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31st January 2024
Wernicke’s encephalopathy and Korsakoff’s syndrome
Background
These are both syndromes caused by thiamine deficiency as a side effect of long-term excessive alcohol consumption, which impedes the absorption and storage of consumed thiamine. Wernicke’s encephalopathy is an acute neurological disorder, whereas Korsakoff’s is a neuropsychiatric syndrome. If left untreated, Korsakoff’s syndrome can develop in a patient already diagnosed with Wernicke’s. Other conditions which can cause Korsakoff’s syndrome include AIDS and certain cancers; however, alcohol is recognised as the most common cause of the syndrome to date.
Thiamine is required for effective brain cell biochemical metabolism, particularly pyruvate metabolism – a deficiency of thiamine disrupts these necessary metabolic processes, which can cause neuronal atrophy, scar tissue formation and microscopic haemorrhages, resulting in cognitive impairment.
Presentation
The table below demonstrates the symptoms and signs seen in Wernicke’s encephalopathy and Korsakoff’s syndrome:
| Wernicke’s encephalopathy | Korsakoff’s syndrome |
|---|---|
| Acute confusion | Anterograde and/or retrograde amnesia |
| Ataxic gait | Confabulation |
| Ophthalmoplegia | Visual hallucinations |
Source: Adapted from: Vasan S, Kumar A. Wernicke encephalopathy – statpearls – NCBI bookshelf [Internet]. Wernicke encephalopathy. 2022 [cited 2022Dec3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470344/ and Alzheimer’s Association. Korsakoff syndrome [Internet]. Alzheimer’s Disease and Dementia. 2022 [cited 2022Dec3]. Available from: https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/korsakoff-syndrome
Diagnosis
Both are primarily clinical diagnoses; therefore, a thorough history and examination are required to rule out other causes of the symptoms first. Imaging and lumbar puncture for CSF fluid may help identify alternate diagnoses if clinically indicated but cannot be used to diagnose Wernicke’s.
Differential diagnoses
Other causes of acute confusion hallucinations, and gait disturbance (such as delirium, primary psychiatric disorders, other substance abuse and neurological conditions) could all be differential diagnoses for either of the above presentations and must be considered during the investigation stage.
Management
Established Wernicke’s encephalopathy
Pabrinex (B vitamins including thiamine with ascorbic acid) given intravenously (IV) is required to treat Wernicke’s encephalopathy – oral thiamine is only suitable for long-term maintenance in those who are alcohol-dependent. The BNF current dosing guidelines recommends two to three pairs of Pabrinex three times a day for up to five days as treatment for established Wernicke’s encephalopathy.
Prophylaxis of Wernicke’s encephalopathy
Prophylaxis dose is 1 pair once a day intramuscularly (IM) for 5-7 days. Dose reduction can be used after this period, but oral preparations of thiamine are not suitable as an acute treatment. Literature suggests Korsakoff’s syndrome should also be treated with the same dosing of IV Pabrinex; however, the effects of this condition are often more chronic, and for some, long-term care provision is often needed, alongside standard oral thiamine maintenance. Physiotherapy and support with alcohol abstinence are also often required.
Medications to support abstinence
Those who successfully manage to abstain from alcohol may be offered additional medication to help them remain sober long-term. NICE guidance currently advises use of either acamprosate (1st line), naltrexone (alternative 1st line, not if concomitant opioid use) or, if needed, disulfiram. These treatments are summarised in the table below:
| Medication | Indication | Cautions/contraindications |
|---|---|---|
| Acamprosate | 1st line for reducing alcohol cravings. It can be taken for up to 6 months or longer if helpful to aid abstinence. Can cause abdominal pain, nausea, and diarrhoea. It should be discontinued if alcohol consumption continues for up to 6 weeks after starting the medication. | Cannot be given to those with severe hepatic or renal impairment or those breastfeeding. Advised to avoid in pregnancy unless necessary. |
| Naltrexone | Also 1st line – it is an opioid-receptor antagonist, so stops opioid-based analgesia from working effectively and reduces alcohol cravings. | Cannot be given to those who are currently opioid dependents, advised to avoid during breastfeeding and in severe hepatic impairment. Reduced dosing may be needed in renal impairment. Advised to avoid in pregnancy unless necessary. |
| Disulfiram | 2nd line – blocks the metabolism of alcohol after consumption. Usually started 1 day or more after the last alcoholic drink. It reacts with alcohol and causes nausea, flushing and dizziness, which is designed to discourage further alcohol intake. | Cannot be used in those with active cardiovascular disease, prior stroke, hypertension, or psychosis. Should be avoided in the first trimester as acetaldehyde (the metabolite of alcohol breakdown) may be a teratogen. |
Source: Adapted from: NICE. Disulfiram [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://bnf.nice.org.uk/drugs/disulfiram/#indications-and-dose, NICE. Alcohol problem drinking: Acamprosate [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://cks.nice.org.uk/topics/alcohol-problem-drinking/prescribing-information/acamprosate/ and NICE. Naltrexone hydrochloride [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://bnf.nice.org.uk/drugs/naltrexone-hydrochloride/#drug-action
References
- Alzheimer’s Association. Korsakoff syndrome [Internet]. Alzheimer’s Disease and Dementia. 2022 [cited 2022Dec3]. Available from: https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/korsakoff-syndrome
- NICE. Alcohol problem drinking: Acamprosate [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://cks.nice.org.uk/topics/alcohol-problem-drinking/prescribing-information/acamprosate/
- NICE. Naltrexone hydrochloride [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://bnf.nice.org.uk/drugs/naltrexone-hydrochloride/#drug-action
- NICE. Recommendations: Alcohol-use disorders: Diagnosis and management of physical complications: Guidance [Internet]. NICE. 2017 [cited 2022Dec3]. Available from: https://www.nice.org.uk/guidance/cg100/chapter/Recommendations
- Vasan S, Kumar A. Wernicke encephalopathy – statpearls – NCBI bookshelf [Internet]. Wernicke encephalopathy. 2022 [cited 2022Dec3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470344/
- NICE. Disulfiram [Internet]. NICE. 2022 [cited 2022Dec3]. Available from: https://bnf.nice.org.uk/drugs/disulfiram/#indications-and-dose
- NICE. Vitamin B substances with ascorbic acid [Internet]. NICE 2022 [cited 2022Dec3]. Available from: https://bnf.nice.org.uk/drugs/vitamin-b-substances-with-ascorbic-acid/#constituent-drugs
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