Association between thiamine decrease and neuropsychiatric symptoms in gastrointestinal and hematological cancer patients receiving chemotherapy.

BACKGROUND: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. METHOD: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. RESULTS: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test). CONCLUSION: Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels.

The Relevance of Thiamine Evaluation in a Practical Setting.

Thiamine is a crucial cofactor involved in the maintenance of carbohydrate metabolism and participates in multiple cellular metabolic processes. Although thiamine can be obtained from various food sources, some common food groups are deficient in thiamine, and it can be denatured by high temperature and pH. Additionally, different drugs can alter thiamine metabolism. In addition, the half-life of thiamine in the body is between 1 and 3 weeks. All these factors could provide an explanation for the relatively short period needed to develop thiamine deficiency and observe the consequent clinical symptoms. Thiamine deficiency could lead to neurological and cardiological problems. These clinical conditions could be severe or even fatal. Marginal deficiency too may promote weaker symptoms that might be overlooked. Patients undergoing upper gastrointestinal or pancreatic surgery could have or develop thiamine deficiency for many different reasons. To achieve the best outcome for these patients, we strongly recommend the execution of both an adequate preoperative nutritional assessment, which includes thiamine evaluation, and a close nutritional follow up to avoid a nutrient deficit in the postoperative period.

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.

Subclinical thiamine deficiency identified by preoperative evaluation in an ovarian cancer patient: Diagnosis and the need for preoperative thiamine measurement.

OBJECTIVE: Although thiamine deficiency (TD) and Wernicke encephalopathy (WE) are not rare in cancer patients, the cases reported to date developed TD and/or WE after treatment had started. METHOD: From a series of cancer patients, we report a patient diagnosed with TD without the typical clinical symptoms of WE at the preoperative psychiatric examination. RESULT: A 43-year-old woman with ovarian cancer was referred by her oncologist to the psycho-oncology outpatient clinic for preoperative psychiatric evaluation. Her tumor had been growing rapidly before the referral. Although she did not develop delirium, cerebellar signs, or eye symptoms, we suspected she might have developed TD because of her 2-month loss of appetite as the storage capacity of thiamine in the body is approximately 18 days. The diagnosis of TD was supported by abnormally low serum thiamine levels. SIGNIFICANCE OF RESULTS: Cancer therapists need to be aware that thiamine deficiency may occur even before the start of cancer treatment. In cases with a loss of appetite of more than 2 weeks' duration, in particular, thiamine deficiency should be considered if the tumor is rapidly increasing, regardless of the presence or absence of delirium.

Stabilization of the hypoxia-inducible transcription Factor-1 alpha (HIF-1α) in thiamine deficiency is mediated by pyruvate accumulation.

Vitamin B1, or thiamine is a critical enzyme cofactor required for metabolic function and energy production. Thiamine deficiency (TD) is common in various diseases, and results in severe neurological complications due to diminished mitochondrial function, oxidative stress, excitotoxicity and inflammation. These pathological sequelae result in apoptotic cell death in both neurons and astrocytes in distinct regions, in particular the thalamus and mammillary bodies. Comparable histological injuries in patients with hypoxia/ischemia (H/I) have also been described, suggesting a congruency between the cellular responses to these stresses. Analogous to H/I, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) even without changes in physiological oxygen levels. However, the mechanism of HIF-1α stabilization in TD is currently unknown. Using a pyruvate assay, we have demonstrated that TD induces pyruvate accumulation in mouse primary astrocytes which correlates to an increase in HIF-1α expression. Additionally, we utilized an enzymatic assay for pyruvate dehydrogenase to demonstrate a reduction in catalytic activity during TD due to lack of available thiamine pyrophosphate cofactor, resulting in the observed pyruvate accumulation. Finally, a pyruvate kinase inhibitor which limited pyruvate accumulation was utilized to demonstrate the role of pyruvate accumulation in HIF-1α stabilization during TD. These results reveal that stabilization of HIF-1α protein in TD centralizes on pyruvate accumulation in mouse primary astrocytes due to metabolic disruption of PDH.

