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Cited by 71Acute Ischemic Stroke ManagementIntracerebral and Subarachnoid Hemorrhage ResearchCerebrovascular and Carotid Artery Diseases

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

Open access
Heitsch, Laura, Ibanez, Laura, Carrera, Caty, Binkley, Michael M., Strbian, Daniel, Tatlisumak, Turgut, Bustamante, Alejandro, Ribó, Marc +43 more·2021·Stroke
DOI 10.1161/strokeaha.119.028687PMC PMC7769959
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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 ΔNIHSS 6 –24h . In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS 6–24h was examined. Finally, the association of ΔNIHSS 6 –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 ΔNIHSS 6 –24h was 2 (interquartile range, 0–5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS 6 –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. ΔNIHSS 6 –24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS 3 –24h was 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, ΔNIHSS 6 –24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

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Crossref · 10.1161/strokeaha.119.028687

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 20 cited sources checked · 7 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Clinically meaningful fluctuations, often defined as changes of at least 4 points, occur within the first 24 hours in more than half of acute ischemic stroke patients.

    “Clinically meaningful fluctuations, frequently defined as changes of ≥ 4 points, within the first 24 hours occur in more than half of acute ischemic stroke (AIS) patients.3–5”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [3] source
    • cites [4] source

      The Introduction discusses NIHSS changes in the first 24 hours, but defines major neurological improvement as a score of 0–1 or an improvement of at least 8 points—not a 4-point fluctuation. In Results > Baseline Characteristics (page unavailable), the overall cohort’s 24-hour NIHSS change has a median of 1 point and an interquartile range of 0–3. Those figures run contrary to the claim that changes of at least 4 points occur in more than half of patients. (LLM, conf=0.85)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [5] source

      The Methods define meaningful deterioration or recovery as an NIHSS change of at least 4 points. The Results report 31 patients with recovery and 8 with deterioration among 75 studied—just over half—but the Methods specify follow-up at days 3–5, not within the first 24 hours. The paper therefore does not support the claim's timing. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    NIHSS measured 24 hours after stroke onset is a strong predictor of functional outcome at 90 days.

    “NIH stroke scale (NIHSS) measured 24 hours after stroke onset is a strong predictor of functional outcome at 90 days.”
    • Also stated in: § INTRODUCTION · boosted
      “NIH stroke scale (NIHSS) measured 24 hours after stroke onset is a strong predictor of functional outcome at 90 days.1, 2”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] source
    • cites [2] source
  • Findingown data

    In the GENISIS cohort, baseline NIHSS had the largest contribution of any variable to the multivariable model of ΔNIHSS6-24h.

    “Of these, baseline NIHSS had the highest contribution of any variable to the model, likely due to greater variability of ΔNIHSS6–24h at higher baseline NIHSS.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the GENISIS cohort, age, site, diabetes, and African descent contributed to the final multivariable model of 90-day favorable outcome.

    “Age, site, diabetes, and race (African descent) contributed to the final model.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the tPA-treated large vessel occlusion subcohort, subjects with early sustained recanalization had a higher likelihood of better outcome across groups, with an odds ratio of 6.8 (95% CI 4.0-11.5).

    “Overall, subjects with ESR had a high likelihood of a better outcome (OR 6.8; 4.0, 11.5) across the groups.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 28
  • The quote only partly states this claim. 4

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    A recent publication indicated that percentile change of NIHSS has better predictive capabilities for 3-month outcomes than arithmetic change.

    “While a recent publication has indicated that percentile change of NIHSS has better predictive capabilities for 3 month outcomes than arithmetic change,36”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A recent multicenter study showed that early tPA-induced recanalization in large vessel occlusion patients significantly improved both early and long-term outcomes.

    “A recent multicenter study showed that early tPA induced recanalization in LVO patients significantly improved both early and long term outcomes.33”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The effect of endovascular treatment on 90-day mRS is in large part mediated by early changes in NIHSS.

    “Similar to this finding, it was recently reported that the effect of endovascular treatment on 90 day mRS is in large part mediated by early changes in NIHSS.34”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies have consistently associated early neurologic improvement with successful reperfusion.

    “Previous studies have also demonstrated that early neurologic improvement has consistently been associated with successful reperfusion.5, 31, 32”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [5] source
    • cites [31] source
    • cites [32] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Hemorrhagic transformation and lack of recanalization have been described as significant factors in neurologic worsening.

