INTRODUCTION:

Wernicke-Korsakoff syndrome (WKS) is defined as an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient. Wernicke encephalopathy (WE) and WKS are most commonly seen in people who are alcoholic, and only 20% of cases are identified before death. This 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 WKS¹. Of those affected, 25% require long-term institutionalization in order to receive effective care¹.

It is a combined manifestation of two disorders:

a) Wernicke encephalopathy and

b) Alcoholic Korsakoff syndrome.

It involves an acute Wernicke-encephalopathy phase, followed by the development of a chronic alcoholic Korsakoff syndrome phase.

a) Wernicke encephalopathy (WE/WD):

It typically comes on sudden, and will need treatment right away. Symptoms include confusion, loss of muscle coordination, and trouble with the vision.

b) Korsakoff’s syndrome (KS):

Korsakoff syndrome happens more slowly. It’s a long-term, ongoing problem that damages the part of the brain that handles memory. It was defined by Victor et al., as “an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient”. Adaptation to every new situation requires the acquisition of new information and its integration with past experience. Failure to make new memories renders the patient capable of performing only the most habitual routines. KS usually follows WE although evidence of this preceding event is not always documented. The challenge is to prevent the patient developing KS but if this fails to manage KS so as to improve brain function and to aid the patient to adapt to their cognitive impairment.

This can happen if a person doesn’t get enough vitamin B₁. The function of vitamin B₁helps the brain turn sugar into energy. When the brain and nervous system don’t get the amount they need, they don’t work as well.

History:

KS is named after the Russian neuropsychiatrist, Sergei Korsakoff, although the first detailed description of the syndrome was probably in a paper by Robert Lawson in 1878. However, Korsakoff was the first to provide a comprehensive account of the syndrome in a series of papers published between 1887 and 1891. He observed that the syndrome was usually associated with peripheral nerve inflammation (alcoholic polyneuritis; first described by Moeli in 1884) and presumed that it resulted from a toxin. Therefore, he called the syndrome “polyneuritic psychosis or cerebropathia psychica toxaemica.” In 1897, the German psychiatrist Friedrich Jolly proposed that the syndrome was better named “Korsakoff’s symptom complex” or “Korsakoff’s syndrome.”

A few years before Korsakoff published his first papers on the syndrome, the German psychiatrist Carl Wernicke described “polio encephalitis superior haemorrhagica” in the second volume of his Lehrbuch der Gehirnkrankheiten.⁹ In this classical description of what was later named “Wernicke encephalopathy,” he characterized the disease by the fairly distinctive triad of eye movement disturbances, ataxia, and mental confusion. The researchers have known since the 1960s that in most cases of histopathologically confirmed WE, only an uncharacteristic mental confusion occurs and that the clinical diagnosis of WE can be challenging and may be missed – in some studies even in the majority of cases. Although the new operational criteria for the clinical diagnosis of WE, established by Caine et al (henceforth referred to as the “Caine criteria”), may lead to a remarkable improvement of the clinical diagnosis, the diagnosis of WE is in essence a histopathological one.

The operational criteria for the clinical diagnosis of WE, as formulated by Caine et al.

Symptoms or Signs	As evidenced by one or more of the following
Occulomotar abnormalities	Ophthalmoplegia Nystagmus Gaze plasy
Cerebellar dysfunction	Unsteadiness or ataxia Impaired heel-shin testing Abnormality of past pointing
Dietary deficiencies	Under nutrition Abnormal thiamine status

Etiology and pathogenesis:

Though it has been doubted by some authors, KS is probably always preceded by WE. The uncertainty that has arisen over this issue can be explained by the fact that the clinical diagnosis of WE is very difficult and therefore often missed.

Causes:

· The first cause of WKS is alcoholism.

· The less common causes of WKS are conditions that limit nutritional absorption. Eating and nutrient absorption can be restricted by:

Ø gastric bypass surgery, which makes it difficult to meet nutritional needs due to limited food portions

Ø gastric cancer, which may limit the absorption of essential nutrients

Ø colon cancer, which can result in pain that causes you to put off eating

Ø eating disorders

Alcoholism is the first cause of WKS because people with the condition generally have a poor diet. Alcohol also prevents vitamin B₁ absorption and storage.

In United States, WKS is usually found in malnourished chronic alcoholics, though it is also found in patients who undergo prolonged intravenous (IV) therapy without vitamin B1 supplementation, gastric stapling, intensive care unit (ICU) stays or hunger strikes. In some regions, physicians have observed thiamine deficiency brought about by severe malnutrition, particularly in diets consisting mainly of polished rice, which is thiamine-deficient. The resulting nervous system ailment is called 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.^5,6,7

Wernicke–Korsakoff syndrome in alcoholics particularly is associated with atrophy/infarction 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, the median and dorsal raphe nuclei⁸, and the cerebellum.⁹

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.¹⁰

Symptoms of Wernicke encephalopathy include:

· Confusion and loss of mental activity that can progress to coma and death.

