Abstract Details

Title Age at Disease Onset Influences Gray Matter and White Matter Integrity in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 141

Objective To determine whether age at disease onset influences brain gray matter (GM) volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients.

Background Clinical phenotype and course of MS are age-dependent. Comparing pediatric- (POMS) vs adult-onset (AOMS) MS patients is a useful model for studying age effect on MS pathophysiology.

Design/Methods Sixty-seven POMS, 143 sex- and disease duration-matched AOMS patients and 208 age- and sex-matched healthy controls (HC) underwent neurological and 3T MRI examinations. MRI variables were standardized based on HC. Associations with disease duration in POMS and AOMS patients were studied with linear models, and validated on 38 younger- vs 67 later-onset (before/after age 25) MS patients and 101 HC. Time to reach clinical and MRI milestones was assessed with the product-limit approach.

Results At disease duration=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS. Significant interaction of age at onset (POMS vs AOMS) into the association with disease duration was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS was at 19 years of disease duration for GMV and 15 for WM FA. For POMS and AOMS, median disease duration was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 19 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.31).

Conclusions In POMS, WM integrity disruption precedes GM atrophy, being initially less severe than in AOMS. The rate of WM damage accumulation is higher in POMS compared to AOMS, resulting in worse WM damage with longer disease duration. Except for WM damage, POMS patients reach clinical and MRI milestones at younger age than AOMS, but take longer time.

Authors/Disclosures
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit) PRESENTER	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.
	No disclosure on file
Alessandro Meani	Alessandro Meani has nothing to disclose.
Elisabetta Pagani	Elisabetta Pagani has nothing to disclose.
	No disclosure on file
Andrea Falini	No disclosure on file
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.

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