Diagnosis and treatment of Wernicke's encephalopathy: A systematic literature review.

BACKGROUND: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention. OBJECTIVES: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included. RESULTS: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine. CONCLUSION: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Thiamine administration in septic shock: a post hoc analysis of two randomized trials.

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Atypical Wernicke's encephalopathy without mental status changes following bariatric surgery in an adolescent patient.

Morbid obesity is a systemic disease which can result in chronic complications, including hypertension, diabetes mellitus, depression, osteoarthritis and low self-esteem in the adolescent population.Bariatric surgery can be indicated to treat more severe forms of obesity, but these procedures are not without long-term risks. Therefore, adequate preoperative and postoperative care, which includes preoperative psychosocial evaluation for compliance, ongoing nutrition counselling and vitamin and micronutrient supplementation, is required for all patients, especially adolescent patients, who generally may not comply with medical therapies and/or be able to developmentally fully appreciate or comprehend the health consequences of their behaviours, prior to as well as after bariatric surgery to prevent complications.Thiamine pyrophosphate, an active form of thiamine (also known as vitamin B1, a water-soluble vitamin), which functions as a coenzyme in glucose and energy metabolism, is one such vitamin that requires supplementation postoperatively. It is mandatory for glucose to be administered concomitantly with thiamine, as glucose alone can precipitate Wernicke's encephalopathy (WE) in thiamine-deficient individuals. WE is a medical emergency, with a mortality rate of up to 20%. WE is best understood as a classic triad of mental confusion, gait ataxia and eye movement abnormalities, and atypical WE or Wernicke's syndrome (WS) is seen when the classic triad is not present. Cases that meet some, but do not necessarily meet all three criteria, are referred to as atypical WE or WS which can lead to delayed diagnosis. Atypical WE has an incidence of 19% which can lead to misdiagnosis of a preventable medical emergency with fatal complications.The following case reviews the consequences of post-bariatric thiamine supplementation therapy non-adherence and resulting in a deficiency in an adolescent patient.

Thiamine deficiency-related neuropathy: A reversible entity from an endemic area.

BACKGROUND AND PURPOSE: Despite thiamine deficiency being a lesser-known entity in modern times, beriberi in various forms, including thiamine deficiency-related neuropathy, remains endemic in Kashmir due to the consumption of polished rice as a staple food. This observational study investigates cases of peripheral neuropathy of unknown etiology and their potential responsiveness to thiamine administration. METHODS: This prospective study enrolled adult patients presenting to the emergency department with weakness consistent with thiamine deficiency-related neuropathy and conducted a therapeutic challenge with thiamine on 41 patients. Response to thiamine therapy was monitored based on subjective and objective improvements in weakness and power. Patients were divided into thiamine responders (n = 25) and nonresponders (n = 16) based on their response to thiamine therapy and nerve conduction studies. RESULTS: Most of the baseline characteristics were similar between responders and nonresponders, except the responders exhibited lower thiamine levels and higher partial pressure of oxygen and lactate levels compared to nonresponders. All patients had a history of consuming polished rice and traditional salt tea. Although weakness in the lower limbs was present in both groups, nonresponders were more likely to exhibit weakness in all four limbs. Clinical improvement was observed within 24 h, but proximal muscle weakness persisted for an extended period of time. CONCLUSIONS: Thiamine deficiency-related neuropathy presents with predominant lower limb weakness, exacerbated by vomiting, poor food intake, psychiatric illness, and pregnancy. Thiamine challenge should be followed by observation of clinical and biochemical response.

Descriptive spectrum of thiamine deficiency in pregnancy: A potentially preventable condition.

OBJECTIVE: Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly affects thiamine reserves. Thiamine deficiency during pregnancy and the postpartum period, presenting with varied manifestations and outcomes, is a relatively common condition in our population. The study aimed to understand the various manifestations and outcomes of acute thiamine deficiency in pregnant and postpartum women, emphasizing the significance of early recognition and thiamine therapy to prevent serious complications during pregnancy and after childbirth. METHODS: This prospective study conducted in a tertiary care center in North India enrolled consecutive pregnant and postpartum women presenting with clinical features consistent with thiamine deficiency disorders, such as thiamine deficiency-related neuropathy, high-output heart failure, heart failure with reduced ejection fraction, Wernicke's encephalopathy, gastric beriberi, and thiamine-responsive acute pulmonary hypertension. In addition to capturing medical history including drug intake, dietary consumption, and comorbidities, women underwent brief relevant clinical examinations and laboratory assessments, including whole-blood thiamine levels. Response to intravenous thiamine supplementation was also monitored. RESULTS: Data of 31 women (12 pregnant, 19 postpartum) with a diagnosis of acute thiamine deficiency and a mean age of 28.88 ± 2.69 years were analyzed. The mean thiamine level was 1.28 ± 0.44 µg/dL with mean blood lactate of 3.46 ± 3.33. The most common presentation was gastric beriberi (n = 10), followed by paraparesis (n = 6), high-output heart failure (n = 6), acute pulmonary hypertension, heart failure with reduced ejection fraction (n = 3 each), and an acute confusional state (n = 2). All patients responded to thiamine challenge. CONCLUSION: In the context of borderline thiamine status, particularly in our population with endemic thiamine deficiency and heightened demand for thiamine during pregnancy and the peripartum period, the deficiency can have varied and serious manifestations of dry and wet beriberi. Early recognition of the clinical features and thiamine therapy can be life-saving. There is a need for validated clinical criteria owing to the non-availability of thiamine testing in resource-limited settings.

