Behavioral Health

Wernicke encephalopathy and Korsakoff syndrome

Clinical Overview and When to Suspect Wernicke Encephalopathy

— Chronic alcohol use disorder (AUD) and altered mental status

— Hyperemesis gravidarum with confusion

— Post-bariatric surgery patient with neurologic decline

— Prolonged TPN without thiamine

— Anorexia nervosa, malabsorption (celiac, IBD), advanced malignancy, dialysis

— Refeeding syndrome

— Encephalopathy (confusion, inattention)

— Oculomotor dysfunction (nystagmus, lateral rectus palsy, conjugate gaze palsy)

— Gait ataxia (wide-based, truncal)

Board pearl: Never give IV dextrose to a malnourished or alcohol-dependent patient before thiamine — glucose loading consumes residual thiamine stores and can precipitate or worsen WE within hours. Always thiamine first, then glucose.

Step 3 management: In the ED or on CCS, the moment you see "chronic alcohol use + confusion," your first orders are: fingerstick glucose, IV thiamine 500 mg, then dextrose if hypoglycemic, plus magnesium repletion (thiamine is ineffective in hypomagnesemia).

Wernicke encephalopathy (WE) is an acute, reversible neurologic emergency caused by thiamine (vitamin B1) deficiency, while Korsakoff syndrome (KS) is the chronic, often irreversible amnestic sequela.

Together they form the Wernicke-Korsakoff spectrum, a single disease process on a temporal continuum.

Suspect WE in any patient with:

Classic triad (only ~10–16% of patients have all three):

Because the triad is rare, the Caine criteria (≥2 of: dietary deficiency, oculomotor signs, cerebellar dysfunction, altered mental status/memory) are used clinically — far more sensitive.

Pathophysiology: thiamine is a cofactor for transketolase, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase. Deficiency → impaired glucose metabolism → neuronal injury in mammillary bodies, periaqueductal gray, medial thalamus, and cerebellar vermis.

Untreated WE → death in ~20% or progression to KS in ~80% of survivors.

Presentation Patterns and Key History

— Global confusion, apathy, inattention, disorientation

— Diplopia, blurred vision, "the room is spinning"

— Unsteady gait, falls, inability to stand without support

— Anorexia, nausea, vomiting (often precedes neuro symptoms)

— Profound anterograde amnesia (cannot form new memories)

— Retrograde amnesia with temporal gradient (remote memories preserved)

— Confabulation — fabricated, often plausible narratives filling memory gaps (not lying — patient believes them)

— Preserved immediate recall and procedural memory

— Apathy, lack of insight, executive dysfunction

— Quantify alcohol: drinks/day, last drink, prior withdrawal/DTs, prior detox

— Diet history: skipped meals, "drinks his calories," recent weight loss

— Bariatric surgery type and date (Roux-en-Y > sleeve risk)

— Hyperemesis gravidarum >3 weeks without prenatal vitamins

— Recent prolonged NPO, ICU stay, TPN without multivitamins

— Chemotherapy, GI malignancy, refractory vomiting

— Medication review: furosemide (urinary thiamine loss), metformin (B12 but relevant for confound)

Key distinction: Confabulation in KS is not delirium and not psychosis — patients are alert, conversant, and not hallucinating. They confidently produce false memories without intent to deceive. Compare to delirium tremens (autonomic hyperactivity, hallucinations, tremor, 48–96 h after last drink) which can coexist but is mechanistically distinct.

Board pearl: A non-alcoholic pregnant woman with hyperemesis presenting with diplopia and ataxia is a classic Step 3 WE stem — do not anchor on "alcoholic only."

Acute Wernicke presentation — subacute over days:

Korsakoff presentation — emerges as WE resolves:

High-yield history clues:

Collateral history is essential — patients often minimize or cannot recall. Call family, prior providers, pharmacy.

Timeline matters: WE evolving over hours-days is the treatable window. Once dense amnesia and confabulation lock in, recovery of memory is limited.

Physical Exam Findings

— Horizontal nystagmus — most common, often gaze-evoked

— Vertical nystagmus (less common, more specific)

— Bilateral lateral rectus (CN VI) palsy → esotropia, diplopia on lateral gaze

— Conjugate gaze palsy, sluggish pupillary light reflex

— Rarely complete ophthalmoplegia; ptosis is uncommon

— Wide-based, truncal ataxia — patient cannot tandem walk or stand with feet together

— Lower extremity ataxia > upper (mammillary body and vermis predominate)

— Romberg often positive

— Dysmetria less prominent than gait disturbance

— Global confusion, inattention, drowsiness

— Disorientation to time/place

— Frank coma in 5–10% (poor prognosis)

— Hypothermia (hypothalamic involvement)

— Hypotension, tachycardia

— Signs of malnutrition: temporal wasting, cheilosis, glossitis, bitot spots

— Stigmata of chronic alcohol use: spider angiomata, palmar erythema, caput medusae, gynecomastia, parotid enlargement, Dupuytren contracture

Hemodynamic assessment: Severe thiamine deficiency can also cause wet beriberi — high-output heart failure with peripheral edema, tachycardia, warm extremities, elevated JVP. Always auscultate heart and check for edema; a WE patient with new HF needs IV thiamine urgently, not standard diuresis alone.

CCS pearl: Document ocular motility, gait (have them walk), and orientation on every encounter — these are the parameters that change with treatment response within 24–72 hours of thiamine.

