Background and Purpose- The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods- We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score-24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score-24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95-100 and modified Rankin Scale score of 0-1), good 3-month functional outcome (modified Rankin Scale score of 0-2), and 3-month infarct volume. Results- There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P=0.045) but not median delta NIHSS (3 versus 2; P=0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROCpercent) was better than delta NIHSS (ROCdelta) and admission NIHSS (ROCadmission) with regards to excellent 3-month Barthel Index (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.75), excellent 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.74; ROCadmission, 0.78), and good 3-month modified Rankin Scale (ROCpercent, 0.83; ROCdelta, 0.76; ROCadmission, 0.78). Conclusions- In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

中文翻译：

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重新定义的早期神经功能改善措施显示，阿替普酶优于安慰剂。

背景和目的-2项NINDS（美国国家神经疾病和中风研究所）研究试验中的第一项并未显示早期神经系统改善显着增加，定义为美国国立卫生研究院卒中量表（NIHSS）改善≥4，并使用阿替普酶治疗。我们假设定义为24小时NIHSS百分比变化（NIHSS百分比变化）的早期神经功能改善在预测3个月的功能结局方面优于其他定义，使用此定义在24小时时阿替普酶优于安慰剂。方法-我们分析了NINDS rt-PA中风研究（第1部分和第2部分）的试验数据。NIHSS的变化百分比定义为（[入学NIHSS分数-24小时NIHSS分数]×100 /入学NIHSS分数]，而增量NIHSS定义为（入学NIHSS分数-24小时NIHSS分数）。我们比较了使用这些定义的阿替普酶组与安慰剂组之间的早期神经功能改善。我们还使用接收器操作特征曲线来确定早期神经功能改善与3个月良好的功能预后（Barthel指数评分为95-100和改良的Rankin Scale评分为0-1），3个月的良好功能预后（修正后）的预测关联Rankin量表评分为0-2）和3个月的梗塞体积。结果-与安慰剂组相比，接受阿替普酶治疗的患者24小时NIHSS的中位数变化百分比显着高于安慰剂组（分别为28％和15％； P = 0.045），而不是中位数增量NIHSS（3比2； P = 0.471）。接收者工作特征曲线比较显示，就3个月的巴特尔指数（ROCpercent，0.83; ROCdelta，0.76; ROCadmission，0.75）而言，NIHSS（ROCpercent）的变化百分比优于NIHSS（ROCdelta）和入院NIHSS（ROCadmission），优秀的3个月改良兰金量表（ROCpercent，0.83; ROCdelta，0.74; ROCadmission，0.78）和良好的3个月改良兰金丁量表（ROCpercent，0.83; ROCdelta，0.76; ROCadmission，0.78）。结论-在NINDS rt-PA试验中，阿替普酶与24小时NIHSS的明显改善百分比相关。NIHSS的百分比变化可能是溶栓活性和3个月预后的更好替代指标。优秀的3个月改良兰金量表（ROCpercent，0.83; ROCdelta，0.74; ROCadmission，0.78）和良好的3个月改良兰金丁量表（ROCpercent，0.83; ROCdelta，0.76; ROCadmission，0.78）。结论-在NINDS rt-PA试验中，阿替普酶与24小时NIHSS的明显改善百分比相关。NIHSS的百分比变化可能是溶栓活性和3个月预后的更好替代指标。优秀的3个月改良兰金量表（ROCpercent，0.83; ROCdelta，0.74; ROCadmission，0.78）和良好的3个月改良兰金丁量表（ROCpercent，0.83; ROCdelta，0.76; ROCadmission，0.78）。结论-在NINDS rt-PA试验中，阿替普酶与24小时NIHSS的明显改善百分比相关。NIHSS的百分比变化可能是溶栓活性和3个月预后的更好替代指标。