Abstract Details

Title Patterns of Grey Matter Atrophy in Patients with MS: A Multivariate Analysis Using Source-based Morphometry

Topic Multiple Sclerosis

Presentation(s) S45 - Multiple Sclerosis: Imaging (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Objective To characterize atrophy of grey matter (GM) patterns across different stages of multiple sclerosis (MS), and its evolution over 1-year follow-up.

Background GM involvement is crucial in MS. Source-based morphometry (SBM) is able to a multivariate GM decomposition into co-varying patterns of GM density.

Design/Methods

MRI and clinical evaluations were obtained at 8 European sites from 170 healthy controls (HC) and 398 MS patients (34 clinically isolated syndromes [CIS], 226 relapsing-remitting [RR], 95 secondary progressive [SP] and 43 primary progressive [PP] MS). Fifty-seven HC and 144 MS patients underwent 1-year follow-up. Baseline GM loss, longitudinal GM atrophy changes, and correlations with disability and 1-year clinical worsening were assessed.

Results SBM identified 26 relevant GM components, which were assigned to cerebellar, subcortical, sensorimotor, visual, temporal, default-mode, fronto-parietal, hippocampal, executive and salience networks. Compared to HC, MS patients showed significant GM atrophy in almost all components (p=range <0.001-0.04). CIS patients showed circumscribed GM atrophy in subcortical, cerebellar, temporal and salience components vs HC, while RRMS patients exhibited widespread GM atrophy involving most GM components. PPMS patients showed GM loss vs HC mainly located in cerebellar, subcortical, sensorimotor, salience and fronto-parietal regions. Such components showed additional GM atrophy in SPMS vs RRMS. At 1-year, 21 (15%) MS patients had clinically worsened. GM atrophy significantly progressed over time in MS patients in subcortical, cerebellar, sensorimotor, temporal and fronto-parietal regions. Baseline higher disability was associated (R²=0.65) with lower normalized brain volume (b=-0.13, p=0.001), higher sensorimotor GM loss (b=-0.12, p=0.002) and longer disease duration (b=0.09, p=0.04). Normalized GM volume (odds ratio=0.98, p=0.008) and cerebellar GM volume (odds ratio=0.40, p=0.01) were independent predictors of clinical worsening (area-under-the-curve=0.83).

Conclusions SBM highlighted a differential regional GM involvement across disease stages and significant atrophy progression at 1-year in MS patients. Sensorimotor and cerebellar GM atrophy were able to explain baseline disability and clinical worsening.

Authors/Disclosures
Maria A. Rocca (Neuroimaging Research Unit) PRESENTER	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.
Paola Valsasina	No disclosure on file
Alessandro Meani	No disclosure on file
Claudio Gobbi, MD (Ospedale Regionale Lugano)	The institution of Dr. Gobbi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Almirall, Biogen Idec, Celgene, Sanofi, Merck, Novartis, Teva Pharma, Roche.. Dr. Gobbi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie, Almirall, Biogen Idec, Celgene, Sanofi, Merck, Novartis, Teva Pharma, Roche..
Chiara C. Zecca, MD (Ente ospedaliero cantonale)	The institution of Dr. Zecca has received research support from Ente Ospedaliero Cantonale.
Alex Rovira	Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofy. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Alex Rovira has stock in Tensor Medical.
	No disclosure on file
Hugh Kearney, MD, PhD	Dr. Kearney has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
Olga Ciccarelli, MD, PhD, FRCP (UCL Institute of Neurology)	Prof. Ciccarelli has received personal compensation in the range of $0-$499 for serving as a Consultant for Lundebeck. Prof. Ciccarelli has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Ciccarelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Prof. Ciccarelli has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Prof. Ciccarelli 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 NEUROLOGY Journal.
	No disclosure on file
Jacqueline Palace (John Radcliff Hospital Oxford Univeristy Hospitals Trust)	Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono, Medimmune, Argenx, Janssen, AMgen, UCB, Roche, Novartis, Amplo, Alexion, . Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche, UCB, Alexion, Amgen. Dr. Palace has stock in Astra Zenica. The institution of Dr. Palace has received research support from Roche, AMPLO, Alexion, UCB,. argenx, amgen. Dr. Palace has received intellectual property interests from a discovery or technology relating to health care.
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.
Alvino Bisecco	Alvino Bisecco has nothing to disclose.
Carsten Lukas, MD (St Josef Hospital)	No disclosure on file
	No disclosure on file
Frederik Barkhof, MD, PhD (Image Analysis Center)	Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Frederik Barkhof has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Combinostics. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IXICO. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Frederik Barkhof has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI.
	No disclosure on file
Paolo Preziosa (Ospedale San Raffaele)	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.

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