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.

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.

Prevalence and Improvement of Caine-Positive Wernicke-Korsakoff Syndrome in Psychiatric Inpatient Admissions.

BACKGROUND: Wernicke-Korsakoff Syndrome (WKS) resulting from thiamine deficiency is classically defined as including encephalopathy, ataxia, and ophthalmoplegia. Only 16% of autopsy-confirmed patients with WKS exhibit all three signs. Caine-positive WKS criteria include two or more of the following: nutritional deficiency, delirium or mild memory impairment, cerebellar dysfunction/ataxia, and oculomotor abnormalities. OBJECTIVE: We describe Caine-positive WKS prevalence among psychiatric inpatients and compare pretreatment-versus-posttreatment neurocognitive improvement to an unaffected group. METHODS: This 6-month quality-improvement evaluation included two-stage screening for Caine-positive WKS, administering high-dose intravenous thiamine (day 1: 1200 mg; days 2-4: 200 mg) with reexamination on day 5. We used descriptive statistics and fitted random effects models to examine rate-of-change differences in pre-/posttreatment Montreal Cognitive Assessment (MoCA), delayed 5-item recall, and gait/coordination scores between treated Caine-positive patients with WKS and untreated Caine-negative patients. RESULTS: Of 262 patients, 32 (12%) had Caine-positive WKS; 17 (53%) used alcohol currently. Treated Caine-positive WKS (n = 26) versus Caine-negative comparison (n = 34) before and after treatment observed a mean change (standard deviation) in the MoCA score of 3.6 (2.5) versus 1.8 (2.5) (P < 0.01); 5-item recall: 1.8 (1.4) versus 0.5 (1.4) (P < 0.001); gait/coordination scores: -0.6 (1.2) versus -0.1 (0.6) (P < 0.001). Oculomotor abnormalities were infrequent (n = 4 in Caine-positive WKS, n = 2 in Caine-negative comparison groups). CONCLUSIONS: Caine-positive WKS prevalence among psychiatric inpatients was 12%; only half used alcohol. Patients treated with high-dose thiamine demonstrated clinically significant neurocognitive improvement.

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.

Beyond Thiamine: Treatment for Cognitive Impairment in Korsakoff's Syndrome.

BACKGROUND: Wernicke's encephalopathy is a condition whose treatment many consultation-liaison psychiatrists know quite well. Less clear, however, is the treatment of its dementia disorder descendent, the Korsakoff's syndrome (KS). OBJECTIVE: This article seeks to review treatment options and provide recommendations for consultation-liaison psychiatrists treating cognitive impairment in KS. METHODS: In this nonsystematic review, we reviewed PubMed, CINAHL Plus, and Google Scholar for published reports and studies regarding treatment of KS. RESULTS: The literature revealed case reports and placebo-controlled trials of various medications for treatment of KS, though the samples sizes were small and were mostly case reports. There is more attention devoted toward medications used in other dementia disorders, such as donepezil and memantine. The literature revealed more studies around behavioral interventions recommended for treatment of memory impairment in KS and they focused on cognitive remediation and environmental adaptation, such as the use of PDAs or alarms. CONCLUSIONS: There is no single, well-studied intervention proven effective as a primary treatment for cognitive impairment in KS. An approach of using environmental modifications in a well-structured living environment, combined with various cognitive interventions, such as pictorial associations, and perhaps a trial of donepezil or memantine, likely represents the best strategy for treating long-term cognitive impairment in KS.

Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy.

BACKGROUND: Wernicke encephalopathy is a common neuropsychiatric syndrome due to thiamine deficiency. There is no consensus regarding thiamine dosing when Wernicke encephalopathy is suspected. A longstanding dosing strategy for Wernicke encephalopathy is 100mg daily, yet updated clinical guidelines suggest using high-dose intravenous (HDIV) thiamine. OBJECTIVE: To describe thiamine prescribing practices at a large, public academic hospital and investigate clinical characteristics and outcomes associated with HDIV thiamine in patients with encephalopathy who received IV thiamine. METHODS: Electronic medical records of hospitalized patients who received thiamine between 4/4/2014 and 11/1/2015 were reviewed. Chi-square tests, Wilcoxon Rank Sum tests, and logistic regression were used to compare clinical variables in patients with encephalopathy who received HDIV thiamine (≥ 200mg twice daily) vs lower doses of IV thiamine. RESULTS: Among the total of 5236 thiamine orders, 29% (n = 1531) were IV; 10% (n = 150) of IV orders met HDIV criteria. In patients with encephalopathy who received IV thiamine (n = 432), HDIV thiamine was administered to 20% (n = 86) and only 2.1% (n = 9) received dosing consistent with Royal College of Physicians guidelines. In bivariable analyses, HDIV thiamine was associated with surgical services (p = 0.001), psychiatric consultation (p < 0.001), and decreased mortality (p = 0.004). In multivariable models, the association between HDIV thiamine and decreased in-hospital mortality did not meet statistical significance (p = 0.061). CONCLUSIONS: In a large, public academic hospital, guideline-concordant thiamine supplementation is rare and HDIV thiamine is infrequently prescribed to patients with encephalopathy. Further studies are needed to confirm the possible benefits of HDIV thiamine for patients with suspected thiamine-deficient encephalopathy.

