Wernicke Encephalopathy

Wernicke encephalopathy is an acute neurological emergency caused by inadequate thiamine, or vitamin B1. Thiamine is converted to thiamine pyrophosphate, a cofactor for enzymes in the Krebs cycle and pentose phosphate pathway. When thiamine is depleted, pyruvate cannot be used efficiently for aerobic energy production. Pyruvate and lactate accumulate, ATP production falls, oxidative injury increases, and vulnerable neurons develop blood–brain barrier disruption and excitotoxic damage. The injury is not distributed evenly. Brain regions with high metabolic demand and substantial thiamine turnover are affected first, particularly the mammillary bodies, medial thalami and periaqueductal grey matter. This distribution helps explain the combination of impaired attention or memory, abnormal eye movements and gait dysfunction. Alcohol use disorder is a common setting, but it is not a prerequisite. Alcohol can reduce intake, impair intestinal absorption and interfere with storage and activation of thiamine. Similar depletion can occur with prolonged vomiting, hyperemesis gravidarum, bariatric or metabolic surgery, malignancy and chemotherapy, dialysis, critical illness, starvation, severe malnutrition, or prolonged parenteral nutrition without adequate vitamin replacement.