Neuroimaging phenotype characterization of early aggressive and late severe multiple sclerosis: a case-control study

Area of Science:

• Neurology
• Neuroimaging
• Multiple Sclerosis Research

Background:

• A subset of multiple sclerosis (MS) patients exhibits severe disease progression.
• Severe MS can manifest in two distinct temporal disability trajectories: early aggressive and late severe.
• Defining severe MS remains challenging, impacting treatment strategies and prognostication.

Purpose of the Study:

• To investigate and compare neuroimaging phenotypes between early aggressive MS and late severe MS.
• To identify specific MRI markers associated with disability progression in severe MS subtypes.
• To differentiate neuroimaging characteristics of severe MS from non-severe MS and healthy controls.

Main Methods:

• Retrospective analysis of the 16-year Biomarker Understanding for Future Findings and Advancements for Long-term Outcomes in Multiple Sclerosis (BUFALO-MS) database.
• Inclusion of 86 early aggressive MS, 368 late severe MS patients, and matched controls (non-aggressive MS, non-severe MS, and neurologically healthy individuals).
• Propensity score matching used for demographic and imaging protocol variables; comprehensive MRI analysis including lesion load and brain/spinal cord volumes.

Main Results:

• All MS patients showed worse MRI outcomes than healthy controls.
• Early aggressive MS was distinguished by higher T2 hyperintense lesion burden and thalamic atrophy.
• Late severe MS was characterized by spinal cord and cortical atrophy; disability correlated with spinal cord atrophy, cortical lesions, and thalamic atrophy.

Conclusions:

• Early and late severe MS share common grey matter pathology.
• Neuroimaging reveals distinct patterns: lesion burden, cortical, and thalamic changes in early aggressive MS.
• Spinal cord, cortical, and thalamic changes are critical in late severe MS, correlating with disability.