What is the management of Neurobehcet syndrome?

Management of Neuro-Behçet Syndrome

For acute parenchymal neuro-Behçet's disease, initiate high-dose intravenous corticosteroids (methylprednisolone 1g daily for 3-5 days) followed by oral prednisone taper over 6-12 months, combined with immunosuppressive therapy using azathioprine or cyclophosphamide for relapse prevention. 1, 2, 3

Classification and Risk Stratification

Neuro-Behçet's disease must be categorized into two distinct subtypes as they require different management approaches 4, 5:

• Parenchymal involvement (80-90% of cases): Brainstem syndrome, hemispheric lesions, meningoencephalitis, myelopathy, or progressive cognitive decline 4, 5
• Non-parenchymal involvement (10-20% of cases): Cerebral venous sinus thrombosis (CVST) with intracranial hypertension 4, 5

Young men with early disease onset represent the highest risk group for severe neurological involvement and require aggressive early immunosuppression. 2, 6

Acute Phase Management

Parenchymal Neuro-Behçet's Disease

Immediate treatment with high-dose intravenous methylprednisolone (1g daily for 3-5 days) is the cornerstone of acute management. 2, 3, 7

Following pulse therapy 3, 7:

• Transition to oral prednisone with gradual taper over 6-12 months depending on severity
• Never use corticosteroids as monotherapy for maintenance

Risk stratification determines immunosuppressive selection 8:

Low-risk patients (single attack, unifocal involvement, normal CSF protein/cell count) 8:

• Azathioprine (2-2.5 mg/kg/day) plus corticosteroids as first-line
• Alternative: Methotrexate (15-25 mg weekly) plus corticosteroids

High-risk patients (multifocal involvement, spinal presentations, >2 attacks/year, progressive course, elevated CSF protein/cells) 8:

• Intravenous cyclophosphamide (0.5-1g/m² monthly for 6-12 months) plus corticosteroids
• Consider first-line infliximab (5 mg/kg at weeks 0,2,6, then every 6-8 weeks) in severe cases with high risk of permanent damage 7

Non-Parenchymal Neuro-Behçet's Disease (CVST)

For cerebral venous sinus thrombosis, use corticosteroids (high-dose initially) with or without immunosuppressants. 1, 2, 8

• Anticoagulation may be added but remains controversial; short-term use with immunosuppression is suggested 8, 5
• Immunosuppressive agents (azathioprine or mycophenolate) should be considered for relapse prevention 5

Maintenance and Relapse Prevention

First-Line Maintenance Therapy

Azathioprine (2-2.5 mg/kg/day) is the preferred maintenance agent for preventing relapses in parenchymal neuro-Behçet's disease. 2, 3, 7

Alternative first-line options 2, 3:

• Mycophenolate mofetil (2-3g daily in divided doses)
• Methotrexate (15-25 mg weekly, particularly for chronic progressive forms)

Chronic Progressive Neuro-Behçet's Disease

Low-dose weekly methotrexate has been specifically suggested for chronic progressive neurological involvement. 7

This represents a distinct clinical entity requiring different management than acute relapsing disease 7.

Refractory Disease Management

When first-line immunosuppressants fail or are not tolerated, escalate to biologic agents with infliximab as the preferred choice. 2, 3, 8

Sequential escalation algorithm for refractory cases 3, 8, 7:

1. Infliximab (5 mg/kg at weeks 0,2,6, then every 6-8 weeks) - strongest evidence among biologics
2. Interferon-alpha (3-9 million units subcutaneously three times weekly)
3. Alternative TNF-alpha inhibitors: Adalimumab or etanercept
4. Tocilizumab (IL-6 inhibitor, 8 mg/kg monthly) for multidrug-resistant cases
5. IL-1 inhibitors (anakinra 100mg daily or canakinumab) for severe refractory disease
6. Cyclophosphamide if not already used
7. Chlorambucil as last resort for most refractory patients

Critical Contraindications

Cyclosporine A must be avoided in all patients with central nervous system involvement due to significant neurotoxicity risk. 1, 2, 6

This is a high-level evidence recommendation from EULAR guidelines and represents an absolute contraindication unless the patient has severe posterior uveitis requiring this agent, in which case extreme caution and close monitoring are mandatory 1.

Monitoring and Follow-Up

Regular clinical assessment with inflammatory markers (ESR, CRP) should be performed at each visit to detect subclinical disease activity. 2, 6

Specific monitoring requirements 5:

• Brain MRI at baseline and with clinical changes to assess for new lesions or atrophy
• CSF analysis during acute attacks: expect pleocytosis, elevated protein, normal glucose in parenchymal disease
• Spinal MRI if myelopathic symptoms develop (look for noncontiguous multifocal cervical/thoracic lesions)
• MR venography or CT venography for suspected CVST
• Regular ophthalmologic examinations for all patients given high risk of concurrent ocular involvement

Common Pitfalls and Caveats

The two subtypes (parenchymal vs. non-parenchymal) rarely coexist in the same patient and likely have different pathogenesis, requiring distinct treatment approaches. 4

Critical management errors to avoid 1, 8, 7:

• Using corticosteroids alone for maintenance therapy (always combine with immunosuppressant)
• Prescribing cyclosporine A in patients with CNS involvement
• Failing to recognize chronic progressive neuro-Behçet's as a distinct entity requiring methotrexate rather than azathioprine
• Delaying aggressive immunosuppression in young men with early-onset disease
• Undertreating high-risk patients with unifocal involvement at presentation

Neurological involvement in Behçet's disease represents a major cause of morbidity and mortality, making early recognition and aggressive treatment essential to prevent permanent disability. 7