Advertisement

Neuroradiology

, Volume 54, Issue 1, pp 5–12 | Cite as

Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes

  • Maria José Magraner
  • Isabel Bosca
  • Maria Simó-Castelló
  • Gracian García-Martí
  • Angel Alberich-Bayarri
  • Francisco Coret
  • Jose C. Álvarez-Cermeño
  • Luís Martí-Bonmatí
  • Luisa M. Villar
  • Bonaventura Casanova
Diagnostic Neuroradiology

Abstract

Introduction

The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume–PCBV–and brain parenchyma fraction–BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination.

Methods

Twenty-four CIS patients were included in this prospective study. IgG oligoclonal bands (OCGB) and LS-OCMB were determined in paired serum and CSF samples within 3 months since clinical onset. Brain MRI studies were scheduled at baseline, 3 months, first and second years after CIS onset. Differences in T2LV, PCBV and BPF between CIS patients according to the type of OCB were studied.

Results

Nine patients had no OCB; 15 had only OCGB, and seven had OCGB + LS-OCMB present in the CSF. LS-OCMB were associated with greater T2LV in all scheduled MRI studies. At the end of follow-up (year 2), it was threefold higher in patients with these antibodies than in those without LS-OCMB (3.95 cm3 vs. 1.36 cm3, p = 0.001). At that point, brain atrophy was also higher in patients with LS-OCMB (BPF, 0.73 in LS-OCMB+ patients vs. 0.76 in negative ones, p = 0.03). The rate in brain atrophy was higher in the first group of patients as well. Considering only patients with OCGB, the presence of LS-OCMB was also related to greater T2LV, T2LV increase and a trend towards higher atrophy rate.

Conclusion

The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB.

Keywords

Multiple sclerosis Clinically isolated syndrome Magnetic resonance imaging IgM oligoclonal bands 

Notes

Acknowledgements

This work has been performed with the financial support from the following national projects: FIS PI060822, FIS PS09/00551, PS09/01652 and PS09/01338 from the Carlos III Institute from Spain. The authors also thank nurses of the MS units (Matilde Escutia and Ana Bernal) and D. Carpio and B. Ovalle for their excellent technical assistance.

Conflict of interest

We declare that we have no conflict of interest.

