Laskowitz Daniel T, Kasner Scott E, Saver Jeffrey, Remmel Kerri S, Jauch Edward C
Department of Medicine Neurology, Duke University Medical Center, Durham, NC 27719, USA.
Stroke. 2009 Jan;40(1):77-85. doi: 10.1161/STROKEAHA.108.516377. Epub 2008 Oct 23.
One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.
A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.
These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.
疑似急性脑缺血患者评估与管理的重大局限之一是缺乏广泛可用、快速且灵敏的诊断检测方法。本研究的目的是评估使用一组生物标志物的检测方法能否通过区分脑缺血患者与急性神经功能缺损的其他病因，在卒中早期评估中提供有用的诊断信息。
在17个不同地点前瞻性纳入了1146例出现与可能卒中相符的神经症状的患者。对定时采集的血样检测基质金属蛋白酶9、脑钠肽、D-二聚体和S100β蛋白。独立纳入343例患者的另一队列以验证多生物标志物模型方法。
将基质金属蛋白酶9、脑钠肽、D-二聚体和S100β的值纳入综合评分的诊断工具对急性脑缺血敏感。多变量模型显示出适度的鉴别能力，出血性卒中的受试者操作特征曲线下面积为0.76，所有卒中的为0.69（似然性检验P<0.001）。当逻辑模型的阈值设定在第一个四分位数时，检测所有卒中的灵敏度为86%，检测出血性卒中的灵敏度为94%。此外，在即时检验平台上对另一队列的检测结果具有可重复性。
这些结果表明，生物标志物组可能在卒中早期评估中增加有价值且对时间敏感的诊断信息。这种方法在即时检验平台上是可行的。快速识别疑似卒中患者将扩大限时治疗策略的可及性。尽管当前生物标志物组的诊断准确性明显不完善，但本研究证明了将基于生物标志物的即时检验算法与现成的临床数据相结合以辅助脑缺血高危患者早期评估和管理的可行性。
