Overview
Wernicke-Korsakoff Syndrome
1. Clinical Overview
Summary
Wernicke-Korsakoff Syndrome (WKS) represents two stages of the same disease caused by acute Thiamine (Vitamin B1) Deficiency.
- Wernicke's Encephalopathy (WE): The acute, potentially reversible neurological emergency characterized by the classic triad of Confusion, Ataxia, and Ophthalmoplegia. Untreated, mortality is 17%.
- Korsakoff's Syndrome (KS): The chronic, irreversible neuropsychiatric sequelae characterized by profound anterograde amnesia (inability to form new memories) and confabulation. It is most commonly associated with chronic alcoholism, but can occur in any state of malnutrition (Hyperemesis gravidarum, Anorexia, post-Bariatric surgery). Treatment is immediate high-dose IV Thiamine (Pabrinex). [1,2]
Key Facts
- The "Classic Triad" (Confusion, Ataxia, Eye signs) is only present in 10-16% of patients. Diagnosis requires a high index of suspicion.
- The "Sugary Death": Thiamine is a co-factor for glucose metabolism. Giving a glucose load (Dextrose) to a thiamine-deficient patient consumes their last reserves of B1, precipitating acute Wernicke's. Always give Thiamine BEFORE (or with) Glucose.
- Prevention: Any patient attending hospital with evidence of alcohol misuse should receive prophylactic thiamine.
- Korsakoff's Reality: Patients are often "pleasantly confused". They have no insight (anosognosia) and fill gaps in memory with invented stories (confabulation). They often require lifelong institutional care.
Clinical Pearls
Test the Eyes: The earliest sign is often Nystagmus (horizontal) or Lateral Rectus (CN VI) Palsy. If the eyes are fixed, it's late. These signs often resolve within hours of IV thiamine.
Magnesium Matters: Thiamine works with Magnesium. If Hypomagnesaemia is present (common in alcoholics), the thiamine won't work. Replace Mg++ aggressively.
Not just Alcohol: Missed Wernicke's is a major cause of litigation in Hyperemesis Gravidarum. If a pregnant woman is vomiting for weeks and becomes confused, it is Wernicke's until proven otherwise.
2. Epidemiology
Incidence
- Prevalence in autopsies of alcoholics: 12.5% (meaning it is massively under-diagnosed in life).
- Clinical diagnosis made in only 20% of cases found at autopsy.
Risk Factors
- Alcohol Dependence: Poor diet + inhibition of B1 absorption.
- Malnutrition: Starvation, Anorexia Nervosa.
- Vomiting: Hyperemesis Gravidarum, Chemotherapy.
- Malabsorption: Gastric Bypass, Coeliac.
3. Pathophysiology
Biochemistry
- Thiamine (B1): Unstable, water-soluble vitamin. Body stores last only 4-6 weeks.
- Mechanism: Thiamine Pyrophosphate (TPP) is an essential co-factor for the Krebs Cycle (Pyruvate Dehydrogenase / Alpha-ketoglutarate dehydrogenase).
- Deficiency: Glucose cannot be metabolised aerobically -> Anaerobic metabolism -> Lactate accumulation -> Excitotoxicity (Glutamate) -> Neuronal Cell Death.
- Target Areas: High metabolic demand areas: Mammillary Bodies, Thalamus, Periaqueductal Grey, Cerebellum (Vermis).
4. Clinical Presentation
Wernicke's Encephalopathy (Acute)
Diagnosis requires 2 of 4 (Caine Criteria):
- Dietary Deficiency: Signs of malnutrition.
- Oculomotor Abnormalities: Nystagmus, Lateral Rectus Palsy, Conjugate Gaze Palsy.
- Cerebellar Dysfunction: Ataxia (wide-based gait), unsteadiness.
- Altered Mental Status: Confusion, apathy, coma. Also: Hypotension, Hypothermia (hypothalamic dysfunction).
Korsakoff's Syndrome (Chronic)
Anterograde Amnesia
Profound inability to learn new information (5 minute retention is zero).
Retrograde Amnesia
Patchy loss of past memories.
Confabulation
Fabricating events to fill memory gaps (not lying; they believe it).
Apathy
Lack of emotional content.
5. Clinical Examination
- General: Stigamata of chronic liver disease (Spider naevi). Malnourished.
- Cranial Nerves: Check eye movements carefully. Look for Nystagmus on lateral gaze.
- Gait: Heel-toe walking (Ataxia).
- Cognition: AMTS/MOCA. (Short term memory is gone).
6. Investigations
Diagnosis is Clinical
Do NOT wait for blood tests before treating.
- Red Cell Transketolase: Measures thiamine activity (Scientific gold standard but rarely available acutely).
- Thiamine Levels: Takes weeks.
Imaging
- MRI Brain: Specific changes seen in Mammillary Bodies (hyperintensity on T2/FLAIR) and medial thalamus. Atrophy of mammillary bodies is seen in chronic KS.
