Wernicke-Korsakoff syndrome

For patient information, click here


 * Associate Editor-In-Chief:

Overview
Wernicke-Korsakoff syndrome is a is a degenerative brain disorder cause by thiamine deficiency. This is usually secondary to alcohol abuse.

Although Wernicke's and Korsakoff's may appear to be two different disorders, they are generally considered to be different stages of the same disorder, which is called Wernicke-Korsakoff syndrome. Wernicke's encephalopathy represents the "acute" phase of the disorder, and Korsakoff's amnesic syndrome represents the "chronic" phase.

Korsakoff's Psychosis and Wernicke's encephalopathy
The syndrome is a combined manifestation of two eponymous disorders, Korsakoff's Psychosis and Wernicke's encephalopathy, named for Drs. Sergei Korsakoff and Carl Wernicke.

Korsakoff's psychosis is characterized by
 * 1) confusion.
 * 2) anterograde and retrograde amnesia.
 * 3) confabulation.

Wernicke's encephalopathy is characterized by
 * 1) nystagmus
 * 2) ophthalmoplegia
 * 3) anisocoria
 * 4) ataxia
 * 5) sluggish pupillary reflexes
 * 6) coma and death if untreated

Symptoms
There are six major symptoms of Korsakoff's syndrome:
 * 1) anterograde amnesia and
 * 2) retrograde amnesia, severe memory loss
 * 3) confabulation, that is, invented memories which are then taken as true due to gaps in memory sometimes associated with blackouts
 * 4) meager content in conversation
 * 5) lack of insight
 * 6) apathy - the patients lose interest in things quickly and generally appear indifferent to change.

These symptoms are caused by a deficiency of thiamine (vitamin B1), which is thought to cause damage to the medial thalamus and possibly to the mammillary bodies of the hypothalamus as well as generalized cerebral atrophy.

When Wernicke's encephalopathy accompanies Korsakoff's syndrome, the combination is called the Wernicke-Korsakoff syndrome. Korsakoff's is a continuum of Wernicke's encephalopathy, though a recognised episode of Wernicke's is not always obvious.

Korsakoff's involves neuronal loss, that is, damage to neurons; gliosis which is a result of damage to supporting cells of the central nervous system; and hemorrhage or bleeding in mammillary bodies. Damage to the dorsomedial nucleus of the thalamus is also associated with this disorder.

Causes
Wernicke-Korsakoff syndrome results from thiamin deficiency. It is generally agreed that Wernicke's Encephalpathy results from severe acute deficiency of thiamine (Vitamin B1), whilst Korsakoff's Psychosis results from chronic deficiency of thiamin. The metabolically active form of thiamin is thiamin diphosphate which plays a major role as a cofactor in glucose metabolism. The enzymes which are dependent on thiamin diphosphate are associated with the TCA Cycle and catalyse the oxidation of pyruvate,alphaketoglutarate and branched chain amino acids. Thus, anything that encourages glucose metabolism will exacerbate an existing clinical or sub-clinical thiamine deficiency.

As stated above, Wernicke-Korsakoff in the United States is usually found in malnourished chronic alcoholics, though it is also found in patients who undergo prolonged intravenous (IV) therapy, gastric stapling or intensive care unit (ICU) stays. In some regions, thiamin deficiency can be brought about by the chronic intake of polished rice, which is thiamine deficient, resulting in BeriBeri. In individuals with sub-clinical thiamine deficiency, a large dose of glucose (either as sweet food etc or glucose infusion), can precipitate the onset of overt encephalopathy.

Wernicke-Korsakoff syndrome in alcoholics especially is associated with atrophy of specific regions of the brain, especially the mamillary bodies. Other regions include the anterior region of the thalamus (accounting for amnesic symptoms), the medial dorsal thalamus, the basal forebrain, and median and dorsal raphe nuclei.

One as-yet-unreplicated study has associated susceptiblity to this syndrome with a hereditary deficiency of transketolase, an enzyme involved in thiamine metabolism.

Diagnosis and findings
Diagnosis of Wernicke-Korsakoff syndrome is by clinical impression and can sometimes be confirmed with formal Neuropsychological assessment. Wernicke's encephalopathy typically presents with ataxia and nystagmus, and Korsakoff's psychosis with anterograde and retrograde amnesia and confabulation upon relevant lines of questioning.

Frequently, for unknown reasons, patients with Korsakoff's psychosis will exhibit marked degeneration of the mamillary bodies. The mechanism of this degeneration is unknown, but it supports current neurological theory that the mamillary bodies play a role in various "memory circuits" within the brain. An example of a memory circuit is the Papez circuit.

Treatment
Treatment consists of reversing the thiamine deficiency by giving supplemental thiamine, usually by starting with an initial intravenous or intramuscular dose followed by supplemental oral doses. It is important to start the thiamine treatment before giving any glucose as the encephalopathy will be worsened by the glucose. (Glucose administration promotes dehydrogenation of pyruvate, a biochemical reaction which consumes thiamine.) By the time amnesia and psychosis have occurred, complete recovery is unlikely.