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Multimodal serum and MRI signatures of neuroaxonal injury in high-frequency migraine

Gallardo VJ, Caronna E, Rosell-Mirmi J, Asskour L, Pareto D, Torres-Ferrús M, Alpuente A, Giné-Ciprés E et al.

The journal of headache and pain, 2026

134 participants

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: We included 134 participants (68 migraine, 66 HC); median migraine duration was 25.0 years. sNf-L was higher in migraine (β[SE] = 0.139[0.052]; adj.P = 0.028). In the MRI subcohort (n = 102), left rostral ACC SWI signal was higher (0.863[0.275]; adj.P = 0.027) and right cuneus FA lower (- 0.202[0.061]; adj.P = 0.017). A multivariable model including clinical and biomarker variables identified depressive symptoms as the strongest predictor, while…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 134 participants or records.

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