Acute Thiamine Deficiency Research Articles

Thiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases.

Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. • South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies. • Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). • Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings. • Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries. • This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Personality traits and personality problems in Korsakoff syndrome patients

ABSTRACT Personality research is of relevance because it provides insights into the psychological strengths and vulnerabilities of a person. Korsakoff’s syndrome (KS) is a severe neuropsychiatric disorder following acute thiamine deficiency, usually as a consequence of alcohol-use disorders. Research on personality traits of KS patients is currently limited. The aim of the current exploratory study was therefore to examine the personality traits and problems of KS patients. We assessed self-reported and informant-reported personality traits and problems in institutionalized KS patients (n = 30). Results indicate that the psychotic personality organization was more frequently present in KS patients compared to a psychiatric reference population, leading to increased vulnerability for the development of severe psychiatric issues. Informants observed more premorbid and current cluster B (“emotional”) and C (“anxious”) personality behavior in comparison to the general population. Also, rigid- and socially avoidant behavior in KS patients was observed to increase over the years. They also observed personality problems such as emotional-, unpredictable-, dramatic-, anxious and fearful behavior in the present and in the past. KS patients reported themselves as healthy individuals, indicating a lack of self-awareness. We recommend training programs for the medical team focussed on psycho-education and supportive interventions for patients with complex personality problems concomitant to KS.

The importance of thiamine (vitamin B1) in humans.

Thiamine (thiamin, B1) is a vitamin necessary for proper cell function. It exists in a free form as a thiamine, or as a mono-, di- or triphosphate. Thiamine plays a special role in the body as a coenzyme necessary for the metabolism of carbohydrates, fats and proteins. In addition, it participates in the cellular respiration and oxidation of fatty acids: in malnourished people, high doses of glucose result in acute thiamine deficiency. It also participates in energy production in the mitochondria and protein synthesis. In addition, it is also needed to ensure the proper functioning of the central and peripheral nervous system, where it is involved in neurotransmitter synthesis. Its deficiency leads to mitochondrial dysfunction, lactate and pyruvate accumulation, and consequently to focal thalamic degeneration, manifested as Wernicke's encephalopathy or Wernicke-Korsakoff syndrome. It can also lead to severe or even fatal neurologic and cardiovascular complications, including heart failure, neuropathy leading to ataxia and paralysis, confusion, or delirium. The most common risk factor for thiamine deficiency is alcohol abuse. This paper presents current knowledge of the biological functions of thiamine, its antioxidant properties, and the effects of its deficiency in the body.

Descriptive spectrum of thiamine deficiency in pregnancy: Apotentially preventable condition.

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. 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. 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. 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.

Acute Thiamine Deficiency Detected by Video Head Impulse Test in a Patient with Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Thiamine deficiency may cause Wernicke encephalopathy (WE) characterized by ataxia, ophthalmoplegia, and confusion. Aside from the triad of cardinal symptoms, selective or predominant impairments of bilateral horizontal canals may be observed in WE. Here, we report a patient with gastric mucosa-associated lymphoid tissue (MALT)-lymphoma complicated by an early stage of WE due to thiamine deficiency manifesting bilateral vestibular dysfunctions. A 78-year-old man recently diagnosed gastric MALT-lymphoma presented with dizziness and disequilibrium for several weeks. He showed mild imbalance while tandem walking and abnormal catch-up saccades bilaterally during bedside head impulse test (HIT). Video HIT revealed decreased vestibulo-ocular reflex gains with catch-up saccades for the bilateral horizontal and several vertical canals. Diagnostic work-up demonstrated decreased serum thiamine and lesions in the mammillary body and periaqueductal gray matter on brain magnetic resonance images. Furthermore, with thiamine replacement, his clinical symptoms were markedly improved. Also, vestibular symptoms and signs may be an early manifestation of WE, and video HIT could be a useful diagnostic tool to aid early detections.

The Use of an Errorless Learning Application to Support Re-Learning of (Instrumental) Activities for People Living with Korsakoff Syndrome.

