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Abstract
Objective To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS).
Methods For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes.
Results Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18–14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001).
Conclusion In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.
Glossary
- AIS=
- acute ischemic stroke;
- CAD=
- coronary artery disease;
- CCS=
- Causative Classification of Ischemic Stroke;
- CE major=
- major cardioembolic stroke;
- CI=
- confidence interval;
- FLAIR=
- fluid-attenuated inversion recovery;
- IQR=
- interquartile range;
- LAA=
- large artery atherosclerosis;
- MRI-GENIE=
- MRI-Genetics Interface Exploration;
- QC=
- quality control;
- SAO=
- small artery occlusion;
- SiGN=
- Stroke Genetics Network;
- TOAST=
- Trial of Org 10172 in Acute Stroke Treatment;
- WMH=
- white matter hyperintensity;
- WMHv=
- WMH volume
Footnotes
Coinvestigators are listed at links.lww.com/WNL/B100.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received April 5, 2019.
- Accepted in final form December 12, 2019.
- © 2020 American Academy of Neurology
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