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Cervical Cord Atrophy as an Indicator of Conversion to Secondary Progressive Disease in Multiple Sclerosis

Study analyzes MRI measures in RRMS patients to predict conversion to SPMS. Cord atrophy rates differ in patient groups, brain volumes show no clear distinction. Cervical cord atrophy seen up to 4 years prior to conversion.

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Cervical Cord Atrophy as an Indicator of Conversion to Secondary Progressive Disease in Multiple Sclerosis

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  1. Accelerated Cord Atrophy Precedes Conversion to Secondary Progressive Disease in Relapsing Multiple Sclerosis Antje Bischof, MD Multiple Sclerosis Research Group University of California, San Francisco

  2. Background • Understanding of progressive disease major challenge in multiple sclerosis (MS) research • MRI measures might provide useful surrogates of disease progression and disability • Among all radiographic measures, spinal cord area shows the strongest correlations with MS disability and discriminates progressive from relapsing-remitting (RR) disease subtypes.

  3. Study Design • Participants: • 54 RRMS patients who converted to SPMS during the 12-year observation period (RRSP) • 54 matching RRMS patients (sex, age, disease duration, EDSS) who remained RRMS during the observation period (RRRR) • 54 age- and sex-matched healthy controls at study baseline (CTRL) • Main Outcomes Baseline and annual change during the pre-conversion period): • Spinal cord area at C1 level • Brain T1, T2 lesion load • Brain volumes: Global: Regional: • Whole brain - Thalamus • White matter - Caudate nucleus • Gray matter - Putamen • Ventricular Volume

  4. Spinal cord area measurement at C1 level on T1-w brain images

  5. Results: Baseline Characteristics Differences were analysed using *Kruskal-Wallis, **Wilcoxon rank sum, or †Chi-square tests.

  6. Annualized cord atrophy rates discriminate between the matched groups pre-conversion • RRRR group: -0.74%/year • RRSP group: -2.15%/year • Measureable up to 4 years before conversion to SPMS • No effect of • Relapse rate • Disease duration • New/enlarging lesions • Disease-modifying treatments • Slowly enlarging lesions p<0.0001* *using a mixed-effects model with adjustment for age and sex

  7. Baseline Brain Volumes are lower in patients, but do not differentiate between the two patient groups Based on least squares regression analyses, adjusted for age and sex * p≤ 0·05, ** p≤ 0·005, ** p≤ 0·0001

  8. Conclusions • Cervical cord atrophy (C1 level), obtained from routine brain MRI, is a strong indicator of impending conversion to SPMS • Brain measures, including T1 and T2 lesion volumes, and regional and global brain volumes at baseline and over timedo not discriminate course compared to those who did not • Could be useful • To study the role of genetic, epidemiologic and immune variables on MS • To measure the long-term impact of treatment in clinical trials • For early stratification of patients at risk for severe disability to guide individualized treatment decisions • Retrospective analysis of large number of legacy brain scans worldwide acquired in clinical trials and observational MS cohort studies

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