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Wernicke-Korsakoff syndrome (WKS) is a spectrum of disease resulting from thiamine deficiency, usually related to alcohol abuse. Wernicke's encephalopathy was originally described by German neurologist Karl Wernicke in 1881 as a classic triad of symptoms (mental confusion, ataxia and ophthalmoplegia). Korsakoff's psychosis is the late manifestation of the condition, where Wernicke's encephalopathy has not been adequately treated.
- 1/1,000 population worldwide.
- A survey of new long-stay mental hospital patients in Scotland found that 9% had a diagnosis of alcohol-related brain damage.
- Peak onset is seen in males aged 40-59 years and in females aged 30-49 years.
- Approximately 2% of alcohol abusers develop the syndrome.
- There is 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.
Chronic alcohol consumption can result in thiamine deficiency by causing:
- Inadequate nutritional thiamine intake.
- Decreased absorption of thiamine from the gastrointestinal tract.
- Impaired thiamine utilisation 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 condition.
Thiamine is a cofactor required by three enzymes in 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 cerebellum.
- 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 compression.
It has also been reported following nutritional stress, eg laparotomy for small bowel obstruction, followed by total parenteral nutrition for one month, bariatric surgery or rapid weight-loss. Follow-up of thiamine status for at least 6 months after bariatric surgery is recommended.
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).
- Vision changes:
- Double vision
- Eye movement abnormalities
- Eyelid drooping
- Loss of muscle co-ordination:
- Unsteady, unco-ordinated walking
- Loss of memory, which can be profound.
- Inability to form new memories.
The patient is usually mentally alert with vocabulary, comprehension, motor skills, social habits and naming ability maintained.
- Examination of the nervous system may show polyneuropathy.
- Reflexes may be decreased (or of abnormal intensity), or abnormal reflexes may be present.
- Gait and co-ordination are abnormal on testing.
- Muscles may be weak and may show atrophy.
- Eyes show abnormalities of movement - nystagmus, bilateral lateral rectus palsy and conjugate gaze palsy.
- 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:
- Falsification of memory in clear consciousness.
- Very characteristic of the syndrome.
- Can answer questions promptly with inaccurate and sometimes bizarre answers.
- Memory loss:
- Anterograde amnesia is the main feature of syndrome.
- This is 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, eg the patient says something happened recently when it took place many years ago.
At least two of the four following criteria should be present to diagnose encephalopathy:
- Dietary deficiencies.
- Oculomotor abnormalities.
- Cerebellar dysfunction.
- Either an altered mental state or mild memory impairment.
Subclinical episodes can occur.
- Drug abuse
- Alcoholic ketoacidosis
- Delirium tremens
- Chronic hypoxia
- Closed head injury
- Hepatic encephalopathy
- Post-ictal state
- Cerebrovascular disease
- Brain tumour
Diagnosis is based mainly on the history and physical examination, and if the condition is suspected, treatment should not be delayed whilst waiting for test results.
- FBC, particularly looking at the MCV.
- U&Es (to exclude hypernatraemia, hypercalcaemia, and uraemia).
- Liver function tests.
- Blood arterial gases (to rule out hypercarbia and hypoxia).
- Serum thiamine levels (Vitamin B1) levels may be low.
- Pyruvate is elevated.
- Red cell transketolase activity is decreased in thiamine deficiency, but not usually necessary to diagnose the condition.
- Lumbar puncture may be needed to exclude nonfocal CNS infections.
If the history is significant for chronic (long-term) alcohol abuse, serum or urine alcohol levels may be elevated.
CT head scan may be useful in the acute phase, but is likely to be less sensitive than MRI. Diffusion-weighted imaging (an enhanced view based on local water diffusion properties) can improve MRI sensitivity.
- Peripheral neuropathy
- Liver disease
- Delirium tremens (around 10%)
- Beriberi (about 5%)
Address the problem of alcohol abuse and diet. Treat as a medical emergency if symptoms are acute. Patients presenting with altered mental state or pre-coma may need oxygen and intravenous rehydration. Comatose patients may require intubation to maintain airway patency.
- Thiamine orally (IM or IV may be used in secondary care) plus vitamin B complex or multivitamins should be given indefinitely. Treatment with thiamine is often started under specialist care, although when deficiency is suspected, it should be started in primary care.
- Offer oral thiamine to harmful or dependent drinkers if any of the following apply:
- They are malnourished (or have a poor diet).
- They have decompensated liver disease.
- They are in acute withdrawal.
- Medically-assisted alcohol withdrawal is planned.
- If the person is in reasonable health with an adequate diet:
- Prescribe oral thiamine 200-300 mg per day (in divided doses) while they are undergoing assisted withdrawal, or are drinking very excessively.
- Prescribe oral thiamine 50 mg per day (as a single dose) during the maintenance stage following withdrawal, and for as long as malnutrition may be present.
- Some improvement has been seen in 50-75% of cases after starting thiamine, with complete remission in 20%.
- A Cochrane review found there was insufficient evidence from randomised controlled clinical trials to guide clinicians in the dose, frequency, route or duration of thiamine treatment of Wernicke-Korsakoff syndrome (WKS) due to alcohol abuse. However, more recent work states that the route of administration and dose depends on the severity of dependence and overall physical health of the patient.
