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

Laura Heitsch; Laura Ibanez; Caty Carrera; Michael M. Binkley; Daniel Strbian; Turgut Tatlisumak; Alejandro Bustamante; Marc Ribó; Carlos Molina; Antoni Dávalos; Elena López-Cancio; Lucia Muñoz-Narbona; Carol Soriano-Tárraga; Eva Giralt-Steinhauer; Victor Obach; Agnieszka Slowik; Joanna Pera; Katarzyna Lapicka-Bodzioch; Justyna Derbisz; Tomás Sobrino; José Castillo; Francisco Campos; Emilio Rodríguez-Castro; Susana Arias-Rivas; Tomas Segura; Gemma Serrano-Heras; Cristófol Vives-Bauza; Rosa Díaz-Navarro; Silva Tur; Carmen Jimenez; Joan Martí-Fàbregas; Raquel Delgado-Mederos; Juan Arenillas; Jerzy Krupinski; Natalia Cullell; Nuria P. Torres-Aguila; Elena Muiño; Jara Cárcel-Márquez; Francisco Moniche; Juan A. Cabezas; Andria L. Ford; Rajat Dhar; Jaume Roquer; Pooja Khatri; Jordi Jiménez-Conde; Israel Fernandez-Cadenas; Joan Montaner; Jonathan Rosand; Carlos Cruchaga; Jin Moo Lee

doi:10.1161/STROKEAHA.119.028687

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

Laura Heitsch, Laura Ibanez, Caty Carrera, Michael M. Binkley, Daniel Strbian, Turgut Tatlisumak, Alejandro Bustamante, Marc Ribó, Carlos Molina, Antoni Dávalos, Elena López-Cancio, Lucia Muñoz-Narbona, Carol Soriano-Tárraga, Eva Giralt-Steinhauer, Victor Obach, Agnieszka Slowik, Joanna Pera, Katarzyna Lapicka-Bodzioch, Justyna Derbisz, Tomás SobrinoJosé Castillo, Francisco Campos, Emilio Rodríguez-Castro, Susana Arias-Rivas, Tomas Segura, Gemma Serrano-Heras, Cristófol Vives-Bauza, Rosa Díaz-Navarro, Silva Tur, Carmen Jimenez, Joan Martí-Fàbregas, Raquel Delgado-Mederos, Juan Arenillas, Jerzy Krupinski, Natalia Cullell, Nuria P. Torres-Aguila, Elena Muiño, Jara Cárcel-Márquez, Francisco Moniche, Juan A. Cabezas, Andria L. Ford, Rajat Dhar, Jaume Roquer, Pooja Khatri, Jordi Jiménez-Conde, Israel Fernandez-Cadenas, Joan Montaner, Jonathan Rosand, Carlos Cruchaga, Jin Moo Lee

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Abstract

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 (NIHSS_baseline- NIHSS_24hours= ΔNIHSS_6-24h), 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 ΔNIHSS₆_-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS_6-24hwas examined. Finally, the association of ΔNIHSS₆_-24hwith 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 ΔNIHSS₆_-24hwas 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS₆_-24h(R²=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R²=0.27), but much of the variance remained unexplained. ΔNIHSS₆_-24hhad a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS₃_-24hwas similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS_6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS₆_-24hpromises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

Original language	English
Pages (from-to)	132-141
Number of pages	10
Journal	Stroke
Volume	52
Issue number	1
DOIs	https://doi.org/10.1161/STROKEAHA.119.028687
State	Published - Jan 1 2021

Keywords

genome-wide association study
phenotype
population
stroke, ischemic

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10.1161/STROKEAHA.119.028687

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Heitsch, L., Ibanez, L., Carrera, C., Binkley, M. M., Strbian, D., Tatlisumak, T., Bustamante, A., Ribó, M., Molina, C., Dávalos, A., López-Cancio, E., Muñoz-Narbona, L., Soriano-Tárraga, C., Giralt-Steinhauer, E., Obach, V., Slowik, A., Pera, J., Lapicka-Bodzioch, K., Derbisz, J., ... Lee, J. M. (2021). Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome. Stroke, 52(1), 132-141. https://doi.org/10.1161/STROKEAHA.119.028687

@article{b0bc3f2a27b14e3897e5635fac1789ba,

title = "Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome",

abstract = "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= ΔNIHSS6-24h), 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 ΔNIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS6-24hwas examined. Finally, the association of ΔNIHSS6-24hwith 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 ΔNIHSS6-24hwas 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h(R2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R2=0.27), but much of the variance remained unexplained. ΔNIHSS6-24hhad a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS3-24hwas similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS6-24hpromises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.",

keywords = "genome-wide association study, phenotype, population, stroke, ischemic",

