In this episode of Hospital Medicine Unplugged, we discuss Wernicke–Korsakoff syndrome—spot it early, slam thiamine, stop the slide to irreversible amnesia. We open with the do-firsts: high clinical suspicion in anyone with alcohol use disorder, malnutrition, bariatric surgery, cancer, hyperemesis, or refeeding. Don’t chase labs; give thiamine now—before glucose—and correct magnesium to make the thiamine work. Clinical diagnosis that doesn’t miss: the classic triad (confusion, ophthalmoplegia, ataxia) is rare. Use Caine criteria (≥2/4: dietary deficiency, oculomotor signs, cerebellar dysfunction, altered mental state/memory). Do not delay for MRI or thiamine levels; imaging is supportive, not decisive. Pathophysiology in one breath: thiamine deficiency → mitochondrial failure → lactate build-up → selective injury (mammillary bodies, thalamus, periaqueductal gray). Alcohol compounds the damage by blocking absorption and utilization, so doses must be higher. Epidemiology & outcomes you’ll actually use: alcohol-related WE is common and progresses to KS more often, while non-alcohol cases are deadlier in-hospital. Most WKS is missed antemortem; once KS lands, profound anterograde/retrograde amnesia with confabulation is often permanent. Treatment—build the thiamine backbone fast:• Suspected WE: High-dose IV thiamine (e.g., 500 mg IV TID) for 2–3 days, then 250–500 mg IV daily for several days, followed by high-dose oral (e.g., 100–300 mg/day).• Magnesium repletion (target normal) to restore thiamine-dependent enzymes.• Nutrition + electrolytes (mind phosphate for refeeding).• Oral thiamine alone is inadequate in high-risk or symptomatic patients. If the backbone buckles:• Escalate/extend parenteral dosing if mental status, ocular signs, or gait don’t improve.• Manage agitation/delirium with low-dose agents; avoid sedating away the exam.• Consider MRI only when the diagnosis stays murky after treatment has started. Prevention plays that save neurons:• Prophylactic parenteral thiamine for all at-risk inpatients (AUD, malnutrition, ICU, post-bariatric, hyperemesis, prolonged NPO/TPN), especially before dextrose.• Order-set defaults: auto-add thiamine to alcohol withdrawal and refeeding pathways; bundle Mg and nutrition consults.• Nix low-value tests (routine serum thiamine) and educate teams that over-treating is safer than missing. KS reality check: once established, expect severe memory impairment and executive dysfunction; focus on rehab, safety, caregiver training, and secondary prevention (nutrition, AUD treatment) to reduce readmissions. We close with the system moves: a WKS bundle that (1) screens risk on admission; (2) fires immediate IV thiamine + Mg with nursing-driven protocols; (3) blocks glucose-first orders in high-risk patients; (4) standardizes dosing/taper with auto-stop reminders to avoid under- or over-treating; (5) tracks outcomes (time-to-thiamine, neuro recovery, readmission); (6) hard-wires prevention into alcohol withdrawal, oncology, ICU, and post-bariatric pathways. Fast, protocolized, and prevention-forward—treat first, test later. Thiamine saves brains; delay steals memories.