Ocular findings (most sensitive early sign):

Cerebellar/gait findings:

Mental status:

Autonomic/systemic:

Peripheral neuropathy — stocking-glove sensory loss, absent ankle reflexes (coexistent thiamine and other B-vitamin deficiency)

In Korsakoff: exam is often surprisingly non-focal — alert, conversant, oriented to self, but unable to retain new information for >1 minute. Test 3-word recall at 5 minutes — fails completely.

Diagnostic Workup — Initial Labs and Imaging

— Fingerstick glucose immediately (hypoglycemia mimics and coexists)

— Vital signs, temperature, pulse oximetry

— ECG — look for arrhythmia from electrolyte derangement, prolonged QT, signs of wet beriberi

— CBC — macrocytosis (alcohol, folate, B12)

— CMP — hyponatremia (risk for osmotic demyelination if overcorrected), transaminitis, AST:ALT >2 in alcoholic liver disease

— Magnesium, phosphorus, potassium — all commonly low; hypomagnesemia blunts thiamine response, must replete

— Ammonia if hepatic encephalopathy on differential

— Lactate (often elevated in thiamine deficiency due to pyruvate accumulation)

— Lipase, INR/PT, albumin

— Ethanol level, urine drug screen, acetaminophen and salicylate levels

— TSH, B12, folate (overlap deficiencies)

— HIV, RPR if mental status change unexplained

— Blood and urine cultures if febrile

— Pregnancy test in any reproductive-age female

Board pearl: An elevated lactate without sepsis or hypoperfusion in a malnourished or alcoholic patient with AMS strongly suggests thiamine deficiency — pyruvate cannot enter the TCA cycle without thiamine-dependent pyruvate dehydrogenase, so it shunts to lactate.

Step 3 management: Order the workup but administer thiamine 500 mg IV q8h within minutes of suspicion, before any results return. Treatment is both diagnostic and therapeutic — clinical improvement in 24–72 hours supports the diagnosis.

WE is a clinical diagnosis — do not delay thiamine for testing. Labs and imaging support, exclude mimics, and identify complications.

Initial bedside:

Initial labs:

Thiamine level — can be sent (whole-blood thiamine or erythrocyte transketolase activity) but results return too late to guide acute therapy. Do not wait.

CT head — obtain to exclude hemorrhage, subdural (alcoholics fall), stroke; usually normal in WE.

Chest X-ray if aspiration risk or hypoxia.

Diagnostic Workup — Advanced and Confirmatory Studies

— T2/FLAIR hyperintensities symmetrically in:

— Mammillary bodies (most characteristic)

— Medial thalami (especially dorsomedial nuclei)

— Periaqueductal gray matter

— Tectal plate, floor of fourth ventricle

— Contrast enhancement of mammillary bodies is highly specific (~90%) but only ~50% sensitive

— DWI may show restricted diffusion acutely

— Chronic phase: mammillary body atrophy — pathognomonic for prior WE/KS

— Severe anterograde amnesia with preserved IQ

— Executive dysfunction

— Confabulation patterns

— Used for capacity, disability, and rehabilitation planning

Key distinction: MRI findings of bilateral symmetric medial thalamic lesions also occur in artery of Percheron infarct, top-of-the-basilar syndrome, deep cerebral vein thrombosis, and CJD — clinical context and additional mammillary body involvement favor WE.

Board pearl: On Step 3, an MRI showing enhancing mammillary bodies in an alcoholic with confusion is essentially diagnostic — but never wait for MRI to start thiamine.

MRI brain with contrast — imaging modality of choice when diagnosis is uncertain or to document baseline:

MRI sensitivity ~53%, specificity ~93% — a negative MRI does NOT rule out WE.

Erythrocyte transketolase activity — measured before and after thiamine pyrophosphate addition; >25% activation indicates deficiency. Confirmatory but rarely used in real time.

Whole-blood thiamine (HPLC) — more available, useful for retrospective confirmation.

EEG — diffuse slowing, nonspecific; helpful if non-convulsive status epilepticus is on the differential.

Lumbar puncture — consider if meningoencephalitis cannot be excluded; CSF usually normal or mildly elevated protein in WE.

Neuropsychological testing — for established KS, formal testing documents:

Cardiac workup if wet beriberi suspected: echocardiogram (high cardiac output, biventricular dysfunction), BNP, troponin.

Risk Stratification and First-Line Management Logic

1. IV thiamine BEFORE glucose in any at-risk altered patient

2. Repeat thiamine dosing on a fixed schedule (not PRN)

3. Replete magnesium, phosphate, potassium concurrently

4. Monitor for refeeding syndrome if reintroducing nutrition

5. Manage concurrent alcohol withdrawal (CIWA-driven benzodiazepines)

6. Address underlying cause (AUD treatment, hyperemesis control, bariatric follow-up)

— Established WE (Caine criteria ≥2): high-dose IV thiamine 500 mg IV over 30 min, three times daily × 2–3 days, then 250 mg IV/IM daily × 5 days, then oral 100 mg daily indefinitely

— At-risk prophylaxis (alcoholic without overt WE, hyperemesis, pre-bariatric, refeeding): thiamine 200–500 mg IV/IM daily × 3–5 days, then oral 100 mg daily

— Outpatient AUD without acute symptoms: oral thiamine 100 mg daily (poorly absorbed — only ~10–15% bioavailability, but reasonable for prevention)

— Confused, ataxic, oculomotor signs → admit, often to step-down or ICU if airway/withdrawal risk

— Stable at-risk patient receiving prophylaxis → can be managed on the medical floor

— Wet beriberi or hemodynamic instability → ICU

CCS pearl: Order set for any suspected WE on CCS: thiamine IV 500 mg q8h, magnesium sulfate 2 g IV, folate 1 mg IV/PO, multivitamin, CIWA protocol, lorazepam PRN, NPO until safe swallow, neurology consult, MRI brain. Advance the clock 4 hours and reassess mental status, ocular exam, gait.

