The Migraine Premonitory Phase

PURPOSE OF REVIEW The premonitory phase of migraine is defined as the presence of nonpainful symptomatology occurring hours to days before the onset of headache. Symptoms can include neck stiffness, yawning, thirst, and increased frequency of micturition. Clinical recognition of these symptoms is important to ensure early and effective attack management. Further understanding of the clinical phenotype and neurobiological mediation of these symptoms is important in the advancement of therapeutics research in both acute and preventive treatments of migraine.

RECENT FINDINGS Since 2014, functional imaging studies have been conducted during the premonitory stage of migraine and have provided novel insights into the early neurobiology and anatomy of the earliest stage of the migraine attack. These studies have shown early involvement of subcortical brain areas including the hypothalamus, substantia nigra, dorsal pons, and various limbic cortical areas, including the anterior cingulate cortex during the premonitory phase. More recent work has revealed altered hypothalamic-brainstem functional connectivity during migraine, which starts before the onset of pain. These exciting findings have provided functional correlation of the symptoms experienced by patients and changes seen on functional brain imaging.

SUMMARY This article focuses on the prevalence, phenotype, and proposed neurobiology of premonitory symptomatology in migraineurs as well as the scope of future research.

Address correspondence to Dr Peter J. Goadsby, National Institute for Health Research/Wellcome Trust Foundation Building, King’s College Hospital, London SE5 9PJ UK, [email protected].

RELATIONSHIP DISCLOSURE: Dr Karsan has received personal compensation for serving as a speaker for Teva Pharmaceutical Industries Ltd and has received research/grant funding from the Association of British Neurologists/Guarantors of Brain Clinical Research Training Fellowship. Dr Bose has received personal compensation as a speaker for Teva Pharmaceutical Industries Ltd and has received research/grant funding from The Migraine Trust Clinical Training Fellowship. Dr Goadsby has received personal compensation for consulting, speaking engagements, and serving on the scientific advisory boards of Alder BioPharmaceuticals, Inc; Allergan; Amgen Inc; Autonomic Technologies, Inc; Dr. Reddy’s Laboratories Ltd; ElectroCore, LLC; Eli Lilly and Company; eNeura Inc; Novartis AG; Scion Pharmaceuticals, Inc; Teva Pharmaceutical Industries Ltd; and Trigemina, Inc. Dr Goadsby has received personal compensation as an editor for MedicoLegal Investigations Ltd; NEJM Journal Watch; UpToDate, Inc; and Wolters Kluwer and receives royalties from Oxford University Press. Dr Goadsby has received grants from Amgen Inc and Eli Lilly and Company. Dr Goadsby holds a patent on magnetic stimulation for headache with eNeura Inc without fee.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Karsan, Bose, and Goadsby report no disclosures.

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