Wernicke Encephalopathy

Updated: Nov 03, 2016
  • Author: Philip N Salen, MD; Chief Editor: Robert E O'Connor, MD, MPH  more...
  • Print

Practice Essentials

An important cause of acute or subacute delirium, Wernicke encephalopathy (WE) is a neurological disorder induced by thiamine, vitamin B1, deficiency. WE is the most important encephalopathy due to a single vitamin deficiency. WE presents with the classic triad of ocular findings, cerebellar dysfunction, and confusion. [1]



Thiamine (vitamin B-1) deficiency can result in Wernicke encephalopathy (WE), a serious neurologic disorder. Dr Carl Wernicke, a German neurologist from Breslau Germany (now Wroclaw Poland), described it in 1881 as a triad of acute mental confusion, ataxia, and ophthalmoplegia. Korsakoff amnestic syndrome is a late neuropsychiatric manifestation of WE with memory loss and confabulation; sometimes, the condition is referred to as Wernicke-Korsakoff syndrome (WKS) or Wernicke-Korsakoff psychosis.

Thiamine deficiency is characteristically associated with chronic alcoholism, because alcohol affects thiamine uptake and utilization. However, WE may develop in nonalcoholic conditions, such as prolonged starvation, hyperemesis gravidarum, bariatric surgery, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and can even develop in healthy infants given the thiamine deficient formulas. [2]

Frequently unrecognized, WE is more prevalent than commonly supposed. Epidemics of WE can occur, as evidenced by a report of Israeli infants with infantile thiamine deficiency who were fed formula deficient in thiamine. [3]





Thiamine deficiency is characteristically associated with chronic alcoholism, because it affects thiamine uptake and utilization. [2] In long-term alcoholics, malnutrition can reduce intestinal thiamine absorption by 70%, decreasing serum levels of thiamine to between 30% and 98% below the lower level established for normal subjects. Thiamine acts as a coenzyme in the metabolism of glucose and lipids, and, as stores of water-soluble vitamins are limited in the body, deficiency can present within 2 to 3 weeks of cessation of intake. [4]

Chronic alcohol consumption does not necessarily result in WE if dietary thiamine intake is adequate. It may induce thiamine deficiency through several potential mechanisms: genetic predisposition, replacement of vitamin-containing foods by the high calorific value of alcohol, impaired absorption of thiamine from the gut, impairment of storage by the liver, thiamine transport problems, other nutritional deficiencies, decreased phosphorylation to thiamine pyrophosphate and excessive requirements for the metabolism of alcohol. [4]

WE may develop in nonalcoholic conditions, such as prolonged starvation, hyperemesis gravidarum, and bariatric surgery. [2] The numerous reports of severe thiamine deficiency after obesity surgery have led to the expression "bariatric beriberi.” [5] Other causes of thiamine deficiency include total parenteral nutrition deficient in thiamine, formula deficient in thiamine, and hemodialysis-induced thiamine deficiency in patients with end-stage renal disease.

Other uncommon etiologies of WE are: forced or self-imposed starvation, protein-energy malnutrition resulting from inadequate diet or malabsorption (from celiac sprue), conditions associated with protracted vomiting (eg, hyperemesis gravidarum), carbohydrate loading in the presence of marginal thiamine stores (feeding after starvation), other gastric bypass surgeries, absence of thiamine from the diet as demonstrated by a case series of infants fed formula without the addition of thiamine, [3] and congenital transketolase function abnormalities. A correlation between hemodialysis and WE has been demonstrated possibly secondary to inadvertent dialysis of the water-soluble thiamine combined with malnutrition in the end-stage renal disease population. [6]

The most common inciting factor precipitating WE in the setting of thiamine deficiency is infection. Concomitant illnesses, such as pneumonia or even meningitis, do not exclude a co-diagnosis of WE. [7]

Iatrogenic exacerbation of WE can occur with prolonged glucose or carbohydrate loading in the setting of thiamine deficiency. However, a single, acute administration of glucose does not appear to cause this effect. Nutritionally deficient patients receiving glucose should also receive thiamine, but urgent administration of glucose should not be delayed pending thiamine administration. [7]



Occurrence in the United States

Autopsy studies indicate that WE is frequently undiagnosed during life. [1]  Specifically, autopsy series identifying typical brainstem lesions of WE have placed the incidence of the condition between 0.8% and 2.8% of the general population. However, the incidence can be as high as 12.5% in a population of alcoholics. [8] WE has been described in many other situations where nutrition has been compromised. These cases include patients with AIDS, individuals receiving hemodialysis, persons with hyperemesis gravidarum, and patients with malignancy with or without chemotherapy.