Board pearl: The Royal College of Physicians and most US references endorse 500 mg IV TID × 2–3 days for established WE — anything less is undertreatment and a common exam distractor.

Every patient with suspected WE is high-risk — there is no "low-acuity" pathway. The decision is not whether to treat but how aggressively.

Universal first-line approach:

Stratify by severity:

Why high IV doses? Oral absorption is saturable (~5 mg/day max); active transport is impaired in alcoholics. IV bypasses gut limitations and achieves CNS penetration.

Disposition logic:

Pharmacotherapy — First-Line Drug Regimen

— 500 mg IV in 100 mL NS over 30 minutes, every 8 hours × 2–3 days

— Then 250 mg IV or IM daily × 5 days or until clinical improvement plateaus

— Then 100 mg PO daily indefinitely (or as long as risk persists)

— 200–300 mg IV/IM daily × 3–5 days, then oral 100 mg daily

— IV preferred for established WE (rapid CNS delivery)

— IM acceptable if no IV access (painful, slower)

— Oral inadequate for acute treatment due to saturable absorption

— Anaphylaxis is extremely rare (~1 per million doses) — historical concern is overstated; do not withhold thiamine over this risk

— Local injection site reactions

— Magnesium sulfate 2–4 g IV — thiamine pyrophosphate requires Mg²⁺ as cofactor

— Phosphate (refeeding risk)

— Potassium

— Folate 1 mg PO/IV daily — alcoholics are commonly deficient, macrocytic anemia

— B12 if deficient (check level, treat with cyanocobalamin)

— Multivitamin daily

— If hypoglycemic, give D50 after initial thiamine dose started, or simultaneously — do not delay glucose for severe hypoglycemia, but ensure thiamine is going in

— Lorazepam or diazepam per CIWA-Ar (lorazepam preferred in liver disease)

— Avoid antipsychotics as monotherapy for withdrawal (lower seizure threshold)

— Glucose-containing fluids without preceding thiamine

— High-carbohydrate enteral feeds without thiamine + electrolyte repletion (refeeding precipitates WE)

Step 3 management: A common exam pitfall — patient hypoglycemic and altered, alcoholic. Correct order: thiamine 500 mg IV push/infusion, then D50, then magnesium. Choosing "D50 alone" or "D50 first" is wrong.

Board pearl: There is no role for vitamin K, niacin, or pyridoxine as primary therapy for WE — distractor answers.

Thiamine (vitamin B1) is the cornerstone — no substitute exists.

Dosing protocol (established WE):

Dosing protocol (prophylaxis in at-risk inpatient):

Route choice:

Adverse effects:

Adjunctive electrolyte repletion (essential):

Other B vitamins:

Glucose administration:

Concurrent alcohol withdrawal:

Avoid:

Expanded Pharmacology and Treatment of Korsakoff Syndrome

— Memantine — small studies suggest mild benefit in memory; not standard of care

— Donepezil/rivastigmine — cholinesterase inhibitors; inconsistent results

— SSRIs — for comorbid depression/apathy, may improve functional engagement

— Antipsychotics — only for agitation; avoid haloperidol/risperidone chronically (extrapyramidal, fall risk); use lowest dose, shortest duration

— Naltrexone (oral 50 mg daily or IM 380 mg monthly) — first-line if no opioid use, no severe hepatic impairment

— Acamprosate 666 mg TID — preferred in hepatic disease; renally dosed

— Disulfiram — only for highly motivated patients with supervision; aversive

— Gabapentin, topiramate — off-label, useful adjuncts

— Motivational interviewing, CBT, 12-step facilitation

— Contingency management

— Dietitian consult, structured meals

— Address food insecurity, social determinants

— Start nutrition at 50% of caloric needs, advance slowly over 5–7 days

— Daily phosphate, magnesium, potassium for first week

— Thiamine 200–300 mg daily before and during refeeding

Key distinction: Naltrexone vs acamprosate — naltrexone reduces craving and heavy drinking (best evidence), acamprosate supports abstinence in those already sober. Both are first-line; choose based on hepatic/renal function and patient preference.

Board pearl: Once dense Korsakoff amnesia is established, only ~20% recover substantially, ~25% have no recovery, the rest partial — emphasize prevention and early aggressive thiamine in any at-risk patient.

For established Korsakoff syndrome, no pharmacotherapy reliably restores memory. Management is supportive and rehabilitative.

Continue thiamine — 100 mg PO daily indefinitely; some authorities advocate periodic IM dosing if ongoing AUD/malabsorption.

Trialed but unproven agents (low-yield for exams but worth knowing):

Treat underlying AUD (the modifiable factor):

Behavioral interventions:

Nutritional rehabilitation:

Refeeding syndrome prophylaxis:

Manage comorbidities: hepatitis C screening, cirrhosis surveillance, osteoporosis, depression, PTSD, tobacco use.

