Marchiafava-Bignami disease (MBD) is a very rare disorder of demyelination/necrosis of the corpus callosum and the near subcortical white matter that is especially predominant in ill-fed alcoholics. It was discovered in 1903 by Italian pathologists Ettore Marchiafava and Amico Bignami. They described men with alcohol use disorder who died of seizures and coma that presented necrosis of their corpus callosum on autopsy. However, few cases have been described in non-alcoholic patients, suggesting that alcohol is not the sole responsible for these lesions.
The disease can be acute, subacute, or chronic. The clinical picture is marked by dementia, dysarthria, spasticity, and walking inability. Also, patients may enter into a coma or a demented condition for many years, and spontaneously recover or die.
Lesions can appear as hypodense regions of the corpus callosum on tomography, and as areas of diminished T1 signal and increased T2 signal on magnetic resonance. Also, an interhemispheric disconnection syndrome has been found in survivors. Alcoholic patients without hepatic disease, amnesia, or cognitive dysfunction present thinning of the corpus callosum on autopsy and neuroimaging (magnetic resonance) suggesting that alcohol or malnutrition can commonly damage the corpus callosum without the necrotic lesions of MBD. These findings can conclude in the possibility of aggressive nutritional supplementation with a reduction in drinking to prevent the development of MBD in alcoholic patients.
The etiology of the disease is still unclear, but it is presumably attributed to the combination of alcohol-induced neurotoxicity (with an uncertain nature) and deficiency of the B-complex vitamins . Other causes can be:
It is most commonly discovered in malnourished patients with chronic alcohol use disorder. However, cases have been described in patients without alcohol use disorder, especially individuals with poorly controlled diabetes mellitus. Marchiafava-Bignami Disease occurs with no ethnic, racial, or geographic predilection. However, there is a higher incidence in men, probably because of its closer association with alcohol consumption than women. The mean age of onset is 45 years It is a very rare condition. In the United States, one study found 250 published cases were reported before 2001, suggesting it is likely many cases have gone undiagnosed. International data is similar, always reminding that the prevalence is underestimated because of the non-autopsied patients. Published in approximately 300 case reports.
MBD pathophysiology is unclear. However, there are some explanations for it:
Histologic diagnosis is performed almost exclusively in a post-mortem autopsy. Diagnostic biopsy in the antemortem patient is rare, and always as a casual finding.
Macroscopic histopathologic features in the corpus callosum (especially in the genu and the body) can consist of necrotizing or cystic lesions. Microscopically there can be white matter necrosis, abundant macrophages (with little inflammatory reaction), foamy histiocyte infiltration (marked by CD68 and CD163), small perivascular lymphocytes (mainly CD3-positive T-cells and incidental CD20-positive B cells), gliosis and prominent demyelination (with relative sparing of the axons) that can extend symmetrically into the centrum semiovale. Oligodendrocytes are reduced in number.
Other anatomical sites affected by demyelination can be:
Although clinical features may be quite variable and nonspecific, MBD should be suspected in patients with chronic alcohol abuse and/or malnutrition who present with certain common neurological symptoms. These symptoms can include psychotic and emotional disorders that can appear somewhat in an acute, subacute, or chronic form:
Another pattern of classification, according to clinical status and brain injury detectable by magnetic resonance can be:
Evaluation relies heavily on imaging findings and correlation with a thorough history and physical exam:
Laboratory exam can be useful through the following:
Magnetic Resonance Imaging (MRI) is the gold standard imaging study of choice although CT may reveal hypodense lesions in the corpus callosum, especially the central portion. The typical pathognomonic features on MRI are symmetrical lesions on the corpus callosum, usually restricted to the genus, body, or splenium:
There are no management guidelines or specific proven treatment to date. Management is similar to the one for Wernicke-Korsakoff syndrome or alcohol abuse disorder. Most of the case reports of MBD have shown a favorable response to the endovenous administration of thiamine, folate, and vitamin B complexes as well as high-dose corticosteroids. Some case reports show significant improvement with high-dose endovenous thiamine intravenously (500 mg/tid), oral vitamin B complex, amantadine, and folate. Management also includes aggressive nutritional supplementation and, undoubtedly, alcohol withdrawal. Treatment can be administered as follows:
Drugs and toxins:
Central Nervous System disorders:
Disease severity is variable. A patient may survive for years with presenting symptoms, recover fully, or deteriorate into comatose state and decease. It is hypothesized that incomplete lesions with relative sparing of the superior commissure fibers are associated with better prognosis when compared with lesions extending into the convolution white matter. Extracallosal lesions, cerebral lobe impairment, severe disturbance of consciousness, and heavy alcohol consumption are associated with poor prognosis and/or severe dementia. Early diagnosis and effective treatment are therefore important to the patient’s recovery, and serial MRI has demonstrated some cases of complete disappearance of lesions with early diagnosis and treatment.
MBD is a very rare disorder that is not only difficult to diagnose but very complex to manage. With very few cases reported, it is best managed by an interprofessional team that includes internists, neurologists, nurses, therapists, and dietitians.
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