Wernicke-Korsakoff syndrome

Background

• Wernicke’s Encephalopathy: acute neurologic symptoms caused by thiamine deficiency
• Korsakoff’s Psychosis: chronic neurologic symptoms caused by thiamine deficiency
• Wernicke-Korsakoff Syndrome (WKS): presence of Wernicke's Encephalopathy + Korsakoff's Psychosis simultaneously

Epidemiology

• Only 20% identified before death, failure of diagnosis leads to 20% mortality and 75% permanent damage

Pathophysiology

• Thiamine plays critical role in:
  • Energy production pathways (Kreb's cycle, pentose phosphate pathway, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase)
    • Deficiency leads to lactic acidosis, altered brain metabolism
  • Lipid metabolism (including myelin sheath formation)
    • Alterations in myelination leads to peripheral neuropathy
• Brain lesions/atrophy usually occur in: mamillary bodies (nearly all cases), thalamus, periaqueductal gray matter, 3rd/4th ventricle, cerebellum, frontal lobe

Causes

• Thiamine (vitamin B1) deficiency caused by
  • Insufficient intake (e.g. chronic alcoholism, starvation/anorexia, severe vomiting/diarrhea, unbalanced TPN)
  • Malabsorption (post-gastrectomy, IBD, pancreatitis)
  • Increased metabolic requirements (malignancy, thyrotoxicosis)
  • Thiamine losses (hemodialysis)
  • Miscellaneous: AIDS, liver disease

Thiamine deficiency types

• Wernicke-Korsakoff syndrome
• Beriberi

Clinical Features

Wernicke’s Encephalopathy

• Classic triad: encephalopathy, oculomotor dysfunction, gait ataxia
• werNICke mnemonic:
  • Nystagmus/ophthalmoplegia
    • Ocular findings may also include bilateral 6th nerve palsy, conjugate gaze palsy, pupillary abnormality, retinal hemorrhage, ptosis.
  • Incoordination/ataxia
  • Confusion/memory impairment
• Other symptoms:
  • Hypotension, tachycardia, ECG abnormalities
  • Dyspnea on exertion, CHF symptoms
  • Hypothermia
  • Dry/wet beriberi
  • Coma

Korsakoff’s Psychosis

• Antero/retrograde amnesia
• Confabulation, confusion, apathy

Differential Diagnosis

Ethanol related disease processes

• Ethanol toxicity
• Alcohol use disorder
• Alcohol withdrawal
  • Alcohol withdrawal seizures
  • Delerium tremens
• Electrolyte/acid-base disorder
  • Alcoholic ketoacidosis
  • Beer potomania syndrome
  • Beriberi
  • Thiamine deficiency
  • Wernicke-Korsakoff syndrome

Vitamin deficiencies

• Vitamin A deficiency
• Vitamin B deficiencies
  • Vitamin B1 deficiency (Thiamine)
    • Beriberi
    • Wernicke-Korsakoff syndrome
  • Vitamin B3 deficiency (Pellagra)
  • Vitamin B9 deficiency (Folate)
  • Vitamin B7 deficiency (Biotin)
  • Vitamin B12 deficiency
• Vitamin C deficiency (Scurvy)
• Vitamin D deficiency (Rickets)
• Vitamin E deficiency
• Vitamin K deficiency
• Zinc deficiency
  • Acrodermatitis enteropathica

Evaluation

Axial MRI FLAIR image showing hyperintense signal in the mesial dorsal thalami, a common finding in Wernicke encephalopathy

Diagnosis

• Clinical diagnosis
• Wernicke's Encephalopathy - at least 2 of the following::
  • Nutritional deficiency
  • Ocular findings (ophthalmoplegia, nystagmus)
  • Ataxia
  • Mental status change

Management

If you suspect, then treat! Confirming diagnosis is difficult, treatment is low risk and effective, and morbidity/mortality is high if untreated

• Thiamine 500mg IV over 30 min TID x 2 days, then 500mg IV/IM q day for 5 days, then 100mg PO q day until patient no longer at risk
  • Give magnesium; hypomagnesemic state may be resistant to thiamine administration
  • Treatment can take days to weeks to work if at all (despite accurate diagnosis)
  • Give thiamine BEFORE glucose in patients requiring glucose who are at risk for thiamine deficiency; glucose without thiamine can precipitate/worsen WE by driving thiamine intracellularly

Disposition

• Admit
• <25% of patients show full recovery, 50% show partial recovery, the remainder show no response despite treatment

Prevention

Vitamin Prophylaxis for Chronic alcoholics

• At risk for thiamine deficiency, but no symptoms: thiamine 100mg PO q day
• Give multivitamin PO; patient at risk for other vitamin deficiencies

Banana bag

The majority of chronic alcoholics do NOT require a banana bag

• Thiamine 100mg IV
• Folate 1mg IV (cheaper PO)
• Multivitamin 1 tab IV (cheaper PO)
• Magnesium sulfate 2mg IV
• Normal saline as needed for hydration

See Also

Ethanol related disease processes

• Ethanol toxicity
• Alcohol use disorder
• Alcohol withdrawal
  • Alcohol withdrawal seizures
  • Delerium tremens
• Electrolyte/acid-base disorder
  • Alcoholic ketoacidosis
  • Beer potomania syndrome
  • Beriberi
  • Thiamine deficiency
  • Wernicke-Korsakoff syndrome