Use of Imaging in Multiple Sclerosis
M. Filippi
Institute of Experimental Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy
Search for more papers by this authorM. A. Rocca
Institute of Experimental Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy
Search for more papers by this authorR. Bakshi
Partners MS Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorN. De Stefano
Institute of Neurological Sciences, University of Siena, Italy
Search for more papers by this authorE. Frohman
University of Texas Southwestern Medical Center at Dallas, USA
Search for more papers by this authorJ. S. Wolinsky
University of Texas Health Science Center, Houston, USA
Search for more papers by this authorM. Filippi
Institute of Experimental Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy
Search for more papers by this authorM. A. Rocca
Institute of Experimental Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy
Search for more papers by this authorR. Bakshi
Partners MS Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Search for more papers by this authorN. De Stefano
Institute of Neurological Sciences, University of Siena, Italy
Search for more papers by this authorE. Frohman
University of Texas Southwestern Medical Center at Dallas, USA
Search for more papers by this authorJ. S. Wolinsky
University of Texas Health Science Center, Houston, USA
Search for more papers by this authorNils Erik Gilhus MD, PhD
Professor
Department of Clinical Medicine, University of Bergen and Department of Neurology, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorMichael P. Barnes MD, FRCP
Professor of Neurological Rehabilitation Medical Director
University of Newcastle, Hunters Moor Neurorehabilitation Ltd, Newcastle upon Tyne, UK
Search for more papers by this authorMichael Brainin MD
Professor
Department of Clinical Medicine and Prevention, and Center for Clinical Neurosciences, Donau-Universität Krems, Department of Neurology, Landesklinikum Donauregion Tulln Tulln, Austria
Search for more papers by this authorNils Erik Gilhus MD, PhD
Professor
Department of Clinical Medicine, University of Bergen and Department of Neurology, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorMichael P. Barnes MD, FRCP
Professor of Neurological Rehabilitation Medical Director
University of Newcastle, Hunters Moor Neurorehabilitation Ltd, Newcastle upon Tyne, UK
Search for more papers by this authorMichael Brainin MD
Professor
Department of Clinical Medicine and Prevention, and Center for Clinical Neurosciences, Donau-Universität Krems, Department of Neurology, Landesklinikum Donauregion Tulln Tulln, Austria
Search for more papers by this authorSummary
This chapter contains sections titled:
-
Introduction
-
Aim of the European Federation of Neurological Society (EFNS) task force
-
MRI assessment of patients at presentation with clinically isolated syndromes suggestive of MS
-
MRI in patients with CDMS
-
References
References
- Bakshi R, Thompson AJ, Rocca MA, et al. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol 2008; 7: 615–25.
- McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121–7.
- Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria’. Ann Neurol 2005; 58: 840–6.
- Filippi M, Rocca MA, Arnold DL, et al. EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis. Eur J Neurol 2006; 13: 313–25.
- Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000; 343: 938–52.
- Filippi M, Horsfield MA, Morrissey SP, et al. Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis. Neurology 1994; 44: 635–41.
- Barkhof F, Filippi M, Miller DH, et al. Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120:(Pt 11): 2059–69.
- Fisniku LK, Brex PA, Altmann DR, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131: 808–17.
- Jacobs LD, Beck RW, Simon JH, et al. Intramuscular inter-feron beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000; 343: 898–904.
- Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357: 1576–82.
- Achiron A, Kishner I, Sarova-Pinhas I, et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch Neurol 2004; 61: 1515–20.
- Kappos L, Polman CH, Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 67: 1242–9.
- Schumacher GA. Problems of multiple sclerosis. N Y State J Med 1966; 66: 1743–52.
- Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227–31.
- Miller DH, Weinshenker BG, Filippi M, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008; 14: 1157–74.
- Ormerod IE, Miller DH, McDonald WI, et al. The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain 1987; 110:(Pt 6): 1579–616.
- Filippi M, Gawne-Cain ML, Gasperini C, et al. Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis. Neurology 1998; 50: 238–44.
- Barkhof F, Filippi M, van Waesberghe JH, et al. Improving interobserver variation in reporting gadolinium-enhanced MRI lesions in multiple sclerosis. Neurology 1997; 49: 1682–8.