Prevalence of clinical thiamine deficiency in individuals with medically complicated obesity.

Thiamine is a vitamin whose deficient can result in multiorgan symptoms. We described an 18% prevalence of clinical thiamine deficiency after gastric bypass surgery. Our hypotheses are that individuals with medically complicated obesity frequently have clinical thiamine deficiency and that diabetes mellitus is a mechanism for development of clinical thiamine deficiency. This is a single institution, retrospective observational study of consecutive patients with a body mass index of at least 35 kg/m2 who were evaluated in preoperative gastrointestinal bariatric clinic from 2013 to 2015. Each patient underwent a symptom survey. Clinical thiamine deficiency is defined by both (1) consistent clinical symptom and (2) either a low whole-blood thiamine concentration or significant improvement of or resolution of consistent clinical symptoms after receiving thiamine supplementation. After excluding 101 individuals with prior bariatric surgery or heavy alcohol consumption, 400 patients were included in the study. Sixty-six patients (16.5% of 400) fulfill a diagnosis of clinical thiamine deficiency, with 9 (14% of 66) having consistent gastrointestinal manifestations, 46 (70% of 66) having cardiac manifestations, 39 (59% of 66) having peripheral neurologic manifestations, and 3 (5% of 66) having neuropsychiatric manifestations. Diabetes mellitus is not a risk factor (P=.59). Higher body mass index is a significant risk for clinical thiamine deficiency (P=.007). Clinical thiamine deficiency is common in these individuals and a higher body mass index is an identified risk factor. Mechanisms explaining development of thiamine deficiency in obese individuals remain unclear.

Treatment of rats with the JAK-2 inhibitor fedratinib does not lead to experimental Wernicke's encephalopathy.

Recent clinical trials suggest that patients with myelofibrosis can develop Wernicke's encephalopathy (WE) when treated with fedratinib, a specific Janus kinase-2 (JAK-2) inhibitor. To investigate this issue, we have examined (1) if fedratinib can produce or alter the course of this disorder, (2) its effects on thiamine-dependent enzyme activity and thiamine status, and (3) its influence on the uptake of thiamine. Animals administered fedratinib for 28days at a comparable dose used to treat human cases of myelofibrosis showed no evidence of clinical signs of thiamine deficiency (TD). Rats treated with a combination of fedratinib and TD exhibited no neurological differences in their progress to the symptomatic stage when compared to thiamine-deficient animals only. Treatment with the JAK-2 inhibitor did not compromise erythrocyte transketolase activity, and thiamine status was not affected in a major way unlike animals with TD. In addition, treatment of cultured astrocytes with fedratinib did not diminish the uptake of thiamine into these cells. Our findings suggest that treatment with fedratinib does not lead to or alter the progress of TD, and do not support the notion that administration of this JAK-2 inhibitor directly results in the development of WE due to inhibition of thiamine transport. Known adverse effects of fedratinib involving compromised gastrointestinal function may be an important indirect contributing factor to previously reported cases of WE in patients with myelofibrosis.

High rate of thiamine deficiency among inpatients with cancer referred for psychiatric consultation: results of a single site prevalence study.

OBJECTIVE: Thiamine deficiency (TD) is increasingly recognized in medically ill patients. The prevalence of TD among cancer patients is unknown. This study aims to characterize the prevalence of TD among inpatients with cancer. METHODS: Retrospective chart review of patients admitted to a large cancer center who were referred for psychiatric consultation and whose serum thiamine concentration was measured. Patients with alcohol use were excluded. RESULTS: Among 217 patients with various cancer types, TD was found in 55.3%. Risk factors included fluorouracil-based chemotherapy, significant weight loss, and undergoing active cancer treatment. Almost all patients were normal weight, overweight, or obese, and few had concomitant vitamin B12 or folate deficiency. A total of 17.5% were receiving multivitamin supplementation. Nearly half (49.8%) did not receive empiric treatment with thiamine and among those who did, treatment delay occurred in the majority of cases (59.6%). Measurement of serum thiamine concentration preceded psychiatric consultation in only 10.6% of cases. CONCLUSIONS: Our findings suggest that TD is highly prevalent among inpatients with cancer, even among normal and overweight individuals, in the absence of other vitamin deficiencies, and while receiving multivitamin supplements. Several potential risk factors were identified, including active cancer treatment. Evaluation of TD was most commonly not initiated by oncologists. Failure to treat and treatment delay were common. Given these findings, oncologists must be vigilant about detecting TD among inpatients with cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Challenges in Diagnosis and Treatment of Wernicke Encephalopathy: Report of 2 Cases.

