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 syndrome is the late manifestation of the condition, where Wernicke's encephalopathy has not been adequately treated.
- Alcohol-related brain damage may contribute to between 10% and 24% of all cases of dementia.
- The incidence of the Korsakoff's syndrome has been reported to be rising in recent years.
- Prevalence rates are likely to be higher in areas of socio-economic deprivation and in those aged 50-60 years.
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 sensitive 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 those with uncomplicated alcoholism, are damaged in people with 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 six 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).
Any patient with alcohol misuse who presents with confusion, nausea and vomiting, fatigue, weakness or apathy should be considered at high risk of Wernicke's encephalopathy and treated appropriately. Unexplained hypotension or hypothermia should also heighten suspicion.
- 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.
- Anterograde amnesia is the main feature of the syndrome. This is loss of memory for events occurring after the onset of the disorder.
- Inability to learn and repeat simple pieces of information or learn new tasks.
- Often disorientated in time and place.
- Loss of memory for events before onset of the 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).
- 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 less sensitive than MRI. Diffusion-weighted imaging (an enhanced view based on local water diffusion properties) can improve MRI sensitivity.
Electroencephalography (EEG) may be required to rule out convulsive or non-convulsive status epilepticus.
- Peripheral neuropathy.
- Liver disease.
- Delirium tremens (around 10%).
- Beriberi (about 5%).
- A multidisciplinary service tailored to the needs of individual patients, including the management of alcohol abuse.
- Assessment and re-assessment of memory and intellectual impairment in the intermediate term.
- Flexible services ranging from specialised residential home care to domiciliary support should be available.
- Occupational therapy assessments of daily living and neuropsychological assessments of current cognitive function can help to determine whether the patient can go home and, if so, the nature and degree of help and supervision needed.
- The Mental Capacity Act and, on occasions, the Mental Health Act may have to be considered in the early stages of the syndrome.
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, which 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 either of the following applies:
- They are malnourished (or have a poor diet); prescribe oral thiamine 50 mg per day (as a single dose) for as long as malnutrition may be present.
- They have decompensated liver disease.
- 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 WKS due to alcohol abuse.However, more recent work states that the route of administration and dose depend on the severity of dependence and overall physical health of the patient.
- Although potentially serious allergic adverse reactions may (rarely) occur during, or shortly after, parenteral administration, the Commission on Human Medicines has recommended that:
- This should not preclude the use of parenteral thiamine in patients where this route of administration is required, particularly in patients at risk of WKS where treatment with thiamine is essential.
- IV administration should be by infusion over 30 minutes.
- Facilities for treating anaphylaxis (including resuscitation facilities) should be available when parenteral thiamine is administered.
A percentage of patients with Wernicke's encephalopathy develop Korsakoff's syndrome. Only 20% of such patients recover completely, and a significant number require long-term care.
One study suggested that the development of Korsakoff's syndrome may depend on the degree of alcohol-related neurotoxicity that occurs before thiamine prevention is instituted.
- Korsakoff's syndrome can develop in untreated or undertreated Wernicke's encephalopathy.
- 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 non-compliance or untreated secondary disease.
- Congestive heart failure may be a complication.
- Vertical nystagmus may resolve slowly, but fine horizontal nystagmus may persist indefinitely. Most other ocular symptoms resolve rapidly.
- Ataxia may persist and cause a slow shuffling gait.
- Global confusion state may be slow to resolve, and there may be persisting learning difficulties and memory impairment.
Wernicke's encephalopathy is a medical emergency. Untreated, it leads to death in up to 20% of cases, or to the Korsakoff's syndrome in 85% of survivors. Up to 25% of the Korsakoff group will require long-term institutionalisation.
- Alcohol avoidance.
- 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.
Further reading and references
Thomson AD, Guerrini I, Marshall EJ; The evolution and treatment of Korsakoff's syndrome: out of sight, out of mind? Neuropsychol Rev. 2012 Jun22(2):81-92. doi: 10.1007/s11065-012-9196-z. Epub 2012 May 9.
Thomson AD, Marshall EJ; The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol Alcohol. 2006 Mar-Apr41(2):151-8. Epub 2005 Dec 29.
Kopelman MD, Thomson AD, Guerrini I, et al; The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol Alcohol. 2009 Mar-Apr44(2):148-54. doi: 10.1093/alcalc/agn118. Epub 2009 Jan 16.
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 Sep27(6):951-61.
Inagaki T, Shimitzu Y, Tsubouchi K, et al; Korsakoff syndrome following chronic subdural hematoma. Gen Hosp Psychiatry. 2003 Sep-Oct25(5):364-6.
Aasheim ET; Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008 Nov248(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.
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 Oct26(9):2306-10.
Alcohol - problem drinking; NICE CKS, December 2011 (UK access only)
Day E, Bentham PW, Callaghan R, et al; Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev. 2013 Jul 17:CD004033. doi: 10.1002/14651858.CD004033.pub3.
Raistrick D et al; Review of the effectiveness of treatment for alcohol problems National Treatment Agency for Substance Misuse, 2006
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-Dec37(6):513-21.