- Bot JC, Barkhof F. Spinal-cord MRI in multiple sclerosis: conventional and nonconventional MR techniques. Neuroimaging Clin N Am 2009; 19: 81–99.
- Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 2005; 236: 254–60.
- Calabrese M, De Stefano N, Atzori M, et al. Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis. Arch Neurol 2007; 64: 1416–22.
- Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346: 158–64.
- Hickman SJ, Dalton CM, Miller DH, Plant GT. Management of acute optic neuritis. Lancet 2002; 360: 1953–62.
- The Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 2008; 65: 727–32.
- Miller DH, Newton MR, van der Poel JC, et al. Magnetic resonance imaging of the optic nerve in optic neuritis. Neurology 1988; 38: 175–9.
- Gass A, Moseley IF, Barker GJ, et al. Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI. Neuroradiology 1996; 38: 317–21.
- Jackson A, Sheppard S, Laitt RD, Kassner A, Moriarty D. Optic neuritis: MR imaging with combined fat-and water-suppression techniques. Radiology 1998; 206: 57–63.
- Davies MB, Williams R, Haq N, Pelosi L, Hawkins CP. MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis. Neuroradiology 1998; 40: 765–70.
- Rocca MA, Hickman SJ, Bo L, et al. Imaging the optic nerve in multiple sclerosis. Mult Scler 2005; 11: 537–41.
- Fazekas F, Offenbacher H, Fuchs S, et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 1988; 38: 1822–5.
- Paty DW, Oger JJ, Kastrukoff LF, et al. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 1988; 38: 180–5.
- Lee KH, Hashimoto SA, Hooge JP, et al. Magnetic resonance imaging of the head in the diagnosis of multiple sclerosis: a prospective 2-year follow-up with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 1991; 41: 657–60.
- Offenbacher H, Fazekas F, Schmidt R, et al. Assessment of MRI criteria for a diagnosis of MS. Neurology 1993; 43: 905–9.
- Tas MW, Barkhol F, van Walderveen MA, Polman CH, Hommes OR, Valk J. The effect of gadolinium on the sensitivity and specificity of MR in the initial diagnosis of multiple sclerosis. AJNR Am J Neuroradiol 1995; 16: 259–64.
- Tintore M, Rovira A, Martinez MJ, et al. Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 2000; 21: 702–6.
- Tintore M, Rovira A, Rio J, et al. New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology 2003; 60: 27–30.
- Dalton CM, Brex PA, Miszkiel KA, et al. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 2002; 52: 47–53.
- Bot JC, Barkhof F, Lycklama a Nijeholt G, et al. Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging. Radiology 2002; 223: 46–56.
- Dalton CM, Brex PA, Miszkiel KA, et al. New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes. Ann Neurol 2003; 53: 673–6.
- Frohman EM, Goodin DS, Calabresi PA, et al. The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003; 61: 602–11.
- Nielsen JM, Korteweg T, Barkhof F, Uitdehaag BM, Polman CH. Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria. Ann Neurol 2005; 58: 781–3.
- Swanton JK, Fernando K, Dalton CM, et al. Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry 2006; 77: 830–3.
- Swanton JK, Rovira A, Tintore M, et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007; 6: 677–86.
- Rovira A, Swanton J, Tintore M, et al. A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis. Arch Neurol 2009; 66: 587–92.
- Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 2009; 72: 800–5.
- Lebrun C, Bensa C, Debouverie M, et al. Association between clinical conversion to multiple sclerosis in radiologically isolated syndrome and magnetic resonance imaging, cerebrospinal fluid, and visual evoked potential: follow-up of 70 patients. Arch Neurol 2009; 66: 841–6.
- Minneboo A, Barkhof F, Polman CH, Uitdehaag BM, Knol DL, Castelijns JA. Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol 2004; 61: 217–21.
- Tintore M, Rovira A, Rio J, et al. Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 2006; 67: 968–72.
- Miller DH, Barkhof F, Frank JA, Parker GJ, Thompson AJ. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 2002; 125: 1676–95.
- Dalton CM, Chard DT, Davies GR, et al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 2004; 127: 1101–7.
