Calcitonin gene-related peptide and migraine with aura: A systematic review

Background: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature on CGRP and MA. Methods: We performed a systematic literature search on MEDLINE for reports of CGRP and MA, covering basic science, animal and human studies as well as randomized clinical trials. Results: The literature search identified 594 citations, of which 38 contained relevant, original data. Plasma levels of CGRP in MA patients are comparable to MO, but CGRP levels varied among studies. A number of animal studies, including knock-ins of familial hemiplegic migraine (FHM) genes, have examined the relationship between CGRP and cortical spreading depression. In patients, CGRP does not trigger migraine in FHM, but is a robust trigger of migraine-like headache both in MA and MO patients. The treatment effect of CGRP antagonists are well proven in the treatment of migraine, but no studies have studied the effect specifically in MA patients. Conclusion: This systematic review indicates that the role of CGRP in MA is less studied than in MO. Further studies of the importance of CGRP for auras and migraine are needed.