Wernicke-Korsakoff Syndrome (WKS): Causes, Risk Factors, and Treatment

Article Highlights

This article will discuss the various elements of WKS in the following sections:

PART I

• What is Wernicke-Korsakoff Syndrome (WKS)?
• What is Korsakoff Syndrome? (KS)
• What is Wernicke’s Encephalopathy (WE)?
• History of Wernicke-Korsakoff Syndrome
• The Relationship of WKS to Alzheimer’s and Dementia

PART II

• Causes of Wernicke-Korsakoff Syndrome
• Alzheimer’s and Other Risk Factors for Wernicke’s
• Symptoms of Wernicke-Korsakoff Syndrome
• Diagnosis of Wernicke-Korsakoff Syndrome (WKS)
• Treatments for Wernicke-Korsakoff Syndrome (WKS)
• Caring for an Individual with WKS
• Final Thoughts for Caregivers of People with WKS

Part I

What is Wernicke-Korsakoff Syndrome (WKS)?

Wernicke-Korsakoff Syndrome, also called Wernicke’s or Korsakoff’s, is a degenerative brain disease that is caused by a chronic thiamine deficiency, or lack of vitamin B-1, that is associated with an elevated level of alcohol consumption over an extended period of time. Cancer, chemotherapy, severe gastrointestinal problems, malnutrition, and several other conditions can also be risk factors for WKS.

Wernicke-Korsakoff syndrome represents the most recognized nervous system irregularities arising from vitamin B-1 deficiency. The label WKS is associated with two distinct conditions, each relating to a disparate phase of the disorder:

1. Korsakoff syndrome (KS)
2. Wernicke’s encephalopathy(WE)

These are different conditions that often work in tandem in the same person, with Wernicke’s encephalopathy representing the acute phase of the disorder and Korsakoff syndrome representing the progression of the disorder to a chronic or longer lasting stage. Both are due to brain damage, mostly in the thalamus and hypothalamus, caused by a lack of vitamin B-1.

What is Korsakoff Syndrome?

Korsakoff, or Korsakoff’s, syndrome (KS) is a brain condition that can develop from deficiencies in vitamin B-1. Boosted by thiamine (vitamin B-1), brain cells are able to generate energy from sugar. When thiamine levels fall too low, these brain cells get deprived of the nutrients that support the production of energy at levels that are sufficient for optimal function. This can result in the brain disorder known as Korsakoff syndrome, characterized by an impairment in memory that is considerably out of proportion to other cognitive damages.

Korsakoff syndrome refers to a chronic neurologic condition that usually occurs as a consequence of WE. Korsakoff syndrome thus frequently occurs following an episode of Wernicke’s encephalopathy, which is a life-threatening severe brain reaction to critical lack of thiamine. It has to be noted, however, that Korsakoff syndrome can also develop in individuals who have not had a prior episode of Wernicke’s encephalopathy (WE).

What is Wernicke’s Encephalopathy (WE)?

Individuals with Wernicke’s encephalopathy have bleeding in the lower sections of the brain, particularly in the thalamus and hypothalamus. These sectors of the brain control the nervous and endocrine systems.

Wernicke’s encephalopathy involves various cognitive (thinking) and nervous system changes. When not recognized or treated early, it can lead to permanent brain damage and death. WE is also recognized as a medical emergency that causes life-threatening brain disruption that is characterized by an acute onset of mental confusion, ophthalmoplegia (referring to weakness or paralysis of muscles that are responsible for eye movements), and unsteady, staggering and stumbling, uncoordinated walking known as gait ataxia (referring to abnormal, erratic movements).

Relentless alcohol consumption is the most common underlying condition of Wernicke’s encephalopathy. Excessive alcohol intake interferes with thiamin absorption from the GI tract and hepatic storage of thiamin; the poor nutrition associated with alcoholism often translates into insufficient vitamin B-1 intake. Not all thiamin-deficient alcohol abusers however need end up with Wernicke’s encephalopathy; this means that other factors may also be at play. Genetic abnormalities that result in a defective form of transketolase, an enzyme that processes thiamin, may additionally constitute a risk factor.

