Tear fluid CGRP changes in epilepsy – evidence from an exploratory pilot study

Background and Objectives Epilepsy and migraine share pathophysiological and clinical features. While calcitonin gene-related peptide (CGRP) is a central player in migraine pathophysiology, it has also been identified in cortical neurons, making CGRP a plausible modulator of cortical excitability. This exploratory trial aimed to investigate whether CGRP levels change following unprovoked seizures and whether they relate to seizure characteristics. Methods The single-center, prospective exploratory study was conducted at the epilepsy monitoring unit of LMU University Hospital Munich. Adults with active epilepsy undergoing video-EEG monitoring were included. Primary headache or postictal headache, arterial hypertension or intake of CGRP targeting medication were excluded. Tear fluid CGRP was collected at 3 standardized timepoints: interictal (≥ 48h seizure-and headache free), early postictal (≤ 1 hour after seizure onset), and late postictal (3 hours after seizure onset). CGRP concentrations were assessed by a-CGRP ELISA. Results 13 patients were included in the final analysis (6 female, 7 males; mean age 32 ± 8.5 years). Tear fluid CGRP levels differed significantly across the 3 timepoints (Friedman χ²(2) = 10.308, p = 0.006) with significantly elevated levels after seizure (4.1 ±1.2 ng/ml vs. 2.9 ± 1.5 ng/ml; Z = -2.433, p = 0.005). Subgroup analyses revealed no significant differences in postictal CGRP elevation between seizure characteristics or epileptogenic zones ( Z = -0.640, p = 0.52). Discussion Our findings demonstrate significant postictal CGRP elevation after seizure, providing preliminary evidence of seizure-associated trigeminovascular activation detectable via non-invasive assessment. These results suggest a potential implication of CGRP in ictogenesis.