Tissue Plasminogen Activator For Stroke Research Articles

Abstract WP6: Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of the BEST-MSU Trial

Introduction: While the goal of IV tissue plasminogen activator (TPA) is to prevent infarction, few data exist on averted stroke. Methods: Secondary analysis of a multicenter trial from 2014-2020 comparing outcomes between patients treated for stroke by mobile stroke unit (MSU) vs standard care (SC). The analytical cohort were patients with suspected stroke treated with IV TPA. The primary outcome was a time-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours. The secondary outcome was a tissue-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours and no acute infarction/hemorrhage on imaging. We used multivariable logistic regression to evaluate associations between study exposures (demographics, comorbidities, stroke characteristics) and outcomes. Results: Among 1009 patients with a median last known well-to-TPA time of 87 minutes, 276 patients (27%) had a time-defined averted stroke (31% MSU, 21% SC) and 159 patients (16%) had a tissue-defined averted stroke (18% MSU, 11% SC). Factors independently associated with time-defined averted stroke were younger age (OR, 0.98; 95% CI, 0.96-0.99), female sex (0R, 0.51; 95% CI, 0.36-0.74), hyperlipidemia (OR, 1.81, 95% CI, 1.24-2.64), normal premorbid function (0R, 2.22; 95% CI, 1.37-3.67), lower glucose (OR, 0.996; 95% CI, 0.993-0.999), lower MAP (OR, 0.991; 95% CI, 0.983-0.998), MSU care (OR, 1.77; 95% CI, 1.21-2.62), lower NIH stroke scale (OR, 0.89; 95% CI, 0.86-0.93), and no large vessel occlusion (LVO) (OR, 0.52; 95% CI, 0.32-0.83). For tissue-based averted stroke, younger age, female sex, hyperlipidemia, lower MAP, MSU treatment, lower NIH stroke scale, and no LVO were significantly associated. Conclusion: In a modern acute stroke trial, one-in-four patients treated with TPA for stroke recovered within 24 hours and one-in-six had no demonstrable brain injury on imaging. Younger age, female sex, hyperlipidemia, lower MAP, MSU care, lower stroke severity, and no LVO may increase the odds of averting stroke.

Multi-targeted anti-inflammatory drugs for the treatment of neurological disorders.

Multi-targeted anti-inflammatory drugs for the treatment of neurological disorders.

PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke

There is a critical need for cerebro-protective interventions to improve the suboptimal outcomes of patients with ischemic stroke who have been treated with reperfusion strategies. We found that nuclear pyruvate kinase muscle 2 (PKM2), a modulator of systemic inflammation, was upregulated in neutrophils after the onset of ischemic stroke in both humans and mice. Therefore, we determined the role of PKM2 in stroke pathogenesis by using murine models with preexisting comorbidities. We generated novel myeloid cell–specific PKM2−/− mice on wild-type (PKM2fl/flLysMCre+) and hyperlipidemic background (PKM2fl/flLysMCre+Apoe−/−). Controls were littermate PKM2fl/flLysMCre– or PKM2fl/flLysMCre–Apoe−/− mice. Genetic deletion of PKM2 in myeloid cells limited inflammatory response in peripheral neutrophils and reduced neutrophil extracellular traps after cerebral ischemia and reperfusion, suggesting that PKM2 promotes neutrophil hyperactivation in the setting of stroke. In the filament and autologous clot and recombinant tissue plasminogen activator stroke models, irrespective of sex, deletion of PKM2 in myeloid cells in either wild-type or hyperlipidemic mice reduced infarcts and enhanced long-term sensorimotor recovery. Laser speckle imaging revealed improved regional cerebral blood flow in myeloid cell–specific PKM2-deficient mice that was concomitant with reduced post-ischemic cerebral thrombo-inflammation (intracerebral fibrinogen, platelet [CD41+] deposition, neutrophil infiltration, and inflammatory cytokines). Mechanistically, PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. To enhance the translational significance, we inhibited PKM2 nuclear translocation using a small molecule and found significantly reduced neutrophil hyperactivation and improved short-term and long-term functional outcomes after stroke. Collectively, these findings identify PKM2 as a novel therapeutic target to improve brain salvage and recovery after reperfusion.

