Abstract Details

Title Cortical remyelination failure predicts cortical atrophy and clinical progression in early multiple sclerosis

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-008

Objective

To evaluate in-vivo cortical myelin loss and repair in all forms of MS using magnetization transfer imaging (MTI), that has been shown to be sensitive to myelin content changes in the cortex, and to investigate whether these processes predict cortical atrophy and clinical progression.

Background Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the contribution of these processes to neurodegeneration and their clinical relevance remain unknown

Design/Methods

140 patients with MS (37 clinically isolated syndromes, 71 relapsing-MS, 32 progressive-MS) and 84 healthy controls underwent an MRI protocol including MTI at baseline and after 1 year. In all patients, the Expanded disability status scale (EDSS) step-changes over 5 years were calculated. Cortical atrophy was computed with a Jacobian integration method. Magnetization transfer ratio was employed to generate patient-specific maps of myelin content and to extract the indices of cortical demyelination at baseline, dynamic demyelination and remyelination. Linear and logistic regressions were used to explore the association between these indices, cortical atrophy and clinical scores.

Results The indices cortical myelin content change were heterogeneous across-patients, with demyelination at baseline ranging from 0.4% to 23%, dynamic demyelination from 0.3% to 20%, and dynamic remyelination from 0.1% to 13% of cortical volume. Failure in cortical remyelination was associated with greater cortical atrophy at 1 year (β=0.19, p=0.024) and was associated with EDSS worsening in the subgroup of patients with a short disease duration (DD, <5 years) and with a limited amount of cortical demyelination at baseline (<8.5%). In this group, an increase of 30% in cortical remyelination reduced by 43.5% the risk of EDSS worsening at 5 years (OR=0.90, p=0.004).

Conclusions Cortical myelin repair prevents cortical atrophy and significantly reduces the risk of clinical progression in patients with a short DD and with a limited amount of cortical demyelination

Authors/Disclosures
Andrea Lazzarotto PRESENTER	Dr. Lazzarotto has nothing to disclose.
	No disclosure on file
	No disclosure on file
Vito A. Ricigliano (ICM)	Mr. Ricigliano has received personal compensation in the range of $500-$4,999 for serving as a Expert with M3 global research, Biogen and Atheneum Partners.
Giacomo Boffa (Department of Neuroscience, University of Genova)	Mr. Boffa has nothing to disclose.
Michael Khalil	Michael Khalil has nothing to disclose.
	No disclosure on file
	No disclosure on file
Christian Enzinger	Christian Enzinger has nothing to disclose.
	No disclosure on file
Maria Laura Stromillo, PhD (Policlinico Le Scotte)	Maria Laura Stromillo, PhD has nothing to disclose.
Nicola De Stefano, MD (University of Siena)	Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Healthcare KGaA. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharma AG. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Serono S.p.A. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. De Stefano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche S.p.A.. The institution of Dr. De Stefano has received research support from Italian MS Society. The institution of Dr. De Stefano has received research support from Merck Healthcare KGaA.
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.
Paolo Gallo, MD (Dompe' Biotec Italy)	Dr. Gallo has nothing to disclose.
Claudio Gasperini, MD	Dr. Gasperini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche, Merck, Genzyme, Novartis,Bayer, Teva, Almirall.
Bruno Stankoff, MD, PhD (Hopital De La Pitie Salpetriere)	The institution of Bruno Stankoff, MD, PhD has received research support from Roche, Sanofi, Serono . The institution of Bruno Stankoff, MD, PhD has received research support from Novartis.
Benedetta Bodini, MD	Dr. Bodini has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche . Dr. Bodini has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Bodini has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bodini has received research support from Biogen.

��ɫ��

��ɫ��