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Wernicke's Encephalopathy

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Description: Wernicke's encephalopathy is a neurological disorder caused by a deficiency in thiamine (vitamin B1), often associated with alcoholism, characterized by confusion, ataxia, and ophthalmoplegia.
Type: Wernicke's encephalopathy is a neurological disorder. It is not typically associated with a specific type of genetic transmission. The condition is most commonly caused by a deficiency in thiamine (vitamin B1), often due to chronic alcoholism, malnutrition, or conditions that impair nutrient absorption.
Signs And Symptoms: The classic triad of symptoms found in Wernicke encephalopathy is:
ophthalmoplegia (later expanded to other eye movement disorders, most commonly affecting the lateral rectus muscle. Lateral nystagmus is most commonly seen although lateral rectus palsy, usually bilateral, may be seen).
ataxia (later expanded to imbalance or any cerebellar signs)
confusion (later expanded to other mental changes. Has 82% incidence in diagnosis cases)Other symptoms found in patients with this condition include:

pupillary changes, retinal hemorrhage, papilledema, impaired vision and hearing, vision loss
hearing loss,
fatigability, apathy, irritability, drowsiness, psycho and/or motor slowing
dysphagia, blush, sleep apnea, epilepsy and stupor
lactic acidosis
memory impairment, amnesia, depression, psychosis
hypothermia, polyneuropathy, hyperhidrosis.Although hypothermia is usually diagnosed with a body temperature of 35 °C (95 °F), or less, incipient cooling caused by deregulation in the central nervous system (CNS) needs to be monitored because it can promote the development of an infection. The patient may report feeling cold, followed by mild chills, cold skin, moderate pallor, tachycardia, hypertension, tremor or piloerection. External warming techniques are advised to prevent hypothermia.Among the frequently altered functions are the cardio circulatory. There may be tachycardia, dyspnea, chest pain, orthostatic hypotension, changes in heart rate and blood pressure. The lack of thiamine sometimes affects other major energy consumers, the myocardium, and also patients may have developed cardiomegaly. Heart failure with lactic acidosis syndrome has been observed. Cardiac abnormalities are an aspect of the WE, which was not included in the traditional approach, and are not classified as a separate disease.
Infections have been pointed out as one of the most frequent triggers of death in WE. Furthermore, infections are usually present in pediatric cases.In the last stage other symptoms may occur: hyperthermia, increased muscle tone, spastic paralysis, choreic dyskinesias and coma.Because of the frequent involvement of heart, eyes and peripheral nervous system, several authors prefer to call it Wernicke disease rather than simply encephalopathy.Early symptoms are nonspecific, and it has been stated that WE may present nonspecific findings. In Wernicke Korsakoff's syndrome some single symptoms are present in about one-third.
Prognosis: The prognosis for Wernicke's encephalopathy largely depends on the timeliness and adequacy of treatment. Early recognition and immediate administration of thiamine (vitamin B1) can significantly improve outcomes and prevent permanent damage. However, if left untreated, the condition can progress to Korsakoff syndrome, characterized by severe and chronic memory issues. In advanced cases, even with treatment, some neurological impairments and cognitive deficits may persist.
Onset: Wernicke's encephalopathy typically has an acute onset, often developing rapidly over a period of days to weeks. It is a neurological disorder resulting from a deficiency of thiamine (vitamin B1), commonly associated with chronic alcohol abuse, malnutrition, or conditions that impair thiamine absorption.
Prevalence: The exact prevalence of Wernicke's encephalopathy (WE) is not well-defined due to underdiagnosis and the challenge of distinguishing it from other neuropsychiatric conditions. However, it is estimated to occur in approximately 1-2% of the general population and is more common among individuals with chronic alcoholism, where estimates suggest a prevalence of up to 12-14%.
Epidemiology: There are no conclusive statistical studies, all figures are based on partial studies.
Wernicke's lesions were observed in 0.8 to 2.8% of the general population autopsies, and 12.5% of people with an alcohol use disorder. This figure increases to 35% of such individuals if including cerebellar damage due to lack of thiamine.Most autopsy cases were from people with an alcohol use disorder. Autopsy series were performed in hospitals on the material available which is unlikely to be representative of the entire population. Considering the slight affectations, previous to the generation of observable lesions at necropsy, the percentage should be higher. There is evidence to indicate that Wernicke encephalopathy is underdiagnosed. For example, in one 1986 study, 80% of cases were diagnosed postmortem. Is estimated that only 5–14% of patients with WE are diagnosed in life.In a series of autopsy studies held in Recife, Brazil, it was found that only 7 out of 36 had consumed excessive amounts of alcohol, and only a small minority had malnutrition. In a reviewed of 53 published case reports from 2001 to 2011, the relationship with alcohol was also about 20% (10 out of 53 cases).WE related to alcohol misuse is more common in males and is more common in females when not related to alcohol misuse. In alcohol-related cases, WE patients average the age of 40, and non-alcohol-related cases typically occur in younger people.
Intractability: Wernicke's encephalopathy can be effectively treated if identified early. It is caused by a deficiency of thiamine (vitamin B1), and prompt administration of thiamine can reverse symptoms and prevent progression. However, if left untreated or if treatment is delayed, it can lead to irreversible damage and complications, making it more difficult to manage. Early intervention is crucial for a favorable outcome.
Disease Severity: Wernicke's encephalopathy is a medical emergency that is characterized as severe. It requires prompt treatment to prevent significant brain damage and potential death.
Healthcare Professionals: Disease Ontology ID - DOID:2384
Pathophysiology: Thiamine deficiency and errors of thiamine metabolism are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B1, helps to break down glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used. The body only has 2–3 weeks of thiamine reserves, which are readily exhausted without intake, or if depletion occurs rapidly, such as in chronic inflammatory states or in diabetes. Thiamine is involved in:
Metabolism of carbohydrates, releasing energy.
Production of neurotransmitters including glutamic acid and GABA.
Lipid metabolism, necessary for myelin production.
Amino acid modification. Probably linked to the production of taurine, of great cardiac importance.
Carrier Status: Wernicke's encephalopathy is not a condition associated with a carrier status. It is an acute neurological disorder caused by thiamine (vitamin B1) deficiency.
Mechanism: Wernicke's encephalopathy is a neurological disorder caused by a deficiency of thiamine (vitamin B1).

