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BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis

Authors: Raed Alroughani, Dirk Deleu, Khalid El Salem, Jasem Al-Hashel, K. John Alexander, Mohamed Assem Abdelrazek, Adel Aljishi, Jaber Alkhaboori, Faisal Al Azri, Nahida Al Zadjali, Majed Hbahbih, Tag Eldin Sokrab, Mohamed Said, Àlex Rovira

Published in: BMC Neurology | Issue 1/2016

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Abstract

Background

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed.

Methods

A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments.

Results

The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of “no evidence of disease activity” (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity.

Conclusion

BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.
Literature
1.
2.
Heydarpour P, Khoshkish S, Abtahi S, Moradi-Lakeh M, Ali SM. Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2015;44:232–44.CrossRefPubMed
3.
4.
Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol. 2011;93:1–12.CrossRefPubMed
5.
De Stefano N, Giorgio BM, et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology. 2010;74:1868–76.CrossRefPubMed
6.
Kappos L, Radue EW, O’Connor P, et al. A placebo controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387–401.CrossRefPubMed
7.
Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402–15.CrossRefPubMed
8.
Calabresi PA, Radue EW, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing–remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13:545–56.CrossRefPubMed
9.
Smith SM, Zhang Y, Jenkinson M, et al. Accurate, robust, and automated, longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17:479–89.CrossRefPubMed
10.
Sahraian MA, Radue E-W, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand. 2010;122:1–8.CrossRefPubMed
11.
Filippi M, Rocca MA, Barkhof F, et al. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 2012;11:349–60.CrossRefPubMed
12.
Filippi M, Rocca M. Preventing brain atrophy should be the gold standard of effective therapy in MS (after the first year of treatment). Mult Scler. 2013;19:1005–6.CrossRefPubMed
13.
Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008;64(3):255–65.CrossRefPubMed
14.
Minneboo A, Jasperse B, Barkhof F, et al. Predicting short-term disability progression in early multiple sclerosis: added value of MRI parameters. J Neurol Neurosurg Psychiatry. 2008;79(8):917–233.CrossRefPubMed
15.
Benedict RH, Hulst HE, Bergsland N, et al. Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients. Mult Scler. 2013;19(11):1478–84.CrossRefPubMed
16.
Deloire MS, Ruet A, Hamel D, Bonnet M, Dousset V, Brochet B. MRI predictors of cognitive outcome in early multiple sclerosis. Neurology. 2011;76(13):1161–7.CrossRefPubMedPubMedCentral
17.
Calabrese M, Rinaldi F, Poretto V, Gallo P. The puzzle of multiple sclerosis: gray matter finds its place. Expert Rev Neurother. 2011;11:1565–8.CrossRefPubMed
18.
Yaldizli Ö, Glassl S, Sturm D, Papadopoulou A, Gass A, Tettenborn B. Fatigue and progression of corpus callosum atrophy in multiple sclerosis. J Neurol. 2011;258(12):2199–205.CrossRefPubMed
19.
Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85(10):1109–15.CrossRefPubMed
20.
Filippi M1, Preziosa P, Copetti M, et al. Gray matter damage predicts the accumulation of disability 13 years later in MS. Neurology. 2013;81(20):1759–67.CrossRefPubMed
21.
Popescu V, Agosta F, Hulst HE, et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013;84:1082–91.CrossRefPubMed
22.
Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL. Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. AJNR Am J Neuroradiol. 2002;23(8):1327–33.PubMed
23.
Hedman AM, van Haren NEM, Schnack HG, Kahn RS, Hulshoff Pol HE. Human brain changes across the life span: a review of 56 longitudinal magnetic resonance imaging studies. Hum Brain Mapp. 2012;33:1987–2002.CrossRefPubMed
24.
Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E, Morris JC, Dale AM, Fischl B. Thinning of the cerebral cortex in aging. Cereb Cortex. 2004;14(7):721–30.CrossRefPubMed
25.
Im K, Lee JM, Lyttelton O, Kim SH, Evans AC, Kim SI. Brain size and cortical structure in the adult human brain. Cereb Cortex. 2008;18(9):2181–91.CrossRefPubMed
26.
Pell GS1, Briellmann RS, Chan CH, Pardoe H, Abbott DF, Jackson GD. Selection of the control group for VBM analysis: influence of covariates, matching and sample size. NeuroImage. 2008;41(4):1324–35.CrossRefPubMed
27.
Barnes J, Ridgway GR. Bartlett, etal. Head size, age and gender adjustment in MRI studies: a necessary nuisance? NeuroImage. 2010;53:1244–55.CrossRefPubMed
