Wernicke’s encephalopathy
Discuss WE?
WE is a reversible biochemical lesion of the CNS caused by overwhelming metabolic demands being made upon depleted B-vitamin reserves, in particular thiamine (B1). Although, usually associated with chronic alcoholism, WE can occur in the setting of poor nutrition caused by any other condition. It has been shown to occur in 12.5% of alcohol misusers. It is fatal in 17% of inappropriately managed patients. Permanent brain damage (Korsakoff’s psychosis) occurs in 85% of inappropriately managed survivors, 25% of whom require long-term institutionalisation.
Discuss the pathogenesis of WE?
- Caused by acute and severe CNS deficiency of thiamine (chronic def lead to Beri beri)
- Thiamine is a cofactor for several key enzymes important in energy metabolism and production of ATP
- Alcohol withdrawal causes CNS over activity leading to increased need for thiamine.
- Thiamine deficiency cause brain cell death by inhibiting metabolism in brain regions with high metabolic requirements and high thiamine turnover.
- WE may be precipitated in susceptible patients by administration of intravenous glucose before thiamine supplementation (glucose lead to utilisation of thiamine)
- Thiamine deficiency in alcohol abusers results from inadequate intake and reduced GI absorption. Thiamine absorption is significantly reduced in malnourished alcoholic abusers. Thus parenteral treatment is needed.
Discuss the clinical features of WE?
- Mental changes- confusion, disorientation, inattentiveness, drowsiness, obtundation, semi coma, coma. Mental changes are most common and may be the only sign of WE. These changes are however non specific and may be caused by alcohol intoxication or withdrawal.
- Oculomotor- nystagmus, lateral rectus palsy, conjugate gaze palsy
- Gait- wide based gait with small steps. When severe- walking may not be possible
- Hypotension and hypothermia
Discuss the diagnosis of WE?
- The classic triad of WE includes acute confusion, ataxia and ophthalmoplegia. However the triad is present in only 10% of patients with WE. Thus if the classic triad is used for diagnosis, WE will be missed or the diagnosis will be delayed till the classic triad becomes obvious.
- A high index of suspicion is therefore needed and the presence of only one sign should be sufficient to assign a diagnosis and commence treatment.
- Untreated WE- most patients progress to coma and death. IV thiamine is safe and effective. Thus treatment takes priority over diagnosis. Response to thiamine may be diagnostic.
- The diagnosis should be based on the presence of any one or more of the following signs:
- Acute confusion
- Decreased consciousness level including unconsciousness or coma
- Memory disturbance
- Ataxia/unsteadiness
- Ophthalmoplegia
- Nystagmus
- Unexplained hypotension with hypothermia.
Discuss treatment?
Treatment is required where WE is suspected or as prophylaxis in patients at high risk. All patients undergoing alcohol withdrawal or treatment for AWS should be treated prophylactically.
- Treatment of WE
- Oral B-vitamin replacement is both inadequate and ineffective owing to limited gastrointestinal absorption in alcohol misusers. Parenteral B-vitamin replacement is therefore required
- Dosage Pabrinex (2 ampoule pairs) tds for 2 – 3 days followed by:
- Pabrinex OD for 3 to 5 days
- Then Thiamine Oral 100mg TDS for 1 week then thiamine 100mg OD
- Multivitamin (One a day) OD
- Prophylaxis against WE
- Dosage Pabrinex OD for 3 to 5 days (each paired ampoule of pabrinex contains 250 mg of thiamine beside other vitamins)
- Then Thiamine Oral 100mg TDS for one week , then thiamine 100mg OD
- Multivitamin (One a day) OD
- There are no RCT to support any particular dosing regimen. However high doses are justified based on reports of failed clinical improvement in WE with low doses.
- 100mg OD of thiamine should be continued after discharge until patients are no longer considered at risk. (NB- dietary requirement of thiamine is only 1-2 mg daily)
- There is a small risk (1 in 1 million IV doses) of anaphylaxis with parenteral thiamine.
Discuss laboratory abnormalities in WE?
Atrophy of the mamillary bodies on MRI is a highly specific finding in WE and Korsakoff syndrome and is present in most cases and can be detected within a week of onset of WE.