**Mechanism:**
The condition primarily affects the central nervous system, particularly the brain. The deficiency of thiamine disrupts glucose metabolism, leading to a decrease in energy production in brain cells. This results in damage to specific brain regions, including the thalamus, hypothalamus, and the mammillary bodies.

**Molecular Mechanisms:**
Thiamine is a crucial cofactor for several enzymes involved in glucose metabolism, including:
1. **Pyruvate dehydrogenase:** Converts pyruvate to acetyl-CoA, facilitating entry into the TCA cycle.
2. **Alpha-ketoglutarate dehydrogenase:** Involved in the TCA cycle.
3. **Transketolase:** Part of the pentose phosphate pathway, important for nucleotide synthesis and reducing oxidative stress.

In Wernicke's encephalopathy, the deficiency of thiamine impairs the functioning of these enzymes, leading to reduced ATP production and increased oxidative stress. This impaired metabolism predominantly affects brain regions with high metabolic demands, resulting in neuronal damage, gliosis, and microhemorrhages.
Treatment: Most symptoms will improve quickly if deficiencies are treated early. Memory disorder may be permanent.In patients suspected of WE, thiamine treatment should be started immediately. Blood should be immediately taken to test for thiamine, other vitamins and minerals levels. Following this an immediate intravenous or intramuscular dose of thiamine should be administered two or three times daily. Thiamine administration is usually continued until clinical improvement ceases.Considering the diversity of possible causes and several surprising symptomatologic presentations, and because there is low assumed risk of toxicity of thiamine, because the therapeutic response is often dramatic from the first day, some qualified authors indicate parenteral thiamine if WE is suspected, both as a resource for diagnosis and treatment. The diagnosis is highly supported by the response to parenteral thiamine, but is not sufficient to be excluded by the lack of it. Parenteral thiamine administration is associated with a very small risk of anaphylaxis.People who consume excessive amounts of alcohol may have poor dietary intakes of several vitamins, and impaired thiamine absorption, metabolism, and storage; they may thus require higher doses.If glucose is given, such as in people with an alcohol use disorder who are also hypoglycaemic, thiamine must be given concurrently. If this is not done, the glucose will rapidly consume the remaining thiamine reserves, exacerbating this condition.The observation of edema in MR, and also the finding of inflation and macrophages in necropsied tissues, has led to successful administration of antiinflammatories.Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease. In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.Other supplements may also be needed, including: cobalamin, ascorbic acid, folic acid, nicotinamide, zinc, phosphorus (dicalcium phosphate) and in some cases taurine, especially suitable when there cardiocirculatory impairment.
Patient-guided nutrition is suggested. In patients with Wernicke–Korsakoff syndrome, even higher doses of parenteral thiamine are recommended. Concurrent toxic effects of alcohol should also be considered.
Compassionate Use Treatment: Compassionate use treatment for Wernicke's encephalopathy typically involves interventions used when standard treatments fail or are inappropriate. Thiamine (vitamin B1) is the standard treatment to reverse the deficiency causing the syndrome. While there are no well-established alternative drugs specifically approved for Wernicke's encephalopathy under compassionate use, some experimental treatments have been considered or explored. These might include higher doses of thiamine beyond the standard recommendations or the use of other B vitamins. However, these approaches remain under investigation and are not universally accepted. For off-label or experimental treatments, involvement in clinical trials or consultation with a specialist in neurology or nutrition is advisable.
Lifestyle Recommendations: Lifestyle recommendations for managing and preventing Wernicke's encephalopathy primarily focus on addressing and reducing risk factors, especially those related to alcoholism and nutritional deficiencies:

