Hearing impairment is a well-recognized sequela caused by bacterial meningitis, but the underlying pathophysiology remains largely unknown. Matrix metalloproteinase-2 (MMP-2) is known to affect neuronal cell damage and survival in different diseases of the brain. We investigated whether levels of MMP-2 in the cerebrospinal fluid (CSF) relate to the extent of hearing impairment in children with bacterial meningitis.
Clinical data of 179 children were obtained from a previous clinical trial examining the adjuvant treatment of bacterial meningitis in Latin America in 1996-2003. At discharge or shortly thereafter, the ability to hear was measured with brain stem evoked response audiometry or traditional pure tone audiometry. Levels of CSF MMP-2 on admission (CSF1, n=161) and 12-24 hours later (CSF2, n=133) were assessed by zymography. The combined results for the detected pro-form and active MMP-2 were compared with the audiological outcome of the patients.
MMP-2 was detected in half of both the CSF1 and CSF2 samples. The median densitometric values with interquartile ranges (IQRs) were 0.04 (IQR 0.00-0.29) for CSF1 and 0.00 (IQR 0.00-0.33) for CSF2. Detectable MMP-2 associated with milder hearing impairment in CSF1 (p = 0.05), but not in CSF2 (p = 0.1). Patients who were deaf at discharge had lower levels of MMP-2 in both samples (CSF1, p = 0.05; CSF2, p = 0.04), compared to patients who were not deaf. A MMP-2 level over the 75th percentile in CSF1 predicted lower odds of any audiological sequelae (odds ratio 0.30, 95% confidence interval 0.14-0.68, p = 0.004).
The upregulation of MMP-2 in the CSF associated with a better audiological outcome in children with bacterial meningitis. The results suggest that MMP-2 might play a protective role in the development of hearing sequelae due to bacterial meningitis.
S. Alassiri, None
T. Tervahartiala, None
O. Helve, None
J. Fernandez, None
H. Peltola, None
T. Sorsa, None
T. Pelkonen, None