White matter microstructural changes vary along the pain cycle in episodic menstrual migraine without aura

Abstract

Abstract Background: Migraine is a neurological disorder exhibiting a cyclic pattern of clinical manifestations. Although both structural and functional brain changes have been reported in comparison with healthy controls, it is not clear to what extent these vary across the migraine cycle. Here, we present a longitudinal study of menstrual migraine using diffusion MRI (dMRI) to investigate changes in white matter (WM) microstructure through the different phases of the pain cycle. Methods: Multi-shell dMRI data was acquired in 14 patients with low-frequency episodic menstrual migraine without aura, in the preictal, ictal, postictal and interictal phases, and 15 healthy controls in matching phases of the menstrual cycle. Following data pre-processing, maps of the diffusion parameters fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK) were obtained and compared across groups in each phase of the cycle. Subsequently, we conducted a region-of-interest analysis to determine whether changes in the diffusion parameters of specific WM tracts in patients, compared to controls, varied across different phases of the migraine cycle. Results: Patients showed a pronounced reduction in AD relative to controls across various brain regions, with weaker reductions also found in FA and MD, and increases found in MK and AK, mostly in the interictal but also in the ictal phases. Interestingly, AD and FA changes relative to controls varied across the migraine cycle in specific WM tracts. Specifically, the AD reduction observed interictally returned to baseline levels (comparable to those of the control group) during peri-ictal phases in the uncinate fasciculus, anterior corona radiata, posterior thalamic radiations, superior longitudinal fasciculus and cingulum tracts. In contrast, the body of the corpus callosum and posterior limb of the internal capsule tracts exhibited normal FA in the interictal phase, but this parameter decreased in the ictal phase. Conclusions: This is the first study documenting transient and fast variations in diffusion parameters of specific WM tracts across the migraine cycle. Microstructural changes in the brain of female migraine patients in different phases of the migraine cycle occur which cannot be explained by their hormonal status.