Acute thrombocytopenia after tissue plasminogen activator for stroke: A Case Report (1416)

Acute thrombocytopenia after tissue plasminogen activator for stroke: A Case Report (1416)

Thrombolysis and Thrombectomy for Acute Ischemic Stroke: Strengths and Synergies.

Acute ischemic stroke is responsible for around 80% of all strokes and is a leading cause of disability and death globally. There are two potential treatment strategies: restoring blood flow (reperfusion) and preventing cellular injury (neuroprotection). As yet, all the successful trials have involved reperfusion with numerous failures of neuroprotectants. There are two proven reperfusion strategies. Intravenous thrombolysis with alteplase was first demonstrated to reduce disability with publication of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator trial in 1995. Since that time further trials have solidified the evidence base and demonstrated benefit when alteplase is administered within 4.5 hours of stroke onset. Exploration of potentially more effective thrombolytics is still underway with tenecteplase but others, such as desmoteplase, have been unsuccessful in clinical trials. The second proven reperfusion strategy is endovascular clot retrieval. This has been practiced for several years but came of age with the publication of five strongly positive trials in 2015. This review discusses the evidence for intravenous and intra-arterial reperfusion strategies and the advantages, disadvantages, and synergies of the two approaches.

A Stroke Registry Data on the Use of Intravenous Recombinant Tissue Plasminogen Activator in Stroke of Unknown Time of Onset

Stroke of unknown time of onset (SUTO) constitutes one fifth of all ischemic stroke admissions, and routine use of intravenous recombinant tissue plasminogen activator (IV rtPA) is recommended only in patients with a symptom onset time of less than 4.5 hours. There are limited data on clinical outcome in patients with SUTO versus patients with symptoms onset less than 4.5 hours from onset time. We hypothesized that efficacy and safety outcomes of IV rtPA therapy in selected SUTO patients are comparable to those with known onset time. We compared 90 days' modified Rankin Scale (mRS), rates of symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, and death due to sICH between 3 groups treated with IV rtPA: SUTO, 3 hours or less, and 3.0-4.5 hours from prospective patient admissions between April 1, 2012, and July 31, 2013. There were 65 participants in the SUTO group, 186 in the 3 hours or less group, and 51 in the 3.0-4.5 hours group. In-hospital mortality rates were 14.5%, 13.5%, and 11.8%, respectively. sICH risks were 1.5%, 1.6%, and 5.8%, and death rates due to sICH were 0%, 1.1%, and 1.9%, respectively. Ninety days' odds of excellent clinical outcome (mRS score 0-1) were not different between the SUTO group (odds ratio [OR] 1.14, 95% confidence interval [CI]: .63-2.10), the 3 hours or less group (OR .87, 95% CI: .48-1.60), and the 3.0-4.5 hours group (OR .79, 95% CI: .48-1.60) (P = .82). Thrombolytic therapy outcome in SUTO is not different from in-license use in our patient population. There is an urgent need to include this patient group in ongoing randomized multicenter trials.

Acute Ischemic Stroke with Very Early Clinical Improvement: A National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trials Exploratory Analysis

A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes. Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3-month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death. In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt-PA treatment effect for improvement seen for all 3 VEPRIM definitions. VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes.

