An 18-year-old woman is brought to the emergency department by her parents for altered mental status that began today. Two months ago, the patient began restricting her dietary intake due to fear of being overweight. Since then, she has experienced notable weight loss and has felt weaker overall. The patient's parents have been encouraging her to eat, and today, she agreed to eat watermelon and pineapple for breakfast. Afterward, she fell while walking and appeared very somnolent. The patient is otherwise healthy with no chronic medical conditions and takes no medications. BMI is 16 kg/m2, decreased from 18.5 kg/m2 a few months ago. The patient is oriented to name only and has a poor attention span. Pupils are equal and reactive, but she has nystagmus and lateral gaze palsy. Strength and sensations are equal in the bilateral extremities. The patient walks in short steps and has difficulty maintaining her balance. Abdominal and skin examinations are unremarkable. Head imaging reveals no hemorrhage. This patient's clinical findings are most likely due to which of the following?
Wernicke encephalopathy | |
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This patient has anorexia (eg, restricted diet, BMI of 16 kg/m2) and acutely developed encephalopathy, ataxia, and oculomotor dysfunction after ingesting glucose, findings suspicious for Wernicke encephalopathy (WE). WE is a complication of thiamine (vitamin B1) deficiency and most commonly occurs in patients with chronic malnutrition (eg, chronic alcohol use, anorexia).
Thiamine is a cofactor for several enzymes involved in glucose metabolism, and deficiency results in decreased glucose use and impaired ATP production. In patients with low glucose intake, thiamine deficiency may be asymptomatic. However, this patient ingested a large quantity of glucose, which likely rapidly depleted her limited thiamine stores.
Without thiamine, cerebral energy production is impaired, increasing neuronal susceptibility to oxidative stress and causing disruption of the tight junctions that form the blood-brain barrier. The resulting neuronal injury primarily affects areas of the brain with the highest metabolic demand and leads to the classic triad of WE:
(Choice A) Anorexia increases the risk for deficiency of fat-soluble vitamins, such as vitamin E, an antioxidant that protects the cerebellum from reactive oxygen species. Deficiency may result in ataxia, but encephalopathy and oculomotor dysfunction would not be expected.
(Choice B) Encephalopathy is common in patients with impaired hepatic clearance of ammonia; ataxia and nystagmus can also occur. However, symptoms are usually insidious, not acute, in onset, and jaundice and asterixis would be expected.
(Choice D) Vitamin K is synthesized by gut microflora and is a cofactor for carboxylase enzymes involved in coagulation factor synthesis. Patients with vitamin K deficiency are at increased risk for bleeding, such as a hemorrhagic stroke causing focal neurologic findings and/or altered mental status. However, this patient's lack of hemorrhage on imaging is inconsistent with this diagnosis.
(Choice E) Clostridium botulinum is a spore-forming bacterium that produces a neurotoxin upon germinating which can cause cranial nerve motor dysfunction (eg, lateral gaze palsy) and descending muscle weakness. However, this patient has normal extremity strength, and spore ingestion is mostly associated with infant botulism.
Educational objective:
Thiamine is a cofactor for several enzymes involved in glucose metabolism. A complication of thiamine deficiency is Wernicke encephalopathy (encephalopathy, ataxia, oculomotor dysfunction), which can be precipitated by a high glucose load causing rapid depletion of limited thiamine stores.