Paediatric Arteriopathy Steroid Aspirin Project

Arterial ischemic stroke (AIS) is a devastating condition, affecting 1.6-5/100,000 children/year. Although their outcome is different, children with stroke do not recover better than adults, with at least 2/3 suffering long term sequels such as developmental (motor, global intellectual, language...) and behavioral disabilities, epilepsy, and low adaptative and academic skills...

Stenotic cerebral arteriopathy is identified as AIS etiology in 60-80% of previously healthy children and the course of this arteriopathy is the strongest predictor of recurrent events. 30-40% of these children have a focal unilateral cerebral arteriopathy (FCA). Childhood FCA is suspected to be an inflammatory vessel wall pathology triggered by varicella and other (viral) infections. As recurrences occur for the great majority in the first 6 months after the index event, aspirin 5 mg/kg/day is recommended for at least 18 months to 2 years.

As there is a rational for using immunomodulatory drugs at the acute stage of FCA, immunotherapies are currently used by neuropaediatricians in AIS, mainly as steroids for children with stenosing arteriopathies. However, due to weak evidences, the literature cannot either encourage or discourage this practice.

The long term course of children with FCA is only approach to date by retrospective studies and controversies about outcome remain (for example, the recurrence risk on antithrombotic treatment varies notably from quasi zero to 25%). And finally, it is shown in childhood stroke, as well as in the global field of longstanding impairment, that parental and medical points of view do not match consistently. Longitudinal studies are needed to deserve this familial approach.


Eligibility Criteria:
Inclusion Criteria:

-- Aged 6 months to \<15 years

* AIS ≤ 48 hours

  * Newly acquired focal neurological deficit with confirmation by magnetic resonance imaging (MRI) of ischaemic lesion in an arterial territory corresponding with the clinical features (definition of Arterial ischemic stroke).
  * Magnetic resonance arteriography showing unilateral proximal stenosis or irregularities of the corresponding carotid trifurcation (i.e. terminal carotid and/or M1-M2 and/or A1 segments) or of the posterior circulation (P1-P2 segments).
  * No evidence of an underlying systemic disorder (e.g. lupus erythematodes) explaining the features.
  * Informed and signed consent of parents or legal guardians.
* French Social Security (Sécurité sociale; i.e. national health coverage) affiliation

Exclusion Criteria:

* Children with secondary central nervous system angiitis due to infections (meningitis, endocarditis, borreliosis), rheumatic or other systemic inflammatory diseases (e.g. lupus erythematodes). These children are already under immune suppression or need other co-medications regarding their underlying disease.
* Children with known syndromal and/or genetic vasculopathies such as phaces syndrome, Neurofibromatosis type 1, trisomy 21.
* Children with moyamoya or sickle cell disease.
* Children with a progressive large to medium vessel childhood primary angiitis of the central nervous system with two out of the following three criteria : Children with progressive neurocognitive dysfunction; Children with bilateral lesions/vessel involvement; Children with distal arterial stenosis (beyond the M2, A1 or P2 segment).

  - Children already on steroid treatment at disease onset or with a contraindication to receive steroid treatment (e.g. congenital or acquired immunodeficiency).
* Children with delayed diagnosis ≥3 days as treatment start is not allowed to be more ≥5 day-delayed.
* Contraindications to steroids (see also summary of product characteristics in chapter 1.1) and notably: Not-manageable infectious, hydro-electrolytic or metabolic (e.g. diabetes mellitus) disorders, or elevated blood pressure, Serious behavioral disorders, Current vaccination with live or attenuated live strains, Allergy/sensibility to any ingredient, Association with some medications such as antiarrhythmic drugs.