Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive...

Area of Science:

• Neuroimaging
• Neurology
• Multiple Sclerosis Research

Background:

• Spinal cord pathology in primary progressive multiple sclerosis (PPMS) significantly contributes to disability progression.
• Previous research indicated abnormal Q-space imaging (QSI) indices in the spinal cord of early PPMS patients, suggesting early neurodegeneration.

Purpose of the Study:

• To investigate the association between changes in spinal cord QSI over 3 years and disability progression in PPMS patients.
• To determine if baseline QSI metrics can predict clinical outcomes in PPMS.

Main Methods:

• Follow-up cervical cord 3T MRI and clinical assessments were conducted on 23 PPMS patients and 23 controls at 1 and 3 years.
• Spinal cord cross-sectional area (CSA) and QSI measures were analyzed alongside standard brain MRI.
• Mixed-effect models and linear regression were used to assess MRI changes, their association with clinical changes, and baseline predictors of disability.

Main Results:

• PPMS patients exhibited clinical deterioration and increased spinal cord QSI perpendicular diffusivity over time, associated with worsening disability.
• This increase in perpendicular diffusivity was independent of any decrease in spinal cord cross-sectional area (CSA).
• Higher baseline perpendicular diffusivity and lower baseline CSA were predictive of worse disability at the 3-year mark.

Conclusions:

• Elevated spinal cord perpendicular diffusivity over time suggests ongoing neurodegeneration in PPMS.
• This neurodegeneration, indicated by QSI changes, underlies disability progression in PPMS, irrespective of spinal cord atrophy.
• QSI metrics at baseline can serve as predictors for future disability progression in PPMS.