It remains unclear whether high-frequency migraine is associated with objective markers of possible neuroaxonal injury and potential expression of neurodegenerative hallmarks. We compared serum and MRI biomarkers in high-frequency migraine versus healthy controls (HC) and tested whether baseline profiles predict 6-month response to erenumab. Adults with migraine (≥ 10 monthly headache days) and age- and sex-matched healthy controls (HC) were prospectively recruited at a tertiary center in Spain (2020–2021). Serum neurofilament light (sNf-L) was measured, and susceptibility-weighted MRI (SWI; iron-related signal) and diffusion MRI (fractional anisotropy, FA) were acquired within 7 days of blood sampling; headache status on the scan day was recorded via an eDiary. Migraine participants received erenumab 140 mg monthly for 24 weeks; response was defined as a ≥ 50% reduction in monthly headache days. Mixed-effects models adjusted for demographic and clinical covariates, with modality-wise FDR correction. We included 134 participants (68 migraine, 66 HC); median migraine duration was 25.0 years. sNf-L was higher in migraine (βSE = 0.1390.052; adj.P = 0.028). In the MRI subcohort (n = 102), left rostral ACC SWI signal was higher (0.8630.275; adj.P = 0.027) and right cuneus FA lower (− 0.2020.061; adj.P = 0.017). A multivariable model including clinical and biomarker variables identified depressive symptoms as the strongest predictor, while elevated sNf-L and reduced FA in the right cuneus remained independent biomarkers distinguishing migraine from HC (Accuracy 95% CI: 0.739 0.516–0.898). None of these biomarkers predicted erenumab response after 6 months. High-frequency migraine was associated with higher sNf-L and focal SWI/FA differences versus HC, consistent with possible neuroaxonal involvement, but these measures did not predict erenumab response at 6 months. EudraCT 2019-002224-32 (Registration Date: 2019-11-12).
Gallardo et al. (Thu,) studied this question.