Wernicke’s encephalopathy (WE) is altered mental status originating from a deficiency of a single vitamin: thiamine (vitamin B1). Thiamine is essential for glucose metabolism in the brain, and its deficiency leads to an accumulation of lactic acid and other toxic metabolic byproducts, resulting in a potentially severe brain tissue injury that particularly affects the mammillary bodies (Sinha S et al, Mayo Clin Proc 2019;94(6):1065–1072). 

Korsakoff’s syndrome (KS) is an amnestic syndrome—with deficits in recent memory more than remote memory—caused by thiamine deficiency and often associated with WE. A hallmark of the syndrome is confabulation, where patients fabricate information to fill memory gaps. Other symptoms include behavioral changes, apathy, and changes in personality similar to those seen in frontal lobe lesions (eg, executive dysfunction, inattention, and poor planning). KS either accompanies or follows untreated WE in most cases and is considered to be irreversible. Thus, recognizing WE and initiating timely treatment are essential to preventing progression to KS. 

High-risk conditions

You probably associate WE with patients suffering from alcohol use disorder, since alcohol impairs thiamine absorption and utilization. But many other conditions also raise the risk, like restrictive eating disorders and excessive vomiting (eg, hyperemesis gravidarum or cannabis hyperemesis syndrome). A low magnesium level (<1.6 mg/dL) also increases the risk since it’s an essential cofactor for thiamine-dependent enzymes. In addition, structural (eg, malabsorptive bariatric surgeries) and functional changes (eg, gastroparesis, or delayed stomach emptying) to the gastrointestinal tract limit thiamine’s absorption. Interventions such as chemotherapy and hemodialysis also deplete thiamine stores (Donnino M et al, Ann Emerg Med 2007;50(6):715–721). Lastly, as thiamine is stored primarily in skeletal muscle and in the heart, brain, liver, and kidneys, any related impairment or end-stage disease will reduce thiamine reserves. 

Presentation conundrum

Diagnosing WE can be tricky as the classic triad of symptoms—confusion, eye movement issues (ophthalmoplegia), and lack of coordination (ataxia)—occurs in only about 10% of cases (Sinha et al, 2019). This infrequency probably contributes to the alarming statistic that approximately 85% of WE cases go undiagnosed until autopsy (Sinha et al, 2019). Since most WE cases are likely undiagnosed, we don’t have accurate estimates of its prevalence or of its morbidity and mortality rates. 

How can you make sure not to miss a case of WE? Look for the most consistent characteristic of this syndrome: a change in mental status. The presentation ranges from mild neurocognitive changes, drowsiness, and apathy to more severe cognitive impairment and even coma in rare cases. 

Ophthalmoplegia is the second most common symptom, with horizontal nystagmus—involuntary rapid horizontal eye movement when patients are asked to follow an object with their eyes only, without moving their head—being the most frequently observed ocular abnormality. However, you might encounter other ocular manifestations, such as strabismus (misalignment of the eyes), ptosis (droopy eyelids), or miosis (constricted pupils). Gait ataxia, the third characteristic in the classic triad, also shows a variable presentation ranging from mild abnormalities in gait to a complete inability to stand or walk. 

Labs and imaging

In WE, thiamine levels will typically be low (<70 nmol/L if whole blood; <8 nmol/L if serum), but a normal serum thiamine level doesn’t rule out WE, as serum concentrations don’t always accurately reflect thiamine levels in the brain. Have a patient fast overnight before obtaining their morning thiamine level. Depending on the lab, you might not get the result for several days.

Magnetic resonance imaging (MRI) of the brain is the most important imaging tool to diagnose and prognosticate WE, and the most significant radiological feature is loss of volume of the mammillary bodies. Cerebral cortex involvement is generally an adverse prognostic indicator (Zhong C et al, Am J Neuroradiol 2005;26(9):2301–2305). Do not assume a normal MRI rules out WE, as findings can be unremarkable in early or mild cases. 

Treatment

Given the acute and potentially reversible nature of WE, if suspected, initiate thiamine treatment rather than waiting for lab or imaging results. Any patients suffering from mental status changes in the setting of high-risk conditions should also be treated immediately. Gastrointestinal thiamine absorption is often unreliable, so intravenous (IV) administration is the most effective route of administration. We recommend administering 200–500 mg IV thiamine three times daily for three to five days, followed by 100 mg oral thiamine three times daily until the patient’s altered mental status resolves. If IV administration is not an option on a psychiatric unit, do not administer by intramuscular injection as this mode of administration is ineffective for WE. Instead, temporarily transfer the patient to a medical floor for the IV thiamine. High-dose IV thiamine best facilitates diffusion across the blood-brain barrier, allowing for quick correction and preventing irreversible cognitive impairment or death (Thomson D et al, Neuropsychol Rev 2012;22(2):81–92). Also, check the patient’s magnesium and replenish as necessary, as thiamine activity requires adequate magnesium levels.

It is critical to initiate parenteral thiamine before administering glucose. Otherwise, glucose will deplete the patient’s meager thiamine stores, risking acute precipitation of WE.

Prevention

A short course of high-dose IV thiamine should be a routine component in the treatment of intoxicated patients admitted to the ED as well as hospitalized patients suffering from delirium with risk factors for WE. inexpensive and safe, making undertreatment of WE more of a concern than overtreatment. Prophylactic and preventative measures in high-risk patients are already considered the standard of care in some populations, such as following bariatric surgery (Lin Q et al, Front Surg 2023;10:1016347). Prophylactic measures include 100 mg PO TID for asymptomatic outpatients, while asymptomatic inpatients can start with 100 mg IV for one day, followed by 200 mg PO daily for the rest of the hospitalization. If new WE symptoms emerge, treat with 500 mg IV for three to five days.

Prognosis

Prompt administration of parenteral thiamine is crucial for optimal outcomes. While ocular issues generally respond favorably to treatment and fully resolve within days to weeks, improvement in gait ataxia tends to be slower, often leaving patients with lingering disturbances. Neurocognitive recovery is a gradual process: While symptoms like apathy, drowsiness, and confusion often improve with treatment, memory and learning deficits often persist. In some cases, patients may not improve and may progress to KS.

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