BACKGROUND: Wernicke encephalopathy (WE) is a medical emergency caused by thiamine deficiency, characterized by cerebellar ataxia, ophthalmoplegia, and cognitive disturbances that may progress to Korsakoff amnesia. We describe 2 patients with WE who needed high-dose and long-term treatment with thiamine to obtain neurological improvement and recovery. CASE DESCRIPTION: The first patient was a woman diagnosed with non-Hodgkin lymphoma. After a gastrointestinal infection, she developed depression, memory loss, disorientation, behavioral changes, and ataxic paraplegia. Brain magnetic resonance imaging (MRI) showed bilateral alterations in thalamic, frontal, and periaqueductal regions, suggestive of WE. The second patient was a man who lost 10 kg after surgical gastrectomy; he developed diplopia, ophthalmoplegia, cerebellar ataxia, lower limb paresthesias, and amnesia. A brain MRI demonstrated contrast enhancement of mammillary bodies, compatible with WE. OUTCOME: The patients were treated with intramuscular (IM) thiamine (1200 mg/d for 2 months and 900 mg/d for a month, respectively) with gradual cognitive and behavioral improvement and brain MRI normalization, while ataxia and oculomotion improved in following months. In both patients, thiamine was gradually reduced to IM 200 mg/d and continued for a year, without clinical relapses. CONCLUSIONS: There is no consensus about dosage, frequency, route, and duration of thiamine administration in WE treatment. Based on our cases, we recommend treating patients with WE with higher doses of IM thiamine for a longer time than suggested (900-1200 mg/d for 1-2 months, in our cases) and to gradually reduce dosage after clinical and radiological improvement, maintaining IM 200 mg/d dosage for at least 1 year.

Thiamin deficiency in people with obesity.

Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included.

Ressonância magnética cardíaca na cardiomiopatia dilatada: atualidades / Cardiac magnetic resonance in dilated cardiomyopathy: an update

JUSTIFICATIVA E OBJETIVOS: A cardiomiopatia dilatada(CMD) é a mais comum das cardiomiopatias, compreendendo mais de 90% de todos os casos. O seu diagnóstico é feito, sobretudo,com a utilização da ecocardiografia, a qual apresenta algumas limitações quanto à identificação da etiologia. A ressonância magnética cardíaca (RMC) tem se destacado como exame coadjuvante, permitindo melhor caracterização morfofuncional e tecidual do músculo cardíaco. O objetivo deste estudo foi descrevero papel da RMC no diagnóstico e avaliação das diversas causas de CMD.CONTEÚDO: A RMC apresentou bons resultados na aplicaçã oclínica em diversas causas de CMD, não possuindo capacidade de diferenciar todos os seus tipos, porém, contribuindo para a presunção diagnóstica.CONCLUSÃO: Com o avanço tecnológico da RMC, múltiplas indicações clínicas têm surgido em algumas ocasiões, com um aspecto complementar a determinados exames, em outras, como solução de dilemas diagnósticos. Tudo isso com acurácia superior aos demais métodos de imagem, poucas contraindicações e mínimos riscos de efeitos adversos.(AU)

BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy (DCM) is the most common cause of cardiomyopathies,including more than 90% of all cases. Its diagnostic is done using, especially, echocardiography; which presents some limitations regarding the etiology's identification. Cardiac magnetic resonance (CMR) has been very useful as a more precise study, allowing better characterization of myocardium tissue and morphology. The objective of this article was to describe the role of the CMR in the diagnosis and evaluation of the diverse causes of DCM.CONTENTS : The CMR presented good results in the clinical applicationin diverse causes of DCM, not having capacity to differentiate all their types; however, better contributing to the diagnostic and patients follow up.CONCLUSION: With the technological development of CMR, several clinical indications have been created, in a few occasions with a complementing aspect to certain exams, in others with solutions of diagnostic dilemmas. All with higher accuracy in comparison to others image modalities, few contraindications and minimum adverse risks effects.(AU)

1,3-Dinitrobenzene-induced metabolic impairment through selective inactivation of the pyruvate dehydrogenase complex.

Prolonged exposure to the chemical intermediate, 1,3-dinitrobenzene (1,3-DNB), produces neuropathology in the central nervous system of rodents analogous to that observed in various conditions of acute energy deprivation including thiamine deficiency and Leigh's necrotizing encephalopathy. Increased production of reactive intermediates in addition to induction of oxidative stress has been implicated in the neurotoxic mechanism of 1,3-DNB, but a clear metabolic target has not been determined. Here we propose that similar to thiamine deficiency, the effects of 1,3-DNB on metabolic status may be due to inhibition of the thiamine-dependent α-ketoacid dehydrogenase complexes. The effects of 1,3-DNB on astroglial metabolic status and α-ketoacid dehydrogenase activity were evaluated using rat C6 glioma cells. Exposure to 1,3-DNB resulted in altered morphology and biochemical dysfunction consistent with disruption of oxidative energy metabolism. Cotreatment with acetyl-carnitine or acetoacetate attenuated morphological and metabolic effects of 1,3-DNB exposure as well as increased cell viability. 1,3-DNB exposure inhibited pyruvate dehydrogenase complex (PDHc) and the inhibition correlated with the loss of lipoic acid (LA) immunoreactivity, suggesting that modification of LA is a potential mechanism of inhibition. Treatment with antioxidants and thiol-containing compounds failed to protect against loss of LA. Alternatively, inhibition of dihydrolipoamide dehydrogenase, the E3 component of the complex attenuated loss of LA. Collectively, these data suggest that 1,3-DNB impairs oxidative energy metabolism through direct inhibition of the PDHc and that this impairment is due to perturbations in the function of protein-bound LA.

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 during parenteral feeding: not an unusual complication.

OBJECTIVE: Wernicke's encephalopathy (WE) is an acute disorder due to thiamine deficiency, characterized by ophthalmoplegia, ataxia, and mental confusion, similar to that classically observed in alcoholism. Some cases of WE were reported to coincide with other conditions such as hyperemesis gravidarum, bariatric surgery, and total parenteral nutrition. In this study the objective was to retrospectively evaluate the prevalence of WE among intravenously fed patients in our hospital during the previous 2 y. METHODS: Among all cases of WE diagnosed by cranial magnetic resonance scan during a 2-y period in the Azienda Ospedaliera of Padua, we identified patients who exhibited WE during parenteral feeding. Albumin plasma levels, measured at the onset of WE symptoms, were used to estimate nutritional status. RESULTS: We found seven cases of WE that coincided with intravenous feeding. WE occurred, on average, 13 d after the start of glucose infusion. The five subjects with albumin plasma levels lower than 35 g/L at the onset of WE received glucose infusion for fewer days. In six cases the clinical signs disappeared the day after thiamine infusion. In one case mental function did not normalize and the patient developed Korsakoff's syndrome despite prolonged thiamine treatment. CONCLUSION: During a 2-y period we observed a high prevalence of WE in intravenously fed patients due to lack of thiamine supplementation. A prophylactic treatment must be performed in at-risk patients and multivitamin infusion containing thiamine must be administered daily during the course of intravenous feeding.