author = "Laura Heitsch and Laura Ibanez and Caty Carrera and Binkley, {Michael M.} and Daniel Strbian and Turgut Tatlisumak and Alejandro Bustamante and Marc Rib{\'o} and Carlos Molina and Antoni D{\'a}valos and Elena L{\'o}pez-Cancio and Lucia Mu{\~n}oz-Narbona and Carol Soriano-T{\'a}rraga and Eva Giralt-Steinhauer and Victor Obach and Agnieszka Slowik and Joanna Pera and Katarzyna Lapicka-Bodzioch and Justyna Derbisz and Tom{\'a}s Sobrino and Jos{\'e} Castillo and Francisco Campos and Emilio Rodr{\'i}guez-Castro and Susana Arias-Rivas and Tomas Segura and Gemma Serrano-Heras and Crist{\'o}fol Vives-Bauza and Rosa D{\'i}az-Navarro and Silva Tur and Carmen Jimenez and Joan Mart{\'i}-F{\`a}bregas and Raquel Delgado-Mederos and Juan Arenillas and Jerzy Krupinski and Natalia Cullell and Torres-Aguila, {Nuria P.} and Elena Mui{\~n}o and Jara C{\'a}rcel-M{\'a}rquez and Francisco Moniche and Cabezas, {Juan A.} and Ford, {Andria L.} and Rajat Dhar and Jaume Roquer and Pooja Khatri and Jordi Jim{\'e}nez-Conde and Israel Fernandez-Cadenas and Joan Montaner and Jonathan Rosand and Carlos Cruchaga and Lee, {Jin Moo}",

year = "2021",

month = jan,

day = "1",

doi = "10.1161/STROKEAHA.119.028687",

language = "English",

volume = "52",

pages = "132--141",

journal = "Stroke",

issn = "0039-2499",

number = "1",

}

Heitsch, L , Ibanez, L, Carrera, C, Binkley, MM, Strbian, D, Tatlisumak, T, Bustamante, A, Ribó, M, Molina, C, Dávalos, A, López-Cancio, E, Muñoz-Narbona, L, Soriano-Tárraga, C, Giralt-Steinhauer, E, Obach, V, Slowik, A, Pera, J, Lapicka-Bodzioch, K, Derbisz, J, Sobrino, T, Castillo, J, Campos, F, Rodríguez-Castro, E, Arias-Rivas, S, Segura, T, Serrano-Heras, G, Vives-Bauza, C, Díaz-Navarro, R, Tur, S, Jimenez, C, Martí-Fàbregas, J, Delgado-Mederos, R, Arenillas, J, Krupinski, J, Cullell, N, Torres-Aguila, NP, Muiño, E, Cárcel-Márquez, J, Moniche, F, Cabezas, JA, Ford, AL , Dhar, R, Roquer, J, Khatri, P, Jiménez-Conde, J, Fernandez-Cadenas, I, Montaner, J, Rosand, J, Cruchaga, C & Lee, JM 2021, 'Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome', Stroke, vol. 52, no. 1, pp. 132-141. https://doi.org/10.1161/STROKEAHA.119.028687

TY - JOUR

T1 - Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

AU - Heitsch, Laura

AU - Ibanez, Laura

AU - Carrera, Caty

AU - Binkley, Michael M.

AU - Strbian, Daniel

AU - Tatlisumak, Turgut

AU - Bustamante, Alejandro

AU - Ribó, Marc

AU - Molina, Carlos

AU - Dávalos, Antoni

AU - López-Cancio, Elena

AU - Muñoz-Narbona, Lucia

AU - Soriano-Tárraga, Carol

AU - Giralt-Steinhauer, Eva

AU - Obach, Victor

AU - Slowik, Agnieszka

AU - Pera, Joanna

AU - Lapicka-Bodzioch, Katarzyna

AU - Derbisz, Justyna

AU - Sobrino, Tomás

AU - Castillo, José

AU - Campos, Francisco

AU - Rodríguez-Castro, Emilio

AU - Arias-Rivas, Susana

AU - Segura, Tomas

AU - Serrano-Heras, Gemma

AU - Vives-Bauza, Cristófol

AU - Díaz-Navarro, Rosa

AU - Tur, Silva

AU - Jimenez, Carmen

AU - Martí-Fàbregas, Joan

AU - Delgado-Mederos, Raquel

AU - Arenillas, Juan

AU - Krupinski, Jerzy

AU - Cullell, Natalia

AU - Torres-Aguila, Nuria P.

AU - Muiño, Elena

AU - Cárcel-Márquez, Jara

AU - Moniche, Francisco

AU - Cabezas, Juan A.

AU - Ford, Andria L.

AU - Dhar, Rajat

AU - Roquer, Jaume

AU - Khatri, Pooja

AU - Jiménez-Conde, Jordi

AU - Fernandez-Cadenas, Israel

AU - Montaner, Joan

AU - Rosand, Jonathan

AU - Cruchaga, Carlos

AU - Lee, Jin Moo

PY - 2021/1/1

Y1 - 2021/1/1

N2 - 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= ΔNIHSS6-24h), 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 ΔNIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS6-24hwas examined. Finally, the association of ΔNIHSS6-24hwith 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 ΔNIHSS6-24hwas 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h(R2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R2=0.27), but much of the variance remained unexplained. ΔNIHSS6-24hhad a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS3-24hwas similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS6-24hpromises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

AB - 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= ΔNIHSS6-24h), 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 ΔNIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS6-24hwas examined. Finally, the association of ΔNIHSS6-24hwith 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 ΔNIHSS6-24hwas 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h(R2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R2=0.27), but much of the variance remained unexplained. ΔNIHSS6-24hhad a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS3-24hwas similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS6-24hpromises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

KW - genome-wide association study

KW - phenotype

KW - population

KW - stroke, ischemic

UR - http://www.scopus.com/inward/record.url?scp=85099034710&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.119.028687

DO - 10.1161/STROKEAHA.119.028687

M3 - Article

C2 - 33317415

AN - SCOPUS:85099034710

SN - 0039-2499

VL - 52

SP - 132

EP - 141

JO - Stroke

JF - Stroke

IS - 1

ER -

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

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