Makindo Medical Notes

Untreated Wernicke's encephalopathy → Korsakoff's syndrome

About

• Commonly occurs in individuals with chronic alcoholism, certain cancers, or severe malnutrition (e.g., hyperemesis gravidarum).
• Wernicke’s encephalopathy, if untreated, can progress to Korsakoff’s syndrome, resulting in lasting memory impairment.

Aetiology

• Thiamine pyrophosphate (TPP) is crucial as a coenzyme for:
  • Pyruvate dehydrogenase: Converts pyruvate to acetyl CoA for the Krebs cycle.
  • Alpha-ketoglutarate dehydrogenase: Another key enzyme in the Krebs cycle.
  • Transketolase: Functions in the pentose phosphate pathway.
• Key role of TPP: Facilitates the transfer of an activated aldehyde group. The nervous system, heavily reliant on glucose for energy, is particularly vulnerable to thiamine deficiency as it requires efficient entry into the Krebs cycle.
• Exposure to heavy metals, like lead and arsenic, can also impair the pyruvate dehydrogenase complex.

Clinical Features

• Wernicke’s Encephalopathy: Presents with a classic triad of symptoms:
  • Ocular Abnormalities: Diplopia, nystagmus, gaze palsies (e.g., difficulty with eye abduction), and internuclear ophthalmoplegia.
  • Cerebellar Dysfunction: Ataxia and lack of coordination.
  • Confusion: Acute confusion and disorientation.
• Typically triggered by stressors such as infection, surgery, trauma, or a carbohydrate load.
• Korsakoff’s Syndrome: Often follows untreated Wernicke's and is marked by:
  • Severe memory impairment, particularly affecting new or recent events.
  • Confabulation and psychosis, with other cognitive functions remaining relatively intact.
• Beri-Beri:
  • Dry Beri-Beri: Generalized sensory polyneuropathy.
  • Wet Beri-Beri: High-output cardiac failure.

Investigations

• Blood Tests:
  • Increased gamma-glutamyl transferase (GGT) if alcohol use is involved.
  • Low red cell transketolase and thiamine levels.
  • Elevated pyruvate levels.
• MRI: T2-weighted changes in the thalamus (linked to memory loss) and periaqueductal grey matter (associated with eye symptoms).
• Lumbar Puncture: Typically normal findings.
• Post-Mortem Findings: Necrosis and gliosis in the brainstem, thalamus, and hypothalamus.

Management

• Immediate administration of thiamine (e.g., Pabrinex) is both diagnostic and therapeutic.
• Give Pabrinex before or alongside any glucose load, as glucose alone can precipitate Wernicke’s encephalopathy.
• Long-term management involves abstinence from alcohol and continued oral thiamine supplementation.
• In Korsakoff’s syndrome, prognosis varies, with some patients experiencing poor recovery outcomes.