What is Wernicke-Korsakoff Syndrome?
Wernicke-Korsakoff syndrome (WKS) is a brain-related disorder triggered by a below-average level of thiamine (also known as vitamin B1) in the brain. The disorder is most common in people who chronically abuse alcohol, but it may also be caused by malnutrition or conditions that disrupt nutrient absorption.
WKS is a combination of two distinct disorders, Wernicke encephalopathy, and Korsakoff syndrome. The symptoms of Wernicke encephalopathy usually develop first, and Korsakoff syndrome symptoms typically develop later if the thiamine deficiency goes untreated. Approximately 90% of people with Wernicke encephalopathy go on to develop Korsakoff syndrome.
Symptoms of Wernicke Encephalopathy
Common symptoms of Wernicke encephalopathy include:
- Problems with muscle coordination
- Vision impairment
- Abnormal eye movements
- Rapid heartbeat
- Low body temperature
- Low blood pressure
Symptoms of Korsakoff Syndrome
Symptoms of Korsakoff syndrome include:
- Short-term memory loss
- Inability to form new memories
- Isolated long-term memory loss
- Creation of false stories (confabulation, a rare symptom)
- Visual impairment
- Muscle tremors
What Causes Wernicke-Korsakoff Syndrome?
WKS is caused by the lack of an adequate level of thiamine, a nutrient essential in the process of energy generation inside cells. The damage caused by thiamine deficiency occurs throughout the body, but it tends to be most pronounced parts of the body that have the highest energy requirements, including the brain and heart.
Thiamine deficiency can be caused either by a lack of sufficient thiamine intake or conditions that interfere with the absorption of thiamine. The disorder may be triggered by any of several factors, including:
- Eating disorders such as anorexia or bulimia
- Chronic illness
- Bariatric surgery
- Extreme chronic vomiting, including during pregnancy (hyperemesis gravidarum)
- Overactive thyroid (thyrotoxicosis)
Is Wernicke-Korsakoff Syndrome Hereditary?
Studies have suggested that some people may be at increased risk of developing WKS because of inherited mutations (abnormal changes) in their genes. The risk seems to be associated with a gene called SLC19A2, which provides instructions for making a protein called thiamine transporter 1. This protein is essential for transferring thiamine into cells, where it’s necessary to help the cells produce energy. Research into possible inherited genetic predisposition for WKS is ongoing.
How Is Wernicke-Korsakoff Syndrome Detected?
The symptoms of Wernicke encephalopathy, the first stage of WKS, typically develop over a few days or weeks. Early detection is important because many of the symptoms of encephalopathy are often reversible if treated promptly. When the disorder progresses to Korsakoff syndrome, the effects are more likely to be permanent.
Early signs of Wernicke encephalopathy may include:
- Problems with attention
- Coordination problems
- Vision impairment or involuntary eye movements
How Is Wernicke-Korsakoff Syndrome Diagnosed?
A doctor may suspect WKS if a person with any of the disorder’s risk factors presents with symptoms consistent with the disorder. If this is the case, the doctor will conduct exams and tests to rule out other possible causes for the symptoms and confirm the WKS diagnosis. The diagnostic process may include:
- Physical exams and neurological exams to rule out other possible causes of the symptoms
- Laboratory tests to assess liver function and check for indicators of thiamine deficiency
- Magnetic resonance imaging (MRI) or computerized tomography (CT) scans to rule out tumors, lesions, or internal bleeding that could be causing the symptoms
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Wernicke-Korsakoff Syndrome Treated?
Treatment of WKS involves the replacement of thiamin in the patient’s body. Supplemental thiamine is usually administered intravenously because the conditions that lead to WKS often prevent the proper absorption of thiamine through the digestive system.
Other possible treatments include:
- Abstinence from alcohol
- Dietary changes
- Supplements such as magnesium, potassium, and other B vitamins
- Treatment of problems related to vision, the heart, and the digestive system
- Psychotherapy to treat underlying mental health-related issues
When treated early, WKS symptoms usually resolve, although complete recovery can take months. In cases where significant brain damage has occurred before treatment, memory and coordination problems can be permanent.
How Does Wernicke-Korsakoff Syndrome Progress?
Left untreated, WKS can lead to severe, potentially life-threatening complications. Long-term complications can include:
- Alcohol withdrawal symptoms
- Permanent impairment of coordination resulting in falls and injuries
- Permanent memory loss
- Permanent impairment of cognitive functions
- Pain and tingling caused by permanent nerve damage (alcoholic neuropathy)
- Relationship problems and social isolation
How Is Wernicke-Korsakoff Syndrome Prevented?
Careful monitoring of a person with any of the risk factors for WKS may help prevent the development of the disorder, and prompt treatment may prevent the worst of the disorder’s complications. Possible preventive measures include:
- Reduction of alcohol consumption
- Dietary changes to ensure an adequate supply of thiamine
- Thiamine supplements for people who are unable to reduce their drinking
Wernicke-Korsakoff Syndrome Caregiver Tips
Many people with alcohol use disorder (AUD), the most common cause of WKS, also suffer from other brain and mental health-related issues, a situation called co-morbidity. Here are a few of the disorders commonly associated with AUD:
Wernicke-Korsakoff Syndrome Brain Science
The body uses thiamine as a component of the process of converting blood sugar (glucose) into energy inside cells. Without enough thiamine, cells cannot carry out their normal functions, are damaged, and eventually die. Alcoholism is the primary cause of thiamine deficiency because alcohol impairs the absorption of thiamine through the digestive system and the storage of thiamine in the liver. It also impairs the function of other enzymes that play essential roles in cellular energy production.