    “Both HT and lack of recanalization have been described as significant factors in neurologic worsening.5, 7”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [5] source
    • cites [7] source

  • May combine two claims.

    Findingown data

    In the GENISIS cohort, ΔNIHSS6-24h approximated a normal distribution, ranged from −34 to +33, and had a mean of +2.78 with a standard deviation of 5.93.

    “ΔNIHSS6–24h approximated a normal distribution (Figure 1C) which ranged from −34 (extreme deterioration) to +33 (extreme improvement) with a mean of +2.78 (SD 5.93).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the GENISIS cohort, TOAST was significantly associated with baseline NIHSS, with more severe strokes in the large artery atherosclerosis and cardioembolic categories and milder strokes in the small vessel disease category.

    “TOAST was significantly associated with baseline NIHSS. More severe strokes fell into the LAA and CE categories; milder strokes in the SVD category, consistent with the findings of others”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the GENISIS cohort, TOAST designation accounted for 7.5% of the variance in baseline NIHSS but less than 0.5% of the variance in ΔNIHSS6-24h.

    “TOAST designation had a strong influence on baseline NIHSS, accounting for 7.5% of the variance — the highest of all baseline variables – but had little influence on ΔNIHSS6–24h, accounting for less than 0.5%.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S4 (based). May combine two claims.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, early sustained recanalization and parenchymal hematoma type 2 were the only variables that remained significant in ordinal logistic regression models of early outcomes without violating the proportional odds assumption.

    “Using ordinal logistic regression multivariable models to evaluate the influence of these variables on early outcomes, the only variables that remained significant and did not violate the proportional odds were ESR and PH2”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In the GENISIS cohort of 2,555 acute ischemic stroke patients, the median baseline NIHSS score was 9, with an interquartile range of 4 to 16.

    “For 2555 AIS patients, median baseline NIHSS was 9 (IQR 4–16)”
    • Also stated in: § Baseline and 24 hour Stroke Severity · plain
      “Median baseline NIHSS was 9 (IQR 4–16).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the GENISIS cohort, baseline NIHSS had a positively skewed distribution, with more patients having milder strokes.

    “Baseline NIHSS demonstrated a positive-skewed distribution with more patients having milder strokes, typical of a cross-sectional population of AIS (Figure 1A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In a multivariable model of GENISIS acute ischemic stroke patients, baseline NIHSS, tPA treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS6-24h, and the model explained about 15% of the variance.

    “In a multivariable model, baseline NIHSS, tPA treatment, age, glucose, site and systolic blood pressure independently predicted ΔNIHSS6–24h (R2=0.15).”
    • Also stated in: § Change in Stroke Severity from Baseline to 24 hours (ΔNIHSS6–24h) · plain
      “Overall, this model accounted for only 14.9% of the variance seen in ΔNIHSS6–24h.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the GENISIS cohort, NIHSS at 24 hours was skewed toward lower scores, with half the subjects scoring 4 or less.

    “NIHSS at 24 hours (Figure 1B) demonstrated a skew towards lower NIHSS with half the subjects scoring ≤ 4.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, early sustained recanalization accounted for most of the explained variance in ΔNIHSS6-24h (partial eta-squared 0.2136; parameter estimate 5.952, 95% CI 4.526-7.377), and parenchymal hematoma type 2 added a smaller portion (partial eta-squared 0.061; parameter estimate −6.907, 95% CI −10.302 to −3.512).

    “ESR accounted for the majority of explained variance (partial eta-square of 0.2136; parameter estimate 5.952 (4.526, 7.377)) with PH2 providing an additional portion (partial eta-square of 0.061; parameter estimate −6.907 (−10.302, −3.512)).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, a multivariable model including recanalization and hemorrhagic transformation explained only 27% of the variance in ΔNIHSS6-24h.

    “Despite inclusion of recanalization and HT, the model explained only 27% of ΔNIHSS6–24h variance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The distribution of ΔNIHSS was compressed in the overall GENISIS population compared with the two NINDS tPA trials, but tPA-treated subjects in both studies had similar distributions with a median change of 3.

