Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

Area of Science:

• Neurology
• Clinical Neuroscience
• Tauopathies

Background:

• Progressive Supranuclear Palsy (PSP)-Richardson's Syndrome and Corticobasal Syndrome (CBS) are distinct clinical syndromes linked to 4R tau pathology.
• The PSP Rating Scale is a key tool in PSP clinical trials, with growing interest in combined trials for 4R tauopathies.

Purpose of the Study:

• To assess the contribution of each PSP Rating Scale domain to overall disease severity.
• To define the likely sequence of clinical progression in PSP compared to CBS.

Main Methods:

• Analysis of data from 545 PSP and 49 CBS patients from multicenter trials and natural history studies.
• Application of proportional odds models to the PSP Rating Scale to estimate impairment probabilities across domains based on overall severity.

Main Results:

• In PSP, Ocular Motor impairment typically appears earliest, followed by Gait/Midline and Daily Activities. Limb Motor, Mentation, and Bulbar domains manifest later.
• CBS shows Limb Motor impairment as the initial symptom, with ocular impairment being less probable throughout the disease course.
• An online tool was developed to visualize predicted disease progression and relative subscale disability.

Conclusions:

• The PSP Rating Scale is a valid measure for assessing disease severity in both PSP and CBS.
• Modeling the interrelationship of PSP Rating Scale domains at different disease severities can enhance the detection of therapeutic effects in clinical trials for 4R tauopathies.