📋 Key Information Summary
- Wernicke-Korsakoff Syndrome (WKS) is an acute neuropsychiatric emergency caused by thiamine (vitamin B1) deficiency, most commonly associated with chronic alcohol misuse.
- The classic Wernicke triad comprises ophthalmoplegia (lateral rectus palsy, nystagmus), ataxia, and confusion — but all three features are present in only ~10–16% of cases.
- Korsakoff syndrome represents the chronic amnestic state: anterograde amnesia, retrograde amnesia, confabulation, and apathy — often irreversible.
- Risk factors extend beyond alcohol: hyperemesis gravidarum, bariatric surgery, malignancy/cachexia, refeeding syndrome, prolonged parenteral nutrition, and haemodialysis.
- Clinical suspicion must trigger immediate parenteral thiamine — NEVER give glucose before thiamine, as glucose loading precipitates or worsens Wernicke encephalopathy.
- First-line treatment: Pabrinex® (thiamine 500 mg IV TDS for 2–3 days), then taper to 250 mg IV/IM daily for 3–5 more days, followed by oral thiamine 100 mg TDS long-term.
- Magnesium replacement is mandatory as magnesium is an essential cofactor for thiamine-dependent enzymes; hypomagnesaemia renders thiamine therapy ineffective.
- Prophylactic thiamine (100–300 mg PO daily or 250 mg IV/IM) should be given to all at-risk patients — especially those presenting with alcohol-related illness or malnutrition.
- Korsakoff amnestic state requires prolonged oral thiamine (≥3–12 months minimum) and comprehensive rehabilitation; full recovery is uncommon.
- Pabrinex® IVHP is available on the Australian Pharmaceutical Benefits Scheme (PBS) as a restricted benefit; anaphylaxis risk necessitates administration in a setting with resuscitation capability.
- Aboriginal and Torres Strait Islander peoples experience disproportionately higher rates of alcohol-related harm and nutritional deficiency — proactive screening and culturally safe thiamine supplementation are essential.
- Diagnosis is clinical; do not delay treatment awaiting investigations. MRI may show periventricular T2/FLAIR signal abnormality around the mammillary bodies, medial thalami, and periaqueductal grey — but a normal MRI does not exclude WKS.
Clinical Features & Risk Factors
Wernicke Encephalopathy — The Classic Triad
Wernicke encephalopathy (WE) is an acute, reversible neurological emergency caused by thiamine deficiency. Thiamine pyrophosphate is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase, and branched-chain ketoacid dehydrogenase. Deficiency impairs cerebral glucose metabolism, leading to neuronal injury in metabolically vulnerable regions — mammillary bodies, medial thalamus, periaqueductal grey, and floor of the fourth ventricle.
| Feature | Clinical Details | Frequency |
|---|---|---|
| Ophthalmoplegia | Lateral rectus palsy (bilateral or unilateral), horizontal nystagmus (most common sign), conjugate gaze palsies, absent pupilillary responses. Responds to thiamine within hours to days. | ~80–90% |
| Ataxia | Wide-based, staggering gait (vestibular and cerebellar dysfunction). Truncal ataxia predominates. Often persists even after ophthalmoplegia resolves. | ~60–80% |
| Confusion | Global confusional state, inattention, apathy, disorientation, impaired short-term memory. May progress to stupor or coma if untreated. | ~80–90% |
Clinical pearl: Only 10–16% of patients exhibit the complete triad. A high index of clinical suspicion is required — any at-risk patient with even one feature should receive immediate parenteral thiamine. Up to 80% of cases are undiagnosed ante mortem.
Korsakoff Syndrome — The Chronic Amnestic State
Korsakoff syndrome (KS) represents the chronic, often irreversible neuropsychiatric sequelae of inadequately treated or repeated episodes of Wernicke encephalopathy. It results from irreversible neuronal loss and gliosis in the diencephalon (mammillary bodies, anterior and dorsomedial thalamic nuclei).
| Feature | Clinical Details |
|---|---|
| Anterograde amnesia | Inability to form new memories — the hallmark of KS. Immediate recall is relatively preserved, but delayed recall is profoundly impaired. |
| Retrograde amnesia | Loss of previously formed memories, often with a temporal gradient (more recent memories more affected). |
| Confabulation | Spontaneous or provoked confabulations — plausible but fabricated accounts to fill memory gaps. Patients are typically not deliberately deceptive. |
| Apathy | Diminished spontaneous behaviour, reduced initiative, emotional blunting. Preserved procedural memory and automatic responses. |
Prognosis: Approximately 25% of patients with Korsakoff syndrome recover partially, 25% remain static, and 50% deteriorate without ongoing treatment. Early aggressive thiamine treatment during the Wernicke phase can prevent progression to Korsakoff syndrome.
