Wernicke-Korsakoff syndrome



Wernicke’s encephalopathy refers to alcohol induced Thiamine (Vitamin B1) deficiency with acute neuropsychiatric process with ocular motor disorder, ataxia, and altered mental status.

WE is the most important encephalopathy due to a single vitamin deficiency.

Caused by thiamine deficiency.

Alcoholism is the most common etiologic factor in the US, but can occur in any patient with a nutritional deficiency such as hyperemesis gravidarum, intestinal obstruction and malignancy.

Caine diagnostic criteria: dietary deficiency, ocular motor abnormalities, and altered mental status.

Wernicke’s encephalopathy is a neurologic process caused by thiamine deficiency and characterized by ocular maladies to include nystagmus and ophthalmoplegia , mental status changes and gait disturbances.

Only 10% of patients have classic triad of symptoms of Wernicke’s syndrome.

Can be of acute or chronic onset.

Approximately 80% of patients with untreated WE develop Korsakoff syndrome characterized by memory impairment and associated confabulation.

Korsakoff’s psychosis refers to antegrade and retrograde amnesia, disorientation and confabulation seen with thiamine deficiency.

Prevalence 8-10 times higher in alcohol dependence than in the general population.

Typically preceded by metabolic stress and a carbohydrate load.

Thiamine should be given to all patients at risk for or with manifestations of the syndrome.

Thiamine (vitamin B-1) deficiency can result in Wernicke encephalopathy, a serious neurologic disorder.




Thiamine levels are not diagnostic for WE, but it can identify patients with very low circulating levels of thiamine who are at risk for the development of WE.




Thiamine levels are important in cases of ambiguous presentation and can be measured before its administration.


A triad of acute mental confusion, ataxia, and ophthalmoplegia.

The common findings of mental status changes, ocular dysfunction, and gait apraxia are present it only 10% of cases.

Diagnosis is improved by the recognition of nutritional deficiency and any part of the classic triad along with, hypothermia, hypotension and coma that raise clinical suspicion for the disease.


Diagnosis requires a high degree of clinical suspicion and disease recognition.

Only a few cases of Wernicke‘s encephalopathy are diagnosed before death-15%.

In an autopsy study WE was suspected it only about 1/3 of alcoholic patients and 6% of non-alcoholic patients during their lifetime.

The syndrome is most often recognized only at autopsy.

Wernicke’s disease is one of the most prevalent neurological or neuropsychiatric diseases.

In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases.[

Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic.

In children, only 58% are diagnosed.

In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more.

Most patients with WE are likely unrecognized and undiagnosed during life.

The most characteristic finding of the syndrome is a change in mental status.

Cognitive changes range from apathy, mild neurocognitive symptoms to severe symptoms including, coma.

The second most common characteristic is ophthalmoplegia.

Horizontal nystagmus is the most common ocular abnormality, but other findings include sixth nerve palsy, ptosis, retinal hemorrhage, papilledema, anisocoria, miosis.

The overdiagnosis and overtreatment of the disease with thiamine is preferred to prevent prolong persistent neurological impairments.

Four criteria for clinical diagnosis includes: dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, and altered mental status or mild memory impairment.

In patients with chronic alcoholism the presence of two of the above criteria have a sensitivity approaching 100% for the clinical diagnosis.

A clinical diagnosis.

Korsakoff amnesia is a late neuropsychiatric manifestation of Wernicke encephalopathy with memory loss and confabulation.

Sometimes referred to as Wernicke-Korsakoff psychosis.

Thiamine deficiency is characteristically associated with chronic alcoholism.

Alcoholism affects thiamine uptake and utilization.

Patients with alcoholism and secondary malnutrition are often deficient in magnesium, which is a cofactor for normal functioning of thiamine dependent enzymes and neurochemical transmission.

Brain lesions found in Wernicke’s encephalopathy are typically in structures that surround the third and fourth ventricles and the aqueduct.

The mammillary bodies are involved in up to 80% of cases of Wernicke’s encephalopathy and are the most commonly affected brain structures.

The syndrome may develop in nonalcoholic conditions, such as starvation, hyperemesis gravidarum, bariatric surgery, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and can even develop in healthy infants given the wrong formulas.

Complications may include; Korsakoff psychosis, alcohol withdrawal, acute precipitation of encephalopathy, congestive heart failure, beriberi, and lactic acidosis.

Administration of dextrose in the presence of thiamine deficiency can be harmful because glucose oxidation is a thiamine-intensive process.