Routine
- Glucose: Check (Hypoglycaemia common).
- U&Es: Magnesium/Phosphate/Potassium (Refeeding syndrome risk).
- LFTs: Alcoholic hepatitis?
7. Management
Management Algorithm
SUSPECTED WERNICKE'S
(Alcoholic/Malnourished)
↓
IMMEDIATE IV ACCESS
↓
┌─────────────┴─────────────┐
ACUTE WE PROPHYLAXIS
(Confusion/Ataxia) (Alcohol withdrawal
or Hypoglycaemia but asymptomatic)
↓ ↓
PABRINEX IV PABRINEX IV
2 pairs TDS 1 pair OD
for 3-5 days for 3 days
↓ ↓
Oral Thiamine Oral Thiamine
100mg TDS 100mg TDS
(When stopping IV) (On discharge)
1. Acute Treatment (Pabrinex)
- Drug: Pabrinex I.V. (Contains Vitamins B1, B2, B3, B6, C).
- Dose: 2 pairs of ampoules (High Potency) diluted in 100ml Saline, infused over 30 mins.
- Frequency: Three times a day (TDS) for 3-5 days.
- Anaphylaxis Risk: Very rare (1 in 250,000). Facilities for resuscitation should be available, but do not let this delay treatment.
2. Electrolytes and Nutrition
- Magnesium: Replacement is crucial.
- Glucose: Can be given AFTER the first dose of Pabrinex.
- Calories: Monitor for Refeeding Syndrome.
3. Long Term
- Oral Thiamine: 100mg TDS indefinitely if continuing to drink. Oral absorption is poor in active alcoholics (intestinal edema/gastritis), hence why IV is needed acutely.
8. Complications
- Korsakoff's Syndrome: 80% of untreated WE survivors develop this.
- Alcohol Withdrawal Seizures: Often co-exist.
- High Output Cardiac Failure: "Wet Beriberi" (Thiamine deficiency affecting heart).
9. Prognosis and Outcomes
- WE: Ocular signs resolve quickly (days). Ataxia improves slowly (weeks). Confusion improves slowly.
- KS: Only 20% recover. 25% need long-term institutionalisation.
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| CG100 | NICE (Alcohol) | Offer prophylactic Pabrinex to all harmful drinkers in hospital. Therapeutic dose for anyone with WE signs. |
| Guidelines | Royal College of Physicians (RCP) | "Do not delay treatment for investigations." "Oral thiamine is inadequate for acute WE." |
Landmark Knowledge
1. The "Banana Bag" Myth
- In the US, a bag of saline with a multivitamin ampoule (yellow/banana colour) is often used.
- Problem: It usually contains only 100mg Thiamine.
- Reality: WE requires 500mg+ IV daily. Standard "banana bags" are insufficient for treatment, leading to cases of iatrogenic Wernicke's. Focus on PABRINEX (High potency).
11. Patient and Layperson Explanation
What is "Wet Brain"?
It is a severe reaction to lack of Vitamin B1 (Thiamine). Heavy drinking stops the body absorbing B vitamins, and alcoholics often don't eat well.
Is it reversible?
The acute confusion (Wernicke's) can be reversed if treated quickly with strong vitamin drips. If it is missed, it turns into permanent brain damage (Korsakoff's).
What is Korsakoff's?
It is a type of dementia. The person cannot make any new memories. You can have a conversation with them, leave the room, come back 5 minutes later, and they will greet you as if for the first time. They often make up stories to fill the blanks, not out of malice, but because their brain is trying to make sense of the gaps.
12. References
Primary Sources
- NICE Clinical Guideline CG100. Alcohol-use disorders: diagnosis and management of physical complications. 2010.
- Royal College of Physicians. Alcohol: Use of Pabrinex.
- Thomson AD, et al. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and emergency department. Alcohol Alcohol. 2002.
13. Examination Focus
Common Exam Questions
- Emergency: "Alcoholic with hypoglycaemia (BM 2.1). Management?"
- Answer: IV Pabrinex FIRST, then IV Glucose.
- Neurology: "Anatomy of Korsakoff's?"
- Answer: Mammillary Bodies (and Dorsomedial Thalamus).
- Psychiatry: "Patient tells vivid detailed story about a trip to Paris yesterday, but has been on ward for 3 weeks. Term?"
- Answer: Confabulation.
- Medicine: "Earliest sign of Wernicke's?"
- Answer: Nystagmus / Ataxia (Confusion is late).
Viva Points
- Caine Criteria: Why do we use them? The classic triad misses 90% of cases. Caine criteria (Diet, Eye, Cerebellar, Confusion) improve sensitivity.
- Wet vs Dry Beriberi:
- Wet: Cardiac failure (edema).
- Dry: Peripheral neuropathy.
- Wernicke's: Cerebral.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.