Fluctuating Regional Brainstem Diffusion Imaging Measures of Microstructure across the Migraine Cycle

Abstract

The neural mechanisms responsible for the initiation and expression of migraines remain unknown. Although there is growing evidence of changes in brainstem anatomy and function between attacks, very little is known about brainstem function and structure in the period immediately prior to a migraine. The aim of this investigation is to use brainstem-specific analyses of diffusion weighted images to determine whether the brainstem pain processing regions display altered structure in individuals with migraine across the migraine cycle, and in particular immediately prior to a migraine. Diffusion tensor images (29 controls, 36 migraineurs) were used to assess brainstem anatomy in migraineurs compared with controls. We found that during the interictal phase, migraineurs displayed greater mean diffusivity (MD) in the region of the spinal trigeminal nucleus (SpV), dorsomedial pons (dmPons)/dorsolateral pons (dlPons), and midbrain periaqueductal gray matter (PAG)/cuneiform nucleus (CNF). Remarkably, the MD returned to controls levels during the 24-h period immediately prior to a migraine, only to increase again within the three following days. Additionally, fractional anisotropy (FA) was significantly elevated in the region of the medial lemniscus/ventral trigeminal thalamic tract in migraineurs compared with controls over the entire migraine cycle. These data show that regional brainstem anatomy changes over the migraine cycle, with specific anatomical changes occurring in the 24-h period prior to onset. These changes may contribute to the activation of the ascending trigeminal pathway by either an increase in basal traffic or by sensitizing the trigeminal nuclei to external triggers, with activation ultimately resulting in perception of head pain during a migraine attack.

Imaging the Premonitory Phase of Migraine

“…This study therefore suggests a pre-headache sensitivity to pain, or reduced threshold to pain, during the migraine attack (and therefore a susceptibility to exogenous triggers) and the subsequent implication of altered or dysfunctional endogenous pain modulation within the pain network in the brain during the migraine attack or cycle, which may be responsible for the sensation of pain felt following premonitory symptoms. The same authors have also recently demonstrated possible structural changes in similar brain areas (dorsolateral pons, periaqueductal gray, and spinal trigeminal nuclei) within 24 h of a migraine attack using mean diffusivity and fractional anisotropy (41).…”

Altered regional cerebral blood flow and hypothalamic connectivity immediately prior to a migraine headache

“…Local Institutional Human Research Ethics Committees approved the study, and we obtained informed written consent from each subject for all procedures according to the Declaration of Helsinki. Data from 28 of the 34 migraineurs and 12 of the control subjects were used in previous studies (10–12), as well as data from 23 of the 34 migraineurs and 12 of the control subjects in our previous study (9).…”

Microstructural changes in the trigeminal nerve of patients with episodic migraine assessed using magnetic resonance imaging

“…This study was approved by the Institutional Human Research Ethics Committee at the University of Sydney and informed written consent was obtained for all participants in accordance with the Declaration of Helsinki. Data from 30 of the 39 migraineurs were used in previous investigations [17][18][19][20].…”