BACKGROUND: Migraine is a phased neurological disorder progressing through prodrome, aura (in approximately one-third of patients), headache, and postdrome. Migraine with aura (MA) and migraine without aura (MO) are pathophysiologically distinct subtypes with potentially different treatment responses. Some acute therapies, including triptans, show reduced efficacy when administered during the aura phase. Whether this extends to neuromodulation remains unclear. This study examined whether the presence of migraine aura-a phase reflecting cortical spreading depolarization-modifies the therapeutic response to acute external trigeminal nerve stimulation (eTNS), using data from the TEAM (Trial of eTNS for the Acute Treatment of Migraine) study. METHODS: This was a post hoc, non-pre-specified analysis from a prospective, multicenter, randomized, double-blind, sham-controlled trial (N = 538). Participants were randomized 1:1 to verum (N = 259) or sham (N = 279) eTNS for 2 h during an active migraine. We compared treatment outcomes between MA (N = 224) and MO (N = 314) participants using logistic regression with interaction terms to test whether aura status modified treatment effect. Models were adjusted for age, sex, and baseline headache severity. RESULTS: The MA group had more male participants and higher rates of severe baseline headache pain compared to the MO group. No significant treatment-by-aura interactions were found for any endpoint, including 2-h pain freedom, most bothersome symptom resolution, 2-h pain relief, sustained outcomes at 24 h, or rescue medication use. Adjusted analyses confirmed these findings. The interaction for rescue medication use approached but did not reach significance (P = .054). CONCLUSIONS: No evidence of an interaction was found for the therapeutic effect of eTNS across MA and MO populations, suggesting that the aura phase does not diminish treatment efficacy. eTNS represents a viable non-pharmacological option for acute migraine management regardless of aura status. Future studies should investigate whether timing treatment to specific migraine phases-particularly the prodrome or early aura-can further optimize neuromodulation outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03465904. Registered 08 March 2018.
Johnson et al. (Wed,) studied this question.