Abstract Details

Title Disentangling Age-related and Disease-specific Upper Cervical Cord Atrophy in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S40 - Multiple Sclerosis: Clinical Trials/Science and Real-world Evidence (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Objective Spinal cord atrophy is a key predictor of clinical disability and disease progression in MS. The distinct contributions of physiological aging versus MS-related neurodegeneration remain poorly characterized.

Background To model aging trajectories of upper cervical cord atrophy in healthy controls (HC) and subsequently identify MS-specific patterns of spinal cord atrophy in a large multicenter cohort.

Design/Methods We analyzed 3D T1-weighted brain MRIs and clinical data from 480 HC and 1295 MS patients (ages:18–70). The mean upper cervical cord cross-sectional area (MUCCA) was measured between the C1 and C2/3 intervertebral disc using the active surface method and normalized for head size (nMUCCA). Aging trajectories of nMUCCA were modelled in HC using a polynomial regression model accounting for age, age², sex, scanner, and interaction terms, thereafter, applied to the MS cohort to quantify nMUCCA Z-scores, capturing disease-specific atrophy beyond normal aging. Analyses were stratified by sex and age at onset (pediatric-onset [POMS], adult-onset [AOMS], late onset [LOMS]).

Results In HC, nMUCCA showed a non-linear relationship with age, significantly declining after 50 years (p<0.008). In MS patients, nMUCCA Z-scores significantly decreased up to 50 years of age (p<0.001), with a rate gradually declining over decades. Sex did not significantly influence atrophy patterns in either HC or MS patients. POMS patients exhibited significantly lower Z-scores compared to AOMS and LOMS (p<0.001), although MS-driven decline with age did not differ among onset groups. Lower Z-scores were associated with longer disease duration and more severe disability (all p<0.001).

Conclusions In MS, upper cervical cord atrophy exceeds effects of normal aging, especially during midlife, and is significantly associated with longer disease duration and disability. Sex and age of disease onset do not influence patterns of MS-driven upper cervical cord atrophy with age. Spinal cord imaging holds promise as a sensitive biomarker for tracking MS progression beyond aging effects.

Authors/Disclosures
Paolo Preziosa (Ospedale San Raffaele) PRESENTER	Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Kshiteeja Jain, MD	Dr. Jain has received research support from Multiple Sclerosis International Federation - European Committee of Treatment and Research in Multiple Sclerosis (2022 MSIF-ECTRIMS McDonald Fellowship).
Loredana Storelli	Loredana Storelli has nothing to disclose.
Paola Valsasina	Paola Valsasina has nothing to disclose.
Alessandro Meani	Alessandro Meani has nothing to disclose.
Patrizia Pantano	Patrizia Pantano has nothing to disclose.
Claudia Piervincenzi (Sapienza University of Rome)	Claudia Piervincenzi has nothing to disclose.
Antonio Gallo	Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Antonio Gallo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis.
Alessandro d'Ambrosio	Alessandro d'Ambrosio has nothing to disclose.
Nicola De Stefano, MD (University of Siena)	Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Healthcare KGaA. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharma AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono S.p.A. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche S.p.A.. The institution of Dr. De Stefano has received research support from Italian MS Society. The institution of Dr. De Stefano has received research support from Merck Healthcare KGaA.
Rosa Cortese, MD, PhD	Dr. Cortese has nothing to disclose.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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