History of Wernicke-Korsakoff Syndrome

In 1881, a German physician, psychiatrist and neuropathologist by the name of Carl Wernicke described an acute encephalopathy characterized by critical mental confusion. His initial diagnosis also highlighted paralyzed eye movements and hemorrhages in the gray matter around the third and fourth ventricles and the cerebral aqueduct (this provides a conduit for important fluids to flow inside the brain). From his early work, he became known for his influential research into the pathological effects of specific forms of encephalopathy, and study of receptive aphasia, both of which are commonly associated with Wernicke’s name and referred to as Wernicke’s encephalopathy.

It was later found that Wernicke’s encephalopathy and Korsakoff’s syndrome are products of the same cause.

A few years after Carl Wernicke, Russian neuropsychiatrist Sergei Korsakoff examined the effects of excessive alcohol consumption over time on dementia-like impairments. He described a chronic amnestic syndrome in which memory was impaired disproportionately to other cognitive faculties. While both observations were described in the context of chronic alcoholism, neither Wernicke nor Korsakoff initially recognized the relationship between the disorders, but the dots were connected by later researchers.

The Relationship of WKS to Alzheimer’s and Dementia

It is referred to as Alcohol-Related Dementia (ARD), with a related field known as alcohol-induced persisting amnestic syndrome (aka Wernicke-Korsakoff syndrome, or WKS). The characteristics of these conditions have received increasing research in recent times, with various imaging studies suggesting that abuse of alcohol over a long period of time can cause permanent functional damage in the brain. There are not clear indications however as to the effect of alcohol’s toxicity, and the impact of vitamin B-1 deficiency on the duration of the damage in the brain. For example, different patterns of a person’s excessive alcohol consumption, and the person’s other alcohol-related lifestyle factors, have led to complications in the interpretation of the results on cognitive function.

The most current diagnostic systems recognize two main conditions of alcohol-related cognitive impairment: Alcohol-Related Dementia (ARD) and Wernicke-Korsakoff Syndrome (WKS). The complication arises nevertheless when “alcohol-related brain damage” is increasingly used as an overarching label to encompass both of these conditions. Put in simpler terms, it is far from being evident what level of alcohol consumption, and how alcohol is ingested (e.g. with or without food), begins to form an underlying cause for the ensuing brain and cognitive damage. The subsequent question also becomes what level of lowered consumption of alcohol might provide protection from different manifestations of dementia or cognitive impairment.

Furthermore, it has been more or less ascertained through epidemiological studies that people who experience alcohol-related dementia (ARD) have a greater likelihood to:

• Be male
• Be socially isolated
• Have a younger age of onset of alcohol-related dementia than those with other types of dementia
• Experience deficits in vision and spatial function
• Experience memory problems
• Experience issues with executive or mentally demanding tasks

There is a slight contrast in these manifestations in that people with Wernicke-Korsakoff Syndrome (WKS) appear to belong to both genders, and impairments on mentally demanding tasks are commonly detected in tandem with memory problems. In addition, persons with alcohol-related impairments can, with prolonged abstinence from alcohol, be at least partially rehabilitated in their functional capabilities.

Part II

Causes of Wernicke-Korsakoff Syndrome

By far the most prevalent cause of Wernicke-Korsakoff Syndrome is excessive alcohol consumption over an extended period of time that is common among alcoholics. Thiamine (vitamin B-1) deficiency is a common consequence of over-indulgence in alcohol consumption. Individuals who fast for extended periods of time can also have a lack of vitamin B-1, as can those who are poorly nourished or whose systems do not properly digest their regular intake of nutrients.

And although heavy drinking commonly comes with inadequate diets (fast and processed food, with sizable amounts of preservatives, dyes and coloring agents), alcohol interferes with the digestive system’s primary task of funneling vital nutrients to the rest of the body. In that context, the body needs thiamine to convert food, and predominantly sugar, into energy. Vitamin B-1 has a short shelf life of only 18 days in the body, and it is stored in minute amounts in the liver.