Risk Factors for Wernicke-Korsakoff Syndrome
Highest Risk
Chronic Alcohol Misuse
Accounts for >80% of WKS cases in Australia. Alcohol impairs thiamine absorption, reduces hepatic storage, and increases metabolic demand. Patients presenting with alcohol withdrawal or alcohol-related liver disease are at highest risk.
Setting: Emergency department, acute medical admissions
Moderate Risk
Bariatric Surgery
Post-bariatric patients (especially Roux-en-Y gastric bypass and sleeve gastrectomy) develop thiamine deficiency due to reduced intake, vomiting, and malabsorption. Onset may be weeks to months post-operatively.
Setting: Surgical follow-up, post-discharge GP care
Moderate Risk
Hyperemesis Gravidarum
Severe protracted vomiting in pregnancy depletes thiamine stores rapidly. WE in pregnancy may present from the first trimester. Associated with both maternal and fetal morbidity.
Setting: Obstetric emergency, antenatal care
Emerging Risk
Refeeding Syndrome
Rapid reintroduction of nutrition in malnourished patients (anorexia nervosa, cancer cachexia, prolonged fasting) causes acute thiamine demand. Thiamine must be given before and during refeeding.
Setting: Nutritional rehabilitation, inpatient medicine
Other Risks
Malignancy, Dialysis, HIV/AIDS
Cancer-related cachexia, chemotherapy-induced vomiting, haemodialysis losses, and HIV-associated wasting all deplete thiamine. Prolonged parenteral nutrition without supplementation is also a risk factor.
Setting: Oncology, renal units, infectious disease clinics
Investigations
Available
Erythrocyte transketolase activity (ETKA) / Thiamine pyrophosphate effect (TPPE)
Most sensitive functional assay. TPPE >25% indicates deficiency. Not rapidly available — treat empirically while awaiting results. MBS item: limited availability.
Available
Serum thiamine (whole blood thiamine pyrophosphate)
Low sensitivity and specificity; normal levels do not exclude tissue deficiency. Useful if measured early. Available at major reference laboratories (e.g., Douglass Hanly Moir, Sullivan Nicolaides).
Available
MRI Brain (with contrast)
T2/FLAIR hyperintensity in periventricular regions: mammillary bodies, medial thalami, periaqueductal grey, tectal plate. T1 enhancement may be seen in acute phase. Sensitivity ~53%, specificity ~93%. A normal MRI does NOT exclude WKS.
Available
Full blood count, liver function tests, serum magnesium, serum phosphate
Assess for concurrent nutritional deficiencies, alcoholic liver disease, and electrolyte disturbances requiring correction. Magnesium is critical — hypomagnesaemia impairs thiamine utilisation.
Specialist
Neuropsychological testing
Formal assessment for Korsakoff syndrome: Wechsler Memory Scale, Rey Auditory Verbal Learning Test. Referral to clinical neuropsychologist.
Management & Prevention
Acute Management of Wernicke Encephalopathy
CRITICAL RULE: Administer parenteral thiamine BEFORE any glucose-containing fluids. Glucose loading depletes residual thiamine stores and can precipitate or worsen Wernicke encephalopathy. This is a medical emergency.
1
Immediate Parenteral Thiamine
Thiamine 500 mg IV over 30 minutes TDS for 2–3 days. Use Pabrinex® IVHP (high potency) — the only IV thiamine formulation available in Australia with adequate dosing. Administer in a setting with resuscitation capability due to anaphylaxis risk (~1 in 5 million doses).
2
Magnesium Replacement
Check serum magnesium urgently. If low, give magnesium sulfate 10–20 mmol IV over several hours. Even with borderline levels, empiric replacement is recommended — magnesium is an essential cofactor for thiamine-dependent enzymes.
3
Glucose Management
Give thiamine first, then correct hypoglycaemia if present. Avoid high-dose dextrose infusions before thiamine loading. Use normal saline for initial resuscitation if fluid bolus is required.
