New spinal cord and infratentorial lesions in early relapse-onset MS are predictive of secondary progressive disease course after 15 years
ECTRIMS Online Library. Brownlee W. 10/26/17; 202456; 101
Wallace Brownlee
Wallace Brownlee
Contributions
Abstract

Abstract: 101

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background: Brain and spinal cord MRI abnormalities are helpful in making a diagnosis of multiple sclerosis (MS) in people with a clinically isolated syndrome (CIS). There has been little previous investigation of how early MRI abnormalities relate to long-term disease course in relapse-onset MS, particularly development of secondary progressive MS (SPMS).
Objective: To investigate the relationship of brain and spinal cord MRI abnormalities over the first 3 years after CIS with the development of SPMS.
Methods: We studied 164 CIS patients who had MRI scans of the brain and spinal cord at the time of presentation and after 1 year (n=136) and 3 years (n=121). MRI variables at baseline included supratentorial, infratentorial and spinal cord lesion number, gadolinium-enhancing (GdE) lesion number, normalised brain volume (NBV) and upper cervical cord cross-sectional area (UCCA). The number of new supratentorial, infratentorial, spinal cord and GdE lesions plus percentage brain volume change (PBVC) and change in UCCA after 1 and 3 years were also studied. We followed up patients prospectively over ~15 years. MS was diagnosed using the McDonald 2010 criteria and disease course classified as CIS, relapsing-remitting MS and SPMS. Multivariable binary logistic regression models were used to identify independent predictors of SPMS after 15 years using MRI data acquired over the first 3 years after CIS.
Results: Baseline spinal cord lesions (odds ratio [OR] 4.54, p< 0.01) and GdE lesions (OR 1.77, p=0.04) were associated with SPMS course at 15 years. After 1 year, baseline GdE lesions (OR 2.31, p=0.03) and new spinal (OR 5.72, p< 0.01) and infratentorial lesions (OR 7.02, p< 0.01) were associated with SPMS. At 3 years, new spinal cord lesions (OR 38.68, p< 0.01) and with borderline significance new infratentorial lesions (OR 3.28, p=0.08) were independently associated with SPMS. In patients with no new spinal or infratentorial lesions over the first 3 years after CIS the estimated risk of SPMS after 15 years was 0.9% (95%CI 0-2.6%), compared with 53.1% (95%CI 31.7-74.5%) in patients with new spinal and infratentorial lesions at 3 years.
Conclusion: The development of new spinal cord and infratentorial lesions may provide important prognostic information in patients with early relapse-onset MS. Accrual of new lesions over time in clinically-eloquent sites may represent one of the mechanisms contributing to secondary progressive disease course in relapse-onset MS.
Disclosure: W Brownlee is supported by the Neurological Foundation of New Zealand and the UK MS Society.
D Altmann has nothing to disclose.
K Miszkiel has nothing to disclose.
F Prados is supported by the Guarantors of Brain.
A Eshaghi has received ECTRIMS-MAGNIMS and MSIF McDonald Fellowships.
S Ourselin has nothing to disclose.
C Gandini Wheeler-Kingshott receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
F Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-Aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, Toshiba. He is on the editorial board of Radiology, Brain, Neuroradiology, MSJ, Neurology.
D Miller has received honoraria through payments to UCL Institute of Neurology for Advisory Committee and/or Consultancy advice in multiple sclerosis studies from Novartis and Mitsubishi Pharma Europe and compensation through payments to UCL Institute of Neurology for performing central MRI analysis of a multiple sclerosis trial from Novartis.
O Ciccarelli receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR UCLH Biomedical Research Centre; she is a consultant for Teva, Roche, Novartis, Biogen, Genzyme and GE. She is an Associate Editor for Neurology, for which she receives an honorarium.

Abstract: 101

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 21 Imaging

Background: Brain and spinal cord MRI abnormalities are helpful in making a diagnosis of multiple sclerosis (MS) in people with a clinically isolated syndrome (CIS). There has been little previous investigation of how early MRI abnormalities relate to long-term disease course in relapse-onset MS, particularly development of secondary progressive MS (SPMS).
Objective: To investigate the relationship of brain and spinal cord MRI abnormalities over the first 3 years after CIS with the development of SPMS.
Methods: We studied 164 CIS patients who had MRI scans of the brain and spinal cord at the time of presentation and after 1 year (n=136) and 3 years (n=121). MRI variables at baseline included supratentorial, infratentorial and spinal cord lesion number, gadolinium-enhancing (GdE) lesion number, normalised brain volume (NBV) and upper cervical cord cross-sectional area (UCCA). The number of new supratentorial, infratentorial, spinal cord and GdE lesions plus percentage brain volume change (PBVC) and change in UCCA after 1 and 3 years were also studied. We followed up patients prospectively over ~15 years. MS was diagnosed using the McDonald 2010 criteria and disease course classified as CIS, relapsing-remitting MS and SPMS. Multivariable binary logistic regression models were used to identify independent predictors of SPMS after 15 years using MRI data acquired over the first 3 years after CIS.
Results: Baseline spinal cord lesions (odds ratio [OR] 4.54, p< 0.01) and GdE lesions (OR 1.77, p=0.04) were associated with SPMS course at 15 years. After 1 year, baseline GdE lesions (OR 2.31, p=0.03) and new spinal (OR 5.72, p< 0.01) and infratentorial lesions (OR 7.02, p< 0.01) were associated with SPMS. At 3 years, new spinal cord lesions (OR 38.68, p< 0.01) and with borderline significance new infratentorial lesions (OR 3.28, p=0.08) were independently associated with SPMS. In patients with no new spinal or infratentorial lesions over the first 3 years after CIS the estimated risk of SPMS after 15 years was 0.9% (95%CI 0-2.6%), compared with 53.1% (95%CI 31.7-74.5%) in patients with new spinal and infratentorial lesions at 3 years.
Conclusion: The development of new spinal cord and infratentorial lesions may provide important prognostic information in patients with early relapse-onset MS. Accrual of new lesions over time in clinically-eloquent sites may represent one of the mechanisms contributing to secondary progressive disease course in relapse-onset MS.
Disclosure: W Brownlee is supported by the Neurological Foundation of New Zealand and the UK MS Society.
D Altmann has nothing to disclose.
K Miszkiel has nothing to disclose.
F Prados is supported by the Guarantors of Brain.
A Eshaghi has received ECTRIMS-MAGNIMS and MSIF McDonald Fellowships.
S Ourselin has nothing to disclose.
C Gandini Wheeler-Kingshott receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
F Barkhof acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme, and Sanofi-Aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis, Toshiba. He is on the editorial board of Radiology, Brain, Neuroradiology, MSJ, Neurology.
D Miller has received honoraria through payments to UCL Institute of Neurology for Advisory Committee and/or Consultancy advice in multiple sclerosis studies from Novartis and Mitsubishi Pharma Europe and compensation through payments to UCL Institute of Neurology for performing central MRI analysis of a multiple sclerosis trial from Novartis.
O Ciccarelli receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR UCLH Biomedical Research Centre; she is a consultant for Teva, Roche, Novartis, Biogen, Genzyme and GE. She is an Associate Editor for Neurology, for which she receives an honorarium.

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