A Veteran With Lesions, Alcohol Use, and Opioid Dependence

R. Hal Scofield, MD


October 27, 2021

Thiamine is required for energy production in both the Krebs cycle and the pentose phosphate shunt pathway (Figure 3).

Figure 3.CoA = coenzyme A; NADPH = nicotinamide adenine dinucleotide phosphate

Because thiamine (vitamin B1) is water-soluble and not stored, signs and symptoms of beriberi occur within about 10 days of eating a diet devoid of thiamine. Acute neurologic beriberi is referred to as Wernicke encephalopathy (WE). Karl Wernicke described the triad of confusion, ataxia, and ophthalmoplegia in 1881, and Sergei Korsakoff described similar patients in papers published from 1887 to1891.[1] The association with and causation by thiamine deficiency were convincingly demonstrated in the 1930s.

Perhaps only 10% of patients with WE have all three signs and symptoms as originally described. This patient had no confusion or nystagmus, for example. In fact, many other signs and symptoms have been described, including hyperhidrosis, hearing loss, retinal hemorrhage with papilledema, and vision loss.[2] Patients may present with only vague symptoms, such as fatigue, irritability, drowsiness, and memory loss.[2,3] Autonomic dysregulation may be present, with hypothermia, tachycardia, and orthostatic hypotension. Wet beriberi, manifested by heart failure, can accompany WE.

Alcoholism with poor nutritional intake is a common scenario for WE, but the disease can occur in many other settings. Associated conditions include thyrotoxicosis, inflammatory bowel disease, hyperemesis gravidarum, post bariatric surgery, renal dialysis, eating disorders, and pancreatitis. Thiamine deficiency and WE should be considered in all patients with poor nutritional status and any sign or symptom compatible with the disease. In fact, WE is probably underdiagnosed, most likely because of its varied presentation. Autopsy studies estimate that less than 20% of patients receive a diagnosis during life.[4]

Although no genetic abnormality of thiamine-requiring enzymes has been found to predispose to WE,[5] mutations in thiamine transporter genes are associated with a WE-like illness.[6] In addition, the apolipoprotein E epsilon 4 allele, which is associated with Alzheimer's disease, may also predispose to worse outcomes in WE.[7] However, no definite genetic predisposition to the disease is recognized, except in extremely rare instances.

MRI occasionally reveals characteristic bilaterally symmetric brain lesions of the mammary bodies, cranial nerve nuclei, and gray matter, but the sensitivity of such findings is too poor to be relied upon for diagnostic purposes.[8,9,10] Thus, the diagnosis of WE is clinical. Measurement of erythrocyte transketolase activity is confirmatory in most cases; however, because the results are not rapidly available, the diagnosis must be made and treatment initiated on a clinical basis. Furthermore, normal levels do not exclude WE. Rapid clinical improvement, as observed in this patient, supports the diagnosis.[11]

The treatment of WE is straightforward: namely, parenteral administration of thiamine. The response to therapy is usually prompt and, for most patients, complete. Furthermore, the risk for adverse reactions is extremely low.[12] Therefore, many physicians recommend parenteral thiamine for any patient admitted to the hospital with nutritional compromise. Because thiamine is required for the metabolism of glucose, administration of intravenous glucose without thiamine may worsen or trigger WE.[13] Thus, administration of intravenous glucose should be accompanied by thiamine in any patients with compromised nutrition. Overdiagnosis and overtreatment are preferable to the consequences of underdiagnosis of this treatable condition,[14] although no clinical trial or evidence-based medicine supports this assertion.[15]

Patients who have one vitamin deficiency are likely to have others. Concomitant deficiencies of multiple vitamins and/or trace elements are common among patients with malnutrition from either malabsorption or poor intake. The combination of scurvy and beriberi, as in this patient, may be underrecognized and underdiagnosed.[16,17,18]


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