1. **Reduce Alcohol Consumption**: Limiting or abstaining from alcohol is crucial, as chronic alcohol use is a major risk factor. Seek support from rehabilitation programs if needed.

2. **Balanced Diet**: Ensure a diet rich in essential nutrients, particularly thiamine (vitamin B1). Foods high in thiamine include whole grains, meat (especially pork), nuts, beans, and green peas.

3. **Nutritional Supplements**: If dietary intake is insufficient or if absorption is impaired, thiamine supplements might be necessary. Consult a healthcare provider for appropriate dosages.

4. **Medical Follow-up**: Regular check-ups with healthcare providers can help monitor nutritional status and provide early intervention if deficiencies are detected.

5. **Avoid Self-Medication**: Avoid taking medications that might affect nutritional absorption or liver function without consulting a doctor.

6. **Educate Yourself**: Being informed about the symptoms and risk factors of Wernicke's encephalopathy can lead to early detection and treatment.

By adhering to these lifestyle recommendations, the risk of developing Wernicke's encephalopathy can be significantly reduced.
Medication: Wernicke's encephalopathy primarily requires urgent administration of thiamine (vitamin B1) to prevent and treat symptoms. Thiamine is usually given intravenously or intramuscularly, followed by oral supplementation. Time is critical in these interventions to avoid permanent neurological damage.
Repurposable Drugs: Wernicke's encephalopathy is a neurological disorder often caused by thiamine (vitamin B1) deficiency. While the primary treatment involves thiamine replacement, some potential repurposable drugs include:

1. **Memantine:** An NMDA receptor antagonist, it may help alleviate neurotoxic effects associated with glutamate, a factor in Wernicke's encephalopathy.

2. **N-acetylcysteine (NAC):** Has antioxidant properties which could theoretically mitigate some neuronal damage.

Always consult medical professionals before using any medication for off-label purposes.
Metabolites: Wernicke's encephalopathy is primarily associated with metabolite imbalances resulting from thiamine (vitamin B1) deficiency. No specific nanometabolites are directly associated with this condition.
Nutraceuticals: Wernicke's encephalopathy is a neurological disorder commonly caused by thiamine (vitamin B1) deficiency. Nutraceuticals, such as thiamine supplements, are pivotal in managing this condition. High-dose thiamine, either orally or intravenously, is typically administered to replenish the deficiency and mitigate symptoms. In cases of severe malnutrition or chronic alcoholism, where absorption is an issue, intravenous administration is preferred to ensure adequate levels. Additionally, a balanced diet rich in essential nutrients can support overall brain health and prevent recurrence. Always consult a healthcare professional for personalized management plans.
Peptides: In the context of Wernicke's encephalopathy, peptides are not a primary focus. Wernicke's encephalopathy is a neurological disorder caused by a deficiency in thiamine (vitamin B1). It is characterized by symptoms like confusion, ataxia, and ophthalmoplegia. Treatment primarily involves thiamine supplementation rather than peptides.