Stroke in Children with Sickle Cell Disease

Children with sickle disease are at high risk for ischemic stroke and transient ischemic attacks, usually secondary to intracranial arteriopathy involving the terminal internal carotid and proximal middle cerebral and anterior cerebral arteries, which may be diagnosed using transcranial Doppler ultrasound or magnetic resonance angiography (MRA). Other central nervous system (CNS) complications include seizures and coma, which may be secondary to ischemic stroke, sinovenous thrombosis, reversible posterior leukoencephalopathy, or acute demyelination. The immediate priority after an acute CNS event is to improve cerebral oxygenation with oxygen supplementation to maintain peripheral saturation measured using pulse oximetry between 96% and 99%, and a simple transfusion of packed cells within an hour of presentation if the patient's hemoglobin is less than 10 g/dL. The patient then should have erythrocytapheresis or manual exchange to reduce the hemoglobin S percentage to below 30%. Computed tomography to exclude hemorrhage is mandatory and MR T2-weighted imaging with MRA, fat-saturated imaging of the neck (dissection), MR venography (sinovenous thrombosis), and diffusion-weighted imaging usually distinguishes between arterial ischemic stroke and the differential diagnoses. Comatose patients with widespread focal or global cerebral edema may have good functional outcome after surgical decompression. Anticoagulation may be indicated for dissection or sinovenous thrombosis and steroids for demyelination. Blood pressure should be reduced slowly if raised in patients with reversible posterior leukoencephalopathy. Seizures should be treated aggressively and electroencephalogram monitoring should be done to exclude subclinical seizures if the patient is unconscious. Hemorrhagic stroke may require craniectomy and drainage and/or management of vasospasm. Interventional neuroradiology with coils is an alternative to surgical clipping for aneurysms. For secondary prevention, regular blood transfusion to hemoglobin S of less than 30% reduces the risk of recurrent stroke from approximately 67% to approximately 10%. Hydroxyurea and phlebotomy may be used in patients who are alloimmunized. Moyamoya syndrome is a risk factor for recurrence despite prophylactic blood transfusion. Revascularization may prevent additional stroke. Bone marrow transplantation may be offered to patients with human leukocyte antigen-compatible siblings. Blood transfusion prevents stroke in patients with velocities greater than 200 cm per second on TCD; a phase III trial studying the prevention of the progression of silent infarction is being done. Emerging primary prophylaxis regimens being tested include citrulline and arginine, aspirin, and overnight oxygen supplementation. Physicians caring for children with sickle cell disease also should ensure adequate nutrition, including five servings of fruit and vegetables a day. The role of vitamin supplementation is controversial, particularly when patients must take daily penicillin prophylaxis.