Wernicke Encephalopathy 

Updated: Nov 20, 2018
Author: Philip N Salen, MD; Chief Editor: Andrew K Chang, MD, MS 

Overview

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]  

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]

Signs and symptoms

In addition to the classical triad of symptoms—encephalopathy, ataxic gait, and oculomotor dysfunction—clinical signs of WE may include the following:

  • Acute confusion
  • Delirium
  • Ataxia
  • Ophthalmoplegia
  • Memory disturbance
  • Hypothermia with hypotension
  • Delirium tremens

Diagnosis

The clinical diagnosis of WE in alcoholics requires two of the following four signs: (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment. 

Although WE remains a clinical diagnosis with no characteristic abnormalities in diagnostic studies, the use of laboratory and radiographic tests remains important to exclude alternate or coexisting medical conditions.

Management

Rapid correction of brain thiamine deficiency is the goal of therapy.[4] Administration of thiamine improves the patient’s condition to some degree in almost all cases; however, persistent neurologic dysfunction is common.[5] Oral absorption is unreliable in patients at risk of Wernicke encephalopathy, which emphasizes the importance of parenteral treatment.[4]

Although as little as 2 mg of thiamine may be enough to reverse symptoms, the dose of thiamine required to prevent or treat WE in most alcoholic patients may be as high as greater than 500 mg given once or, preferably, 2 or 3 times daily parenterally, intravenous is preferred to intramuscular administration. 

Etiology

Causes

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.[6]

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.[6]

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.”[7] 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.[8]

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.[5]

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.[5]

Epidemiology

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.[9] 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.[5]

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.

Prognosis

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.[5] 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.[6]

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.[5]

Late-stage WE is associated with elevated spinal fluid protein levels and diffuse slowing of postsynaptic potentials on electroencephalography.[7]

Studies suggest that up to 80% of patients with WE may not be diagnosed, which make estimates of morbidity and mortality rates unreliable.[10]

Pathophysiology

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.[4]

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.[5]  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.[5]

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]

 

Presentation

History

The three components of the classic triad of WE are encephalopathy, ataxic gait, and some variant of oculomotor dysfunction. However, a complicating factor of WE identification is that its presentation may not be associated with the classical clinical triad in up to 90% of patients.

Consideration for WE should be given to patients with any evidence of long-term alcohol abuse or malnutrition and any of the following: acute confusion, delirium, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens.

A high proportion of patients with acute WE who survive develop WKS, characterized by potentially irreversible retrograde amnesia (inability to recall information) and anterograde amnesia (inability to assimilate new information), with varying degrees of other cognitive deficits.[13]

Consider WE when any patient with long-term malnutrition presents with confusion or altered mental status. Significant overlap exists between WE and Korsakoff psychosis. For this reason, the two entities are often described together as WKS.

Alcohol abuse, AIDS, malignancy, hyperemesis gravidarum, prolonged total parenteral nutrition, iatrogenic glucose loading in a thiamine deficient patient, and other disorders associated with grossly impaired nutritional status are associated with WKS.

Bariatric surgery, of which there are more than 100,000 weight-loss procedures performed annually in the United States, has been associated with both malnutrition and WE.[7] Post–bariatric surgery patients have a limited capacity for food intake during the initial weeks after a bariatric procedure and a body's reserves of thiamine can be depleted after only 20 days of inadequate supply. Paradoxically, post–bariatric surgery patients may still be frankly obese when presenting with WE symptoms caused by thiamine deficiency.[7]

Physical Examination

Ocular abnormalities are the hallmarks of WE. The oculomotor manifestations are: nystagmus, bilateral lateral rectus palsies, and conjugate gaze palsies reflecting cranial nerve involvement of the oculomotor, abducens, and vestibular nuclei. Less frequently noted manifestations are: pupillary abnormalities such as sluggishly reactive pupils, ptosis, scotomata, and anisocoria. The most common ocular abnormality is nystagmus, not abducens (Cranial Nerve VI) ophthalmoplegia.[5]

Encephalopathy is characterized by a global confusional state, disinterest, inattentiveness, or agitation. The most common presenting symptoms of WE are mental status changes.[5] Stupor and coma are rare manifestations of WE.

