Synonyms of Wernicke-Korsakoff Syndrome

General Discussion

Wernicke syndrome and Korsakoff syndrome (WKS) are distinct but overlapping disorders that occur due to a deficiency of thiamine (vitamin B1). Wernicke syndrome, also known as Wernicke encephalopathy, is a neurological disease characterized by three main clinical symptoms: confusion, the inability to coordinate voluntary movement (ataxia) and eye (ocular) abnormalities. Wernicke syndrome is considered the acute phase of WKS and if left untreated, transitions to the chronic irreversible Korsakoff syndrome. When these two disorders occur together, the term Wernicke-Korsakoff syndrome is used. In the United States, most cases occur associated with chronic consumption of alcohol but can occur in individuals who have malnutrition, eating disorders or other conditions that cause a deficiency in thiamine. Additionally, studies indicate that there may be some genetic predisposition for the disease.

Signs & Symptoms

WKS is the result of thiamine deficiency that leads to acute symptoms (Wernicke syndrome) that if left untreated lead to the chronic irreversible Korsakoff syndrome. Patients that experience an overlap of symptoms from both are diagnosed with WKS.

Wernicke syndrome is characterized by three main clinical symptoms: mental status changes (e.g., confused state), the inability to coordinate voluntary movement (ataxia) and eye abnormalities. Affected individuals may not display all three symptoms.

Confusion and disorientation associated with Wernicke syndrome develops over a few days or weeks and is the main problem associated with the disorder. It is an acute syndrome precipitated by thiamine deficiency. Affected individuals may experience lethargy, inattentiveness, drowsiness and indifference. Delirium often occurs especially in alcoholic patients who are also withdrawing from alcohol. If left untreated, affected individuals may develop stupor or loss of consciousness (coma). Some affected individuals may have a slow, unsteady gait. In the acute stage of the disease, this may prevent an affected individual from standing or walking without assistance.

Ocular abnormalities associated with Wernicke syndrome include double vision, rapid, involuntary eye movements (nystagmus), paralysis of certain eye muscles (ophthalmoplegia) and rarely, drooping of the upper eyelids (ptosis).

Approximately 80-90 percent of individuals with Wernicke syndrome develop Korsakoff syndrome. The symptoms of Korsakoff syndrome often develop as the mental symptoms of Wernicke syndrome begin to lessen.

Korsakoff syndrome is characterized by memory impairment, specifically short-term memory loss (i.e., the inability to form new memories or retain new information). Some affected individuals may also have random loss of long-term memories. Rarely, individuals may create imaginary events to fill in gaps in their memory (confabulation).

Attention and social behavior are relatively preserved. Affected people are able to carry on a socially appropriate conversation that may seem normal. People with Korsakoff syndrome are usually unaware of their illness.

WKS may be long lasting or permanent and affects many nerves (polyneuropathy), especially those outside of the central nervous system (peripheral neuropathy). Peripheral neuropathy may cause weakness of the arms and legs and contribute to difficulty walking. A variety of cardiovascular abnormalities may also occur in individuals with WKS including a rapid heartbeat (tachycardia), low blood pressure upon standing (postural hypotension) and loss of consciousness (syncope). Hypothermia (body losing heat too quickly) can also be a symptom of WKS.

Other symptoms can include weakness in limbs, poor muscle coordination, unsteady gait, slow walking, rapid eye movements, paralysis of eye muscles, poor fine motor function and decreased sense of smell.

Advanced stages of the acute phase of WKS lead to coma and death in 10-20% of patients.

Causes

WKS is caused by a deficiency of thiamine (vitamin B1). Thiamine is an important nutrient required to metabolize glucose used by the brain for energy. The lack of thiamine affects brain functions in the most metabolically active brain regions, including the activity of the hypothalamus which regulates temperature, appetite, emotions and growth. Thiamine deficiency affects the cells of the nervous and cardiovascular systems to a greater degree than the cells of other organ systems.

In the United States, most cases of WKS occur in alcoholics. Alcohol reduces the absorption of thiamine by the body, diminishes stores of thiamine in the liver and hampers the activity of the enzyme that converts thiamine into an active state.

