Objective:

To determine whether status migrainosus (SM) is associated with transient, diffuse alterations in white matter microstructure that may underlie attack refractoriness and network instability.

Background:

Design/Methods:

This preplanned secondary analysis of a prospective within-subject MRI cohort included all participants (n=11) with ICHD-3 migraine who completed diffusion MRI during SM and at interictal baseline. Diffusion preprocessing and tract-based spatial statistics (TBSS) were performed in FSL. Fractional anisotropy maps defined the white matter skeleton onto which mean diffusivity (MD) maps were projected. The primary outcome, peak width of skeletonized mean diffusivity (PSMD), was calculated as the difference between the 95th and 5th percentiles of MD values within the skeleton. Linear mixed-effects models with random intercepts tested ictal–interictal differences, adjusted for age. Exploratory voxelwise analyses used single-tailed signed-rank tests (p<0.05).

Results:

Participants had a mean age of 47.6±17.2 years; nine (82%) were women, and all had chronic migraine. Median SM duration was 600 hours (IQR 264–936). PSMD values were higher during SM than at baseline. In adjusted models, right-hemispheric PSMD was significantly greater during SM (p=0.037), with a trend on the left (p=0.062). Voxelwise TBSS showed multifocal clusters of increased diffusivity across the subcortical white matter (corpus callosum, internal and external capsules, cingulum, longitudinal fasciculi, and corona radiata) extending into superficial white matter.

Conclusions:

SM is associated with diffuse, reversible increases in white matter diffusivity heterogeneity. Elevated PSMD, a validated marker of microvascular and microstructural disease burden, indicates that SM induces a transient, “disease-like” white matter state. These findings support a model of widespread but reversible white matter disruption consistent with transient brain-network instability.