What is Marchiafava-Bignami Disease?
Marchiafava-Bignami disease (MBD) is an incredibly rare condition causing damage to a part of the brain called the corpus callosum and nearby white matter. This is often seen in malnourished individuals who heavily consume alcohol. It was first identified in 1903 by two Italian pathologists, Ettore Marchiafava and Amico Bignami. They found it in men who frequently drank alcohol, had seizures and ended up in a coma. After these men died, their autopsies showed damage to the corpus callosum. However, there have been a few cases found in people who do not drink alcohol, which suggests that alcohol may not be the only cause of this damage.
The effects of this disease can be immediate, develop over a short period, or occur slowly. Symptoms may include memory loss, difficulty speaking, muscle stiffness, and inability to walk. Some patients may end up in a coma or experience severe mental decline for several years, after which they may either recover unexpectedly or die.
Using imaging techniques like tomography and magnetic resonance, doctors can see that the affected areas in the brain might appear less dense or show changes in signal intensity. They also noticed a reduced connection between the two hemispheres of the brain in people who survived this condition. Some patients who drank alcohol but didn’t have liver disease, memory loss, or cognitive problems were found to have a thinner corpus callosum during autopsies and brain imaging. This suggests that alcohol or malnutrition could harm the corpus callosum even without the severe damage seen in MBD. Based on this, it appears that aggressive nutritional support and cutting down on alcohol may prevent the development of Marchiafava-Bignami disease in people who consume alcohol.
What Causes Marchiafava-Bignami Disease?
The exact cause of this disease isn’t fully understood yet, but it’s believed to be a combination of two main factors: damage to the nervous system caused by alcohol (though it’s not clear exactly how this damage occurs) and a lack of B-complex vitamins.
There can be other causes as well:
* Rapid changes in the level of certain substances in the blood, a condition called callosal myelinolysis. This can be a complication from a condition known as ketoacidosis, which can be caused by diabetes or excessive drinking.
* Malnourishment that isn’t related to alcohol, such as after having a type of weight loss surgery called gastric bypass.
* It can also occur alongside other conditions that aren’t linked to alcohol, including carbon monoxide poisoning, sepsis (a serious infection), cerebral malaria (a severe type of malaria), sickle cell disease, and following surgery for heart cancer.
Risk Factors and Frequency for Marchiafava-Bignami Disease
Marchiafava-Bignami Disease is most often found in people who are malnourished or have a chronic issue with alcohol consumption. That being said, it has been also observed in some individuals who don’t have an alcohol problem but have poorly managed diabetes. This disease doesn’t discriminate based on race, ethnicity, or location.
- Although this disease affects both men and women, men are more likely to get it, probably due to their higher rates of alcohol consumption.
- The average age when people get this disease is around 45.
- It’s a pretty rare condition. For example, only 250 cases were reported in the U.S. before 2001, which suggests a lot of cases might have gone undiagnosed.
- Information from other countries also indicates that the condition is likely underreported, particularly in cases where an autopsy wasn’t performed.
- There are only about 300 case reports published on this disease.
Signs and Symptoms of Marchiafava-Bignami Disease
Marchiafava-Bignami disease (MBD) is a rare brain condition often related to chronic alcohol use and malnutrition. It can have a variety of symptoms and effects, which could change over time or depending on the individual. Some people may have neurological symptoms, including emotional issues and psychosis. These symptoms can come on suddenly or slowly, and last for different lengths of time.
If someone has MBD, they might show these symptoms:
- Sudden loss of consciousness and seizures (acute onset)
- Apathy, aggression, confusion, and psychosis (acute onset)
- Depression, difficulty coordinating movement, challenged motor skills, trouble with writing or naming objects, speech disturbances, and visual dyslexia (subacute symptoms)
- Deteriorating mental capability, visual and auditory hallucinations and behavioral abnormalities (chronic symptoms)
Doctors can often identify MBD through brain scans like magnetic resonance imaging (MRI). These scans might reveal two types of injuries:
- Type A: severe impact on consciousness, seizures, speech disturbances, and paralysis on one side of the body. The MRI might reveal a swollen corpus callosum (the part of the brain connecting the two hemispheres). This type of MBD usually has a poorer prognosis.
- Type B: the symptoms include speech disturbances, walking problems, connection issues between the two brain hemispheres and mild consciousness impairment. The MRI might show partial injuries on the corpus callosum. This type of MBD tends to have a better prognosis.
Testing for Marchiafava-Bignami Disease
When checking for a suspected health problem, doctors rely a lot on both a thorough review of your medical history and a physical examination. In some cases, they might also use certain scales or tests to evaluate specific bodily functions:
– The Modified Oxford Handicap Scale and the modified Rankin Scale examine your nervous system (basically how your brain and nerves are working).
– The Abbreviated Mental Test, Montreal Cognitive Assessment, or Mini-Mental State Examination checks your cognitive function (this is a fancy term for your memory, attention, and other mental abilities).
– The Glasgow Coma Scale measures how severe a loss of consciousness is.
– The Michigan Alcoholism Screening Test can help assess how much you drink alcohol.
In addition, your doctor might order lab tests to help figure out what’s happening in your body. Here are some examples of what they might check:
– Serum electrolytes: these are minerals in your body that help your nerves and muscles function, and imbalances can potentially cause a coma, impaired consciousness, or seizures.
– Liver health: by checking your serum transaminases and bilirubin levels, doctors can tell whether your liver has been damaged.
– Blood sugar: a serum glucose test can rule out if your symptoms are due to too high or too low blood sugar.
– Complete blood count: this test can find signs of infection or inflammation, check your hemoglobin and platelet levels, or find evidence of excessive alcohol use.