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline risk: polypharmacy (loop diuretics increase urinary thiamine loss), reduced intake, malabsorption, dementia masking presentation

— WE is widely underdiagnosed in elderly — often misattributed to dementia, delirium, or stroke

— Threshold to give empiric thiamine should be very low in any elderly patient with unexplained delirium, gait disturbance, or failure to thrive

— Dose adjustment: standard thiamine dosing is safe; no reduction needed

— Watch for: falls, aspiration, pressure injuries, deconditioning

— Furosemide accelerates urinary thiamine excretion — chronic use → subclinical deficiency

— Consider thiamine 100 mg daily in chronic loop diuretic users with HF and unexplained worsening

— Alcoholic liver disease is the typical context — coexisting cirrhosis, hepatic encephalopathy

— Differentiate WE from hepatic encephalopathy: HE has asterixis, elevated ammonia, response to lactulose/rifaximin; WE has ocular signs and ataxia

— Both can coexist — treat both

— Thiamine has no hepatic dose adjustment

— Use lorazepam (not diazepam/chlordiazepoxide) for withdrawal in cirrhosis — shorter half-life, no active metabolites

— Dialysis patients lose water-soluble vitamins including thiamine — routine thiamine supplementation is standard

— Acute WE has been reported after intensive dialysis without supplementation

— Standard thiamine dosing applies; no renal adjustment

— Assess decision-making capacity before discharge planning

— Falls risk assessment, PT/OT consultation

Step 3 management: Elderly cirrhotic on furosemide presents with confusion. Check ammonia AND give empiric thiamine. Order lactulose if HE suspected. Don't anchor — dual diagnosis is common.

Board pearl: A dialysis patient with new ataxia and confusion after intensified ultrafiltration → think dialysis-associated thiamine deficiency and treat with IV thiamine immediately.

Elderly patients:

Loop diuretic users (CHF, cirrhosis):

Hepatic impairment:

Renal impairment / dialysis:

Frailty and capacity:

Special Populations — Pregnancy, Bariatric, and Pediatrics

— Persistent vomiting >3 weeks depletes thiamine stores

— WE has been reported as early as 14–15 weeks gestation

— Always give IV/IM thiamine 100–500 mg BEFORE IV dextrose in any HG patient requiring rehydration

— Add thiamine to all maintenance IV fluids in HG admissions

— Antiemetic ladder: pyridoxine + doxylamine → metoclopramide/ondansetron → corticosteroids (third trimester only)

— Untreated WE in pregnancy: high rates of fetal loss (~50%), maternal disability

— Highest risk: Roux-en-Y gastric bypass > sleeve gastrectomy > adjustable band

— Risk peaks 4–12 weeks post-op, often after persistent vomiting

— Symptoms may be vague: paresthesias, leg weakness, vision changes, confusion

— All bariatric patients require lifelong multivitamin including thiamine; routine post-op B1, B12, iron, calcium, vitamin D monitoring

— Treat suspected post-bariatric WE with IV thiamine 500 mg TID immediately

— Rare but described in:

— Infants of mothers with poor nutrition

— Children on total parenteral nutrition without thiamine (TPN compounding errors — sentinel event)

— Anorexia nervosa adolescents

— Children with malignancy on chemotherapy with prolonged vomiting

— Maple syrup urine disease, congenital lactic acidosis

— Presentation: nystagmus, vomiting, ophthalmoplegia, lethargy, seizures

— Dose: thiamine 10–25 mg IV/IM in infants; 100–500 mg in older children

— Always pre-treat with thiamine 200–300 mg before refeeding

— Start at 50% calories, advance over a week

— Monitor phosphate, magnesium, potassium daily × 5–7 days

Board pearl: A pregnant woman with hyperemesis given IV D5NS without thiamine who develops confusion and nystagmus is a classic Step 3 stem — the error is omission of thiamine, a preventable adverse event.

Step 3 management: All HG admissions: thiamine 100 mg IV daily added to maintenance fluids, even if asymptomatic. Document it.

Hyperemesis gravidarum (HG):

Post-bariatric surgery patients:

Pediatrics:

Anorexia nervosa / refeeding:

Complications and Adverse Outcomes

— Untreated WE: 17–20% mortality acutely

— Even with treatment: ~10% mortality, often from comorbidities (sepsis, aspiration, withdrawal, hepatic failure)

— ~80% of WE survivors develop persistent KS if treatment is delayed or inadequate

— Only ~20% achieve full recovery of memory

— ~25% have no recovery; remainder partial

— Persistent ataxia (cerebellar vermis atrophy) — falls, disability

— Chronic ophthalmoplegia (rare with treatment)

— Peripheral neuropathy (often coexists, persists)

— Mammillary body atrophy on imaging — pathognomonic chronic finding

— High-output heart failure: tachycardia, peripheral vasodilation, edema, pulmonary congestion

— Shoshin beriberi — fulminant cardiac collapse with lactic acidosis, can be fatal within hours

— Responds dramatically to IV thiamine — sometimes within minutes

— Seizures (typically 12–48 h after last drink)

— Delirium tremens (48–96 h, mortality ~5%)

— Hallucinations (alcoholic hallucinosis vs DTs)

— Apathy, anosognosia (lack of insight in KS)

— Depression, suicidality

— Loss of independence, need for long-term care

— Loss of employment, housing instability

— Inability to manage finances or medications

— Need for guardianship in advanced KS

Key distinction: Shoshin beriberi vs septic shock — both have distributive physiology, but shoshin has lactic acidosis disproportionate to clinical picture, no infection source, and rapid reversal with thiamine. Always include thiamine in undifferentiated lactic acidosis workup.