- 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 randomised, double-blind, placebo-controlled trial. Lancet 2004; 364: 1489–96.
- Dalton CM, Brex PA, Jenkins R, et al. Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry 2002; 73: 141–7.
- Brex PA, Leary SM, O'Riordan JI, et al. Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis. J Neurol Neurosurg Psychiatry 2001; 70: 544–7.
- Fernando KT, Tozer DJ, Miszkiel KA, et al. Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2005; 128: 2911–25.
- Rocca MA, Agosta F, Sormani MP, et al. A three-year, multi-parametric MRI study in patients at presentation with CIS. J Neurol 2008; 255: 683–91.
- Iannucci G, Tortorella C, Rovaris M, Sormani MP, Comi G, Filippi M. Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation. AJNR Am J Neuroradiol 2000; 21: 1034–8.
- Rovaris M, Gallo A, Riva R, et al. An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS. Neurology 2004; 63: 584–5.
- Gallo A, Rovaris M, Riva R, et al. Diffusion-tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis. Arch Neurol 2005; 62: 803–8.
- Rovaris M, Judica E, Ceccarelli A, et al. A 3-year diffusion tensor MRI study of grey matter damage progression during the earliest clinical stage of MS. J Neurol 2008; 255: 1209–14.
- Filippi M, Bozzali M, Rovaris M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 2003; 126: 433–7.
- Fernando KT, McLean MA, Chard DT, et al. Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2004; 127: 1361–9.
- Wattjes MP, Harzheim M, Lutterbey GG, et al. Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Neuroradiology 2008; 50: 123–9.
- Rocca MA, Mezzapesa DM, Falini A, et al. Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 2003; 18: 847–55.
- Filippi M, Rocca MA, Mezzapesa DM, et al. Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Hum Brain Mapp 2004; 21: 108–17.
- Rocca MA, Mezzapesa DM, Ghezzi A, et al. A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis. AJNR Am J Neuroradiol 2005; 26: 1136–9.
- Longstreth WT Jr, Arnold AM, Beauchamp NJ Jr, et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 2005; 36: 56–61.
- Kidd D, Thorpe JW, Thompson AJ, et al. Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 1993; 43: 2632–7.
- Miller DH, Filippi M, Fazekas F, et al. Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis. Ann Neurol 2004; 56: 273–8.
- Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 2007; 188: 1447–74.
- Thomsen HS. European Society of Urogenital Radiology guidelines on contrast media application. Curr Opin Urol 2007; 17: 70–6.
- Thompson AJ, Montalban X, Barkhof F, et al. Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 2000; 47: 831–5.
- Barkhof F, Filippi M, Miller DH, Tofts P, Kappos L, Thompson AJ. Strategies for optimizing MRI techniques aimed at monitoring disease activity in multiple sclerosis treatment trials. J Neurol 1997; 244: 76–84.
- Filippi M, Horsfield MA, Ader HJ, et al. Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis. Ann Neurol 1998; 43: 499–506.
- Thompson AJ, Miller DH, MacManus DG, McDonald WI. Patterns of disease activity in multiple sclerosis. BMJ 1990; 301: 44–5.
- Filippi M, Rocca MA. Conventional MRI in multiple sclerosis. J Neuroimaging 2007; 17 (Suppl. 1): 3S–9S.
- Sormani MP, Rovaris M, Comi G, Filippi M. A composite score to predict short-term disease activity in patients with relapsing-remitting MS. Neurology 2007; 69: 1230–5.
- Li DK, Held U, Petkau J, et al. MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology 2006; 66: 1384–9.
- Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 1990; 113 (Pt 5): 1477–89.
- Thompson AJ, Miller D, Youl B, et al. Serial gadolinium-enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. Neurology 1992; 42: 60–3.
- Thompson AJ, Kermode AG, Wicks D, et al. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 1991; 29: 53–62.
- Filippi M, Rossi P, Campi A, Colombo B, Pereira C, Comi G. Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability. AJNR Am J Neuroradiol 1997; 18: 1549–56.
-
Koudriavtseva T, Thompson AJ, Fiorelli M, et al. Gadolinium enhanced MRI predicts clinical and MRI disease activity in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 1997; 62: 285–7.
