Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol

Abstract

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research. Methods: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. Study Significance: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke

“…Unlike pre-existing systems,(29) the ACCESS software reduced this limitation by introducing a well-referenced, well-defined, and rule-based assignment of etiological subtypes according to the ASCO, TOAST and SMASH-U systems. (7;15–21)…”

“…temporal, frontal, occipital, parietal, basal ganglia, brainstem; cortical, subcortical, cortical/subcortical and characteristics of lesions such as laterality, size, volume, age and inference such as stroke subtype (Supplementary Table 1). (7;15–21)…”

“…Therefore, we incorporated rules based on the SIREN investigation algorithm (7) (Supplementary Figure 1) to synthetize neuroimaging, clinical and laboratory data to subtype, (7) stroke based on these classification systems. To enhance reliability while activating the Hawthorne effect, we utilize a three-tier adjudication process within SIREN.…”

“…The first step involves the neurologist/neuroradiologist team in each site for an initial/first review, then another neurologist/neuroradiologist team from a different site and finally a central adjudication panel to review selected cases. (7)…”

“…Combined large accurate datasets from diverse settings are required to fully understand the genomic and environmental underpinnings of stroke and its discrete subtypes as well as the relationship between stroke neuroimaging phenotype and its clinical manifestations, prognosis and outcome (6;7). Such multicenter research involving multiple investigators and large datasets require secure archiving, as well as accurate and reproducible standard classification formats.…”