Original ArticleEarly and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke
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.
References (38)
- et al.
Percent change on the National Institutes of Health Stroke Scale: a useful acute stroke outcome measure
J Stroke Cerebrovasc Dis
(2009) - et al.
Prediction of long-term outcome by percent improvement after the first day of thrombolytic treatment in stroke patients
J Neurol Sci
(2009) - et al.
Myths regarding the NINDS rt-PA Stroke Trial: setting the record straight
Ann Emerg Med
(1997) Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group
N Engl J Med
(1995)- et al.
Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials
Lancet
(2004) - et al.
Early dramatic recovery during intravenous tissue plasminogen activator infusion: clinical pattern and outcome in acute middle cerebral artery stroke
Stroke
(2002) - et al.
Is the benefit of early recanalization sustained at 3 months? A prospective cohort study
Stroke
(2003) - et al.
Predictors of major neurologic improvement after thrombolysis in acute stroke
Neurology
(2005) - et al.
High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial Doppler monitoring
Stroke
(2000) - et al.
Predictors for recanalization after intravenous thrombolysis in acute ischemic stroke
J Stroke Cerebrovasc Dis
(2007)
Accuracy of serial National Institutes of Health Stroke Scale scores to identify artery status in acute ischemic stroke
Circulation
Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement
Circulation
Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke
Stroke
Factors affecting the angiographic recanalization and early clinical improvement in middle cerebral artery territory infarction after thrombolysis
Arch Neurol
Differential pattern of tissue plasminogen activator-induced proximal middle cerebral artery recanalization among stroke subtypes
Stroke
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment
Stroke
Predicting major neurological improvement with intravenous recombinant tissue plasminogen activator treatment of stroke
Stroke
Endovascular therapy for acute ischemic stroke
Stroke
Timing of recanalization after intravenous thrombolysis and functional outcomes after acute ischemic stroke
Arch Neurol
Cited by (59)
A 2-point difference of NIHSS as a predictor of acute ischemic stroke outcome at 3 months after thrombolytic therapy
2020, Clinical Neurology and NeurosurgeryRedefining Early Neurological Improvement After Reperfusion Therapy in Stroke
2020, Journal of Stroke and Cerebrovascular DiseasesCirculating Aquaporin-4 as A biomarker of early neurological improvement in stroke patients: A pilot study
2020, Neuroscience LettersCitation Excerpt :Taking all this into account, the early measurement of circulating AQP4 in ischemic stroke patients may facilitate the decision-making process of clinicians, such as in admitting patients to specialized stroke units or recovery programs, evaluating complementary treatments, or recruiting patients into clinical trials. Moreover, early neurological improvement in ischemic stroke patients treated with thrombolytic therapies has been also suggested to be a straightforward surrogate indicator of good outcome [29,30]. Therefore, the usage of AQP4 as a biomarker for early stroke prognosis might help in optimal patients’ management in order to improve their functional outcome and quality of life after ischemic stroke.
Novel Definition of Stroke “Good Responders” Predicts 90-Day Outcome after Thrombolysis
2019, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :Prior literature has reported on variables that may be correlated with rapid neurologic recovery as well. Some relevant ones include clinical indices such as the NIHSS at 24 hours combined with 7 days7 and prestroke mRS,12-14 radiographic indices such as the size of the core stroke lesion on perfusion CT,20 subsequent MRI,21 or even biomarkers to predict outcome.22 Other predictors of rapid neurologic recovery generally include age, admission glucose, time to treatment, and atrial fibrillation.8
Disclosures: None of the authors declare any conflicts of interest.