A 62-year-old man is brought to the office by his son due to memory impairment and frequent falls. The patient has been living alone since the death of his wife a year ago. His son, who is visiting from out of town, found his father in poor living conditions. The patient was forgetful and did not know the location of various items in his house, where he has lived for more than 20 years. His gait is also unsteady, and he had had several falls. The son says his father has always been "a drinker" and may have been drinking more recently. The patient is indifferent to his son's concerns and says he feels fine. Vital signs are within normal limits. On physical examination, bilateral lateral gaze palsy and nystagmus are present. Muscle strength and deep tendon reflexes are normal, but the gait is ataxic. On memory testing, he recalls 0 out of 3 objects after 5 minutes. A lesion of which of the following labeled structures on a normal brain MRI is most specifically associated with this patient's current condition?
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This patient with a suspected history of alcohol use disorder has oculomotor dysfunction (nystagmus, ophthalmoplegia), ataxia, and encephalopathy (confusion, anterograde amnesia). This presentation is consistent with the classic triad of Wernicke encephalopathy (WE), a complication of thiamine (vitamin B1) deficiency. Thiamine is a cofactor for multiple enzymes involved in glucose metabolism; deficiency results in the brain's inability to use glucose and turn it into energy, leading to neuronal damage and necrosis. Areas of the brain with high metabolic demand are particularly susceptible; the mammillary bodies are nearly universally affected and demonstrate focal hemorrhage or atrophy on imaging. Other commonly involved areas include the thalamus, periaqueductal gray substance, and locus caeruleus.
Thiamine deficiency occurs most commonly in patients with alcohol use disorder but can also manifest with any form of malnutrition (eg, anorexia, advanced malignancy). Infusion of dextrose-containing solutions without concurrent thiamine supplementation acutely lowers thiamine levels and can precipitate WE; however, some patients with severe deficiency can develop symptoms without a clear inciting event. The chronic effects of thiamine deficiency lead to Korsakoff syndrome, which is characterized by anterograde and retrograde amnesia, apathy, lack of insight, and confabulation. Attention, social behavior, and long-term memory are relatively preserved.
(Choice A) Demyelination of the pons (central pontine myelinolysis) can occur with overly rapid correction of chronic hyponatremia. It can result in locked-in syndrome, in which patients can move their eyes but cannot move or verbally communicate. The pons is not typically involved in WE.
(Choice C) The fornix is a bundle of axons originating from the hippocampal subiculum that projects to the mammillary bodies. Although it can (rarely) be involved in WE, the mamillary bodies are more specifically associated.
(Choice D) The splenium of the corpus callosum is not typically affected in WE. Lesions (demyelinating or ischemic) in this structure will clinically result in alexia without agraphia.
(Choice E) The pineal gland synthesizes melatonin and is involved in circadian rhythm; it is not typically involved in WE.
(Choice F) Alcohol-associated cerebellar degeneration also causes ataxia but does not typically cause confusion or ophthalmoplegia. The cerebellum is less frequently involved in WE.
Educational objective:
Wernicke encephalopathy is a complication of thiamine deficiency and is characterized by oculomotor dysfunction, encephalopathy, and ataxia. Chronic deficiency results in Korsakoff syndrome (eg, anterograde and retrograde amnesia, confabulation, apathy). Thiamine is involved in glucose metabolism, and areas of the brain with high metabolic demands are particularly susceptible; the mammillary bodies are most commonly affected.