Korsakoff's syndrome

Korsakoff's syndrome (also called Korsakoff's dementia, Korsakoff's psychosis, or amnesic-confabulatory syndrome) is a neurological disorder caused by a lack of thiamine (vitamin B₁) in the brain. Its onset is linked to chronic alcohol abuse and/or severe malnutrition. The syndrome is named after Sergei Korsakoff, a Russian neuropsychiatrist who discovered the syndrome during the late 19th century.

Signs and symptoms

There are six major symptoms of Korsakoff's syndrome:

1. anterograde amnesia
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. minimal 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).^[1] Thiamine is essential for the carboxylation of pyruvate and deficiency during this metabolic process is thought to cause damage to the medial thalamus and mammillary bodies of the posterior hypothalamus as well as generalized cerebral atrophy.^[2] These brain regions are all parts of the limbic system, which is heavily involved in emotion and memory.

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 recognized 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 or anterior group of the thalamus (limbic-specific nuclei) is also associated with this disorder. Cortical dysfunction may have arisen from thiamine deficiency, alcohol neurotoxicity, and/ or structural damage in the diencephalon.^[3]

Originally it was thought that a lack of initiative and a flat affect were important characteristics of emotion. Studies have questioned this, proposing that it is not necessarily a symptom of Korsakoff’s. Research suggesting that Korsakoff patients are emotionally unimpaired has made this a controversial topic. It can be argued that apathy, which usually characterizes Korsakoff patients, reflects a deficit of emotional expressions, without affecting the experience or perception of emotion.^[4]

Korsakoff's Syndrome causes deficits in declarative memory in most patients,^[5] but keeps implicit spatial, verbal, and procedural memory functioning intact.^[6] People who have Korsakoff’s syndrome have deficits in the processing of contextual information. Context memories refers to the where and when of experiences and is an essential part of recollection. The ability to store and retrieve this information, such as spatial location or temporal order information is impaired.^[7] Research has also suggested that Korsakoff patients have impaired executive functions, which can lead to behavioral problems and interfere with daily activities. It is unclear however, which executive functions are affected most.^[8] However, IQ is usually not affected by the brain damage associated with Korsakoff's syndrome.^[9]

At first it was thought that Korsakoff patients used confabulation to fill in memory gaps. However, it has been found that confabulation and amnesia do not necessarily co-occur. Studies have shown that there is dissociation between provoked confabulation, spontaneous confabulation (which is unprovoked) and false memories.^[5] That is, patients could be led to believe certain things that haven’t happened, just like people without Korsakoff’s syndrome.

Causes

Conditions resulting in the vitamin deficiency and its effects include chronic alcoholism and severe malnutrition. Alcoholism may be an indicator of poor nutrition, which in addition to inflammation of the stomach lining, causes thiamine deficiency.^[10] Other causes include dietary deficiencies, prolonged vomiting, eating disorders, or the effects of chemotherapy. It can also occur in pregnant women who have a form of extreme morning sickness known as hyperemesis gravidarum.^[11] Mercury poisoning can also lead to Korsakoff's syndrome.^[12] It has also been caused by centipede (mukade) bites in Japan.^[13] Though not always, this disorder frequently can emerge as a consequential result of Wernicke’s encephalopathy.^[14]

PET scans show that there is a decrease of glucose metabolism in the frontal, parietal and cingulated regions of the brain in Korsakoff patients. This may contribute to memory loss / amnesia. Structural neuroimaging has also shown the presence of midline diencephalic lesions and cortical atrophy.^[3]

Structural lesions of the central nervous system, though rare, can also contribute to symptoms of Korsakoff’s syndrome. Severe damage to the medial dorsal nucleus inevitably results in memory deficit. Additionally, autopsies of patients with Korsakoff have showed lesions in both the midline and anterior thalamus and thalamic infarctions. Bilateral infarctions to the thalamus can result in Korsakoff-induced amnesia as well. These findings imply damage to anterior thalamic nuclei can result in disruptive memory.^[15][16]

Risk factors

A number of factors may increase a person's risk to develop Korsakoff's syndrome. These factors are often related to patients' general health and their food intake habits.^[17]

• Chemotherapy
• Dialysis
• Extreme dieting
• Age
• Genetic factors

The prevalence varies from country to country, but is estimated to be between 0.8-3% of the population.^[18]

Treatment

It was once assumed that anyone suffering from Korsakoff's syndrome would eventually need full-time care. This is still often the case, but rehabilitation can help regain some, often limited, level of independence.^[16] Treatment involves the replacement or supplementation of thiamine by intravenous (IV) or intramuscular (IM) injection, together with proper nutrition and hydration. However, the amnesia and brain damage caused by the disease does not always respond to thiamine replacement therapy. In some cases, drug therapy is recommended. Treatment of the patient requires taking thiamine orally for 3 to 12 months, though only about 20 percent of the cases are reversible. If treatment is successful, improvement will become apparent within two years although recovery is slow and often incomplete.

As an immediate form of treatment, a pairing of IV or IM with a high concentration of B-complex vitamins can be administered three times daily for period of 2–3 days. In most cases, an effective response from patients will be observed. A dose of 1 gram of thiamine can also be administered to achieve a clinical response.^[1] In patients who are seriously malnourished, the sudden availability of glucose without proper bodily levels of thiamine to metabolize is thought to cause damage to cells. Thus the administration of thiamine along with an intravenous form of glucose is often good practice.^[19]

Treatment for the memory aspect of Korsakoff’s syndrome can also include domain-specific learning, which when used for rehabilitation is called the method of vanishing cues. Such treatments aim to use patients’ intact memory processes as the basis for rehabilitation. Patients who used the method of vanishing cues in therapy were found to learn and retain information more easily.^[20]

People diagnosed with Korsakoff’s are reported to have a normal life expectancy presuming that they abstain from alcohol. Empirical research has suggested that good health practices have beneficial effects.^[19]

Prevention

The most effective method of preventing Korsakoff's syndrome is to avoid B vitamin/thiamine deficiency. In Western nations, the most common causes of such a deficiency are alcoholism and weight disorders.^[16] Because these are behavioral-induced causes, Korsakoff syndrome is essentially considered a preventable disease. Thus, fortifying foods with thiamine, or requiring companies that sell alcoholic beverages to supplement them with B vitamin/thiamine would avert many cases of Korsakoff's Syndrome.^{[21] [22]}

Case studies

A famous case study is recounted by Oliver Sacks in "The Lost Mariner" and "A Matter of Identity", which can be found in The Man Who Mistook His Wife for a Hat. Other cases include German entertainer Harald Juhnke, artist Charles Blackman,^[23] and entertainer Graham Kennedy.^{[15] [24]}

In a case of a non-alcoholic 63-year old man with severe right hippocampal hemorrhaging, neuropsychological assessments showed that he displayed severe anterograde amnesia, loss of recall, impaired recognition, and overall disorientation. He knew his birthday and could recall genuine memories of his childhood, but consistently asked about his parents who had died 25 years ago. Thalamic damage is thought to have been the trigger for the amnestic syndrome.^[15]

See also

• Alcoholic dementia

• Alcoholism
• Beriberi
• Dementia
• Malabsorption
• Wernicke–Korsakoff syndrome
• Wernicke's encephalopathy

References

External links

• The Merck Manual: Function And Dysfunction Of The Cerebral Lobes - Amnesias - Korsakoff's syndrome
• An Amnesic Patient With An Extraordinary Distorted Memory