Longitudinal assessment of white matter alterations in progressive supranuclear palsy variants using diffusion tractography

Introduction: White matter (WM) tract degeneration is a characteristic feature of progressive supranuclear palsy (PSP), with longitudinal changes observed in PSP-Richardson's syndrome (PSP-RS). Little, however, is known about the other PSP variants. We assessed cross-sectional and longitudinal WM degeneration across PSP variants using diffusion tractography. Methods: Forty-eight PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two diffusion MRI, 1-year apart. We measured fractional anisotropy and mean diffusivity from eight WM tracts reconstructed using deterministic tractography. Baseline and rates of change were compared across PSP variants grouped into PSP-RS, PSP-cortical, and PSP-subcortical, and correlated with clinical disease severity. Results: PSP-RS, PSP-cortical and PSP-subcortical showed overlapping but distinct baseline patterns of WM alterations. Longitudinally, faster rates of degeneration were observed in the superior cerebellar peduncle (SCP) and dentatorubrothalamic tract (DRTT) in all groups compared to controls. In PSP-RS, the anterior thalamic radiation also showed faster rates of degeneration compared to controls. PSP-cortical had faster rates of degeneration in many WM tracts compared to controls and other PSP groups, including body of corpus callosum, superior thalamic radiation, superior corticostriatal tract, superior longitudinal fasciculus, and frontal aslant tract. Progression in the PSP-subcortical group was limited to SCP and DRTT. Greater rates of degeneration in the corpus callosum and SCP correlated with worsening disease severity. Conclusions: Different progression patterns of WM degeneration characterize the PSP variants, although degeneration of the SCP is a common feature and could be a useful potential biomarker for clinical treatment trials in PSP.