Lifetime Prevalence of Stroke within an Adult Population with Sickle Cell Disease: A Cross-Sectional Study

Background

Stroke is a potentially devastating complication among patients with sickle cell disease (SCD). Stroke has been well described in children with SCD and can now be prevented in most cases through early screening by transcranial doppler and intensification of treatment for those at risk. In adult patients with SCD, systematic data on stroke prevalence, etiology, and long-term functional impacts are limited. The primary goal of this study was to determine the lifetime prevalence of stroke within an adult population with SCD followed in a specialized referral centre. Secondary objectives included stratification by stroke type, etiology, treatment received and functional outcome.

Methods

The study was designed as a retrospective cross-sectional study that quantified the prevalence of stroke at the end of the observation period (December 2023 or at the last visit) in a large monocentric cohort. All adult patients (≥18 years old) with any SCD genotype (HbSS, HbS β°/β+-thalassemia and HbSC), that had at least one visit between 2011 and 2023 at CHUM were included. Patients were evaluated by vascular neurologists in a specialized clinic in which standard assessment included a National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Montreal Cognitive Assessment (MoCA) test. Symptomatic stroke was defined as any cerebral infarction or intracranial hemorrhage on brain imaging with a corresponding focal neurological deficit or related symptoms. Clinical patient characteristics were extracted from the electronic medical record. Summary statistics were calculated as mean (standard deviation), median [range] and proportions, as appropriate. The project was approved by the local ethics committee.

Results

Overall, 450 patients met the inclusion criteria, 258 (57%) of which were women. The median age was 32 years [range 18-79]. Genotypes included 215 patients with HbSS (48%), 10 HbSβ⁰ (2%), 190 HbSC (42%) and 35 HbSβ+ (8%).

Sixteen patients (3.6%) were identified with at least one symptomatic stroke (median age at presentation 36 years [range 4-65]), including 10 (2.2%) with cerebral infarction (median age 25 years [range 4-58], 6 (1.3%) with intracranial hemorrhage (median age 45 years [range 20-65]). For the SS/Sβ⁰ and SC/Sβ⁺ genotypes, stroke prevalence was 9/225 (4.0%) and 7/225 (3.1%), respectively.

Three patients (0.7%) suffered at least one recurrent stroke during follow-up.

Etiologies for ischemic strokes included carotid stenosis (n=1), Moya-Moya syndrome (n=1), cardio-embolic origin (n=3), acute vaso-occlusive crisis (n=2) and unknown etiology (n=3). Underlying causes for intracranial hemorrhage included aneurysm rupture (n=5) and underlying severe microangiopathy (n=1).

Acute hematological treatment included blood transfusions within 24 hours of admission for 3 patients. None received acute reperfusion therapy (including IV thrombolysis or mechanical thrombectomy). Aneurysms were treated by endovascular (n=4) or neurosurgical procedures (n= 1). Thirteen patients began long-term exchange transfusions, 10 antiplatelet therapy, and 2 oral anticoagulants.

On the last follow-up, nine stroke patients had residual neurological deficits with a median NIHSS score of 0 [range 0-9] and a median mRS of 2 [range 0-3]; seven patients were unable to work. Patients after stroke had a median MoCA of 20 [range 11-29]; 11 had MoCA scores below 26.

Discussion

This large cross-sectional study confirms that the lifetime prevalence of symptomatic stroke in adults with SCD is high with at times long term functional impairment. Stroke etiologies include intracranial large vessel disease, but also common causes such as underlying carotid stenosis or cardiac embolism. Studies with longitudinal neurovascular follow-up are needed to identify risk factors and opportunities for improving primary and secondary stroke prevention.