eMedicine Specialties > Emergency Medicine > Neurology

Wernicke Encephalopathy

Author: Philip N Salen, MD, Clinical Professor, Department of Emergency Medicine, PA Program, Desales University; Adjunct Clinical Associate Professor, Department of Emergency Medicine, Temple University Medical School; Research Director, Emergency Medicine Education, Saint Luke's Hospital
Contributor Information and Disclosures

Updated: Jan 13, 2009

Introduction

Background

Thiamine (vitamin B-1) deficiency can result in Wernicke encephalopathy, a serious neurologic disorder. Dr Carl Wernicke, a Polish neurologist, described it in 1881 as a triad of acute mental confusion, ataxia, and ophthalmoplegia. Korsakoff amnestic syndrome is a late neuropsychiatric manifestation of Wernicke encephalopathy with memory loss and confabulation; sometimes, the condition is referred to as Wernicke-Korsakoff syndrome or psychosis. It is most often seen in alcoholics, but it can be seen in persons with disorders associated with malnutrition and also in patients on long-term hemodialysis or with AIDS. Frequently unrecognized, Wernicke encephalopathy is more prevalent than commonly supposed.

Pathophysiology

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.¹  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.¹

Both pyruvate dehydrogenase and alpha-ketoglutarate are essential enzymes in the Krebs cycle and 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.² 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.³

Thiamine pyrophosphate is also essential for nucleotide synthesis, production of nicotinamide adenine dinucleotide phosphate (NADPH), and maintenance of reduced glutathione within erythrocytes.³

Frequency

United States

Autopsy series identifying typical brainstem lesions of Wernicke encephalopathy have placed the incidence 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.⁴ It has been described in many other situations where nutrition has been compromised. These cases include patients with AIDS, individuals receiving hemodialysis, those with hyperemesis gravidarum, and those with malignancy with or without chemotherapy.

International

Although it may not be diagnosed as frequently in third and fourth world nations, the incidence is probably higher in areas where there is more malnutrition and less vitamin supplementation.

Mortality/Morbidity

Studies suggest that up to 80% of patients with Wernicke encephalopathy may not be diagnosed, which makes estimates of mortality rates unreliable.⁵ Wernicke encephalopathy is a significantly disabling and potentially lethal condition that can be prevented or reversed if treated early. Established Wernicke encephalopathy can have major long-term consequences among patients requiring permanent institutional care.

Race

No racial predilection is known to exist for Wernicke encephalopathy.

Sex

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

Age

Average age at onset is 50 years. However, Wernicke encephalopathy 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.⁶

Clinical

History

The 3 components of the classic triad of Wernicke encephalopathy are encephalopathy, ataxic gait, and some variant of oculomotor dysfunction. All 3 features of the triad are recognized in only about one third of cases.

• Consideration for Wernicke encephalopathy should be given to patients with any evidence of long-term alcohol abuse or malnutrition and any of the following: acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens.
• A high proportion of patients with acute Wernicke encephalopathy who survive develop Korsakoff psychosis, also called Korsakoff syndrome, characterized by retrograde and anterograde amnesia with varying degrees of other cognitive deficits.⁷
• Wernicke encephalopathy should be considered when any patient with long-term malnutrition presents with confusion or altered metal status. Significant overlap exists between Wernicke encephalopathy and Korsakoff psychosis, in which patients experience delayed and potentially irreversible anterograde and retrograde amnesia. For this reason, the two entities have been described together as Wernicke-Korsakoff syndrome.
• Alcohol abuse, AIDS, malignancy, hyperemesis gravidarum, prolonged total parenteral nutrition, iatrogenic glucose loading in any predisposed patient, and other disorders associated with grossly impaired nutritional status have been associated with Wernicke-Korsakoff syndrome.
• Recent reports of Wernicke encephalopathy in patients who have undergone bariatric surgery illustrate that advances in medicine may predispose new groups of patients to this syndrome.¹
• Epidemics of Wernicke encephalopathy can occur as evidenced by a recent report of Israeli infants with infantile thiamine deficiency who were fed formula deficient in thiamine.⁶

