CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis

Abstract

Background and objectives: Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis.

Methods: We measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses. We identified independent predictors of an unfavorable outcome (Glasgow Outcome Scale scores 1-4) by logistic regression.

Results: CSF NfL concentrations were evaluated in 429 episodes of 425 patients with community-acquired bacterial meningitis. The median age of 429 episodes was 62 years (interquartile range, 50-69 years). Of note, 290 of 422 (68%) episodes presented with an altered mental status (Glasgow Coma Scale score < 14). Most common causative pathogens were Streptococcus pneumoniae (73%), Neisseria meningitidis (7%), and Listeria monocytogenes (5%). The overall case fatality rate was 62 of 429 (15%), and unfavorable outcome occurred in 57 (37%) of 429 episodes. In multivariate analysis, predictors of unfavorable outcome were older age (OR 1.03, 95% CI 1.01-1.05), cranial nerve palsy (OR 4, 95% CI 1.6-10.3), high serum C-reactive protein concentration (OR 1.3, 95% CI 1.01-1.05), and high CSF NfL concentration (OR 1.5, 95% CI 1.07-2.00). CSF NfL concentrations were higher in patients presenting with focal cerebral deficits (717 pg/mL [416-1,401] vs 412 pg/mL [278-731]; p < 0.001). The area under the curve (AUC) for predicting unfavorable outcome in bacterial meningitis of CSF NfL concentration was 0.69 (95% CI, 0.64-0.74).

Discussion: CSF NfL concentration is independently associated with unfavorable outcome in adults with community-acquired bacterial meningitis, suggesting that CSF NfL concentration may be a useful biomarker for prognostic assessment in bacterial meningitis.

Classification of evidence: Can the level of NfL in CSF (the index test) predict unfavorable outcome in patients with bacterial meningitis, in a cohort of bacterial meningitis patients with a favorable and unfavorable outcome? This study provides Class II evidence that NfL level in CSF is a moderate predictor, with the AUC for predicting unfavorable outcome in bacterial meningitis being 0.69 (95% CI, 0.64-0.74).

Figure 1. Comparison of NfL Level (Median) in CSF Between Different Causative Pathogens

*Significant difference in NfL level between pneumococcal (N = 314) vs nonpneumococcal (N = 115) cases, after correction for age (respectively, 616 pg/mL [IQR 361–1,043 pg/mL] and 541 pg/mL [IQR 319–1,054 pg/mL], F[1,426] = 3.93, p = 0.048). **Significant difference in NfL level between Listeria monocytogenes (N = 21) vs non-Listeria (N = 408) cases, after correction for age (respectively, 1,049 pg/mL [IQR 741–2,219 pg/mL] and 572 pg/mL [IQR 342–1,007 pg/mL], F[1,426] = 6.29, p = 0.013). Haemophilus influenzae (N = 13) and Staphylococcus aureus (N = 11). Other pathogens: Streptococcus agalactiae (N = 7), Streptococcus pyogenes (N = 11), Streptococcus suis (N = 3), Streptococcus salivarius (N = 2), Streptococcus anginosus (N = 3), Streptococcus dysgalactiae (N = 1), Streptococcus intermedius (N = 2), Streptococcus oralis (N = 1), Escherichia coli (N = 2), Klebsiella pneumoniae (N = 1), Campylobacter fetus (N = 1), Nocardia farcinica (N = 1), Group C streptococcus not other specified (N = 1), viridans group streptococci not other specified (N = 1), and Fusobacterium necrophorum (N = 1). IQR = interquartile range; NfL = neurofilament light chain.

Figure 2. Comparison of NfL Level Between Total Cohort (N = 429) and Different Outcome Groups (Median, Interquartile Range)

NfL level in deceased (N = 62) vs alive (N = 367) patients (respectively, 1,152 pg/mL [IQR 594–2043 pg/mL] and 541 pg/mL [IQR 335–924 pg/mL]; p < 0.001). NfL level in patients with unfavorable (N = 157) vs favorable outcome (N = 272) (respectively, 928 pg/mL [IQR 494–1765 pg/mL] and 506 pg/mL [IQR 314–809 pg/mL); p < 0.001]. IQR = interquartile range; NfL = neurofilament light chain.