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Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0000000000000249
Original Studies

Predictive Value of Cerebrospinal Fluid Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Concentrations in Childhood Bacterial Meningitis

Roine, Irmeli MD, PhD*; Pelkonen, Tuula MD, PhD†‡; Bernardino, Luis MD; Lauhio, Anneli MD, PhD§; Tervahartiala, Taina DDS, PhD; Lappalainen, Maija MD, PhD; Kataja, Matti PhD**; Pitkäranta, Anne MD, PhD††‡‡; Sorsa, Timo DDS, PhD¶§§; Peltola, Heikki MD, PhD

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Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

© 2014 by Lippincott Williams & Wilkins, Inc.


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