Wernicke Encephalopathy
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Wernicke Encephalopathy
Disease Entity
Disease
Wernicke Encephalopathy (WE) is an acute neurologic condition that occurs in the setting of a thiamine (vitamin B1) deficiency and is characterized by a triad of mental status changes, ophthalmoplegia/nystagmus, and gait ataxia. However, the full triad is not present in every case of WE. Inadequately treated, patients may progress to suffer from Korsakoff syndrome, leaving patients with permanent memory impairment.
Etiology
The neurologic deficits associated with WE are caused by an inadequate supply of the vitamin thiamine to the brain. The absence of thiamine as an enzymatic cofactor leads to decreased energy availability and subsequent neurotoxicity. This neurotoxicity manifests acutely as ophthalmoplegia/nystagmus, ataxia, and mental status changes.
Risk Factors
WE is most commonly associated with chronic alcoholism but can be precipitated by any state in which thiamine consumption or absorption is reduced (e.g., anorexia, malabsorption or gastrointestinal/bariatric surgeries, starvation, hyperemesis gravidarum, parenteral feedings without vitamin replacement, or gastric malignancies). There may be a genetic disposition for the development of WE.
Pathophysiology
Thiamine is a co-factor for key metabolic enzymes. These include alpha-ketoglutarate dehydrogenase (involved in the Krebs’ cycle), transketolase (involved in the pentose phosphate pathway), and pyruvate dehydrogenase (involved in creating acetyl-CoA from pyruvate to fuel the Krebs’ cycle). Collective dysfunction of these enzymes due to thiamine deficiency leads to failure of oxidative metabolism, an ATP shortage, and eventually selective neuronal death. Additionally, in chronic alcoholics, thiamine transport pathways are thought to be impaired. This exacerbates symptoms in the setting of a deficiency, and leads to a greater incidence of residual deficits, progression to Korsakoff syndrome, and higher thiamine replacement dosing requirements.
Pathology
On autopsy, lesions tend to surround the third ventricle, fourth ventricle, and cerebral aqueduct. The mamillary bodies are almost always involved, and other sites of lesions can include the dorsomedial thalamus, locus ceruleus, periaqueductal gray, oculomotor nuclei, and vestibular nuclei.
Primary prevention
The risk of WE can be reduced by reducing or discontinuing excess alcohol consumption, maintaining a balanced diet, and adequately replacing vitamins in the setting of an anticipated deficiency (e.g. parenteral feeds, GI surgery). Additionally, WE can be precipitated iatrogenically in patients who are already deficient in vitamin B1 but are in advertantly given glucose (e.g., to treat dehydration) prior to parenteral thiamine replacement in the hospital setting. Prevention under these circumstances requires administering thiamine prior to glucose administration if there is any suspicion at all of WE.
Diagnosis
Diagnosis of WE is usually clinical, though a thiamine blood level via erythrocyte thiamine transketolase (ETKA) testing and neuroimaging can be supportive. Many patients present without all three classic signs (mental status changes, ophthalmoplegia, ataxia), and patients should be suspected of having WE if any of the following are present. If two of the following four signs (Caine’s criteria) are present, the diagnosis is likely: Dietary thiamine deficiency, oculomotor abnormalities (nystagmus or ophthalmoplegia), cerebellar dysfunction (ataxia), or either altered mental status or mild memory impairment.
Signs
The clinical signs of WE include ophthalmoplegia, gait ataxia, nystagmus, or mental status changes. There may be physical exam findings of dehydration or malnourishment. In addition, stupor, hypothermia, hypotension, vestibular dysfunction, and peripheral neuropathy can also be seen.
Management
Patients with suspected WE should be immediately treated with high dose parenteral thiamine. Most authors have recommended very high dose initial replacement regimen (e.g., IV thiamine 500mg TID for 2 days followed by 250mg daily for 5 days via IV or intramuscular administration). Patients should then be maintained on oral therapy until they are no longer at risk for thiamine deficiency. Additionally, thiamine should be administered concurrently with magnesium, an important cofactor.
Prognosis
With prompt thiamine replacement, WE can be reversible, but residual deficits may occur if treatment is delayed or if the dose is inadequate. Unfortunately, if treatment is delayed, progression to Korsakoff syndrome with permanent anterograde amnesia frequently occurs. Progression to Korsakoff syndrome is also more common in alcoholics.
References
1. Galvin, R., Bråthen, G., Ivashynka, A., Hillbom, M., Tanasescu, R., & Leone, M. A. (2010). EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. European Journal of Neurology. https://doi.org/10.1111/j.1468-1331.2010.03153.x
2. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6: 442–455.
3. So YT, MD. Wernicke Encephalopathy. Aminoff M, MD, Wilterdink J, MD, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/wernicke-encephalopathy?search=wernicke&source=search_result&selectedTitle=1~48&usage_type=default&display_rank=1#H14 (Accessed on March 14, 2019.)
4. Thomson AD, Guerrini I, Marshall EJ. The evolution and treatment of Korsakoff's syndrome: out of sight, out of mind?. Neuropsychol Rev. 2012;22(2):81-92.