Thiamine deficiencies affect cells throughout the body, but damage and cell death are most severe in the parts of the body that use the most energy. The brain as a whole demands a great deal of energy to be able to function normally, but some specific brain areas are especially sensitive to the effects of thiamine deficiencies. These areas include:
- Mamillary bodies
- Brain stem
Wernicke-Korsakoff Syndrome Research
Title: Alzheimer’s Autism and Cognitive Impairment Stem Cell Treatment Study (ACIST)
Principal investigator: Jeffrey Weiss, MD
MD Stem Cells
The study aims to evaluate the use of Autologous Bone Marrow-Derived Stem Cells (BMSC) as a means to improve cognitive impairment as occurs in Alzheimer’s Disease and other dementias and to improve behavior and socialization issues that arise in adult Autism Spectrum Disorder. The use of Near-Infrared Light, in conjunction with the use of BMSC, will also be assessed.
Cognition is the process of generating thoughts, recalling memories, processing information, and higher-order associations including social interactivity that all take place in the brain. It requires sufficient health and interactivity of neurons in the brain, including their ability to form and maintain synaptic connections.
Cognitive impairment results from the loss of these abilities. ACIST will test the hypothesis that the delivery of Bone Marrow-Derived Stem Cells (BMSC) via the methods in the study, with or without the addition of Near-Infrared Light, will improve cognition through the ability of BMSC to positively affect the health and function of neurons and the brain.
Patients enrolling with cognitive impairment will require assessment with the Mini-Mental Status Exam (MMSE). A score of 24 or less will be required. Progressive dementias such as Alzheimer’s Disease (ALZ) show a decline of 2 to 4 points per year on MMSE. The goal for ACIST in progressive and stable dementia will be stable over the 1-year follow-up and ideally an improvement of 3 points on MMSE.
Patients enrolling with Autism Spectrum Disorder (ASD) will be required to be adults (over 18 years of age) and to have a score on the Autism Spectrum Quotient of 20 or above. The goal will be a decrease of 5 or more on the scale over the 1-year follow-up period.
Title: Alcohol: Thiamine and or Magnesium 1 (AToM1)
Principal Investigator: Donogh Maguire, MB BCh
Glasgow Royal Infirmary
Patients who suffer from Alcohol Use Disorder (AUD) have a 30-80% incidence of thiamine deficiency, causing Wernicke’s Encephalopathy (WE).
Intravenous (IV) thiamine replacement is standard practice in the treatment of alcoholic patients presenting to the Accident & Emergency (A&E) department; however routine co-supplementation with magnesium (administered IV as magnesium sulphate), which is required as a co-factor for thiamine in some metabolic processes, e. g. on the activity of the enzyme transketolase in red blood cells, is not routine practice in the treatment of these patients. Without correction of concomitant magnesium deficiency, there may be impaired utilization of thiamine, resulting in a failure to treat WE.
This study is designed to determine if the administration of magnesium to AUD patients affects red cell transketolasae and serum lactate concentrations by itself, or only acts to increase the effect of thiamine on the activity of this enzyme.
This is a 3- arm randomized, open-label, controlled study in a cohort of alcoholic patients admitted through A&E. Patients will be randomized to concurrent infusion of one of the following:
Arm 1: IV thiamine
Arm 2: IV magnesium sulphate followed by delayed IV thiamine
Arm 3: IV thiamine and IV magnesium sulphate Thiamine will be administered as IV Pabrinex, a compound preparation that also contains B vitamins and vitamin C. Administration of IV Pabrinex is standard care in this patient group and magnesium sulphate is routinely co-administered at Glasgow Royal Infirmary.
Title: Optimum Thiamine Intervention (OpTIn) Trial (OpTIn)
Principal Investigator: Kylie Dingwall, PhD
Menzies School of Health Research
Alice Springs, Australia
Wernicke-Korsakoff syndrome (WKS), once considered a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients because alcohol dependence predisposes them to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. While effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists regarding optimal dosing regimens. This project proposes to develop quality evidence for the effective treatment of WKS in an Aboriginal setting.
The need for evidence-based thiamine treatment protocols is of great clinical importance for two related reasons. First, in relation to acute symptomatic WKS, a failure to treat immediately or adequately may result in profound and often permanent cognitive and neurological disability. Secondly, the need for evidence-based treatment guidelines is greatly magnified when it is recognized that milder, subclinical WKS may be preventable with adequate thiamine treatment.
This study aims to determine the optimal thiamine dose required for:
- Treatment of acute symptomatic WKS among Aboriginal and non-Aboriginal alcohol-dependent patients.
- Reducing or preventing subclinical WKS-related brain damage in at-risk Aboriginal and non-Aboriginal alcohol-dependent patients.
- Among alcohol-dependent patients with acute symptomatic WKS, higher doses of parenteral thiamine (1500mg) will lead to greater improvements in specific cognition and neurological functions than lower doses (900mg or 300mg).
- Among alcohol-dependent patients at high risk for subclinical WKS-related brain damage, higher doses of parenteral thiamine (900mg) will lead to greater improvements in specific cognition and neurological functions compared to lower doses (300mg or 100mg).
- Thiamine deficient patients will show poorer performance on cognitive and neurological measures.
- Patients with a concurrent magnesium deficiency will show greater impairment at baseline.
- Nutritional risk and alcohol frequency will correlate with thiamine pyrophosphate levels.
- The number of previous admissions with thiamine supplementation in the past 3 months will correlate with thiamine pyrophosphate levels