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Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early

Damiano Marastoni1, Elisa Colato1,2,3, Matteo Foschi4,5

  • 1Neurology B, Department of Neurosciences, University of Verona, Italy.

Neurology(R) Neuroimmunology & Neuroinflammation
|May 1, 2025
PubMed
Abstract

Insights

Early multiple sclerosis patients with specific inflammatory markers in cerebrospinal fluid (CSF) and MRI findings indicating brain atrophy are at higher risk for progression independent of relapse activity (PIRA). This profile aids in predicting disease worsening at diagnosis.

Area of Science:

  • Neuroimmunology
  • Neurology
  • Radiology

Background:

  • Relapsing-remitting multiple sclerosis (RRMS) is characterized by unpredictable relapses and progressive disability.
  • Progression independent of relapse activity (PIRA) represents a significant challenge in managing MS, as it indicates disability accumulation unrelated to clinical relapses.
  • Identifying early predictors of PIRA is crucial for timely therapeutic intervention and personalized treatment strategies.

Purpose of the Study:

  • To identify a predictive profile for Progression Independent of Relapse Activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS) at the time of diagnosis.
  • To correlate cerebrospinal fluid (CSF) inflammatory markers and Magnetic Resonance Imaging (MRI) features with PIRA development.
  • To establish an early diagnostic tool for predicting long-term disability in RRMS patients.

Main Methods:

  • A five-year prospective study involving 80 treatment-naïve RRMS patients.
  • Collection of CSF for analysis of 68 inflammatory molecules, alongside regular neurological assessments (including EDSS) and annual 3T brain MRIs.
  • Definition of PIRA as confirmed disability progression independent of relapse activity.

Main Results:

  • 28.8% of RRMS patients developed PIRA within five years.
  • Older age and higher baseline EDSS scores were associated with PIRA.
  • Key CSF markers (e.g., sTNFR1, sTNFR2, LIGHT) and MRI findings (thalamus volume, middle frontal gyrus thickness, cortical lesion number) predicted PIRA development.

Conclusions:

  • A distinct intrathecal inflammatory profile, including TNF superfamily markers, combined with MRI-detected white matter lesions and gray matter atrophy, can predict PIRA in early MS.
  • These findings highlight the importance of assessing both inflammatory markers and structural brain changes at diagnosis.
  • The identified profile offers a potential tool for early risk stratification and personalized management of RRMS patients.

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