Marchiafava-Bignami Disease

Marchiafava-Bignami disease is a rare disorder with demyelination and necrosis of the corpus callosum and sometimes other white matter, seen mainly in people with chronic alcohol use disorder and malnutrition. It causes encephalopathy, dementia, seizures and gait disturbance, and can be fatal.

It is rare, with fewer than 400 reports, and the true incidence is unknown. It affects mainly men aged 40 to 60 years, and rare cases occur in non-drinkers with malnutrition or diabetes.

Causes. Chronic alcohol use disorder (especially red wine in the original description), malnutrition, vitamin B complex deficiency, and rarely other states such as poorly controlled diabetes.

Forms. Acute (coma, seizures, rigidity), subacute (dementia, dysarthria, frontal signs) and chronic (slow dementia and disconnection syndrome).

Course. Variable. Acute disease has a high mortality, while early treatment with thiamine and B vitamins may lead to recovery in some. Survivors often have lasting cognitive and gait problems.

Pathophysiology.

Deficiency of B vitamins and direct toxic effects of alcohol cause oedema and demyelination of the corpus callosum, which has a high metabolic demand.

Interruption of interhemispheric fibres produces the callosal disconnection syndrome.

• Confusion, apathy, behavioural change, memory loss and dementia over weeks.
• Dysarthria, gait disturbance, rigidity, primitive reflexes, and hemiparesis in some.
• Callosal disconnection: alien hand, apraxia, agraphia and interhemispheric transfer deficits.
• Seizures, stupor or coma in acute forms.
• Features of Wernicke encephalopathy and malnutrition in many.

Red flags.

• Coma, status epilepticus or rapid deterioration.
• Ophthalmoplegia, ataxia and confusion (Wernicke encephalopathy, which needs immediate thiamine).
• Alcohol withdrawal, hypoglycaemia or aspiration.

• MRI of the brain: T2 and FLAIR hyperintensity of the corpus callosum (genu, body and splenium) with swelling, restricted diffusion early and callosal thinning later; lesions may extend to adjacent white matter.
• Blood tests: glucose, electrolytes, liver and renal function, ammonia, B12, folate, thiamine (or red cell transketolase), magnesium and alcohol level.
• EEG for seizures and encephalopathy; cerebrospinal fluid analysis to exclude infection.
• Exclude Wernicke encephalopathy, hepatic encephalopathy, hypoglycaemia, infection and stroke.

Differential diagnosis. Wernicke encephalopathy, hepatic encephalopathy, multiple sclerosis, osmotic demyelination, lymphoma, glioma, posterior reversible encephalopathy syndrome, hypoxic injury and stroke.

• Give thiamine at once, before glucose, to cover Wernicke encephalopathy: 200 to 500 mg intravenously every 8 hours for 3 to 5 days, then 100 mg orally three times daily. Maximum 1500 mg intravenously each day. Monitor for anaphylaxis (give with resuscitation facilities available), and for response in eye movements and confusion. Avoid in thiamine hypersensitivity; no renal or hepatic adjustment; acceptable in pregnancy.
• Replace other B vitamins and folate, magnesium and potassium; correct hypoglycaemia and electrolytes.
• Methylprednisolone 1000 mg intravenously once daily for 3 to 5 days has been reported to help some patients with acute disease; the evidence is limited and it is a specialist decision. Maximum 5 g in a course. Monitor blood pressure, glucose, mood and infection. Avoid with active untreated infection.
• Alcohol withdrawal management with benzodiazepines under specialist supervision, nutrition support and alcohol cessation.
• Treat seizures: levetiracetam 500 mg orally or intravenously twice daily, increased by 500 mg twice daily every 2 weeks as needed to a maximum of 1500 mg twice daily. Monitor mood and renal function. Reduce dose when creatinine clearance is 50 to 80 mL/min (500 to 1000 mg twice daily), 30 to 50 mL/min (250 to 750 mg twice daily) and under 30 mL/min (250 to 500 mg twice daily).
• Supportive care in high dependency or intensive care for coma; swallowing assessment, nutrition and rehabilitation.
• Alcohol relapse prevention and social support after recovery.

Monitoring. Daily neurological observation initially; repeat MRI at 4 to 8 weeks; review at 3 and 6 months.

Referral and escalation. Neurology, addiction services and dietetics; intensive care for coma or refractory seizures.

Special groups. Non-drinkers with diabetes or malnutrition: treat the underlying cause. Women: pregnancy needs specialist nutritional care.