Physical

• Ocular abnormalities are the hallmarks of Wernicke encephalopathy. The oculomotor signs are nystagmus, bilateral lateral rectus palsies, and conjugate gaze palsies reflecting cranial nerve involvement of the oculomotor, abducens, and vestibular nuclei. Less frequently noted are pupillary abnormalities such as sluggishly reactive pupils, ptosis, scotomata, and anisocoria. The most common ocular abnormality is nystagmus, not complete ophthalmoplegia.¹
• Encephalopathy is characterized by a global confusional state, disinterest, inattentiveness, or agitation. The most constant symptoms of Wernicke encephalopathy are the mental status changes.¹ Stupor and coma are rare.
• Gait ataxia is often a presenting symptom.³  Ataxia is likely to be a combination of polyneuropathy, cerebellar damage, and vestibular paresis. Vestibular dysfunction, usually without hearing loss, is universally impaired in the acute stages of Wernicke encephalopathy.³ In less severe cases, patients walk slowly with a broad-based gait. However, gait and stance may be so impaired as to make walking impossible. Cerebellar testing in bed with finger-to-nose and heel-to-shin tests may not illicit any notable deficit; thus, it is important to test for truncal ataxia with the patient sitting or standing. Other symptoms that may occur in addition to, or in place of, the classic triad include vestibular dysfunction, hypothermia, hypotension, and coma.⁷
• In addition to ophthalmoplegia and ataxia, 80% of adults will have some degree of peripheral neuropathy, which may include weakness, foot drop, and decreased proprioception.
• Thiamine deficiency has recently been shown to possibly cause a gastrointestinal syndrome of nausea, vomiting, abdominal pain, and lactic acidosis.⁸
• Thiamine deficiency often affects the temperature-regulating center in the brainstem, which can result in hypothermia.
• Hypotension can be secondary to thiamine deficiency either through cardiovascular beriberi or thiamine deficiency–induced autonomic dysfunction.³ Hypotension can also be the result of significant alcoholic liver disease.  
• Coma is rarely the sole manifestation of Wernicke encephalopathy.
• Of patients surviving Wernicke encephalopathy, a large percentage have Korsakoff psychosis, characterized by the following: retrograde amnesia (inability to recall information), anterograde amnesia (inability to assimilate new information), decreased spontaneity and initiative, and confabulation.
• Other manifestations of thiamine deficiency involve the cardiovascular system (wet beriberi) and peripheral nervous system (nutritional polyneuropathy).
• Manifestations of thiamine deficiency in infants are constipation, agitation, apathy, vomiting, lack of appetite, and later, diarrhea, grunting, nystagmus, convulsions, unconsciousness, and cardiomyopathy.⁶

Causes

• Long-term alcohol abuse is the most common cause of Wernicke encephalopathy. In long-term alcoholics, malnutrition can reduce intestinal thiamine absorption by 70%, decreasing serum levels of thiamine from between 30% and 98% below the lower level established for normal subjects. Alcohol alone can also decrease thiamine absorption by 50% in one third of patients who are not malnourished.
• Other less common etiologies are forced or self-imposed starvation, protein-energy malnutrition resulting from inadequate diet or malabsorption (from sprue), conditions associated with protracted vomiting (eg, hyperemesis gravidarum), chronic renal failure, carbohydrate loading in the presence of marginal thiamine stores (feeding after starvation), bariatric surgery and other gastric bypass surgeries, absence of thiamine from the diet (in the case of infants fed formula without the addition of thiamine), and congenital transketolase function abnormalities.
• The most common inciting factor contributing to Wernicke encephalopathy in the setting of thiamine deficiency is infection. Concomitant illnesses, such as pneumonia or even meningitis, do not exclude a codiagnosis of Wernicke encephalopathy.¹
• Iatrogenic exacerbation of Wernicke encephalopathy can occur with prolonged glucose or carbohydrate loading in the setting of thiamine deficiency. 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.¹

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