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.