Subclinical Cerebral Lesions in Migraine: A Proof‐of‐Concept Study on Platelet Aggregation

Background Migraine patients exhibit cerebral white matter lesions (WMLs) more frequently than the general population, with a potential micro‐ischemic origin. Although platelet function in migraine patients has been extensively studied, no previous research has evaluated platelet function in those with WMLs. Our aim was to assess platelet aggregation in migraine patients with WMLs, to investigate their potential correlation with ischemic pathophysiology. Methods We enrolled consecutive 34 patients diagnosed with episodic or chronic migraine, with or without aura (ICHD3 criteria), out of attacks, including 20 with WMLs and 14 without lesions. Patients on antiplatelet therapy, or those with inherited platelet disorders or thrombophilia, were excluded. All patients underwent MRI to identify and quantify WMLs in mm 3 . Platelet aggregation was assessed in response to various agonists (ADP, collagen, epinephrine, and arachidonic acid) and compared to a group of matched healthy volunteers (HV). Results Platelet aggregation in response to epinephrine was lower in migraine patients compared to HV. Among migraine patients, those with a lesion load ≥ 146.25 mm 3 (forth quartile of the WMLs total volume) showed significantly higher platelet aggregation in response to epinephrine (1.25 and 2.5 μM), compared to those with a lesion load < 146.25 mm 3 or no lesions ( p = 0.043 and p = 0.0047, respectively). Conclusions Migraine is associated with reduced platelet aggregation compared to HV, which may serve as a protective mechanism. However, in patients with a higher burden of WMLs, platelet aggregation levels were comparable to those of HV, raising the possibility of an ischemic contribution to WMLs in migraine patients.