10.1136/jnnp.62.3.285 Google Scholar
- Molyneux PD, Filippi M, Barkhof F, et al. Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis. Ann Neurol 1998; 43: 332–9.
- Simon JH. From enhancing lesions to brain atrophy in relapsing MS. J Neuroimmunol 1999; 98: 7–15.
- Stone LA, Smith ME, Albert PS, et al. Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 1995; 45: 1122–6.
- Losseff NA, Kingsley DP, McDonald WI, Miller DH, Thompson AJ. Clinical and magnetic resonance imaging predictors of disability in primary and secondary progressive multiple sclerosis. Mult Scler 1996; 1: 218–22.
- Simon JH, Li D, Traboulsee A, et al. Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines. AJNR Am J Neuroradiol 2006; 27: 455–61.
- Filippi M, Rocca MA. MRI aspects of the ‘inflammatory phase’ of multiple sclerosis. Neurol Sci 2003; 24 (Suppl. 5): S275–8.
- Fazekas F, Barkhof F, Filippi M, et al. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology 1999; 53: 448–56.
- PRISMS (Prevention of Relapses and Disability by Inter-feron beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498–504.
- Simon JH, Jacobs LD, Campion M, et al. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol 1998; 43: 79–87.
- Li DK, Paty DW. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis. Ann Neurol 1999; 46: 197–206.
- Sorensen PS, Wanscher B, Jensen CV, et al. Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 1998; 50: 1273–81.
- O'Connor P, Comi G, Montalban X, et al. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study. Neurology 2009; 72: 73–9.
- Kappos L, Antel J, Comi G, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 2006; 355: 1124–40.
- Mikol DD, Barkhof F, Chang P, et al. Comparison of sub-cutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 2008; 7: 903–14.
- Comi G, Filippi M, Wolinsky JS. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis. European/ Canadian Glatiramer Acetate Study Group. Ann Neurol 2001; 49: 290–7.
- Clanet M, Radue EW, Kappos L, et al. A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology 2002; 59: 1507–17.
- Comi G, Pulizzi A, Rovaris M, et al. Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008; 371: 2085–92.
- Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003; 348: 15–23.
- Goodman AD, Rossman H, Bar-Or A, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009; 72: 806–12.
- 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.
- Metz LM, Zhang Y, Yeung M, et al. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 2004; 55: 756.
- Rose JW, Watt HE, White AT, Carlson NG. Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 2004; 56: 864–7.
- Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004; 363: 1607–8.
- O'Connor PW, Li D, Freedman MS, et al. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006; 66: 894–900.
- Kappos L, Gold R, Miller DH, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008; 372: 1463–72.
- Paty DW, Li DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology 1993; 43: 662–7.
- Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285–94.
- Panitch H, Goodin DS, Francis G, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial. Neurology 2002; 59: 1496–506.
- Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911–23.
- Smith DR, Weinstock-Guttman B, Cohen JA, et al. A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 2005; 11: 573–82.
- Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910.
- Andersen O, Lycke J, Tollesson PO, et al. Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis. Neurology 1996; 47: 895–900.
- Millefiorini E, Gasperini C, Pozzilli C, et al. Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 1997; 244: 153–9.
- Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358: 676–88.
- Fazekas F, Lublin FD, Li D, et al. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial. Neurology 2008; 71: 265–71.
- Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008; 7: 796–804.
- Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786–801.
- Miller DH, Molyneux PD, Barker GJ, MacManus DG, Moseley IF, Wagner K. Effect of interferon-beta1b on magnetic resonance imaging outcomes in secondary progressive multiple sclerosis: results of a European multicenter, randomized, double-blind, placebo-controlled trial. European Study Group on Interferon-beta1b in secondary progressive multiple sclerosis. Ann Neurol 1999; 46: 850–9.
- Paolillo A, Coles AJ, Molyneux PD, et al. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 1999; 53: 751–7.
- Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology 2000; 54: 1145–55.
- Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG. Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology 2007; 69: 785–9.
- Garren H, Robinson WH, Krasulova E, et al. Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann Neurol 2008; 63: 611–20.
- Bar-Or A, Calabresi PA, Arnold D, et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63: 395–400.
