What is the treatment for primary central nervous system (CNS) vasculitis?

Treatment of Primary CNS Vasculitis

For primary CNS vasculitis, initiate combination therapy with high-dose corticosteroids plus cyclophosphamide, as this regimen achieves favorable response in approximately 80% of patients and is supported by the highest quality evidence. 1

Initial Treatment Approach

First-Line Therapy

• Administer high-dose corticosteroids (prednisone 1 mg/kg/day, maximum 60 mg/day) combined with cyclophosphamide as the standard induction regimen for primary CNS vasculitis 1, 2
• Cyclophosphamide can be given as either pulse intravenous therapy or continuous oral dosing (2 mg/kg/day, maximum 200 mg/day) 1
• This combination achieves treatment response in 80% of patients with primary CNS vasculitis 2

Corticosteroid Monotherapy Considerations

• Prednisone alone may be considered in select cases, achieving favorable response in 85% of patients 2
• However, corticosteroid monotherapy carries significantly higher relapse risk (odds ratio 2.90) compared to combination therapy 2
• Monotherapy is associated with poorer long-term outcomes and higher rates of disease recurrence 1

Maintenance and Steroid-Sparing Therapy

Steroid Tapering Strategy

• Implement slow tapering of oral steroids to a target of ≤5 mg/day after 1 year to prevent disease exacerbation 1
• Rapid steroid withdrawal is associated with disease flare and should be avoided 1

Addition of Steroid-Sparing Agents

• Add a steroid-sparing immunosuppressive agent rather than continuing long-term steroid monotherapy, as monotherapy results in higher relapse rates and worse outcomes 1
• Commonly used maintenance agents include:
  • Mycophenolate mofetil 1, 3
  • Azathioprine 1
  • Methotrexate 1
  • Rituximab 1, 3
• No robust comparative data exist between these agents, so selection should be based on individual patient comorbidities and side effect profiles 1

Treatment for Refractory Disease

Second-Line Options

• For patients unresponsive to corticosteroids and cyclophosphamide, consider alternative immunosuppressants including mycophenolate mofetil, tumor necrosis factor-α blockers, or rituximab 3
• Refer refractory cases to centers of expertise for specialized management 4

Special Considerations by Disease Subtype

Small Vessel vs. Large Vessel Disease

• Small cortical/leptomeningeal vessel involvement is associated with more benign course and better treatment response 5, 2
• Large vessel involvement (odds ratio 6.14) predicts poor treatment response and requires more aggressive therapy 2
• Patients with cerebral infarctions at diagnosis have significantly worse treatment response (odds ratio 3.32) and higher mortality (hazard ratio 4.44) 2

Nonprogressive Arteriopathy

• Some children with arteritis stabilize or improve without specific treatment, particularly in cases of post-varicella angiopathy or transient cerebral arteriopathy 1
• Distinguishing between transient/nonprogressive and progressive arteriopathies at presentation remains challenging and is subject of ongoing research 1

Monitoring and Follow-Up

Treatment Response Assessment

• Perform structured clinical examination, blood test monitoring, and urine analysis at each clinical visit to assess disease activity and medication toxicity 1, 4
• Monitor for acute leukopenia or progressive decline in white blood cell count, which may require dose adjustment or discontinuation of immunosuppressive therapy 1
• Assess renal function periodically, as declining function may necessitate dose modification 1
• Monitor blood glucose while on glucocorticoid therapy 1

Relapse Management

• Relapses occur in approximately 27% of patients with primary CNS vasculitis 2
• Treatment with corticosteroids plus another immunosuppressant reduces relapse rates compared to monotherapy 6

Prognostic Factors

Predictors of Poor Outcome

• Increasing age at diagnosis is associated with higher disability scores (odds ratio 1.44) and increased mortality (hazard ratio 1.39) 2
• Cerebral infarction at diagnosis predicts higher disability (odds ratio 3.74) and mortality (hazard ratio 4.44) 2
• Large vessel involvement carries substantially increased mortality risk (hazard ratio 4.98) 2
• Longer duration of illness before diagnosis is associated with poorer functional outcomes 6
• Presence of myelitis predicts worse outcomes 6

Predictors of Better Outcome

• Gadolinium-enhanced cerebral lesions or meningeal enhancement are associated with lower disability scores (odds ratio 0.35) and reduced mortality (hazard ratio 0.20) 2
• These findings may indicate more responsive disease that benefits from immunosuppressive therapy 2

Critical Pitfalls to Avoid

• Do not use infliximab for CNS vasculitis, as it is associated with higher risk of disease activity and lower remission rates 1
• Avoid rapid steroid withdrawal, which increases risk of disease exacerbation 1
• Do not rely on corticosteroid monotherapy for long-term management due to high relapse rates 1, 2
• Recognize that approximately 25% of patients will have discontinued therapy by last follow-up, indicating potential for disease remission in select cases 2