Multimodal convergence is needed before inferring neuroaxonal injury in migraine

Gallardo and colleagues reported higher serum neurofilament light (sNf-L), greater susceptibility-weighted imaging signal in the left rostral anterior cingulate cortex, and lower fractional anisotropy in the right cuneus in patients with high-frequency migraine. Their prospective phenotyping and multimodal approach are valuable. However, these modality-specific findings do not necessarily indicate a shared neuroaxonal-injury process. Serum Nf-L is anatomically non-specific, susceptibility-weighted signal is an indirect marker of iron-related changes, and fractional anisotropy reflects several aspects of tissue architecture. In addition, the imaging findings were focal, cross-modal associations were not reported, and the classification model had a small held-out test set with a wide confidence interval. We therefore suggest describing the results as independent candidate markers associated with high-frequency migraine. Evidence of multimodal convergence would require replicated cross-modal relationships or related longitudinal changes. This distinction preserves the value of the study while avoiding a mechanistic interpretation that extends beyond the available data.Clinical trial number Not applicable.