From the *Faculty of Medicine, University Diego Portales, Santiago, Chile; †David Bernardino Children's Hospital, Luanda, Angola; ‡Children´s Hospital; §Division of Infectious Diseases, Department of Medicine; ¶Department of Oral and Maxillofacial Diseases; ‖Department of Virology and Immunology, Laboratory Services (HUSLAB), Helsinki University Central Hospital; **National Institute for Health and Welfare; ††Institute of Clinical Medicine; ‡‡Department of Otorhinolaryngology, Helsinki University Central Hospital; and §§Institute of Dentistry, University of Helsinki, Helsinki, Finland.
Pediatr Infect Dis J. 2014 Jul;33(7):675-9. doi: 10.1097/INF.0000000000000249.
Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM.
Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae.
Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12.
Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.
脑脊髓液中基质金属蛋白酶（MMP）浓度的增加是细菌性脑膜炎（BM）宿主反应的一部分。我们研究了 MMP-9 和金属蛋白酶组织抑制剂（TIMP）-1 的浓度是否能预测儿童 BM 的结局。
通过酶联免疫吸附试验分别定量检测 264 例和 335 例患者的脑脊液 MMP-9 和 TIMP-1，43 例无 BM 的儿童作为对照。将结果与先前已知的死亡和后遗症的独立预测因素进行比较。
较高的 MMP-9 和 TIMP-1 值将对照组与 BM 患者区分开来（P<0.0001）。MMP-9 浓度>940ng/ml 是死亡的独立预测因子[校正比值比：4.03；95%置信区间（CI）：2.09-7.77；P<0.0001]。如果患者的格拉斯哥昏迷评分（GCS）低于 9，则比值增加至 13.21（95%CI：5.44-32.08；P<0.0001）。TIMP-1 水平与后遗症的严重程度相关（ρ：0.30；P<0.0001），但与死亡无关。其浓度高于 390ng/ml 使发生后遗症的可能性增加 3.43 倍（95%CI：1.73-6.79；P=0.0004），如果患者的格拉斯哥昏迷评分（GCS）也<12，则可能性增加 31.18 倍（95%CI：4.05-239.8；P=0.0009）。
脑脊液中 MMP-9 和 TIMP-1 浓度升高可预测儿童 BM 的 2 个重要结局。与临床评估相结合，这些指标的定量可增加识别最需要更好治疗方法的患者的机会。
