Plasma Neurofilament Light Chain Is Associated with Poor Functional Outcome and Mortality Rate After Spontaneous Subarachnoid Hemorrhage

The initial clinical status after subarachnoid hemorrhage (SAH) is an important outcome predictor, but the mechanisms behind the early brain injury (EBI) remains incompletely understood. Elevated neurofilament levels in the cerebrospinal fluid at protracted stages after SAH are associated with poor outcome, but the potential association between plasma neurofilament (pNfL) levels during EBI, disease severity on admission, and poor outcome remains unaddressed. Plasma NfL (pNfL) was measured by single molecule array in 44 SAH patients on admission and 24 h after ictus, as well as in 44 controls. Disease severity on admission was assessed by validated scoring systems, and day 30 modified Rankin Scale (mRS) score was registered. Admission levels of pNfL correlated with clinical disease severity scores (rho = 0.43, p < 0.01 and rho = 0.48, p < 0.001) as well as day 30 mRS score (rho = 0.53, p < 0.001). Each quartile increase in pNfL was independently associated with poor functional status (mRS > 4) [odds ratio = 1.98, 95% confidence interval (CI): 1.01-3.88, p = 0.05]. Non-survivors had higher pNfL than survivors; on admission [17.6 pg/mL (IQR 11.4) vs. 8.4 pg/mL (IQR: 8.9), p < 0.01] and 24 h after ictus [29.9 pg/mL (IQR 90.4) vs 7.8 pg/mL (IQR 26.9), p = 0.01]. Each quartile increase in pNfL was independently associated with reduced survival rate [log-rank = 0.02, hazard ratio = 2.29 (95% CI): 1.15-4.57), p = 0.02]. PNfL levels are associated with disease severity during the EBI phase of SAH. Higher pNfL levels during EBI are associated with poor functional outcome on day 30 after ictus and increased mortality rate.