Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. METHODS: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT-treatment interaction. Tests for OTT-treatment interactions adjusting for potential masking confounders were performed. An OTT-treatment interaction was considered significant if p < or = 0.10, implying that treatment effectiveness was related to OTT. RESULTS: For 24-hour improvement, there were no masking confounders identified and there was an OTT-treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT-treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. CONCLUSIONS: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.     

Predicting prognosis after stroke: a placebo group analysis from the National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial

BACKGROUND: Physicians are often asked to predict outcome after acute stroke. Very little information is available that can reliably predict the likelihood of severe disability or death. OBJECTIVE: To develop a practical method for predicting a poor outcome after acute ischemic stroke. METHODS: Data from the placebo arms of Parts 1 and 2 of the National Institute of Neurological Disorders and Stroke rt-PA [recombinant tissue plasminogen activator] Stroke Trial were used to identify variables that could predict a poor outcome, defined as moderately severe disability, severe disability, or death (Modified Rankin Scale score >3) 3 months after stroke. RESULTS: Baseline variables that predicted poor outcome were the NIH Stroke Scale (NIHSS) >17 plus atrial fibrillation, yielding a positive predictive value (PPV) of 96% (95% CI, 88 to 100%). The best predictor at 24 hours was NIHSS >22, yielding a PPV of 98% (95% CI, 93 to 100%). The best predictor at 7 to 10 days was NIHSS >16, yielding a PPV of 92% (95% CI, 85 to 99%). CONCLUSIONS: Patients with a severe neurologic deficit after acute ischemic stroke, as measured by the NIHSS, have a poor prognosis. During the first week after acute ischemic stroke, it is possible to identify a subset of patients who are highly likely to have a poor outcome. These findings require confirmation in a separate study.     

Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators.

BACKGROUND AND PURPOSE: No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS. METHODS: We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome. RESULTS: The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity. CONCLUSIONS: This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome.     

Admission glucose level in relation to mortality and morbidity outcome in 252 stroke patients

In a prospective study to correlate admission glucose level with neurologic outcome in stroke, 252 acute stroke patients without prior disability and admitted within 24 hours of onset of ictus were assessed. The stroke was classified into one of three types--cortical infarct, lacunar infarct, or intracerebral hemorrhage--by clinical, computed tomographic, and necropsy findings. Fifty-one diabetic patients were excluded from the entire cohort to form a nondiabetic category for analysis. We found that admission glucose level showed a significantly higher degree of correlation with mortality and morbidity (measured as arm function, leg function, and activities of daily living) when cortical (n = 118) and lacunar (n = 58) infarcts were pooled compared with when they were assessed separately. For intracerebral hemorrhage (n = 76), admission glucose level correlated with mortality but not morbidity. This trend persisted despite exclusion of diabetic patients. These results are consistent with previous observations of a correlation between a high admission glucose level and the severity of stroke. The importance of segregating cortical from lacunar infarcts, two groups with a different natural history and prognosis, in any future analysis is emphasized.     

Blood pressure declines and less favorable outcomes in the NINDS tPA stroke study

BACKGROUND AND PURPOSE: Hypertension is the most important modifiable risk factor for secondary stroke prevention but the immediate management of blood pressure after stroke is uncertain. We evaluated outcomes in the NINDS tPA stroke study in relation to blood pressure declines during the first 24 h after randomization. METHODS: Declines in blood pressure compared to baseline and preceding time points were analyzed in relationship to favorable outcomes (by a global test), poor outcomes (Rankin scale >3) and death at 3 months. RESULTS: 551 patients did not receive immediate pre-randomization anti-hypertensive treatment and had available blood pressures. Multivariate analysis showed significantly and progressively reducing likelihoods of a favorable outcome with each 10 mmHg decline in systolic blood pressure (SBP) >50 mmHg compared to any preceding measurement. Poor outcomes were significantly more likely in patients with >50 mmHg SBP reduction (or >30 mmHg compared to any immediately preceding measurement). There was an increased risk of death with blood pressure declines >60 mmHg. tPA treatment still produced favorable outcomes compared with placebo even with blood pressure declines. The median largest SBP reduction from baseline in patients treated with tPA was 35 mmHg compared to 30 mmHg in placebo-treated patients (p<0.01). CONCLUSIONS: In this post hoc analysis, progressively reducing likelihoods of a favorable outcome were seen with increasing declines in SBP. Despite a greater likelihood of favorable outcomes, tPA treatment was associated with a greater reduction in blood pressure than placebo. Randomized trials of blood pressure management are needed.     