– Toxicology screening: this checks for the presence of other drugs in your body.
– Serum and spinal fluid infectious serology panel: this can help doctors find out if you have an infection in your central nervous system (i.e., brain and spinal cord).
Magnetic Resonance Imaging (MRI) is the preferred imaging study to see what’s going on inside your brain. But sometimes a CT scan can also show changes, especially in a part of the brain called the corpus callosum.
A common characteristic of certain brain problems seen on an MRI is lesions (or damaged areas) seen in the corpus callosum, and other parts of the brain. In the acute stage (the early phase of illness), the damaged area can have changes due to swelling or loss of myelin, the insulating layer around nerve fibres. Over time, if treated early, these lesions can go away and the MRI might return to normal. But if left untreated (or if treatment fails), there can be lasting damage and the MRI will show atrophy (or shrinkage) and cyst formation.
In studies of men with chronic alcohol use disorder, MRIs showed significant changes in the corpus callosum and other brain areas compared to men who did not use alcohol. In fact, the higher the lifetime dose of alcohol, the more the brain was affected. These changes can even be seen during an autopsy after death.
Treatment Options for Marchiafava-Bignami Disease
Currently, there are no established guidelines or specific treatments for managing Marchiafava-Bignami disease (MBD), a rare condition often linked to chronic alcohol abuse. However, treatments used for similar disorders, such as Wernicke-Korsakoff syndrome or alcohol use disorder, are typically used.
Several case reports have shown that some patients with MBD responded well to treatments including thiamine (a type of vitamin B1), folate (a type of vitamin B), and vitamin B complexes, all given via an IV (a drip into the vein). High-dose corticosteroids, a type of medication that reduces inflammation, have also shown positive results. Similar benefits have been observed with high-dose IV thiamine, oral vitamin B complex, a medication called amantadine, and folate.
Another important part of managing MBD involves nutritional supplementation and stopping alcohol consumption. Applying this treatment plan requires input from a trained medical professional and commence in a medical setup.
An IV injection of thiamine, given in either normal saline or 5% dextrose (a type of sugar solution), has been used successfully in treating patients with alcohol withdrawal syndrome. For this condition, thiamine is typically administered IV three to five times a day for three to five days, then once a day by mouth for one to two weeks. Following this, the patient would continue to take thiamine orally once a day. Most patients also require a medication called benzodiazepines.
In patients with MBD or Wernicke encephalopathy (a severe neurological disorder often linked to alcohol misuse), thiamine can be also be used, first as a prophylactic (preventive treatment), then, if the response is good, as a treatment. Once patients respond positively to the thiamine, they typically continue using it in different forms and doses as per the doctor’s recommendation.
In addition to thiamine, vitamin B complex and folic acid are usually recommended as part of the treatment plan for MBD. Folic acid helps prevent or treat anemias that cause red blood cells to be larger than normal. Amantadine, though not proven through robust scientific testing, may also benefit patients’ symptoms.
What else can Marchiafava-Bignami Disease be?
Patients with symptoms of sudden confusion, loss of muscle control, or structural abnormalities seen in brain scans may be experiencing a range of conditions. The following issues could be the cause:
Nutritional problems:
- Wernicke encephalopathy: This typically affects areas of the brain including the hypothalamus and thalamus. It’s diagnosed using the 4 Caine Criteria.
- Vitamin B12 and folate deficiencies
Drug and toxin related:
- Certain medications (like opioids, sedatives, and benzodiazepines)
- Substances like heroin and hallucinogens
- Poisonous substances like methanol, carbon monoxide, cyanide, and hydrogen sulfide
Infections such as:
- Sepsis
- Fever-induced confusion
- Meningitis and inflammation of the brain (encephalitis)
Metabolic problems, including:
- Hormone imbalances involving the thyroid or parathyroid glands, or pituitary and adrenal glands
- Electrolyte imbalances: sodium, calcium, magnesium, phosphate
- Increased levels of carbon dioxide in the blood and reduced oxygen levels
- Changes in blood sugar levels
- Changes in the concentration of particles in body fluids
- Genetic (inborn) metabolism disorders like porphyria and Wilson’s disease
Problems related to the central nervous system:
- Seizures
- Brain injury
- Hypertensive encephalopathy (a condition caused by high blood pressure)
- Increased pressure within the skull
- Mental health conditions like psychosis and dementia
- Multiple sclerosis
- Morel laminar sclerosis (commonly found in patients with Marchiafava-Bignami disease)
- A condition called central pontine myelinolysis
- Brain tumors
Systemic (whole-body) disorders:
- Heart Failure
- Blood disorders like thrombocytosis, leukemic blast cell crisis, and polycythemia
- Acute or chronic liver failure (especially if it leads to hepatic encephalopathy, a condition that affects the brain)
- Acute or chronic kidney failure
- Acute or chronic respiratory failure
What to expect with Marchiafava-Bignami Disease
The severity of a disease can vary greatly. Some patients may live for years with symptoms, recover completely, or worsen and become comatose and possibly die. It’s believed that lesions that don’t completely damage the superior commissure fibers, which are crucial nerve fibers in the brain, are associated with a better prognosis compared to lesions that extend into the white matter of the brain’s convolutions, the folds on its surface.
The presence of lesions outside the corpus callosum (the part of the brain that connects the two hemispheres), impairment of the cerebral lobes, significant disturbances in consciousness, and heavy alcohol consumption are all correlated with poor outcomes and/or severe dementia.
Therefore, early diagnosis and effective treatment are vital for a patient’s potential recovery. Serial MRI, a type of imaging that can visualize internal structures of the body, has shown in some cases the complete disappearance of lesions with early diagnosis and treatment.
