Focal Cerebral Arteriopathy Steroid Trial (FOCAS)

This comparative effectiveness trial (CET) in children with suspected focal cerebral arteriopathy (FCA) presenting with arterial ischemic stroke (AIS) or transient ischemic attack (TIA) will compare the use of early corticosteroid treatment (Arm A) versus delayed/no corticosteroid treatment (Arm B). Delayed corticosteroid treatment is given only for those demonstrating disease progression and is initiated as soon as the progression is detected (at any time after randomization). All participants will also receive standard of care therapy (aspirin and supportive care). Sites will randomize participants 1:1 to Arm A or B. Participants will be enrolled and randomized as soon as possible after their stroke/TIA up until 96 hours following the initial stroke/TIA event.

Inclusion Criteria

• Age 1 year through 18 years at stroke/TIA ictus (ineligible as of 19th birthday).
• Acute arterial ischemic stroke (AIS) or transient ischemic attack (TIA) in prior 4 days (96 hours).
  1. AIS definition: neurological deficit with acute onset (including seizures) and acute infarct(s) corresponding to arterial territory(ies) on brain imaging.
  2. TIA definition: neurological deficit with acute onset (not including seizures) consistent with ischemia of an arterial territory(ies) but without acute infarction on brain imaging.
• Imaging inclusion criteria:
  • ​Baseline imaging findings consistent with FCA: i. unilateral focal irregularity, banding, stenosis, wall thickening/enhancement, or occlusion of the distal internal carotid artery (ICA) and/or its proximal branches (A1, M1, posterior communicating artery, proximal PCA), OR ii. unilateral infarction in the territory of the lenticulostriate arteries with normal MRA.
  • Ability to return at 1-month (±7 days) post-stroke for an MRI/MRA (non-contrast) on a scanner of the same magnet strength as baseline MRI/MRA.*
• Consent to study procedures.
  • ​A repeat baseline MRI/MRA can be performed as a research scan within 24 hours of enrollment if needed to meet this requirement.

Exclusion Criteria

• Prior stroke.
• Another identified cause of stroke/TIA, other than FCA. (Intracranial dissection is considered a subtype of FCA and will be included if the patient is not predisposed to dissection for the reasons listed below.)
• Presence of childhood stroke risk factors (known to be present at the time of enrollment):
  1. Risk factors for arterial dissection: connective tissue disorder (e.g., Ehlers-Danlos type IV, Marfan syndrome, osteogenesis imperfect); severe head or neck trauma in the two weeks preceding AIS/TIA (defined as skull or cervical fracture, or an ICU admission for trauma).
  2. Risk factors for moyamoya: genetic disorder or syndrome that predisposes to moyamoya (e.g., trisomy 21, neurofibromatosis type 1, tuberous sclerosis, sickle cell anemia, MOPD type II, PHACE syndrome); prior cranial radiation therapy.
  3. Risk factors for secondary vasculitis or vasospasm: acute meningitis, systemic lupus erythematosus or other autoimmune disorder that can cause vasculitis, recent cocaine/amphetamine use (prior 7 days), recent subarachnoid hemorrhage (prior 14 days).
  4. Risk factors for cardioembolism: complex congenital heart disease; recent cardiac surgery or catheterization (prior week); endocarditis or other cardiac valve disease with vegetations; right-to-left cardiac shunting lesion with deep vein thrombosis (DVT) or a known thrombophilia.
• Imaging exclusion criteria:
  • Baseline parenchymal imaging demonstrating remote or bilateral infarcts
  • Vascular imaging demonstrating bilateral arteriopathy or moyamoya collaterals
• Contraindication to corticosteroid therapy (e.g., baseline immunosuppression, significant infection, etc.) as determined by the treating physicians.
• Current or recent (within prior week) treatment with corticosteroids.
• Pregnant, post-partum (within 6 months of childbirth), or nursing.