The disorder may also occur due to malnutrition. Causes of malnutrition that may result in WKS include starvation, eating disorders (e.g., anorexia), prolonged or chronic vomiting as found in certain disorders such as hyperemesis gravidarum (vomiting of pregnancy). In addition, chronic disorders such as cancer, AIDS, disorders of the stomach (gastropathies) and kidney disorders may also cause WKS.

Hereditary factors may cause some individuals to have a genetic predisposition to developing WKS. Variants in the high affinity thiamine transporter gene have been implicated. The SLC19A2 gene provides instructions for making a protein called thiamine transporter 1. This protein is located on the surface of cells, where it works to bring vitamin B1 (thiamine) into cells. More research is necessary to determine what role genetics plays in the development of the disorder.

Affected Populations

WKS occurs in 1-2 percent of the general population in the United States. The disorder affects slightly more males than females and is evenly distributed between ages 30-70. Certain subpopulations such as the homeless, elderly living in isolation and psychiatric patients have higher prevalence rates.

Related Disorders

Symptoms of the following disorder can be similar to those of Wernicke-Korsakoff syndrome. Comparisons may be useful for a differential diagnosis:

Leigh syndrome is a rapidly progressive neurological disorder that begins between 3 months to 2 years. Another form of this disease occurs during adolescence into early adulthood and is called the adult-onset form of Leigh syndrome. Visual disturbances are generally the early symptoms followed by progressive difficulty coordinating voluntary movements (ataxia), sudden muscle spasms, seizures and varying degrees of dementia. The adult onset form of Leigh syndrome is rare and progresses slower than the classic form of the disease. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database).

Additional diseases to consider in differential diagnosis:

·  Alzheimer disease

·  Anoxic encephalopathy (lack of blood flow to brain tissue)

·  Temporal lobe epilepsy

·  Concussive head injury

·  Dementia with Lewy bodies (protein deposits in brain regions involved with memory, movement and thinking)

·  Herpes simplex virus affecting the brain (encephalitis)

·  Temporal lobe infarction (stroke)

·  Transient global amnesia (sudden temporary episode of memory loss not attributed to a neurological cause such as stroke or seizure)

·  Third ventricle tumor

Diagnosis

A diagnosis of WKS is made based upon a thorough clinical evaluation and a detailed patient history. This includes obtaining a person’s nutrition and daily drinking habits and current and past behaviors to identify if there has been a long-term abuse of alcohol. Tests such as routine laboratory screens and liver function tests can rule out other disorders with similar presentations. Tests that measure thiamine and erythrocyte transketolase acitivity (both which are reduced in WKS) may also help in attaining a diagnosis. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be necessary to rule out tumors, infarcts and bleeding (hemorrhaging). CT scans and MRIs may also reveal brain changes that are indicative of WKS (e.g., shrunken mammillary bodies, enlarged ventricles). The mammillary bodies are a pair of small round structures found within the brain that form part of the limbic system. The limbic system is a group of structures within the brain that are involved with emotions and in the formation of memory.

Standard Therapies

Treatment
The immediate administration of thiamine (replacement therapy) is used to treat individuals with WKS. Thiamine is given intravenously because abdominal absorption can be hampered in affected individuals. Mental status changes, vision abnormalities and ataxia all usually improve upon administration of thiamine. Thiamine administration may continue daily for several months. With early treatment, Wernicke syndrome will not necessarily progress to WKS.

Abstinence from alcohol and proper dietary changes are recommended. Magnesium and potassium are often low in people with WKS. These and other electrolytes may need to be supplemented in addition to the thiamine. Chronically malnourished patients should receive supplementation of all B vitamins until normal intake resumes. A multidisciplinary team may be required depending upon patient’s level of recovery. Specialists in neurology, psychiatry (mental health), ophthalmology (eye doctor), cardiology (heart) and gastroenterology (stomach and bowel issues) may be needed to manage patient symptoms. In addition, some affected individuals may benefit from psychological methods designed to treat mental and emotional disorders (psychotherapy).

The challenges that patients face with movement and gait can be treated with physical therapy. The walking difficulties may be permanent depending on the initial loss of movement and the timeliness of therapy.

If the disorder is caught early and treatment started promptly a full or significant recovery can be made. In some patients, confusion and mental problems may take months to resolve. In severe cases, brain damage may cause lasting problems with memory and gait. Despite early intervention, patients with WKS may not fully recover and can require long term rehabilitation and support.

Other treatment is symptomatic and supportive.