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Abstract Details

Accelerated Cord Atrophy Precedes Conversion to Secondary Progressive Disease in Relapsing Multiple Sclerosis
Multiple Sclerosis
S12 - Progressive Multiple Sclerosis (1:00 PM-1:11 PM)
001

A major challenge in multiple sclerosis (MS) research is the understanding of progressive disease. Magnetic resonance imaging (MRI) measures might provide useful surrogates of disease progression and disability. Among all radiographic measures, spinal cord area shows the strongest correlations with MS disability and discriminates progressive from relapsing-remitting (RR) disease subtypes.

To longitudinally evaluate the utility of spinal cord atrophy measured from brain scans as a surrogate marker for impending conversion to secondary progressive MS (SPMS), in addition to brain measures.

In a single center observational study, 57 of 507 RRMS subjects converted to SPMS during the 12-year observation period. Using demographic and clinical criteria, we matched them to 57 RRMS subjects who remained RRMS during the observation period. From brain MRI, we analyzed brain volumetrics and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched groups during the pre-conversion period.

Subjects who developed SPMS showed accelerated rates of spinal cord atrophy (-2.28 mm2/year, standard error (SE) 0.21) before conversion to a SP course compared to their RRMS matches who did not convert to SPMS (-0.74 mm2/year, SE 0.21, p<0.0001), with men demonstrating a more rapid decline. Our data suggest that this difference exists at least four years before conversion to SPMS. Measures of brain atrophy and white matter lesions did not discriminate between the groups.

Upper cervical cord atrophy, as obtained from routine T1-weighted brain MRI, is a strong indicator of impending conversion to SPMS. As cervical atrophy likely reflects neurodegenerative processes, it could be used to identify RRMS patients at risk for secondary progression, assess the role of genetic, epidemiologic and immune variables on MS, and measure the long-term impact of treatment in clinical trials.

Authors/Disclosures
Antje Bischof, MD
PRESENTER
Dr. Bischof has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
William Stern No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Refujia Gomez Refujia Gomez has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Carolyn J. Bevan, MD (Jesse Brown VAMC) Dr. Bevan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bevan has received intellectual property interests from a discovery or technology relating to health care.
Riley Bove, MD, FAAN (University of California, San Francisco) Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for NeurologyLive. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadenza. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. The institution of Dr. Bove has received research support from Eli Lilly.
Elizabeth Crabtree-Hartman, MD (Tulane University School of Medicine) Dr. Crabtree-Hartman has nothing to disclose.
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco) Dr. Gelfand has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities.
Douglas S. Goodin, MD (Univ of Calif at San Francisco) No disclosure on file
Jennifer Graves, MD, PhD (UCSD) Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Graves 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 MSJ. The institution of Dr. Graves has received research support from Octave. The institution of Dr. Graves has received research support from Sanofi. The institution of Dr. Graves has received research support from EMD Serono.
Jorge Oksenberg, MD (UCSF) No disclosure on file
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center) The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.
Michael R. Wilson, MD, FAAN (University of California San Francisco) Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.
Scott S. Zamvil, MD, PhD, FAAN (University of CA, San Francisco) Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Zamvil has received research support from Sumaira Foundation. Dr. Zamvil has received personal compensation in the range of $5,000-$9,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion.
Ari Green, MD (UCSF) Dr. Green has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pipeline Therapeutics. Dr. Green has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bionure. Dr. Green 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 JAMA Neurology. The institution of Dr. Green has received research support from NINDS. The institution of Dr. Green has received research support from NMSS. The institution of Dr. Green has received research support from NIA. The institution of Dr. Green has received research support from Adelson Research Foundation. Dr. Green has received intellectual property interests from a discovery or technology relating to health care. Dr. Green has received personal compensation in the range of $500-$4,999 for serving as a Study Section with NINDS. Dr. Green has a non-compensated relationship as a Author with Viela Bio that is relevant to AAN interests or activities.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center) The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences) Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
Roland G. Henry, PhD (University of California, San Francisco) Dr. Henry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDDAY. Dr. Henry 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. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi/Genzyme.