Wernicke–Korsakoff Syndrome

Primer

Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine (vitamin B1) deficiency, commonly found in chronic alcoholism. This primarily alcohol-induced disorder is characterized by amnesia, confabulation, disorientation, and neurological findings. WKS occurs due to necrotic lesions to the mammillary bodies, thalamus, and brainstem. The syndrome itself consists of 2 components: Wernicke’s encephalopathy (WE), and Korsakoff’s amnesia (KA), hence the combined name Wernicke-Korsakoff Syndrome.

Underdiagnosis

Terminology

Wernicke's vs. Korsakoff's

Course Symptoms
Wernicke's Encephalopathy (WE) Acute, but reversible The classic triad of:
• Eye abnormalities (nystagmus, oculomotor paralysis, paralysis of conjugate gaze), CN VI palsy AKA lateral gaze palsy (lateral rectus)
• Ataxia of stance and gait
• Mental status changes, including withdrawal, confusion, retro/anterograde amnesia
Korsakoff's Syndrome/Amnesia (KS)* Chronic and only 20% of cases are reversible with treatment • Anterograde amnesia
• Confabulations
• Personality changes
* = Cannot occur during an acute delirium or dementia and must persist beyond usual duration of intoxication or withdrawal management

Classically, Korsakoff's syndrome presents after an episode of Wernicke's encephalopathy though this is not always the case.

Diagnosis

WKS is a clinical diagnosis, but neuroimaging findings may help confirm the diagnosis.

Pathophysiology

Vitamin B1 (Thiamine) Deficiency

WKS is caused by an underlying B1 (thiamine) deficiency. Thiamine is a cofactor in the decarboxylation of pyruvate. The absence of vitamin B1 for this reaction leads to damage to the limbic system, specifically the mammillary bodies and anterior/medial thalamus.

A Quick Review on Vitamins

Vitamins are either water-soluble (vitamins B and C), or fat-soluble (vitamins A, D, E, K)
  • Fat-soluble vitamins are dependent on absorption from the ileum and pancreas. Toxicity is easier with fat soluble vitamins because these vitamins accumulate in fat. Malabsorption syndromes such as cystic fibrosis and/or celiac disease) can result in fat-soluble vitamin deficiencies.
  • Water-soluble vitamins are usually important coenzymes in cellular processes or precursors to coenzymes. All are excreted easily from the body, except for vitamins B12 and B9. B vitamin deficiency can result in glossitis, dermatitis, and diarrhea. For certain vitamin B deficiencies (B1 and B12), there can be neuropsychiatric and cognitive symptoms as well. Broadly, the B vitamins include:

Physical Exam

In patients with chronic alcohol use disorder with only an ataxic gait and stance found on physical exam, and no other neurological findings, they most likely have alcoholic cerebellar degeneration (midline cerebellar degeneration).

Investigations

  • CBC, lytes, Cr
  • GGT - indicator of acute liver injury from EtOH use, for detecting people drinking > 4 drinks/day
  • AST, ALT, ALP, GGT
    • AST > ALT x 3 (in EtOH hepatitis)
    • AST/ALT ratio also > 2
  • INR
  • B12 and thiamine

Neuroimaging

  • MRI brain may show mammillary body atrophy, volume loss in the thalamus, volume loss in the corpus callosum.

Differential Diagnosis

Although thiamine deficiency often occurs in the context of alcohol use disorders, it can also occur in eating disorders, malnutrition, hyperemesis gravidarum, chronic vomiting, extreme dieting, and cancer patients undergoing chemotherapy.

Treatment

Treatment is with preventative therapy. If the Korsakoff Syndrome has already occurred, the chance of recovery is slim.

  • Low risk patients: Thiamine 100mg TID should be prescribed as ongoing supplementary therapy in alcohol use disorder patients identified as at risk for thiamine deficiency.[1]
  • High-risk or patients:
    • 200mg IV thiamine x 3 days, followed by oral supplementation
  • Suspected Wernicke’s encephalopathy:
    • Thiamine 100mg IM/IV x 3 days (can be as high as 500mg TID),[2] then 300mg PO x 3-12 months
    • Don’t forget to give fluids as well!

References

1) RebelEM:Should You Prescribe Oral Thiamine for Chronic Alcoholics?
2) Nishimoto, A., Usery, J., Winton, J. C., & Twilla, J. (2017). High-dose parenteral thiamine in treatment of Wernicke's encephalopathy: case series and review of the literature. in vivo, 31(1), 121-124.