4
Taper & Transition to Oral Therapy
After 2–3 days of IV therapy, reduce to thiamine 250 mg IV/IM daily for 3–5 days, then transition to thiamine 100 mg PO TDS. Continue oral thiamine for a minimum of 3–12 months.
Pharmacotherapy — Key Medications
Thiamine (Pabrinex® IVHP)
Pabrinex® · IV High Potency Injection · Vitamin B1
Adult dose
500 mg IV over 30 min TDS × 2–3 days; then 250 mg IV/IM daily × 3–5 days; then 100 mg PO TDS ≥3 months
Paediatric dose
Not routinely used in paediatrics; specialist guidance — 50–100 mg IV if WE suspected
Route
IV infusion (dilute in 100 mL NS, infuse over 30 min)
Renal adjustment
No dose adjustment required
Hepatic adjustment
No dose adjustment required
Key caution
Anaphylaxis risk — administer with resuscitation equipment available. Oral or IM route if IV access difficult.
PBS status
⚠ PBS Restricted Benefit
Thiamine (Oral)
Vitamin B1 Tablets · Generic · Nutritional supplement
Adult dose
100 mg PO TDS for maintenance / prophylaxis. Higher doses (300 mg PO daily) may be used in high-risk settings.
Paediatric dose
10–50 mg PO daily depending on age and indication
Route
Oral
Duration
Minimum 3–12 months; lifelong in persistent alcohol misuse
Renal adjustment
No dose adjustment required
PBS status
✔ PBS General Benefit
Magnesium Sulfate
Generic IV · Electrolyte replacement
Adult dose
10–20 mmol IV in 250–500 mL NS over 2–4 hours for acute deficiency; then 5–10 mmol PO/IV BD–TDS
Monitoring
Serum magnesium q12–24h during IV replacement; monitor for hypotension during rapid infusion
PBS status
✔ PBS General Benefit
Thiamine dose matters: Standard multivitamin tablets containing 1–2 mg of thiamine are grossly insufficient for treating or preventing Wernicke encephalopathy. At-risk patients require pharmacological doses of thiamine (≥100 mg PO daily or ≥250 mg IV/IM).
Management of Established Korsakoff Syndrome
Korsakoff syndrome requires prolonged treatment and multidisciplinary rehabilitation:
- Thiamine: Continue oral thiamine 100 mg TDS for a minimum of 3–12 months; many experts recommend lifelong treatment in patients with ongoing alcohol misuse.
- Alcohol cessation support: Referral to addiction medicine, consider pharmacotherapy for relapse prevention (naltrexone, acamprosate, disulfiram — all PBS-listed).
- Nutritional rehabilitation: Dietetic assessment and supplementation of other B vitamins, folate, and micronutrients. Monitor for refeeding syndrome if reintroducing nutrition.
- Cognitive rehabilitation: Neuropsychological assessment, environmental strategies (calendars, alarms, external memory aids), and occupational therapy.
- Psychiatric support: Screen for depression, anxiety, and suicidal ideation. Psychosocial engagement and supported accommodation may be required.
Prevention in At-Risk Populations
| At-Risk Population | Prevention Strategy | Setting |
|---|---|---|
| Alcohol-related presentations (ED, inpatient) | Thiamine 250 mg IV/IM immediately, then 100 mg PO TDS for ≥5 days. Continue oral supplementation on discharge. | Emergency department, acute medicine |
| Alcohol withdrawal units | Thiamine 100–300 mg PO daily as standard prophylaxis. Escalate to IV if confusion, ataxia, or ophthalmoplegia develops. | Drug and alcohol units |
| Post-bariatric surgery | Thiamine 100 mg PO daily as part of routine post-operative supplementation. Any vomiting + neurological symptoms → IV thiamine urgently. | Surgical follow-up |
| Hyperemesis gravidarum | Thiamine 100 mg PO daily prophylactically in moderate–severe HG. IV thiamine 500 mg TDS if neurological symptoms develop. | Antenatal / obstetric |
| Refeeding syndrome risk | Thiamine 200–300 mg PO daily (or 250 mg IV if unable to take orally) starting ≥30 min before first feed and continuing ≥3 days. | Nutritional rehabilitation |
| Haemodialysis patients | Thiamine 100–300 mg PO daily. Monitor nutritional status and serum thiamine periodically. | Renal dialysis units |
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
📚 References
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