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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish
Pages (from-to)132-141
Number of pages10
Issue number1
StatePublished - Jan 1 2021


  • genome-wide association study
  • phenotype
  • population
  • stroke, ischemic


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