Wernicke–Korsakoff syndrome
Wernicke-Korsakoff syndrome | |
---|---|
Other names | Korsakoff's psychosis, alcoholic encephalopathy,[1] "wet brain"[2] |
Thiamine | |
Specialty | Psychiatry, neurology |
Wernicke-Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.[1]
The cause of the disorder is thiamine (vitamin B1) deficiency. This can occur due to Wernicke encephalopathy, eating disorders, malnutrition, and alcohol abuse. These disorders may manifest together or separately. WKS is usually secondary to prolonged alcohol abuse.
Wernicke encephalopathy and WKS are most commonly seen in people with an
Signs and symptoms
The syndrome is a combined manifestation of two namesake disorders,
Wernicke encephalopathy
WE is characterized by the presence of a triad of symptoms:[6]
- Ocular disturbances (ophthalmoplegia)
- Changes in mental state (confusion)
- Unsteady stance and gait (ataxia)
This triad of symptoms results from a deficiency in
About 19% of patients have none of the symptoms in the classic triad at first diagnosis of WE; however, usually one or more of the symptoms develops later as the disease progresses.[6]
Korsakoff syndrome
The DSM-5 classifies Korsakoff syndrome under Substance/Medication-Induced Major or Mild Neurocognitive Disorders, specifically alcohol-induced amnestic confabulatory.[7] The diagnostic criteria defined as necessary for diagnosis includes prominent amnesia, forgetting quickly, and difficulty learning. Presence of thiamine deficient encephalopathy can occur in conjunction with these symptoms.[7]
Despite the assertion that alcoholic Korsakoff syndrome must be caused by the use of alcohol, there have been several cases where it has developed from other instances of thiamine deficiency resulting from gross malnutrition due to conditions such as stomach cancer, anorexia nervosa, and gastrectomy.[8]
Cognitive effects
Several cases have been documented where Wernicke-Korsakoff syndrome has been seen on a large scale. In 1947, 52 cases of WKS were documented in a prisoner of war hospital in Singapore where the prisoners' diets included less than 1 mg of thiamine per day. Such cases provide an opportunity to gain an understanding of what effects this syndrome has on
In a study conducted in 2003 by Brand et al. on the cognitive effects of WKS, the researchers used a
Memory deficits
The amnesic symptoms of WKS include both retrograde and anterograde amnesia.
Other studies have shown deficits in recognition memory and stimulus-reward associative functions in patients with WKS.[12] The deficit in stimulus-reward functions was demonstrated by Oscar-Berman and Pulaski who presented patients with reinforcements for certain stimuli but not others, and then required the patients to distinguish the rewarded stimuli from the non-rewarded stimuli. WKS patients displayed significant deficits in this task. The researchers were also successful in displaying a deficit in recognition memory by having patients make a yes/no decision as to whether a stimulus was familiar (previously seen) or novel (not previously seen). The patients in this study also showed a significant deficit in their ability to perform this task.[12]
Confabulation
People with WKS often show confabulation, spontaneous confabulation being seen more frequently than provoked confabulation.[13] Spontaneous confabulations refer to incorrect memories that the patient holds to be true, and may act on, arising spontaneously without any provocation. Provoked confabulations can occur when a patient is cued to give a response, this may occur in test settings. The spontaneous confabulations viewed in WKS are thought to be produced by an impairment in source memory, where they are unable to remember the spatial and contextual information for an event, and thus may use irrelevant or old memory traces to fill in for the information that they cannot access. It has also been suggested that this behaviour may be due to executive dysfunction where they are unable to inhibit incorrect memories or because they are unable to shift their attention away from an incorrect response.[13]
Causes
WKS is usually found in people who have used
As stated above, Wernicke-Korsakoff syndrome in the United States is usually found in malnourished
Wernicke-Korsakoff syndrome in people with chronic alcohol use particularly is associated with
One as-yet-unreplicated study has associated susceptibility to this syndrome with a hereditary deficiency of transketolase, an enzyme that requires thiamine as a coenzyme.[20]
Post-gastrectomy
The fact that gastrointestinal surgery can lead to the development of WKS was demonstrated in a study that was completed on three patients who recently undergone a gastrectomy. These patients had developed WKS but were not alcoholics and had never suffered from dietary deprivation. WKS developed between 2 and 20 years after the surgery.[21] There were small dietary changes that contributed to the development of WKS but overall the lack of absorption of thiamine from the gastrointestinal tract was the cause. Therefore, it must be ensured that patients who have undergone gastrectomy have a proper education on dietary habits, and carefully monitor their thiamine intake. Additionally, an early diagnosis of WKS, should it develop, is very important.[21]
Alcohol-thiamine interactions
Strong evidence suggests that ethanol interferes directly with thiamine uptake in the gastrointestinal tract. Ethanol also disrupts thiamine storage in the liver and the transformation of thiamine into its active form.