Board pearl: Mammillary body atrophy on MRI in a patient with chronic memory problems = prior WE/KS, even if no acute episode was documented.

Mortality:

Progression to Korsakoff syndrome:

Neurologic sequelae:

Wet beriberi (cardiovascular):

Aspiration pneumonia — confused, ataxic patients with impaired swallow

Falls and trauma — head injury, hip fracture, subdural hematoma

Refeeding syndrome — hypophosphatemia, hypomagnesemia, hypokalemia, arrhythmia, respiratory failure

Concurrent alcohol withdrawal complications:

Psychiatric:

Social/functional:

When to Escalate Care — ICU, Consult, and Triage

— Coma or GCS ≤8

— Severe alcohol withdrawal requiring high-dose benzodiazepines, phenobarbital, dexmedetomidine, or propofol

— Delirium tremens with hemodynamic instability

— Shoshin beriberi — cardiogenic/distributive shock

— Respiratory failure, need for intubation (airway protection in coma)

— Status epilepticus from withdrawal

— Severe electrolyte derangement (e.g., refeeding hypophosphatemia <1.0 mg/dL)

— Hepatic failure with encephalopathy and coagulopathy

— Moderate withdrawal on scheduled benzodiazepines

— Aspiration risk requiring close airway monitoring

— Hemodynamic monitoring for wet beriberi

— Stable established WE on scheduled IV thiamine

— Mild–moderate withdrawal on CIWA protocol

— Neurology — confirm diagnosis, interpret MRI, manage residual deficits

— Psychiatry/Addiction Medicine — AUD treatment, MAT initiation, motivational interviewing

— Nutrition/Dietitian — refeeding protocol, long-term plan

— Social work — housing, insurance, AA/NA referral, transportation

— PT/OT — gait training, ADLs, fall prevention

— Speech-language pathology — swallow eval (aspiration), cognitive rehab

— Ophthalmology — if persistent diplopia or visual complaints

— Cardiology — if wet beriberi or new HF

— OB — for HG-related WE; coordinate fetal monitoring

— Bariatric surgery — for post-bariatric WE; revise supplementation

— Limited specialty support at current facility

— Need for neurorehabilitation (inpatient rehab facility)

CCS pearl: On CCS, the right cadence is: reassess every 4–8 hours initially during acute WE management. Check ocular exam, gait when able, mental status, electrolytes. If no improvement in 48–72 hours of high-dose IV thiamine, reconsider diagnosis (CT/MRI, LP, broader workup) and confirm magnesium is repleted.

Step 3 management: Always pair acute neuro management with early addiction medicine consult — initiating naltrexone or acamprosate in-hospital improves post-discharge engagement.

ICU admission criteria:

Step-down/intermediate care:

Medical floor:

Consultations:

Transfer criteria:

Key Differentials — Behavioral Health / Cognitive Causes

— Intoxication: dysarthria, ataxia, disinhibition, no thiamine deficiency signs

— Withdrawal: tremor, autonomic hyperactivity, hallucinations, seizures 12–48 h after last drink; DTs at 48–96 h

— Can coexist with WE — treat all simultaneously

— Acute, fluctuating attention, altered consciousness

— Underlying cause: infection, metabolic, drug, hypoxia

— Lacks specific ocular and ataxia findings of WE

— Empiric thiamine still reasonable if any risk

— Asterixis, fetor hepaticus, elevated ammonia

— Responds to lactulose, rifaximin

— Common in same population — treat both empirically

— Chronic, gradual decline; preserved attention early

— No ocular signs, no acute ataxia

— KS may be confused with dementia, but KS has abrupt onset following WE episode and disproportionate amnesia with preserved IQ

— Sudden anterograde amnesia lasting <24 hours, then resolves

— No ocular signs, no ataxia, no chronic confabulation

— Selective memory loss, often for personal identity

— Normal neuro exam, normal imaging

— Hallucinations, delusions, mood symptoms predominate

— Memory generally intact

— Young women, psychiatric symptoms, seizures, dyskinesias, autonomic instability

— CSF NMDA antibodies; ovarian teratoma

— Subacute memory loss, seizures, behavioral change

— Anti-Hu, anti-Ma2, anti-LGI1 antibodies

— MRI: medial temporal lobe T2 hyperintensity (not mammillary bodies)

Key distinction: Korsakoff vs Alzheimer dementia — KS has profound anterograde amnesia with relatively preserved language, visuospatial, and executive function early on, plus confabulation; Alzheimer has progressive multi-domain decline with insidious onset and no temporal precipitant.

Board pearl: Confabulation is not specific to KS — it also occurs in ruptured anterior communicating artery aneurysms (basal forebrain injury) and frontal lobe lesions. Context (alcohol use, mammillary body involvement) clinches WE/KS.