Intravenous Thrombolysis for Acute Ischemic Stroke Occurring during Hospitalization for Transient Ischemic Attack

There are limited data regarding the use of intravenous thrombolysis in patients who experienced acute ischemic symptoms during their hospitalization for prior transient ischemic attack. We sought to prospectively evaluate the safety and efficacy of intravenous thrombolysis for the treatment of acute ischemic stroke occurring during hospitalization for transient ischemic attack in an international, multicenter study. Consecutive patients with acute ischemic stroke that occurred during hospitalization for prior transient ischemic attack were treated with intravenous thrombolysis in five tertiary-care stroke centers. Early arterial recanalization was determined by transcranial Doppler at the end of recombinant tissue plasminogen activator infusion using previously validated criteria. Symptomatic intracranial hemorrhage complicating intravenous thrombolysis was evaluated using the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study definition. Functional independence at three-months was defined as Modified Rankin Scale score of 0-2. Systemic recombinant tissue plasminogen activator infusion (median onset-to-treatment time 70 mins, interquartile range 50-150) was given in 25 consecutive patients (mean age 66 ± 10 years) who developed acute ischemic stroke symptoms (median National Institutes of Health Stroke Scale score 10 points; interquartile range 8-14) during hospitalization for prior transient ischemic attack (median ABCD(2) score 5 points; median time-to-symptom recurrence 24 h, interquartile range 24-48). No symptomatic intracranial hemorrhage (0%; 95% confidence interval 0-12%) was documented. Early complete recanalization occurred in 64% of patients (95% confidence interval 44-80%), and 84% (95% confidence interval 65-94%) achieved three-month functional independence. The rate of three-month functional independence was higher in patients treated with intravenous tissue plasminogen activator within 90 mins from symptom onset compared with those with onset-to-treatment time>90 mins (81% vs. 33%; P = 0.031). Intravenous thrombolysis for symptoms of acute ischemic stroke occurring after hospitalization for transient ischemic attack appears to be safe. These pilot data support resetting the clock if new symptoms recur shortly after transient ischemic attack.

Validation of Minor Stroke Definitions for Thrombolysis Decision Making

Patients with low National Institutes of Health Stroke Scale (NIHSS) scores are frequently excluded from thrombolysis, but more than 25% of them remain disabled. We sought to define a validated minor stroke definition to reduce the inappropriate treatment exclusion. From an outcome database, untreated patients with an NIHSS score of 5 or less presenting within a 4.5-hour window were identified and 3-month modified Rankin Scale (mRS) outcomes were analyzed according to individual isolated symptoms and total NIHSS scores. The validity of the following minor stroke definitions were assessed: (1) the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator (NINDS-TPA) trials' definition, (2) the total NIHSS score, varying a cutoff point from 0 to 4, and (3) our proposed definition that included an NIHSS score = 0 or an NIHSS score = 1 on the items of level of consciousness (LOC), gaze, facial palsy, sensory, or dysarthria. Of 647 patients, 172 patients (26.6%) had a 3-month unfavorable outcome (mRS score 2-6). Favorable outcome was achieved in more than 80% of patients with an NIHSS score of 1 or less or with an isolated symptom on the LOC, gaze, facial palsy, sensory, or dysarthria item. In contrast, unfavorable outcome proportion was more than 25% in patients with an NIHSS score of 2 or more. When the NINDS-TPA trials' definition, our definition, or the definition of an NIHSS score of 1 or less were applied, more than 75% of patients with an unfavorable outcome were defined as a non-minor stroke and less than 15% of patients with an unfavorable outcome were defined as a minor stroke. Implementation of an optimal definition of minor stroke into thrombolysis decision-making process would decrease the unfavorable outcomes in patients with low NIHSS scores.

Use of intravenous recombinant tissue plasminogen activator in patients outside the defined criteria: safety and feasibility issues

Currently, intravenous thrombolysis is by far the most effective treatment of acute ischemic stroke, and its use can independently strongly increase the proportion of stroke patients surviving. While the use of recombinant tissue plasminogen activator in accordance to licensed criteria has continuously risen, off-label use is also frequent. In this review the most important reasons to transcend current license criteria are discussed and evidence is summarized from new studies, such as IST-3, contributing to the balance of increased benefit as opposed to possible harm in situations of off-label use of recombinant tissue plasminogen activator in stroke. In addition, several scores to predict risk and outcome in patients undergoing thrombolysis are compared.