· Loss of muscle coordination (ataxia) that can cause leg tremor.

· Vision changes such as abnormal eye movements (back and forth movements called nystagmus), double vision, eyelid drooping.

· Alcohol withdrawal.

Symptoms of Korsakoff syndrome:

· Inability to form new memories

· Loss of memory, can be severe

· Making up stories (confabulation)

· Seeing or hearing things that are not really there (hallucinations)

· Exaggerated storytelling, or confabulation

How is WKS diagnosed?

Diagnosing WKS isn’t always easy.

An individual with WKS is often mentally confused. This can make communication with the doctor difficult. The doctor may overlook the possibility of a physical disorder, if patient was confused.

Signs of alcoholism:

Liver damage caused by chronic alcoholism can elevate the liver enzymes. Diagnosis of chronic alcoholism includes a physical examination to assess:

· Heart rate

· Eye movements

· Reflexes

· Blood pressure

· Body temperature

Signs of nutritional deficiency:

Nutritional tests to make sure, the patients aren’t malnourished include:

· Serum albumin test:

This test measures the levels of albumin, a protein in the blood. Low levels of albumin may signal nutritional deficiencies as well as kidney or liver problems.

· Serum vitamin B-1 test:

This test checks vitamin B-1 levels in the blood. Enzyme activity in the red blood cells (RBCs) can be tested. Low enzyme activity in the RBCs signals a vitamin B-1 deficiency.

Other Tests:

There are also imaging tests, which can help the doctor to find any damage that’s characteristic of WKS. Diagnostic imaging tests for WKS include:

· An electrocardiogram (ECG or (EKG) before and after taking vitamin B-1, which can help the doctor to find abnormalities

· A CT scan to check for brain lesions related to WD

· An MRI scan to look for brain changes related to WD

Wet Brain – Wernicke Korsakoff Syndrome:

Obviously “wet brain” is not a very scientific term or phrase. It is a very real condition that also goes by the more scientific names Wernicke-Korsakoff Syndrome (WKS), Wernicke’s Encephalopathy (WE), Korsakoff’s Psychosis and Beriberi.

People with a long history of alcoholism are prone to this chronic brain syndrome, which is caused by a deficiency of Thiamine (Vitamin B₁) in the body.

The Common Symptoms of Korsakoff Syndrome?

· Severe memory loss

· An inability to form new memories

· Confabulation, memory of events that never occurred

· Confusion, drowsiness and a paralysis of eye movements

· Ataxia, a staggering or irregular gait

· Auditory and visual hallucinations

The syndrome is named after Carl Wernicke and Sergei Korsakoff. These doctors, working independent of one another, diagnosed two different stages of this condition in the late 1800s.

Here are 10 Facts to Understand about “Wet Brain”^11-13

1. Alcohol interferes with the body’s ability to absorb Thiamine, or Vitamin B₁, which is a complex vitamin essential to overall health. Thiamine is found in foods like whole grains, brown rice, asparagus, kale, pork, beef, chicken, eggs and potatoes.

2. A severe lack of thiamine can cause wet brain even in the absence of chronic alcoholism. For instance, periods of vomiting from “morning sickness” or bulimia can cause a thiamine deficiency. Even a diet solely consisting of polished white rice can cause wet brain.

3. Korsakoff Syndrome has a sudden onset, and does not occur gradually. It can be brought on by a large dose of glucose in someone with a Vitamin B₁ deficiency. It’s hazardous for malnourished drinkers to consume a lot of sweets and foods with no vitamins.

4. This condition has been unwittingly caused by physicians administering a glucose drip to under-nourished alcoholics in their care.

5. The syndrome is generally believed to happen in two stages. First, Wernicke’s Encephalopathy presents itself as mental confusion, staggering, and the paralysis of eye movements. This is followed by Korsakoff’s Psychosis, which is the loss of memory function in the brain.

6. Failure to diagnose this syndrome leads to death in 20 percent of cases, while brain damage occurs in 75 percent of cases.

7. If caught early, during the Wernicke’s Encephalopathy phase, thiamine injections can sometimes reverse the damage and allow patients a full recovery. After the second stage of this condition, the injury to the brain is not reversible.

8. Wernicke-Korsakoff Syndrome is generally treated with thiamine and abstinence from alcohol. Over time there can be some improvements, but total recovery is very unlikely.

9. The National Institute of Health’s Office of Rare Diseases lists Wernicke-Korsakoff syndrome as a rare disease due to the fact it affects less than 200,000 in the United States.

10. Preventing wet brain is a matter of limiting alcohol intake or abstaining from it all together, while maintaining a nutritional diet that includes a regular intake of Vitamin B₁.

