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Korsakoff's Syndrome

This syndrome involves profound impairment of memory due to thiamine deficiency, most commonly due to long term alcohol abuse.

Epidemiology
Incidence 1/1000 population in US. A survey of new long-stay mental hospital patients in Scotland found that 9% had a diagnosis of alcohol-related brain damage, mainly Korsakoff's¹.

• Peak onset in males 40-59 years, females 30-49 years.
• Approximately 2% of alcohol abusers develop syndrome.
• Much greater risk in continuous rather than binge drinking.
• No racial predilection is observed.
• The condition affects males slightly more frequently than it affects females.

Pathogenesis Chronic alcohol consumption can result in thiamine deficiency by causing;

• inadequate nutritional thiamine intake
• decreased absorption of thiamine from the gastrointestinal tract
• impaired thiamine utilization in the cells.

People differ in their susceptibility to thiamine deficiency, however, and different brain regions also may be more or less sensitive to this condition²
Thiamine is a cofactor required by three enzymes involved in two pathways of carbohydrate metabolism. A reduction in thiamine can interfere with numerous cellular functions. Alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex, hypothalamus and cerebellum³. No change is found in basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of these regions which are normal in uncomplicated alcoholics are damaged in people with Wernicke-Korsakoff syndrome (WKS).

Chronic subdural haematoma has been documented as a cause of WKS. The symptoms persisted after resolution of the haematoma as a result of organic atrophic changes of both the frontal and temporal lobes due to long-term compression⁴.
It has also been reported following nutritional stress e.g. laparotomy for small bowel obstruction, followed by total parenteral nutrition for one month⁵, bariatric surgery or rapid weight-loss⁶.Other chronic conditions that may cause a thiamine deficiency include AIDS, Hyperemesis gravidarum, thyrotoxicosis, cancers that have spread throughout the body, long-term dialysis and congestive heart failure (when treated with long-term diuretic therapy).

Presentation
Symptoms

• Vision changes; Double vision; Eye movement abnormalities; Eyelid drooping.
• Loss of muscle coordination; Unsteady, uncoordinated walking.
• Loss of memory, can be profound.
• Inability to form new memories
• Hallucinations

Signs.

• Examination of the nervous system may show polyneuropathy
• Reflexes may be decreased (or of abnormal intensity), or abnormal reflexes may be present.
• Testing of gait and coordination.
• Muscles may be weak and may show atrophy.
• Eyes show abnormalities of movement.
• Blood pressure and body temperature may be low.
• Pulse may be rapid.
• The person may appear cachectic.

In addition there are the following cognitive features;

• Confabulation : falsification of memory in clear consciousness. Very characteristic of the syndrome. Can answer questions promptly with inaccurate and sometimes bizarre answer.
• Memory loss: anterograde amnesia is the main feature of syndrome. Loss of memory for events occurring after the onset of the disorder. Unable to learn and repeat simple pieces of information or learn new tasks. Often disorientated in time and place.
• Retrograde amnesia. Loss of memory for events before onset of disorder. Some memory of distant events may be preserved. Telescoping of events is characteristic e.g. says something happened recently when it took place many years ago.
• Patient usually mentally alert with vocabulary, comprehension, motor skills, social habits and naming ability maintained.

Differential Diagnosis

• Dementia
• cerebral ischaemia
• brain tumour

Investigations FBC, MCV, U&E's, liver function tests, urea, creatinine, glucose and cholesterol should be taken.

• Serum B1 levels may be low.
• Pyruvate is elevated.
• Red cell Transketolase activity is decreased.
• If the history is significant for chronic (long-term) alcohol abuse, serum or urine alcohol levels may be elevated.

Associated Diseases

• Wernicke's encephalopathy
• peripheral neuropathy
• paraesthesia
• malnutrition
• liver disease
• delirium tremens (around 10%)
• beriberi (about 5%)

Management

Non-Drug Address problem of alcohol abuse and diet.

Drugs

• Thiamine IM or IV plus vitamin B complex or multi-vitamins. Some improvement in 50-75% of cases, complete remission in 20%⁷. A Cochrane Review found there was insufficient evidence from randomized controlled clinical trials to guide clinicians in the dose, frequency, route or duration of thiamine treatment of WKS due to alcohol abuse⁸. Although one randomised controlled trial showed a significant difference in favour of the 200mg/day compared with the 5 mg/day dose.
• The CSM (1989) has advised that there is a small risk of serious allergic (anaphylactic) reactions occurring during or shortly after the administration of parenteral thiamine. It recommends that use is restricted to people in whom parenteral treatment is essential; Intravenous injections are given slowly, over 10 minutes; and that facilities for treating anaphylaxis should be available when it is administered.
• Memantine, a NMDA antagonist,(10 mg) has been reported as safe and well tolerated in small clinical trials. The preliminarily findings of a study with 16 patients suggested that memantine was effective in the treatment of dementia in Wernicke-Korsakoff syndrome. A mini mental state examination demonstrated a significant and clinically relevant benefit for memantine relative to placebo⁹.

Prognosis The mortality rate is 10-20%. Prognosis depends on the stage of disease at presentation and on prompt treatment.

• Full recovery of ocular function generally occurs.
• Fine horizontal nystagmus can persist in as many as 60% of cases.
• Approximately 40% of patients have complete recovery from ataxia.
• Only 20% of patients recover completely from amnestic deficit.

With co-existing Wernicke's encephalopathy death occurs in 10-15% within 3 weeks and less than 50% within 3 years.

Prevention

• Vitamins
• alcohol avoidance

References Used

1. Smith ID, Flanigan C. Korsakoff's psychosis in Scotland: evidence for increased prevalence and regional variation. Alcohol Alcohol Suppl. 2000 May-Jun;35(1):8-10.
2. Martin PR, Singleton CK, Hiller-Sturmhofel S.: The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003;27(2):134-42.
3. Harper C, Dixon G, Sheedy D, Garrick T.: Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):951-61.
4. Inagaki T, Shimitzu Y, Tsubouchi K et al. Korsakoff syndrome following chronic subdural hematoma.Gen Hosp Psychiatry. 2003 Sep-Oct;25(5):364-6.
5. Deb S, Law-Min R, Fearnley D. Wernicke-Korsakoff syndrome following small bowel obstruction. Behav Neurol. 2001-2002;13(3-4):89-94.
6. Chaves LC, Faintuch J, Kahwage S, et al; A cluster of polyneuropathy and Wernicke-Korsakoff syndrome in a bariatric unit.;Obes Surg. 2002 Jun;12(3):328-34.[abstract]
7. Cook CC, Thomson AD; B-complex vitamins in the prophylaxis and treatment of Wernicke-Korsakoff syndrome.;Br J Hosp Med 1997 May 7-20;57(9):461-5.[abstract]
8. Day E, Bentham P, Callaghan R, et al; Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse.;Cochrane Database Syst Rev. 2004;(1):CD004033.[abstract]
9. Rustembegovic A, Kundurovic Z, Sapcanin A, et al; A placebo-controlled study of memantine (Ebixa) in dementia of Wernicke-Korsakoff syndrome.;Med Arh. 2003;57(3):149-50.[abstract]

Internet and Further Reading

• Prodigy Guidance; Problem drinking.
• DeAngelo A, Halliday A; Wernike-Korsakoff syndrome. eMedicine (2002)

Acknowledgements EMIS is grateful to Dr Hayley Willacy for rewriting this article. The final copy has passed peer review of the independent Mentor GP authoring team. ©EMIS 2006.

Last issued 05 Jul 2006