Abstract Details

Title MRI-derived Subtypes Identified by SuStaIn Capture Distinct Clinical, Cognitive, and Disability Profiles in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 19-004

Objective To apply Subtype and Stage Inference (SuStaIn) algorithm to identify MRI-based subtypes that better stratify the heterogeneous clinical profiles in multiple sclerosis (MS).

Background Clinical MS classifications incompletely capture disease heterogeneity. Data-driven subtyping may uncover endophenotypes that better reflect MS pathobiology and explain variability in disability and cognition.

Design/Methods We retrospectively studied 1017 MS patients and 548 healthy controls who underwent standardized clinical, neuropsychological, and brain 3T MRI assessments. Z-scores of 21 MRI features, including white matter (WM) lesion volume, microstructural abnormalities of the major WM tracts, and normalized global and regional brain volumes, were input into SuStaIn to derive subtypes and stages. Associations with clinical phenotype (relapsing-remitting [RR] vs progressive), age at onset (AAO) (pediatric [POMS], adult [AOMS], late [LOMS]), disability (Expanded Disability Status Scale [EDSS]), and cognition (Brief Repeatable Battery of Neuropsychological Tests) were explored.

Results SuStaIn identified four MRI subtypes: lesion-led (44%), cortex-led (23%), tract-led (23%), and deepGM-led (10%). Subtypes differed by clinical phenotype and AAO (p<0.001). Cortex-led and deepGM-led were enriched in progressive forms (47% and 56%), whereas lesion-led and tract-led were mainly RRMS (66–71%). By AAO, tract-led was overrepresented in POMS (70/184, 38%) and underrepresented in AOMS (152/783, 19%), lesion-led predominated in AOMS (372/783, 48%), whereas deepGM-led was more frequent in LOMS (7/50, 14%). Disability milestones were reached more often in cortex-led and deepGM-led patients (EDSS≥4.0: 45% and 56%; EDSS≥6.0: 28% and 29%) than in lesion-led (34% and 20%) or tract-led (32% and 19%) (p<0.001). Although cognitive performance did not differ across subtypes (p≥0.513), within each subtype advancing SuStaIn stage was consistently associated with worsening global and domain-specific scores (p≤0.030).

Conclusions MRI-based subtypes from SuStaIn capture clinically meaningful heterogeneity in phenotype, age at onset, disability, and cognition. This data-driven approach may support personalized therapeutic strategies tailored to the pathological mechanisms underlying MS progression.

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.
Loredana Storelli	Loredana Storelli has nothing to disclose.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
Nicolò Tedone (San Raffaele hospital)	Nicolò Tedone has nothing to disclose.
Monica Margoni	Monica Margoni has received research support from MAGNIMS. Monica Margoni has received research support from Merck-Serono. Monica Margoni has received research support from Sanofi-Genzyme.
Federica Esposito	Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Federica Esposito has received research support from Italian MS Society. The institution of Federica Esposito has received research support from Italian Ministry of Health. The institution of Federica Esposito has received research support from ERA Net. The institution of Federica Esposito has received research support from European Commission. Federica Esposito has received intellectual property interests from a discovery or technology relating to health care.
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.
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.

��ɫ��

��ɫ��