Pathophysiology
The vitamin thiamine, also referred to as vitamin B1, is required by three different enzymes to allow for conversion of ingested nutrients into energy.
Brain atrophy associated with WKS occurs in the following regions of the brain:
- the mammillary bodies,
- the thalamus,
- the periaqueductal grey,
- the walls of the 3rd ventricle,
- the floor of the 4th ventricle,
- the cerebellum, and
- the frontal lobe.
In addition to the damage seen in these areas there have been reports of damage to cortex, although it was noted that this may be due to the direct toxic effects of alcohol as opposed to thiamine deficiency that has been attributed as the underlying cause of Wernicke-Korsakoff Syndrome.[25]
The amnesia that is associated with this syndrome is a result of the atrophy in the structures of the
Diagnosis
Diagnosis of Wernicke-Korsakoff syndrome is by clinical impression and can sometimes be confirmed by a formal neuropsychological assessment. Wernicke
Frequently, secondary to thiamine deficiency and subsequent cytotoxic edema in Wernicke encephalopathy, patients will have marked degeneration of the
-
Axial MRI FLAIR image showing hyperintense signal in the mesial dorsal thalami, a common finding in Wernicke encephalopathy. This patient was nearly in coma when IV thiamine was started, he responded moderately well but was left with some Korsakoff type deficits.
-
Axial MRI B=1000 DWI image showing hyperintense signal indicative of restricted diffusion in the mesial dorsal thalami
-
Axial MRI FLAIR image showing hyperintense signal in the periaqueductal gray matter and tectum of the dorsal midbrain
Prevention
As described, Korsakoff syndrome usually follows or accompanies Wernicke encephalopathy. If treated quickly, it may be possible to prevent the development of WKS with thiamine treatments. This treatment is not guaranteed to be effective and the thiamine needs to be administered adequately in both dose and duration. A study on Wernicke-Korsakoff syndrome showed that with consistent thiamine treatment there were noticeable improvements in mental status after only 2–3 weeks of therapy.[6] Thus, there is hope that with treatment Wernicke encephalopathy will not necessarily progress to WKS.[vague]
In order to reduce the risk of developing WKS it is important to limit the intake of alcohol in order to ensure that proper nutrition needs are met. A healthy diet is imperative for proper nutrition which, in combination with thiamine supplements, may reduce the chance of developing WKS. This prevention method may specifically help heavy drinkers who refuse to or are unable to quit.[1]
A number of proposals have been put forth to fortify alcoholic beverages with thiamine to reduce the incidence of WKS among those heavily abusing alcohol. To date, no such proposals have been enacted.[27][28][29][30][31][excessive citations]
Daily recommendations of thiamine requirements are 0.66 mg per 8,400 kilojoules (2,000 kilocalories) of food energy intake—approximately equivalent to 1.2 mg for men and 1.1 mg for women.[14]
Treatment
The onset of Wernicke encephalopathy is considered a medical emergency, and thus thiamine administration should be initiated immediately when the disease is suspected.
Epidemiology
WKS occurs more frequently in men than women and has the highest prevalence in the ages 55–65. Approximately 71% are unmarried.[4]
Internationally, the prevalence rates of WKS are relatively standard, being anywhere between zero and two percent. Despite this, specific sub-populations seem to have higher prevalence rates including people who are homeless, older individuals (especially those living alone or in isolation), and psychiatric inpatients.[35] Additionally, studies show that prevalence is not connected to alcohol consumption per capita. For example, in France, a country that is well known for its consumption and production of wine, prevalence was only 0.4% in 1994, while Australia had a prevalence of 2.8%.[36]
History
Wernicke encephalopathy
Korsakoff syndrome
Although WE and AKS were discovered separately, these two syndromes are usually referred to under one name, Wernicke-Korsakoff syndrome, due to the fact that they are part of the same cause and because the onset of AKS usually follows WE if left untreated.[citation needed]
Society and culture
The British neurologist Oliver Sacks describes case histories of some of his patients with the syndrome in the book The Man Who Mistook His Wife for a Hat (1985).[citation needed]
Frontman and lead vocalist of the hard rock band Breaking Benjamin, Benjamin Burnley, is well known to be living with Wernicke-Korsakoff syndrome due to his past alcoholism. He has written multiple songs about addiction and his experiences with alcohol, with many of such songs being found on the band's 2009 album Dear Agony as it was the first album Burnley had written and recorded completely sober.[citation needed]
See also
- Alcoholic dementia
- Dementia
- Malabsorption
References
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- ^ Centerwall, Brandon (February 12, 1979). "Put Thiamine in Liquor". The New York Times. Retrieved December 30, 2018.
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- ^ Meikle, James (November 18, 2002). "A pint of best and be generous with the B1, please landlord". The Guardian. Retrieved December 30, 2018.
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