Patterns of Longitudinal Regional Brain Atrophy in Patients With Different Progressive Supranuclear Palsy Clinical...

Area of Science:

• Neuroimaging
• Neurology
• Clinical Trials

Background:

• Progressive supranuclear palsy (PSP) involves progressive atrophy in brainstem, subcortical, and frontal regions.
• Distinct clinical variants of PSP include PSP-Richardson syndrome (PSP-RS), PSP-cortical, and PSP-subcortical.
• Longitudinal atrophy patterns and their utility as outcome measures in PSP variants are not well understood.

Purpose of the Study:

• To determine if regional atrophy rates differ across PSP clinical variants.
• To estimate sample sizes for clinical treatment trials using atrophy rates and clinical metrics.

Main Methods:

• Longitudinal 3T MRI scans from 2 annual visits were analyzed for 50 PSP-RS, 18 PSP-cortical, 20 PSP-subcortical patients, and 32 controls.
• Mixed-effects regression compared annualized atrophy rates in 10 regions of interest across groups.
• Sample size calculations were performed for treatment trials using atrophy rates and the PSP Rating Scale.

Main Results:

• All PSP variants showed greater atrophy in the midbrain, cerebellar dentate, and subthalamic nucleus compared to controls.
• PSP-RS exhibited greater midbrain atrophy rates than PSP-subcortical and PSP-cortical variants.
• PSP-cortical variants showed increased pallidum, putamen, and caudate atrophy compared to PSP-RS.
• PSP-RS and PSP-cortical groups had greater superior frontal and precentral atrophy than controls.

Conclusions:

• Distinct regional brain atrophy patterns characterize PSP clinical variants, though midbrain atrophy is a common feature.
• Combining the PSP Rating Scale with specific MRI volumetric data offers the most efficient outcome measure for PSP clinical trials.
• These findings aid in designing future therapeutic intervention studies for PSP.