    “Although there was a compression of ΔNIHSS distribution in the overall GENISIS population compared to the two NINDS tPA stroke trials (please see https://www.ahajournals.org/journal/str, Supplement Figures IVE–F), a comparison of the tPA-treated subjects in both GENISIS and NINDS revealed very similar distributions with a median change of 3.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, early sustained recanalization and severe hemorrhagic transformation (parenchymal hematoma type 2) were associated with extreme neurologic improvement and deterioration, respectively.

    “In a subcohort of tPA-treated LVO patients, ESR and severe hemorrhagic transformation (PH2) were associated with extreme degrees of neurologic improvement or deterioration, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, neither parenchymal hematoma type 2 nor early sustained recanalization had a significant influence on favorable 90-day outcome in multivariable modeling.

    “In multivariable modeling of 90 day outcomes within the LVO cohort, neither PH2 nor ESR had a significant influence on favorable outcome despite meeting the univariate threshold”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In the tPA-treated large vessel occlusion subcohort, for favorable 90-day outcome (n=241), only baseline NIHSS and ΔNIHSS6-24h remained in the model, explaining 41.3% of the variance (baseline NIHSS PR2 0.136, OR 0.74, 95% CI 0.68-0.81; ΔNIHSS6-24h PR2 0.150, OR 1.3, 95% CI 1.2-1.4).

    “For favorable outcome (n=241), only baseline NIHSS and ΔNIHSS6–24h remained in the model, explaining 41.3% of the variance (with respective PR2 and ORs of 0.136 and 0.74 (0.68, 0.81) and 0.150 and 1.3 (1.2, 1.4)).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Hemorrhagic transformation and early sustained recanalization occur in a minority of patients, which supports the suggestion that other mechanisms determine ΔNIHSS6-24h.

    “Moreover, HT and early sustained recanalization develop in a minority of patients, supporting the suggestion that other mechanisms are involved in the determination of ΔNIHSS6–24h.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The success of candidate drugs is greatly enhanced when the drug target is independently confirmed by human genetic data.

    “There is accumulating evidence that the success of candidate drugs is greatly enhanced if the drug target is independently confirmed by human genetic data.16, 17”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] source
    • cites [17] source

  • May combine two claims.

    Study design and conductown data

    In the GENISIS study, a stepwise ordinal logistic regression for all mRS categories was attempted, but all significant models failed the proportional odds assumption, so a valid model could not be constructed.

    “A stepwise ordinal logistic regression analysis was performed for all categories of the mRS scale, but all significant models failed to maintain the proportional odds assumption. Therefore, a valid model was unable to be constructed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ΔNIHSS is both an important early metric associated with long-term outcome and a phenotype for discovering additional mechanisms that influence neurological changes during the early window.

    “Thus, ΔNIHSS is not only an important early metric that is associated with long-term outcome but also a phenotype for discovering additional mechanisms to influence the neurological changes that occur during that window.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the GENISIS analyses, the false discovery rate was controlled using the Benjamini-Hochberg procedure.

    “The false discovery rate was controlled using the Benjamini-Hochberg procedure to evaluate the resultant p-values in the final models (and all subsequent modeling).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Because of site differences in baseline NIHSS, a nested model was performed and did not differ significantly in covariates or explained variance in ΔNIHSS6-24h.

    “Due to site differences for baseline NIHSS, a nested model was performed and did not differ significantly in terms of the covariates and explained variance in ΔNIHSS6–24h”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the GENISIS analyses, collinearity and heteroscedasticity were checked for all variables in the models using variance inflation factor and residual plots.

    “Collinearity and heteroscedasticity were checked for all variables included in the models (and in all subsequent modeling) using the variance inflation factor and residual plots respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    In the GENISIS study, hemorrhagic transformation was classified according to European Cooperative Acute Stroke Study criteria with centralized adjudication.

    “When follow-up imaging was available, HT was classified according to European Cooperative Acute Stroke Study criteria, with centralized adjudication.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In the GENISIS study, covariates were collected and aligned according to a study-specific data dictionary, using NIH NINDS common data elements when available.

    “All co-variates were collected and aligned according to a data dictionary generated for the study, utilizing NIH NINDS common data elements when available”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The GENISIS cohort is consistent with the real-world population amenable to acute interventions and is therefore relevant to the study.

