Longitudinal Neuroimaging over 30 Days: Temporal Characteristics of Migraine

Abstract

Objective Although migraine is defined by the headache and headache‐associated symptoms, the true beginning of a migraine attack lies in the premonitory phase. To understand the generation of attacks, one needs to investigate the phase before headache starts. The premonitory phase of migraine is characterized by a well‐described complex of symptoms. Its duration, however, is not clearly defined, and there are no biomarkers to help define when this phase starts. Methods Here, we used functional magnetic resonance imaging (MRI) to elucidate the duration of the premonitory phase in spontaneous human migraine attacks. Because migraine attacks are hardly predictable and thereby the premonitory phase is difficult to catch, we scanned 9 patients daily over a minimum period of 30 days using a well‐established paradigm for functional MRI of trigeminal nociception. Results Seven patients were included in the analysis, thus providing cumulative data of 27 spontaneous human migraine attacks including scans before, during, and after migraine pain as well as interictal scans. As a response to painful trigeminal stimulation, activation of the hypothalamus was present within the last 48 hours before headache onset but not earlier. Interpretation Using hypothalamic activation as a potential marker for the premonitory phase of migraine in this unique dataset, our data corroborated a duration of 48 hours for the premonitory phase of migraine. We suggest applying this time criterion in future studies when focusing on this phase of the migraine cycle. ANN NEUROL 2020;87:646–651

Cortical morphological changes in chronic migraine in a Taiwanese cohort: Surface- and voxel-based analyses

“…The dynamic alterations of functional connectivity between the hypothalamus and some specific nuclei within the brainstem (e.g. the dorsal pons, and the spinal trigeminal nucleus) have been shown to be responsible for the cyclic nature of migraine attacks (49,50). Also, the hyper-responsiveness to painful trigeminal stimulation in the anterior part of the hypothalamus is involved in migraine chronification (51).…”

“…Further studies using a longitudinal follow-up design are needed. Finally, given the inherent limitation, SBM is not capable of analyzing subcortical regions (46,47), including the hypothalamus and the brainstem, both of which have been recognized recently to play crucial roles in migraine pathogenesis (48)(49)(50)(51). The dynamic alterations of functional connectivity between the hypothalamus and some specific nuclei within the brainstem (e.g.…”

Migraine as a Cortical Brain Disorder

“…The timeline of the migraine attack documents the sequential development of 4 distinct clinical phases named prodrome, aura, headache, and postdrome. Research in migraine pathophysiology has been focused on the earliest attack’s stage, the premonitory phase, considered “the true beginning of a migraine attack,” as suggested also by recent fMRI evidence of an activation of the anterior‐lateral part of the hypothalamus during the 48 hours preceding pain onset in a longitudinal neuroimaging study with daily sessions over 3 days in 1 migraine patient, an important N = 1 study 22 …”

Are some patient-perceived migraine triggers simply early manifestations of the attack?

“…Recently, functional neuroimaging studies have suggested that there is early engagement of various brain areas during the premonitory phase; namely the hypothalamus, thalamus, limbic areas, sensory processing cortex and brainstem regions [18][19][20][21][22][23][24]. These areas functionally correlate with commonly reported symptoms during this time, such as thalamus and sensory cortices with photophobia, hypothalamus with homeostatic dysregulation and altered arousal and limbic areas with mood and cognitive change.…”