The PFOCUS Study aims to clarify the relationship between patent foramen ovale (PFO) and migraine with aura (MA). Patients diagnosed with MA according to ICHD-3 criteria will be classified as cases (PFO+) or controls (PFO-) based on the presence or absence of a right-to-left shunt detected by transcranial Doppler or a previously documented PFO. The study will enroll 240 adult participants over 36 months. The primary objective is to determine whether genetic variants differ significantly between patients with MA with and without PFO. Secondary objectives include assessing cerebral blood flow regulation and platelet function in patients with MA with and without PFO. Participants will undergo a single study visit including the collection of demographic and clinical data and a comprehensive neurosonological assessment. This will include microembolic signal counts, cerebrovascular reactivity testing, and a contrast-enhanced transcranial Doppler study for shunt detection. Blood samples will be collected for whole-exome sequencing (with a focus on NOTCH3 and an expanded gene panel) and for platelet aggregometry. The study is expected to provide new insights into the biological mechanisms linking PFO and MA-potentially involving endothelial dysfunction, altered vascular smooth muscle responses, or platelet activation-thereby informing prevention strategies and guiding future research.