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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

The Pediatric Infectious Disease Journal: July 2014 - Volume 33 - Issue 7 - p 675–679
doi: 10.1097/INF.0000000000000249
Original Studies

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.

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.

Accepted for publication November 25, 2013.

This work was supported by grants from the Päivikki and Sakari Sohlberg Foundation, the Sigrid Jusélius Foundation and the Foundation for Pediatric Research, Finland.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).

Address for correspondence: Irmeli Roine, MD, PhD, Los Misioneros 2237, 7520179 Santiago, Chile. E-mail: irmeli.roine@gmail.com.

© 2014 by Lippincott Williams & Wilkins, Inc.