Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry.

Area of Science:

• Neuroscience
• Radiology
• Clinical Neurology

Background:

• Progressive gray matter (GM) atrophy is a key feature of multiple sclerosis (MS), often leading to cognitive impairment in 40%-70% of patients.
• Previous studies in relapsing-remitting MS (RRMS) suggested estriol treatment may preserve GM and improve cognitive function, as measured by the Paced Auditory Serial Addition Test (PASAT).

Purpose of the Study:

• To investigate the relationship between estriol-induced GM sparing and clinical outcomes in RRMS patients.
• To identify specific brain regions where GM sparing is associated with cognitive improvement.

Main Methods:

• Sixty-two estriol- and forty-nine placebo-treated RRMS patients underwent clinical assessments and brain MRI.
• Voxel-based morphometry (VBM) was employed to analyze voxelwise GM changes and identify treatment-induced sparing (TIS) regions.
• A cognitive disability-specific atlas (DSA) was created by correlating GM volumes with PASAT scores.

Main Results:

• A region of TIS was identified, primarily in the frontal and parietal cortices, and its volume directly correlated with PASAT improvement.
• Overlap analysis between TIS and the cognitive DSA revealed a specific region of cortical GM preservation associated with better PASAT performance.
• This region included the medial frontal cortex, known for its role in attention and problem-solving.

Conclusions:

• Localized GM sparing during estriol treatment in RRMS is associated with cognitive function improvement.
• The identified region of preserved GM may serve as a clinically relevant, disability-specific biomarker for neuroprotective treatments in MS clinical trials.