Primary Lateral Sclerosis Natural History Study: Primary Lateral Sclerosis Functional Rating Scale and Other Outcomes...

Area of Science:

• Neurology
• Neurodegenerative Diseases
• Clinical Trials

Background:

• Primary Lateral Sclerosis (PLS) is a rare, slowly progressive motor neuron disease.
• Recent establishment of PLS diagnostic criteria and the PLSFRS aims to improve clinical trials.
• Understanding functional decline trajectory is crucial for PLS research.

Purpose of the Study:

• To evaluate the performance of the PLSFRS and other functional outcomes in a prospective PLS cohort.
• To examine the rate of functional decline in different stages of PLS.
• To identify potential biomarkers for PLS progression.

Main Methods:

• Prospective, longitudinal, multicenter PLS Natural History Study (PLS NHS) with 76 participants.
• Categorization into early, probable, and definite PLS based on disease duration.
• Collection of PLSFRS scores and functional measures at multiple time points over 12 months.
• Analysis using linear mixed-effect models and linear regression.

Main Results:

• The PLSFRS total score declined by 0.33 points/month in the overall cohort.
• Functional decline was steepest in the early PLS group, followed by probable and definite PLS.
• Higher baseline neurofilament light chain levels were associated with a faster rate of PLSFRS decline (p=0.001).

Conclusions:

• Functional decline in PLS, measured by PLSFRS, is more rapid in the early disease phase.
• Neurofilament light shows potential as a prognostic biomarker for PLS.
• Findings support the utility of PLSFRS in tracking disease progression in clinical trials.