    “Thus, the GENISIS cohort is consistent with the real-world population that is amenable to acute interventions and therefore relevant to our study.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Stroke etiology has a major influence on initial stroke severity but limited influence on the processes that account for early neurological deterioration or improvement.

    “These findings are consistent with previous studies,7, 29 and indicate that stroke etiology has a major influence on initial stroke severity, but limited influence on the processes that account for early neurological deterioration or improvement.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] source
    • cites [29] source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    In the GENISIS study, NIHSS was prospectively recorded within 6 hours after onset and again 24 hours later.

    “Patients with NIHSS prospectively recorded within 6h after onset and then 24h later were enrolled in the GENISIS (Genetics of Early Neurological InStability after Ischemic Stroke) study.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because of the retrospective approach, the GENISIS study did not conduct an a priori power analysis on univariate predictors.

    “Due to the retrospective approach, no a priori power analysis was conducted on univariate predictors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Institutional Review Boards at all participating sites approved patient enrollment and data sharing for the GENISIS study.

    “The Institutional Review Boards at all participating sites approved patient enrollment and data sharing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationown data

    A variety of mechanisms likely contribute to ΔNIHSS6-24h.

    “A variety of mechanisms are likely to contribute to ΔNIHSS6–24h.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    ΔNIHSS6-24h will be a valuable quantitative phenotype in large genetic studies of acute ischemic stroke patients for identifying novel mechanisms involved in neurological change after stroke that are relevant to human disease.

    “Therefore, ΔNIHSS6–24h will be a valuable quantitative phenotype in large genetic studies of AIS patients, to identify novel mechanisms involved in neurological change after stroke that are relevant to human disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Failure to translate experimental models into human trials has slowed the drug development pipeline.

    “Indeed, failure of translation from experimental models to human trials has slowed the drug development pipeline.14, 15”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] source
    • cites [15] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study had strengths including a large sample size, real-world standard-of-care patients, careful documentation of NIHSS at standardized time intervals, and replication in an independent randomized controlled trial cohort.

    “This study has several strengths, including the large sample size, involving patients in real-world standard-of-care practice, careful documentation of NIHSS at standardized time intervals after stroke onset, and replication in an independent cohort of patients enrolled in a randomized controlled trial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In the large vessel occlusion cohort, recanalization and hemorrhagic transformation explain a minority of the variance in ΔNIHSS6-24h, leaving most variance unexplained and suggesting that other factors captured by ΔNIHSS6-24h are involved.

    “While this holds true in our analysis of the LVO cohort, recanalization and HT explain a minority of variance in ΔNIHSS6–24h, leaving the majority of variance unexplained and suggesting that there are other contributing factors that are being captured by ΔNIHSS6–24h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Dynamic changes in early neurological function are likely time-dependent, with a higher likelihood of change earlier in the ischemic course.

    “It is likely that dynamic changes in early neurological function are time-dependent, with a higher likelihood of change earlier in the ischemic course”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ΔNIHSS6-24h is likely to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of acute ischemic stroke.

    “Thus, ΔNIHSS6–24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study could not estimate recruitment bias or assess intra-site and inter-site reliability for NIHSS and mRS assessment.

    “As such we are unable to provide an estimation of bias in recruitment (i.e. potential selection and/or bidirectional ascertainment bias) or an assessment of intra-site and inter-site reliability for assessment of NIHSS and mRS”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The dynamic phenotype ΔNIHSS6-24h captures both explained and unexplained mechanisms involved in acute ischemic stroke and is significantly and independently associated with long-term outcomes.

    “The dynamic phenotype, ΔNIHSS6–24h, captures both explained and unexplained mechanisms involved in AIS, and is significantly and independently associated with long-term outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ΔNIHSS6-24h captures mechanisms related to early neurological change after acute ischemic stroke and thereby has a significant association with long-term outcomes.

    “Thus, ΔNIHSS6–24h captures mechanisms related to early neurological change after AIS, thereby creating a significant association with long-term outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The current study excludes patients treated with thrombectomy.

    “A final limitation is that the current study excludes patients treated with thrombectomy.”
    Quote in the paperNot a substantial claim
44 of 44

  • The paper relies on this without support.

    A meaningful quantitative phenotype for acute ischemic stroke can be obtained in large patient populations.

    “However, meaningful quantitative phenotypes attainable in large patient populations are needed.”