Severe Infections are Common in Thiamine Deficiency and May be Related to Cognitive Outcomes: A Cohort Study of 68 Patients With Wernicke-Korsakoff Syndrome.

BACKGROUND: Wernicke encephalopathy can have different clinical outcomes. Although infections may precipitate the encephalopathy itself, it is unknown whether infections also modify the long-term outcome in patients developing Korsakoff syndrome. OBJECTIVE: To determine whether markers of infection, such as white blood cell (WBC) counts and absolute neutrophil counts in the Wernicke phase, are associated with cognitive outcomes in the end-stage Korsakoff syndrome. METHOD: Retrospective, descriptive study of patients admitted to Slingedael Korsakoff Center, Rotterdam, The Netherlands. Hospital discharge letters of patients with Wernicke encephalopathy were searched for relevant data on infections present upon hospital admission. Patients were selected for further analysis if data were available on WBC counts in the Wernicke phase and at least 1 of 6 predefined neuropsychological tests on follow-up. RESULTS: Infections were reported in 35 of 68 patients during the acute phase of Wernicke-Korsakoff syndrome-meningitis (1), pneumonia (14), urinary tract infections (9), acute abdominal infections (4), sepsis (5) empyema, (1) and infection "of unknown origin" (4). The neuropsychological test results showed significant lower scores on the Cambridge Cognitive Examination nonmemory section with increasing white blood cell counts (Spearman rank correlation, ρ = -0.34; 95% CI: -0.57 to -0.06; 44 patients) and on the "key search test" of the behavioral assessment of the dysexecutive syndrome with increasing absolute neutrophil counts (ρ= -0.85; 95% CI: -0.97 to -0.42; 9 patients). CONCLUSIONS: Infections may be the presenting manifestation of thiamine deficiency. Patients with Wernicke-Korsakoff syndrome who suffered from an infection during the acute phase are at risk of worse neuropsychological outcomes on follow-up.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

Interactions between chronic ethanol consumption and thiamine deficiency on neural plasticity, spatial memory, and cognitive flexibility.

BACKGROUND: Many alcoholics display moderate to severe cognitive dysfunction accompanied by brain pathology. A factor confounded with prolonged heavy alcohol consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus, thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can progress into Wernicke-Korsakoff syndrome and these disorders have a high prevalence among alcoholics. Animal models are critical for determining the exact contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the interactions of those factors to brain and cognitive dysfunction. METHODS: Adult rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6 months; severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD-early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats were tested on spontaneous alternation and attentional set-shifting. After behavioral testing, brains were harvested for determination of mature brain-derived neurotrophic factor (BDNF) and thalamic pathology. RESULTS: Moderate TD combined with CET, regardless of treatment order, produced significant impairments in spatial memory, cognitive flexibility, and reductions in brain plasticity as measured by BDNF levels in the frontal cortex and hippocampus. These alterations are greater than those seen in moderate TD alone, and the synergistic effects of moderate TD with CET lead to a unique cognitive profile. However, CET did not exacerbate thalamic pathology seen after moderate TD. CONCLUSIONS: These data support the emerging theory that subclinical TD during chronic heavy alcohol consumption is critical for the development of significant cognitive impairment associated with ARBD.

Improvement of a woman's alcohol-related dementia via off-label memantine treatment: a 16-month clinical observation.

OBJECTIVE: To report a case of long-term treatment of moderate alcohol-related dementia (ARD) with memantine. CASE SUMMARY: We present the case of a 48-year-old German woman with a long history of alcohol dependence and cognitive impairments, who was diagnosed with moderate ARD (according to ICD-10 criteria) after having ruled out other dementias. Her cognitive functioning improved with off-label use of memantine (up to 20 mg/d) under abstinent conditions. Discontinuation and reinstitution of memantine were associated with a worsening and an improving of her cognitive performance, respectively, which was documented in neuropsychiatric tests. The patient had 2 alcohol relapses during this study. Only the first relapse was associated with discontinuation of memantine and cognitive deterioration. The second relapse happened during receiving of memantine and was not associated with a decline in cognitive functioning. After 16 months of treatment, moderate ARD had been improved to the grade of an amnestic mild cognitive impairment (according to DemTect) and to mild dementia (according to Clinical Dementia Rating Scale), respectively. DISCUSSION: The on-off-on pattern of the memantine treatment supports the assumption that this antidementia agent played a key role in the improvement of ARD. An alcohol relapse did not attenuate the improvement of cognition with memantine. CONCLUSION: The use of memantine improved cognitive functioning of a female patient with ARD.

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.

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.

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.

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.

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.

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.

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.