Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency

R. Mancinelli; M. Ceccanti

doi:10.1093/alcalc/agn117

Case Report: Intensive Inpatient Neurorehabilitation Achieves Sustained Real-World Benefits in Severe Alcohol-Related Wernicke-Korsakoff Syndrome: A Case Study With 7-Years Follow-Up

Frontiers in Psychology ◽

10.3389/fpsyg.2021.693920 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mareike Schrader ◽

Stephan Bamborschke ◽

Ute Lenk ◽

Annette Sterr

Keyword(s):

Thiamine Deficiency ◽

Alcohol Misuse ◽

Psychological Treatment ◽

Care Staff ◽

Inpatient Setting ◽

Neurocognitive Deficits ◽

Persistent Symptoms ◽

Korsakoff Syndrome

About 85% of survivors of acute Wernicke's Encephalopathy (WE), a frequent and serious consequence of thiamine deficiency and alcohol misuse, sustain chronic neurocognitive deficits also known as chronic Wernicke-Korsakoff syndrome (WKS). If alcoholism is combined with smoking, tobacco alcohol optic neuropathy (TAON) may occur which leads to visual impairment. In contrast to WKS, TAON may be treated successfully by early vitamin substitution and detoxification. Little research has been conducted on WKS longterm outcomes. Existing literature suggests poor prognosis. Symptoms remaining beyond the acute treatment with thiamine are thought to be irreversible. Whether neurorehabilitation may be an effective route to help recovery of those persistent symptoms is an open question. At our neurorehabilitation center, which specializes in the treatment of severe chronic deficits after brain injury, the opportunity arose to treat a 35 year old male with WKS, and to conduct follow-up assessments 3- and 7-years post discharge, respectively. Initially MK was admitted to emergency care with suspected postconcussive syndrome, alcohol-related thiamine deficiency, and TAON. Thiamin, cobalamin, and folate substituion improved TAON but major cognitive deficits remained. When admitted to our center 4 months later, he was fully reliant on care staff for all activities of daily living (ADL). Through intensive neurocognive training and psychological treatment he improved gradually and, after 26 months, was well enough to be discharged into the community and pursue work in a sheltered setting. Neuropsychological tests, as well as patient reports obtained at the follow-ups showed that the benefits apparent at discharge had been sustained, and for some scores, improved further. This was particularly evident in the Rey-Osterrieth Complex Figure Test which improved from percentage ranges <1 for immediate recognition and recall at discharge to rank 16 for immediate recognition and rank 5 for recall at the 7-year follow-up. This case study illustrates the immense benefits neurorehabilitation can have for WKS induced by alcohol misuse. It further demonstrates how skills and strategies, learned in the inpatient setting, translate into living well and independently, and how the latter promotes further improvement long after discharge.

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Alteration of Mitochondria in Oxythiamine-Induced, Acute Thiamine Deficiency in the Mouse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100091408 ◽

1976 ◽

Vol 34 ◽

pp. 284-285

Author(s):

Itaru Watanabe ◽

Dante G. Scarpelli

Keyword(s):

Electron Microscopy ◽

Adult Male ◽

Thiamine Deficiency ◽

Light And Electron Microscopy ◽

Fatty Change ◽

Deficient Diet ◽

Subcutaneous Injections ◽

Swiss Mice ◽

Time Period ◽

Ad Libitum

Acute thiamine deficiency was produced in mice by the administration of oxythiamine, a thiamine analogue, superimposed upon a thiamine deficient diet. Adult male Swiss mice (30 gm. B.W.) were fed with a thiamine deficient diet ad libitumand were injected with oxythiamine (170 mg/Kg B.W.) subcutaneously on days 4 and 10. On day 11, severe lassitude and anorexia developed, followed by death within 48 hours. The animals treated daily with subcutaneous injections of thiamine (300 μg/Kg B.W.) from day 11 through 15 were kept alive. Similarly, feeding with a diet containing thiamine (600 μg/Kg B.W./day) from day 9 through 17 reversed the condition. During this time period, no fatal illness occurred in the controls which were pair-fed with a thiamine deficient diet.The oxythiamine-treated mice showed a significant enlargement of the liver, which weighed approximately 1.5 times as much as that of the pair-fed controls. By light and electron microscopy, the hepatocytes were markedly swollen due to severe fatty change and swelling of the mitochondria.

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Serum Thiamine Values in End-Stage Renal Disease Patients under Maintenance Hemodialysis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000242 ◽

2015 ◽

Vol 85 (5-6) ◽

pp. 348-355 ◽

Cited By ~ 2

Author(s):

Masamitsu Ubukata ◽

Nobuyuki Amemiya ◽

Kosaku Nitta ◽

Takashi Takei

Keyword(s):

Thiamine Deficiency ◽

Risk Index ◽

Nutritional Risk ◽

Maintenance Hemodialysis ◽

Dialysis Patients ◽

Significant Difference ◽

Nutritional Risk Index ◽

Serum Aspartate Aminotransferase ◽

Stage Renal Disease ◽

End Stage

Abstract. Objective: Hemodialysis patients are prone to malnutrition because of diet or many uremic complications. The objective of this study is to determine whether thiamine deficiency is associated with regular dialysis patients. Methods: To determine whether thiamine deficiency is associated with regular dialysis patients, we measured thiamine in 100 patients undergoing consecutive dialysis. Results: Average thiamine levels were not low in both pre-hemodialysis (50.1 ± 75.9 ng/mL; normal range 24 - 66 ng/mL) and post-hemodialysis (56.4 ± 61.7 ng/mL). In 18 patients, post-hemodialysis levels of thiamine were lower than pre-hemodialysis levels. We divided the patients into two groups, the decrease (Δthiamine/pre thiamine < 0; - 0.13 ± 0.11) group (n = 18) and the increase (Δthiamine/pre thiamine> 0; 0.32 ± 0.21)) group (n = 82). However, there was no significance between the two groups in Kt/V or type of dialyzer. Patients were dichotomized according to median serum thiamine level in pre-hemodialysis into a high-thiamine group (≥ 35.5 ng/mL) and a low-thiamine group (< 35.4 ng/mL), and clinical characteristics were compared between the two groups. The low-thiamine value group (< 35.4 ng/ml; 26.8 ± 5.3 ng/ml) exhibited lower levels of serum aspartate aminotransferase and alanine aminotransferase than the high-thiamine value group (≥ 35.4 ng/ml; 73.5 ± 102.5 ng/ml) although there was no significance in nutritional marker, Alb, geriatric nutritional risk index , protein catabolic rate and creatinine generation rate. Conclusion: In our regular dialysis patients, excluding a few patients, we did not recognize thiamine deficiency and no significant difference in thiamine value between pre and post hemodialysis.

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HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000159 ◽

2013 ◽

Vol 83 (3) ◽

pp. 188-197 ◽

Cited By ~ 21

Author(s):

Rebecca L. Sweet ◽

Jason A. Zastre

Keyword(s):

Gene Expression ◽

Thiamine Deficiency ◽

Glucose Transporter ◽

Neuroblastoma Cell ◽

Hypoxia Inducible Factor ◽

Clinical Manifestations ◽

Vitamin B1 ◽

Low Oxygen ◽

Glucose Transporter 1 ◽

Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

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