Wernicke Encephalopathy and Korsakoff Syndrome

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 encephalopathy (WE), and Korsakoff’s amnesia (KA), hence the combined name Wernicke-Korsakoff Syndrome.

• The prevalence is estimated to be up to 2% among the general population and as high as 12.5% in patients with alcohol use disorders.^[1]
• Autopsy studies indicate that Wernicke is frequently undiagnosed during life, and is first diagnosed postmortem in over 80% of case.^[2][3]

• Wernicke encephalopathy is an acute presentation that when identified and treated in a timely manner, can lead to quick improvement of symptoms.
  • Failure to diagnose and treat Wernicke encephalopathy can result in death in up to 20% of patients
• If untreated, up to 75% may develop Korsakoff syndrome (irreversible cognitive impairment), and the chance of full recovery is low^[4] (but not impossible^[5]).
  • Wernicke-Korsakoff syndrome thus is sometimes referred to as alcoholic dementia or alcohol-related dementia.

• Alcohol use disorder is highly common.
  • In industrialized countries, 90% of the cases of thiamine deficiency are associated with alcohol use disorder.^[6]
  • However! This is not a disease that affects only alcohol users, most cases of missed WKS are in those without an alcohol misuse history.
• Thiamine deficiency also presents in several syndromes other than Wernicke’s encephalopathy, including cardiac beriberi, neuropathic beriberi.

• Alcohol use disorder, cancer patients,^[7] gastrointestinal surgery (e.g. - bariatric, gastric bypass), hyperemesis gravidarum, and starvation/fasting are risk factors.^[8]

• Wernicke encephalopathy may be overlooked in 68% of patients with alcoholism and 94% of patients without alcoholism (e.g. - cancer patients).^[9][10]

WKS is a clinical diagnosis. Although often described as a triad (oculomotor abnormalities, cerebellar dysfunction, and an altered mental state) in the classic literature, it is rare for all three clinical signs to be present. ^[11] Less than 16% of individuals with WKS will have all three signs. Neuroimaging findings may help in confirming the diagnosis but it is not diagnostic.

In 1997, Caine et al. proposed that a diagnosis can be made when patients have any 2 of the following 4 features:^[12]

1. Nutritional deficiency
2. Ocular signs
3. Cerebellar signs
4. Altered mental status or mild memory impairment

• A dramatic improvement of neurologic signs often indicates adequate treatment and confirms the clinical diagnosis of Wernicke encephalopathy.^[13]

Classically, Wernicke encephalopathy is an acute presentation, while Korsakoff syndrome is a late, chronic manifestation of Wernicke encephalopathy that typically presents as anterograde and retrograde amnesia with preserved long-term memory.

• The daily thiamine requirement for healthy individuals is between 1 and 2 mg per day, and is related to overall carbohydrate intake.
  • The thiamine requirement increases with alcohol misuse.
  • There are several mechanisms behind this, including inadequate dietary intake, malabsorption of thiamine from the gastrointestinal tract due to alcohol’s effects, and impaired utilization of thiamine in the cells.
• Since the body stores are only between 30 and 50 mg of thiamine, it is estimated that this store is depleted in 4–6 weeks.^[14]

• Other medical issues resulting in thiamine deficiency
  • 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^[15] undergoing chemotherapy.
• Delirium
  • Confusion and memory impairment may be due to delirium
• Traumatic brain injury
  • There is a risk of the Wernicke being missed in patients with acute head injury. A history of alcohol use may not be available, and the signs and symptoms of Wernicke encephalopathy may be misattributed to the head injury.^[16]
• Alcohol-induced psychosis
• Neurodegenerative disorders

• B12, thiamine (not all laboratories may have thiamine available)
• CBC, electrolytes, creatinine, GGT (indicator of acute liver injury from alcohol use, for individuals drinking > 4 drinks/day), AST, ALT, ALP, GGT
• Elevated AST/ALT ratio may be suggestive of alcoholic liver disease.^[17]
• INR

• Nystagmus and ophthalmoplegia are the most common ocular findings in Wernicke.^[18]
• 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).

• MRI brain may show mammillary body atrophy, volume loss in the thalamus, volume loss in the corpus callosum.
  • Lesions from Wernicke are characterized by petechial hemorrhages and can be often found with a symmetrical distribution around the cerebral aqueduct, third ventricle, and fourth ventricle.^[19]
• CT head are unfortunately poor at identifying mammillary body lesions and thus not recommended.^[20]

Thiamine resupplementation is the primary treatment. Oculomotor deficits should resolve over hours to days, while cognitive impairment may resolve within days to weeks. Most patients will exhibit some residual deficits.^[21]

• Treatment is with intravenous thiamine therapy, but the optimum dosage remains controversial.^[22] Some clinicians base dosing from a study published by Cook et al. in 1998, which recommended up to 1 g of thiamine daily to achieve a clinical response.^[23][24][25]
• In individuals with suspected clinical signs of Wernicke, they should be prescribed thiamine 500mg IV x 3 days (some may prescribe as high as 500mg TID), followed by 250mg IV x 3 days (some may prescribe as high as 250mg TID) followed by oral supplementation 100mg PO daily.^[26]
  • A significant improvement in neurologic symptoms or cognitive function helps confirm the diagnosis.
• Most patients should thereafter have indefinite oral thiamine supplementation (i.e. - 100 mg thiamine daily) until there is resolution of their nutritional compromise.^[27]

• Remember that oral thiamine is difficult to absorb, so even for individuals with adequate oral intake, IV administration is recommended. In individuals with gut absorption changes (e.g. - bariatric surgery), IV supplementation is a must.
  • It could also be argued that in general, the oral doses of thiamine are so low, and that is that it would provide a negligible effect on symptoms.
• In situations where IV thiamine is not available, thiamine 300mg PO TID could be prescribed.
• In 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.^[28]

• EM Resident: Detecting Wernicke-Korsakoff Syndrome
• Day, G. S., & Del Campo, C. M. (2014). Wernicke encephalopathy: a medical emergency. Cmaj, 186(8), E295-E295.
• Thomson, A. D., Guerrini, I., & Marshall, E. J. (2012). The evolution and treatment of Korsakoff's syndrome. Neuropsychology review, 22(2), 81-92.
• Day, E. et al. (2013). Thiamine for prevention and treatment of Wernicke‐Korsakoff Syndrome in people who abuse alcohol. Cochrane Database of Systematic Reviews, (7).