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

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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 1000 mg 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. CONCLUSION: 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.

Thiamine fortification strategies in low- and middle-income settings: a review.

Thiamine (vitamin B1 ) is an essential micronutrient in energy metabolism and cognitive and neurological health. Thiamine deficiency disorders (TDDs) have a range of clinical presentations that result in various morbidities and can be fatal if not promptly recognized and treated, especially in infants. To intervene, thiamine intakes by breastfeeding mothers and others at risk of thiamine deficiency should be increased to ensure adequate thiamine intake. Although thiamine fortification programs have a long history in high-income countries, there are few mandatory fortification programs to address TDDs in low- and middle-income countries (LMICs), particularly in the regions of greatest concern, South and Southeast Asia. This review highlights essential aspects for consideration in the development of a mandatory fortification program in LMICs, including an overview of the data required to model fortification dosing schemes, available thiamine fortificants, and potential fortification vehicles, as well as identifies current knowledge gaps.

Pathophysiology, prevention, and treatment of beriberi after gastric surgery.

Beriberi is a nutritional complication of gastric surgery, caused by deficiency of vitamin B1, or thiamine. Thiamine deficiency leads to impaired glucose metabolism, decreased delivery of oxygen by red blood cells, cardiac dysfunction, failure of neurotransmission, and neuronal death. This review describes the history and pathophysiology of beriberi as well as the relationship between beriberi and nutritional deficiencies after gastric surgery. A literature review of the history and pathophysiology of beriberi and the risk factors for thiamine deficiency, particularly after gastric resection or bariatric surgery, was performed. Recommendations for nutritional follow-up post gastric surgery are based on current national guidelines. Patients may have subclinical thiamine deficiency after upper gastrointestinal surgery, and thus beriberi may be precipitated by acute illness such as sepsis or poor dietary intake. This may occur very soon or many years after gastrectomy or bariatric surgery, even in apparently well-nourished patients. Prompt recognition and administration of supplemental thiamine can decrease morbidity and mortality in patients with beriberi. Dietary education post surgery and long-term follow-up to determine nutritional status, including vitamin and mineral assessment, is recommended for patients who undergo gastric surgery.

Early recognition of thiamine deficiency: ocular motor deficits in a patient with nutritional deprivation due to persistent antibiotic-related nausea.

CASE DESCRIPTION: A 73-year-old male presented with new onset dizziness and a 22-kg weight loss due to antibiotic-induced nausea/vomiting. Due to gaze-evoked nystagmus (GEN), thiamine deficiency was suspected. Within 12 h after replacement, his GEN decreased. CONCLUSION: In patients with nutritional deprivation, new onset GEN should prompt further diagnostics and immediate thiamine supplementation to avoid disease progression.

Infantile Thiamine Deficiency: New Insights into an Old Disease.

CONTEXT: The wide spectrum of clinical presentation in infantile thiamine deficiency is difficult to recognize, and the diagnosis is frequently missed due to the lack of widespread awareness, and non-availability of costly and technically demanding investigations. EVIDENCE ACQUISITION: The topic was searched by two independent researchers using online databases of Google scholar and PubMed. We considered the related studies published in the last 20 years. The terms used for the search were 'thiamine', 'thiamine deficiency', 'beri-beri', 'B-vitamins','micronutrients', 'malnutrition', 'infant mortality'. 'Wernicke's syndrome','Wernicke's encephalopathy', and 'lactic acidosis'. RESULTS: In the absence of specific diagnostic tests, a low threshold for a therapeutic thiamine challenge is currently the best approach to diagnose infantile thiamine deficiency in severe acute conditions. The practical approach is to consider thiamine injection as a complementary resuscitation tool in infants with severe acute conditions; more so in presence of underlying risk factors, clinically evident malnutrition or where a dextrose-based fluid is used for resuscitation. Further, as persistent subclinical thiamine deficiency during infancy can have long-term neuro-developmental effects, reasonable strategy is to treat pregnant women suspected of having the deficiency, and to supplement thiamine in both mother and the baby during breastfeeding. CONCLUSIONS: Health care professionals in the country need to be sensitized to adopt a high level of clinical suspicion for thiamine deficiency and a low threshold for the administration of thiamine, particularly when infantile thiamine deficiency is suspected.