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.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Diagnosis of Wernicke's Encephalopathy in Patients With a Psychiatric History: A Case Series and Literature Review.

Objective: To review the literature on diagnostic criteria and management of Wernicke's encephalopathy (WE) and its application in psychiatric populations.Evidence Review: A PubMed MEDLINE search was conducted in February 2022 and updated in April 2022 for articles published in English between 2012 and 2022 describing clinical findings and treatment of WE. Reference lists of included articles and treatment guidelines were reviewed. Search terms included Wernicke's encephalopathy, thiamine, thiamine administration dosage, and prescribing. Additionally, 2 cases with co-occurring psychiatric and WE manifestations were selected from the consult-psychiatry service between July and December 2021. Pertinent clinical findings and management were extracted from the literature and compared with that of the cases.Findings: 113 titles were retrieved; 39 studies were excluded. Exclusion criteria included studies done in patients < 18 years old, animal studies, studies with no abstract, and studies with no clinical discussion. Twelve articles were added from the grey literature. Eighty-six articles were included in the review. Only 7 studies discussed WE in psychiatry. The results reaffirm the lack of information regarding diagnosis and treatment of WE in the general population. Clinical cases suggest further increased risk in the psychiatric population.Conclusion and Relevance: Evidence suggests underdiagnosis and undertreatment of WE in general populations and psychiatric patients at increased risk for malnutrition. An interdisciplinary approach improves time to diagnosis and management of comorbidities. We recommend dosing guided by clinical response; however, evidence suggests lengthier and higher doses of thiamine may be needed. Addition of neuroleptics may be necessary for management of psychiatric symptoms and relapse prevention.Prim Care Companion CNS Disord 2023;25(4)22nr03447. Author affiliations are listed at the end of this article.

Can thiamine substitution restore cognitive function in alcohol use disorder?

AIMS: While clinical consequences of thiamine deficiency in alcohol use disorder (AUD) are severe, evidence-based recommendations on dosage, type of administration and duration of thiamine substitution (TS), and its' target levels remain sparse. This study aimed to compare the effect of two best practice TS regimens on thiamine blood levels (i.e. thiamine pyrophosphate, TPP) and cognitive function. METHODS: In 50 patients undergoing in-patient alcohol-withdrawal treatment, TPP levels were determined at baseline and end of weeks 1, 2 and 8 following administration of oral TS (3 × 100 mg/day for 7 days followed by 1 × 100 mg/day thereafter) either with or without preceding intravenous TS (3 × 100 mg/day for 5 days). An extensive psychiatric assessment was conducted at baseline, including an evaluation of AUD severity and depressive symptoms. Additionally, cognitive function and depressive symptoms were repeatedly evaluated. RESULTS: Relevant increases (mean increase by 100.2 nmol/l [CI 76.5-123.8], P < 0.001) in peripheral blood TPP levels were observed in all patients at the end of weeks 1 and 2. Furthermore, no relevant difference between the intravenous and the oral group was found (average difference between increases: 2.3 nmol/l, P = 0.912). Importantly, an association between the 'extent of the response' to TS and the performance in a memory task was revealed in secondary analyses. CONCLUSION: TS was associated with improving cognitive function in patients with AUD, independently of the substitution regime. Thus, in clinical practice, oral TS might be a sufficient but obligatory medication to prevent cognitive decline in AUD in the absence of Wernicke-Korsakoff Syndrome.

Thiamine responsive high output heart failure of adults: an under-recognized entity.

