A 61-year-old man is brought to the emergency department after being found unresponsive on a sidewalk. Paramedics notice that the patient's breath smells of alcohol and that he has vomitus in his mouth. The patient also has agonal respirations, and cardiac monitoring shows pulseless electrical activity. Resuscitation efforts are unsuccessful, and he is pronounced dead on arrival. Autopsy reveals that the cause of death is airway occlusion by aspirated vomitus. In addition, foci of hemorrhage and necrosis are seen in the mammillary bodies and gray matter surrounding the third and fourth ventricles. This patient's brain findings are most likely associated with a decrease in which of the following?

Question

A 61-year-old man is brought to the emergency department after being found unresponsive on a sidewalk.  Paramedics notice that the patient's breath smells of alcohol and that he has vomitus in his mouth.  The patient also has agonal respirations, and cardiac monitoring shows pulseless electrical activity.  Resuscitation efforts are unsuccessful, and he is pronounced dead on arrival.  Autopsy reveals that the cause of death is airway occlusion by aspirated vomitus.  In addition, foci of hemorrhage and necrosis are seen in the mammillary bodies and gray matter surrounding the third and fourth ventricles.  This patient's brain findings are most likely associated with a decrease in which of the following?

Quizplus · Accepted Answer

Wernicke encephalopathy classically presents with the triad of ophthalmoplegia, ataxia, and confusion, and can lead to coma and death if left untreated. Foci of hemorrhage and necrosis in the mammillary bodies and periaqueductal gray matter are typically found on autopsy. This condition occurs due to chronic thiamine deficiency, which is common in patients with alcohol use disorder. Thiamine (vitamin B₁) participates in glucose metabolism and is a cofactor for the following enzymes: Thiamine deficiency, therefore, results in decreased glucose utilization, which is especially pronounced in the central nervous system. If a patient with chronic thiamine deficiency is given a glucose infusion without thiamine supplementation, acute cerebral damage may occur. Thiamine deficiency can be diagnosed if baseline erythrocyte transketolase activity is low but increases after addition of thiamine pyrophosphate. In actual practice, if heavy alcohol use or malnutrition is suspected, thiamine deficiency should be presumed and thiamine supplementation with glucose infusion should be administered. (Choice A) Protoporphyrin is a precursor of heme. Increased erythrocyte protoporphyrin concentration is the hallmark of erythropoietic protoporphyria; however, this elevation is nonspecific and can be seen in other conditions (eg, iron deficiency anemia, lead poisoning). (Choice B) Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-limiting step in the pentose phosphate pathway, which is necessary for production of NADPH and proper functioning of the erythrocyte antioxidant system. Decreased G6PD levels cause hemolytic anemia. (Choices C and F) NADH and NADPH are both derived from niacin (vitamin B₃). NADPH is a cofactor for glutathione reductase, an enzyme that helps metabolize harmful reactive oxygen species. Neither NADPH nor erythrocyte glutathione reductase is used for diagnosing thiamine deficiency. (Choice E) Methylmalonic acid, a product of fatty acid oxidation, is converted to succinyl-CoA by the enzyme methylmalonyl-CoA mutase (uses vitamin B₁₂ as a cofactor). Consequently, methylmalonic acid levels are increased in vitamin B₁₂ deficiency. Educational objective: Chronic thiamine (vitamin B₁) deficiency impairs glucose utilization in the central nervous system. This occurs due to decreased activity of the enzymes that use thiamine as a cofactor (eg, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, transketolase). Thiamine deficiency can be diagnosed if baseline erythrocyte transketolase activity is low but increases after addition of thiamine pyrophosphate. __________ References: Thiamine deficiency and delirium. (http://www.ncbi.nlm.nih.gov/pubmed/23696956)

A 61-Year-Old Man Is Brought to the Emergency Department After