Alcohol intoxication / withdrawal:

Delirium (any cause):

Hepatic encephalopathy:

Dementia (Alzheimer, vascular, Lewy body, frontotemporal):

Transient global amnesia:

Dissociative amnesia / psychogenic:

Psychosis / mania:

Anti-NMDA receptor encephalitis:

Limbic encephalitis (paraneoplastic):

Key Differentials — Neurologic and Other Causes

— Acute onset, focal deficits, possible coma

— MRI shows diffusion restriction in vertebrobasilar territory

— Top-of-the-basilar syndrome can cause bilateral thalamic infarcts mimicking WE imaging

— Bilateral paramedian thalamic + midbrain infarct

— Sudden coma, vertical gaze palsy, memory loss

— Differentiate from WE by acute onset, vascular risk factors, DWI restriction in stroke pattern

— Acute ataxia, vomiting, headache, possible brainstem signs

— CT/MRI confirms

— Chronic gait ataxia from vermis atrophy; coexists with WE/KS but lacks acute ocular findings

— Young adult, movement disorder, psychiatric symptoms, Kayser-Fleischer rings, low ceruloplasmin

— Relapsing-remitting neurologic deficits, optic neuritis, INO

— MRI: periventricular white matter lesions, not mammillary bodies

— Rapidly progressive dementia, myoclonus, ataxia, periodic sharp waves on EEG

— MRI: cortical ribboning, basal ganglia DWI restriction

— Quadriparesis, dysarthria, locked-in syndrome

— History of rapid sodium correction

— Bacterial/viral meningoencephalitis, HSV encephalitis (temporal lobe)

— Fever, meningismus, CSF pleocytosis

— Reversible AMS; check labs

Key distinction: Phenytoin toxicity classically produces nystagmus + ataxia + confusion — checking a level is essential in any seizure patient with this triad before anchoring on WE.

Board pearl: Pellagra (niacin/B3 deficiency) and WE can coexist in chronic alcoholics — give a full B-complex, not thiamine alone, if pellagra features (photosensitive dermatitis, diarrhea) are present.

Posterior circulation stroke / basilar artery thrombosis:

Artery of Percheron infarct:

Cerebellar stroke / hemorrhage:

Cerebellar degeneration (alcoholic):

Wilson disease:

Multiple sclerosis:

Creutzfeldt-Jakob disease:

Central pontine myelinolysis / osmotic demyelination:

CNS infection:

Hypoglycemia, hyponatremia, hypothyroidism (myxedema):

Drug intoxication: benzodiazepines, opioids, GHB, anticonvulsant toxicity (phenytoin causes nystagmus and ataxia — common mimic)

Carbon monoxide poisoning — bilateral globus pallidus lesions; delayed neuropsychiatric syndrome

Heavy metal toxicity (lead, mercury, arsenic)

Vitamin deficiencies: B12 (subacute combined degeneration, dementia), niacin (pellagra triad: dermatitis, diarrhea, dementia)

Secondary Prevention and Long-Term Plan

— Thiamine 100 mg PO daily indefinitely

— Consider IM thiamine every 1–3 months if ongoing AUD with poor adherence

— Multivitamin daily

— Pharmacotherapy — discuss with every patient:

— Naltrexone PO 50 mg daily or IM 380 mg monthly — first-line

— Acamprosate 666 mg TID — preferred in hepatic disease

— Disulfiram — supervised, motivated patients only

— Off-label: gabapentin, topiramate, baclofen

— Behavioral — CBT, motivational enhancement therapy, 12-step facilitation, SMART Recovery

— Peer support — AA, SMART Recovery, recovery community centers

— Residential treatment if severe or recurrent

— Hepatitis B/C screening and treatment

— HIV screening

— Cirrhosis surveillance (twice-yearly US ± AFP if cirrhotic)

— Osteoporosis screening

— Depression, anxiety, PTSD screening

— Tobacco cessation (~80% of AUD patients smoke)

— Polysubstance use assessment

— Dietitian follow-up

— Food security assessment (SNAP, food banks)

— Address dental issues impairing intake

— Cognitive impairment from KS may require driving evaluation

— Some states mandate reporting (varies)

Step 3 management: On discharge from a WE admission, every patient should leave with: oral thiamine, multivitamin, folate, naltrexone or acamprosate prescription (if appropriate), follow-up appointment within 1–2 weeks, addiction medicine referral, and warm handoff to outpatient AUD treatment.

Board pearl: Initiating naltrexone before discharge (during the inpatient stay) significantly improves post-discharge engagement and reduces relapse — a Step 3-favored transition-of-care intervention.

Lifelong thiamine supplementation for any patient with prior WE/KS or ongoing risk:

Treat alcohol use disorder (the modifiable driver):

Address comorbidities:

Nutritional rehabilitation:

For post-bariatric patients: lifelong multivitamin with thiamine, B12, iron, calcium, vitamin D; annual labs.

For HG survivors: prenatal vitamins through pregnancy and lactation; counseling for future pregnancies (recurrence risk ~15–80%).

Driving and safety:

Vaccinations: influenza annually, pneumococcal, hepatitis A/B, COVID-19, Tdap.