Gait ataxia is often a presenting physical examination manifestation.[12] Ataxia is likely to be a combination of polyneuropathy, cerebellar damage, and vestibular paresis. Vestibular function, usually without hearing loss, is universally impaired in the acute manifestation of WE. 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.[13]

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 associated with a gastrointestinal syndrome of nausea, vomiting, abdominal pain, and lactic acidosis.[14]

Other symptoms that may occur in addition to, or in place of, the classic triad include hypothermia, hypotension, and coma.[13] 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.[12] Coma is rarely the sole manifestation of WE.

Of patients surviving WE, an important percentage will manifest WKS, 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.[3]

Complications

Thiamine deficiency may also result in other manifestations such as dry beriberi (neuropathy), wet beriberi (neuropathy with high-output congestive heart failure), gastrointestinal beriberi (abdominal pain, vomiting and lactic acidosis), and coma. Heart failure with lactic acidosis is an important syndrome to be noted, because of reports of favorable outcome after thiamine treatment.[1]

Complications of WE may include the following:

  • Hypotension

  • Hypothermia

  • WKS

  • Alcohol withdrawal[6]

  • Acute precipitation of WE

  • Congestive heart failure

  • Gastrointestinal beriberi[14]

  • Lactic acidosis[15]

 

DDx

Diagnostic Considerations

Because WE is reversible, the diagnosis of subclinical cases permits treatment and, probably, improvement of the patient's nutritional, metabolic, and neurological status.[13]

Consider acute WE in all alcoholic patients with any neurologic symptoms, especially in those with evidence of caloric or protein malnutrition or of peripheral neuropathy. Conditions to include in the differential diagnosis of WE include the following:

  • Psychosis

  • Normal pressure hydrocephalus

  • Cerebrovascular accident

  • Chronic hypoxia

  • Closed-head injury

  • Hepatic encephalopathy

  • Postictal state

Differential Diagnoses

 

Workup

Approach Considerations

Patients with WE present with altered mental status and other neurologic abnormalities. Obtaining a detailed patient history, performing a detailed physical examination with a focus on the neurological exam, laboratory workup, and radiographic evaluation are essential to exclude other causes of central nervous system (CNS) dysfunction.

The clinical diagnosis of WE in alcoholics requires two of the following four signs: (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment. Sensitivity of the classic triad was 23%, but rose to 85% if the patients had at least two of the four following features: dietary deficiencies, eye signs, cerebellar signs, and either mild memory impairment or an altered mental state.[1]

No specific laboratory test is available for diagnosing WE. WE is a clinical diagnosis, and normal electrolyte levels may give only false reassurance and delay therapy. This is particularly the case when malnutrition is likely to be present. The motto should be "If in doubt, treat," as administration of thiamine does not pose potential harm.

Moreover, neither a normal computed tomography (CT) scan nor a normal magnetic resonance imaging (MRI) scan of the brain rule out the presence of acute WE or chronic WKS.[13]

Although WE remains a clinical diagnosis with no characteristic abnormalities in diagnostic studies, the use of laboratory and radiographic tests remains important to exclude alternate or coexisting medical conditions. The patient’s history and initial evaluation guide the selection of these tests.

 

Biomarkers

Biomarkers, including an assay for thiamine, are not typically available for timely diagnostic purposes. In addition, no study has clearly described the sensitivity, specificity, and accuracy of thiamine levels in relation to active disease.[15] However, the thiamine levels can help the clinician assuming care of the patient in ambiguous cases, and obtaining a thiamine level can be considered for diagnostic dilemmas.[5]

Complete discrimination of WE patients and controls has been reported for thiamine monophosphate, a dephosphorylation product of the coenzyme thiamine pyrophosphate. However, evidence is sparse, and thiamine assays have limited availability and usually do not allow for an immediate diagnosis.[7]

Serum Electrolyte Levels

Alterations in serum electrolyte levels, such as hypernatremia or hypercalcemia, can cause encephalopathy and must be excluded.