Abstract TP64: Optimal Minor Stroke Definition For Thrombolysis Decision-making

Background and purpose: Patients with a low National Institutes of Health Stroke Scale (NIHSS) score are frequently excluded from thrombolysis, but &gt;25% of those patients remain disabled. We sought to define a minor stroke definition that helps guide treatment decision-making. Methods: From a stroke outcome database, untreated patients with NIHSS ≤5 presenting within a 4.5-hour window were identified. The validity of the following minor stroke definitions were assessed: 1) the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator (NINDS-TPA) trials’ definition; 2) the total NIHSS score, varying a threshold from 0 to 4; 3) our proposed definition which included NIHSS=0 or NIHSS=1 in the items of level of consciousness, gaze, facial palsy, sensory, or dysarthria. Results: Of 647 included patients, 172 (26.6%) had a 3-month unfavorable outcome (modified Rankin Scale 2-6). When the NINDS-TPA trials’ definition, our proposed definition, or NIHSS ≤1 definition was applied, &gt;75% of patients with an unfavorable outcome were defined as a non-minor stroke and &gt;85% of those defined as a minor stroke had a favorable outcome. For a hypothetical population of 1000 patients with NIHSS ≤5, as compared to the NINDS-TPA trials’ definition, our definition would treat additional 23 patients and increase 17-18 favorable outcomes at the expense of 1-2 symptomatic hemorrhagic transformations (SHTs), whereas the NIHSS ≤1 definition would further exclude 54 patients from treatment and the benefit of avoiding 1-4 SHTs would be negated by the increase of three unfavorable outcomes among untreated patients. Conclusion: A validated criterion should be applied to thrombolysis decision-making for patients with a mild deficit. Our definition would further increase the treatment rate and favorable outcomes.

Medicolegal Considerations with Intravenous Tissue Plasminogen Activator in Stroke: A Systematic Review

Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.

Spotlight on the January 1 Issue

When applied to the National Institute of Neurological Disorders and Stroke tissue plasminogen activator (tPA) trial data, the combination of age plus NIH Stroke Scale score (SPAN-100) was associated with higher risk of intracerebral hemorrhage in SPAN-100–positive (score ≥ 100) patients, whether receiving tPA or not, compared to SPAN-100–negative patients. The benefit of tPA was apparent in the SPAN-100–positive group, but not in the SPAN-100–negative group. See p. 21 From editorialists Rabinstein & Rundek: “Should any score predicting very poor outcome despite thrombolysis, or a high risk of hemorrhage with thrombolysis, be deemed sufficient to withhold IV tPA administration?” See p. 15 Eighteen recently diagnosed, mildly disabled patients, all …

The iScore Predicts Efficacy and Risk of Bleeding in the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator Stroke Trial

The iScore is a validated tool to estimate outcomes after an acute ischemic stroke. A previous study showed the iScore can predict clinical response and risk of intracerebral hemorrhage (ICH) after administration of tissue plasminogen activator (tPA). We applied the iScore (www.sorcan.ca/iscore) to participants in the National Institute of Neurological Disorders and Stroke tPA stroke trials to evaluate its ability to estimate clinical response and risk of ICH after thrombolysis. Based on results from our previous study, patients were stratified a priori into iScore <200 and iScore ≥ 200. The main outcome measure was ICH. Secondary outcomes included favorable composite outcome (defined as a modified Rankin Scale score of 0 or 1, National Institutes of Health Stroke Scale score ≤ 1, Barthel Index ≥ 95, or Glasgow Outcome Scale <1 at 3 months) and functional outcomes. The iScore was calculated in all 624 patients enrolled in the trial. The cohort comprised 507 patients (81%) with an iScore <200 and 117 (19%) with an iScore ≥ 200. An iScore ≥ 200 was associated with greater risk of symptomatic ICH in the tPA group compared with the placebo group (15.4% v 3.9%; P = .04). Similar findings were found for ICH of any type (30.8% v 11.5%; P = .014), with higher ICH mortality (69.2% v 23.8%; P < .001). Despite the higher favorable composite outcome of tPA therapy in patients with an iScore <200 (58.7% v 41.9%; P < .001), this therapy had no benefit in patients with an iScore ≥ 200 (15.4% v 13.4%; P = .77). In patients receiving tPA in the National Institute of Neurological Disorders and Stroke trial, the iScore estimated the clinical response and risk of hemorrhagic complications. Further prospective studies are needed before a change in practice can be recommended.