Follow-Up, Monitoring, and Rehab

— 1–2 weeks post-discharge: primary care or addiction medicine — assess adherence, withdrawal recurrence, side effects of MAT, mood

— 4–6 weeks: repeat neuro exam, neuropsych testing if KS suspected, labs (CMP, CBC, magnesium, phosphate)

— 3 months: functional status, AUD engagement, depression screening (PHQ-9)

— 6–12 months: reassess cognitive status, ongoing thiamine adherence

— Then annually with primary care

— Mental status, gait, ocular exam at each visit

— LFTs, CBC, MCV (MCV decreases with sustained abstinence — useful biomarker)

— CDT (carbohydrate-deficient transferrin) or PEth (phosphatidylethanol) — biomarkers of recent alcohol use

— Urine ethyl glucuronide (EtG) for short-term abstinence monitoring

— Errorless learning techniques — present correct information only, avoid trial-and-error which reinforces incorrect memories

— Spaced retrieval training

— External memory aids: smartphones, calendars, notebooks, alarms

— Environmental cues, structured routines

— Family/caregiver education

— PT for gait, balance, fall prevention

— OT for ADLs, home safety evaluation

— Cane, walker, home modifications as needed

— Home with caregiver support and home health

— Assisted living with memory care

— Long-term care facility

— Guardianship if capacity lost

— Education on confabulation (not lying)

— Respite resources

— Support groups (Al-Anon for family)

CCS pearl: On the post-discharge CCS-style scenario, schedule follow-up in 1–2 weeks, order PHQ-9, repeat magnesium and LFTs, confirm naltrexone adherence, and reinforce thiamine compliance. Do not advance the clock weeks without a touchpoint.

Board pearl: MCV is a low-cost, longitudinal biomarker of alcohol use — a falling MCV over months supports sustained abstinence.

Follow-up cadence:

Monitoring parameters:

Cognitive rehabilitation (for KS):

Physical rehabilitation:

Disposition options for severe KS:

Reassess driving capacity — formal driving evaluation if cognitive deficits

Family/caregiver support:

Ethical, Legal, and Patient Safety

— Acute WE patients are typically incapacitated during the encephalopathic phase — use surrogate decision-makers per state hierarchy (spouse → adult children → parents → siblings)

— Reassess capacity as encephalopathy clears

— KS patients often have impaired capacity for complex medical/financial decisions despite appearing conversational — formal capacity assessment is required for major decisions

— Consider guardianship referral if no surrogate and persistent incapacity

— A confabulating patient may "agree" to procedures without true understanding — document capacity assessment, involve surrogate

— Do not accept consent from an acutely intoxicated or encephalopathic patient

— Administering IV glucose without thiamine to a malnourished patient is a recognized preventable harm

— Institutional protocols should bundle thiamine with any IV dextrose order in at-risk populations

— This is a frequent root cause analysis (RCA) scenario and a Step 3 patient-safety stem

— Driving impairment: some states require physician reporting of cognitively impaired drivers (e.g., California, Pennsylvania); know your state law

— Elder abuse/self-neglect: report if KS patient is unable to care for self and at risk

— Child welfare: if patient has dependent children at risk due to AUD or cognitive impairment

— 42 CFR Part 2 governs substance use disorder records — separate consent required to share with non-treating providers

— Recent updates align some sharing with HIPAA, but caution is needed

— Discharge without thiamine, MAT, and follow-up is a high-risk handoff

— Medication reconciliation must include thiamine and AUD pharmacotherapy

— Warm handoff to outpatient addiction services reduces readmission

— An encephalopathic patient cannot refuse life-saving thiamine — proceed under implied/emergency consent

— Once lucid, a capacitated patient may refuse further AUD treatment — respect autonomy but document counseling

— Discuss in stable KS patients while capacity remains

Step 3 management: A patient with confabulation insists he wants to leave AMA. Capacity assessment is required — ability to understand, appreciate, reason, and express a choice. If lacking, involve surrogate; do not simply discharge.

Board pearl: The single most preventable harm in WE is omission of thiamine before glucose — recognize it as a sentinel event in QI/safety stems.

Decision-making capacity:

Informed consent edge cases:

Patient safety — the IV dextrose error:

Mandatory reporting:

Confidentiality:

Transition-of-care risks:

Refusal of treatment:

Advance directives:

High-Yield Associations and Rapid-Fire Facts

Board pearl: When in doubt on any malnourished, alcoholic, or post-bariatric patient with neurologic symptoms — give thiamine 500 mg IV. It is cheap, safe, and potentially lifesaving.

Key distinction: Wernicke is acute and reversible; Korsakoff is chronic and largely irreversible — the spectrum hinges on time-to-thiamine.

Thiamine cofactor for: transketolase, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase

Body stores of thiamine last ~2–3 weeks without intake

Daily thiamine requirement: ~1.1–1.2 mg/day (adults); higher in pregnancy, lactation, alcoholism

Oral thiamine absorption is saturable (~5 mg/day maximum)

Caine criteria (≥2 of 4): dietary deficiency, oculomotor signs, cerebellar dysfunction, altered mental status — far more sensitive than classic triad

Classic triad present in only ~10–16% of WE cases

Mammillary body atrophy on MRI — pathognomonic chronic finding

Enhancement of mammillary bodies on contrast MRI — highly specific for acute WE

80% of untreated WE survivors develop Korsakoff syndrome

Confabulation — not lying; involuntary fabrication to fill memory gaps

Anterograde amnesia >> retrograde in KS; temporal gradient preserves remote memories

Loop diuretics → urinary thiamine loss → subclinical deficiency in chronic HF

Bariatric surgery → WE risk peaks at 4–12 weeks post-op

Hyperemesis gravidarum → WE possible as early as 14 weeks gestation

Wet beriberi = high-output HF; dry beriberi = peripheral neuropathy; shoshin = fulminant cardiac form