There are various other risk factors for WKS, the risk being higher for people who have:

• AIDS
• Chronic infection
• Colon cancer; this type of cancer can cause pain, which in turn inhibits appetite and adequate food consumption
• Other type of cancer that has metastasized and spread into other parts of the body
• Effects of chemotherapy
• Chewing, swallowing, choking or other eating disorders, such as Alzheimer’s and other patients with eating complications such as hyperemesis, which refers to relentless and rigorous vomiting
• Anorexia, which is an emotional disorder characterized by an obsessive desire to lose weight by refusing to eat
• Congestive heart failure, when treated with long-term diuretic therapy
• Gastric bypass surgery, commonly for obesity, which makes it difficult to meet nutritional needs due to limited food portions
• Long-term kidney dialysis
• Prolonged periods of strict dieting or fasting

Alzheimer’s and Other Risk Factors for Wernicke’s

Any patient with alcohol misuse whose symptomatic manifestations include confusion, gastrointestinal problems, nausea and vomiting, exhaustion, weakness, apathy or indifference, should be considered at high risk of Wernicke’s encephalopathy and treated appropriately. Other risk factors include:

• Anyone with Alzheimer’s, or someone with another type of dementia, who also indulges in heavy drinking
• Malnutrition, nutrient-poor diets, or other factors that inhibit nutritious eating
• Individuals with unexplained hypotension or hypothermia
• Individuals with AIDS
• Individuals who consume alcoholic beverages who also cannot afford to obtain medical care or a regular supply of adequate food
• Individuals undergoing long-term kidney dialysis

Symptoms of Wernicke-Korsakoff Syndrome

Symptoms of WKS divide into two areas:

1. Wernicke’s encephalopathy (WE)
2. Korsakoff syndrome (KS)

Symptoms of  Wernicke’s encephalopathy (WE)

Symptoms of Wernicke’s encephalopathy may include:

• A severe onset of mental confusion that develops over a few days or weeks
• Disorientation and loss of mental activity that can lead to a coma or death
• Altered mental status and possible severe pain due to alcohol withdrawal manifestations
• Lethargy, inattentiveness, drowsiness and indifference
• Ophthalmoplegia, which is associated with failing or paralysis of muscles that are responsible for jerky or involuntary eye movements
• Side to side, or back and forth eye movements known as nystagmus
• Double vision and droopy eyelids
• In extreme cases, delirium may occur. If left untreated, affected individuals may develop stupor or loss of consciousness (coma)
• Tachycardia (rapid heart beat)
• Gait ataxia, associated with abnormal, erratic movements, an unsteady and wobbly bearing, stumbling, and awkward or clumsy walking
• Lanky appearance, as though malnourished
• Appearance of being drunk when they are not drunk, due to their lack of coordinated movements (known as ataxia)
• Appearance of being cold, caused by low body temperature

Symptoms of Korsakoff syndrome

A vast majority of persons with Wernicke’s syndrome (over 80 percent) advance to Korsakoff syndrome. The manifestations of Korsakoff syndrome often occur as the mental symptoms of Wernicke’s start to subside, and they may include:

• Difficulties managing or performing activities of daily living (ADLs)
• Disorientation with time and place
• Anterograde amnesia – associated with the loss of memory for the most recent happenings, particularly those that developed post-onset of the syndrome
• Occasional loss of long-term memories
• Confabulation, which means the subconscious and non-deliberate creation of illusory or manufactured events or dialogues that happen when the brain is trying to fill the gaps in their recollections (this is also known as “fictitious memories”)
• Ineptitude or failure to absorb and repeat simple bits of information or learn new functions
• Personality changes may occur, displaying indifference and lack of curiosity or repetitive behavior and chattiness
• Telescoping of occurrences – or referring to an event as if it took place lately when in reality it occurred many years earlier.

Diagnosis of Wernicke-Korsakoff Syndrome (WKS)

Diagnosing Wernicke-Korsakoff Syndrome at best represents the doctor’s best judgment about the perceived signs and symptoms. Its symptoms may moreover be mistaken for those of a person with a head injury, or for common symptoms among individuals who drink excessive amounts of alcohol such as intoxication-related disorientation, or even infection-related delirium.

Nevertheless, the first step usually is to check blood alcohol levels for alcoholism, often followed by a liver test since liver damage commonly results from over indulgence in alcohol consumption.

The physician would also want to check for malnutrition and, more specifically, for thiamine.

A serum albumin test can be undertaken to measure the levels of a protein in the blood known as albumin. Low levels of albumin may reflect on issues with the liver or kidney, or low levels of vitamin B-1.

Another blood test can be initiated to check for levels of thiamine. Low enzyme presence in the red blood cells can indicate a lack of vitamin B-1 in the blood system.

