TY - JOUR
T1 - White matter hyperintensity burden in acute stroke patients differs by ischemic stroke subtype
AU - Giese, Anne Katrin
AU - Schirmer, Markus D.
AU - Dalca, Adrian V.
AU - Sridharan, Ramesh
AU - Donahue, Kathleen L.
AU - Nardin, Marco
AU - Irie, Robert
AU - McIntosh, Elissa C.
AU - Mocking, Steven J.T.
AU - Xu, Huichun
AU - Cole, John W.
AU - Giralt-Steinhauer, Eva
AU - Jimenez-Conde, Jordi
AU - Jern, Christina
AU - Kleindorfer, Dawn O.
AU - Lemmens, Robin
AU - Wasselius, Johan
AU - Lindgren, Arne
AU - Rundek, Tatjana
AU - Sacco, Ralph L.
AU - Schmidt, Reinhold
AU - Sharma, Pankaj
AU - Slowik, Agnieszka
AU - Thijs, Vincent
AU - Worrall, Bradford B.
AU - Woo, Daniel
AU - Kittner, Steven J.
AU - McArdle, Patrick F.
AU - Mitchell, Braxton D.
AU - Rosand, Jonathan
AU - Meschia, James F.
AU - Wu, Ona
AU - Golland, Polina
AU - Rost, Natalia S.
N1 - Funding Information:
Funding provided by NIH–National Institutes of Neurological Disorders and Stroke (MRI-GENIE: R01NS086905—principal investigator N. Rost; K23NS064052, R01NS082285—N. Rost; SiGN: U01 NS069208—J. Rosand, S. Kittner; R01NS059775, R01NS063925, R01NS082285, P50NS051343, R01NS086905, U01 NS069208—O. Wu), NIH National Institute of Biomedical Imaging and Bioengineering (P41EB015902—P. Golland, U01NS030678—B. Kissela, D. Kleindorfer; EB015325—O. Wu), ISGS: R01NS423733—principal investigator J. Meschia, Swedish Heart and Lung Foundation, Lund University, Region Skåne, the Freemasons Lodge of Instruction Eos Lund, Skåne University Hospital, the Foundation of Färs&Frosta—one of Sparbanken Skåne’s ownership foundations, and the Swedish Stroke Association—A. Lindgren, Swedish Research Council and the Swedish Heart and Lung Foundation, the Swedish State under the ALF agreement—C. Jern, Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (Funding for Research in Health [PI051737], [PI10/02064], [PI12/01238], and [PI15/00451—J. Jiménez-Conde]), Fondos FEDER/EDRF Red de Investigación Cardiovascular (RD12/0042/0020—J. Jimenez-Conde), Fundació la Marató TV3 (76/C/2011—J. Jiménez-Conde) and Recercaixa’13 (JJ086116—J. Jiménez-Conde), and Wistron Corp (P. Golland). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 753896 (M.D. Schirmer). R.L. is a senior clinical investigator of FWO Flanders.
Publisher Copyright:
© 2020 American Academy of Neurology.
PY - 2020/7/7
Y1 - 2020/7/7
N2 - ObjectiveTo 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).MethodsFor 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.ResultsPatients 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).ConclusionIn 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.
AB - ObjectiveTo 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).MethodsFor 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.ResultsPatients 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).ConclusionIn 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.
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U2 - 10.1212/WNL.0000000000009728
DO - 10.1212/WNL.0000000000009728
M3 - Article
C2 - 32493718
AN - SCOPUS:85088211081
SN - 0028-3878
VL - 95
SP - 79
EP - 88
JO - Neurology
JF - Neurology
IS - 1
ER -