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Background <p>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.</p> Methods <p>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&#xa0;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.</p> Results <p>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.<i>P</i> = 0.028). In the MRI subcohort (<i>n</i> = 102), left rostral ACC SWI signal was higher (0.863[0.275]; adj.<i>P</i> = 0.027) and right cuneus FA lower (− 0.202[0.061]; adj.<i>P</i> = 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.</p> Conclusions <p>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.</p> Trial registration <p>EudraCT 2019-002224-32 (Registration Date: 2019-11-12).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月14日

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  • Víctor J. Gallardo,
  • Edoardo Caronna,
  • Joana Rosell-Mirmi,
  • Laila Asskour,
  • Deborah Pareto,
  • Marta Torres-Ferrús,
  • Alicia Alpuente,
  • Eulàlia Giné-Ciprés,
  • Nara Ikumi,
  • Àlex Rovira,
  • Patricia Pozo-Rosich

摘要

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 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.

Conclusions

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.

Trial registration

EudraCT 2019-002224-32 (Registration Date: 2019-11-12).