Disability progression in multiple sclerosis is associated with plasma neuroactive steroid profile

Area of Science:

• Neuroendocrinology
• Neuroimmunology
• Clinical Neurology

Background:

• Neuroactive steroids (NASs) influence biological processes including inflammation.
• The role of NASs in multiple sclerosis (MS) progression remains unclear.
• Understanding NAS profiles during the transition from clinically isolated syndrome (CIS) to relapsing-remitting MS (RRMS) is crucial.

Purpose of the Study:

• To analyze and compare plasma NAS and amino acid (AA) concentrations in individuals with CIS, RRMS, and healthy controls (HCs).
• To investigate the relationship between NAS/AA profiles and disease progression, specifically disability worsening.
• To identify potential biomarkers for MS progression.

Main Methods:

• Recruitment of subjects with CIS, RRMS, and HCs.
• Collection of demographic, clinical data, and Expanded Disability Status Scale (EDSS) scores.
• Measurement of plasma NAS and AA concentrations using matched samples.

Main Results:

• RRMS patients showed higher allopregnanolone, aspartate, and taurine, and lower epiallopregnanolone compared to CIS patients.
• RRMS patients had higher L-serine-O-phosphate and lower alanine, arginine, and glutamine than HCs.
• Higher plasma tetrahydrodeoxycorticosterone (THDOC) concentrations were associated with disability worsening in CIS and RRMS groups.

Conclusions:

• Distinct plasma NAS and AA profiles differentiate CIS and RRMS patients.
• Tetrahydrodeoxycorticosterone (THDOC) and pregnanolone show potential as biomarkers for predicting disability worsening in MS.