Wernicke-Korsakoff Syndrome

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, leading 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. [5][6][7] 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. 

Other common causes of Wernicke Korsakoff syndrome include:

• Eating disorders (anorexia)
• Terminal cancer
• Starvation
• Strict diets
• Inflammatory bowel disease
• Bowel obstruction
• AIDS
• Breastfeeding without supplements
• Systemic disorders like tuberculosis, uremia, etc

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. Interestingly, 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%.[8]

Pathophysiology

Brain atrophy associated with Wernicke-Korsakoff Syndrome occurs most predominantly at the mammillary bodies, though it can also occur in other places, including the dorsomedial thalami, the periaqueductal gray, the walls of the third ventricle, and the tectal plate. This is best visualized by increased signal intensity on T2/FLAIR on MRI. 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.

The ocular motor lesions are due to damage to the abducens nuclei and eye movement centers in the midbrain/pons. Ataxia is due to damage in the superior vermis.

History and Physical

An individual with Wernicke-Korsakoff syndrome classically presents 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, a paucity of speech, and indifference to the environment. However, patients commonly do not present with this full triad. As the disorder progresses, other symptoms that may develop include agitation, anger, hallucinations, and confabulations.

Evaluation

The diagnosis of Wernicke-Korsakoff syndrome is made primarily by the history and clinical findings supplemented by labs and imaging. One should maintain a high level of suspicion because of the severe morbidity and mortality that results if treatment is delayed. Prophylactic thiamine administration is relatively safe and should be started even if the diagnosis has not been confirmed. Importantly, thiamine should be administered before glucose to avoid precipitating or exacerbating Wernicke-Korsakoff syndrome.[9][10][11]

Treatment / Management

Unfortunately, it is 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 the 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.[12][13][14][15](A1)

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. The patients that depend on long-term care often have one or more comorbidities (somatic and psychiatric).

Mental Status Complications

Global confusion often resolves gradually after treatment.

One in five patients who demonstrate signs of the amnestic state after initiating treatment will have a complete recovery. The remaining patients will have varying degrees of persistent learning and memory impairments.

Maximum recovery may take years and is dependent on abstinence from alcohol.

Ataxic Complications

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

Vestibular dysfunction improves in about half of all patients.

Ocular Complications

After starting treatment, patients typically recover from Wernicke-Korsakoff syndrome in a predictable pattern. Improvement of ocular abnormalities is the most dramatic, usually occurring within hours after thiamine administration.

If the ocular abnormality does not improve after administrating thiamine, the diagnosis of Wernicke-Korsakoff syndrome should be reevaluated.

Vertical nystagmus may persist for months while the fine horizontal nystagmus can persist indefinitely.

Sixth nerve palsies, ptosis, and vertical-gaze palsies all typically recover completely. 

Mortality 

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

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

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