Structural alterations of the brainstem in migraine

Abstract

Atypical brainstem modulation of pain might contribute to changes in sensory processing typical of migraine. The study objective was to investigate whether migraine is associated with brainstem structural alterations that correlate with this altered pain processing.MRI T1-weighted images of 55 migraine patients and 58 healthy controls were used to: (1) create deformable mesh models of the brainstem that allow for shape analyses; (2) calculate volumes of the midbrain, pons, medulla and the superior cerebellar peduncles; (3) interrogate correlations between regional brainstem volumes, cutaneous heat pain thresholds, and allodynia symptoms.Migraineurs had smaller midbrain volumes (healthy controls = 61.28 mm3, SD = 5.89; migraineurs = 58.80 mm3, SD = 6.64; p = 0.038), and significant (p < 0.05) inward deformations in the ventral midbrain and pons, and outward deformations in the lateral medulla and dorsolateral pons relative to healthy controls. Migraineurs had a negative correlation between ASC-12 allodynia symptom severity with midbrain volume (r = − 0.32; p = 0.019) and a positive correlation between cutaneous heat pain thresholds with medulla (r = 0.337; p = 0.012) and cerebellar peduncle volumes (r = 0.435; p = 0.001).Migraineurs with greater symptoms of allodynia have smaller midbrain volumes and migraineurs with lower heat pain thresholds have smaller medulla and cerebellar peduncles. The brainstem likely plays a role in altered sensory processing in migraine and brainstem structure might reflect severity of allodynia and hypersensitivity to pain in migraine.

Preventing Episodic Migraine With Caloric Vestibular Stimulation: A Randomized Controlled Trial

“…While the mechanism of action for CVS‐mediated migraine prevention remains unknown, we hypothesize that our effects are mediated by neuromodulation of relevant brainstem centers. While migraine is often associated with vascular flow abnormalities, neuroimaging studies provide evidence that migraine is a neurological disorder involving brainstem dysfunction . The time‐varying CVS waveforms used in this study (Fig.…”

“…First, while the precise pathology underlying migraine remains largely unknown and the neural circuits involved are widespread, results from a number of neuroimaging studies consistently suggest that migraine is a neurological disorder involving brainstem dysfunction. [9][10][11] This hypothesis is relevant because the brainstem is among the many neural regions activated by CVS, 12,13 a set of strong pathways corroborated by the wellestablished diagnostic sensitivity of CVS to brainstem dysfunction. Although neuroimaging data The mechanism of action of CVS and projections of the vestibular nuclei to brain regions implicated in migraine.…”

“…The potential for CVS to provide effective prophylaxis for episodic migraine is supported by several findings. First, while the precise pathology underlying migraine remains largely unknown and the neural circuits involved are widespread, results from a number of neuroimaging studies consistently suggest that migraine is a neurological disorder involving brainstem dysfunction . This hypothesis is relevant because the brainstem is among the many neural regions activated by CVS, a set of strong pathways corroborated by the well‐established diagnostic sensitivity of CVS to brainstem dysfunction.…”

Migraine Subclassification via a Data‐Driven Automated Approach Using Multimodality Factor Mixture Modeling of Brain Structure Measurements

“…Allodynia symptom severity was measured using the ASC‐12, a questionnaire that collects information about thermal, mechanical static, and mechanical dynamic allodynia . Several imaging studies have shown differences in brain structure and function that are associated with symptoms of allodynia during migraine attacks . Moulton and colleagues demonstrated that interictal migraineurs who reported symptoms of allodynia during migraine attacks had pain‐induced hypoactivation of the brainstem in the area of the nucleus cuneiformis compared to healthy controls, a finding that suggests inadequate pain inhibition leading to development of allodynia .…”

“…A resting state functional connectivity study demonstrated atypical functional connectivity of the periaqueductal gray and nucleus cuneiformis with other pain processing brain regions in migraineurs, the strength of which positively correlated with the severity of allodynia symptoms during migraine attacks . A study investigating brainstem structure demonstrated that migraineurs have smaller midbrain volumes compared to healthy controls and that there was a negative correlation between midbrain volume and severity of allodynia symptoms . In addition, allodynia has also been identified as a risk factor for developing more frequent migraines and for inadequate response to migraine treatment .…”