CGRP, SLEEP, AND CORTICAL EXCITABILITY IN MIGRAINE: A REAL-LIFE STUDY WITH SOUND-INDUCED FLASH ILLUSION IN PATIENTS TREATED WITH ANTIBODIES AGAINST CGRPr (ERENUMAB) OR CGRP (GALCANEZUMAB, FREMANEZUMAB)

Migraine is a highly prevalent and disabling neurological disorder characterized by cortical hyperexcitability and a strong bidirectional relationship with sleep disturbances. Calcitonin gene-related peptide (CGRP) is considered as key mediator in migraine pathophysiology, leading to the development of monoclonal antibodies targeting either the CGRP receptor (erenumab) or the CGRP ligand (galcanezumab and fremanezumab). Beyond their established efficacy in migraine prevention, their effects on sleep regulation and cortical excitability remain incompletely understood.The present real-life study investigated the relationship among migraine burden, sleep quality, and visual cortical excitability in patients treated with anti-CGRP monoclonal antibodies. Visual cortical excitability was assessed using the Sound-Induced Flash Illusion (SIFI), a validated non-invasive paradigm of multisensory perception known to reflect cortical excitability. Clinical efficacy was evaluated through Monthly Headache Days (MHD) and Migraine Disability Assessment (MIDAS), while sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Sleep Condition Indicator (SCI), Epworth Sleepiness Scale (ESS), sleep efficiency, and chronotype measures. Patients treated with erenumab, galcanezumab, or fremanezumab showed a significant reduction in migraine frequency and disability during follow-up, with no differences between the two groups.Neurophysiological analyses revealed a progressive normalization of SIFI responses, with an increase in illusion susceptibility. Improvements in sleep were observed across treatment groups, although differences between receptor-targeting and ligand-targeting antibodies were not significant. Concerning efficacy markers, our data indicate that the transition from extreme chronotypes to intermediate chronotypes, an index of better circadian regularity, is associated with a greater clinical response to erenumab.A particularly relevant finding was the significant association between improvements in sleep quality and changes in SIFI measures in patients receiving ligand-targeting antibodies (galcanezumab and fremanezumab), suggesting a common neurobiological mechanism linking CGRP, sleep regulation and cortical excitability. In conclusion, the present research suggests that anti-CGRP therapy acts at both the peripheral and central levels, fostering a progressive restoration of neurobiological stability in the migraine patient and outlining a new vision of migraine as a multisystem disorder in which pain, sleep, and sensory processes share a common peptidergic substrate.