Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study

Migraine is underpinned by central nervous system neuroplastic alterations thought to be caused by the repetitive peripheral afferent barrage the brain receives during the headache phase (cortical hyperexcitability). Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) are highly effective migraine preventative treatments. Their ability to alter brain morphometry in treatment-responders vs. non-responders is not well understood. Our aim was to determine the effects of the anti-CGRP-mAb galcanezumab on cortical thickness after 3-month treatment of patients with high-frequency episodic or chronic migraine. High-resolution magnetic resonance imaging was performed pre- and post-treatment in 36 migraine patients. In this group, 19 patients were classified responders (≥50 % reduction in monthly migraine days) and 17 were considered non-responders (<50 % reduction in monthly migraine days). Following cross-sectional processing to analyze the baseline differences in cortical thickness, two-stage longitudinal processing and symmetrized percent change were conducted to investigate treatment-related brain changes. At baseline, no significant differences were found between the responders and non-responders. After 3-month treatment, decreased cortical thickness (compared to baseline) was observed in the responders in regions of the somatosensory cortex, anterior cingulate cortex, medial frontal cortex, superior frontal gyrus, and supramarginal gyrus. Non-responders demonstrated decreased cortical thickness in the left dorsomedial cortex and superior frontal gyrus. We interpret the cortical thinning seen in the responder group as suggesting that reduction in head pain could lead to changes in neural swelling and dendritic complexity and that such changes reflect the recovery process from maladaptive neural activity. This conclusion is further supported by our recent study showing that 3 months after treatment initiation, the incidence of premonitory symptoms and prodromes that are followed by headache decreases but not the incidence of the premonitory symptoms or prodromes themselves (that is, cortical thinning relates to reductions in the nociceptive signals in the responders). We speculate that a much longer recovery period is required to allow the brain to return to a more ‘normal’ functioning state whereby prodromes and premonitory symptoms no longer occur.