Korsakoff syndrome (KS) is a severe neuropsychiatric syndrome derived from acute thiamine deficiency and concomitant alcohol use disorders. KS patients need lifelong assistance because of the severity of their cognitive problems. In clinical practice and research, errorless learning has proven to be an effective cognitive rehabilitation method for patients with KS. Our study focused on optimizing errorless learning by introducing new software technology to support the training process of errorless learning. Although the benefits of errorless learning for patients with Korsakoff's syndrome have been thoroughly investigated, it is currently unclear whether new technology could contribute to better learning and maintenance of everyday tasks. Therefore, an errorless learning application was built. This device is a web application and can be used on a tablet, laptop, or smartphone. The application allows clinicians and researchers to insert pictures, videoclips, timers, and audio fragments in the different steps of an errorless learning training plan. This way, the different steps are visible and easy to follow for patients. Moreover, it ensures as a learning method that the training is executed exactly the same way for each and every training. The aim of this study was twofold: to examine whether the use of the errorless learning application is effective, and whether it leads to better results than a regular errorless learning of everyday activities. In total, 13 patients with KS were trained in instrumental activities of daily living by means of the application, and 10 patients were trained with traditional instructions. Results showed an equal improvement for both training methods. Importantly, the technology group could better remember the training when probed at a later moment than the traditional errorless learning group. These results are promising for further development of novel technology to support errorless learning applications in clinical practice.

Clinical diagnosis, outcomes and treatment of thiamine deficiency in a tertiary hospital

Acute thiamine deficiency can occur in patients with or without history of alcohol abuse and can lead to life-threatening complications. Clinical diagnosis is challenging, often resulting in delayed recognition and treatment. Patients may present with heterogenous symptoms, more diverse than the historical neurological description. Cerebral MRI can contribute to the diagnosis in patients with neurological signs but it is not always feasible in emergency settings. Prompt parenteral supplementation is required to obtain the improvement of symptoms and avoid chronic complications. To describe the clinical presentation of reported cases of thiamine deficiency, assess prescription and results of cerebral imaging, review treatments that had been prescribed in accordance or not with available guidelines, and study the short-term outcome of these patients. This is a monocentric retrospective analysis of all reported cases of thiamine deficiency in a French tertiary hospital between January 1st 2008 and December 31st 2018. Fifty-six cases were identified during the study period. Forty-five (80%) patients had a history of alcohol abuse. Most patients were diagnosed based on neurological symptoms but non-specific and digestive symptoms were frequent. Thirty-four percent of patients fulfilled clinical criteria for malnutrition. A brain MRI was performed in 54% of patients and was abnormal in 63% of these cases. Eighty-five percent of patients were treated by parenteral thiamine administration and the supplementation was continued orally in 55% of them. The majority of patients initially received 1000mg daily of IV thiamine but the dose and duration of thiamine supplementation were variable. At the time of discharge, partial or complete improvement of symptoms was noted in 59% of patients. This study highlights the clinical and radiological heterogeneity of thiamine deficiency. These observations should encourage starting thiamine supplementation early in patients with risk factors or suggestive symptoms even in non-alcoholic patients, and underline the importance of early nutritional support.

Reversible Wernicke encephalopathy caused by hyperemesis gravidarum in the second trimester of pregnancy: a case report

Wernicke encephalopathy is a potentially life-threatening neurologic syndrome caused by acute thiamine (vitamin B1) deficiency. It is usually associated with excessive alcohol consumption. Less frequently, this syndrome can be caused by persistent vomiting. This is a case report of a 33-year-old woman diagnosed with Wernicke encephalopathy (WE) during the second trimester of pregnancy. The presence of neurological and ophthalmological symptoms in the context of hyperemesis gravidarum led us to evoke the diagnosis of WE, and it was confirmed when specific lesions were found in the brain magnetic resonance imaging (MRI). Luckily for our patient, WE was diagnosed promptly and the signs were reversible after thiamine supplementation. In conclusion, any first line care taker or midwife must know the symptoms of Wernicke encephalopathy because prompt diagnosis and treatment can lead to recovery

Neuro-ophthalmic Manifestations of Wernicke Encephalopathy.

Wernicke encephalopathy (WE) is a life-threatening but reversible syndrome resulting from acute thiamine deficiency that is frequently overlooked and underdiagnosed. It is classically characterized by a triad of ocular dysfunction, ataxia, and altered mental status. However, less than 1/3 patients have the complete triad, so it is crucial to have a high index of suspicion. Awareness of the early signs of WE is essential to prevent clinical progression, as patients with the full triad already have a profoundly thiamine-deficient state. This review highlights the neuro-ophthalmic manifestations of WE to guide the clinician in identifying the condition. In addition, we provide an update regarding the clinical characteristics, pathophysiology, neuroimaging and laboratory findings, treatment options, and prognosis of WE.

