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Review
. 2020 Mar;16(3):171-182.
doi: 10.1038/s41582-020-0314-x. Epub 2020 Feb 24.

MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice

Jaume Sastre-Garriga  1 , Deborah Pareto  2 , Marco Battaglini  3 , Maria A Rocca  4 , Olga Ciccarelli  5   6 , Christian Enzinger  7 , Jens Wuerfel  8 , Maria P Sormani  9   10 , Frederik Barkhof  6   11   12 , Tarek A Yousry  5   13 , Nicola De Stefano  3 , Mar Tintoré  14 , Massimo Filippi  4   15 , Claudio Gasperini  16 , Ludwig Kappos  17 , Jordi Río  14 , Jette Frederiksen  18 , Jackie Palace  19 , Hugo Vrenken  11 , Xavier Montalban  14   20 , Àlex Rovira  21 ; MAGNIMS study group
Affiliations
Review

MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice

Jaume Sastre-Garriga et al. Nat Rev Neurol. 2020 Mar.

Abstract

Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.

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Conflict of interest statement

J.S.-G. declares grants and personal fees from Genzyme, personal fees from Almirall, Biogen, Celgene, Merck, Novartis, Roche and Teva and is a member of the Editorial Committee of Multiple Sclerosis Journal and Director of the Scientific Committee of Revista de Neurologia, all unrelated to this Consensus Statement. D.P. declares personal fees from Novartis and Sanofi-Genzyme, unrelated to this Consensus Statement. M.A.R. declares personal fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis and Teva, all unrelated to this Consensus Statement. O.C. declares grants from the Spinal Cord Research Foundation, the Rosetree Trust, the Progressive MS Alliance, Bioclinica, GE Neuro, EU-H2020, the UK MS Society, the National MS Society, and the National Institute for Health Research Biomedical Research Centre, University College London Hospitals, and declares personal fees from Merck, Neurology, Novartis, Roche and Teva, all unrelated to this Consensus Statement. O.C. also declares grants from the UK MS Society, the National Institute for Health Research Biomedical Research Centre, University College London Hospitals, and the National MS Society during the course of this Consensus Statement. C.E. declares personal fees from Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Sanofi-Aventis, Shire and Teva, all unrelated to this Consensus Statement. J.W. declares employment with Medical Image Analysis Center, scientific advisory board membership for Biogen, Genzyme, Novartis, TEVA and Roche, personal fees from Bayer, Novartis and Roche, and grants from the European Union (Horizon2020), German Federal Ministries of Education and Research (BMBF), and Economic Affairs and Energy (BMWI), all unrelated to this Consensus Statement. M.P.S. declares personal fees from Actelion, Biogen, Genzyme, Merck, Novartis, Roche, Serono, Synthon and Teva, all unrelated to this Consensus Statement. F.B. acts as a consultant for Apitope, Bayer-Schering, Biogen-Idec, GeNeuro, Sanofi-Genzyme, Ixico, Janssen Research, Merck-Serono, Novartis, Roche and TEVA. He has received grants, or grants are pending, from the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) initiative, the Biomedical Research Centre at University College London Hospitals, the Dutch MS Society, ECTRIMS–MAGNIMS, EU-H2020, the Dutch Research Council (NWO), the UK MS Society, and the National Institute for Health Research, University College London. He has received payments for the development of educational presentations from Ixico and to his institution from Biogen-Idec. He is on the editorial board of Radiology, Brain, European Radiology, Multiple Sclerosis Journal and Neurology. T.A.Y. declares research support from Biogen, GlaxoSmithKline, Novartis and Schering, and honoraria from Bayer Schering, Biogen, Hikma and Novartis. N.D.S. declares personal fees from Biogen-Idec, Celgene, Sanofi-Genzyme, Merck Serono, Novartis, Roche and Teva, grants from Merck Serono, Novartis and the Italian MS Society, and nonfinancial support from Biogen-Idec, Sanofi-Genzyme, Merck Serono, Novartis, Roche and Teva, all unrelated to this Consensus Statement. M.T. declares personal fees from Almirall, Bayer Healthcare, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva, grants from Sanofi-Genzyme, and other competing interests related to Biogen Idec, all unrelated to this Consensus Statement. M.F. declares personal fees from Biogen Idec, Merck-Serono, Novartis and Teva, and grants from Biogen Idec, Merck-Serono, Novartis, Roche and Teva, all unrelated to this Consensus Statement. He is the Editor-in-Chief of the Journal of Neurology. C.G. declares advisory board membership for Biogen, Genzyme, Merck-Serono, Roche and Teva, and honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva. L.K. declares competing interests related to Actelion, Almirall, Alkermes, Bayer, Biogen, df-mp, The European Union, Excemed, GeNeuro, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Neurostatus, Novartis, Receptos–Celgene, Roche, Roche Research Foundations, Sanofi-Aventis, Santhera, the Swiss Multiple Sclerosis Society, Swiss National Research Foundation, Teva and Vianex, all unrelated to this Consensus Statement. J.R. declares personal fees from Biogen, Merck, Novartis and Roche, and other competing interests related to Merck and Mylan, all unrelated to this Consensus Statement. J.F. declares personal fees from Biogen Idec, Merck Serono and Sanofi-Aventis, participation in scientific advisory boards for Almiral, Genzyme and Novartis, personal fees (speaker honoraria) from Biogen Idec, Merck Serono, Santhera and Teva, and participation as an advisor on preclinical development for Takeda, all unrelated to this Consensus Statement. J.P. declares grants and personal fees from Alexion, Biogen Idec, Chugai, and Merck Serono, personal fees from ABIDE, ARGENX, Med Day, Novartis, Roche and Teva, and grants from ABIDE and MedImmun, all unrelated to this Consensus Statement. She also has a patent (patent number 13704627.2-1408) with Isis: Diagnosing Multiple Sclerosis. H.V. declares grants from Merck Serono, Novartis and Teva, and other competing interests related to Merck and Novartis, all unrelated to this Consensus Statement. He also has a patent related to brain atrophy measurement pending. X.M. declares personal fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, all unrelated to this Consensus Statement. À.R. declares personal fees from Bayer, Biogen, Icometrix, Merck Serono, Novartis, Sanofi-Genzyme, Roche and Teva, and other competing interests related to Bayer, Novartis, OLEA Medical, Sanofi-Genzyme and Synthetic MRI, all unrelated to this Consensus Statement. M.B. declares no competing interests.

Figures

Fig. 1
Fig. 1. Lesion load and brain atrophy in relapsing–remitting multiple sclerosis.
a | Transverse T2-weighted fluid attenuation inversion recovery images from a patient with highly active relapsing–remitting multiple sclerosis (MS) who started a disease-modifying therapy at baseline. The T2 lesion load (T2LL) is stable during the first 3 years of treatment while the patient remained clinically stable (no relapses and no disability worsening), but markedly increases at the fourth year after treatment discontinuation associated with clinical activity (the rebound effect). b | Contrast-enhanced T1-weighted images from the same patient showing the change in brain parenchymal fraction (BPF) over time. The decrease in global brain volume in the first 3 years is mild (annualized percentage of brain volume change (aPBVC) −0.089%), but the volume loss at the fourth year is severe (aPBVC −3.8%), matching the change in T2LL and clinical evolution. The severe loss observed in year 4 is well beyond the −0.4% suggested as a pathological cut-off for brain volume loss in MS. c | Graphical representation of the changes in BPF over time, emphasizing the dramatic loss of volume in year 4.
See this image and copyright information in PMC

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