Abstract Details

Title Spinal Cord Lesions and Brain Grey Matter Atrophy Independently Predict Clinical Worsening in Multiple Sclerosis: A 5-Year, Multicentre Study

Topic Multiple Sclerosis

Presentation(s) P16 - Poster Session 16 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-004

Objective To evaluate the independent role of brain and cervical cord damage in predicting 5-year clinical disability worsening in a multicentre cohort of multiple sclerosis (MS) patients, recruited from 9 European sites.

Background In MS, the combined role of brain and spinal cord damage in predicting medium-term disease evolution still needs to be fully elucidated.

Design/Methods Baseline 3.0 T brain and cervical cord T2- and 3D T1-weighted MRI sequences were acquired in 367 MS patients (326 relapse-onset, 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (interquartile range=4.5-5.5). Generalized linear mixed models with L1-penalized variable selection identified the 5-year predictors of EDSS worsening, secondary progressive (SP) MS conversion in relapsing-remitting (RR) MS, and reaching EDSS=3.0, 4.0 and 6.0 milestones.

Results At follow-up, 120/367 (33%) MS patients worsened clinically; 36/256 (14%) RRMS patients evolved to SPMS. Predictors of EDSS worsening were progressive- vs relapse-onset MS (standardized beta [b]=0.97), baseline EDSS score (b=0.41), higher cord lesion number (b=0.41), lower normalized cortical volume (b=-0.15) and cord cross-sectional area (CSA) (b=-0.28) (C-index=0.81). Older age (b=0.86), higher EDSS score (b=1.40) and cord lesion number (b=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 at 5-years (C-index=0.88) were higher baseline EDSS score (b=1.49) and cord lesion number (b=1.02), and lower normalized cortical volume (b=-0.56). Baseline age (b=0.30), higher EDSS score (b=2.03) and cord lesion number (b=0.66), and lower cord CSA (b=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS score (b=1.87) and cord lesion number (b=0.54) predicted EDSS=6.0 (C-index=0.91).

Conclusions In MS patients, cortical atrophy and spinal cord lesions and cord atrophy independently predicted 5-year disability worsening, reaching of EDSS milestones and SPMS conversion. The combined assessment of brain and spinal cord damage may better identify MS patients who will have disease progression after 5 years.

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.
Paola Valsasina	Paola Valsasina has nothing to disclose.
Alessandro Meani	Alessandro Meani has nothing to disclose.
Claudio Gobbi, MD (Ospedale Regionale Lugano)	Dr. Gobbi has nothing to disclose.
Chiara Zecca, MD (Ente ospedaliero cantonale)	Prof. Zecca has nothing to disclose.
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
Eva Strijbis, MD, PhD (Amsterdam UMC)	Dr. Strijbis has nothing to disclose.
	No disclosure on file
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.
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
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.
Jaume Sastre-Garriga	The institution of Jaume Sastre-Garriga 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 Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Orchid Pharma. The institution of Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOGEN. Jaume Sastre-Garriga has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal. Jaume Sastre-Garriga has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Revista de Neurologia. The institution of Jaume Sastre-Garriga has received research support from Fondo de Investigación Sanitaria.
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 or had 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.
	No disclosure on file
Achim Gass, MD (U Hospital Mannheim, U of Heidelberg)	Dr. Gass has nothing to disclose.
	No disclosure on file
Carsten Lukas, MD (St Josef Hospital)	No disclosure on file
	No disclosure on file
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.
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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