Wernicke syndrome is an acute neuropsychiatric disorder characterized by the classic triad of ophthalmoplegia, ataxia, and disturbances of mental activity or consciousness due to a deficiency of thiamine often associated with chronic alcoholism or other causes of malnutrition or decreased GI absorption such as gastric bypass or other GI surgery.

Wernicke encephalopathy (WE)

Gayet-Wernicke encephalopathy

Cerebral beriberi

Wernicke superior hemorrhagic polioencephalitis

Wernicke-Korsakoff syndrome

• A higher prevalence of WE noted on autopsy studies (0.4% to 2.8%) compared with clinical studies (0.04% to 0.13%)^1-3

• WE is a clinical diagnosis with a classic triad of ophthalmoplegia, ataxia, and altered mental status, although this full triad is only seen in 16% of all patients and 20% display none of these symptoms.^1-3
• Eye movement abnormalities include nystagmus, external rectus palsies, and reduced conjugate gaze.
• Ophthalmoscopic findings include swelling of the optic discs and retinal hemorrhages.
• Ataxia of gait or truncal ataxia.
• Clinical suspicion must remain high in patients with risk factors listed earlier, especially in the setting of poor nutrition, even without the classic triad. Severe vomiting and weight loss should raise suspicions.²
• Diagnosis is confirmed by improvement of neurologic signs after administration of parenteral thiamine.
• Laboratory tests and radiologic studies may aid diagnosis, but these should not delay a trial of parenteral administration of thiamine.

• The biologically active form of vitamin B₁, thiamine pyrophosphate (TP), is a coenzyme for several important biochemical pathways involved in energy production, lipid metabolism, and production of amino acids and glucose-derived neurotransmitters.
• Body’s reserve for thiamine is sufficient for 18 days.
• Malnutrition for more than 2 to 3 wk or a diet disproportionately high in carbohydrates and low in thiamine intake can lead to an impaired function of enzymes requiring TP.

• Other acute encephalopathies (Table E1)
• Paramedian thalamic infarction
• Ventriculoencephalitis, paraneoplastic encephalitis, herpes simplex encephalitis
• Miller-Fisher syndrome
• Primary central nervous system lymphoma
• Multiple sclerosis, Behçet disease, Leigh disease
• Variant Creutzfeldt-Jakob disease

• WE is a clinical diagnosis based on the triad of features listed previously, though the full triad is rarely seen. A high level of suspicion is required.
• Laboratory tests and radiologic studies as listed in the following section may be obtained to confirm diagnosis.

• Do not hold thiamine treatment for the results of blood tests or imaging when there is clinical suspicion
• Blood thiamine concentration
• Serum magnesium concentration (depletion of magnesium may mimic features of WE)
• Optionally, functional measurement of erythrocyte thiamine transketolase (ETKA) before and after administration of parenteral thiamine. A diagnosis may be confirmed if ETKA is low followed by a 25% increase after thiamine supplementation¹
• Optionally, high-performance liquid chromatography for assessment of thiamine, thiamine monophosphate, and diphosphate in human erythrocytes

MRI of the brain may show bilaterally symmetric increase in T2 signal at the paraventricular regions of the thalamus and mammillary bodies. Petechial hemorrhage or diffuse restriction can be seen.⁴ Other areas of increased signal include hypothalamus, periaqueductal region, floor of the fourth ventricle, and midline cerebellum.

• Treatment should be initiated in all patients with clinical suspicion of WE. Thiamine supplementation should precede glucose administration in all patients at risk for WE.
• Alcoholics with WE: Treat with 500 mg of thiamine hydrochloride (dissolved in 100 ml of normal saline) infused intravenously over 30 min three times daily for 2 to 3 days.³
• If a response is observed, continue with 250 mg of thiamine hydrochloride intravenously or intramuscularly daily until clinical improvement ceases.
• Nonalcoholics with WE: Treat with 200 to 500 mg of thiamine hydrochloride (dissolved in 100 ml of normal saline) infused intravenously over 30 min three times daily for 2 to 3 days.
• Undertreatment with thiamine results in less clinical response.^2-3
• Parenteral magnesium must be infused concurrently with thiamine.
• Side effects of parenteral thiamine hydrochloride may include generalized pruritus, transient local irritation, or rarely, anaphylactic or anaphylactoid reactions.

Recommended oral dose after completed parenteral treatment for WE: Thiamine 30 to 100 mg twice daily

• If prompt treatment with thiamine is not administered during the potential reversible stages of WE, Korsakoff syndrome may develop consisting of a typical pattern of irreversible memory loss emerging after the acute global confusional state of WE resolves.
• ∼80% of patients who survive WE develop Korsakoff syndrome.

In cases of altered mental status, ophthalmoplegia, or ataxia of gait, consider neurology consultation. Treatment should be initiated as soon as WE is suspected.

• WE should be suspected in all patients with poor nutrition, especially patients with alcohol use disorder, hyperemesis gravidarum, cancer, or history of bariatric surgery or other GI surgery.
• WE is a clinical diagnosis composed of a triad of confusion, ataxia, and ophthalmoplegia, but the full triad is rarely present.
• Thiamine infusion should be initiated upon clinical suspicion of WE.
• Thiamine infusion should precede infusion of fluids with glucose in all patients with poor nutrition or clinical suspicion of WE.

• Prophylactic treatment for patients with severe alcohol withdrawal, poor nourishment, or signs of malnutrition: Thiamine 250 mg/day intramuscularly for 3 to 5 days.
• In individuals susceptible to WE, 100 mg of intravenous thiamine should precede any glucose infusion.
• Recommended daily dose of thiamine for an average, healthy adult: 1.4 mg or 0.5 mg/1000 kcal of carbohydrates consumed.¹
• Higher daily dose of thiamine recommended for children, critically ill patients, and during pregnancy and lactation.

In cases of known alcohol abuse, in severe illness, or after bariatric surgery, the patient and family should be counseled on the importance of proper nutrition, including vitamin supplementation.

Alcohol Use Disorder (Related Key Topic)

Korsakoff Psychosis (Related Key Topic)

Vitamin Deficiency (Related Key Topic)