Alcohol is the oldest and most widely abused drug in the world. It is estimated that 15 million people in U.S. alone are currently struggling with alcohol abuse and dependence. Proper treatment can help those struggling with addiction lead happy, healthy and sober lives. No one should ever have to endure the debilitating effects of a severe brain condition caused by prolonged use of alcohol.

The mechanism of brain degeneration is unknown, but it supports the current neurological theory that the mammillary bodies play a role in various "memory circuits" within the brain. An example of a memory circuit is the Papez circuit. The following three Axial MRI images shows the diagnosis of WKS

a b c

a) 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.

b) Image showing hyperintense signal indicative of restricted diffusion in the mesial dorsal thalami.

c) Image showing hyperintense signal in the periaqueductal gray matter and tectum of the dorsal midbrain.

Treatment:

Treatment may first involve hospitalization. At the hospital, patient will be monitored to ensure the digestive system is absorbing food properly³.

The treatment for WKS includes:

· Vitamin B-1 given through an intravenous line (IV) in the arm or hand

· Vitamin B-1 given by mouth

· A balanced diet to keep vitamin B-1 levels up

· Treatment for alcoholism

After diagnosis, the doctor will most likely give you vitamin B-1 intravenously. Fast treatment may reverse many of the neurological symptoms of WKS.

In a small number of cases, treatment of vitamin B-1 deficiency produces a negative reaction. This is more common in people with alcoholism.

Negative reactions to receiving vitamin B-1 may vary, and can include alcohol withdrawal symptoms such as insomnia, sweating, or mood swings. They may also experience hallucinations, confusion, or agitation.

Prevention:

As described, alcoholic Korsakoff syndrome usually follows or accompanies Wernicke encephalopathy. If treated quickly, it may be possible to prevent the development of AKS 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. Thus, there is hope that with treatment Wernicke encephalopathy will not necessarily progress to WKS.

In order to reduce the risk of developing WKS it is important to limit the intake of alcohol or drink 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^14-19. This prevention method may specifically help heavy drinkers who refuse to or are unable to quit.

REFERENCES:

1. Thomson Allan D and Marshall E Jane. The natural history and pathophysiology of Wernicke's Encephalopathy and Korsakoff's Psychosis. Alcohol and Alcoholism. 2006, 41 (2): 151–158.

2. Vetreno Ryan Peter. Thiamine deficiency-induced neurodegeneration and neurogenesis (PhD Thesis). Binghampton University.2011.

3. Sechi, Gian Pietro and Serra Alessandro. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. The Lancet Neurology. 2007, 6 (5): 442–455.

4. Kyoko Konishi. The Cognitive Profile of Elderly Korsakoff's Syndrome Patients. 2009.

5. Zimitat Craig and Nixon PF. Glucose loading precipitates acute encephalopathy in thiamin-deficient rats. Metabolic Brain Disease. 1999, 14 (1): 1–20.

6. Navarro D, Zwingmann C, Chatauret N, Butterworth RF. Glucose loading precipitates focal lactic acidosis in the vulnerable medial thalamus of thiamine-deficient rats. Metabolic Brain Disease. 2008, 23 (1): 115–122.

7. Watson AJS, Walker JF, Tomkin GH, Finn MMR, Keogh JAB. Acute Wernickes Encephalopathy precipitated by glucose loading. Irish Journal of Medical Science. 1981, 150 (10): 301–3.

8. Mann Karl, Agartz Ingrid, Harper, et al. Neuroimaging in Alcoholism: Ethanol and Brain Damage. Alcoholism: Clinical and Experimental Research. 2001; 25 (5 Suppl ISBRA): 104S–109S.

9. Butterworth RF. Pathophysiology of cerebellar dysfunction in the Wernicke-Korsakoff syndrome. The Canadian Journal of Neurological Sciences. 1993; 20 (3): S123–6.

10. Nixon Peter F, Kaczmarek MJ, Tate J, Kerr RA and Price John. An erythrocyte transketolase isoenzyme pattern associated with the Wernicke-Korsakoff syndrome. European Journal of Clinical Investigation. 1984; 14 (4): 278–81.

11. https://emedicine.medscape.com/article/288379 overview

12. https://medlineplus.gov/ency/article/000771.htm

13. https://www.webmd.com/brain/wernicke-korsakoff-syndrome-facts#1

14. https://www.caregiver.org/pilotIntegration/indexPersistent.html?uri=%2Fwernicke-korsakoff-syndrome

15. https://www.medicalnewstoday.com/articles/220007.php

16. https://pmj.bmj.com/content/73/855/27

17. https://www.omicsonline.org/scholarly/wernickekorsakoff-syndrome-journals-articles-ppts-list.php

18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545191/

19. https://www.healthline.com/health/wernicke-korsakoff-syndrome#diagnosis

Received on 24.12.2018 Accepted on 21.01.2019

Asian J. Pharm. Res. 2019; 9(2): 104-108.

DOI: 10.5958/2231-5691.2019.00017.0