Aging with alcohol-related brain damage: Critical brain circuits associated with cognitive dysfunction.

Alcoholism is associated with brain damage and impaired cognitive functioning. The relative contributions of different etiological factors, such as alcohol, thiamine deficiency and age vulnerability, to the development of alcohol-related neuropathology and cognitive impairment are still poorly understood. One reason for this quandary is that both alcohol toxicity and thiamine deficiency produce brain damage and cognitive problems that can be modulated by age at exposure, aging following alcohol toxicity or thiamine deficiency, and aging during chronic alcohol exposure. Pre-clinical models of alcohol-related brain damage (ARBD) have elucidated some of the contributions of ethanol toxicity and thiamine deficiency to neuroinflammation, neuronal loss and functional deficits. However, the critical variable of age at the time of exposure or long-term aging with ARBD has been relatively ignored. Acute thiamine deficiency created a massive increase in neuroimmune genes and proteins within the thalamus and significant increases within the hippocampus and frontal cortex. Chronic ethanol treatment throughout adulthood produced very minor fluctuations in neuroimmune genes, regardless of brain region. Intermittent "binge-type" ethanol during the adolescent period established an intermediate neuroinflammatory response in the hippocampus and frontal cortex, that can persist into adulthood. Chronic excessive drinking throughout adulthood, adolescent intermittent ethanol exposure, and thiamine deficiency all led to a loss of the cholinergic neuronal phenotype within the basal forebrain, reduced hippocampal neurogenesis, and alterations in the frontal cortex. Only thiamine deficiency results in gross pathological lesions of the thalamus. The behavioral impairment following these types of treatments is hierarchical: Thiamine deficiency produces the greatest impairment of hippocampal- and prefrontal-dependent behaviors, chronic ethanol drinking ensues mild impairments on both types of tasks and adolescent intermittent ethanol exposure leads to impairments on frontocortical tasks, with sparing on most hippocampal-dependent tasks. However, our preliminary data suggest that as rodents age following adolescent intermittent ethanol exposure, hippocampal functional deficits began to emerge. A necessary requirement for the advancement of understanding the neural consequences of alcoholism is a more comprehensive assessment and understanding of how excessive alcohol drinking at different development periods (adolescence, early adulthood, middle-aged and aged) influences the trajectory of the aging process, including pathological aging and disease.

384. Wernicke’s encephalopathy: An uncommon complication from Hyperemesis Gravidarum

Hyperemesis Gravidarum (HG) is a complication of pregnancy associated with severe nausea and vomiting that can lead to fluid-electrolyte imbalances and nutritional deficiencies. HG is distinguished from the benign nausea and vomiting of pregnancy by the presence of ketonuria and weight loss. Wernicke’s Encephalopathy is a neurologic manifestation of acute thiamine (Vitamin B1) deficiency. We describe a case of Hyperemesis Gravidarum presenting with gait ataxia and nystagmus which led to Wernicke’s encephalopathy. An 18-year-old Prima Gravida at 18 weeks gestation with a history of HG presented to our hospital with a 5-day history of vertigo. She was diagnosed with dehydration secondary to HG and was admitted for further workup of her vertigo. On neurologic examination, bilateral horizontal and vertical nystagmus were present. A magnetic resonance imaging (MRI) of the brain demonstrated an area of restricted diffusion in the medial thalamic nuclei. This abnormality paired with the patient’s history of malnutrition secondary to HG supported a diagnosis of Wernicke’s Encephalopathy. The patient was administered IV thiamine 200 mg and then subsequently transitioned to oral thiamine 100 mg daily. The patient was discharged home on hospital day 5 with out-patient follow up. Hyperemesis Gravidarum is defined as persistent vomiting with a weight loss exceeding 5% of pre-pregnancy weight, in addition to ketonuria unexplained by other causes. Wernicke’s Encephalopathy presents with a classic triad of gait ataxia, ophthalmoplegia, and confusion. Wernicke’s Encephalopathy is most commonly caused by chronic alcoholism, but it can also occur rarely as a complication of HG. In conclusion, vertigo during pregnancy should be carefully evaluated and physicians should maintain a broad differential diagnosis, including Wernicke’s Encephalopathy. When treating Hyperemesis Gravidarum, clinicians should have a high level of suspicion for Wernicke’s encephalopathy if neurologic complaints occur, as failure to provide timely treatment could lead to fatal maternal and fetal consequences.