Complete recovery in Wernicke's encephalopathy complicating hyperemesis gravidarum.

Wernicke's encephalopathy (WE) is an uncommon neurological complication in pregnancies complicated with hyperemesis due to thiamine deficiency. In women with hyperemesis, inadvertent glucose administration prior to thiamine supplementation triggers the development of neurological manifestations. Delay in the diagnosis can lead to maternal morbidity, and in one-third of cases may lead to persistence of some neurological deficit. With early recognition and thiamine supplementation, complete recovery is reported. We report a case of WE complicating a case of triplet pregnancy with hyperemesis gravidarum, which highlights the importance of early recognition and treatment, resulting in complete recovery as in the index case.

[Thiamine-responsive megaloblastic anemia or Rogers syndrome: A literature review]. / L'anémie mégaloblastique thiamine dépendante ou syndrome de Rogers : une revue de la littérature.

Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive disease characterized by three main components: megaloblastic anemia, diabetes mellitus and sensorineural deafness. Those features occur in infancy but may arise during adolescence. Diagnosis relies on uncovering genetic variations (alleles) in the SLC19A2 gene, encoding for a high affinity thiamine transporter. This transporter is essentially present in hematopoietic stem cells, pancreatic beta cells and inner ear cells, explaining the clinical manifestations of the disease. Based on a multidisciplinary approach, treatment resides on lifelong thiamine oral supplementation at pharmacological doses, which reverses anemia and may delay development of diabetes. However, thiamine supplementation does not alleviate already existing hearing defects.

Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs.

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month-specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high-risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.

Thiamine status, metabolism and application in dairy cows: a review.

As the co-enzyme of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, thiamine plays a critical role in carbohydrate metabolism in dairy cows. Apart from feedstuff, microbial thiamine synthesis in the rumen is the main source for dairy cows. However, the amount of ruminal thiamine synthesis, which is influenced by dietary N levels and forage to concentrate ratio, varies greatly. Notably, when dairy cows are overfed high-grain diets, subacute ruminal acidosis (SARA) occurs and results in thiamine deficiency. Thiamine deficiency is characterised by decreased ruminal and blood thiamine concentrations and an increased blood thiamine pyrophosphate effect to >45 %. Thiamine deficiency caused by SARA is mainly related to the increased thiamine requirement during high grain feeding, decreased bacterial thiamine synthesis in the rumen, increased thiamine degradation by thiaminase, and decreased thiamine absorption by transporters. Interestingly, thiamine deficiency can be reversed by exogenous thiamine supplementation in the diet. Besides, thiamine supplementation has beneficial effects in dairy cows, such as increased milk and component production and attenuated SARA by improving rumen fermentation, balancing bacterial community and alleviating inflammatory response in the ruminal epithelium. However, there is no conclusive dietary thiamine recommendation for dairy cows, and the impacts of thiamine supplementation on protozoa, solid-attached bacteria, rumen wall-adherent bacteria and nutrient metabolism in dairy cows are still unclear. This knowledge is critical to understand thiamine status and function in dairy cows. Overall, the present review described the current state of knowledge on thiamine nutrition in dairy cows and the major problems that must be addressed in future research.

A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan Africa?

Staple diets that are deficient in thiamine can result in low body thiamine levels, which may be subclinical or may manifest as a thiamine-deficiency syndrome. In many communities in the developing countries of Africa, the staple diets of polished rice or processed cassava are deficient in thiamine, and thus the communities are at high risk for marginal or frank thiamine deficiency unless their diets are supplemented by other sources of thiamine, such as protein meals and vegetables. African communities with large numbers of individuals in low socioeconomic strata are more likely to subsist on a monotonous diet of rice or cassava with minimal or no protein supplementation and are therefore particularly at risk of thiamine-deficiency disorders. Indeed, there is evidence of widespread biochemical thiamine deficiency from community-based studies in Africa. The protean manifestations of thiamine deficiency disorders in the developing countries of Africa are presented in this paper. We present evidence supporting the contention that there is a diagnosis and treatment gap for thiamine-deficiency disorders in Africa. We discuss research and clinical options for bridging the putative diagnosis and treatment gap for thiamine-deficiency disorders in the developing countries of Africa.

Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.

BACKGROUND: Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. MATERIALS AND METHODS: A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. RESULTS: Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. OUTCOMES: The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery.

Cardiac beriberi: often a missed diagnosis.

Thiamine deficiency leads to various manifestations due to dysfunction of nervous or cardiovascular system, commonly known as dry and wet beriberi, respectively. The latter, also known as cardiac beriberi is usually missed in clinical practice because of the absence of classically described symptoms such as pedal edema/anasarca. We investigated 55 such infants and prospectively followed their clinical course. All the babies were exclusively breast-fed and their mothers belonged to low socio-economic status with their staple diet consisting of non-parboiled polished rice. Majority presented with tachypnea, chest indrawing and tachycardia and cardiomegaly with dilatation of right heart and pulmonary hypertension on 2D-echocardiography. Low levels of erythrocyte transketolase activity suggested thiamine deficiency that was confirmed by reversion of several clinical features including cardiologic abnormalities to normalcy on thiamine supplementation. We recommend thiamine therapy for infants with unexplained congestive cardiac failure or acute respiratory failure from precarious socio-economic background since it is life-saving in many instances.

Need for thiamine in peripheral parenteral nutrition after abdominal surgery in children.

BACKGROUND: Thiamine blood concentrations of pediatric patients receiving peripheral parenteral nutrition change during the postoperative period. In addition, the need to administer thiamine after surgery has not yet been fully studied in children receiving peripheral parenteral nutrition. OBJECTIVE: The objective of this prospective study is to clarify whether pediatric patients require the administration of thiamine while receiving peripheral parenteral nutrition after abdominal surgery. PATIENTS: Fifteen children were divided into 2 groups; 1 group received peripheral parenteral nutrition without thiamine after surgery (n = 7), whereas the other group received peripheral parenteral nutrition with thiamine after surgery (n = 8). In both groups, thiamine blood concentrations were measured on the preoperative day, and changes in thiamine concentration over time were measured during the starvation period from the first to the fifth postoperative day. RESULTS: Preoperative thiamine blood concentrations were within the normal range in both groups. In the group receiving peripheral parenteral nutrition without thiamine, the thiamine concentration gradually decreased with time after the operation, whereas the concentration remained within the normal range in the group receiving peripheral parenteral nutrition with thiamine. Among the 7 patients receiving peripheral parenteral nutrition without thiamine, the thiamine concentration in 3 patients was below the normal range on the fifth postoperative day. CONCLUSION: During the starvation period after abdominal surgery, thiamine blood concentrations decreased in pediatric patients receiving peripheral parenteral nutrition without thiamine. Therefore, clinicians treating pediatric patients should add thiamine to the peripheral parenteral nutrition solution during the short starvation period after abdominal surgery.

Wernicke's syndrome after sleeve gastrectomy.

We report a case of Wernicke's encephalopathy after sleeve gastrectomy, which had been complicated by stomach wall edema and aggravated by dietary non-compliance. Despite intense parenteral nutrition, thiamine deficiency became clinically evident. It suggests that nutritional preparations used were unable to cover the increased thiamine requirement. After intense thiamine supplementation, gradual improvement occurred during the 6 months after the diagnosis, without permanent cognitive impairment. Clinicians involved in postoperative management of bariatric surgery patients must consider Wernicke's syndrome in hyper-emetic patients, who show unclear neurological deterioration. Early diagnosis and treatment can instantly improve the patient's condition without permanent sequelae.

Severe lactic acidosis and thiamine deficiency during total parenteral nutrition--case report.

