Contributions
Abstract: P1745
Type: Poster Sessions
Abstract Category: N/A
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. Here, a novel method to accurately capture upper cervical cord area from legacy brain MRI scans was utilised to longitudinally evaluate the utility of spinal cord atrophy as a surrogate marker for impending conversion to secondary progressive MS (SPMS).
Methods: In a single centre observational study, 57 of 507 RRMS subjects converted to SPMS during the 12-year observation period. We matched them, using demographic and clinical criteria, to 57 RRMS subjects who remained RRMS during the observation period. From brain MRI, we analysed brain measures and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched subgroups during the pre-conversion period.
Results: Subjects who developed SPMS showed accelerated spinal cord atrophy rates (-2·28 mm2/year, standard error (SE) 0·21) before conversion to a SP course compared to their RRMS matches (-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.
Conclusion: Upper cervical cord atrophy, as obtained from routine brain MRI, is a strong indicator of impending conversion to SPMS. As cervical atrophy likely reflects a generalised neurodegenerative process, it could be used to study the role of genetic, epidemiologic and immune variables on MS, and to measure the long-term impact of treatment in clinical trials.
Disclosure: AB reports travel fees from Actelion. RMB has received research support from the National Multiple Sclerosis Society, Hilton Foundation, California Initiative to Advance Precision Medicine, Doris Duke Award, Sherak Foundation, and Akili Interactive; and has received personal compensation for medical legal consulting and for consulting or serving on the advisory boards of F. Hoffmann-La Roche Ltd, Sanofi-Genzyme and Novartis. JMG is funded by NIH KL2TR000143. He has received compensation from Medimmune for consulting on a scientific advisory board; compensation from Quest Diagnostics for work developing a dementia care pathway; and compensation for medical-legal consulting. DSG has participated as principal investigator in several clinical trials in MS and has given many public lectures regarding the epidemiology of MS and/or its treatment. These clinical trials and many of these lectures have been sponsored by various pharmaceutical companies including Biogen Idec, Bayer Schering, Novartis, EMD Serono, Genzyme, and Teva pharmaceuticals. EW has not received any pharmaceutical company honorarium. She is site PI for Novartis and Roche multicentre trials. She volunteers on an advisory board for a Novartis trial. She is a non-remunerated advisor for clinical trial design to Novartis, Biogen-IDEC, Sanofi, Genentech, Serono, Celgene, Emerald Health Pharmaceuticals and DBV. She has funding from the NMSS, PCORI and the Race to Erase MS. She receives compensation as the section editor for Annals of Clinical and Translational Neurology, and co-Chief editor for MSARD. AJG reports personal fees from Inception Sciences and Mylan, Pharmaceuticals and grants/awards from the National Multiple Sclerosis Society, Novartis, UCSF CTSI, and That Man May See as well as philanthropic support from the Rachleff Family and the Robert Dale Family. He also reported serving on end point adjudication committees for Biogen and Medimmune. He serves on trial steering committees for Novartis and Scientific Advisory Board for Bionure.BACC has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, GeNeuro, Novartis and Sanofi Genzyme. SLH currently serves on the SAB of Symbiotix, Annexon, and Bionure. RGH has received grants from Stem Cells Inc, Hoffmann La Roche, and Sanofi Genzyme outside the submitted work, and advisory board honoraria from Abbvie, Roche, and Novartis. NP, AK, XZ, AR, SS, GK, TG, WAS, EC, CZ, YZ, YL, RG, NR, AS, AHZ, JJ, CJB and ElC: nothing to disclose.
Abstract: P1745
Type: Poster Sessions
Abstract Category: N/A
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. Here, a novel method to accurately capture upper cervical cord area from legacy brain MRI scans was utilised to longitudinally evaluate the utility of spinal cord atrophy as a surrogate marker for impending conversion to secondary progressive MS (SPMS).
Methods: In a single centre observational study, 57 of 507 RRMS subjects converted to SPMS during the 12-year observation period. We matched them, using demographic and clinical criteria, to 57 RRMS subjects who remained RRMS during the observation period. From brain MRI, we analysed brain measures and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched subgroups during the pre-conversion period.
Results: Subjects who developed SPMS showed accelerated spinal cord atrophy rates (-2·28 mm2/year, standard error (SE) 0·21) before conversion to a SP course compared to their RRMS matches (-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.
Conclusion: Upper cervical cord atrophy, as obtained from routine brain MRI, is a strong indicator of impending conversion to SPMS. As cervical atrophy likely reflects a generalised neurodegenerative process, it could be used to study the role of genetic, epidemiologic and immune variables on MS, and to measure the long-term impact of treatment in clinical trials.
Disclosure: AB reports travel fees from Actelion. RMB has received research support from the National Multiple Sclerosis Society, Hilton Foundation, California Initiative to Advance Precision Medicine, Doris Duke Award, Sherak Foundation, and Akili Interactive; and has received personal compensation for medical legal consulting and for consulting or serving on the advisory boards of F. Hoffmann-La Roche Ltd, Sanofi-Genzyme and Novartis. JMG is funded by NIH KL2TR000143. He has received compensation from Medimmune for consulting on a scientific advisory board; compensation from Quest Diagnostics for work developing a dementia care pathway; and compensation for medical-legal consulting. DSG has participated as principal investigator in several clinical trials in MS and has given many public lectures regarding the epidemiology of MS and/or its treatment. These clinical trials and many of these lectures have been sponsored by various pharmaceutical companies including Biogen Idec, Bayer Schering, Novartis, EMD Serono, Genzyme, and Teva pharmaceuticals. EW has not received any pharmaceutical company honorarium. She is site PI for Novartis and Roche multicentre trials. She volunteers on an advisory board for a Novartis trial. She is a non-remunerated advisor for clinical trial design to Novartis, Biogen-IDEC, Sanofi, Genentech, Serono, Celgene, Emerald Health Pharmaceuticals and DBV. She has funding from the NMSS, PCORI and the Race to Erase MS. She receives compensation as the section editor for Annals of Clinical and Translational Neurology, and co-Chief editor for MSARD. AJG reports personal fees from Inception Sciences and Mylan, Pharmaceuticals and grants/awards from the National Multiple Sclerosis Society, Novartis, UCSF CTSI, and That Man May See as well as philanthropic support from the Rachleff Family and the Robert Dale Family. He also reported serving on end point adjudication committees for Biogen and Medimmune. He serves on trial steering committees for Novartis and Scientific Advisory Board for Bionure.BACC has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, GeNeuro, Novartis and Sanofi Genzyme. SLH currently serves on the SAB of Symbiotix, Annexon, and Bionure. RGH has received grants from Stem Cells Inc, Hoffmann La Roche, and Sanofi Genzyme outside the submitted work, and advisory board honoraria from Abbvie, Roche, and Novartis. NP, AK, XZ, AR, SS, GK, TG, WAS, EC, CZ, YZ, YL, RG, NR, AS, AHZ, JJ, CJB and ElC: nothing to disclose.