Dextrose therapy that may drive insufficient circulating vitamin B-1 intracellularly, precipitating neurologic injury.

Thiamine has a vital role in carbohydrate metabolism as a cofactor for several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase.

In the presence of thiamine deficiency, thiamine-dependent cellular systems fail, resulting in cell death.

Thiamine-dependent enzymes play an essential role in cerebral energy utilization.

Thiamine deficiency may result in brain tissue injury by inhibiting metabolism in brain regions with higher metabolic demands and high thiamine turnover.

Pyruvate dehydrogenase and alpha-ketoglutarate are essential enzymes in the Krebs cycle, and deficiency of these enzymes alters cerebral energy utilization.

With thiamine deficiency cerebral energy production drops, and neuronal damage ensues.

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.

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

Thiamine deficiency is characteristically associated with chronic alcoholism.

Alcohol affects thiamine uptake and utilization.

In long-term alcoholic intake 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.

Alcohol alone can also decrease thiamine absorption by 50% in one third of patients who are not malnourished.

Wernicke encephalopathy may develop in nonalcoholic conditions, such as starvation, hyperemesis gravidarum, and bariatric surgery.

Thiamine deficiency after obesity surgery have led to the expression “bariatric beriberi.”

Thiamine deficiency is most commonly associated with alcoholism, but other causes of thiamine deficiency are malnutrition, total parenteral nutrition deficient in thiamine, formula deficient in thiamine, postbariatric surgery–induced malnutrition, hyperemesis gravidarum, and hemodialysis-induced thiamine deficiency in patients with end-stage renal disease.

Less common etiologies are starvation, protein-energy malnutrition resulting from inadequate diet or malabsorption, conditions associated with protracted vomiting, carbohydrate loading in the presence of marginal thiamine stores, bariatric surgery and 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), and congenital transketolase function abnormalities.

An association between hemodialysis and Wernicke encephalopathy has been demonstrated.

Iatrogenic exacerbation of Wernicke encephalopathy can occur with prolonged glucose or carbohydrate loading in the setting of thiamine deficiency.

Nutritionally deficient patients receiving glucose should also receive thiamine.

Typical brainstem lesions of Wernicke encephalopathy in autopsy series have found the incidence of the condition between 0.8% and 2.8% of the general population.

The incidence can be as high as 12.5% in a population of alcoholics.

Wernicke encephalopathy has been described in situations where nutrition has been compromised: AIDS, individuals on hemodialysis, persons with hyperemesis gravidarum, and patients with malignancy with or without chemotherapy.

The overall prevalence of Wernicke encephalopathy averages approximately 2%.

The incidence of Wernicke encephalopathy is higher in developing nations because of the higher incidence of malnutrition and less vitamin supplementation in poorer regions.

Male-to-female ratio for Wernicke encephalopathy is 1.7:1related to alcoholism being 3-4 times more frequent in men than in women.

Average age at onset is 50 years.

Can occur rarely in unusual situations, such as in total parenteral nutrition without vitamins, in persons hyperemesis gravidarum, or in infants who fed thiamine-deficient infant formula.

No racial predisposition.

A significantly disabling and potentially lethal condition that can be prevented or reversed if treated early.

Administration of thiamine improves the patient’s condition to some degree in many cases.

Persistent neurologic dysfunction is common after treatment.

Wernicke encephalopathy ophthalmoplegia usually resolves briskly with thiamine repletion if administered early in the disease course.

Global confusion can improve with thiamine therapy given within hours or days.

Patients with Wernicke encephalopathy have significant morbidity and mortality related to thiamine deficiency, particularly if there is no early signs of neurologic improvement after thiamine repletion.

Among patients surviving Wernicke encephalopathy, a percentage develop Korsakoff psychosis.

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.

When Wernicke encephalopathy is not identified and managed early residual manifestation include nystagmus, gait ataxia, and Korsakoff syndrome.

A worse outcome may be expected in late-stage Wernicke encephalopathy.

Late stage Wernicke encephalopathy is associated with elevated spinal fluid protein levels and diffuse slowing of postsynaptic potentials on electroencephalography.

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

The 3 components of the classic triad of Wernicke encephalopathy are encephalopathy, ataxic gait, and some variant of oculomotor dysfunction.

About 80% of patients with untreated Wernicke’s encephalopathy have the development of Korsakoff syndrome.

Korsakoff Syndrome consists of permanent memory impairment associated with confabulation.

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, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens.

Ataxia can range from mild gait abnormality to a complete inability to stand.

A high proportion of patients with acute Wernicke encephalopathy who survive develop Korsakoff syndrome, characterized by potentially irreversible retrograde and anterograde amnesia with varying degrees of other cognitive deficits.

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, and are 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.

Bariatric surgery weight-loss procedures have been associated with both malnutrition and Wernicke syndrome.

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.

Ocular abnormalities are the hallmarks of Wernicke encephalopathy, with oculomotor signs of 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.

Encephalopathy is characterized by a global confusional state, disinterest, inattentiveness, or agitation.

The most constant symptoms of Wernicke encephalopathy are the mental status changes.

Stupor and coma are rare in Wernicke encephalopathy.

Gait ataxia is often a presenting symptom.

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 stages of Wernicke encephalopathy. 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.[12]

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.[3]

Other symptoms that may occur in addition to, or in place of, the classic triad include hypothermia, hypotension, and coma.[12] 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.[7] Coma is rarely the sole manifestation of Wernicke encephalopathy.

Of patients surviving Wernicke encephalopathy, an important 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).

Eating disorders such as anorexia nervosa, nutritional deprivation can lead to thiamine deficiency and vulnerability to development of WE. 

Comorbidity exists between eating disorders and substance-abuse disorders and such groups have a higher risk of developing WE.

Patients having undergone bariatric surgery are at risk for the development of thiamine malabsorption and WE with a greater incidence alcohol abusers.

Manifestations of thiamine deficiency in infants are constipation, agitation, apathy, vomiting, lack of appetite, and later, diarrhea, grunting, nystagmus, convulsions, unconsciousness, and cardiomyopathy.

Because Wernicke encephalopathy is reversible, the diagnosis of subclinical cases permits treatment and, potential improvement of the patient’s nutritional, metabolic, and neurological status.

Acute Wernicke encephalopathy should be ruled out in all alcoholic patients with any neurologic symptoms, especially in those with evidence of caloric or protein malnutrition or of peripheral neuropathy.

Conditions to consider in the differential diagnosis:


Normal pressure hydrocephalus

Cerebrovascular accident

Chronic hypoxia

Closed-head injury

Hepatic encephalopathy

Postictal state

Differential Diagnoses includes:

Alcohol and Substance Abuse Evaluation

Alcoholic Ketoacidosis

Delirium Tremens

Delirium, Dementia, and Amnesia

Stroke, Ischemic

Withdrawal Syndromes

No specific laboratory test is available for diagnosing Wernicke encephalopathy.

A clinical diagnosis.

Findings of normal electrolyte levels may give only false reassurance and delay therapy.

A normal computed tomography scan of the brain nor a normal MRI scan rule out the presence of acute or chronic Wernicke-Korsakoff syndrome.

Classic MRI findings are symmetrical lesions in the mammillary bodies, thalami, and periaqueductal and periventricular regions.

The use of laboratory and radiographic tests are important to exclude alternate or coexisting medical conditions.

Evaluation includes: Complete blood count (CBC),

Serum glucose levels, arterial oximetry measurement,

toxic drug screening, Consider LP to exclude CNS infections, if indicated, erythrocyte transketolase levels

MRI is the most useful test to support the diagnosis with a sensitivity and specificity

of 53% and 93%, respectively.

Erythrocyte transketolase levels reliably detect thiamine deficiency but are not necessary for the diagnosis of Wernicke encephalopathy.

In the erythrocyte transketolase activity assay, a value of 15-25% indicates thiamine deficiency, and a value of greater than 25% indicates severe deficiency.

Blood pyruvate and lactate measurements, are sensitive and helpful, as thiamine is a cofactor of the pyruvate dehydrogenase enzyme, an important enzyme in aerobic metabolism.

No study has clearly described the sensitivity, specificity, and accuracy of thiamine levels in relation to active disease.

However, in ambiguous cases, and obtaining a thiamine level can be considered for diagnostic purposes.

CT of the head does not appear to be useful in screening for this syndrome.

Brain CT is not a reliable test for WE. 

MRI imaging performs better and can identify WE related lesions in 2/3 of patients.

MRI shows areas of increased T2 and fluid-attenuated inversion recovery signals, decreased T one signal, and diffusion abnormality surrounding the aqueduct and third ventricle and within the medial calamus, dorsal medullary , tectal plate, and mammillary bodies.

Imaging testing should not delay treatment in individuals suspected of having WE.