We encountered a case of total parenteral nutrition-associated lactic acidosis that did not respond to sodium bicarbonate or other conventional emergency treatments. He was characterized by minimal food intake before surgery, delayed gastric emptying after pylorus-preserving pancreatoduodenectomy due to pancreas head cancer and long-term total parenteral nutrition without food intake and vitamin supplements after surgery. After thiamine administration, the patient very quickly recovered with dramatic reestablishment of the acid-base balance. We emphasize the need to supplement total parenteral nutrition with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements and to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of severe lactic acidosis with unknown cause. In conclusion, thiamine deficiency should be included in the differential diagnosis of lactic acidosis for the patients who received total parenteral nutrition without food intake and vitamin supplements.

[Cardiac beriberi]. / Béribéri cardiaque.

Interest has recently risen regarding thiamine deficiency (beriberi). In industrial countries, not only alcoholics, but also deprived people with malnutrition, elderly patients and patients with AIDS are at risk of thiamine deficiency. Moreover, long-term furosemide use may be associated with thiamine deficiency through urinary loss, contributing to cardiac insufficiency in patients with congestive heart failure. Cardiovascular (wet beriberi) manifestations of thiamine deficiency are characterized by peripheral vasodilatation with increased cardiac output, myocardial lesion, sodium and water retention and biventricular myocardial failure. Treatment consists of thiamine administration with rapid clinical improvement after supplementation.

B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol misuse and alcohol withdrawal are associated with a variety of neuropsychiatric syndromes, some of which are associated with significant morbidity and mortality. B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wernicke Korsakoff syndrome (WKS). due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on WKS.

Thiamine deficiency-induced gestational polyneuropathy and encephalopathy. A case report.

A 22-year-old multigravida presented with polyneuropathy and encephalopathy at 18 weeks' pregnancy. After excluding other applicable conditions, the diagnosis of a hyperemesis-induced thiamine deficiency was made. With the necessary vitamin supplementation the patient gradually recovered over a period of 4 months and was delivered of a normal infant at term. Gestational polyneuropathy and encephalopathy due to thiamine deficiency has very rarely been reported. The literature is reviewed with discussion of the differential diagnosis, the treatment and the prognosis.

The assessment of thiamine status

There is indirect evidence that Jamaican children with protein energy malnutrition and adult alcoholics with cirrhosis may be thiamine deficient because of sudden death of some malnourished children during rehabilitation and observation of a good clinical response to thiamine supplements by the alcoholic patients with cirrhosis. The aim of this study is to examine the thiamine status of severely malnourished children aged 6-24 months and in adult patients with alcoholic liver disease. Erythrocyte transketolase activity (ETLA) was determined in 25 children (14 boys, 11 girls) aged 7 weeks to 27 months, consecutively admitted to hospital for the treatment of severe protein energy malnutrition, before any vitamin supplementation and twice during rehabilitation. ETKA determinations were carried out upon 9 adult alcoholics with liver disease (8males, 1 female) aged 32 and 73 years, before and after thiamine supplementation, as well as 28 normal healthy control children attending child well-baby clinic and 22 normal healthy adult blood donors. In 36 percent of the malnourished children, the thiamine pyrophosphate stimulation effect (TPP-E) was greater than 15 percent (mean TPP-E percent 23.6ñ6.2 SD) with moderate thiamine deficiency in 4 and severe deficiency in 5. All survived. Of the 16 with normal thiamine status on admission, 5 died subsequently. In two of these, TPP-E percent of 21 and 103 was found in ante-mortem specimen. Specific clinical features were associated with biochemical thiamine deficiency in only one child. Of the 9 adult alcoholics, 3 were found to be thiamine deficient (mean TPP-E percent 20.6ñ7.3 SD), 1 marginally and 2 severely. Although all appeared to improve with thiamine therapy, responses were slow. Unlike the malnourished children the adults' clinical features appeared to validate the biochemical findings. It was concluded that (1) thiamine deficiency is present in 7 percent of control children, 14 percent control adults, 36 percent severely malnourished children and 33 percent adult alcoholics: this may represent a public health problem in Jamaica; (2) thiamine status improves with the standard therapeutic regime in most infants and adult alcoholics, but slow response was seen with pharmacological doses; (3) there are no specific features associated with the deficiency; and (4) in very sick children, a masked thiamine deficiency on admission may become overt on the standard therapeutic regimen (AU)