Marchiafava Bignami Disease

Article Author:
Terrence Tian
Article Editor:
John Liang
Updated:
10/27/2018 12:31:42 PM
PubMed Link:
Marchiafava Bignami Disease

Introduction

Marchiafava-Bignami disease (MBD) is a very rare disorder that was first discovered in 1903 by two Italian pathologists, Ettore Marchiafava and Amico Bignami, who described three men with alcoholism who died of seizures and coma and were subsequently found to have necrosis of the middle two-thirds of their corpus callosum on autopsy. The disease is characterized by the demyelination and necrosis of the corpus callosum and may involve the adjacent subcortical white matter.

Etiology

The etiology of Marchiafava-Bignami disease is still unclear, but it is presumably attributed to the combination of alcohol-induced neurotoxicity and deficiency of the B-complex vitamins.[1] Possible mechanisms include cytotoxic edema, the breakdown of the blood-brain barrier, demyelination, and necrosis. In the early stage of the disease, cytotoxic edema may play a dominant role as evidenced by hyperintense lesions on diffusion-weighted (DW) magnetic resonance imaging (MRI) sequence. In later stages, demyelination and necrosis may play a role.[2]

Epidemiology

It is most commonly discovered in malnourished patients with chronic alcoholism[3]. However, cases have been described in patients without alcoholism, especially individuals with poorly controlled diabetes mellitus.[4],[5],[6] Marchiafava-Bignami Disease occurs in both genders, with a higher incidence in men. The mean age of onset is 46 years.[7] It is a very rare condition. In the United States, one study found 250 published cases were reported before 2001, although it is likely many cases have gone undiagnosed.[8]

History and Physical

Although clinical features may be quite variable and nonspecific, Marchiafava-Bignami Disease should be suspected in patients with chronic alcohol abuse or malnutrition who present with certain common neurological symptoms. These symptoms include dementia, altered mental status, spasticity, dysarthria, ataxia, gait abnormalities, and seizures.[9] Other reported clinical findings include desynchronization of bilateral symmetric movements, and unilateral signs of agraphia, apraxia, dyspraxia, and anomia.[10]

The disease acuity may be categorized as acute or chronic. The acute disease manifests with dysarthria, confusion, seizure, limb hypertonia, and/or delirium. Acute disease can be further subdivided into two types, Type A and Type B, with the following differentials[9]:  

Type A

  • Greater impairment in consciousness, seizures, dysarthria, and hemiparesis
  • 100% of the corpus callosum is affected 
  • Associated with a worse prognosis

Type B

  • Presents with dysarthria, gait disturbance, interhemispheric disconnection symptoms and less impairment in consciousness
  • 10% of the corpus callosum is affected

Chronic disease manifests with progressive dementia, behavior abnormalities, and signs of interhemispheric disconnection.[11]

Evaluation

Evaluation relies heavily on imaging findings and correlation with a thorough history and physical exam, along with laboratory workup. MRI is the gold standard imaging study of choice although CT may reveal hypodense lesions in the corpus callosum, especially the central portion.[10]

In the acute stage, cytotoxic edema dominates. MRI may reveal hypointense T1 signal, hyperintense T2/Fluid-attenuated inversion recovery (FLAIR) signal in middle layer of the corpus callosum (sandwich sign), diffusion restriction on DW sequence, and/or variable reduction in apparent diffusion coefficient (ADC) sequence.[10][12] Lesions may also be found in other parts of the brain, including the cerebral lobes, hemispheric white matter, and basal ganglia, which indicates a poorer prognosis. As the acute stage passes, the edema resolves, and hyperintensities on MRI may normalize. If diagnosed and treated early, MRI may demonstrate complete resolution of the lesions in the corpus callosum.[13] However, if not treated, there will be permanent demyelination and necrosis, and MRI will show thinning and atrophy of the corpus callosum and cystic transformation.[3][13]

In one study, Estruch et al. compared MRI findings of 28 males with chronic alcoholism with 14 subjects who were non-alcoholic and found statistically significant differences between the group with alcoholism and the control group in the mean of all planimetric brain indices calculated. They found the group with alcoholism had a significant reduction in anterior thickness, middle thickness, posterior thickness, corpus callosum area, corpus callosum percentage, frontal lobe index, and cortical sulci size compared to the control group. In fact, Estruch et al. found the mean corpus callosum body area of two-thirds of the subjects in the group with alcoholism were less than two standard deviations of the mean of the subjects in the control group. There was an 18% decrease in genu size, 16% decrease in truncus size, and 15% decrease in splenium in the group with alcoholism compared to the control group.[3] Thinning of the corpus callosum can also be seen on autopsy. Furthermore, Estruch et al. were able to show a correlation between increasing lifetime dose of alcohol consumption and reduction of corpus callosum indices.[3]

There are no laboratory findings specific for Marchiafava-Bignami disease, but a complete blood count and the comprehensive metabolic panel should be performed to exclude other differentials. For example, it may be useful to evaluate liver enzymes and ammonia level to rule out hepatic encephalopathy or electrolytes to rule out central pontine myelinolysis.

Treatment / Management

There are no management guidelines to date. Case reports of Marchiafava-Bignami disease have shown a favorable response to thiamine, folate, and vitamin B complexes as well as high-dose corticosteroids.[6],[7],[10],[12] One case reported significant improvement of symptoms within 7 days of symptom onset after a 5-day course of high-dose thiamine intravenously (500 mg, 3 times/day) and vitamin B complex orally.[7] Another case reported improvement after giving amantadine together with thiamine, vitamin B12, and folate.[2] Management also includes aggressive nutritional supplementation. Reducing alcohol abuse may help prevent the development of Marchiafava-Bignami disease in those with alcoholism.

Differential Diagnosis

Based on MRI findings, clinical presentation, and history, differential diagnosis may include the following:

  • Wernicke encephalopathy
  • Hepatic encephalopathy
  • Stroke
  • Dementia
  • Normal pressure hydrocephalus
  • Cerebellar degeneration
  • Multiple sclerosis
  • Central pontine myelinolysis
  • Morel laminar sclerosis

Staging

Marchiafava-Bignami disease may be categorized into acute and chronic stages. Acute stage may be subdivided into Type A and Type B based on symptom presentation. [See History and Physical section]

Prognosis

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. Eextracallosal 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 patient’s recovery, and serial MRI has demonstrated complete disappearance of lesions with early diagnosis and treatment. [13]