2017 NPB-12

This case was originally published in 2017. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

The patient was a 56-year-old woman with a history of Cushing’s disease, Graves disease, type II diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, osteoporosis, and chronic back pain. In addition, she had a decade-long history of alcoholism and opioid dependence over her final four years of life. This patient’s neurologic symptoms began at age 37 with an insidious onset of loss of balance, dizziness, dysarthria, and memory loss. Imaging performed at that time revealed a small cerebellar hemangioma and a cyst in the parahippocampal region. Over the next fifteen years the patient’s symptoms evolved to include fatigue, tremors, leg pain, ataxia, and bilateral leg weakness, as well as short-term memory loss. When diagnosed with Cushing’s disease at age 52, brain imaging was obtained to evaluate the pituitary. In addition to an asymmetric enlargement of the pituitary gland, imaging displayed some superior cerebellar atrophy and abnormally enhancing lesions within the mid-portion of the corpus callosum. These were thought to be suggestive of demyelinating plaques, but no other similar lesions were detected anywhere else in the CNS, and CSF testing for oligoclonal bands was negative. A pituitary adenoma was resected without complication, but her overall neurological status remained essentially unchanged. The patient died unexpectedly of a myocardial infarction at age 56.

Tissue Site
Corpus collosum

The whole slide image provided is an H&E stained slide of corpus callosum (brain) from autopsy.

Marchiafava-Bignami disease (MBD) is a rare neurologic condition that causes degeneration and demyelination of the corpus callosum. Classically, this disease has been described in malnourished male alcoholics, although a handful of cases have also been reported in women and nonalcoholic patients with other diseases such as diabetes. The etiology and pathogenesis are unknown, although direct alcohol toxicity, complex vitamin deficiencies, and malnutrition have all been postulated. This is somewhat supported by the finding of callosal atrophy in chronic alcoholics without liver disease or neurological problems. One of the persistent difficulties in specifically defining MBD, other than its rarity, is the existence of sporadic cases with other coexistent neuropathological changes. This presents the conundrum of whether such changes are part of the MBD spectrum or are distinct lesions that coincidentally exist (eg, Morel cortical laminar sclerosis).

Three clinical subtypes of the MBD have been proposed. In type A disease, a patient presents acutely with seizures and impaired consciousness, which can progress to coma and death within several days. Type B disease presents with dementia, often accompanied by dysarthria and hypertonia, with declining function until death within a few months. Type C, chronic MBD, has a complex and insidious presentation of nonspecific neurologic symptoms, the most commonly reported being disorientation, agraphia, apraxia, and memory impairments. Additional reported symptoms of MBD include dysarthria, spasticity, ataxia, and sensory disturbances.

MBD is infrequently diagnosed in the clinical setting. Thus, effective therapy based on clinical trials has not been defined. There are no laboratory tests that are specific for the condition, and antemortem diagnosis depends on CNS imaging, familiarity with the entity and a high index of suspicion. MRI changes are typically restricted to the corpus callosum. In the acute phase the lesions are associated with edema. Lesions appear as hypodense areas of decreased T1 signal and have increased signal on FLAIR sequences (Image A). Ultimately the callosum becomes thin and atrophic.

The pathology of MBD is unique. Grossly the corpus callosum is discolored and shrunken (Image B) and may become partially cystic in later stages (Image C, Image D, and Image E). At the outset the essential nature of the lesion is a focus of demyelination often sparing the outer and inner surfaces of the callosum (Image F and Image G). There is relative sparing of the axons (Image H). As the lesions age they become gliotic (Image I and Image J), atrophic, infiltrated by lipid-laden macrophages, and may ultimately create cystic cavities (Image D, Image J, and Image K). Blood vessels in the lesion may show hyalinized walls and vascular proliferation (Image E and Image L). Similar lesions can be found in other structures carrying axons across the midline of the brain such as: anterior commissure, optic chiasm, and middle cerebellar peduncle.

Differential diagnoses of MBD include infarct, multiple sclerosis (MS), and lesions associated with heroin vapor inhalation. The vascular supply to the corpus callosum is via tiny pericallosal arteries derived from the posterior and anterior cerebral arteries. Infarction in this area is rare. The MBD lesions differ from MS plaques given the relative absence of inflammatory elements in the tissue and their restriction to the callosum. The lesions associated with heroin vapor inhalation, “chasing the dragon,” include spongiform degeneration in the hemispheric white matter, typically sparing of subcortical U-fibers. Axons are typically spared, and demyelination is not a prominent feature. The corpus callosum is vulnerable to ripping during brain removal, but such a postmortem artifact would not result in discoloration, thinning, and cyst formation in that structure.

• MBD is rare and its etiology and pathogenesis remain unknown.
• Demyelination is a consistent feature of MBD.
• While the pathologic features are relatively distinct, the clinical presentation of MBD is highly variable and nonspecific.
• The diagnosis of MBD is almost always made postmortem.

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