White matter changes in the trigeminal spinal tract in chronic migraineurs: an ex vivo study combining ultra-high field diffusion tensor imaging and polarized light imaging microscopy.

ABSTRACT: Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. The aim of this study was to test the hypothesis that white matter changes in the sp5 are a key feature of brain alterations in CM patients. We used diffusion Magnetic Resonance Imaging (dMRI) and polarized light imaging (PLI) of post mortem brainstem specimens from healthy controls (n = 5) and CM patients (n = 5) to study white matter alterations in the sp5. Within the sp5, dMRI metrics included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values. PLI was used to assess myelin density by measure of the retardance values in the sp5. The present study provides histological evidence that structural alterations occur in the sp5 in CM patients as compared to healthy controls. Myelin-density, as assessed by retardance values, showed to be higher and a corresponding increase in FA-values was observed. In addition, accompanying decreases in MD-, AD- and RD-values were observed. This study shows that the sp5 undergoes neuroplastic changes, a feature which substantiates evidence for the hyperactivity of the Sp5 in migraine patients. More insights are needed to observe whether these changes only occur in CM patients.