Thiamine deficiency, commonly presenting as dry and wet beriberi, a lesser-known entity in the present era, is increasingly being reported from Kashmir, a north Indian state. The present study aims to present the clinical profile of patients presenting with high-output heart failure (HOHF). Subjects with a primary diagnosis of denovo heart failure and features suggestive of HOHF were recruited; those who responded to intravenous administration of thiamine alone (responders) were adults with no co-morbidities and those who required other medications particularly diuretics (non-responders) were elderly with co-morbidities and underlying heart disease. Responders showed considerably lower mean thiamine pyrophosphate (TPP) levels and higher mean lactate and venous oxygen saturation than non-responders. More importantly, the mean drop in lactate and SVO2 following thiamine therapy was more in responders. In a setting of high risk for thiamine deficiency, features suggestive of HOHF along with elevated lactate and higher venous oxygen saturation, a response to thiamine challenge may serve as surrogate marker of thiamine deficiency.

Further evidence of relationship between thiamine blood level and cognition in chronic alcohol-dependent adults: Prospective Pilot Study of an inpatient detoxification with oral supplementation protocol.

BACKGROUND: The relationship between thiamine blood level (TBL) and cognition remains uncertain, including among alcohol-dependent persons (ADP). AIM: To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD + Th). METHODS: Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7 ± 11 years old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD + Th) and discharge (t3, post-AD + Th). Frontal Assessment Battery (FAB) was performed at t1. AD + Th included abstinence, pharmacological alcohol withdrawal syndrome treatment, and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships. RESULTS: We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD + Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years, and depression score weakly modified the relationship. CONCLUSION: TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD + Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. The TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels.

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.

Wernicke encephalopathy and beriberi disease presenting as STEMI-equivalent.

Thiamine deficiency is commonly associated with malnutrition, alcoholism and bariatric surgery. Thiamine deficiency can manifest in different ways, especially in developing countries: as peripheric neuropathy, as Wernicke encephalopathy or as beriberi disease. The authors present the case of a 72-year-old male, with a hiatal hernia that led to thiamine deficiency due to malnutrition. The initial clinical manifestation was an ST-elevation myocardial infarct equivalent, an ECG with a shark-fin pattern that evolved to a Wellens type B pattern. The patient evolved with severe altered mental status. A Wernicke encephalopathy diagnosis was confirmed by MRI; the patient was medicated with high-dose thiamine, with quick recovery, both neurologic and cardiac. The clinical history and response to treatment confirm the diagnosis of Wernicke encephalopathy and beriberi disease.

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.

A Case of Sensorineural Hearing Loss in Wernicke Encephalopathy.

Extremely rare cases of Wernicke encephalopathy (WE) can involve sensorineural hearing loss (SNHL). Here, we present a 46-year-old female with SNHL and clinical and radiologic suspicion for WE. After initiating thiamine therapy, the patient experienced robust improvement. Laryngoscope, 133:1492-1494, 2023.

Thiamine responsive megaloblastic anaemia complicated with acute Parvovirus infection: A case report.

Thiamine responsive megaloblastic anaemia syndrome also known as Rogers syndrome is a very rare autosomal recessive disorder. The hallmark of the disease is the presence of the classic triad of anaemia, diabetes mellitus, and sensorineural deafness. We report the case of a 14-year-old boy who presented to us with severe megaloblastic anaemia, diabetes mellitus, and sensorineural deafness. The anaemia was further complicated by acute parvovirus infection. He was put on high doses of thiamine (vitamin B1) which led to an improvement.

Can depressed cancer patients with a borderline thiamine concentration develop deficiency within a short time period?

BACKGROUND: Despite increasing reports of thiamine deficiency (TD) among cancer patients, there remain some patients with borderline thiamine concentrations (BTC). However, it is unclear whether such patients subsequently develop TD. METHODS: Here, we report cases of cancer patients progressing to TD within a short time period after presentation with BTC (24-28 ng/ml). CASE 1: A 49-year-old female with lung cancer. During treatment for depression, the patient showed a decreased appetite, and a blood sample revealed BTC (25 ng/ml). Fourteen days later, she reported a continued loss of appetite, and despite the absence of the 3 classical signs of Wernicke encephalopathy (WE), additional testing showed a thiamine level of 23 ng/ml, leading to a diagnosis of TD. CASE 2: A 65-year-old female developed depression during chemotherapy for angiosarcoma. Her blood sample revealed BTC (25 ng/ml). Seven days later, despite the absence of the classical signs of WE, a further testing revealed a thiamine level of 20 ng/ml. CASE 3: A 41-year-old female developed depression during chemotherapy for ovarian cancer. No loss of appetite was observed, but a blood sample revealed BTC (25 ng/ml). Seven days later, despite the absence of the classical signs of WE or decreased appetite, further testing revealed a thiamine level of 19 ng/ml. SIGNIFICANCE OF RESULTS: Depressed cancer patients with BTC may develop TD within a short time frame. To prevent TD, health-care professionals should maintain an awareness of its potential and the need for regular testing of thiamine level or prophylactic replacement therapy.