Abstract Details

Title Gray Matter Damage Predicts Disability Worsening, Cognitive Decline, and Mortality in Multiple Sclerosis after 26 Years

Topic Multiple Sclerosis

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

Poster/Presentation
Number 19-002

Objective To evaluate whether baseline and 12-month changes in lesional, volumetric, and magnetization transfer (MT) MRI measures of white matter (WM) and gray matter (GM) damage predict long-term clinical outcomes in relapse-onset multiple sclerosis (MS).

Background GM damage is a critical determinant of disability and cognitive decline in MS, yet its long-term prognostic value remains unclear.

Design/Methods Seventy-three MS patients underwent 1.5T brain MRI scans at baseline and after 12 months. Baseline and 12-month changes of T2-hyperintense and T1-hypointense lesion volumes, fractions (F) of GM, WM and thalamus, and MT ratio (MTR) of WM lesions, GM, normal-appearing WM, and thalamus were measured. MS patients were prospectively followed for a median of 25.9 years (IQR=18.1;27.1). A neuropsychological assessment was also performed at follow-up when feasible. Stepwise multivariable logistic regressions identified predictors of Expanded Disability Status Scale (EDSS) score worsening, progression to a more severe disease stage, cognitive decline, and MS-related death.

Results At follow-up, 58 (79%) MS patients showed EDSS worsening, 46 (63%) progressed to a more severe disease stage, 18 (25%) died from MS, and 17/43 (40%) exhibited cognitive decline. Lower baseline GM fraction (odds ratio [OR]=0.58; p=0.002), greater 12-month GM MTR decline (OR=0.86; p=0.042), and treatment escalation (OR=6.46; p=0.040) independently predicted EDSS worsening (c-index=0.872). Higher 12-month EDSS score change (OR=6.73, p=0.028), higher 12-month T2-hyperintense WM lesion volume increase (OR=1.20, p=0.069), and lower baseline GMF (OR=0.84, p=0.084) (c-index=0.821) predicted disease phase progression. Higher baseline EDSS score (OR=1.68, p=0.015), lower baseline GMF (OR=0.74, p=0.046), and higher 12-month thalamic MTR percentage decrease (OR=0.92, p=0.049) predicted MS-related death (c-index=0.914). Older age (OR=1.23, p=0.013) and lower baseline GM MTR (OR=0.51, p=0.027) predicted cognitive deterioration (c-index=0.932).

Conclusions Atrophy and microstructural abnormalities of the GM predict long-term outcomes in MS. Their use may help identify high-risk patients, inform prognosis, and guide timely use of HE-DMTs.

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.
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.
Alessandro Meani	Alessandro Meani has nothing to disclose.
Nicolò Tedone (San Raffaele hospital)	Nicolò Tedone has nothing to disclose.
Irene Gattuso, MD	Dr. Gattuso has nothing to disclose.
Marco Rovaris	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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