Long-term evolution of white and gray matter structural properties in migraine

To elucidate the specific brain changes linked to clinical diagnoses and distinct temporal progression in migraine.

Gray (GM) and white matter (WM) differences were previously identified in chronic migraine (CM) compared to episodic migraine (EM). Regarding GM, patients with CM showed increased cortical thickness in the inferior temporal gyrus, and reduced surface area in the precuneus cortex, superior frontal and temporal gyri, and supramarginal gyrus. In the WM, widespread reduced axial and mean diffusivity have been observed in patients with CM in tracts such as the middle cerebellar peduncle, the internal capsule, the corticospinal tract, and the sagittal stratum. However, no longitudinal studies with a long follow-up have been conducted to comprehend how those differences evolve over an extended period, in relation to the clinical evolution of the disease.

A longitudinal study with a cohort design was conducted. Brain T1- and diffusion-weighted magnetic resonance imaging data were acquired in patients with migraine at two different timepoints, the first between May 2015 and July 2018, and the second between November 2021 and February 2022. Three WM descriptors and four GM morphometry parameters were extracted. Next, longitudinal changes were analyzed using generalized linear mixed models, after considering three different clinical groups: patients with a stable diagnosis (CM or EM) at both timepoints (24 CM, 31 EM), and 24 patients with CM who improved to EM.

Different patterns of structural longitudinal changes were found depending on the clinical evolution. Regarding GM, patients with stable EM showed a longitudinal cortical thickness increase in the parietal and temporal cortex (annual relative change between 0.38% and 0.52% in five regions, adjusted p between 0.013 and 0.017), and the postcentral gyrus (annual relative change of 0.37%, adjusted p = 0.014). Patients with stable CM and EM showed a longitudinal cortical thickness decrease in the posterior cingulate gyrus (annual relative change of 0.51%, adjusted p = 0.027, and 0.34%, adjusted-p = 0.019, respectively), and patients who improved from CM to EM showed no changes (corrected p > 0.05). Moreover, regarding WM, the patients with stable EM showed a longitudinal increase in fractional anisotropy in the cerebral peduncle (annual relative change of 0.24%, adjusted p = 0.014).

Differences in clinical evolution are linked to distinct patterns of structural changes, suggesting a heterogeneous impact of disease evolution on brain structure. Patients with CM who improved to EM showed no significant GM differences while those with longitudinally stable diagnoses showed cortical thickness maladaptation in pain processing-related regions and adaptation in other regions associated with migraine. Patients who improved from CM to EM showed an opposite longitudinal trend in large WM regions compared to stable patients, possibly as an adaptation to a distinct entity.