Wernicke–Korsakoff syndrome

Wernicke–Korsakoff syndrome (WKS), colloquially referred to as wet brain syndrome, 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.

The cause of the disorder is thiamine (vitamin B<sub>1</sub>) deficiency. This can occur due to 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 alcohol use disorder. Failure in diagnosis of WE and thus treatment of the disease leads to death in approximately 20% of cases, while 75% are left with permanent brain damage associated with WKS. Of those affected, 25% require long-term institutionalization in order to receive effective care.

Ocular disturbances (ophthalmoplegia)
Changes in mental state (confusion)
Unsteady stance and gait (ataxia)

This triad of symptoms results from a deficiency in vitamin B<sub>1</sub>, which is an essential coenzyme. The aforementioned changes in mental state occur in approximately 82% of patients; symptoms include confusion, apathy, inability to concentrate, and a decrease in awareness of the immediate situation they are in. If left untreated, WE can lead to coma or death. In about 29% of patients, ocular disturbances consist of nystagmus and paralysis of the lateral rectus muscles or other muscles in the eye. A smaller percentage of patients experience a decrease in reaction time of the pupils to light stimuli and swelling of the optic disc, which may be accompanied by retinal hemorrhage. Finally, the symptoms involving stance and gait occur in about 23% of patients and result from dysfunction in the cerebellum and vestibular system. Other symptoms that have been present in cases of WE are stupor, low blood pressure (hypotension), and elevated heart rate (tachycardia), as well as hypothermia, epileptic seizures and a progressive loss of hearing.

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. The criteria defined as necessary for diagnosis include prominent amnesia, forgetting quickly, and difficulty learning. Presence of thiamine-deficient encephalopathy can occur in conjunction with these symptoms. Brain testing shows that Korsakoff patients have greater problems with tasks involving planning and decision-making, linked to prefrontal cortex dysfunction overall.

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 cognition. In this particular case, cognitive symptoms included insomnia, anxiety, difficulties in concentration, loss of memory for the immediate past, and gradual degeneration of mental state consisting of confusion, confabulation, and hallucinations.

In a study conducted in 2003 by Brand et al. on the cognitive effects of WKS, the researchers used a neuropsychological test battery that included tests of intelligence, speed of information processing, memory, executive function and cognitive estimation. They found that subjects with WKS showed impairments across all aspects of the test battery, with the most pronounced deficits observed in cognitive estimation tasks. These tasks required participants to estimate physical properties such as size, weight, quantity, or time (for example, estimating the average length of a shower). Patients with WKS performed worse than control participants on all tasks in this category. Estimations involving time proved to be the most difficult, while those involving quantity were the easiest. The study also included a category for “bizarre” responses, defined as answers that fell far outside the typical range of expected values. Individuals with Wernicke–Korsakoff syndrome frequently exhibit disorientation and confabulation, often generating fabricated explanations to compensate for memory deficits. (Schnider2023). WKS patients did give answers that could fall into such a category, such as 15 seconds or 1 hour for the estimated length of a shower, or 4 kg or 15 tonnes as the weight of a car.

Memory deficits

The amnesic symptoms of WKS include both retrograde and anterograde amnesia. The retrograde deficit has been demonstrated through an inability of WKS patients to recall or recognize information for recent public events. The anterograde memory loss is demonstrated through deficits in tasks that involve encoding and then recalling lists of words and faces, as well as semantic learning tasks. WKS patients have also demonstrated difficulties in perseveration, as evidenced by a deficit in performance on the Wisconsin Card Sorting Test. It has been widely accepted that the critical structures that lead to the memory impairment in WKS are the mammillary bodies and the thalamic regions. Despite the aforementioned memory deficits, non-declarative memory functions appear to be intact in WKS patients. This has been demonstrated through measures that assess perceptual priming. 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 patients are unable to inhibit incorrect memories or to shift their attention away from an incorrect response.

Wernicke–Korsakoff syndrome in people with chronic alcohol use particularly is associated with atrophy/infarction of specific regions of the brain, especially the mammillary bodies. Other regions include the anterior region of the thalamus (accounting for amnesic symptoms), the medial dorsal thalamus, the basal forebrain, the median and dorsal raphe nuclei, and the cerebellum.

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.

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 underwent 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. 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. The role of alcohol consumption in the development of WKS has been experimentally confirmed through studies in which rats were subjected to alcohol exposure and a low-thiamine diet. In particular, studies have demonstrated that clinical signs of the neurological problems that result from thiamine deficiency developed faster in rats that received alcohol and were also deficient in thiamine than rats who did not receive alcohol. Thiamine cannot be produced in the body and must be obtained through diet and supplementation. The 2022 trial supported giving thiamine right away when Wernicke's encephalopathy is suspected, rather than waiting for test results. (Oudman2022). The duodenum is responsible for absorbing thiamine. The liver can store thiamine for 18 days. It has been argued that the memory impairments can occur as a result of damage along any part of the mammillothalamic tract, which explains how WKS can develop in patients with damage exclusively to either the thalamus or the mammillary bodies.

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. 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.

Daily recommendations of thiamine requirements are 0.66 mg per of food energy intake—approximately equivalent to 1.2 mg for men and 1.1 mg for women. Banana bags, a bag of intravenous fluids containing vitamins (including B1) and minerals, may be used as a treatment.

Epidemiology

WKS occurs more frequently in men than women and has the highest prevalence in the ages 55–65. Approximately 71% are unmarried.

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. 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%.

History

Wernicke encephalopathy

Carl Wernicke discovered Wernicke encephalopathy in 1881. His first diagnosis noted symptoms including paralyzed eye movements, ataxia, and mental confusion. Also noticed were hemorrhages in the gray matter around the third and fourth ventricles and the cerebral aqueduct. Brain atrophy was only found upon post-mortem autopsy. Wernicke believed these hemorrhages were due to inflammation and thus the disease was named polioencephalitis haemorrhagica superior. Later, it was found that Wernicke encephalopathy and Korsakoff syndrome are products of the same cause.

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.

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).

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.