Thiamine is a cofactor of several enzymes involved in glucose metabolism and cerebral energy utilization.

Thiamine depletion results in the neuronal damage as seen on MRI, including the mamillary bodies, periventricular thalamus, and periaqueductal gray matter.

MRI offers a definitive diagnosis antemortem, but it’s sensitivity is poor, and is typically impractical and unnecessary in the emergency department.

The reported sensitivity of MRI is 53% and the reported specificity is 93%, for acute and chronic Wernicke-Korsakoff syndrome.

Because of the low sensitivity of MRI for Wernicke encephalopathy, particularly an acute presentation, and because many patients with Wernicke encephalopathy may not exhibit diagnostic features on MRI, normal MRI results should not be used to exclude the diagnosis of acute illness.

Acute Wernicke encephalopathy on MRI demonstrates abnormal hyperdensity of the mammillary bodies and periaqueductal gray matter with associated abnormal enhancement on T1-weighted images.

In chronic Wernicke encephalopathy and Korsakoff syndrome, 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.

MRI imaging with Wernicke-Korsakoff syndrome show excessive mamillary body and cerebellar shrinkage, indicating that these are highly specific MRI findings for this kind of encephalopathy.

Cytotoxic and vasogenic edema that may occur at the same time in Wernicke encephalopathy, findings that may result from different vulnerability of brain regions to thiamine deprivation and the corresponding time delay between the development of lesions.

Wernicke encephalopathy is a medical emergency.

The timely administration of thiamine is the mainstay of treatment.

Higher doses may be necessary in chronic alcohol users.

Thiamine half-life is only 96 minutes, so administration to to three times daily might achieve better bioavailability.

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.

Despite thiamine therapy, persistent neurologic dysfunction is common.

Prehospital care focuses on stabilizing the airway, ensuring oxygenation, and maintaining blood pressure and euvolemia.

As little as 2 mg of thiamine may be enough to reverse symptoms.

To prevent or treat Wernicke encephalopathy in most alcoholic patients the dose of thiamine may be as high as greater than 500 mg given once or, preferably, 2 or 3 times daily parenterally.

Multiple daily doses may be necessary to replete levels because of a short half life, and allow for optimal blood-brain diffusions.

While ataxia and confusion may resolve dramatically, improvement may not be noted for days or months.

All poorly nourished patients should be treated with large doses of parenteral thiamine, particularly if intravenous glucose administration is necessary, even in the absence of symptoms and signs of Wernicke encephalopathy.

The administration of dextrose to an individual in a thiamine-deficient state exacerbates cell death by providing more substrate for biochemical pathways that lack sufficient amounts of coenzymes.

In nutritionally depleted individuals intravenous thiamine should be administered before glucose to avoid iatrogenic occurrence of WE.

Magnesium serves as a cofactor for thiamine activity and its level should be checked to make sure hypomagnesemia is not present.


Thiamine is safe and inexpensive and quick administration can prevent progression of WE to irreversible deficits of the Korsakoff syndrome.

No consensus on the effective dose of thiamine, its administration, dose frequency, or duration of treatment has been established.

Traditional recommendation is parenteral  intravenous thiamine at 100 mg a day.

Start thiamine prior to or concurrently with treatment of intravenous glucose solutions.

The administration of dextrose or other carbohydrates in this setting can be hazardous, 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.

Patients with Wernicke encephalopathy are frequently hypomagnesemic and should be treated empirically with parenteral magnesium sulfate, as they may be unresponsive to parenteral thiamine in the presence of hypomagnesemia.

Patients treated for Wernicke encephalopathy should avoid alcohol consumption and other behaviors that predispose to thiamine deficiency.


Ocular changes respond well to treatment, with gaze palsies and ptosis recovering completely within days to weeks. 

Horizontal nystagmus recovers soon after treatment but can persist suddenly for many months and up to 60% of patients.

Delayed recovery is seen in gait ataxia in contrast to ocular findings.

Mental status changes in acute and chronic encephalopathy recede, but residual neurological deficits common and persistent.

Therapy for prevention or treatment of Wernicke encephalopathy in most alcoholic patients is thiamine until the patient resumes a normal diet.

Alcoholics should be on daily oral thiamine,100 mg, on a long-term basis, with 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 administration should begin prior to treating the patient with intravenous glucose solutions, as 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 is a cofactor in a number of enzyme systems, and it is involved in neurochemical transmission and muscular excitability.

In long-term alcoholism and patients have inadequate magnesium stores.



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