Original Article
Early and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.07.024Get rights and content

Background

Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months.

Methods

Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1.

Results

Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P = .024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P < .001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P = .001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P = .001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P = .004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P < .001) were independent predictors of favorable outcomes at 3 months.

Conclusions

Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

Introduction

Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for achieving arterial recanalization in acute ischemic stroke (AIS). Although wide variations in the rates and timing of neurologic recovery are observed, IV tPA leads to good clinical outcomes at 3 months in about half of those treated within 4.5 hours.1, 2

Neurologic recovery of variable grades is noted in a significant proportion of patients during the first 24 hours of initiation of treatment with IV tPA. Early neurologic improvement (ENI) after intravenous thrombolysis is considered a favorable prognostic sign3, 4, 5, 6, 7 because of recanalization of the occluded artery.8, 9, 10, 11, 12, 13 It may also be regarded as a surrogate indicator of effective thrombolytic therapy.3, 10, 11, 12, 13, 14 However, the definition of ENI remains poorly defined. The pivotal National Institute of Neurological Disorders and Stroke trial1 described ENI as complete resolution of the neurologic deficits or an improvement from baseline in the National Institutes of Health Stroke Scale (NIHSS) score by 4 or more points. Because a considerable proportion of patients in the placebo group also achieved a reduction in NIHSS score by 4 or more points at 24 hours, the difference between IV tPA and placebo group was not statistically significant. However, a post hoc analysis demonstrated that a neurologic improvement of 5 or more points on the NIHSS at 24 hours significantly predicted favorable outcomes at 3 months.15 Many studies have attempted to define the relationship between the change in NIHSS scores at different time points during the first 24 hours and functional outcomes at 3 months. A single-center study demonstrated that an 8-point improvement in NIHSS score or a total NIHSS score of 0 or 1 at 24 hours independently predicted favorable outcomes at 3 months, whereas another study showed that a 10-point improvement is sustainable at 3 months.7, 16

Some AIS patients achieve considerable clinical recovery at 2 hours after IV tPA bolus. However, literature regarding ENI at 2 hours is scarce. Furthermore, there are hardly any data on the course of neurologic recovery in the subacute period between 2 and 24 hours of IV tPA treatment initiation. During this period, some patients with ENI continue to have further neurologic improvement (CNI), and some additional patients start to improve later because of delayed recanalization or delayed recovery, whereas some deteriorate because of arterial re-occlusion or other systemic causes. In this study, we aimed to evaluate the relationship between ENI, CNI, and favorable functional outcomes at 3 months in our IV tPA–treated cohort of AIS patients.

Section snippets

Methods

A retrospective cohort design was used to analyze the prospectively collected stroke thrombolysis registry data from our center. Consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset between January 2007 and December 2011 were included. Our tertiary care center provides round-the-clock acute stroke thrombolysis service. The study was approved by the Ethics Committee of our institution.

In addition to the demographic characteristics and information about the pre-existing

Results

A total of 2460 patients with AIS were admitted to our center during the study period. Of these, 263 (10.7%) were treated with IV tPA in a standard dose (.9 mg/kg body weight; maximum 90 mg) within 4.5 hours of symptom onset. Patients underwent a CT angiography of the brain on arrival to the hospital and 24 hours after treatment unless contraindicated.

Baseline characteristics of the study population are presented in Table 1. Briefly, our cohort had a male preponderance (63.9%) and the median

Discussion

Our study demonstrates that ENI during the first 24 hours after intravenous thrombolysis is associated with better functional outcomes at 3 months in AIS patients.

Estimation of the neurologic status at 3 months after IV tPA therapy has been the major end point in most AIS thrombolysis studies. However, this surrogate marker is useful neither during the first few hours for decision-making regarding various rescue therapies nor during the first few days and weeks regarding the optimal

Conclusions

ENI at 2 hours and CNI from 2 to 24 hours after IV tPA bolus are strong predictors of favorable functional outcomes at 3 months in AIS patients. At centers with limited resources for serial imaging and angiographic studies, serial estimation of NIHSS scores may serve as an important tool in the armamentarium of stroke neurologists.

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    Disclosures: None of the authors declare any conflicts of interest.

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