Triglia Thibaut, Mezzapesa Anna, Martin Jean Charles, Verdier Monique, Lagier David, Dufour Henry, Bruder Nicolas, Alessi Marie-Christine, Velly Lionel J
From the Department of Anaesthesiology and Critical Care Medicine, University Hospital Timone (TT, DL, NB, LV), NORT Inserm 1062, Inra 1260 (AM, JCM, MV, MCA), and Department of Neurosurgery, University Hospital Timone, Aix Marseille University, Marseille, France (HD).
Eur J Anaesthesiol. 2016 Sep;33(9):662-9. doi: 10.1097/EJA.0000000000000494.
Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia.
Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage.
Single-centre prospective observational study.
Neuroscience Critical Care Unit of a teaching hospital.
Thirty consecutive patients with severe subarachnoid haemorrhage requiring external ventricular drainage were enrolled during 2013 and 2014.
Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h and between 48 and 72 h after admission. We evaluated the activity and concentrations of MMP-9 and endothelin-1 with zymography and ELISA. Patients were allocated to groups with delayed cerebral ischaemia (n = 16) or without delayed cerebral ischaemia (n = 14).
Within 24 h, median [interquartile range] MMP-9 concentrations in CSF were significantly higher in patients with delayed cerebral ischaemia (47 [21 to 102] ng ml) than in those without delayed cerebral ischaemia (4 [2 to 13] ng ml, P = 0.001). CSF MMP-9 activity and endothelin-1 concentrations were correlated (r = 0.6, P = 0.02). The areas under the receiver operating characteristic curves were 0.73 (95% confidence interval [0.53 to 0.87]) and 0.91 (95% confidence interval [0.75 to 0.98]) for MMP-9 concentrations in plasma and CSF, respectively, at 24 h to predict delayed cerebral ischaemia CSF MMP-9 concentrations more than 14.3 ng ml at 24 h predicted the occurrence of delayed cerebral ischaemia with a sensitivity and specificity of 88 and 86%, respectively. After multivariate logistic analysis, only CSF MMP-9 concentrations at 24 h predicted the occurrence of delayed cerebral ischaemia (P = 0.01).
MMP-9 concentrations in both plasma and CSF, measured within 48 h after subarachnoid haemorrhage, were highly predictive of the occurrence of delayed cerebral ischaemia within the first 2 weeks.
Clinicaltrials.gov identifier: NCT02397759.
血管痉挛导致的迟发性脑缺血是动脉瘤性蛛网膜下腔出血后并发症和死亡的重要原因。目前尚无用于识别迟发性脑缺血高危患者的确立生物标志物。
鉴于炎症在迟发性脑缺血发病机制中的重要作用，我们研究基质金属蛋白酶-9（MMP-9）是否可能是预测蛛网膜下腔出血后迟发性脑缺血的有效生物标志物。
单中心前瞻性观察性研究。
一家教学医院的神经科学重症监护病房。
2013年至2014年期间连续纳入30例需要进行脑室外引流的严重蛛网膜下腔出血患者。
入院后24小时内以及48至72小时之间采集血液和脑脊液（CSF）样本。我们通过酶谱分析和酶联免疫吸附测定法评估MMP-9和内皮素-1的活性及浓度。将患者分为发生迟发性脑缺血组（n = 16）和未发生迟发性脑缺血组（n = 14）。
在24小时内，发生迟发性脑缺血患者脑脊液中MMP-9浓度的中位数[四分位间距]（47[21至102] ng/ml）显著高于未发生迟发性脑缺血的患者（4[2至13] ng/ml，P = 0.001）。脑脊液MMP-9活性与内皮素-1浓度相关（r = 0.6，P = 0.02）。在24小时时，血浆和脑脊液中MMP-9浓度用于预测迟发性脑缺血的受试者工作特征曲线下面积分别为0.73（95%置信区间[0.53至0.87]）和0.91（95%置信区间[0.75至0.98]）。24小时时脑脊液MMP-9浓度超过14.3 ng/ml可预测迟发性脑缺血的发生，敏感性和特异性分别为88%和86%。经过多因素逻辑回归分析，仅24小时时的脑脊液MMP-9浓度可预测迟发性脑缺血的发生（P = 0.01）。
蛛网膜下腔出血后48小时内测得的血浆和脑脊液中MMP-9浓度对前2周内迟发性脑缺血的发生具有高度预测性。
Clinicaltrials.gov标识符：NCT02397759。