Lactic acidosis in undifferentiated AMS — think thiamine deficiency (PDH failure → pyruvate to lactate)

Magnesium is required for thiamine pyrophosphate activity — replete Mg before expecting thiamine response

Anaphylaxis to IV thiamine: ~1 per million doses — risk grossly overstated

Refeeding syndrome — hypophosphatemia hallmark; pre-treat with thiamine + electrolytes

Dialysis patients lose water-soluble vitamins — supplement routinely

Cells most vulnerable: neurons in mammillary bodies, medial thalamus, periaqueductal gray, cerebellar vermis

Korsakoff recovery: ~20% full, ~25% none, rest partial

Naltrexone first-line for AUD without opioid use; acamprosate if hepatic disease

MCV, GGT, CDT, PEth — biomarkers of alcohol use

Pellagra (niacin) and WE can coexist — give B-complex, not B1 alone

42 CFR Part 2 governs SUD records confidentiality

Board Question Stem Patterns

— Answer: IV thiamine 500 mg, magnesium repletion. Anchor: thiamine before/with glucose.

— Answer: Wernicke encephalopathy. Pitfall: clinicians forget thiamine in non-alcoholic stems.

— Answer: WE; treat with IV thiamine.

— Answer: Korsakoff syndrome.

— Answer: failure to administer thiamine before/with glucose.

— Answer: prior WE / Korsakoff.

— Answer: thiamine deficiency; treat with IV thiamine, dramatic improvement.

— Answer: refeeding syndrome; pre-treat with thiamine and electrolytes, advance slowly.

— Answer: formal capacity assessment, involve surrogate if lacking.

— Answer: initiate naltrexone or acamprosate before discharge, oral thiamine 100 mg daily, addiction medicine follow-up within 1–2 weeks.

— Answer: empiric thiamine.

Board pearl: When the stem includes "IV fluids with dextrose were started" in a malnourished or alcoholic patient, the next-step question almost always pivots on thiamine omission.

Step 3 management: Stems frequently test transition-of-care: the right discharge bundle is thiamine + MAT + follow-up appointment + addiction referral.

Classic alcoholic stem: 52-year-old man with chronic alcohol use brought in confused, ataxic, with horizontal nystagmus. EMS gave D5NS in the field. Next step?

Hyperemesis stem: 28-year-old at 16 weeks gestation, vomiting for 4 weeks, admitted for IV hydration. After 2 days she develops diplopia and confusion. Most likely diagnosis?

Post-bariatric stem: 35-year-old woman 8 weeks post-Roux-en-Y, persistent vomiting, now with leg weakness, gait ataxia, ophthalmoplegia.

Confabulation stem: 60-year-old recovered from acute confusion 3 weeks ago, now alert and conversant but cannot remember today's events; tells elaborate plausible stories about lunch he never had. Diagnosis?

Glucose-before-thiamine error stem: Hypoglycemic alcoholic given D50 alone, develops worsening confusion and nystagmus. What was the error?

MRI stem: Patient with chronic memory impairment; MRI shows bilateral mammillary body atrophy. Diagnosis?

Wet beriberi stem: Malnourished patient with high-output heart failure, warm extremities, lactic acidosis without infection.

Refeeding stem: Anorexia patient started on full-calorie feeds, develops hypophosphatemia, weakness, confusion.

Capacity stem: KS patient with confabulation refuses AMA discharge. Next step?

Discharge planning stem: Patient stabilized after WE admission. Best intervention to prevent recurrence?

Loop diuretic stem: Elderly HF patient on chronic furosemide presents with confusion and gait disturbance, normal labs except mild Mg low.

One-Line Recap

Wernicke encephalopathy is an acute, reversible neurologic emergency from thiamine deficiency — most often in alcohol use disorder, hyperemesis, post-bariatric, or refeeding contexts — treated with high-dose IV thiamine 500 mg TID before any glucose, while Korsakoff syndrome is its chronic amnestic-confabulatory sequela that develops in ~80% of inadequately treated survivors.

Board pearl: If you remember nothing else: thiamine is cheap, safe, and lifesaving — when in doubt, give it.

The reflex: any at-risk patient with altered mental status → thiamine before glucose, every time. Pair with magnesium repletion. Do not wait for labs or imaging.

The triad trap: classic confusion + ophthalmoplegia + ataxia is present in <20%. Use Caine criteria (≥2 of: dietary deficiency, oculomotor signs, cerebellar dysfunction, altered mental status) to keep sensitivity high.

The dosing: established WE = 500 mg IV over 30 min TID × 2–3 days, then 250 mg daily × 5 days, then 100 mg PO daily indefinitely. Prophylaxis = 200–500 mg IV/IM daily × 3–5 days.

The transition: discharge bundle = oral thiamine + multivitamin + folate + naltrexone or acamprosate + addiction medicine follow-up in 1–2 weeks + treatment of comorbidities (hepatitis C, depression, malnutrition).

The safety net: glucose-before-thiamine is a sentinel preventable harm; institutional order sets should bundle thiamine with any IV dextrose in at-risk patients.

The prognosis: with prompt treatment, ocular findings resolve in hours, ataxia and confusion over days–weeks; once Korsakoff amnesia consolidates, only ~20% recover fully — making prevention and early aggressive thiamine the single highest-yield intervention in this entire disease spectrum.