Accelerated Cord Atrophy Precedes Conversion to Secondary Progressive

Background • Understanding of progressive disease major challenge in multiple sclerosis (MS) research •

Study Design • Participants: – 54 RRMS patients who converted to SPMS during the

Spinal cord area measurement at C 1 level on T 1 -w brain images

Results: Baseline Characteristics Baseline Sex Age* Disease Duration** EDSS** MSSS** Conversion Age** Disease Duration**

Annualized cord atrophy rates discriminate between the matched groups pre-conversion RR RR group: -0.

Baseline Brain Volumes are lower in patients, but do not differentiate between the two

Conclusions • Cervical cord atrophy (C 1 level), obtained from routine brain MRI, is

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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

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.

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 C 1 level – Brain T 1, T 2 lesion load – Brain volumes: Global: - Whole brain - White matter - Gray matter - Ventricular Volume Regional: - Thalamus - Caudate nucleus - Putamen

Spinal cord area measurement at C 1 level on T 1 -w brain images

Results: Baseline Characteristics Baseline Sex Age* Disease Duration** EDSS** MSSS** Conversion Age** Disease Duration** Treatment† Level CTRL (n=54) RR RR ) n=54( RR SP )n=54( p F M (59) 32 (41) 22 (14) 44 (59) 32 (41) 22 49 (15· 3) (59) 32 (41) 22 47 (14· 5) 0· 191 - 10 (14· 3) (5· 1) 5· 1 (5· 2) 5· 1 12 (14· 0) 2· 5 (1· 5) (5· 3) 6· 2 0· 995 0· 0002 0· 002 F M - - 54 (12) (14) 52 0· 208 F M Naïve Low Intermediate High - 10 (19) (65) 35 (6) 3 (11) 6 19 (11) (9) 15 (9) 5 (65) 35 (7) 4 10 (19) 0· 096 0· 104 Differences were analysed using *Kruskal-Wallis, **Wilcoxon rank sum, or †Chi-square tests.

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 p<0. 0001* No effect of - Relapse rate - Disease duration - New/enlarging lesions - Disease-modifying treatments - Slowly enlarging lesions *using a mixed-effects model with adjustment for age and sex

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· 0001

Conclusions • Cervical cord atrophy (C 1 level), obtained from routine brain MRI, is a strong indicator of impending conversion to SPMS • Brain measures, including T 1 and T 2 lesion volumes, and regional and global brain volumes at baseline and over time do 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