- Panitch H, Miller A, Paty D, Weinshenker B. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004; 63: 1788–95.
- 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.
- Rovaris M, Comi G, Rocca MA, et al. Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial. Mult Scler 2007; 13: 502–8.
- Rudick RA, Lee JC, Simon J, Ransohoff RM, Fisher E. Defining interferon beta response status in multiple sclerosis patients. Ann Neurol 2004; 56: 548–55.
- Rio J, Rovira A, Tintore M, et al. Relationship between MRI lesion activity and response to IFN-beta in relapsing-remitting multiple sclerosis patients. Mult Scler 2008; 14: 479–84.
- Prosperini L, Gallo V, Petsas N, Borriello G, Pozzilli C. One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis. Eur J Neurol 2009; 16: 1202–9.
- Tomassini V, Paolillo A, Russo P, et al. Predictors of long-term clinical response to interferon beta therapy in relapsing multiple sclerosis. J Neurol 2006; 253: 287–93.
- Fazekas F, Soelberg-Sorensen P, Comi G, Filippi M. MRI to monitor treatment efficacy in multiple sclerosis. J Neuroimaging 2007; 17 (Suppl. 1): 50S–5S.
- Simon JH, Lull J, Jacobs LD, et al. A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group. Neurology 2000; 55: 185–92.
- Barkhof F, van Waesberghe JH, Filippi M, et al. T(1) hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment. Brain 2001; 124: 1396–402.
- Filippi M, Rovaris M, Rice GP, et al. The effect of cladribine on T(1) ‘black hole’ changes in progressive MS. J Neurol Sci 2000; 176: 42–4.
- Patti F, Amato MP, Filippi M, Gallo P, Trojano M, Comi GC. A double blind, placebo-controlled, phase II, add-on study of cyclophosphamide (CTX) for 24 months in patients affected by multiple sclerosis on a background therapy with interferon-beta study denomination: CYCLIN. J Neurol Sci 2004; 223: 69–71.
- Filippi M, Rovaris M, Rocca MA, Sormani MP, Wolinsky JS, Comi G. Glatiramer acetate reduces the proportion of new MS lesions evolving into ‘black holes’. Neurology 2001; 57: 731–3.
- Dalton CM, Miszkiel KA, Barker GJ, et al. Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis. J Neurol 2004; 251: 407–13.
- Brex PA, Molyneux PD, Smiddy P, et al. The effect of IFNbeta-1b on the evolution of enhancing lesions in secondary progressive MS. Neurology 2001; 57: 2185–90.
- Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol 2006; 5: 158–70.
- Giorgio A, Battaglini M, Smith SM, De Stefano N. Brain atrophy assessment in multiple sclerosis: importance and limitations. Neuroimaging Clin N Am 2008; 18: 675–86.
- Lanz M, Hahn HK, Hildebrandt H. Brain atrophy and cognitive impairment in multiple sclerosis: a review. J Neurol 2007; 254 (Suppl. 2): II43–8.
- Fisher E, Rudick RA, Simon JH, et al. Eight-year follow-up study of brain atrophy in patients with MS. Neurology 2002; 59: 1412–20.
- Khaleeli Z, Ciccarelli O, Manfredonia F, et al. Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study. Ann Neurol 2008; 63: 790–3.
- Chard DT, Griffin CM, Parker GJ, Kapoor R, Thompson AJ, Miller DH. Brain atrophy in clinically early relapsing-remitting multiple sclerosis. Brain 2002; 125: 327–37.
- De Stefano N, Matthews PM, Filippi M, et al. Evidence of early cortical atrophy in MS: relevance to white matter changes and disability. Neurology 2003; 60: 1157–62.
- Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M. Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology 2005; 65: 1126–8.
- Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 2008; 64: 255–65.
- Pagani E, Rocca MA, Gallo A, et al. Regional brain atrophy evolves differently in patients with multiple sclerosis according to clinical phenotype. AJNR Am J Neuroradiol 2005; 26: 341–6.
- Ceccarelli A, Rocca MA, Pagani E, et al. A voxel-based morphometry study of grey matter loss in MS patients with different clinical phenotypes. Neuroimage 2008; 42: 315–22.
- Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 1999; 53: 1698–704.
- Filippi M, Rovaris M, Iannucci G, Mennea S, Sormani MP, Comi G. Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology 2000; 55: 1714–8.
- Molyneux PD, Kappos L, Polman C, et al. The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis. European Study Group on Interferon beta-1b in secondary progressive multiple sclerosis. Brain 2000; 123 (Pt 11): 2256–63.
- Rovaris M, Comi G, Rocca MA, Wolinsky JS, Filippi M. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications. Brain 2001; 124: 1803–12.
- Sormani MP, Rovaris M, Valsasina P, Wolinsky JS, Comi G, Filippi M. Measurement error of two different tech-niques for brain atrophy assessment in multiple sclerosis. Neurology 2004; 62: 1432–4.
- Ropele S, Fazekas F. Magnetization transfer MR imaging in multiple sclerosis. Neuroimaging Clin N Am 2009; 19: 27–36.
- Rovaris M, Agosta F, Pagani E, Filippi M. Diffusion tensor MR imaging. Neuroimaging Clin N Am 2009; 19: 37–43.
- Sajja BR, Wolinsky JS, Narayana PA. Proton magnetic resonance spectroscopy in multiple sclerosis. Neuroimaging Clin N Am 2009; 19: 45–58.
- Rovaris M, Agosta F, Sormani MP, et al. Conventional and magnetization transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study. Brain 2003; 126: 2323–32.
- Agosta F, Absinta M, Sormani MP, et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain 2007; 130: 2211–9.
- Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M. Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis. Brain 2006; 129: 2620–7.
- Richert ND, Ostuni JL, Bash CN, Leist TP, McFarland HF, Frank JA. Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult Scler 2001; 7: 49–58.
- Kita M, Goodkin DE, Bacchetti P, Waubant E, Nelson SJ, Majumdar S. Magnetization transfer ratio in new MS lesions before and during therapy with IFNbeta-1a. Neurology 2000; 54: 1741–5.
- Richert ND, Ostuni JL, Bash CN, Duyn JH, McFarland HF, Frank JA. Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b. AJNR Am J Neuroradiol 1998; 19: 1705–13.
- Inglese M, van Waesberghe JH, Rovaris M, et al. The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS. Neurology 2003; 60: 853–60.
- Filippi M, Rocca MA, Pagani E, et al. European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis. Arch Neurol 2004; 61: 1409–12.
- Horsfield MA, Barker GJ, Barkhof F, Miller DH, Thompson AJ, Filippi M. Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis. J Magn Reson Imaging 2003; 17: 389–97.
- Ropele S, Filippi M, Valsasina P, et al. Assessment and correction of B1-induced errors in magnetization transfer ratio measurements. Magn Reson Med 2005; 53: 134–40.
- Sarchielli P, Presciutti O, Tarducci R, et al. 1H-MRS in patients with multiple sclerosis undergoing treatment with interferon beta-1a: results of a preliminary study. J Neurol Neurosurg Psychiatry 1998; 64: 204–12.
- Narayanan S, De Stefano N, Francis GS, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 2001; 248: 979–86.
- Schubert F, Seifert F, Elster C, et al. Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of inter-feron-beta therapy on absolute metabolite concentrations. MAGMA 2002; 14: 213–22.
- Khan O, Shen Y, Bao F, et al. Long-term study of brain 1H-MRS study in multiple sclerosis: effect of glatiramer acetate therapy on axonal metabolic function and feasibil-ity of long-Term H-MRS monitoring in multiple sclerosis. J Neuroimaging 2008; 18: 314–9.
- Narayana PA, Wolinsky JS, Rao SB, He R, Mehta M. Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 2004; 10 (Suppl. 1): S73–8.
- Sajja BR, Narayana PA, Wolinsky JS, Ahn CW. Longitudinal magnetic resonance spectroscopic imaging of primary progressive multiple sclerosis patients treated with glatiramer acetate: multicenter study. Mult Scler 2008; 14: 73–80.
- De Stefano N, Filippi M, Miller D, et al. Guidelines for using proton MR spectroscopy in multicenter clinical MS studies. Neurology 2007; 69: 1942–52.