One case series suggested that patients with WE may exhibit a distinctive acid-base pattern consisting of a primary metabolic acidosis in conjunction with a primary respiratory alkalosis. The primary metabolic acidosis is secondary to thiamine's role in aerobic metabolism and the Krebs cycle; without thiamine, aerobic metabolism cannot progress and metabolic products, including lactate and pyruvate, are produced, which result in an anion gap acidosis (see the Anion Gap calculator). The role of thiamine in causing a primary respiratory alkalosis is unclear.[15]

Imaging Studies

CT scanning

A head CT scan is an essential initial test for emergency diagnosis of focal neurologic disease, such as intracerebral hemorrhage. In patients who are comatose, CT scan can detect not only intracranial lesions but also fractures of the skull and minute amounts of blood. However, with a reported 13% sensitivity for WE, CT of the head does not appear to be useful in screening for WE.[13]

MRI

Thiamine is a cofactor of several enzymes involved in glucose metabolism and cerebral energy utilization, and its depletion results in the neuronal damage as seen on MRI, including T2 and fluid-attenuated inversion recovery hyper-intense signaling in the mammillary bodies, periventricular thalamus, and periaqueductal gray matter, as well as diffusion-weighted imaging to differentiate vasogenic from cytotoxic edema.[2]

The sensitivity and specificity of MRI has been reported at 53% and 93% with a positive predictive value of 89%; in other words, MRI is better at confirming the diagnosis of WE than ruling it out.[1]  MRI offers a technique to make a definitive diagnosis antemortem, but the sensitivity is poor, and obtaining an MRI for this indication is typically impractical and unnecessary in the emergency department (ED).[5]

Although the clinical evidence for the utility of MRI is based on a study in which the sample size was small, the reported sensitivity of MRI was 53% and the reported specificity was 93%, for acute and chronic WKS. Because of the low sensitivity of MRI for WE, particularly an acute presentation, and because many patients with WE may not exhibit diagnostic features on MRI, normal MRI results does not preclude the diagnosis of acute illness.[13]

The appearance of acute WE on MRI demonstrates abnormal hyper-density of the mammillary bodies and periaqueductal gray matter with associated abnormal enhancement on T1-weighted images.[16] In chronic WE and WKS, radiographic imaging, especially MRI, may be normal or may show mamillary body, cerebellar, and cerebral shrinkage, as well as symmetrical, low-density abnormalities in periventricular areas, the diencephalon, and the midbrain.[13] Such symmetrical lesions are uncommon in other cerebral encephalopathic disorders and are suggestive of WKS.[13]

Morphometric studies of MRI imaging confirm that patients with WKS show excessive mammillary body and cerebellar shrinkage, indicating that these are highly specific MRI findings for this kind of encephalopathy.[13]

The image below shows brain morphologic studies as demonstrated on MRI. A 60-year-old man presented with bilateral gaze-evoked nystagmus, severe ataxia, and memory impairment. Brain fluid-attenuated inversion recovery (FLAIR)–weighted MRI shows concurrent cytotoxic and vasogenic edema patterns. This case demonstrates cytotoxic and vasogenic edema that may occur at the same time in WE. These findings may result from different vulnerability of brain regions to thiamine deprivation and the corresponding time delay between the development of lesions.[17]

This MRI shows typical high signal intensities (SI This MRI shows typical high signal intensities (SIs) in the medial thalamus (A), periaqueductal gray (B), mamillary bodies (C), cerebellar vermis (B, C, D), and paravermian superior cerebellum (D). All the lesions represent high SIs on the DWI (E–H). The ADC images of the cerebellar vermis (K, L) and paravermian superior cerebellum (L) show low SIs (arrowheads), whereas other described areas (I, J) show iso-SIs (arrows). Image courtesy of Neurology. Apr 8 2008;70(15):e48.

Laboratory Studies

Tests to perform include the following:

  • Complete blood count (CBC) - Rules out severe anemias and leukemias as causes of altered mental status.

  • Serum glucose levels - To exclude hypoglycemia and hyperglycemia as causes of encephalopathy.

  • Liver function tests and ammonia levels- To exclude hepatic and some medicinal causes of encephalopathy.

  • Basic metabolic profile (BMP)- To exclude hyponatremia and uremia as causes of encephalopathy.

  • Pulse oximetry and/or arterial blood gas (ABG) measurement - Exclude hypoxia and hypercarbia as causes of encephalopathy.

  • Toxic drug screening - Excludes some causes of drug-induced altered mental status.

  • Consider lumbar puncture (LP) - Consider LP to exclude CNS infections, such as meningitis and encephalitis, if indicated.

Erythrocyte transketolase levels

Erythrocyte transketolase levels reliably detect thiamine deficiency but are not necessary for the diagnosis of WE. In the erythrocyte transketolase activity assay, the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline levels (the thiamine pyrophosphate effect). Normal values range from 0-15%; a value of 15-25% indicates thiamine deficiency, and a value of greater than 25% indicates severe deficiency.[3]  The erythrocyte transketolase activity assay including thiamine pyrophosphate effect has been replaced by direct measurement of thiamine and its phosphate esters in human blood by high-performance liquid chromatography.[1]  

Blood pyruvate and lactate measurements

Blood pyruvate and lactate measurements, although not specific for thiamine deficiency illnesses, are sensitive and helpful, as thiamine is a cofactor of the pyruvate dehydrogenase enzyme, an important enzyme in aerobic metabolism (i.e. the Kreb cycle).[3]

High-Performance Liquid Chromatography for Thiamine Detection

This thiamine assay is now commercially available in many countries. Adult normal range (60–220 nM) and the lowest detectable level (3–35 nM) are given. The sample (2 ml EDTA blood) should be taken before administration of thiamine and should be protected from light.[1] This assay has largely supplanted the erythrocyte transketolase assay.

Other Tests

Electroencephalogram

Consider an electroencephalogram (EEG) if nonconvulsive status epilepticus is suspected as a potential cause of coma and altered mental status.

 

Treatment

Approach Considerations

Rapid correction of brain thiamine deficiency is the goal of therapy.[4]  WE must be viewed as a medical emergency, even if other, competing diagnoses of CNS processes are being considered. Because the condition is potentially reversible, institution of treatment is indicated in patients exhibiting any combination of symptoms and signs, particularly if the patient is in a high-risk population. Onset of the disease may be acute, subacute, or chronic. Administration of thiamine improves the patient’s condition to some degree in almost all cases; however, persistent neurologic dysfunction is common.[5]  Oral absorption is unreliable in patients at risk of Wernicke encephalopathy, which emphasizes the importance of parenteral treatment.[4]

Prehospital care

Because patients with WE present with altered mental status in the prehospital setting, focus prehospital care on stabilizing the airway, ensuring oxygenation, ruling out hypoglycemia, and maintaining blood pressure and euvolemia.

Emergency Department Care

Although as little as 2 mg of thiamine may be enough to reverse symptoms, the dose of thiamine required to prevent or treat WE in most alcoholic patients may be as high as greater than 500 mg given once or, preferably, 2 or 3 times daily parenterally, intravenous is preferred to intramuscular administration. 

Thiamine has a short half-life so multiple daily administrations may be necessary to replete levels and allow for optimal blood-brain diffusions.[5] Thiamine solution should be fresh, since old solutions may be inactive. Oral preparations have been shown to vary in bioavailability, but in hospital practice, thiamine is usually administered parenterally to patients thought to be at high risk of WKS. Parenteral administration is associated with some risk of anaphylaxis.

Treat all malnourished patients with large doses of parenteral thiamine, particularly if intravenous glucose administration is necessary, even in the absence of symptoms and signs of WE. Administering dextrose to an individual in a thiamine-deficient state exacerbates the process of cell death by providing more substrate for biochemical pathways that lack sufficient amounts of coenzymes.[11]

Start thiamine prior to or concurrently with treatment of intravenous glucose solutions, and continue until the patient resumes a normal diet. The administration of dextrose or other carbohydrates in this setting has the potential for harm, because glucose oxidation is a thiamine-intensive process that may drive the last reserves of circulating vitamin B-1 toward the intracellular compartment, thereby aggravating neurologic damage.[3]

Magnesium deficiency could also contribute to the poor recovery from WE in alcoholics.[1]  Patients with WE are likely hypomagnesemic and should be treated empirically with parenteral magnesium sulfate, as they may be unresponsive to parenteral thiamine in the presence of hypomagnesemia.[6] After correction of hypomagnesemia in conjunction with thiamine repletion, the blood transketolase activity can return to normal and clearing of the clinical signs of WE may occur.

There is evidence that suggests thiamine treatment brings about rapid resolution of the ataxia and ophthalmoplegia and slow but significant improvement in the severity of nystagmus. The global confusional state also appears to improve rapidly within hours of thiamine treatment, but other issues remain unresolved. Impairment of memory and learning responds more slowly and often incompletely, suggesting a different mechanism of effect.[6]

 

Inpatient and Outpatient Care

Inpatient care

Depending on mental status and the ability to protect his or her airway, admit a patient with suspected or confirmed WE to an inpatient internal medicine or neurology service.

Admission ensures that the patient receives continued intravenous thiamine and magnesium administration, observation for possible development of WKS, and evaluation for possible cardiovascular beriberi.

Inpatient therapy for infants with thiamine deficiency involves administration of high-dose, parenteral thiamine 50 mg/day for 2 weeks.[3]

Outpatient care

Patients who are malnourished, whether from alcohol or other causes, should continue to receive thiamine supplementation on an outpatient basis.

Alcohol also appears to significantly increase the amount of thiamine required to treat the patient successfully compared with individuals in whom thiamine deficiency has a predominantly nutritional cause.[6]

Consultations, Monitoring, and Prevention

An internist and/or metabolic specialist can evaluate the encephalopathic patient for metabolic causes of acute mental status abnormalities. Consult a neurologist for further evaluation and treatment of altered mental status or other focal neurologic deficits. A psychiatrist may be helpful in evaluating comorbid psychiatric conditions. Refer patients with alcoholism to alcohol-cessation programs and monitor them for signs of alcohol withdrawal.

Patients who have been treated for WE should be advised to avoid alcohol consumption and other behaviors that predispose to thiamine deficiency.

In the United States, many foods (but not alcoholic beverages) are supplemented with multiple vitamins and minerals. Some health policy experts have hypothesized that fortifying alcoholic beverages with thiamine would lower healthcare costs.

Complications

In addition, the administration of dextrose in the setting of thiamine deficiency can be harmful because glucose oxidation is a thiamine-intensive process that may drive the insufficient circulating vitamin B-1 intracellularly, thereby precipitating neurologic injury.[3]

 

Guidelines

Guidelines Summary

The diagnostic sensitivity for the diagnosis of WE is optimized utilizing the Caine criteria. Sensitivity of the Caine criteria approaches 100% in patients with alcoholism without hepatic encephalopathy. The Caine criteria state that a diagnosis of WE should be considered in any patient with two of the following: nutritional deficiency, altered mental state or memory, oculomotor abnormalities, cerebellar dysfunction.[4]

After bariatric surgery it is recommended to follow up on thiamine status for at least 6 months.[1]

EFNS Guidelines

The European Federation of Neurologic Societies (EFNS) guidelines for WE recommend the following:[1]

  • The clinical diagnosis of WE should take into account the different presentations of clinical signs between alcoholics and non alcoholics (Recommendation Level C); although prevalence is higher in alcoholics, WE should be suspected in all clinical conditions which could lead to thiamine deficiency.
  • The clinical diagnosis of WE in alcoholics requires two of the following four signs; (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment (Level B).
  • Total thiamine in blood sample should be measured immediately before its administration.
  • MRI should be used to support the diagnosis of acute WE both in alcoholics and non alcoholics (Level B).
  • Thiamine is indicated for the treatment of suspected or manifest WE. It should be given, before any carbohydrate, 200 mg thrice daily, preferably intravenously (Level C).
  • The overall safety of thiamine is very good (Level B).
  • After bariatric surgery we recommend follow-up of thiamine status for at least 6 months (Level B) and parenteral thiamine supplementation.
  • Parenteral thiamine should be given to all at-risk subjects admitted to the Emergency Room.
  • Patients dying from symptoms suggesting WE should have an autopsy.
 

Medication

Medication Summary

The cornerstone of therapy for prevention or treatment of WE in most alcoholic patients is thiamine until the patient resumes a normal diet. Administer daily oral thiamine (100 mg) on a long-term, outpatient basis.

As previously stated, patients with WE are likely hypomagnesemic and should be treated empirically with parenteral magnesium sulfate, as they may be unresponsive to parenteral thiamine in the presence of hypomagnesemia.[6] After correction of hypomagnesemia in conjunction with thiamine repletion, the blood transketolase activity can return to normal and clearing of the clinical signs of WE may occur.

Nutrients

Class Summary

The primary objective is to replenish vitamin B-1 stores. In adults, 60-180 mEq of potassium, 10-30 mEq of magnesium, and 10-40 mmol/L of phosphate per day appear necessary to achieve optimum metabolic balance.

Thiamine

Begin thiamine administration prior to treating the patient with intravenous glucose solutions. Glucose infusions may precipitate Wernicke disease or acute cardiovascular beriberi in a previously unaffected patient or cause rapid worsening of an early form of the disease.

Magnesium sulfate

Magnesium is a cofactor in a number of enzyme systems; it is also involved in neurochemical transmission and muscular excitability. Persons with long-term alcoholism and patients who are malnourished usually have inadequate magnesium stores.

Potassium acid phosphate (K-Phos)

Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through gastrointestinal loss, or because of low intake. Patients with chronic alcoholism and those who are malnourished usually have inadequate nutrient stores. Potassium depletion sufficient to cause a 1-mEq/L drop in serum potassium requires a loss of about 100-200 mEq of potassium from the total body store.

 

Questions & Answers

Overview

What is Wernicke encephalopathy (WE)?

What is the role of thiamine (vitamin B-1) in the etiology of Wernicke encephalopathy (WE)?

What causes Wernicke encephalopathy (WE)?

What is the prevalence of Wernicke encephalopathy (WE) in the US?

What is the global prevalence of Wernicke encephalopathy (WE)?

Which patient groups have the highest prevalence of Wernicke encephalopathy (WE)?

What is the prognosis of Wernicke encephalopathy (WE)?

What is the pathophysiology of Wernicke encephalopathy (WE)?

Presentation

Which clinical history findings are characteristic of Wernicke encephalopathy (WE)?

Which physical findings are characteristic of Wernicke encephalopathy (WE)?

What are the possible complications of thiamine deficiency in Wernicke encephalopathy (WE)?

What are the possible complications of Wernicke encephalopathy (WE)?

DDX

Which conditions should be considered in the differential diagnosis of Wernicke encephalopathy (WE)?

What are the differential diagnoses for Wernicke Encephalopathy?

Workup

How is Wernicke encephalopathy (WE) diagnosed?

What is the role of biomarkers in the workup of Wernicke encephalopathy (WE)?

What is the role of serum electrolyte levels in the workup of Wernicke encephalopathy (WE)?

What is the role of CT scanning in the diagnosis of Wernicke encephalopathy (WE)?

What is the role of MRI in the diagnosis of Wernicke encephalopathy (WE)?

What is the role of lab testing in the diagnosis of Wernicke encephalopathy (WE)?

What is the role erythrocyte transketolase levels in the workup of Wernicke encephalopathy (WE)?

What is the role of blood pyruvate and lactate measurements in the workup of Wernicke encephalopathy (WE)?

What is the role of liquid chromatography in the workup of Wernicke encephalopathy (WE)?

What is the role of EEG in the workup of Wernicke encephalopathy (WE)?

Treatment

How is Wernicke encephalopathy (WE) treated?

What is included in prehospital care for Wernicke encephalopathy (WE)?

What is included in the emergency department (ED) care for Wernicke encephalopathy (WE)?

What is included in the inpatient treatment of Wernicke encephalopathy (WE)?

What is included in the long-term monitoring of patients with Wernicke encephalopathy (WE)?

Which specialist consultations are beneficial to patients with Wernicke encephalopathy (WE)?

How is Wernicke encephalopathy (WE) prevented?

What are the possible complications of dextrose in the treatment of Wernicke encephalopathy (WE)?

Guidelines

What are the Caine diagnostic criteria for Wernicke encephalopathy (WE)?

What are the EFNS guidelines for the diagnosis and management of Wernicke encephalopathy (WE)?

Medications

Which medications are used in the treatment of Wernicke encephalopathy (WE)?

Which medications in the drug class Nutrients are used in the treatment of Wernicke Encephalopathy?