Wernicke-Korsakoff Syndrome

Article Author:
Shweta Akhouri
Article Editor:
Edward Newton
Updated:
1/8/2019 6:03:26 PM
PubMed Link:
Wernicke-Korsakoff Syndrome

Introduction

When a patient presents with confusion, persistent memory, and learning deficits, one should suspect the presence of Wernicke-Korsakoff syndrome. This syndrome usually presents with a clinical triad consisting of altered mental status (i.e., confusion or dementia), nystagmus (or ophthalmoplegia), and ataxia. Unfortunately, less than a third of patients present with this clinical triad.

To better understand this disorder, practitioners should think of Wernicke encephalopathy and Wernicke-Korsakoff syndrome as two separate syndromes: (1) Wernicke encephalopathy is characterized by an acute confusional state and often reversible clinical features, and (2) Wernicke-Korsakoff syndrome with persistent but often irreversible clinical features including dementia and gait abnormalities.

Etiology

The cause of Wernicke-Korsakoff syndrome is a deficiency of thiamine or vitamin B1. Individuals with poor nutrition for any reason are at risk for this disorder. The most common social factor associated with Wernicke-Korsakoff syndrome is chronic alcohol abuse which leads to decreased absorption and utilization of thiamine. However, it is important to note that there are nonalcoholic causes of thiamine deficiency which can also produce Wernicke-Korsakoff syndrome. These include individuals with malnutrition, starvation, schizophrenia, anorexia nervosa, prisoners of war, and terminal malignancies. In the past, baby formula which was deficient in thiamine also led to Wernicke-Korsakoff syndrome. Wernicke-Korsakoff syndrome also can develop during the first trimester of pregnancy in women who develop hyperemesis gravidarum. Another common cause is bariatric surgery and malignancies of the gastrointestinal (GI) tract.

Epidemiology

The prevalence is between 0% and 2% worldwide. Specific subpopulations have higher prevalence rates including people who are homeless, older individuals living alone or in isolation, and psychiatric inpatients. Prevalence is not connected to alcohol consumption per capita. For example, in France, a country that is well known for its consumption of wine, the prevalence is approximately 0.4%, while Australia has a prevalence of approximately 3%.

Pathophysiology

Brain atrophy associated with Wernicke-Korsakoff Syndrome occurs in the mammillary bodies, the cerebellum, the thalamus, the frontal lobe, the periaqueductal grey, the walls of the third ventricle, and the floor of the fourth ventricle. In addition to the damage seen in these areas, there may be damage to the cortex, although this may be due to the direct toxic effects of alcohol as opposed to thiamine deficiency. 

The amnesia associated with Wernicke-Korsakoff Syndrome is a result of atrophy of the structures of the diencephalon (thalamus, hypothalamus, and mammillary bodies) and is similar to amnesia that is present as a result of damage to the medial temporal lobe. It has been argued that the memory impairment can occur as a result of damage along any part of the mammillothalamic tract, which may explain how Wernicke-Korsakoff Syndrome can develop in patients with damage exclusively to either the thalamus or the mammillary bodies.

History and Physical

An individual with Wernicke-Korsakoff syndrome will usually present with (1) ocular disturbances which may include diplopia, painless vision loss, or strabismus, (2) gait abnormalities that include a wide-based, short-stepped gait and an inability to stand or ambulate without assistance, and (3) mental status changes that include apathy, paucity of speech, and indifference to the environment. As the disorder progresses, other symptoms that may develop include agitation, anger, hallucinations, and confabulations.

Evaluation

The diagnosis of Wernicke-Korsakoff syndrome is made by the history and clinical findings supplemented with lab studies showing thiamine deficiency. Treatment aims to prevent the disorder from getting worse. One should maintain a high level of suspicion for thiamine deficiency to avoid precipitation of severe symptoms of Wernicke-Korsakoff syndrome. Prophylactic thiamine administration is relatively safe and should be started even if the diagnosis has not been confirmed.

Treatment / Management

Unfortunately, unlike Wernicke encephalopathy, Wernicke-Korsakoff syndrome is a long-term disorder which is often progressive. It is very rare for the individual with Wernicke-Korsakoff syndrome to recover fully even with aggressive treatment. After thiamine treatment, the symptoms of encephalopathy will improve in 5 to 12 days. The patient should be offered oral thiamine and consulted for rehabilitation and treatment of other comorbid conditions. Most patients with Wernicke-Korsakoff syndrome need long-term care in a chronic care facility. Their prognosis is guarded.

Differential Diagnosis

The differential diagnosis includes the following:

  • Anoxic encephalopathy
  • Alzheimer disease
  • Temporal lobe epilepsy
  • Concussive head injury
  • Dementia with Lewy bodies
  • Herpes simplex virus
  • Temporal lobe infarction
  • Transient global amnesia
  • Third ventricle tumor

Prognosis

Approximately 25% of patients with Wernicke-Korsakoff syndrome require long-term institutionalization. Patients depending on long-term care often have one or more comorbidity (somatic and psychiatric).

Mental Status Complications

Global confusional often resolves gradually after treatment.

If an amnestic deficit is present, it may manifest as the signs of apathy and global confusion resolve.

One in five patients who demonstrate signs of the amnestic state after treatment has been initiated will have a complete with most patients having varying degrees of persistent learning and memory impairment.

Maximum recovery may take years and depends on abstinence from alcohol.

Once patients with Korsakoff psychosis have recovered, they do not demand alcohol, but they will accept it if offered.

Ataxic Complications

Approximately half of the patients recover completely from ataxic symptoms, and the other half have incomplete recovery, with a residual slow, shuffling, wide-based gait and the inability to tandem walk.

Vestibular dysfunction also improves about half the time.

Ocular Complications

Patients who recover do so in a particular sequence.

Improvement of ocular abnormalities is the most dramatic, usually occurring within hours of thiamine administration.

Failure of ocular abnormalities to respond to thiamine should raise doubt as to the diagnosis.

Vertical nystagmus may persist for months.

Fine horizontal nystagmus can persist indefinitely, but patients completely recover from sixth nerve palsies, ptosis, and vertical-gaze palsies.

Mortality 

Mortality may occur secondary to infections and hepatic failure, but some deaths are attributable to defects of prolonged thiamine deficiency.

The mortality rate is 10-15% in severe cases.

Prognosis depends on the stage of disease at presentation and time of treatment.

Pearls and Other Issues

Korsakoff syndrome often follows or accompanies Wernicke encephalopathy.

  • If treated quickly, Korsakoff syndrome development may be prevented with thiamine treatments.
  • Thiamine needs to be administered quickly in both dose and duration.
  • Thiamine treatment may result in noticeable improvements in mental status after only 2 to 3 weeks of therapy.
  • With treatment, Wernicke's encephalopathy will not necessarily progress to Wernicke-Korsakoff syndrome.

To reduce the risk of Wernicke-Korsakoff syndrome, limit the intake of alcohol and ensure that proper nutrition needs are met.

  • Proper nutrition which, in combination with thiamine supplements, may reduce the risk of development of Wernicke-Korsakoff syndrome.
  • Supplemental thiamine and good nutrition may help heavy drinkers who refuse to or are unable to quit.