28.
Rovira A, Auger C, Alonso J. Magnetic resonance monitoring of lesion evolution in multiple sclerosis. Ther AdvNeurol Disord. 2013;6:298–310.CrossRef
29.
Zivadinov R, Stosic M, Cox JL, Ramasamy DP, Dwyer MG. The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome. J Neurol. 2008;255 Suppl 1:61–74.CrossRefPubMed
30.
De Stefano N, Airas L, Grigoriadis N, et al. Clinical relevance of brain volume measures in multiple sclerosis. CNS Drugs. 2014;28:147–56.CrossRefPubMed
31.
Ziemssen T, Derfuss T, De Stefano N, et al. Optimizing treatment success in multiple sclerosis. J Neurol. 2015;24.
32.
De Stefano N, Stromillo ML, Giorgio A, et al. Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87(1):93–9.PubMed
33.
Rudick RA, Fisher E, Lee JC, Duda JT, Simon J. Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon beta-1a. Mult Scler. 2000;6:365–72.CrossRefPubMed
34.
Kappos L, Traboulsee A, Constantinescu C, et al. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing–remitting MS. Neurology. 2006;67:944–53.CrossRefPubMed
35.
Rovaris M, Comi G, Rocca MA et al. Long-term follow-up of patients treated with glatiramer acetate: a multicenter, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial. Mult Scler. 2007;13:502–8.
36.
Comi G, Cohen JA, Arnold DL, et al. Phase III dose comparison study of glatiramer 36. acetate for multiple sclerosis. Ann Neurol 2011;69:75–82.
37.
Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicenter, randomized, parallel, open-label trial. Lancet Neurol. 2008;7:903–14.CrossRefPubMed
38.
O’Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomized, multicenter study. Lancet Neurol. 2009;8:889–97.CrossRefPubMed
39.
Lublin FD, Cofield SS, Cutter GR, et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis: the CombiRx Study. Ann Neurol. 2013;73:327–40.CrossRefPubMedPubMedCentral
40.
Miller DH, Soon D, Fernando KT, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology. 2007;68:1390–401.CrossRefPubMed
41.
Radue E-W, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis. J Neurol Sci. 2010;292:28–35.CrossRefPubMed
42.
O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293–303.CrossRefPubMed
43.
Arnold DL, Gold R, Kappos L, et al. Effects of delayed release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study. J Neurol. 2014;261:1794–802.CrossRefPubMedPubMedCentral
44.
Miller DH, Fox RJ, Phillips JT, et al. Effects of delayed release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study. Neurology. 2015;84:1145–52.CrossRefPubMedPubMedCentral
45.
Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing–remitting multiple sclerosis: a randomized controlled phase 3 trial. Lancet. 2012;380:1819–28.CrossRefPubMed
46.
Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease modifying therapy: a randomized controlled phase 3 trial. Lancet. 2012;380:1829–39.CrossRefPubMed
47.
Comi G, Jeffery D, Kappos L, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366:1000–9.CrossRefPubMed
48.
Vollmer TL, Sorensen PS, Selmaj K, et al. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol. 2014;261:773–83.CrossRefPubMed
49.
Kappos L, Wiendl H, Selmaj K, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2015;373(15):1418–28.CrossRefPubMed
50.
Filippi M, Rovaris M, Inglese M, et al. Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Lancet. 2004;364:1489–96.CrossRefPubMed
51.
Kappos L, Freedman MS, Polman CH, et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007;370:389–97.CrossRefPubMed
52.
Simon JH. Brain atrophy in multiple sclerosis: what we know and would like to know. Mult Scler. 2006;12(6):679–87.CrossRefPubMed
53.
Zivadinov R, Reder AT, Filippi M, et al. Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis. Neurology. 2008;71(2):136–44.CrossRefPubMed
54.
Kappos L, Freedman MS, Polman CH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009;8:987–97.CrossRefPubMed
55.
Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmierer K, Marta M. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4:329–33.CrossRefPubMed
56.
Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015;72:152–8.CrossRefPubMed
57.
Kappos L, De Stefano N, Freedman MS, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2015. [Epub ahead of print].
Metadata
Title
A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis
Authors
Raed Alroughani
Dirk Deleu
Khalid El Salem
Jasem Al-Hashel
K. John Alexander
Mohamed Assem Abdelrazek
Adel Aljishi
Jaber Alkhaboori
Faisal Al Azri
Nahida Al Zadjali
Majed Hbahbih
Tag Eldin Sokrab
Mohamed Said
Àlex Rovira
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0762-5

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