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Abstract

Objective:

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.

Background:

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.

Design/Methods:

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.

Results:

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.

Conclusions:

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.
Disclosure: Dr. Bischof has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Actelion. Dr. Papinutto has nothing to disclose. Dr. Keshavan has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Rajesh has nothing to disclose. Dr. Sacco has nothing to disclose. Dr. Kirkish has nothing to disclose. Dr. Gundel has nothing to disclose. Dr. Stern has nothing to disclose. Dr. Caverzasi has nothing to disclose. Dr. Zhao has nothing to disclose. Dr. Zhou has nothing to disclose. Dr. Lu has nothing to disclose. Dr. Gomez has nothing to disclose. Dr. Ragan has nothing to disclose. Dr. Santaniello has nothing to disclose. Dr. Zhu has nothing to disclose. Dr. Juwono has nothing to disclose. Dr. Bevan has nothing to disclose. Dr. Bove has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Genentech and Genzyme Sanofi. Dr. Bove has received research support from Akili Interactive. Dr. Crabtree-Hartman has received research support from has received educational grants from the MS Foundation, Teva neurosciences, Biogen, Genzyme, and Novartis. Dr. Gelfand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Medimmune, Quest Diagnostics, and government and commercial entities for medical legal consulting. Dr. Gelfand has received personal compensation in an editorial capacity for Dynamed. Dr. Gelfand has received research support from Genentech and MedDay. Dr. Goodin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Bayer Schering, Novartis, EMD Serono, Genzyme, and Teva Pharmaceuticals. Dr. Graves has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genentech, Inc. and S3 Group. Dr. Graves has received research support from Biogen and Genentech. Dr. Oksenberg has received research support from JRO has received research grant funding from Genentech. Dr. Waubant has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AAN for Frontiers in neurology talk, The Corpus for talks, compensation for editorial work for Annals of Clinical and Translational Neurology and MS and Related Disorders. Site PI for clinical trials with Roche, Biogen Idec and Novartis Dr. Wilson has received research support from Roche and Genentech. Dr. Zamvil has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Genzyme, Teva. Dr. Zamvil has received personal compensation in an editorial capacity for AAN. Dr. Zamvil has received research support from Biogen, Teva and Celgene. Dr. Green has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green has received personal compensation in an editorial capacity for Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen, and Novartis. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Annexon, Symbiotix, Bionure and Neurona; he has also received travel reimbursement from F. Hoffmann-La Roche Ltd and Novartis for CD20-related meetings and presentation. Dr. Henry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultancy from Novartis, Medday, Roche, Sanofi-Genzyme, Abbvie. Educational programs from Sanofi-Genzyme, TEVA. Dr. Henry has received research support from Research support from Sanofi-Genzyme, Roche/Genentech, Medday.

Information & Authors

Information

Published In

Neurology®
Volume 92Number 15_supplementApril 9, 2019

Publication History

Published online: April 9, 2019
Published in print: April 9, 2019

Authors

Affiliations & Disclosures

Antje Bischof
University of California, San Francisco San Francisco CA United States
Nico Papinutto
University of California, San Francisco San Francisco CA United States
Anisha Keshavan
University of California, San Francisco San Francisco CA United States
Xinheng Zhang
University of California, San Francisco San Francisco CA United States
Anand Rajesh
University of California, San Francisco San Francisco CA United States
Simone Sacco
University of California, San Francisco San Francisco CA United States
Gina Kirkish
University of California, San Francisco San Francisco CA United States
Tristan Gundel
University of California, San Francisco San Francisco CA United States
William Stern
University of California, San Francisco San Francisco CA United States
Eduardo Caverzasi
University of California, San Francisco San Francisco CA United States
Chao Zhao
University of California, San Francisco San Francisco CA United States
Yifan Zhou
University of California, San Francisco San Francisco CA United States
Ying Lu
Stanford University School of Medicine Stanford CA United States
Refujia Gomez
University of California, San Francisco San Francisco CA United States
Nicholas Ragan
University of California, San Francisco San Francisco CA United States
Adam Santaniello
University of California, San Francisco San Francisco CA United States
Alyssa Zhu
University of California, San Francisco San Francisco CA United States
Jeremy Juwono
University of California, San Francisco San Francisco CA United States
Carolyn Bevan
University of California, San Francisco San Francisco CA United States
Riley Bove
University of California, San Francisco San Francisco CA United States
Elizabeth Crabtree-Hartman
University of California, San Francisco San Francisco CA United States
Jeffrey Gelfand
University of California, San Francisco San Francisco CA United States
Douglas Goodin
University of California, San Francisco San Francisco CA United States
Jennifer Graves
University of California, San Francisco San Francisco CA United States
Jorge Oksenberg
University of California, San Francisco San Francisco CA United States
Emmanuelle Waubant
University of California, San Francisco San Francisco CA United States
Michael Wilson
University of California, San Francisco San Francisco CA United States
Scott Zamvil
University of California, San Francisco San Francisco CA United States
Ari Green
University of California, San Francisco San Francisco CA United States
Bruce Cree
University of California, San Francisco San Francisco CA United States
Stephen Hauser
University of California, San Francisco San Francisco CA United States
Roland Henry
University of California, San Francisco San Francisco CA United States

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