Avoiding refeeding syndrome in anorexia nervosa

The term refeeding syndrome has been used to describe the adverse consequences that can occur in all malnourished patients in the early stages of nutrition repletion whether the method of refeeding is oral, enteral or parenteral. Those consequences include acute thiamine deficiency resulting in Wernicke's encephalopathy and Korsakoff syndrome, with the potential for permanent cognitive impairment; hypophosphatemia, hypokalemia, hypomagnesemia and fluid overload resulting in cardiac failure. Adaptive changes in metabolism occur during a period of starvation or fasting: levels of glucose fall within 24 to 72 hours, as response, glucagon levels rise and insulin concentrations decrease. Glucose levels are maintained by glycogenolysis at first and gluconeogenesis latter. The reintroduction of nutrition leads to a switch from fat to carbohydrate metabolism and an increase of insulin concentration. Insulin stimulates the movement of potassium, phosphate, and magnesium into the cell leading to its depletion in extracellular compartment. Reactivation of carbohydrate metabolism increases degradation of thiamine, a cofactor required for cellular enzymatic reactions in Kreb's cycle. Deficiency in all these nutrients can then occur. Patients with anorexia nervosa are at risk of suffering from refeeding syndrome. This psychiatric disorder causes potentially life-threatening, physical complications and has the highest mortality rate among psychiatric disorders. The purpose of this review is to clarify recommendations for prevention and treatment of refeeding syndrome in anorexia nervosa.Disclosure of interestThe authors have not supplied their declaration of competing interest.

John Angus Black

Polymathic paediatrician dedicated to ethnic minority needs When John Black landed by ship at Singapore five days after the Japanese surrender he was faced with an unsolved problem: restoring to...

Use of a thiamine antagonist to evaluate the effects of thiamine deficiency on lake trout embryonic development

To more fully understand the secondary effects of thiamine deficiency on embryo development of lake trout Salvelinus namaycush, we used an immersion protocol to administer graded doses of the thiamine antagonist oxythiamine (OXY) (e.g., 0, 12.5, 25, 50, 100, 200, and 400mg/L). OXY was administered to eggs of six families at water hardening (fertilization) with the intent that early mortality syndrome (EMS), an acute thiamine deficiency mortality, would only occur at the highest OXY concentration. We assessed the effect of OXY and family on the occurrence of EMS and other embryonic mortality, and alevin growth dynamics up until 2weeks post emergence. EMS reached only 4% at the highest OXY concentration (400mg/L) where there was a significant decline in alevin length and yolkless alevin dry weight but not the dry weight of alevins whose yolk-sac was still attached. The dry weight of the yolk-sac as a percentage of total alevin dry weight was lower than controls at low concentrations of OXY (12.5, 25mg/L), but higher than controls at the highest concentration of OXY (400mg/L). OXY appeared to exert its effect on growth through reduced yolk-sac utilization although the mechanism(s) involved is unknown. Reduced growth and yolk-sac utilization of alevins resulting from thiamine deficiency may contribute to mortality through decreased ability of affected alevins to secure food and avoid predation. We conclude that even for very low EMS, alevin growth effects resulting from thiamine deficiency may pose a significant impediment to lake trout reproduction.

Case Report of Acute Thiamine Deficiency Occurring as a Complication of Vitamin‐Free Parenteral Nutrition

Parenteral nutrition (PN) is a relatively recent life-saving development in medicine but brings with it a range of new potential complications. Much of our knowledge about the signs and symptoms of individual micronutrient deficiencies comes from observations of patients receiving PN, and an example of this is the pivotal paper by Velez and colleagues published in Journal of Parenteral and Enteral Nutrition in 1985. This case report was the first published study to identify acute thiamine deficiency with cardiopathy and metabolic acidosis occurring in adult patients receiving vitamin-free PN. Although the importance of thiamine has been recognized since the late 19th century, it is still unclear exactly what dose is required for full repletion of a deficient patient, and further research would be useful to elucidate this question.

