Neurologic Symptoms and Cerebrovascular Events During Atogepant Therapy: A Case Series with Contextual Comparison with a Non-Gepant–Treated Migraine Cohort

<b>Background:</b> CGRP contributes to cerebrovascular regulation, mainly based on experimental and translational data; human evidence remains limited. Gepants, including atogepant, are effective migraine preventives and achieve partial penetration across the blood-brain barrier. However, their neurologic and cerebrovascular safety in heterogeneous patient populations remains incompletely characterized. <b>Objective:</b> To describe acute neurologic events observed during atogepant therapy, provide contextual information regarding their baseline occurrence, and explore potential mechanisms by which CGRP receptor blockade may influence neurovascular resilience. <b>Methods:</b> We report five adults treated with atogepant (30-60 mg/day) who developed acute neurologic symptoms prompting emergency hospital admission. All patients underwent comprehensive diagnostic assessment including neuroimaging, vascular studies, cardiac evaluation, and laboratory testing. To provide context, a retrospective comparison cohort of migraine patients not treated with gepants during a similar period was analyzed. Baseline characteristics were summarized, and event occurrence was compared using Fisher's exact test. <b>Results:</b> Among 575 individuals treated with atogepant, five experienced acute neurologic events, including one cerebellar infarction and several transient focal syndromes without structural correlates. No cerebrovascular events requiring hospitalization were identified in the non-gepant cohort (<i>n</i> = 610). In an unadjusted analysis, this difference was statistically significant (<i>p</i> = 0.027). The events were clinically heterogeneous, and several lacked radiologic confirmation of ischemia. Conventional vascular risk factors were present in some patients. <b>Conclusions:</b> These findings do not imply causality but raise the possibility that CGRP receptor blockade may reduce cerebrovascular adaptability in susceptible individuals. Clinicians should remain vigilant for ischemia or microvascular dysfunction when patients receiving atogepant present with acute vertigo, diplopia, ptosis, or hemisensory symptoms-even when CT and CTA are normal-and obtain timely MRI and vascular assessment. The absence of comparable events in a retrospective non-gepant cohort provides contextual information but does not permit inference regarding increased risk due to potential confounding and unmeasured factors. The findings are exploratory and hypothesis-generating, underscoring the need for prospective controlled studies to clarify the cerebrovascular safety of CGRP receptor antagonists in routine clinical practice.