What are the clinical presentation, diagnostic approach, and management of Marchiafava‑Bignami disease in chronic heavy‑alcohol‑using middle‑aged to older men?

Marchiafava-Bignami Disease: Clinical Presentation, Diagnosis, and Management

Marchiafava-Bignami disease (MBD) is a rare toxic demyelinating disorder of the corpus callosum seen predominantly in chronic alcoholics with malnutrition, requiring immediate high-dose parenteral thiamine (500 mg IV three times daily for 3-5 days) before any glucose-containing solutions, as early treatment within 14 days of symptom onset significantly improves outcomes from historically fatal to less than 8% mortality. 1

Clinical Presentation

MBD presents with varied and non-specific neurological symptoms that overlap significantly with other alcohol-related encephalopathies:

Core Neurological Features

• Acute dementia and impaired consciousness ranging from confusion to coma 1
• Dysarthria and speech disturbances 1
• Motor deficits including hemiparesis and pyramidal tract signs 1
• Ataxia and gait disturbances 1
• Seizure activity 2, 1
• Signs of interhemispheric disconnection (alien hand syndrome, apraxia) 1

Patient Demographics

• Middle-aged to older men (typically 30-55 years) with chronic heavy alcohol use exceeding 10 years 3, 2
• History of consuming more than 90 grams of alcohol daily for more than 5 years 3
• Associated malnutrition and thiamine deficiency 1, 4

Critical Pitfall: The clinical presentation is non-specific and cannot be differentiated from Wernicke's encephalopathy, hepatic encephalopathy, or alcohol withdrawal syndrome by examination alone. 5 Always suspect and treat for both Wernicke's encephalopathy and MBD simultaneously in any chronic alcoholic presenting with altered mental status. 5

Diagnostic Approach

Immediate Evaluation

Do not delay treatment while awaiting diagnostic confirmation - the diagnosis is clinical plus radiological, and waiting for laboratory or imaging results worsens outcomes. 5, 1

Essential Imaging

• MRI is the diagnostic modality of choice showing hyperintensity of the corpus callosum on T2 and FLAIR sequences, with or without extracallosal white matter lesions 1, 6
• Progressive demyelination and necrosis of the corpus callosum extending laterally into neighboring white matter and occasionally to subcortical regions 7, 2
• CT scan has limited sensitivity but may show hypodensity in the corpus callosum 6

Laboratory Assessment

• Blood glucose, electrolytes (especially sodium, potassium, magnesium), calcium, CBC, and liver function tests to identify precipitating factors and rule out differential diagnoses 5
• Thiamine diphosphate (ThDP) measurement in whole blood or red blood cells if available, though treatment should never be delayed for results 5
• Lactate, pyruvate, alpha-ketoglutarate levels may support thiamine deficiency 5

Critical Differential Diagnoses to Exclude

• Wernicke's encephalopathy (frequently coexists and requires identical treatment) 5, 1
• Hepatic encephalopathy (cannot be differentiated clinically and may coexist) 8, 5
• Hypoglycemia, hyponatremia, hypokalemia, hypomagnesemia 5
• Multiple sclerosis, encephalitis, infectious or paraneoplastic leukoencephalopathy 1
• Stroke, multi-infarct dementia, frontotemporal lobar degeneration 1

Management Protocol

Immediate Treatment (First 3-5 Days)

Step 1: Thiamine Administration BEFORE Any Glucose

• Administer 500 mg thiamine IV three times daily for 3-5 days 5
• Thiamine MUST be given before any glucose-containing IV solutions to prevent precipitating or worsening encephalopathy 8, 5
• This is particularly crucial in patients receiving IV dextrose, requiring fluid resuscitation, or before commencing parenteral nutrition 5

Step 2: Alcohol Withdrawal Management

• Long-acting benzodiazepines (chlordiazepoxide 25-100 mg PO every 4-6 hours or diazepam 5-10 mg PO/IV every 6-8 hours) for prevention of seizures and delirium tremens 8
• Lorazepam 1-4 mg PO/IV every 4-8 hours in patients with severe liver disease, advanced age, or respiratory compromise 8
• Monitor for alcohol withdrawal syndrome complications including delirium tremens, seizures, and cardiovascular instability 8

Step 3: Comprehensive Micronutrient Replacement

• Daily multivitamins, electrolytes, and trace elements from the beginning of treatment 5
• Replace zinc, vitamin D, folate, and pyridoxine as deficiencies are common in alcohol use disorders 5
• Magnesium supplementation for prevention of seizures and correction of electrolyte abnormalities 8

Continuation Phase (Days 5-14)

• Thiamine 250 mg IV daily for at least 3-5 additional days 5
• Continue benzodiazepine taper following resolution of withdrawal symptoms 8
• Nutritional support: 35-40 kcal/kg ideal body weight daily with 1.2-1.5 g/kg/day protein 8, 5
• Small frequent meals throughout the day with late-night snack 5

Long-Term Management

• Transition to oral thiamine 50-100 mg daily after parenteral treatment 5
• Mandatory alcohol abstinence - continued drinking results in 40-50% mortality within 3-6 years 3, 9
• Psychiatric consultation for alcohol dependence treatment and relapse prevention 8
• Consider baclofen or acamprosate for alcohol pharmacotherapy in patients without severe liver disease 8
• Avoid naltrexone and disulfiram due to hepatotoxicity risk in patients with alcoholic liver disease 8

Monitoring and Follow-Up

• Assess for improvement in neurological symptoms, cognitive function, and resolution of ocular abnormalities, mental status changes, and ataxia 5
• Serial MRI to document resolution or progression of corpus callosum lesions 6
• Screen for other alcohol-related organ damage: alcoholic cardiomyopathy, pancreatitis, peripheral neuropathy 8
• Evaluate for hepatic complications including cirrhosis, portal hypertension, and hepatocellular carcinoma 8

Critical Pitfalls to Avoid

1. Administering glucose before thiamine - this can precipitate acute decompensation and worsen encephalopathy 8, 5
2. Assuming altered mental status is solely hepatic encephalopathy - Wernicke's encephalopathy and MBD must be ruled out first 8, 5
3. Delaying treatment while awaiting laboratory or imaging confirmation - empiric high-dose thiamine is safe and should be started immediately 5, 1
4. Failing to consider MBD in non-alcoholic patients with malnutrition, post-bariatric surgery, prolonged vomiting, or hyperemesis gravidarum 5, 1
5. Using therapeutic doses of paracetamol without caution in malnourished alcoholic patients, as this may produce liver injury 8
6. Restricting protein in liver disease patients - this worsens malnutrition and increases mortality risk 5

Prognosis

Early treatment within 14 days of symptom onset demonstrates statistically better outcomes compared to delayed treatment, improving prognosis from historically fatal to mortality less than 8%. 1 Complete abstinence from alcohol is mandatory for any meaningful recovery, as continued drinking results in progressive neurological deterioration and death. 3, 9, 4