Wernicke encephalopathy and Korsakoff syndrome

Epidemiology

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Etiology

• Wernicke encephalopathy and Korsakoff syndrome are caused by a severe deficiency of thiamine (vitamin B1).
• Thiamine deficiency can be due to:
  • Chronic heavy alcohol use (most common): due to inadequate intake, absorption, and hepatic storage of thiamine
  • Inadequate intake
    • Thiamine-deficient diets
    • Anorexia nervosa, starvation
      • In patients with low glucose intake, thiamine deficiency may be asymptomatic. However, this patient ingested a large quantity of glucose, which likely rapidly depleted her limited thiamine stores.
  • Malabsorption

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Pathophysiology

• Core Pathophysiology
  • Caused by Thiamine (Vitamin B1) deficiency, which is a critical cofactor for several key enzymes involved in glucose metabolism.
  • Most common cause is chronic alcoholism due to poor nutrition, malabsorption, and impaired thiamine storage/utilization.
• Key Affected Enzymes
  • Pyruvate dehydrogenase: Links glycolysis to the TCA cycle (Pyruvate → Acetyl-CoA).
  • α-ketoglutarate dehydrogenase: A rate-limiting enzyme in the TCA cycle.
  • Transketolase: An enzyme in the pentose phosphate pathway (HMP shunt).
• Cellular & Anatomic Consequences
  • Impairment of these enzymes leads to a severe ↓ in ATP production, particularly affecting brain regions with high metabolic demand.
  • This energy deficit causes neuronal injury, cell death, and focal lactic acidosis.
  • Selectively damages specific brain structures:
    • Mamillary bodies
    • Medial dorsal nuclei of the thalamus
    • Periaqueductal and periventricular gray matter
    • Cerebellum

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Clinical features

Wernicke encephalopathy (acute, reversible)

• Should be suspected in any patient with a history of chronic heavy alcohol use who presents with one/more symptoms of the classic triad of Wernicke encephalopathy
  1. Confusion (most common)
     • Disorientation, impaired vigilance, and cognitive deficits
  2. Oculomotor dysfunction
     • Due to involvement of the CN III, CN IV, and CN VI nuclei
     • Gaze-induced horizontal/vertical nystagmus (most common)
     • Diplopia
     • Conjugate gaze palsy
  3. Gait ataxia: wide-based, small steps
     • Due to a combination of peripheral neuropathy, vestibular dysfunction, and cerebellar dysfunction
     • Romberg test positive

When to suspect

Wernicke encephalopathy should be suspected in any patient with chronic alcohol abuse or any form of malnutrition and any of the following: acute altered mental status, ophthalmoplegia, ataxic gait, delirium, and hypotension.

Korsakoff syndrome (chronic, irreversible)

Korsakoff syndrome is a late development in patients with persistent vitamin B1 deficiency. It is most often seen in thiamine deficiency due to chronic heavy alcohol use.

• Confabulation: Patients produce fabricated memories to fill in lapses of memory.
• Anterograde and retrograde amnesia (anterograde is more common than retrograde)
• Personality changes (in frontal lobe lesions): apathy, indifference, decrease in executive function
• Disorientation to time, place, and person
• Hallucinations

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Diagnostics

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Treatment

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