Wernicke encephalopathy is an acute, reversible condition caused by severe thiamine (vitamin B1) deficiency, often due to chronic heavy alcohol use. Inadequate intake, impaired absorption, or increased excretion of thiamine can also cause Wernicke encephalopathy. The classical triad of confusion, oculomotor dysfunction, and gait ataxia is seen in about a third of patients. Chronic thiamine deficiency, especially in patients with alcohol use disorder, frequently progresses to Korsakoff syndrome, which is characterized by irreversible personality changes, anterograde and retrograde amnesia, and confabulation. The diagnosis of both Wernicke encephalopathy and Korsakoff syndrome is clinical, but laboratory tests confirming thiamine deficiency and brain imaging may be considered in ambiguous cases. Wernicke encephalopathy is an emergency and requires immediate high-dose IV thiamine therapy followed by long-term thiamine supplementation. Abstaining from alcohol is vital in both conditions. While the prognosis in Wernicke encephalopathy is good if treated accordingly, that in Korsakoff syndrome is generally poor.
- 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
- Increased demand (hypermetabolic states)
- Increased loss
- Thiamine pyrophosphate (TPP) is the active form of thiamine.
- TPP is a cofactor for important enzymes involved in cerebral glucose and energy metabolism (see ).
- The brain requires a constant source of thiamine to function properly.
- Thiamine deficiency → decreased cerebral glucose metabolism and mitochondrial dysfunction → depleted ATP and increased free radicals → injury of neuronal elements (e.g., myelin sheaths, blood-brain-barrier, decreased neurotransmitters, etc.) → impaired axonal conduction → symptoms of Wernicke encephalopathy and Korsakoff syndrome
- In patients with Korsakoff syndrome: long term thiamine deficiency → permanent damage to components of the limbic system (e.g., mammillary bodies, anterior thalamic nuclei) → atrophy of these components → memory loss, apathy, and disrupted emotional processing
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
- Other manifestations
Korsakoff syndrome (chronic, irreversible)
- 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
Wernicke's COAT: Confusion, Oculomotor dysfunction, Ataxia, and Thiamine administration (see Treatment section)
Korsakoff's CART: Confabulation, Anterograde and Retrograde amnesia, and altered Temper
Although often grouped together as a single syndrome (Wernicke-Korsakoff syndrome), the two conditions are distinct entities with different presentations, and, while both are due to severe chronic thiamine deficiency, Wernicke encephalopathy is reversible whereas Korsakoff syndrome is not.
- Usually a clinical diagnosis
- In ambiguous cases:
- Laboratory tests
- Brain MRI: T2-weighted hyperintense lesions in the mammillary bodies, midbrain tectal plate, dorsomedial nuclei of the thalamus, cerebellum, and around the aqueduct and the third ventricle
Laboratory tests or imaging should not delay treatment!
- Petechial lesions and small vessel hemorrhage in the mesencephalon, mammillary bodies, ventricle walls, and dorsomedial nucleus of thalamus
- Atrophy of anterior thalamic nuclei and mammillary bodies (both are part of the limbic system)
- Microscopic spongiosis, capillary proliferation, and hemosiderin deposits (due to recurrent bleeding)
- Wernicke encephalopathy (conditions that manifest with an acute onset of delirium/ataxia)
- Korsakoff syndrome (conditions that present with amnesia, disorientation)
The differential diagnoses listed here are not exhaustive.
- Immediate IV administration of high-dose vitamin B1/thiamine upon suspicion of Wernicke encephalopathy until symptoms recede, followed by a lower dose
- Thiamine must be administered before IV glucose infusions because glucose administration without thiamine can worsen encephalopathy.
- Long-term oral replacement of vitamin B1, vitamin B6, vitamin B12, and folic acid (vitamin B complex)
- Abstinence from alcohol
- Korsakoff syndrome