References

  1. 1.
    Miller D, Barkhof F, Montalbán X et al (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 4:281–288PubMedCrossRefGoogle Scholar
  2. 2.
    Miller D, Barkhof F, Montalbán X et al (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management. Lancet Neurol 4:341–348PubMedCrossRefGoogle Scholar
  3. 3.
    Confavreux C, Vukusic S (2006) Natural history of multiple sclerosis: a unifying concept. Brain 129:606–616PubMedCrossRefGoogle Scholar
  4. 4.
    Poser CM, Paty DW, Scheinberg L et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231PubMedCrossRefGoogle Scholar
  5. 5.
    Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846PubMedCrossRefGoogle Scholar
  6. 6.
    Barkhof F, Filippi M, Miller DH et al (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120:2059–2069PubMedCrossRefGoogle Scholar
  7. 7.
    Brex PA, Ciccarelli O, O'Riordan JI et al (2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158–164PubMedCrossRefGoogle Scholar
  8. 8.
    Fisniku LK, Brex PA, Altmann DR et al (2008) Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 131:808–817PubMedCrossRefGoogle Scholar
  9. 9.
    Tintoré M, Rovira A, Rio J et al (2006) Baseline MRI predicts future attacks and disability in clinically isolated syndrome. Neurology 67:968–972PubMedCrossRefGoogle Scholar
  10. 10.
    Sailer M, O'Riordan JI, Thompson AJ et al (1999) Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination. Neurology 52:599–606PubMedGoogle Scholar
  11. 11.
    Di Filippo M, Anderson VM, Altmann DR et al (2008) Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry 81:204–208CrossRefGoogle Scholar
  12. 12.
    van den Elskamp IJ, Boden B, Dattola V et al (2010) Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis. Neuroradiology 52:875–881PubMedCrossRefGoogle Scholar
  13. 13.
    Martola J, Bergström J, Fredrikson S et al (2010) A longitudinal observational study of brain atrophy rate reflecting four decades of multiple sclerosis: a comparison of serial 1D, 2D, and volumetric measurements from MRI images. Neuroradiology 52:109–17PubMedCrossRefGoogle Scholar
  14. 14.
    Anderson VM, Fernando KT, Davies GR et al (2007) Cerebral atrophy measurement in clinically isolated syndromes and relapsing remitting multiple sclerosis: a comparison of registration-based methods. J Neuroimaging 17:61–68PubMedCrossRefGoogle Scholar
  15. 15.
    Dalton CM, Brex PA, Jenkins R et al (2002) Progressive ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis. J Neurol Neurosurg Psychiatry 73:141–147PubMedCrossRefGoogle Scholar
  16. 16.
    Villar LM, Masjuan J, González-Porqué P et al (2002) Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS. Neurology 59:555–559PubMedGoogle Scholar
  17. 17.
    Villar LM, Masjuan J, González-Porqué P et al (2003) Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis. Ann Neurol 53:222–226PubMedCrossRefGoogle Scholar
  18. 18.
    Perini P, Ranzato F, Calabrese M et al (2006) Intrathecal IgM production at clinical onset correlates with a more severe disease course in multiple sclerosis. J Neurol Neurosurg Psychiatry 77:953–955PubMedCrossRefGoogle Scholar
  19. 19.
    Mandrioli J, Sola P, Bedin R et al (2008) A multifactorial prognostic index in multiple sclerosis. Cerebrospinal fluid IgM oligoclonal bands and clinical features to predict the evolution of the disease. J Neurol 255:1023–1031PubMedCrossRefGoogle Scholar
  20. 20.
    Villar LM, Sádaba MC, Roldán E et al (2005) Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest 115:187–194PubMedGoogle Scholar
  21. 21.
    Villar LM, García-Barragán N, Espiño M et al (2008) Influence of oligoclonal IgM specificity in multiple sclerosis disease course. Mult Scler 14:183–187PubMedCrossRefGoogle Scholar
  22. 22.
    Sádaba MC, González Porqué P, Masjuan J et al (2004) An ultrasensitive method for the detection of oligoclonal IgG bands. J Immunol Methods 284:141–145PubMedCrossRefGoogle Scholar
  23. 23.
    Pascual AM, Martínez-Bisbal MC, Boscá I et al (2007) Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis. Neurology 69:63–67PubMedCrossRefGoogle Scholar
  24. 24.
    Smith SM, De Stefano N, Jenkinson M et al (2001) Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr 25:466–475PubMedCrossRefGoogle Scholar
  25. 25.
    Smith SM, Zhang Y, Jenkinson M et al (2002) Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17:479–489PubMedCrossRefGoogle Scholar
  26. 26.
    Miller DH, Barkhof F, Frank JA et al (2002) Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain 125:1676–1695PubMedCrossRefGoogle Scholar
  27. 27.
    Molyneux PD, Filippi M, Barkhof F et al (1998) Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis. Ann Neurol 43:332–339PubMedCrossRefGoogle Scholar
  28. 28.
    Filippi M, Rovaris M, Inglese M et al (2004) 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 364:1489–1496PubMedCrossRefGoogle Scholar
  29. 29.
    Sharief MK, Thompson EJ (1991) The predictive value of intrathecal immunoglobulin synthesis and magnetic resonance imaging in acute isolated syndromes for subsequent development of multiple sclerosis. Ann Neurol 29:147–151PubMedCrossRefGoogle Scholar
  30. 30.
    Jongen PJ, Lycklama a Nijeholt G, Lamers KJ et al (2007) Cerebrospinal fluid IgM index correlates with cranial MRI lesion load in patients with multiple sclerosis. Eur Neurol 58:90–95PubMedGoogle Scholar
  31. 31.
    Zivadinov R, Locatelli L, Cookfair D et al (2007) Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy. Mult Scler 13:490–501PubMedGoogle Scholar
  32. 32.
    Jacobs LD, Cookfair DL, Rudick RA et al (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39:285–294PubMedCrossRefGoogle Scholar
  33. 33.
    (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 352:1498–1504Google Scholar
  34. 34.
    Paty DW, Li DK, UBC MS/MRI Study Group, IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43:662–667PubMedGoogle Scholar
  35. 35.
    Boscá I, Magraner MJ, Coret F et al (2010) The risk of relapse after a clinically isolated syndrome is related to the pattern of oligoclonal bands. J Neuroimmunol 226:143–146PubMedCrossRefGoogle Scholar
  36. 36.
    Tintoré M, Rovira A, Rio J et al (2005) Is optic neuritis more benign than other first attacks in multiple sclerosis? Ann Neurol 57:210–215PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Maria José Magraner
    • 1
  • Isabel Bosca
    • 1
  • Maria Simó-Castelló
    • 1
  • Gracian García-Martí
    • 2
    • 6
  • Angel Alberich-Bayarri
    • 2
  • Francisco Coret
    • 3
  • Jose C. Álvarez-Cermeño
    • 4
  • Luís Martí-Bonmatí
    • 2
  • Luisa M. Villar
    • 5
  • Bonaventura Casanova
    • 1
  1. 1.Multiple Sclerosis Unit, Neurology DepartmentHospital La FeValenciaSpain
  2. 2.Magnetic Resonance UnitHospital QuirónValenciaSpain
  3. 3.Multiple Sclerosis Unit, Neurology DepartmentHospital Clinic UniversitariValenciaSpain
  4. 4.Neurology DepartmentHospital Ramón y CajalMadridSpain
  5. 5.Immunology DepartmentHospital Ramón y CajalMadridSpain
  6. 6.CIBER Mental Health Network, ISCIIIValenciaSpain

Personalised recommendations