Retrospective cohort study
A retrospective cohort study examined pediatric patients (ages 0-18 years) on CTT at the sickle cell programs of the Nemours Alfred I. duPont Hospital for Children in Delaware and Nemours Specialty Care, University of Florida - Jacksonville and Wolfson Children’s Hospital from 2006 to 2018. This study was approved by both institutional review boards with a waiver of informed consent. Patients diagnosed with SCD and MMS were included in the study. The diagnosis of MMS was determined by documented imaging findings on magnetic resonance angiography (MRA), computerized tomographic angiography or digital subtraction angiography. Diagnostic criteria of MMS on MRA includes characteristic angiographic findings of stenosis or occlusion of the terminal portion of the internal carotid artery and the proximal portions of the anterior cerebral and middle cerebral arteries along with abnormal collateral vessels at the base of the brain.10
Conservative and surgical treatment groups were defined retrospectively. The conservative treatment group consisted of patients treated with CTT and medical therapy, including aspirin and iron chelation. The surgical group consisted of patients treated with the same conservative methods with the addition of surgical cerebral revascularization (indirect or direct vascular bypass). All revascularizations were performed by the senior authors (P.A., R.H. and J.P.).
The follow-up period was defined as the interval between the first transfusion on CTT and the last follow-up appointment for patients in the conservative treatment group, or the interval between the first surgical treatment and the last follow-up appointment for patients in the surgical treatment group. The study endpoints included symptomatic stroke, stroke-related death, other cerebrovascular events [CVE – defined as asymptomatic stroke or transient ischemic attack (TIA)]. Major surgical complications within 90 days of surgery were reported.
Patient characteristics were compared in domains such as: age at first stroke and subsequent strokes, age at initiation of CTT, aspirin intake, and iron chelation therapy. Vasculopathy scores were graded by a pediatric neuroradiologist based on the vascular occlusion present on the patient’s MRA imaging according to the SWiTCH trial. The trial standardized a grading scale from 0 to 6 to assess the location, extent and severity of vasculopathy, with increasing severity.11 A student T-test was used for continuous variables, a chi-square test was used for categorical variables, and the Wilcoxon rank-sum test for ordinal variables. Incidence of stroke recurrence was compared between the conservative treatment group and the surgical treatment group using a Kaplan-Meier survival curve and the Logrank test. Statistical significance was defined as p<0.05.