Vascular Protection to Increase the Safety of Tissue Plasminogen Activator for Stroke

Thrombolytic therapy with tissue plasminogen activator (tPA) remains the most effective treatment for acute ischemic stroke, but can cause vascular damage leading to edema formation and hemorrhagic transformation (HT). In this review, we discuss how tPA contributes to the pathogenesis of vascular damage and highlight evidence to support combination therapy of tPA with pharmacological agents that are vascular protective. There is an unmet need to develop therapeutic interventions which target the underlying mechanisms of vascular damage after acute ischemic stroke in order to prevent HT and improve the safety and impact of tPA.

Contemporary Outcome Measures in Acute Stroke Research

See related articles, p 1163 and 1171. The 2 articles in this issue1,2 are based on the recent European Stroke Organization Outcomes Workshop and provide an excellent basis for discussion of outcomes used in stroke trials. Bath, Lees, and colleagues raise important points to consider when choosing an outcome measure or an analysis plan. The authors speculate that trials to identify therapeutic benefits of effective drugs may fail to find benefits because of problems inherent in choice of outcome measures or methods of analysis. Early in their article, Bath and colleagues give examples of multiple ways to define an outcome and show that trial results vary based on the definitions used. The emphasis throughout the article is on increasing power to detect differences so effective treatments will not be missed. There are many ways to increase power, but not all lead to the identification of clinically meaningful differences. The authors give little mention to the possibility of a Type 1 error, that is, declaring an ineffective therapy effective. Type I errors can result from searches for outcomes and analytic approaches to increase the power to detect treatment differences after a trial is completed. It is as important to patients that ineffective treatments are kept out of clinical practice as it is to assure that effective treatments are not missed. The authors recognize that 1 outcome and 1 analytic approach may not fit all trials. In choosing an outcome or approach, the most important consideration is the research question of interest. It is the trial hypothesis that should drive the choices. As an example, at a workshop to identify outcomes and an analytic approach for the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator (NINDS tPA) Stroke Trial,3 Thomas Brott stated that he would …

Editorial on “A Simple, Assumption-Free, and Clinically Interpretable Approach for Analysis of Modified Rankin Outcomes”

See related article, p 664. The perfect stroke outcome scale remains the holy grail of our field—ever-elusive and sorely needed. Fifty years ago, Dr. John Rankin, working in a rehabilitation setting, devised a simple 6-point scale that made intuitive sense to all users; later, a category was added for death, resulting in a modified Rankin scale (mRS) as used today.1 Despite the simplicity and intuitive sense of the scale, the mRS was used little until it was rediscovered for many stroke therapy trials 15 years ago. Notably, the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator for Acute Stroke trial used the mRS as 1 of 4 outcomes; the success of that trial catapulted the mRS to the forefront of stroke clinical trial design, and it has been ubiquitous ever since.2 In approaching the mRS for use in the National Institute of Neurological Disorders and Stroke Tissue Plasminogen Activator for …

Minimal sufficient balance-a new strategy to balance baseline covariates and preserve randomness of treatment allocation.

