Temporal Patterns of Serum Neuroprotectin D1 and Resolvin D1 After Motor and Nonmotor Epileptic Seizures: A Prospective Repeated-Measures Study

Objective: Neuroinflammatory activation is well recognized in epilepsy, whereas the temporal behavior of specialized pro-resolving mediator (SPM) responses after seizures remains poorly defined. We evaluated changes in serum neuroprotectin D1 (NP-1) and resolvin D1 (RvD1) between the early postictal period and a seizure-free period of at least 1 month and compared both time points with healthy controls. Methods: This prospective controlled repeated-measures study included 48 adults with epilepsy and 50 healthy controls. Blood was obtained within 3 h after a seizure and again after at least 1 month of seizure freedom; controls provided one sample. Serum NP-1 and resolvin D1 (RvD1) were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. The prespecified primary analysis compared paired postictal and seizure-free measurements using the Wilcoxon signed-rank test. Patient-control comparisons were considered secondary/exploratory. Results: Median NP-1 increased from 50.01 ng/mL (IQR 3.58–98.62) postictally to 67.78 ng/mL (59.81–121.81) during the seizure-free period (Z = −5.333, p < 0.001, r = 0.770). RvD1 did not change significantly (326.67 [207.77–899.95] vs. 441.47 [223.67–710.81] pg/mL; p = 0.139, r = 0.215). Both mediators were lower than controls postictally (both p < 0.001). During seizure freedom, NP-1 and RvD1 remained lower than controls (p = 0.008 and p < 0.001, respectively). The absolute percentage difference from the control median was greater for RvD1 than for NP-1 during seizure freedom (60.74% vs. 42.84%; p = 0.001, r = 0.462). Conclusions: The pro-resolving response in epilepsy appears temporally heterogeneous. NP-1 showed substantial within-patient recovery, whereas Resolvin D1 remained persistently reduced. These findings are hypothesis-generating and support larger serial-sampling studies with targeted lipidomic validation rather than establishing either mediator as a diagnostic biomarker.