Berger_subbed 16/2/09 5:17 pm Page 96
Multiple Sclerosis
Another severe adverse advent during treatment with natalizumab Conclusion
regards the risk of progressive multifocal leukoencephalopathy (PML), The heterogeneity of MS in terms of clinical presentation, genetic
wh-ch has been estimated as one case per 1,000 natalizumab-treated background and pathological and immunological features requires
reliable (differential) diagnostic and prognostic markers for individual
counselling and therapeutic management. Numerous studies have tried
The heterogeneity of multiple
to identify such a (panel of) biomarker(s) with high specificity and
sensitivity to define patients according to their suggested immunological
sclerosis requires reliable (differential)
phenotype, to determine the prognosis of disease progression and to
diagnostic and prognostic markers
predict treatment responses. Some substantial progress can be noted,
such as new MRI techniques, NMO-IgG antibodies or NAb to IFN-β or
for individual counselling and
natalizumab. However, much more effort is necessary to reach the goal
therapeutic management. of prognostically valuable biological markers to anticipate future disease
course and treatment response in individual patients. Emerging
biotechnical methods and increasing insight into the underlying
patients over 18 months.
48
Despite extensive studies, no prognostic pathomechanisms will discover new biomarker candidates, which
marker could be identified that allows determination of the risk of PML should, after careful validation, improve the perspective and
in advance.
49
management of MS patients. ■
1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker Bg, synthesis in multiple sclerosis. Relationship with clinical and Neuromyelitis optica IgG predicts relapse after longitudinally
Multiple sclerosis, N Engl J Med, 2000;343:938–52. cerebrospinal fluid parameters, Brain, 1991;114(Pt 1A):181–95. extensive transverse myelitis, Ann Neurol, 2006;59:566–9.
2. O'Riordan JI, Thompson AJ, Kingsley DP, et al., The prognostic 19. Villar LM, Masjuan J, Gonzalez-Porque P, et al., Intrathecal IgM 36. Keegan M, Pineda AA, McClelland RL, et al., Plasma exchange
value of brain MRI in clinically isolated syndromes of the CNS. synthesis in neurologic diseases: relationship with disability in for severe attacks of CNS demyelination: predictors of response,
A 10-year follow-up, Brain, 1998;121(Pt 3):495–503. MS, Neurology, 2002;58:824–6. Neurology, 2002;58:143–6.
3. Weinshenker BG, Bass B, Rice GP, et al., The natural history of 20. Brunner C, Lassmann H, Waehneldt TV, et al., Differential 37. Cree BA, Lamb S, Morgan K, et al., An open label study of the
multiple sclerosis: a geographically based study. I. Clinical ultrastructural localization of myelin basic protein, effects of rituximab in neuromyelitis optica, Neurology,
course and disability, Brain, 1989;112(Pt 1):133–46. myelin/oligodendroglial glycoprotein, and 2’,3’-cyclic nucleotide 2005;64:1270–72.
4. Polman CH, Reingold SC, Edan G, et al., Diagnostic criteria for 3’-phosphodiesterase in the CNS of adult rats, J Neurochem, 38. Stone LA, Frank JA, Albert PS, et al., Characterization of MRI
multiple sclerosis: 2005 revisions to the “McDonald Criteria”, 1989;52:296–304. response to treatment with interferon beta-1b: contrast-
Ann Neurol, 2005;58:840–46. 21. Boggs JM, Myelin basic protein: a multifunctional protein, Cell enhancing MRI lesion frequency as a primary outcome measure,
5. Molyneux PD, Filippi M, Barkhof F, et al., Correlations between Mol Life Sci, 2006;63:1945–61. Neurology, 1997;49:862–9.
monthly enhanced MRI lesion rate and changes in T2 lesion 22. Berger T, Rubner P, Schautzer F, et al., Antimyelin antibodies as 39. Waubant E, Vukusic S, Gignoux L, et al., Clinical characteristics
volume in multiple sclerosis, Ann Neurol, 1998;43:332–9. a predictor of clinically definite multiple sclerosis after a first of responders to interferon therapy for relapsing MS, Neurology,
6. Bruck W, Bitsch A, Kolenda H, et al., Inflammatory central demyelinating event, N Engl J Med, 2003;349:139–45. 2003;61:184–9.
nervous system demyelination: correlation of magnetic 23. Tomassini V, De Giglio L, Reindl M, et al., Anti-myelin 40. Deisenhammer F, Reindl M, Harvey J, et al., Bioavailability of
resonance imaging findings with lesion pathology, Ann Neurol, antibodies predict the clinical outcome after a first episode interferon beta 1b in MS patients with and without neutralizing
1997;42:783–93. suggestive of MS, Mult Scler, 2007;13:1086–94. antibodies, Neurology, 1999;52:1239–43.
7. Rocca MA, Agosta F, Sormani MP, et al., A three-year, multi- 24. Greeve I, Sellner J, Lauterburg T, et al., Anti-myelin antibodies 41. Neutralizing antibodies during treatment of multiple sclerosis
parametric MRI study in patients at presentation with CIS, in clinically isolated syndrome indicate the risk of multiple with interferon beta-1b: experience during the first three years.
J Neurol, 2008;255:683–91. sclerosis in a Swiss cohort, Acta Neurol Scand, 2007;116: The IFNB Multiple Sclerosis Study Group and the University of
8. Tintore M, Rovira A, Rio J, et al., Baseline MRI predicts future 207–10. British Columbia MS/MRI Analysis Group, Neurology,
attacks and disability in clinically isolated syndromes, Neurology, 25. Rauer S, Euler B, Reindl M, Berger T, Antimyelin antibodies and 1996;47:889–94.
