Wernicke-Korsakoff syndrome Health Article

Definition

Wernicke-Korsakoff syndrome is a severe memory disorder usually associated with chronic excessive alcohol consumption, although the direct cause is a deficiency in the B vitamin thiamin.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), the professional handbook that aids clinicians in diagnosing patients' mental disorders, refers to Korsakoff syndrome as alcohol-induced persisting amnestic disorder and includes it under the category of substance-induced persisting amnestic disorders.

Description

The disorder was first identified in the late nineteenth century. The first phase of the condition, called Wernicke's encephalopathy, was described by German neurologist and psychiatrist Karl Wernicke in 1881. He noted three key symptoms in three patients—two with alcoholism and one who had swallowed sulfuric acid. These patients suffered from mental confusion, eye movement disorders, and ataxia (poor motor coordination). A few years later, S. S. Korsakoff, a Russian psychiatrist, began publishing reports describing a syndrome of anterograde amnesia—an inability to form new memories—and confabulation in individuals with severe alcoholism or certain medical illnesses. (Confabulation refers to the practice of filling in gaps in memory by fabrication.) By 1900, researchers and clinicians studying alcoholism recognized a connection between the two conditions. The typical syndrome begins with acute Wernicke's encephalopathy, with Korsakoff syndrome emerging when the acute phase resolves. The symptoms of Wernicke's encephalopathy appear suddenly. The most prominent symptom initially is mental confusion including memory problems. On examination, patients have difficulty moving their eyes to follow a visual stimulus due to paralysis of the muscles controlling eye movements. For instance, a patient may have trouble looking upward or to the side with one or both eyes. Problems maintaining balance while standing or walking, a condition known as ataxia, are frequently observed as well. If left untreated, most of these symptoms may resolve spontaneously, but the severe memory disorder characteristic of Korsakoff syndrome remains.

The typical person with Korsakoff syndrome appears fairly normal on first impression. Intelligence is intact, and individuals with the syndrome can carry on a conversation quite naturally. They are usually able to recall and talk about incidents that took place before the onset of the disorder and recognize family members and old friends without much difficulty. The ability to form new memories is nearly absent, however. In the course of conversation, people with Korsakoff syndrome may repeat comments or questions several times. They will fail to recognize people they met minutes before or greet a friend with excitement and surprise after a brief trip to another room. These are the characteristics of anterograde amnesia. Research shows that anterograde amnesia results from a failure of memory formation and storage. New information is processed normally, but almost immediately forgotten, never making it into the regions of the brain where memories of the past are stored. People with Korsakoff syndrome thus have no memories of events that happened after the onset of the illness. Many previously stored memories are still available, however, explaining why individuals with Korsakoff syndrome can usually remember the distant past quite well.

Causes

Wernicke-Korsakoff syndrome is caused by thiamin deficiency. It is most commonly observed in people with alcoholism since heavy drinkers often eat poorly, and alcoholism interferes with absorption of nutrients from the digestive system. It can also occur in people who are malnourished for other reasons. Thiamin helps produce energy needed to make neurons function properly. Insufficient thiamin can lead to damage or death of neurons.

Thiamin deficiency damages regions of the brain, particularly the thalamus and the mammillary bodies. The thalamus is a structure deep within the brain that serves many important functions. It is often called the major relay station of the brain, and many neurons make connections in the thalamus. The mammillary bodies are part of the hypothalamus, located just below the thalamus. The mammillary bodies receive many neural connections from another part of the brain called the hippocampus, which appears to be the primary part of the brain involved in the formation of memories. Neurons in the mammillary bodies make connections with the thalamus, which in turn makes connections with the cortex of the brain, where long-term memories are stored. This may explain why damage to the mammillary bodies and thalamus can lead to anterograde amnesia. Memories formed in the hippocampus are never stored since connections between hippocampus and cortex are disrupted.

Eye movement disorders observed in the acute phase of the condition are probably due to damage to other nearby brain regions that make connections to the nerves controlling eye muscles. These nerves emerge from the brainstem located right below the thalamus and mammillary bodies. Nerves involved in balance also make connections with other nerves in the brainstem, but a separate part of the brain called the cerebellum may also contribute to ataxia. Reasons why some regions of the brain are selectively affected by thiamin deficiency are not yet fully understood, but selective vulnerability of certain neurotransmitters is suspected.