Longitudinal changes in gray matter (GM) volume are distinct in individual migraine patients secondary to predisposing brain traits and experience-dependent responses, according to a new study published in Neurology.
“It is now clear that migraine is not simply a trigeminovascular disorder, but a more complex brain condition that involves multiple cortical, subcortical, and brainstem regions,” stated authors, led by Massimo Filippi, MD, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Findings from previous structural and functional studies have indicated that migraine patients sustain widespread alterations to pain and multisensory processing areas both during and outside the occurrence of migraine attacks. Whether such changes, however, signify a predisposing trait or a repercussion of migraine headaches remains to be elucidated.
On the basis of volumetric MRI techniques, various cross-sectional studies have demonstrated that the coexistence of regions of increased and decreased GM volume were not affected by clinical characteristics of migraine patients and could thus serve as a potential migraine biomarker.
Experts have posited that brain abnormalities evident in migraine patients might be dynamic, and vary by migraine phase, frequency of attacks, and disease duration.
One potential approach to analyzing the mechanisms mediating volumetric changes in migraine patients is longitudinal study. But to date, few such longitudinal studies have been performed, with short follow-up durations.
“In this exploratory study, we applied a voxel-wise longitudinal volumetric approach to map modifications of GM volume in a cohort of patients with episodic migraine over 4 years to identify those brain regions that are more susceptible to structural plasticity over the period,” stated the researchers.
Furthermore, the investigators determined the relevance of observed structural modifications with regard to migraine pathophysiology and phenotypic manifestations by assessing individual patient clinical characteristics and disease activity.
In the current study, the team performed T2-weighted and 3-dimensional T1-weighted brain scans at baseline on 73 right-handed subjects with episodic migraine and 46 age- and sex-matched right-handed, nonmigraine controls. The controls had no previous medical history of neurological disease or family history of migraine, as well as a neurological examination within normal limits.
After a mean follow-up of 4 years, 24 migraine patients and 25 controls volunteered to be reexamined. Principal baseline demographic, clinical, and MRI characteristics were the same between the initial sample and the sample tested during follow-up. The subjects assessed at follow-up, however, were younger than those tested at baseline.
The investigators divided migraine patients into subgroups based on aura, baseline disease duration (short: 16 years or less; long: greater than 16 years), baseline attack frequency (low: 4 or less attacks/month; high: more than 4 attacks/month), and disease progression (decreased or stable at follow-up or increased at follow-up).
After lowering the threshold for significance, researchers found that, at baseline, patients with migraine had increased GM volume of the right cingulum, superior temporal gyrus, superior and inferior frontal gyri, left middle temporal gyrus, and bilateral temporal pole compared with controls (uncorrected P < 0.001), and a reduced GM volume of the left anterior cerebellum. Migraineurs also had an increased GM volume of the right inferior parietal gyrus compared with controls, and those with worsening migraine had an increased GM volume of the left superior frontal gyrus.
Changes over time
The primary finding of this study was that GM volume changes of both the pain and visual processing brain areas in migraine patients are dynamic and remodeled over time, as mediated by clinical features of the individual patient.
“Whether such abnormalities represent a brain trait that predisposes to the development of migraine or a brain state secondary to the recurrence of migraine attacks is unclear,” the authors wrote.
The team found that migraine patients experienced both increases and decreases in GM volume at the level of the frontotemporal regions involved in nociception. They suggested that these changes could recapitulate a compensatory response in migraine patients with heightened disease activity at baseline, including longer disease duration and attack frequency. These alterations, however, could be maladaptive if they yield migraine worsening at follow-up.
The investigators also found that with regard to disease duration, frequency of attacks, and pain intensity, the level of disease severity can affect GM volume changes in visual areas. This notable finding ties the visual and trigeminal systems, and implicates visual cortex interplay in migraine attacks.
“Our results support the notion that the brain of predisposed migraine patients can be remodeled over time and different pathophysiologic mechanisms can occur in response to patients’ disease severity,” the researchers concluded. “In the future, a better understanding of neural plasticity and network remodeling in migraineurs may pave the way for novel therapeutic approaches.”