Imaging tests can also be used. For example, an EKG electrocardiogram before and subsequent to giving vitamin B-1 can tell the physician if there are irregularities. Other imaging tests can check for brain lesions or other brain changes.

Treatments for Wernicke-Korsakoff Syndrome (WKS)

When caught at an early stage, and with sustained abstinence from alcohol, WKS is a preventable, treatable disease. A marked recovery under those conditions is possible, with the person being able to pick up on simple chores once again and on their own relatively quickly. A complete recovery from symptoms of confusion however may take a longer period of time. If it is not caught in the early stages, brain damage may prove irreversible, and individuals will have lasting issues with memory and other typical symptoms.

When it comes to Wernicke-Korsakoff Syndrome (WKS), the goal of therapy starts with rapid correction of low levels of thiamine. Physicians thus often recommend taking vitamin B-1 and other vitamins to heavy drinkers. Injectable thiamine can also be administered until other diagnostic tools can be made.

Vitamin B-1 depletion can occur in the body within a few weeks since the body stores thiamine in minuscule amounts. Thiamine can be found in various foods, most prominent of which include red meat and pork, rice, beans and lentils, dairy products and yeast, seeds, oats and other nuts, and fruits like oranges.

Treatment that starts with hospitalization for emergency intravenous injections of vitamin B-1 needs to be followed up with lifestyle adaptations that naturally include sustained sobriety. Long-term dietary modifications with supplements of thiamine need to be implemented as well to avoid a recurrence in the impairments caused by WKS. Data suggest that about 25% of those who develop Korsakoff’s syndrome eventually recover from the disease with treatment, about half improve but don’t recover completely, and about 25% remain unchanged.

Caring for an Individual with WKS

The first task for families and caregivers of a loved one with Wernicke-Korsakoff Syndrome (WKS) is to ensure that they abstain from further binging on alcohol, and that their daily diet is balanced and infused with natural thiamine and thiamine supplements. Even then however, some of the brain damage that occurred may take a year or more, if at all, to start reversing. In that interim, the person will likely continue displaying some WKS symptoms such as agitation, other behavior problems, lack of coordination, shuffled walking, side to side eye movements, and more.

During this recovery period, the family should focus on keeping their loved one safe and always in the company of someone else as the confused state of mind can lead to house fires, falls and other hazards.

Here is what you, the caregiver, will be up against:

1. People with WKS may talk repeatedly and asking the same questions over and over again. Try to remain calm and see if introducing a new activity or a change in the environment reduces the stress and quiets down the agitation.
2. Your loved one will pick up on your tone, your pitch, and the rest of your body language. The best thing you can do for yourself and them is to avoid them getting additionally frustrated by reading anger into your demeanor.
3. Reduce uncertainty and nervousness by labeling doors and drawers with notes or pictures. You can spell out the day’s highlights with notes such as “walk in the backyard at 3:00 pm”, or “dinner at 5:00 pm.” Such reminders can help the person feel secure.
4. If agitation becomes uncontrollable, seek the help of your loved one’s physician. The physician may be able to prescribe medications to calm your loved one down and mitigate their anxiety.

Individuals with a history of alcohol abuse have often isolated themselves from family and friends, leading to strained or difficult relationships. As a caregiver, you might feel some resentment caring for a parent or spouse with a history of alcoholism. It can be helpful to seek out the support of mental health professionals or case workers who have training in working with alcoholism. Family meetings and support groups can also be beneficial to increase the support network.

Final Thoughts for Caregivers of People with WKS

The best advice to give someone caring for a person with WKS is the same advice commonly given to anyone caring for an individual with Alzheimer’s disease:

• Remember to look after yourself as diligently as you look after your loved one
• You can’t be any good to anyone if you are not well yourself
• Seek relief or respite from your responsibilities on a daily basis, if possible, and try to take advantage of quality time with other friends
• Join a support group
• Remember you are not alone – seek out resources and talk to others going through similar experiences

Sources

• National Institute of Neurological Disorders and Stroke
• Alzheimer’s Association
• Isenberg-Grzeda, Kutner, & Nicolson (2012). Wernicke-Korsakoff-Syndrome: Under-Recognized and Under-Treated,
  Psychosomatics, Volume 53, Issue 6,507-516,
• Mount Sinai Health Library

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