Predictive value of cerebrospinal fluid matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 concentrations in childhood bacterial meningitis.
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.
Irmeli
I
Roine
Tuula
T
Pelkonen
Luis
L
Bernardino
Anneli
A
Lauhio
Taina
T
Tervahartiala
Maija
M
Lappalainen
Matti
M
Kataja
Anne
A
Pitkäranta
Timo
T
Sorsa
Heikki
H
Peltola
D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D016920:Meningitis, Bacterial / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid*
D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9