Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

Heitsch, L; Ibanez, L; Carrera, C; Binkley, MM; Strbian, D; Tatlisumak, T; Bustamante, A; Ribo, M; Molina, C; Davalos, A; Lopez-Cancio, E; Munoz-Narbona, L; Soriano-Tarraga, C; Giralt-Steinhauer, E; Obach, V; Slowik, A; Pera, J; Lapicka-Bodzioch, K; Derbisz, J; Sobrino, T; Castillo, J; Campos, F; Rodriguez-Castro, E; Arias-Rivas, S; Segura, T; Serrano-Heras, G; Vives-Bauza, C; Diaz-Navarro, R; Tur, S; Jimenez, C; Marti-Fabregas, J; Delgado-Mederos, R; Arenillas, J; Krupinski, J; Cullell, N; Torres-Aguila, NP; Muino, E; Carcel-Marquez, J; Moniche, F; Cabezas, JA; Ford, AL; Dhar, R; Roquer, J; Khatri, P; Jimenez-Conde, J; Fernandez-Cadenas, I; Montaner, J; Rosand, J; Cruchaga, C; Lee, JM

Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, def...

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Autores:	Heitsch, L, Ibanez, L, Carrera, C, Binkley, MM, Strbian, D, Tatlisumak, T, Bustamante, A, Ribo, M, Molina, C, Davalos, A, Lopez-Cancio, E, Munoz-Narbona, L, Soriano-Tarraga, C, Giralt-Steinhauer, E, Obach, V, Slowik, A, Pera, J, Lapicka-Bodzioch, K, Derbisz, J, Sobrino, T, Castillo, J, Campos, F, Rodriguez-Castro, E, Arias-Rivas, S, Segura, T, Serrano-Heras, G, Vives-Bauza, C, Diaz-Navarro, R, Tur, S, Jimenez, C, Marti-Fabregas, J, Delgado-Mederos, R, Arenillas, J, Krupinski, J, Cullell, N, Torres-Aguila, NP, Muino, E, Carcel-Marquez, J, Moniche, F, Cabezas, JA, Ford, AL, Dhar, R, Roquer, J, Khatri, P, Jimenez-Conde, J, Fernandez-Cadenas, I, Montaner, J, Rosand, J, Cruchaga, C, Lee, JM
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2021
País:	España
Institución:	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:	oai:iibsantpau.fundanetsuite.com:p5809
Acceso en línea:	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5809
Access Level:	acceso abierto
Palabra clave:	genome-wide association study phenotype population stroke ischemic

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spelling	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day OutcomeHeitsch, LIbanez, LCarrera, CBinkley, MMStrbian, DTatlisumak, TBustamante, ARibo, MMolina, CDavalos, ALopez-Cancio, EMunoz-Narbona, LSoriano-Tarraga, CGiralt-Steinhauer, EObach, VSlowik, APera, JLapicka-Bodzioch, KDerbisz, JSobrino, TCastillo, JCampos, FRodriguez-Castro, EArias-Rivas, SSegura, TSerrano-Heras, GVives-Bauza, CDiaz-Navarro, RTur, SJimenez, CMarti-Fabregas, JDelgado-Mederos, RArenillas, JKrupinski, JCullell, NTorres-Aguila, NPMuino, ECarcel-Marquez, JMoniche, FCabezas, JAFord, ALDhar, RRoquer, JKhatri, PJimenez-Conde, JFernandez-Cadenas, IMontaner, JRosand, JCruchaga, CLee, JMgenome-wide association studyphenotypepopulationstrokeischemicBackground and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.LIPPINCOTT WILLIAMS & WILKINS2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5809STROKEISSN: 00392499ISSNe: 15244628reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p58092026-06-14T12:41:47Z
dc.title.none.fl_str_mv	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
title	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
spellingShingle	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome Heitsch, L genome-wide association study phenotype population stroke ischemic
title_short	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
title_full	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
title_fullStr	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
title_full_unstemmed	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
title_sort	Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
dc.creator.none.fl_str_mv	Heitsch, L Ibanez, L Carrera, C Binkley, MM Strbian, D Tatlisumak, T Bustamante, A Ribo, M Molina, C Davalos, A Lopez-Cancio, E Munoz-Narbona, L Soriano-Tarraga, C Giralt-Steinhauer, E Obach, V Slowik, A Pera, J Lapicka-Bodzioch, K Derbisz, J Sobrino, T Castillo, J Campos, F Rodriguez-Castro, E Arias-Rivas, S Segura, T Serrano-Heras, G Vives-Bauza, C Diaz-Navarro, R Tur, S Jimenez, C Marti-Fabregas, J Delgado-Mederos, R Arenillas, J Krupinski, J Cullell, N Torres-Aguila, NP Muino, E Carcel-Marquez, J Moniche, F Cabezas, JA Ford, AL Dhar, R Roquer, J Khatri, P Jimenez-Conde, J Fernandez-Cadenas, I Montaner, J Rosand, J Cruchaga, C Lee, JM
author	Heitsch, L
author_facet	Heitsch, L Ibanez, L Carrera, C Binkley, MM Strbian, D Tatlisumak, T Bustamante, A Ribo, M Molina, C Davalos, A Lopez-Cancio, E Munoz-Narbona, L Soriano-Tarraga, C Giralt-Steinhauer, E Obach, V Slowik, A Pera, J Lapicka-Bodzioch, K Derbisz, J Sobrino, T Castillo, J Campos, F Rodriguez-Castro, E Arias-Rivas, S Segura, T Serrano-Heras, G Vives-Bauza, C Diaz-Navarro, R Tur, S Jimenez, C Marti-Fabregas, J Delgado-Mederos, R Arenillas, J Krupinski, J Cullell, N Torres-Aguila, NP Muino, E Carcel-Marquez, J Moniche, F Cabezas, JA Ford, AL Dhar, R Roquer, J Khatri, P Jimenez-Conde, J Fernandez-Cadenas, I Montaner, J Rosand, J Cruchaga, C Lee, JM
author_role	author
author2	Ibanez, L Carrera, C Binkley, MM Strbian, D Tatlisumak, T Bustamante, A Ribo, M Molina, C Davalos, A Lopez-Cancio, E Munoz-Narbona, L Soriano-Tarraga, C Giralt-Steinhauer, E Obach, V Slowik, A Pera, J Lapicka-Bodzioch, K Derbisz, J Sobrino, T Castillo, J Campos, F Rodriguez-Castro, E Arias-Rivas, S Segura, T Serrano-Heras, G Vives-Bauza, C Diaz-Navarro, R Tur, S Jimenez, C Marti-Fabregas, J Delgado-Mederos, R Arenillas, J Krupinski, J Cullell, N Torres-Aguila, NP Muino, E Carcel-Marquez, J Moniche, F Cabezas, JA Ford, AL Dhar, R Roquer, J Khatri, P Jimenez-Conde, J Fernandez-Cadenas, I Montaner, J Rosand, J Cruchaga, C Lee, JM
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	genome-wide association study phenotype population stroke ischemic
topic	genome-wide association study phenotype population stroke ischemic
description	Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
publishDate	2021
dc.date.none.fl_str_mv	2021
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5809
url	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=5809
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	LIPPINCOTT WILLIAMS & WILKINS
publisher.none.fl_str_mv	LIPPINCOTT WILLIAMS & WILKINS
dc.source.none.fl_str_mv	STROKE ISSN: 00392499 ISSNe: 15244628 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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repository.mail.fl_str_mv
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Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

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