Korsakoff syndrome
Korsakoff syndrome is an amnestic disorder caused by thiamine deficiency associated with prolonged use of alcohol. There is a similar condition seen in non-alcoholic Korsakoff syndrome. The syndrome and psychosis are named after Sergei Korsakoff, the Russian neuropsychiatrist who discovered it during the late 19th century.
This neurological disorder is caused by a lack of thiamine in the brain, and is also exacerbated by the neurotoxic effects of alcohol. When Wernicke encephalopathy accompanies alcoholic Korsakoff syndrome the combination is called Wernicke–Korsakoff syndrome; however, a recognized episode of Wernicke encephalopathy is not always obvious.
Signs and symptoms
There are seven major symptoms of alcoholic Korsakoff syndrome :- anterograde amnesia, memory loss for events after the onset of the syndrome
- retrograde amnesia, memory loss extends back for some time before the onset of the syndrome
- amnesia of fixation, also known as fixation amnesia
- confabulation, that is, invented memories which are then taken by the patient as true due to gaps in memory, with such gaps sometimes associated with blackouts
- minimal content in conversation
- lack of insight
- apathy – the patients lose interest in things quickly, and generally appear indifferent to change.
Thiamine is essential for the decarboxylation 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. These brain regions are all parts of the limbic system, which is heavily involved in emotion and memory.
AKS 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 also occurs in mammillary bodies. Damage to the medial dorsal nucleus or anterior group of the thalamus is also associated with this disorder. Cortical dysfunction may have arisen from thiamine deficiency, alcohol neurotoxicity, and/or structural damage in the diencephalon.
Originally, it was thought that a lack of initiative and a flat affect were important characteristics of emotional presentation in sufferers. Studies have questioned this, proposing that neither is necessarily a symptom of AKS. 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.
AKS causes deficits in declarative memory in most patients, but leaves implicit spatial, verbal, and procedural memory functioning intact. People with AKS 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.
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. Nonetheless, IQ is usually not affected by the brain damage associated with Korsakoff's syndrome.
At first it was thought that AKS 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, and false memories. That is, patients could be led to believe certain things had happened which actually had not, but so could people without alcoholic Korsakoff syndrome.
Causes
Conditions resulting in thiamine deficiency and its effects include chronic alcoholism and severe malnutrition. Alcoholism may co-occur with poor nutrition, which in addition to inflammation of the stomach lining, causes thiamine deficiency. Other causes include dietary deficiencies, prolonged vomiting, eating disorders, and the effects of chemotherapy. It can also occur in pregnant women who have a form of extreme morning sickness known as hyperemesis gravidarum. Mercury poisoning can also lead to Korsakoff's syndrome. Though it does not always co-occur, this disorder can emerge frequently as a consequential result of Wernicke's encephalopathy.PET scans show that there is a decrease of glucose metabolism in the frontal, parietal and cingulated regions of the brain in Korsakoff's patients. This may contribute to memory loss and amnesia. Structural neuroimaging has also shown the presence of midline diencephalic lesions and cortical atrophy.
Structural lesions of the central nervous system, though rare, can also contribute to symptoms of AKS. Severe damage to the medial dorsal nucleus inevitably results in memory deficit. Additionally, autopsies of patients with AKS 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.
Risk factors
A number of factors may increase a person's risk to develop alcoholic Korsakoff syndrome. These factors are often related to patients’ general health and their food intake habits.- Age
- Alcoholism
- Chemotherapy
- Dialysis
- Extreme dieting
- Genetic factors
Diagnosis
Prevention
The most effective method of preventing AKS is to avoid B vitamin/thiamine deficiency. In Western nations, the most common causes of such a deficiency are alcoholism and eating disorders. Because these are behavioral-induced causes, alcoholic 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 vitamins in general or thiamine in particular, could avert many cases of AKS.Treatment
It was once assumed that anyone suffering from AKS would eventually need full-time care. This is still often the case, but rehabilitation can help regain some, albeit often limited, level of independence. Treatment involves the replacement or supplementation of thiamine by intravenous or intramuscular 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 typically requires taking thiamine orally for 3 to 12 months, though only about 20 percent of 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 thiamine 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. 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.
Treatment for the memory aspect of AKS 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.
People diagnosed with AKS are reported to have a normal life expectancy, presuming that they abstain from alcohol and follow a balanced diet. Empirical research has suggested that good health practices have beneficial effects in alcoholic Korsakoff syndrome.