WE after COVID-19-complicated obesity surgery. She experienced the full triad of WE symptoms, including eye-movement disorders, delirium, and ataxia, and suffered for over 70 days before receiving her initial WE diagnosis. Late treatment resulted in progression of WE symptoms. Despite the severity, the patient achieved remission of some of the symptoms in the post-acute phase due to prolonged parenteral thiamine injections and intensive specialized rehabilitation designed for young traumatic brain injury (TBI) patients. The rehabilitation resulted in gradual remission of amnesia symptomatology, mainly increasing her autonomy. The late recognition of this case highlights the importance of early diagnosis and prompt, targeted intervention in the management of nonalcoholic WE, as well as underscores the potential for positive outcomes after delayed treatment through intensive cognitive rehabilitation in specialized treatment centers. Full article

Background: Alcoholic cerebellar degeneration is a restricted form of cerebellar degeneration, clinically leading to an ataxia of stance and gait and occurring in the context of alcohol misuse in combination with malnutrition and thiamine depletion. However, a similar degeneration may also develop after non-alcoholic malnutrition, but evidence for a lasting ataxia of stance and gait and lasting abnormalities in the cerebellum is lacking in the few patients described with purely nutritional cerebellar degeneration (NCD). Methods: We present a case of a 46-year-old woman who developed NCD and Wernicke’s encephalopathy (WE) due to COVID-19 and protracted vomiting, resulting in thiamine depletion. We present her clinical course over the first 6 months after the diagnosis of NCD and WE, with thorough neuropsychological and neurological examinations, standardized clinical observations, laboratory investigations, and repeated MRIs. Results: We found a persistent ataxia of stance and gait and evidence for an irreversible restricted cerebellar degeneration. However, the initial cognitive impairments resolved. Conclusions: Our study shows that NCD without involvement of alcohol neurotoxicity and with a characteristic ataxia of stance and gait exists and may be irreversible. We did not find any evidence for lasting cognitive abnormalities or a cerebellar cognitive-affective syndrome (CCAS) in this patient. Full article

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. Full article

The purpose of this article is to improve recognition and treatment of Wernicke-Korsakoff syndrome. It is well known that Korsakoff syndrome is a chronic amnesia resulting from unrecognized or undertreated Wernicke encephalopathy and is caused by thiamine (vitamin B1) deficiency. The clinical presentation of thiamine deficiency includes loss of appetite, dizziness, tachycardia, and urinary bladder retention. These symptoms can be attributed to anticholinergic autonomic dysfunction, as well as confusion or delirium, which is part of the classic triad of Wernicke encephalopathy. Severe concomitant infections including sepsis of unknown origin are common during the Wernicke phase. These infections can be prodromal signs of severe thiamine deficiency, as has been shown in select case descriptions which present infections and lactic acidosis. The clinical symptoms of Wernicke delirium commonly arise within a few days before or during hospitalization and may occur as part of a refeeding syndrome. Wernicke encephalopathy is mostly related to alcohol addiction, but can also occur in other conditions, such as bariatric surgery, hyperemesis gravidarum, and anorexia nervosa. Alcohol related Wernicke encephalopathy may be identified by the presence of a delirium in malnourished alcoholic patients who have trouble walking. The onset of non-alcohol-related Wernicke encephalopathy is often characterized by vomiting, weight loss, and symptoms such as visual complaints due to optic neuropathy in thiamine deficiency. Regarding thiamine therapy, patients with hypomagnesemia may fail to respond to thiamine. This may especially be the case in the context of alcohol withdrawal or in adverse side effects of proton pump inhibitors combined with diuretics. Clinician awareness of the clinical significance of Wernicke delirium, urinary bladder retention, comorbid infections, refeeding syndrome, and hypomagnesemia may contribute to the recognition and treatment of the Wernicke-Korsakoff syndrome. Full article

Wernicke–Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated with impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, either isolated or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation (TDD)), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior which appeared to be dependent on TDD. Additionally, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS. Full article

Alcohol works on the brain to produce its desired effects, e.g., sociability and intoxication, and hence the brain is an important organ for exploring subsequent harms. These come in many different forms such as the consequences of damage during intoxication, e.g., from falls and fights, damage from withdrawal, damage from the toxicity of alcohol and its metabolites and altered brain structure and function with implications for behavioral processes such as craving and addiction. On top of that are peripheral factors that compound brain damage such as poor diet, vitamin deficiencies leading to Wernicke-Korsakoff syndrome. Prenatal alcohol exposure can also have a profound impact on brain development and lead to irremediable changes of fetal alcohol syndrome. This chapter briefly reviews aspects of these with a particular focus on recent brain imaging results. Cardiovascular effects of alcohol that lead to brain pathology are not covered as they are dealt with elsewhere in the volume. Full article