Influência da terapia com diuréticos nos níveis séricos de tiamina em pacientes com insuficiência cardíaca / Influence of diuretic therapy on thiamin blood levels in patients with heart failure

Fundamento - A importância de micronutrientes como tiamina há muito é conhecida, visto que sua deficiência associa-se com insuficiência cardíaca (IC) de alto débito. Vários trabalhos mostram a influência dos diuréticos nos níveis de tiamina. Objetivos - Avaliar se o uso de furosemida isolada ou associada a espironolactona (espiro) determina níveis de tiamina diferentes em pacientes (pc) com IC. Verificar se a tiamina é influenciada por fatores nutricionais, comorbidades e outros fármacos. Métodos - Estudo em duas etapas: Estudo 1 - análise transversal (uso prévio de furosemida isoladamente ou em associação com espiro) de 22 pc com IC (classes III/IV da NYHA) divididos em: grupo I - com epiro (n=11) e grupo II - sem espiro (n=11); Estudo 2 - ensaio clínico randomizado, aberto, com três grupos paralelos de 53 pc com IC divididos em grupo "sem diuréticos" (n=15), "com diurético" (n=15) (uso de furosemida até o dia 90 e depois associar espiro até o dia 180) e "com espiro" (n=23) (usar furosemida e espiro desde a visita inicial até o dia 180). Os pc realizaram três visitas: inicial, em 90 dias e 180 dias, sendo coletadas amostras de sangue para tiamina e outros exames, assim como análise clínica. Determinamos os níveis de tiamina por recombinação de apoenzima e por cromatografia líquida de alta performance. Utilizamos testes t de Student, qui-quadrado, Mann-Whitney, Kruskal-Wallis, Spearman e como a variância foi cerca de três vezes maior que a estimada, usamos a simulação robusta de Monte Carlo. Resultados: no estudo 1, os grupos I e II eram similares em relação à ingesta alimentar, doses diárias de furosemida (I=110,9 +- 30,2 vs II=105,5 +-26,9mg; p>0,05) e dados demográficos. Os pacientes do grupo I mostraram níveis maiores de tiamina (277,2+-89,8), comparados aos do grupo II (154,7+-35,7) (p<0,001). Nenhuma outra variável esteve associada com a tiamina. No estudo 2, os grupos também eram semelhantes quanto às características clínicas e laboratoriais...

Background: The importance of micronutrients such as thiamine known since its deficiency is associated with the development of high-output heart failure (HF). Several studies show the influence of diuretic therapy in thiamine blood levels. Objectives: assess whether the use of furosemide alone or in combination with spironolactone (spiro) can determine different thiamine blood levels in patients (pt) with HF. To determinat whether thiamine blood levels were influenced by nutritional factors, comorbidities and other drugs. Methods: Study 1 - cross-sectional analysis (previous use of furosemide alone or with spiro) of 22 HF pt (NYha class III/IV) divided in two groups: I - with spiro (n=11) and II - without spiro (n=11); Study 2 - randomized, open-label, with three parallel groups of 53 HF pt divided into group "without diuretics" (n=15), "with diuretic" (n=15) (use of furosemide until day 90 and then adding spiro from day 90 until day 180) and "with spiro" (n=23) (using furosemide and spiro through all study). Patients were scheduled to three visits: day 0, day 90 and day 180, and blood samples were collected for thiamine and other tests, as well as clinical analysis. Thiamine levels were determined using an apoenzyme recombination method and high-performance liquid chromatography. The tests used were t-Student, chi-square, Mann-Whitney, Kruskal-Wallis, Spearman correlation, and as the variance was about three times higher than estimated, we used a robust Monte Carlo simulation. Results: in study 1, group I and II were similar regarding food intake, daily furosemide doses (I=110.9+-30.2 vs II=105.5+-26.9 mg; p>0.05) and demographics. Pts in group I (277.2+-89.8) showed significantly higher thiamine levels when compared to pts in group II (154.7+-35.7) (p<0.001). No other variables were associated with thiamine. In study 2, the groups were also similar regarding clinical and laboratory assessments. We found no statistical differences in thiamin blood levels...