In many clinical trials, baseline covariates could affect the primary outcome. Commonly used strategies to balance baseline covariates include stratified constrained randomization and minimization. Stratification is limited to few categorical covariates. Minimization lacks the randomness of treatment allocation. Both apply only to categorical covariates. As a result, serious imbalances could occur in important baseline covariates not included in the randomization algorithm. Furthermore, randomness of treatment allocation could be significantly compromised because of the high proportion of deterministic assignments associated with stratified block randomization and minimization, potentially resulting in selection bias. Serious baseline covariate imbalances and selection biases often contribute to controversial interpretation of the trial results. The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial and the Captopril Prevention Project are two examples. In this article, we propose a new randomization strategy, termed the minimal sufficient balance randomization, which will dually prevent serious imbalances in all important baseline covariates, including both categorical and continuous types, and preserve the randomness of treatment allocation. Computer simulations are conducted using the data from the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Trial. Serious imbalances in four continuous and one categorical covariate are prevented with a small cost in treatment allocation randomness. A scenario of simultaneously balancing 11 baseline covariates is explored with similar promising results. The proposed minimal sufficient balance randomization algorithm can be easily implemented in computerized central randomization systems for large multicenter trials.

Bayesian Hierarchical Modeling and the Integration of Heterogeneous Information on the Effectiveness of Cardiovascular Therapies

When making therapeutic decisions for an individual patient or formulating treatment guidelines on a population level, it is often necessary to utilize information arising from different study designs, settings, or treatments. In clinical practice, heterogeneous information is frequently synthesized qualitatively, whereas in comparative effectiveness research and guideline development, it is imperative that heterogeneous data are integrated quantitatively and in a manner that accurately captures the true uncertainty in the results. Bayesian hierarchical modeling is a technique that utilizes all available information from multiple sources and naturally yields a revised estimate of the treatment effect associated with each source. A hierarchical model consists of multiple levels (ie, a hierarchy) of probability distributions that represent relationships between information arising within single populations or trials, as well as relationships between information arising from different populations or trials. We describe the structure of Bayesian hierarchical models and discuss their advantages over simpler models when multiple information sources are relevant. Two examples are presented that illustrate this technique: a meta-analysis of immunosuppressive therapy in idiopathic dilated cardiomyopathy and a subgroup analysis of the National Institute of Neurological Disorders and Stroke Intravenous Tissue Plasminogen Activator Stroke Trial.

Rapid Neurological Recovery after Intravenous Tissue Plasminogen Activator in Stroke: Prognostic Factors and Outcome

Background: Treatment with tissue plasminogen activator (tPA) is associated with improved outcome in acute ischemic stroke. Of note, a proportion of patients demonstrate rapid and significant neurological recovery within 24 h. This has previously not been systematically studied. We aimed to examine its incidence, predictive factors and correlation with clinical outcomes. Methods: We included 161 patients with acute ischemic stroke who received intravenous tPA within 4.5 h. Patient demographics and clinical data were collected. Rapid neurological recovery was defined as an improvement of at least 50% within 24 h as measured by the National Institute of Health Stroke Scale (NIHSS) score, and long-term outcomes were assessed by 3-month modified Rankin Scale. The incidence of rapid neurological recovery and its correlation with outcomes were studied. The predictors of the phenomenon were examined by univariate analysis. Results: Rapid neurological recovery was present in 44 of the 161 patients (27.3%). This correlated with favorable outcomes at 3 months (p < 0.0005). Lower baseline NIHSS score (p = 0.006), mild (NIHSS score <12) versus severe stroke (NIHSS score ≧12; p = 0.002), normal serum glucose levels on admission (3.3–7.7 mmol/l; p = 0.009) and younger age (p = 0.043) predicted rapid neurological recovery. However, there was no association with time to treatment (p = 0.3). Conclusion: Rapid neurological recovery defines a rapid responder population and was demonstrated in a quarter of patients treated with intravenous tPA. It strongly predicts a good clinical outcome.