Maintenance Treatment of Childhood Primary Angiitis of Central Nervous System with Aspirin and Azathioprine

Abstract

Objectives: We aimed to assess the efficacy and safety of Aspirin and Azathioprine in prevention of recurrence of childhood primary angiitis of central nervous system (cPACNS) after induction therapy with intravenous pulse Methylprednisolone/ Immunoglobulin, and describe long-term neurological outcomes in a cohort of children with this disorder. Study type: Case series Methods: The cohort comprised of consecutive patients diagnosed as having childhood primary angiitis of central nervous system (cPACNS), based on clinical and vascular imaging findings, including identification of arterial stenosis on conventional angiography or Magnetic Resonance (MR) angiography. Over the period of 2 years, 68 children with cPACNS were admitted, who presented within 14 days of onset of the symptoms. Patients with ischemic infarcts were initially treated in conjunction with Heparin/ Oral Anticoagulant and IV Methylprednisolone and/or Immunoglobulin, and this was followed by long term use of Aspirin and Azathioprine. Patient were followed in the out patients clinics and were systemically assessed for clinical presentation, hospital course, adverse effects of anticoagulants, aspirin and Azathioprine. The primary outcomes were 1) morbidity and mortality, 2) Paediatric Stroke Outcome Measure (PSOM) scores after the median follow-up of 34 months. Statistical analysis: Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 12.0 (Chicago, IL). Frequencies were calculated for categorical data including gender, final outcome and complications of anticoagulation therapy. Mean with 95% SD was calculated for nominal variables including age. Fisher’s exact test or chi squared test were used, where appropriate to determine any significant difference in outcome with different presenting features, taking p<0.05 as significant. Results: From January 2008, to December 2010, 94 patients with cPACNS were enrolled, 68 of whom met the inclusion criteria and were given induction therapy. The median age at diagnosis was 8.5 years (range 1•6-16 years). 56 patients (boys 35/56, 62%, girls 21/56, 38%) completed induction therapy (with acute mortality of 12/68, 18.5%) and received maintenance therapy with aspirin (n=40) or aspirin and azathioprine (n=16). At the median follow-up of 34 months, of the total 56 patients is; total 30 (30/56, 53.5%) had relapse/flare: first relapse within 24 months after discharge 35.7%: 20 (20/56, 35.7%) died, 15 (15/56, 26.7%) in association with relapse of cPACNS, 5 (5/56, 9%) died due to other causes:14 (14/56, 25%) were receiving Aspirin only: 11 (11/56, 19.6%) were off any medication : 7 (7/56, 12.3%) were receiving both Azathioprine and Aspirin and 4 (4/56, 7.2%) were lost in follow-up. The Neurological findings among 32 patients available to be assessed at last follow up by Paediatric Stroke Outcome Measurement (PSOM) were; normal 8 (8/32, 25%); minor disabilities 10 (10/32, 31.25%; moderate disabilities 10 (10/32, 31.25%) and severe disabilities 4 (4/32, 12.5%). No serious side effects were documented due to low dose aspirin and azathioprine therapy. Conclusion: The spectrum of cPACNS in children includes both progressive and non-progressive forms. Recurrence of cPACNS was high within six months after discharge with high mortality, more among the patients treated with Aspirin than with Azathioprine in conjunction with Aspirin, after initial treatment with IV Methylprednisolone / Immunoglobulin and heparin/ oral anticoagulants.