急性脑梗死超早期重组组织型纤溶酶原激活物溶栓治疗的临床研究

目的:探讨发病6h内急性脑梗死给予重组组织型纤溶酶原激活物(rt-PA)溶栓治疗的疗效及并发症,并分析预后相关因素。方法:共收集本院2001-2005年70例溶栓治疗的急性脑梗死病例,其中52例静脉溶栓,18例动脉溶栓,分析比较两组病例溶栓前后及3个月随访的ESS评分及Barthel指数结果;同时分析与预后相关的因素。结果:静脉和动脉溶栓组溶栓前及溶栓30min后ESS评分及Barthel指数迅速增加,溶栓前后分值有显著差异。1个月内颅内出血率为5.77%(静脉组)和16.67%(动脉组)。3个月时ESS评分及Barthel指数较溶栓后30min的评分有显著改善。结论:6h内动脉、静脉溶栓治疗均安全有效。     

NINDS clinical trials in stroke: lessons learned and future directions

Since 1977 the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) has sponsored 28 phase 3 trials to evaluate treatments of stroke, which when all completed will have randomized a total of 44 862 patients in the United States and other countries. NINDS stroke clinical trials have been successful in finding beneficial and cost-effective treatments for cerebrovascular disease. Future trials are likely to be larger and have simpler designs which allow for the inclusion of more patients and which collect less data for each patient. In addition, measures of cognitive outcomes, particularly timed tests of executive function, disability scales, and quality-of-life outcomes will become more common. The stroke research community can take pride in the solid base of evidence that has been built over the past 2 decades. If we continue to follow the discoveries of science, continue to create new trial methodology, and increase participation in clinical trials, significant advances in the treatment of cerebrovascular disease will continue.     

Stroke in ovarian hyperstimulation syndrome in early pregnancy treated with intra-arterial rt-PA

Ovarian hyperstimulation syndrome (OHSS) caused by fertility medications can predispose women to thrombosis. The authors present a case of a previously healthy woman who underwent in vitro fertilization and experienced a middle cerebral artery thrombosis that was subsequently lysed with intra-arterial recombinant tissue plasminogen activator (rt-PA). To the authors' knowledge, this is the first reported case of successful use of rt-PA to lyse a cerebral arterial thrombus resulting from severe OHSS. The patient made a near complete neurologic recovery and delivered a healthy infant at term, illustrating that intra-arterial thrombolysis can be used with relative safety even in very early pregnancy.     

Infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank: neurologic examination.

To gain insight into neurologic signs relevant to the diagnosis of cardiogenic embolism, we analyzed data from 1,290 patients with cerebral infarcts in the NINDS Stroke Data Bank. Based solely on the presence of potential cardiac sources of embolism, we divided patients into groups of high (N = 250), medium (N = 167), and low (N = 873) risk of a cardiogenic mechanism for their stroke. Diminished level of consciousness was highly associated with the presence of a cardiac source of embolism. Of the four primarily cortical deficits assessed, three (visual field abnormalities, neglect, and aphasia) showed a highly significant graded relationship to the cardiac risk groups. For the fourth cortical deficit (other nonlanguage cognitive functions), this relationship did not attain statistical significance. Conversely, hemiparesis without sensory or cortical deficits had a strong inverse association to the presence of a cardiac source of embolism. This inverse association was weaker for sensorimotor strokes and nonexistent for pure sensory strokes. Although some neurologic findings had highly significant associations with the presence of a cardiac source of embolism, their predictive value for an embolic source was low.