What is the recommended treatment regimen for neuro‑Behçet’s disease with central nervous system involvement?

Treatment of Neuro-Behçet's Disease

For acute parenchymal neuro-Behçet's disease, initiate high-dose intravenous methylprednisolone (1 g/day for 3-7 days) followed by oral prednisolone (1 mg/kg/day) with gradual tapering over 6-12 months, combined with azathioprine (2.5 mg/kg/day) as a steroid-sparing immunosuppressive agent from the outset. 1, 2

Distinguishing CNS Involvement Types

The treatment approach differs based on the type of neurological involvement:

• Parenchymal involvement (majority of cases): Presents with brainstem-diencephalic symptoms, focal deficits, and carries worse prognosis requiring aggressive immunosuppression 1, 3
• Cerebral venous sinus thrombosis (10-20% of cases): Presents primarily with intracranial hypertension symptoms and has significantly better prognosis 1, 3, 4

These two forms rarely occur in the same patient and require different management strategies. 1

Acute Treatment Protocol

Initial Corticosteroid Regimen

• Start with intravenous methylprednisolone 1 g/day for 3-7 days (may extend up to 10 days for severe cases) 1, 2, 3
• Follow with oral prednisolone 1 mg/kg/day for 1 month 1, 2
• Taper by 5-10 mg every 10-15 days, aiming for maintenance dose of 5-10 mg/day 1, 2
• Continue tapering over 6-12 months depending on disease severity and response 2, 3

Concurrent Immunosuppressive Therapy

• Azathioprine 2.5 mg/kg/day should be started immediately alongside corticosteroids, not after steroid failure 1, 2
• Alternative first-line agents include methotrexate (15-25 mg/week) or mycophenolate mofetil if azathioprine is contraindicated 2, 5, 6
• Continue immunosuppressive therapy for at least 2 years and at least 12 months after normalization of inflammatory markers 7

Treatment for Severe or Refractory Disease

For patients with severe disease at onset, persistent symptoms despite conventional therapy, or chronic progressive neuro-Behçet's, TNF-alpha inhibitors (particularly infliximab) should be considered as first-line or early escalation therapy. 1, 2

• Infliximab has shown rapid response (within 1-5 days) in refractory cases 7, 5
• Consider first-line infliximab in young men with early disease onset who have higher risk of severe disease 2, 8, 7
• Other biologic options for multidrug-resistant cases include tocilizumab, IL-1 inhibitors (anakinumab, canakinumab), and interferon-alpha 5, 6

Chronic Progressive Neuro-Behçet's

• Low-dose weekly methotrexate has been specifically suggested for chronic progressive forms 5
• This differs from acute parenchymal involvement where azathioprine is preferred 5

Cerebral Venous Sinus Thrombosis Management

• Treat with high-dose corticosteroids followed by tapering (same regimen as parenchymal involvement) 1
• Anticoagulation may be added for short duration only (typically fractionated heparin), but this is controversial 1, 3
• Long-term oral anticoagulation is unnecessary as prognosis is favorable compared to other causes of cerebral venous thrombosis 1, 3
• Screen for extracranial vascular disease, particularly pulmonary or peripheral aneurysms, before considering anticoagulation due to bleeding risk 1, 3
• Long-term azathioprine is recommended to prevent recurrences 3

Critical Contraindications

Cyclosporine A must be avoided in all patients with CNS involvement due to significant neurotoxicity risk, despite its efficacy in ocular Behçet's disease. 1, 2, 8, 7

This is one of the most important pitfalls to avoid, as cyclosporine is effective for other manifestations of Behçet's but can worsen neurological involvement. 1, 7

Monitoring and Long-Term Management

• Assess clinical symptoms and inflammatory markers (ESR, CRP) regularly 2, 8
• Young male patients require more aggressive treatment and closer monitoring due to higher risk of severe disease 2, 8, 7
• Disease manifestations often ameliorate over time, allowing potential tapering and discontinuation of treatment in stable patients 2, 8
• Neurological involvement is associated with poor prognosis and can cause serious disability or death if inadequately treated 2
• Multidisciplinary approach involving neurology and rheumatology is essential for optimal outcomes 2, 5

Treatment Algorithm Summary

1. Confirm type of CNS involvement (parenchymal vs. cerebral venous thrombosis)
2. Initiate IV methylprednisolone 1 g/day for 3-7 days immediately
3. Start azathioprine 2.5 mg/kg/day concurrently (or methotrexate/mycophenolate if contraindicated)
4. Transition to oral prednisolone 1 mg/kg/day after IV pulse
5. Taper steroids gradually over 6-12 months
6. For severe/refractory cases: Add infliximab early
7. For chronic progressive disease: Consider low-dose weekly methotrexate
8. Continue immunosuppression for minimum 2 years after achieving remission
9. Never use cyclosporine A in neuro-Behçet's patients