[Thiamine deficiency polyneuropathy after gastrectomy associated with high level of serum vascular endothelial growth factor (VEGF). A case report].

We report a 66-year-old man who developed vitamin B1 deficiency polyneuropathy long after a gastrectomy. After a preceding bronchial infection, the patient noticed numbness and weakness in his extremities, followed by generalized edema and exertional dyspnea. He had undergone subtotal gastrectomy due to duodenal ulcer at age 19. His daily oral intake of food was normal without any alcoholic abuse. He was admitted to our hospital with rapidly progressive gait disturbance due to muscle weakness, and sensory disturbance. Neurological examination showed peripheral polyneuropathy with distal dominant muscular weakness and sensory disturbance. Chest X-ray film showed marked cardiomegaly and pleural effusion. Nerve conduction studies showed decreases in the action potentials of both the motor and sensory nerves, with the sensory nerves being more severely affected than the motor nerves. Sural nerve biopsy demonstrated severe axonal degeneration without any inflammatory change. The blood concentration of thiamine (vitamin B1) was slightly decreased below the normal range (19 ng/ml; normal, 20-50), and the serum vascular endothelial growth factor (VEGF) was high (890 pg/ml; normal < 200 pg/ml). Intravenous administration of vitamin B1 (50 mg per day) dramatically improved his symptoms in a few days and the level of VEGF returned to nearly normal. In this gastrectomized patient many years ago, vitamin B1 deficiency neuropathy is warranted in view of a prompt response to thiamine administration. This case suggests that VEGF is involved in the pathogenesis of vitamin B1 deficiency polyneuropathy.

Postgastrectomy polyneuropathy with thiamine deficiency.

OBJECTIVE: Polyneuropathy has been reported after gastrectomy performed to treat various lesions. Although thiamine deficiency is a possible cause of this neuropathy, the pathogenesis still remains to be clarified. Seventeen patients with peripheral neuropathy with thiamine deficiency after gastrectomy are described. METHODS: Seventeen patients with polyneuropathy after gastrectomy accompanied by thiamine deficiency were selected. Patients were restricted to those with total or subtotal gastric resection to treat ulcer or neoplasm. Patients who had undergone operations to treat morbid obesity were excluded. RESULTS: Intervals between the operation and onset of neuropathy varied from 2 months to 39 years. Most patients did not seem malnourished. Serum concentrations of B vitamins other than thiamine were nearly normal. Symmetric motor-sensory polyneuropathy, predominantly involving the lower limbs, had progressed over intervals varying from 3 days to 8 years. Relative degrees of motor and sensory impairment also varied extensively. Some cases that progressed rapidly mimicked Guillain-Barré syndrome. Electrophysiological and pathological findings were those of axonal neuropathy. Substantial functional recovery from polyneuropathy was seen in most patients by 3 to 6 months after initiating thiamine supplementation. Motor recovery was better than sensory recovery. CONCLUSIONS: Various symptoms were seen in patients with postgastrectomy neuropathy. Thiamine deficiency should be considered in the differential diagnosis of motor-sensory polyneuropathy after gastrectomy.

[Severe lactic acidosis and thiamine deficiency during parenteral nutrition in a child]. / Acidose lactique sévère et déficit en thiamine au cours d'une nutrition parentérale chez un enfant.

We report the case of a leukemic child treated with chemotherapy and parenteral nutrition for three weeks, who developed a severe lactic acidosis. Clinical features included both digestive and neurological disorders associated with a moderate cardiovascular collapse. After elimination of a toxic, a neoplastic or a septic cause, a thiamin (or vitamin B1) deficiency was suspected because of the lack of vitamin supply to parenteral nutrition. Intravenous administration of thiamin rapidly controlled lactic and clinical features. The diagnosis was confirmed by a low plasmatic concentration of thiamin. Thiamin deficiency must be suspected in case of severe lactic acidosis during parenteral nutrition and systematically prevented by supply of vitamins.