  • The paper relies on this without support.

    The first 24 hours after acute ischemic stroke onset is a period in which neurological deterioration can be prevented or improvement can be enhanced.

    “This critical period is a window for preventing neurological deterioration, or enhancing improvement.”
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Authors
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., 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, N. P., Muiño, E., Cárcel-Márquez, J., Moniche, F., Cabezas, J. A., Ford, A. L., Dhar, R., Roquer, J., Khatri, P., Jiménez-Conde, J., Fernandez-Cadenas, I., Montaner, J., Rosand, J., Cruchaga, C., Lee, J.-M., & on behalf of the International Stroke Genetics Consortium
Affiliations
  • Washington University in St. Louis (US)
  • Department of Psychiatry (L.I., C. Cruchaga), Washington University School of Medicine, St Louis, MO.
  • Universitat Autònoma de Barcelona (ES)
  • Helsinki University Hospital (FI)
  • Hospital Universitari Germans Trias i Pujol (ES)
  • Department of Neurology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain (E.L.-C.).
  • Institut Hospital del Mar d’Investigacions Mediques (IMIM), Barcelona, Spain (L.M.-N., C.S.-T., E.G.-S., J.R., J.J.-C.).
  • Department of Neuroscience, Hospital Clinic, University of Barcelona and August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain (V.O.).
  • Department of Neurology (A.S., J.P., J.D.), Jagiellonian University Medical College, Krakow, Poland.
  • Jagiellonian University (PL)
  • Universidade de Santiago de Compostela (ES)
  • Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, Hospital Clinico Universitario, Universidade de Santiago de Compostela, Spain (T.S., J.C., F.C., E.R.-C., S.A.-R.).
  • Department of Neurology, Hospital Universitario de Albacete, Spain (T.S., G.S.-H.).
  • Department of Neurology, Son Espases University Hospital, IdISBa, Palma de Mallorca, Spain (C.V.-B., R.D.-N., S.T., C.J.).
  • Health Research Institute of the Balearic Islands (ES)
  • Department of Neurology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain (J.M.-F., R.D.-M.).
  • Hospital Clínico Universitario de Valladolid (ES)
  • Department of Neurology, Hospital Mutua de Terrassa, Spain (J.K., I.F.-C.).
  • Stroke Pharmacogenomics and Genetics, Fundacio Docencia I Recerca Mutua de Terrassa, Spain (N.C., E.M., J.C.-M., I.F.-C.).
  • Stroke Pharmacogenomics and Genetics, Sant Pau Institute of Research, Sant Pau Hospital, Barcelona, Spain (N.C., N.P.T.-A., E.M., J.C.-M.).
  • Hospital de Sant Pau (ES)
  • Hospital Universitario Virgen del Rocío (ES)
  • Harvard University (US)
  • University of Cincinnati (US)
  • Hospital Del Mar (ES)
  • Neurovascular Research Laboratory and Neurovascular Unit, Vall d’Hebron Institute of Research (VHIR) (C. Carrera, A.B., I.F.-C., J.M.), Universitat Autonoma de Barcelona, Spain.
Corresponding author
Cruchaga, Carlos
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-01
Volume
52
Issue
1
Pages
132-141
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/strokeaha.119.028687
PMC
PMC7769959
OpenAlex
W3112147170
Cited by
70
References
41
Citations by year
2026: 11 · 2025: 16 · 2024: 8 · 2023: 8 · 2022: 22 · 2021: 4 · 2020: 1
FWCI
6.27
Type
journal article
Language
en
Open access
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
  • Jagiellonian University Repository (Jagiellonian University) (submittedVersion, other-oa)
Funders
  • National Institute on Aging (P50AG005681, P30AG066444)
  • National Heart, Lung, and Blood Institute (R01HL129241)
  • National Institute of Neurological Disorders and Stroke (R01NS085419, K23NS099487, K23NS099440, U24NS107230)
Topics
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
Keywords
acute ischemic stroke, functional outcome, large vessel occlusion, alteplase, tissue plasminogen activator, recanalization, hemorrhagic transformation, stroke prognosis, modified Rankin Scale, glucose, systolic blood pressure, age, stroke phenotypes
MeSH terms
Ischemic Stroke, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Severity of Illness Index, Recovery of Function

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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