Lebensbedrohliche Komplikation bei Schizophrenie

The Wernicke Encephalopathy (WE) as a result of a (sub)acute thiamine deficiency remains, unfortunately, still under-diagnosed, especially among non-alcoholics. It should be considered in each occurrence of delirium as well as in any ocular motor disorder and ataxia, in particular if there is a history of weight loss with or without gastrointestinal symptoms. In cases with suspected WE an immediate intravenous substitution of 3×200 mg/d is recommended.

Acute thiamine deficiency in diabetic ketoacidosis: Diagnosis and management

Persistent encephalopathy in a patient with diabetic ketoacidosis is often feared as a sign of cerebral edema. Although thiamine deficiency is a rare diagnosis in children, marginal nutritional status and osmotic diuresis may be risk factors. The objective was to describe a heretofore unreported cause of encephalopathy in a child with diabetic ketoacidosis and review the mechanisms and pathophysiology of thiamine deficiency in this clinical scenario. Case report and review of the literature. Pediatric intensive care unit of a tertiary care pediatric hospital. A 13-yr-old girl. Treatment of dehydration and hyperglycemia, osmotherapy, and intravenous thiamine administration. The patient presented with new-onset diabetes mellitus, severe diabetic ketoacidosis, and significant encephalopathy. Despite biochemical improvement with treatment of dehydration and hyperglycemia, her encephalopathy persisted. Computed tomography did not show cerebral edema and she showed no response to osmotherapy. Quantitative and functional assays revealed severe thiamine deficiency. The patient showed an immediate and dramatic response to intravenous thiamine administration. The clinical improvement as well as lab investigations suggests that thiamine deficiency was the cause of this child's encephalopathy. Because potential mechanisms exist for thiamine deficiency in diabetes mellitus and institution of insulin and glucose therapy may stress thiamine body stores, thiamine deficiency should be considered in children with diabetic ketoacidosis whose encephalopathy does not improve with improvement of biochemical status.

Wernicke encephalopathy after bariatric surgery: Losing more than just weight

Foster et al. describe a complication well known to bariatric surgeons—acute thiamine deficiency.1 This tremendously disabling complication is nearly always preceded by persistent vomiting weeks or months after bariatric surgery and is most often caused by a stricture of the gastrojejunal anastomosis. While highlighting …

Restricted Diffusion of the Splenium in Acute Wernicke's Encephalopathy

Acute Wernicke's encephalopathy (WE) is caused by profound vitamin B1 (thiamine) deficiency and commonly presents with the classic clinical triad of mental confusion, ataxia, and ophthalmoplegia. This characteristic presentation results from the propensity of acute thiamine deficiency to preferentially injure specific brain regions: the dorsomedial thalamus, periaqueductal gray, and mamillary bodies. In these regions, abnormal magnetic resonance signaling on conventional sequences has been well described; however, diffusion restriction has only recently been reported. The authors demonstrate diffusion-weighted imaging (DWI) abnormalities of the splenium of the corpus callosum in a patient with acute WE, which has not been reported previously, and suggest a potential pathological mechanism. With the recent addition of DWI, MRI is becoming more sensitive to the changes in acute WE. Furthermore, the use of apparent diffusion coefficient mapping to evaluate the extent of likely underlying cytotoxic injury may help determine long-term response to vitamin therapy and, thus, disability.

Restricted Diffusion of the Splenium in Acute Wernicke's Encephalopathy

ABSTRACTAcute Wernicke's encephalopathy (WE) is caused by profound vitamin B1 (thiamine) deficiency and commonly presents with the classic clinical triad of mental confusion, ataxia, and ophthalmoplegia. This characteristic presentation results from the propensity of acute thiamine deficiency to preferentially injure specific brain regions: the dorsomedial thalamus, periaqueductal gray, and mamillary bodies. In these regions, abnormal magnetic resonance signaling on conventional sequences has been well described; however, diffusion restriction has only recently been reported. The authors demonstrate diffusion‐weighted imaging (DWI) abnormalities of the splenium of the corpus callosum in a patient with acute WE, which has not been reported previously, and suggest a potential pathological mechanism. With the recent addition of DWI, MRI is becoming more sensitive to the changes in acute WE. Furthermore, the use of apparent diffusion coefficient mapping to evaluate the extent of likely underlying cytotoxic injury may help determine long‐term response to vitamin therapy and, thus, disability.