Triggers, prodrome, aura, and headache interactions in migraine with typical aura: a prospective deep-phenotyping study

This study aimed to prospectively and comprehensively phenotype migraine with typical aura (MwA) attacks, with a particular focus on the interaction between trigger factors and clinical features of the prodrome, aura, and headache phases. A secondary aim was to examine how characteristics of individual phases influence the subsequent course of an attack and to provide data-driven hypotheses relevant for future MwA classification. This was a prospective, multicenter observational study conducted at two tertiary headache clinics. Participants recorded up to three MwA attacks over 12 months using an electronic questionnaire completed within one day after each attack. Data on potential triggers, prodromal symptoms, detailed aura features (visual, somatosensory, and higher cortical dysfunctions), and headache characteristics were collected. Associations between attack phases, including trigger factors, were analyzed. A total of 90 participants (74% female) reported 144 MwA attacks. Triggers were reported in 82% of attacks, with lack of sleep (36%) and the menstrual cycle (24%) being the most frequent. Prodromal symptoms occurred in 75% of attacks, most commonly neck stiffness (29%) and photophobia (28%). The number of triggers positively correlated with the number of prodromal symptoms (r=0.372, p<0.001). Visual aura occurred in 98% of attacks, with 43% showing sudden onset and 31% presenting as monocular visual disturbances. Somatosensory symptoms were reported in 50% of attacks, and dysphasic symptoms in 40%. The aura preceded headache in 81% of attacks. Severe headache intensity was reported in 62% of cases, while exhaustion occurred in 81%. The presence of tingling, numbness, and dyspraxia during the aura phase was significantly associated with the development of cutaneous allodynia. These findings suggest that MwA attacks represent a continuous and complex neurobiological process rather than a sequence of isolated phases, in which triggers and prodromal symptoms shape aura complexity, headache severity, and central sensitization. The frequent occurrence of atypical aura durations, sudden onset, and monocular-like visual disturbances in a prospective setting indicates that current MwA diagnostic frameworks may be overly restrictive. A more inclusive classification approach may be required to better capture the clinical heterogeneity of MwA and reduce underdiagnosis or misclassification.