2006;67:968–72. the risk of relapse in patients with a primary demyelinating 42. Sorensen PS, Ross C, Clemmesen KM, et al., Clinical
9. Kappos L, Moeri D, Radue EW, et al., Predictive value of event, J Neurol Neurosurg Psychiatry, 2006;77:739–42. importance of neutralising antibodies against interferon beta in
gadolinium-enhanced magnetic resonance imaging for relapse 26. Kuhle J, Lindberg Rl, Regeniter A, et al., Antimyelin antibodies patients with relapsing-remitting multiple sclerosis, Lancet,
rate and changes in disability or impairment in multiple in clinically isolated syndromes correlate with inflammation in 2003;362:1184–91.
sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis MRI and CSF, J Neurol, 2007;254:160–68. 43. Ross C, Clemmesen KM, Svenson M, et al., Immunogenicity of
Group, Lancet, 1999;353:964–9. 27. Pelayo R, Tintore M, Montalban X, et al., Antimyelin antibodies interferon-beta in multiple sclerosis patients: influence of
10. McFarland HF, Barkhof F, Antel J, Miller DH, The role of MRI as with no progression to multiple sclerosis, N Engl J Med, preparation, dosage, dose frequency, and route of
a surrogate outcome measure in multiple sclerosis, Mult Scler, 2007;356:426–8. administration. Danish Multiple Sclerosis Study Group,
2002;8:40–51. 28. Lim Et, Berger T, Reindl M, et al., Anti-myelin antibodies do not Ann Neurol, 2000;48:706–12.
11. Barkhof F, The clinico-radiological paradox in multiple sclerosis allow earlier diagnosis of multiple sclerosis, Mult Scler, 44. Sorensen Ps, Deisenhammer F, Duda P, et al., Guidelines on
revisited, Curr Opin Neurol, 2002;15:239–45. 2005;11:492–4. use of anti-IFN-beta antibody measurements in multiple
12. Trapp BD, Peterson J, Ransohoff RM, et al., Axonal transection 29. Kuhle J, Pohl C, Mehling M, et al., Lack of association between sclerosis: report of an EFNS Task Force on IFN-beta antibodies
in the lesions of multiple sclerosis, N Engl J Med, 1998;338: antimyelin antibodies and progression to multiple sclerosis, in multiple sclerosis, Eur J Neurol, 2005;12:817–27.
278–85. N Engl J Med, 2007;356:371–8. 45. Baranzini SE, Mousavi P, Rio J, et al., Transcription-based
13. Fisher E, Rudick RA, Cutter G, et al., Relationship between 30. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker prediction of response to IFNbeta using supervised
brain atrophy and disability: an 8-year follow-up study of BG, The clinical course of neuromyelitis optica (Devic’s computational methods, PLoS Biol, 2005;3:e2.
multiple sclerosis patients, Mult Scler, 2000;6:373–7. syndrome), Neurology, 1999;53:1107–14. 46. Hoffmann S, Cepok S, Grummel V, et al., HLA-DRB1*0401 and
14. Freedman MS, Thompson EJ, Deisenhammer F, et al., 31. Lennon VA, Wingerchuk DM, Kryzer TJ, et al., A serum HLA-DRB1*0408 are strongly associated with the development
Recommended standard of cerebrospinal fluid analysis in the autoantibody marker of neuromyelitis optica: distinction from of antibodies against interferon-beta therapy in multiple
diagnosis of multiple sclerosis: a consensus statement, Arch multiple sclerosis, Lancet, 2004;364:2106–12. sclerosis, Am J Hum Genet, 2008;83:219–27.
Neurol, 2005;62:865–70. 32. Lucchinetti CF, Mandler RN, McGavern D, et al., A role for 47. Calabresi PA, Giovannoni G, Confavreux C, et al., The incidence
15. Kabat EA, Moore DH, Landow H, An Electrophoretic Study of humoral mechanisms in the pathogenesis of Devic’s and significance of anti-natalizumab antibodies: results from
the Protein Components in Cerebrospinal Fluid and Their neuromyelitis optica, Brain, 2002;125:1450–61. AFFIRM and SENTINEL, Neurology, 2007;69:1391–1403.
Relationship to the Serum Proteins, J Clin Invest, 1942;21: 33. Lennon VA, Kryzer TJ, Pittock SJ, et al., IgG marker of optic- 48. Yousry TA, Major EO, Ryschkewitsch C, et al., Evaluation of
571–7. spinal multiple sclerosis binds to the aquaporin-4 water patients treated with natalizumab for progressive multifocal
16. Koch M, Heersema D, Mostert J, et al., Cerebrospinal fluid channel, J Exp Med, 2005;202:473-477. leukoencephalopathy, N Engl J Med, 2006;354:924–33.
oligoclonal bands and progression of disability in multiple 34. Interferon beta-1b in the treatment of multiple sclerosis: final 49. Goodin DS, Cohen BA, O’Connor P, et al., Assessment: the use
sclerosis, Eur J Neurol, 2007;14:797–800. outcome of the randomized controlled trial. The IFNB Multiple of natalizumab (Tysabri) for the treatment of multiple sclerosis
17. Amato MP, Ponziani G, A prospective study on the prognosis of Sclerosis Study Group and The University of British Columbia (an evidence-based review): report of the Therapeutics and
multiple sclerosis, Neurol Sci, 2000;21:S831–8. MS/MRI Analysis Group, Neurology, 1995;45:1277–85. Technology Assessment Subcommittee of the American
18. Sharief MK, Thompson EJ, Intrathecal immunoglobulin M 35. Weinshenker BG, Wingerchuk DM, Vukusic S, et al., Academy of Neurology, Neurology, 2008;71:766–73.
96 EUROPEAN NEUROLOGICAL REVIEW
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124