- The Committee on Safety of Medicines (CSM) advised (1989) 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 be restricted to people in whom parenteral treatment is essential.
- IV injections should be given slowly, over 10 minutes.
- Facilities for treating anaphylaxis should be available when it is administered.
- The magnesium level should be checked and corrected if low, as this can prevent the therapeutic effects of parenteral thiamine.
- Memantine, an N-methyl-D-aspartate (NMDA) antagonist, (10 mg) has been reported as safe and well tolerated in small clinical trials:
A percentage of patients with Wernicke's encephalopathy develop Korsakoff's psychosis. Only 20% of such patients recover completely, and a significant number require long-term care.
One study suggested that the development of Korsakoff's psychosis may depend on the degree of alcohol-related neurotoxicity that occurs before thiamine prevention is instituted.
- Korsakoff's psychosis can develop in untreated or undertreated Wernicke's encephalopathy. One study in Glasgow found an increase in incidence which was thought to be related to a reduction by physicians in the use of parenteral thiamine after the CSM warning.
- Symptoms of alcohol withdrawal syndrome (tremors, hallucinations, convulsions) can complicate the picture.
- Recurrence of encephalopathy can recur in patients who continue to drink alcohol and fail to maintain their thiamine intake, and in non-alcoholics with persisting thiamine deficiency due to noncompliance or untreated secondary disease.
- Congestive heart failure may be a complication and appears to be related to intracellular oedema and fibrosis of the cardiac muscle.
- Vertical nystagmus may resolve slowly, but fine horizontal nystagmus may persist indefinitely in up to 60% of cases. Most other ocular symptoms resolve rapidly.
- Ataxia may persist in 40% of patients, who continue to suffer from a slow shuffling gait.
- Global confusion state may be slow to resolve, and there may be persisting learning difficulties and memory impairment.
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.
The mortality rate is 10-20% in Wernicke-Korsakoff syndrome (WKS).
Patients with significant alcohol dependency should be given thiamine supplementation. Identifying which patients are at risk is not always easy, but retrospective studies suggest that homeless patients with inadequate social support are at greatest risk. Institution of adequate discharge and follow-up arrangements for such individuals may be as important as thiamine replacement.
- Alcohol avoidance
Further reading & references
- Drinking, Office for National Statistics, November 2006
- Links to documents on alcohol, Dept of Health
- Thomson AD, Marshall EJ; The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol. 2006 Mar-Apr;41(2):151-8. Epub 2005 Dec 29.
- Harper C, Fornes P, Duyckaerts C, et al; An international perspective on the prevalence of the Wernicke-Korsakoff Metab Brain Dis. 1995 Mar;10(1):17-24.
- 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.
- Martin PR, Singleton CK, Hiller-Sturmhofel S; The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003;27(2):134-42.
- Harper C, Dixon G, Sheedy D, et al; 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.
- Inagaki T, Shimitzu Y, Tsubouchi K, et al; Korsakoff syndrome following chronic subdural hematoma. Gen Hosp Psychiatry. 2003 Sep-Oct;25(5):364-6.
- Deb S, Law-Min R, Fearnley D; Wernicke-Korsakoff syndrome following small bowel obstruction. Behav Neurol. 2001-2002;13(3-4):89-94.
- Aasheim ET; Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008 Nov;248(5):714-20.
- Galvin R, Brathen G, Ivashynka A, et al; EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Jul 19.
- Hope LC, Cook CC, Thomson AD; A survey of the current clinical practice of psychiatrists and accident and emergency specialists in the United Kingdom concerning vitamin supplementation for chronic alcohol misusers. Alcohol Alcohol. 1999 Nov-Dec;34(6):862-7.
- Escobar A, Aruffo C, Rodriguez-Carbajal J; Wernicke's encephalopathy. A case report with neurophysiologic and CT-scan studies. Acta Vitaminol Enzymol. 1983;5(2):125-31.
- Antunez E, Estruch R, Cardenal C, et al; Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's encephalopathy. AJR Am J Roentgenol. 1998 Oct;171(4):1131-7.
- White ML, Zhang Y, Andrew LG, et al; MR imaging with diffusion-weighted imaging in acute and chronic Wernicke encephalopathy. AJNR Am J Neuroradiol. 2005 Oct;26(9):2306-10.
- Salen P; Wernicke's Encephalopathy. eMedicine, May 2010.
- Alcohol - problem drinking, Clinical Knowledge Summaries (September 2010)
- 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.
- 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.
- Raistrick, D., Heather, N. and Godfrey, C. (2006) Review of the effectiveness of treatment for alcohol problems. National Treatment Agency for Substance Misuse.
- 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.
- Xiong GL et al; Wernicke-Korsakoff Syndrome, eMedicine, Nov 2009
- Ramayya A, Jauhar P; Increasing incidence of Korsakoff's psychosis in the east end of Glasgow. Alcohol Alcohol. 1997 May-Jun;32(3):281-5.
- Ikram H, Maslowski AH, Smith BL, et al; The haemodynamic, histopathological and hormonal features of alcoholic cardiac beriberi. Q J Med. 1981 Autumn;50(200):359-75.
- Thomson AD, Cook CC, Touquet R, et al; The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department. Alcohol Alcohol. 2002 Nov-Dec;37(6):513-21.
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Dr Laurence Knott
Dr Hayley Willacy