The overall prevalence of WE averages approximately 2%, although this figure is variable and may be decreasing secondary to nutritional supplements in processed foods. [7]

International occurrence

The incidence of WE is believed to be higher in developing nations than more modern nations because of the higher incidence of malnutrition and less vitamin supplementation in poorer regions; however, it may not be diagnosed as frequently in these settings because of more limited access to healthcare.

Sex-, age, and race-related demographics

The male-to-female ratio for WE is 1.7:1, likely owing to alcoholism being 3-4 times more frequent in men than in women.

Average age at onset of WE is 50 years. However, WE can occur in small numbers in unusual situations, such as in total parenteral nutrition ̶ dependent patients during a multivitamin shortage, in persons with hyperemesis gravidarum, or in infants who are fed thiamine-deficient infant formula. [3] WE typically occurs in adults with risk factors (alcoholism, post bariatric surgery, malnutrition), but can occur even in formula-fed infants if their formula lacks thiamine supplementation.

Race does not predispose to WE.



WE is a significantly disabling and potentially lethal condition that can be prevented or reversed if identified and treated early in the course of illness. Administration of thiamine improves the patient’s condition to some degree in many cases; however, neurologic dysfunction can persist even after treatment. [7] WE ataxia and ophthalmoplegia usually resolve briskly, within hours, after thiamine repletion if administered early in the disease course; the global confusional state also appears to improve rapidly within hours of thiamine treatment. However, impairment of memory and learning responds more slowly and often incompletely, suggesting a different mechanism of effect. [4]

WE patients have significant morbidity and mortality related to their thiamine deficiency, particularly if there are no early signs of neurologic improvement after thiamine repletion. Among patients surviving WE, a percentage develop WKS. Patients with Korsakoff psychosis often have permanent neurological disability and require long-term institutionalization. Only about 20% eventually recover completely during long-term follow-up care.

Persistent residual manifestations of WE that are not identified and treated early in the disease include nystagmus, gait ataxia, and Korsakoff syndrome. [7]

Late-stage WE is associated with elevated spinal fluid protein levels and diffuse slowing of postsynaptic potentials on electroencephalography. [5]

Studies suggest that up to 80% of patients with WE may not be diagnosed, which make estimates of morbidity and mortality rates unreliable. [9]



Thiamine is an essential vitamin critical to glucose metabolism. Without thiamine, glucose is metabolized through less efficient anaerobic pathways that produce lactic acid. Acidosis affecting periventricular structures (i.e., thalami, mammillary bodies, oculomotor nuclei, cerebellar vermis) accounts for the clinical presentation. Because thiamine crosses the blood–brain barrier via passive and active transport, correction of brain thiamine deficiency is promoted by maximizing serum thiamine concentrations. [10]

Thiamine plays a vital role in the metabolism of carbohydrates. Thiamine is a cofactor for several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase. [7]  In the setting of thiamine deficiency, thiamine-dependent cellular systems begin to fail, resulting eventually in cell death. Because thiamine-dependent enzymes play an essential role in cerebral energy utilization, thiamine deficiency may propagate brain tissue injury by inhibiting metabolism in brain regions with higher metabolic demands and high thiamine turnover. [7]

Pyruvate dehydrogenase and alpha-ketoglutarate are essential enzymes in the Krebs cycle, and the lack of these enzymes alters cerebral energy utilization. If cells with high metabolic requirements have inadequate stores of thiamine to draw from, energy production drops, and neuronal damage ensues. Increased cell death then feeds the localized vasogenic response. [11]  Additionally, the reduced production of succinate, which plays a role in gamma-aminobutyric acid (GABA) metabolism and the electrical stimulation of neurons, leads to further central nervous system injury.

Increased lactic acid production ensues in the absence of pyruvate dehydrogenase function, as the reduced conversion of pyruvate to acetyl coenzyme A results in less efficient oxidative phosphorylation. [12]

Thiamine pyrophosphate is also essential for nucleotide synthesis, production of nicotinamide adenine dinucleotide phosphate (NADPH), and maintenance of reduced glutathione within erythrocytes. [12]