Serial CSF and serum IL-6 and neuron-specific enolase after aneurysmal subarachnoid hemorrhage: temporal profiles and association with discharge outcome

BACKGROUND: Inflammation and neuronal injury contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). We examined whether serial cerebrospinal fluid (CSF) and serum interleukin-6 (IL-6) and neuron-specific enolase (NSE) concentrations change over time after aSAH and whether these unadjusted biomarker patterns are associated with discharge outcome. METHODS: Seventy-five patients with aSAH underwent serial biomarker assessment across predefined hospital windows: days 1-3, 4-13, and 14-30. Outcomes were dichotomized by discharge modified Rankin Scale (mRS 1-3 vs 4-6). CSF/serum ratios were interpreted as compartmental gradients, not direct evidence of blood-brain barrier dysfunction. RESULTS: CSF IL-6 increased from 124.7 ± 57.5 pg/mL on days 1-3 to 464.2 ± 38.7 pg/mL on days 4-13 (p < 0.01). During days 4-13, CSF IL-6 was higher in patients with unfavorable versus favorable outcomes (671.0 ± 67.4 vs 347.8 ± 42.8 pg/mL; p < 0.01), whereas NSE was numerically higher but not statistically significant (21.3 ± 7.0 vs 10.0 ± 1.5 ng/mL; p = 0.15). Serum IL-6 was also higher in the unfavorable group (27.0 ± 9.6 vs 8.8 ± 1.3 pg/mL; p = 0.03). Two patients had intracranial nosocomial infections, both with unfavorable outcomes. CONCLUSIONS: CSF IL-6 showed the clearest temporal rise and strongest unadjusted association with unfavorable discharge outcome. NSE provided complementary neuronal-injury information but was less discriminatory. Findings should be interpreted cautiously because of the observational design, modest subgroup sizes, and heterogeneous CSF sampling route.