Wernicke's Encephalopathy

Wernicke’s encephalopathy (WE) is a neuropsychiatric disorder which arises as a result of thiamine deficiency. In 80% of cases, the diagnosis is not made clinically prior to autopsy and inadequate treatment can leave the patient with permanent neurological sequelae and can possibly lead to Korsakoff syndrome. Therefore over-dignosis is preferred over under-diagnosis. Just like several other disease entities, Wernicke’s encephalopathy can be precipitated by other clinical diseases such as sepsis. 

Many physicians consider this only restricted to alcoholics which is not the case. Especially among non-alcoholics, the diagnosis is missed. 

WE is a result of thiamine deficiency, which can occur in ANY nutritionally deficient state. 

Classic Triad

The classic clinical triad of Wernicke’s encephalopathy consists of mental status changes, ophthalmoplegia, and gait ataxia. Complete triad is present only in about 10% cases. Other signs of disease such as hypothermia, vestibular dysfunction, and other ocular abnormalities can be present. Out of the eye signs, nystagmus is the most common ocular abnormality, not complete ophthalmoplegia. 

Reliance on the presence of the clinical triad as the sole criterion for disease is often inadequate and may lead to under diagnosis.

Risk Factors for WE:

• Alcohol Abuse (inadequate dietary intake, reduced GI absorption, and decreased hepatic storage)
• AIDS
• Malignancy
• Hyperemesis Gravidarum
• Post Surgical Patients
• Post Gastric Bypass

Thiamine Deficiency Syndromes

Why thiamine is so important?

Thiamine is a cofactor for several essential enzymes. Because thiamine-dependent enzymes play an important role in cerebral energy use, deficiency may initiate tissue injury by inhibiting metabolism in brain regions with high metabolic requirements. A decrease in their activity may lead to increased buildup of toxic intermediates. Lactate accumulation occurs both in the brain and serum because pyruvate cannot enter the Krebs cycle. 

Malnutrition + elevated lactate - Think thiamine deficiency

CNS lesions

The lesions of Wernicke’s encephalopathy occur in a symmetrical distribution in structures surrounding the third ventricle, aqueduct, and fourth ventricle. MRI is the imaging of choice. The mammillary bodies are involved in up to 80% of cases; atrophy of these structures is specific for Wernicke’s encephalopathy. However, empiric treatment is a norm in ED. 

Korsakoff Syndrome
Korsakoff syndrome refers to a persistent state of mental dysfunction characterized by memory impairment associated with confabulation. 

Differential Diagnosis

• Intracranial Hemmorhage
• Stroke
• Cerebral Venous Thrombosis
• Delirium Tremens
• Hepatic Encephalopathy
• Intracranial Space Occupying Lesions
• Cerebellar Disease
• Meningitis
• Marchiafava-Bignami disease (demyelination of the corpus callous due to nutritional deficiencies)

Treatment

Low suspicion of disease - a minimum of 100 mg IV
Highly suspected disease - 500 mg IV

Administration of thiamine improves disease to some degree in almost all cases; however, persistent neurologic dysfunction is common. 

All patients presumed to have Wernicke’s Encephalopathy or at risk of developing Wernicke’s Encephalopathy should receive two pairs* of vials of Pabrinex in 100 ml of crystalloid i.v. over 30 minutes initially in A&E.

*(1 pair = ampoule 1 + ampoule 2). Pabrinex is available as 5ml or 10ml pairs of ampoules. 

IV thrice daily dosing is generally continued for 3-5 days for an established diagnosis and then oral Thiamine 100mg OD is continued for a month. On extremely rare occasions, Thiamine may cause allergic reactions and anaphylaxis. 

Glucose before thiamine Myth!

Iatrogenic exacerbation of Wernicke’s encephalopathy can occur with prolonged glucose or carbohydrate loading in the absence of adequate thiamine. A single acute administration of glucose does not appear to cause this effect. Urgent administration of glucose should not be withheld pending thiamine administration. 


IV Fluids to sober them up?
There is no evidence that intravenous fluids expedite sobriety in patients with acute alcohol intoxication. Read more on REBELEM and St.Emlyn's. 


References:

1. Reuler JB, Girard DE, Cooney TG. Current concepts. Wernicke’s encephalopathy. N Engl J Med. 1985;312:1035-1039.
2. Watson AJ, Walker JF, Tomkin GH, et al. Acute Wernicke’s encephalopathy precipitated by glucose loading. Ir J Med Sci. 1981;150:301-303.
3. Zimitat C, Nixon PF. Glucose loading precipitates acute encephalopathy in thiamin-deficient rats. Metab Brain Dis. 1999; 14:1-20.
4. Zimitat C, Nixon PF. Glucose induced IEG expression in the thiamin-deficient rat brain. Brain Res. 2001;892:218-227. 59. Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA. 1998;279:583-584. 
5. https://www.medicines.org.uk/emc/medicine/6571
6. Donnino MW, Vega J, Miller J, Walsh M. Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know. Annals of emergency medicine. 2007 Dec 31;50(6):715-21.

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic