eMedicine Specialties > Psychiatry > Adult

Wernicke-Korsakoff Syndrome

Glen L Xiong, MD, Assistant Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California Davis School of Medicine; Attending Psychiatrist, Sacramento Mental Health Treatment Center; Attending Physician, Sacramento County Primary Care Clinic
G Patrick Daubert, MD, Assistant Professor, Assistant Medical Director, Sacramento Division, California Poison Control System; Director of Clinical and Medical Toxicology Education, Department of Emergency Medicine, University of California, Davis Medical Center; Alan DeAngelo, MD, Consulting Staff, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Dwight David Eisenhower Army Medical Center; Alan W Halliday, MD, Chief of Neurology Service, Brooke Army Medical Center; Clinical Professor, Department of Neurology, University of Texas Health Science Center at San Antonio; Associate Professor of Neurology, Uniformed Services University of the Health Sciences

Updated: May 29, 2008

Introduction

Background

In 1881, Carl Wernicke first described an illness that consisted of paralysis of eye movements, ataxia, and mental confusion in 3 patients. The patients, 2 males with alcoholism and a female with persistent vomiting following sulfuric acid ingestion, exhibited these findings, developed coma, and eventually died. On autopsy, Wernicke detected punctate hemorrhages affecting the gray matter around the third and fourth ventricles and aqueduct of Sylvius. He felt these to be inflammatory and therefore named the disease polioencephalitis hemorrhagica superioris.

S.S. Korsakoff, a Russian psychiatrist, described the disturbance of memory in the course of long-term alcoholism in a series of articles from 1887-1891. He termed this syndrome psychosis polyneuritica, believing that these typical memory deficits, in conjunction with polyneuropathy, represented different facets of the same disease.

In 1897, Murawieff first postulated that a single etiology was responsible for both syndromes. 

The term Wernicke encephalopathy is used to describe the clinical triad of confusion, ataxia, and nystagmus (or ophthalmoplegia). When persistent learning and memory deficits are present, the symptom complex is often called Wernicke-Korsakoff syndrome. Clinically, this term is best conceptualized as 2 distinct syndromes with acute/subacute confusional state and often reversible findings of Wernicke encephalopathy versus persistent and irreversible findings of Korsakoff dementia. 

Pathophysiology

A deficiency of thiamine (vitamin B-1) is responsible for the symptom complex manifested in Wernicke-Korsakoff syndrome, and any condition resulting in a poor nutritional state places patients at risk. Heavy, long-term alcohol use is the most common association with Wernicke-Korsakoff syndrome. Alcohol interferes with active gastrointestinal transport, and chronic liver disease leads to decreased activation of thiamine pyrophosphate from thiamine, as well as a decreased capacity of the liver to store thiamine.

Thiamine is absorbed from the duodenum. The body has approximately 18 days of thiamine stores. Thiamine is converted to its active form, thiamine pyrophosphate, in neuronal and glial cells. Thiamine pyrophosphate serves as a cofactor for several enzymes, including transketolase, pyruvate dehydrogenase, and alpha ketoglutarate, that function in glucose use. The main function of these enzymes in the brain is lipid (myelin sheath) and carbohydrate metabolism, production of amino acids, and production of glucose-derived neurotransmitters. Thiamine appears to have a role in axonal conduction particularly in acetylcholinergic and serotoninergic neurons. A reduction in the function of these enzymes leads to diffuse impairment in the metabolism of glucose in key regions of the brain resulting in impaired cellular energy metabolism.

Within 2-3 weeks of decreased intake and thiamine depletion, areas of the brain with the highest thiamine content and turnover will demonstrate cellular impairment and injury. The main consequence of these metabolic changes is the loss of osmotic gradients across cell membranes. The earliest biochemical change is the decrease in a -ketoglutarate-dehydrogenase activity in astrocytes. Additional findings include increased astrocyte lactate and edema, increased extracellular glutamate concentrations, increased nitric oxide from endothelial cell dysfunction, DNA fragmentation in neurons, free radical production and increase in cytokines, and breakdown of the blood brain barrier. Thiamine appears to have a role in acetylcholinergic and serotoninergic synaptic transmission and axonal conduction.
 
Symptoms of Wernicke-Korsakoff syndrome are attributed to these focal areas of damage. Ocular motor signs are attributable to lesions in the brainstem affecting the abducens nuclei and eye movement centers in the pons and midbrain. These lesions are characterized by a lack of significant destruction to nerve cells, which accounts for the rapid improvement and degree of recovery observed with thiamine repletion. Ataxia is a manifestation of damage to the cerebellum, particularly the superior vermis. The cerebellar changes consist of a degeneration of all layers of the cortex, particularly the Purkinje cells. The loss of neurons leads to persistent ataxia of gait and stance. In addition to cerebellar dysfunction, the vestibular apparatus is also affected. In addition, chronic alcohol consumption results in a 35% decrease in transketolase activity within the cerebellum, which is likely due to thiamine deficiency.

Vestibular paresis, confirmed by abnormal results on caloric testing, is observed in the early stages of disease and generally improves with treatment. The amnestic component is related to damage in the diencephalon, including the medial thalamus, and connections with the medial temporal lobes and amygdala. The slow and incomplete recovery of memory deficits suggests that amnesia is related to irreversible structural damage.

McEntee and colleagues demonstrated decreased levels of a metabolite of norepinephrine (3-methoxy-4-hydroxyphenolglycol or MHPG) in the cerebrospinal fluid (CSF) of some patients with Wernicke-Korsakoff syndrome. They point out that the diencephalic lesions are located within monoamine-containing pathways. Clonidine, an alpha-noradrenergic agonist, seemed to improve the memory disorder of their patients. They postulated that damage to these pathways may be the basis for the amnestic features of Wernicke-Korsakoff syndrome.¹ These results have not been reproduced in any large prospective study. Patients with permanent Korsakoff psychosis are not routinely treated with clonidine.

Frequency

United States

Long-standing alcohol use is the most common association with development of Wernicke-Korsakoff syndrome, although poor nutrition can also be an important factor. Prevalence data have come primarily from necropsy studies, with rates of 1-3%, and have indicated that prevalence at autopsy exceeds clinical detection. The rate has been found to be significantly higher in specific populations, ie, homeless people, older people (especially those living alone or in isolation), and psychiatric inpatients, where alcohol use and poor nutritional states predominate. 

International

International and US rates of occurrence are essentially the same. In a survey of neuropathologists from several countries (Australia, Austria, Belgium, Czechoslovakia, France, Germany, Norway, United Kingdom, and United States), prevalence ranged from 0-2.8%.  Prevalence did not correlate with per capita alcohol consumption in each country.²

Mortality/Morbidity

The mortality rate is up to 10-15% in severe cases. Since the presentation is variable and often clinically missed, the exact mortality rate is difficult to estimate. Prognosis depends on the stage of disease at presentation and prompt treatment.

• In general, full recovery of ocular function occurs. Fine horizontal nystagmus can persist in as many as 60% of cases.
• Approximately 40% of patients have complete recovery from ataxia.
• Only 20% of patients recover completely from amnestic deficit.

Race

No racial predilection is observed.

Sex

The condition affects males slightly more frequently than it affects females.

Age

Age of onset is evenly distributed from 30-70 years.

Clinical

History

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) does not consider Wernicke-Korsakoff syndrome as a distinct entity. However, if dementia is prominent, for Axis I purposes, dementia due to [General Medical Condition] (294.1) may be used for coding purposes. If acute confusion is prominent, then the code for delirium [due to medical condition] (293.0) may be considered.

The International Statistical Classification of Diseases and Related Health Problems (ICD-9) code includes (291.1) Alcohol-induced persisting amnestic disorder; Wernicke-Korsakoff Syndrome (alcohol). Since the ICD-9 codes link the diagnosis to alcohol-related conditions, non-alcohol associated Wernicke-Korsakoff syndrome would require other nonspecific codes, eg, (265.1) Other and unspecified manifestations of thiamine deficiency; Other vitamin B1 deficiency states.

• Ocular/visual disturbances
  • Painless vision abnormalities
  • Diplopia (double vision)
  • Strabismus
• Gait abnormalities
  • New wide-based, short-stepped gait
  • Inability to stand or walk without assistance
• Mental status changes
  • Apathy, indifference, paucity of speech
  • Hallucination, agitation
  • Confabulation: Patient fills in gaps of memory with data that can be recalled at that moment.

Physical

• The classical triad of confusion, ataxia, and nystagmus is only present in about 16-38% of patients.³
• Ocular abnormalities: The diagnosis of Wernicke encephalopathy is made most reliably on the basis of the following ocular abnormalities, which can occur singly or in combination:
  • Nystagmus, vertical and horizontal
  • Weakness or paralysis of lateral rectus muscles - Occurs bilaterally but can be asymmetric and is accompanied by diplopia and internal strabismus
  • Weakness or paralysis of conjugate gaze
  • Nonreacting miotic pupils and complete loss of ocular movements (in advanced cases)
  • Ptosis, small retinal hemorrhages, involvement of near-far focusing mechanism, and optic neuropathy (occasionally)
  • Papilledema (very rare)
• Ataxia is manifested as an abnormality of both stance and gait. Vestibular paresis also plays a role in ataxia in the early stages of disease.
  • Mildest form evident on tandem walking only
  • Wide-based stance
  • Slow and uncertain short-stepped gait
  • In the most severe form, inability to walk without support
  • Abnormal results on caloric testing (indicates vestibular paresis)
• Mental status changes: Alterations in consciousness can present simultaneously with ophthalmoplegia and ataxia but more commonly follow these signs and symptoms by days to weeks. These changes are present in 90% of patients and present in various forms.
  • Mental status examination
    • General description: Patients with long-term alcoholism are likely to present disheveled and unkempt, but appearance on presentation can range to a well-kept individual.
    • Mood and affect: Patients' mood can range from calm and blunted or apathetic affect to stupor, as well as agitation in acute delirium and tremens in a patient with alcohol withdrawal. The rare patient presenting in the Korsakoff amnestic state is alert and oriented but lacks the ability to provide adequate history.
    • Speech: No characteristic speech pattern exists. Vocal tremor may be present in a patient undergoing alcohol withdrawal. Reduced verbal content may occur in those with apathy.
    • Perceptual disturbances: No characteristic disturbances exist, but those of delirium tremens are present if it coexists.
    • Thought: Form and content vary depending on patient presentation. Themes may include a lack of concern about current health status or state of affairs.
    • Sensorium and cognition vary with level of consciousness. A state of altered sensorium, with decreased attention and concentration (inability to perform "serial 7's" or spell "WORLD" backwards); disorientation is present in the acute state, consistent with other delirium (or encephalopathy). For a patient who is not in delirium, impaired recall or orientation to date or location may occur. Knowledge of historical facts (eg, naming of presidents) is often impaired for those with Korsakoff syndrome. A patient may cover up the memory deficit by confabulating information.
    • Suicidal or homicidal ideation is generally not associated with this disorder, although any person in the midst of delirium can become self-injurious or violent.
    • A global confusional state is the most common early manifestation and is characterized by apathy, inattentiveness, and indifference to surroundings. Spontaneous speech is minimal, and provoked speech indicates general disorientation to time, place, and purpose. Prompt administration of thiamine often results in increased attentiveness and orientation.
    • Stupor or coma can be observed in more severe cases but is rare as an initial presentation. If patients remain untreated, the condition will progress to death, as in the initial cases described by Wernicke.
  • Patients may present with varying degrees of alcohol withdrawal. Alcohol use is the most common etiology leading to a poor nutritional state that results in Wernicke-Korsakoff syndrome.
• Korsakoff amnestic state
  • The Korsakoff amnestic state is observed in a small number of patients. Individuals present alert and responsive. On examination, they demonstrate the amnestic features of Korsakoff psychosis as the only manifestation of mental confusion. This state appears after the initial confusional state begins to resolve with thiamine administration and persists to some degree in the most severely affected individuals.
  • The Korsakoff state is characterized by both anterograde (ie, learning) and retrograde (ie, memory of past events) amnesia. Anterograde amnesia is severe but incomplete. This is demonstrated by patients' ability to repeat a series of numbers or objects as they are stated but not able to recall the registered information after 3-5 minutes. Retrograde amnesia is demonstrated by gaps in patients' memories of recent and remote past that antedate the onset of illness. These gaps in memory are what lead to the characteristic feature of confabulation. Confabulation represents filling in of memory gaps with data the patient can readily recall. Debate continues as to whether this action represents a deliberate attempt of patients to hide their memory deficits. In either case, confabulation is a fascinating defense mechanism.
  • Confabulation is classically described in Korsakoff dementia, although it may be present in other dementias and is not necessarily present to make the diagnosis.
    • In actual patient scenarios, the patient often greets the examiner cordially as if he knows the examiner from the past (although the examiner has never met the patient).
    • When asked about prior encounters, the patient tells the examiner that they met 2 weeks ago in the hospital but does not recall exactly the topic of the conversation. The patient then proceeds to tell the examiner that currently he is doing well and is able to give basic history about current symptoms and uncertainty about where he will live. However, when asked about the year and the president, the patient replies (usually without hesitation) that it is 1955 and the president is Eisenhower. The actual year is 2005 and the president is G.W. Bush. In this case, the examiner may not have detected any deficits until specific orientation questions are asked. Other aspect of conversation generally lacks specificity and/or depth.
• Other manifestations
  • Hypothermia presents secondary to damage in temperature regulating centers.
  • Associated peripheral neuropathy is found in 80% of patients.
  • Cardiovascular dysfunction may be observed. Overt signs of beriberi heart disease are rare in patients with Wernicke-Korsakoff syndrome. The following symptoms may be observed and generally improve with administration of thiamine:
    • Postural hypotension
    • Tachycardia
    • Syncope

Causes

• Chronic alcoholism
• Nutritional deficiency
• Thiamine-deficient formula⁴
• Persistent emesis
  • Hyperemesis gravidarum: In a study of 49 cases of Wernicke encephalopathy in pregnancy, pregnancy loss attributable to Wernicke encephalopathy was nearly 48%.⁵
  • Gastric malignancy
  • Intestinal obstruction
  • Bariatric surgery: Wernicke encephalopathy can present as early as 2 weeks after surgery. Recovery typically occurs within 3-6 months of initiation of therapy but may be incomplete if this syndrome is not recognized promptly and treated. The highest risk is in young women with vomiting.⁶
• Systemic diseases
  • Malignancy
  • Disseminated tuberculosis
  • Acquired immunodeficiency syndrome (AIDS)⁷
  • Uremia
• Starvation
  • Anorexia nervosa (see the Medscape Resource Center on Eating Disorders)
  • Prisoners of war
  • Schizophrenia⁸ (see the Medscape Resource Center on Schizophrenia)
  • Terminally ill cancer patient⁹
• Iatrogenic
  • Intravenous hyperalimentation
  • Refeeding after starvation
  • Chronic hemodialysis¹⁰

Differential Diagnoses

Other Problems to Be Considered

Wernicke encephalopathy should be differentiated from acute delirium secondary to hypoxia, hypercarbia, CNS infections, and postictal state (seizure). Ataxic disorders also can result from cerebellar infarction. Ocular disorders also can result from vasculitis or infarction.

The differential diagnosis of Korsakoff psychosis includes the following:

Temporal lobe epilepsy
Temporal lobe infarction
Concussive head injury

Dementia with Lewy bodies
Transient global amnesia
Anoxic encephalopathy

Alzheimer disease
Third ventricle tumor
Herpes simplex virus

Workup

Laboratory Studies

• Electrolytes: Initial laboratory studies are directed at the differential diagnostic possibilities that can be identified and corrected rapidly. Electrolyte studies are used to rule out an acute metabolic derangement causing mental confusion.
• Serum thiamine levels have been used in case reports to confirm Wernicke-Korsakoff syndrome. However, studies have not directly examined the correlation between a critical serum thiamine level and the development of neurologic symptoms and Wernicke-Korsakoff syndrome itself. One small study did show that serum thiamine level correlated well with cerebellar vermal atrophy.¹¹ For now, the role of serum thiamine level remain uncertain, though there might be role in confirming the diagnosis and/or to monitor adequacy of treatment.
• Complete blood count: Rule out an acute infectious process, thrombocytosis, or erythrocytosis predisposing to thrombosis and infarction.
• Coagulation panel: Evaluate for a potential bleeding diathesis.
• Arterial blood gas: Evaluate for hypoxemia, hypercarbia, acidosis, or alkalosis.
• Serum/urine toxic drug screen: Rule out acute toxic ingestion. This is most helpful if results are available rapidly.
• Liver-associated enzymes: This may provide evidence of alcohol abuse or liver dysfunction.

Imaging Studies

• CT brain scan (noncontrast): CT scan can help in rapid assessment for hemorrhage, mass effect, edema, and large subacute stroke.
• MRI of the brain with contrast: MRI demonstrates acute lesions of Wernicke-Korsakoff syndrome in dorsal medial thalamic, periventricular region of the third ventricle, periaqueductal area, mamillary bodies, and dorsal medulla. Contrast enhancement of the mamillary bodies were correlated with alcohol¹² and nonalcoholic causes¹³ so whether MRI findings may be specific to etiology of Wernicke-Korsakoff Syndrome remains uncertain. This can be a useful diagnostic procedure in patients presenting with suggestive history and stupor or coma, where ataxia and ophthalmoplegia are not detectable.

Procedures

• Lumbar puncture/CSF analysis: Seriously consider this procedure for any confused patient with fever and/or headache, particularly elderly patients, to rule out infectious etiology. Patients with Wernicke-Korsakoff syndrome have a protein content that is within the reference range or mildly elevated without pleocytosis on CSF analysis.

Treatment

Medical Care

Wernicke encephalopathy is a medical emergency. Prompt recognition of the symptom complex and a high index of suspicion are crucial to ensure early treatment. Parenteral thiamine (100 mg) is the treatment of choice. Early treatment can rapidly reverse the ophthalmoplegia and improve ataxia/dysequilibrium and early mental confusion, as well as prevent development of the amnestic state. In advanced cases, where severe prolonged deficiency has led to permanent structural damage, permanent deficits are most often manifested as the amnestic state and severe ataxia.

After the initial IV dose, continue daily doses of thiamine (100 mg) as IV, IM, or oral doses depending on patient status. Supplementation of electrolytes, particularly magnesium and potassium (often low in people with alcoholism), may be required in addition to thiamine. Magnesium acts as a cofactor for many enzymes (eg, transketolase for the conversion of thiamine to thiamine pyrophosphate) and, therefore, its deficiency may lead to refractory response to thiamin supplementation.¹⁴ In patients who are chronically malnourished, the remainder of the B vitamins also should be supplemented. Administration of intravenous glucose to patients who are severely malnourished can exhaust their supply of thiamine and precipitate Wernicke-Korsakoff syndrome. Thus, good practice demands administration of thiamine prior to glucose infusion in patients at high risk for Wernicke-Korsakoff syndrome.

Emergency psychiatry hospitalization and evaluation is indicated when the patient is having active psychotic symptoms that pose a danger to self or others. Many such patients also meet the criteria of grave disability (ie, inability to provide basic needs such as food and shelter). In such cases, however, the patient should generally be medically and neurologically stable prior to transfer to a psychiatric facility, where acute medical work-up and monitoring may be available (eg, IV access, neuroimaging, nutritionist, neurology consultation). In most cases, patients with psychotic symptoms may require inpatient medical hospitalization and psychiatric consultation. Once medically stabilized, patients may need continued psychiatric care if severe psychotic symptoms persist.

In patients with comorbid acute alcohol withdrawal, treatment with IV/IM thiamine occurs concurrently with the indicated alcohol withdrawal procedures.

Consultations

Long-term alcohol use is the most common etiology for Wernicke-Korsakoff syndrome, and abstinence provides the best chance for recovery. Referral to an alcohol recovery program should be part of the treatment regimen. Inpatient treatment versus outpatient rehabilitation depends on the needs of the individual and risks of relapse. Several other risk factors for Wernicke-Korsakoff syndrome are recognized (see Causes). Patients with these risk factors also could benefit from referral or consultation to help prevent future episodes.

Diet

A balanced diet should be resumed as early as possible. Vitamin and electrolyte supplementation should be adhered to in addition to a well-balanced diet initially, and supplementation can be tapered as the patient resumes normal intake and demonstrates symptomatic improvement.

Activity

Due to gait abnormalities, unassisted ambulation is discouraged during the initial phase of treatment. Patients may require physical therapy evaluation for gait assistance. Gait abnormalities may be permanent, depending on the severity at initial presentation and the timeliness of therapy.

Medication

Wernicke-Korsakoff syndrome is a result of thiamine deficiency. The treatment is replacement of this essential vitamin. The usual dose is 100 mg/d PO/IV/IM. However, the dosing and duration of thiamine treatment has not been sufficiency studied. In a systematic review from the Cochrane Database, Day et al only found 2 randomized studies that were of sufficient quality.¹⁵ There was a significant difference in favor of 200 mg/d, as compared to 5 mg/d, when the outcomes were measure after 2 days. 

Overall, the current standard-of-care involves use of thiamine 100 mg/d for acute prophylaxis. Duration of treatment varies greatly and depends on the comorbid conditions and etiology. For example, thiamine would be administered indefinitely for patients with absorption problems. However, when use as prophylaxis for acute alcohol withdrawal/detoxification, thiamine could be discontinued once dietary intake is adequate. When in doubt, a serum thiamine level may be obtained to guide treatment.     

For persistent cognitive impairment (eg, Korsakoff dementia), cognitive enhancers such as acetylcholinesterase inhibitors and memantine have demonstrated some benefit.^16,17 However, the findings were negative in one small comparison study with rivastigmine.¹⁸

Nutrients

In treating this disorder, the 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 (Thiomalate)

Water-soluble vitamin that combines with adenosine triphosphate to form the coenzyme thiamine pyrophosphate, which is necessary for carbohydrate metabolism. The B vitamins are readily absorbed from the GI tract (except in cases of malabsorption syndromes). Alcohol inhibits absorption of thiamine, which occurs primarily in the duodenum.

Dosing

Adult

100-200 mg PO/IV/IM

Pediatric

Not established

Interactions

May alter theophylline, uric acid, and urobilinogen laboratory values

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Sensitivity reactions can occur (intradermal test dose is recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy following glucose intake may occur in patients who are thiamine deficient; administer before or together with dextrose-containing fluids in suspected thiamine deficiency

Magnesium sulfate

Cofactor in a number of enzyme systems, it also is involved in neurochemical transmission and muscular excitability. Patients with chronic alcoholism and patients who are malnourished usually have inadequate magnesium stores.

Dosing

Adult

2-4 g IV at rate of 1 g/h initially, switch to PO when tolerated; dose is determined by level of deficiency

Pediatric

Not established

Interactions

Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine

Contraindications

Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Possible alteration of cardiac conduction, leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when electrolyte is administered parenterally; magnesium may produce significant hypertension or asystole, so caution is needed when administering dose; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be administered as antidote for clinically significant hypermagnesemia

Potassium acid phosphate (K-Phos)

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 GI loss, or because of low intake. Patients with chronic alcoholism and patients 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.

Dosing

Adult

10 mEq/h IV, switch to PO when tolerated; dose is determined by level of deficiency

Pediatric

Not established

Interactions

Concurrent use with ACE inhibitors may result in elevated serum potassium concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin toxicity; caution if discontinuing potassium administration in patients maintained on digoxin

Contraindications

Hyperkalemia; renal failure; conditions in which potassium retention is present; oliguria or azotemia; crush syndrome; severe hemolytic reactions; anuria; adrenocortical insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

High plasma concentrations may cause death due to cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels; monitor potassium replacement therapy whenever possible by continuous or serial ECG

Follow-up

Further Inpatient Care

Evaluation for progression or recovery from Wernicke-Korsakoff syndrome symptom complex is the primary reason for further inpatient care. Patients also require monitoring for alcohol withdrawal and the potential cardiac manifestations of Wernicke-Korsakoff syndrome (eg, congestive heart failure).

Further Outpatient Care

• Recovering patients will require outpatient follow-up care to evaluate for continued progress or relapse.
• Patients with long-term alcoholism may benefit from further inpatient or outpatient rehabilitation, depending on the likelihood of compliance.

Inpatient & Outpatient Medications

Patients should continue taking thiamine supplementation, as well as other vitamins and electrolytes, until a well-balanced diet can be maintained. Long-term supplementation may be required in patients who cannot maintain adequate nutritional intake, whether from noncompliance or the underlying disorder.

Deterrence/Prevention

• Long-term alcohol use is the most common etiology for development of Wernicke-Korsakoff syndrome. Abstinence from alcohol provides the best chance for recovery, in conjunction with thiamine replacement. Refer patients for alcohol abuse counseling, community alcohol abuse treatment programs (eg, alcoholics anonymous and other consumer support programs), and couples/family therapy, on an individual basis to deter future use and prevent future episodes. Also, see Medscape's CME course, Video Cases From NIAAA: Helping Patients Who Drink Too Much.
• In patients at risk for malnutrition (eg, after gastric bypass surgery), appropriate thiamine and other B vitamin supplementation should be taken with the advice of a nutritionist.    
• In emergency management of patients with acute confusion and concurrent risk factors (eg, alcohol dependence and malnutrition), thiamine administration should be highly considered, especially prior to glucose administration.¹⁹  Generally, high carbohydrate diets increase the demand for thiamine.³
• In a large prospective study, the introduction of thiamine enriched bread flour was shown to reduce the prevalence of Wernicke-Korsakoff syndrome in Australia.²⁰  However, whether thiamine fortification in general or additional supplementation in alcoholic beverages could reduce Wernicke-Korsakoff syndrome has not been systematically studied. 

Complications

• Ocular complications
  • Patients who recover generally do so in a particular sequence. Improvement of ocular abnormalities is the earliest and most dramatic, usually occurring within hours of the initial thiamine dose. Failure of ocular abnormalities to respond to thiamine in this manner should raise doubt as to the veracity of the diagnosis.
  • Vertical nystagmus may persist for months. Fine horizontal nystagmus may persist indefinitely in as many as 60% of patients, but patients completely recover from sixth nerve palsies, ptosis, and vertical gaze palsies.
• Ataxic complications
  • Approximately 40% of patients recover completely from their ataxic symptoms. The remainder have varying degrees of incomplete recovery, with a residual slow, shuffling, wide-based gait and the inability to tandem walk.
  • Vestibular dysfunction generally responds to a similar degree.
• Mental status complications: The symptoms of global confusional state often resolve gradually after treatment is initiated. If an amnestic deficit is present, it will manifest as the early signs of apathy and global confusion resolve. Only 20% of patients who demonstrate signs of the amnestic state after treatment has been initiated have complete recovery. The remaining patients have varying degrees of persistent learning and memory impairment. Maximum recovery may take 1 or more years and depends on abstinence from alcohol. According to reports, once patients with Korsakoff psychosis have recovered, they do not demand alcohol, but they will accept it if offered.

Prognosis

• Mortality may be secondary to infections and hepatic failure, but some deaths are directly attributable to irreversible defects of severe and prolonged thiamine deficiency (eg, coma).

Patient Education

• In alcohol-related Wernicke-Korsakoff syndrome, abstinence from alcohol and maintenance of a balanced diet offer the best chance for recovery and prevention of future episodes.
• Patients who have undergone gastric bypass surgery are recommended to adhere to a balanced diet and continue vitamin supplementation.
• Family education and support is an important component of taking care of anyone with a dementia illness, including Wernicke-Korsakoff syndrome. Patients with persistent dementia usually require 24-hour supervision because they usually have poor insight into their illness and significant functional impairments in activities of daily living. Some patients with alcohol dependence may continue to prefer alcohol use, despite their cognitive deficits. In severe cases, private or public guardianships (or conservatorships) may need to be sought from the courts. 
• Some helpful web sites for patients include the following:
  • Family Caregiver Alliance, Wernicke-Korsakoff Syndrome
  • National Institute of Neurological Disorders and Stroke, Wernicke-Korsakoff Syndrome Information Page 
  • Alzheimer's Association, Wernicke-Korsakoff Syndrome

Miscellaneous

Medicolegal Pitfalls

• Maintain a high level of suspicion for thiamine deficiency to avoid iatrogenic precipitation of Wernicke-Korsakoff syndrome. Heightened awareness should lead to prophylactic supplementation in at-risk patients.
  • This syndrome is most commonly observed in patients with alcoholism, so, when these patients present to an emergency department, they are routinely administered thiamine prior to glucose infusion.
  • Several other categories of patients are at increased risk for thiamine deficiency, including inpatients receiving total parental nutrition, which necessitates vigilant monitoring for indicative signs and symptoms to ensure prompt treatment.

Special Concerns

• Alcohol use is the most common etiology for Wernicke-Korsakoff syndrome. Health care providers usually need to treat varying degrees of withdrawal symptoms in any patient who presents with Wernicke-Korsakoff syndrome.

References

1. McEntee WJ, Mair RG. Memory enhancement in Korsakoff's psychosis by clonidine: further evidence for a noradrenergic deficit. Ann Neurol. May 1980;7(5):466-70. [Medline].

2. Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis. Mar 1995;10(1):17-24. [Medline].

3. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. May 2007;6(5):442-55. [Medline].

4. Kesler A, Stolovitch C, Hoffmann C, Avni I, Morad Y. Acute ophthalmoplegia and nystagmus in infants fed a thiamine-deficient formula: an epidemic of Wernicke encephalopathy. J Neuroophthalmol. Sep 2005;25(3):169-72. [Medline].

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Keywords

Wernicke-Korsakoff syndrome, Wernicke encephalopathy, Wernicke's encephalopathy, polioencephalitis hemorrhagica superioris, Korsakoff's psychosis, Korsakoff psychosis, amnestic-confabulatory state, psychosis polyneuritica, thiamine deficiency, confusion, ataxia, nystagmus, alcoholism, Korsakoff amnestic state, confabulation, Korsakoff dementia, nutritional deficiency

Contributor Information and Disclosures

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Glen L Xiong, MD, Assistant Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California Davis School of Medicine; Attending Psychiatrist, Sacramento Mental Health Treatment Center; Attending Physician, Sacramento County Primary Care Clinic
Glen L Xiong, MD is a member of the following medical societies: American College of Physicians, American Psychiatric Association, and Sierra Sacramento Valley Medical Society
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G Patrick Daubert, MD, Assistant Professor, Assistant Medical Director, Sacramento Division, California Poison Control System; Director of Clinical and Medical Toxicology Education, Department of Emergency Medicine, University of California, Davis Medical Center
G Patrick Daubert, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, and Society for Academic Emergency Medicine
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Alan DeAngelo, MD, Consulting Staff, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Dwight David Eisenhower Army Medical Center
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Alan W Halliday, MD, Chief of Neurology Service, Brooke Army Medical Center; Clinical Professor, Department of Neurology, University of Texas Health Science Center at San Antonio; Associate Professor of Neurology, Uniformed Services University of the Health Sciences
Alan W Halliday, MD is a member of the following medical societies: American Academy of Neurology, Texas Medical Association, and Texas Neurological Society
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Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
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