Marchiafava-Bignami disease
Key points
- Toxic demyelination and necrosis of the corpus callosum, classically in chronic alcoholism/malnutrition
- Preferentially involves the central layer of the callosum, sparing outer layers ("sandwich sign")
- Body involved first and most severely, then genu, then splenium
- Type A (extensive) has poor prognosis; type B (focal) more favourable
- Acute phase shows restricted diffusion; chronic phase shows cavitation and callosal atrophy
Epidemiology & risk factors
- Classic association: chronic alcoholism with nutritional deficiency (especially B vitamins/thiamine)
- Middle-aged to elderly males predominate
- Originally described in Italian red wine drinkers, but occurs worldwide and with any alcohol type
- Rare reports in non-alcoholic malnutrition states
Pathophysiology
Chronic alcohol/nutritional deficiency → selective demyelination of the central myelinated fibres of the corpus callosum → progresses to necrosis and cavitation. The central layer is most vulnerable, likely due to watershed-type vascular supply. Mechanism not fully understood but thought to involve direct toxic effect of alcohol metabolites combined with B-vitamin deficiency. May coexist with Wernicke encephalopathy.
Clinical features
- Acute: confusion, dysarthria, seizures, gait abnormality, coma
- Subacute/chronic: cognitive decline, interhemispheric disconnection syndrome (alien hand, agraphia, apraxia)
- Split-brain syndrome in severe cases (callosal disconnection)
- May present with concurrent Wernicke encephalopathy features
Imaging
MRI
- Location: corpus callosum body > genu > splenium; may extend to involve entire callosum
- Central layer involvement: characteristic sparing of dorsal and ventral outer layers - "sandwich sign" on sagittal/coronal images (best seen on T1/FLAIR)
- Acute:
- T2/FLAIR hyperintense swelling of the callosum
- Restricted diffusion (cytotoxic oedema)
- May show faint enhancement
- Chronic:
- T1 hypointensity with cavitation/necrosis (key distinguishing feature from MERS)
- Callosal atrophy and thinning
- Cystic change in the central layer
- Extracallosal involvement possible: symmetric hemispheric white matter, cortical involvement (especially frontal)
Classification
|Type A|Type B|
|---|---|---|
|Extent|Entire callosum +/- extracallosal|Partial or focal callosal|
|Outcome|Poor - stupor, coma, death|More favourable - may recover|
|Imaging|Extensive swelling, necrosis|Focal lesion, less necrosis|
CT
- Often normal acutely; chronic cases may show callosal hypodensity/atrophy
- MRI far superior for diagnosis
Differentials
| Differential | Distinguishing feature |
|---|---|
| MERS/RESLES | Post-infectious, splenium predominant, full-thickness involvement, complete resolution |
| Diffuse axonal injury | Trauma, haemorrhagic foci, grey-white junction + brainstem involvement |
| Callosal lymphoma | Enhancing mass, irregular margins, may cross midline ("butterfly") |
| Callosal MS plaque | Calloso-septal interface, Dawson fingers, temporal dissemination |
| Wernicke encephalopathy | Periaqueductal grey, medial thalami, mammillary bodies (may coexist with MBD) |
| Osmotic demyelination | Central pontine or extrapontine, rapid sodium correction history |
Management
- Alcohol cessation
- Thiamine and B-vitamin supplementation (high-dose IV thiamine acutely)
- Nutritional rehabilitation
- Corticosteroids - some reported benefit in acute phase (limited evidence)
- Prognosis variable: type B may recover; type A often fatal or severe disability
Exam pearls
- Alcoholic + corpus callosum necrosis + sandwich sign = MBD
- Sandwich sign: spared outer layers flanking necrotic/demyelinated central layer (sagittal T1 or FLAIR)
- Body predominance (vs MERS which is splenium predominant)
- Irreversible cavitation/atrophy (vs MERS which resolves completely)
- May coexist with Wernicke - check periaqueductal grey and mammillary bodies
