Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2005 Sep;76(9):1255–1258. doi: 10.1136/jnnp.2004.036590

Is inflammation important in early PPMS? a longitudinal MRI study

G Ingle 1, J Sastre-Garriga 1, D Miller 1, A Thompson 1
PMCID: PMC1739783  PMID: 16107362

Abstract

Background: Magnetic resonance imaging (MRI) studies in primary progressive multiple sclerosis (PPMS) have shown a reduced frequency of enhancement with the contrast agent gadolinium-DTPA (Gd-DTPA), in comparison with relapsing-remitting multiple sclerosis (RRMS), and it has been suggested that there may be a less important role for inflammation in its pathogenesis. However, the earliest clinical stages of PPMS have not been studied and thus it has not been possible to exclude the existence of an early inflammatory phase.

Objective: To study the presence, characteristics, and implications of inflammation in early PPMS.

Methods: 45 patients with a mean disease duration of 3.3 years had triple dose Gd enhanced MRI, expanded disability status scale (EDSS), and multiple sclerosis functional composite (MSFC) assessments at baseline. Repeat MRI was done at 1 and 2 months in 24 patients, and at 6 months in 38.

Results: Enhancing brain lesions were present in 42% of patients at baseline but enhancing cord lesions were uncommon (7%); 85% of enhancing lesions enhanced for one month or less. Patients with enhancing lesions had greater disability (EDSS, p = 0.027; MSFC, p = 0.026) and more MRI abnormalities (greater T2 load, p = 0.008; greater T1 hypointensity load, p = 0.001; and reduced partial brain volume, p = 0.012) than those without enhancement. Enhancement at 6 months was seen in 32% of patients and was restricted to a subset of patients who enhanced at baseline.

Conclusions: Enhancement is present in some cases of early PPMS and is associated with greater disease impact in terms of both clinical and MRI measures.

Full Text

The Full Text of this article is available as a PDF (73.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abstracts of the Association of British Neurologists, University of Oxford, 3 April-5 April 2002. J Neurol Neurosurg Psychiatry. 2002 Aug;73(2):213–236. doi: 10.1136/jnnp.73.2.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bashir K., Whitaker J. N. Clinical and laboratory features of primary progressive and secondary progressive MS. Neurology. 1999 Sep 11;53(4):765–771. doi: 10.1212/wnl.53.4.765. [DOI] [PubMed] [Google Scholar]
  3. Brex P. A., Jenkins R., Fox N. C., Crum W. R., O'Riordan J. I., Plant G. T., Miller D. H. Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology. 2000 Apr 25;54(8):1689–1691. doi: 10.1212/wnl.54.8.1689. [DOI] [PubMed] [Google Scholar]
  4. Brück W., Bitsch A., Kolenda H., Brück Y., Stiefel M., Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997 Nov;42(5):783–793. doi: 10.1002/ana.410420515. [DOI] [PubMed] [Google Scholar]
  5. Cutter G. R., Baier M. L., Rudick R. A., Cookfair D. L., Fischer J. S., Petkau J., Syndulko K., Weinshenker B. G., Antel J. P., Confavreux C. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999 May;122(Pt 5):871–882. doi: 10.1093/brain/122.5.871. [DOI] [PubMed] [Google Scholar]
  6. Filippi M., Campi A., Martinelli V., Colombo B., Yousry T., Canal N., Scotti G., Comi G. Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 1995 Nov;59(5):540–544. doi: 10.1136/jnnp.59.5.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Filippi M., Rovaris M., Capra R., Gasperini C., Yousry T. A., Sormani M. P., Prandini F., Horsfield M. A., Martinelli V., Bastianello S. A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials. Brain. 1998 Oct;121(Pt 10):2011–2020. doi: 10.1093/brain/121.10.2011. [DOI] [PubMed] [Google Scholar]
  8. Grossman R. I., Gonzalez-Scarano F., Atlas S. W., Galetta S., Silberberg D. H. Multiple sclerosis: gadolinium enhancement in MR imaging. Radiology. 1986 Dec;161(3):721–725. doi: 10.1148/radiology.161.3.3786722. [DOI] [PubMed] [Google Scholar]
  9. Katz D., Taubenberger J. K., Cannella B., McFarlin D. E., Raine C. S., McFarland H. F. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann Neurol. 1993 Nov;34(5):661–669. doi: 10.1002/ana.410340507. [DOI] [PubMed] [Google Scholar]
  10. Kidd D., Thorpe J. W., Kendall B. E., Barker G. J., Miller D. H., McDonald W. I., Thompson A. J. MRI dynamics of brain and spinal cord in progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996 Jan;60(1):15–19. doi: 10.1136/jnnp.60.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leary S. M., Miller D. H., Stevenson V. L., Brex P. A., Chard D. T., Thompson A. J. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology. 2003 Jan 14;60(1):44–51. doi: 10.1212/wnl.60.1.44. [DOI] [PubMed] [Google Scholar]
  12. Losseff N. A., Wang L., Lai H. M., Yoo D. S., Gawne-Cain M. L., McDonald W. I., Miller D. H., Thompson A. J. Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain. 1996 Dec;119(Pt 6):2009–2019. doi: 10.1093/brain/119.6.2009. [DOI] [PubMed] [Google Scholar]
  13. Losseff N. A., Webb S. L., O'Riordan J. I., Page R., Wang L., Barker G. J., Tofts P. S., McDonald W. I., Miller D. H., Thompson A. J. Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain. 1996 Jun;119(Pt 3):701–708. doi: 10.1093/brain/119.3.701. [DOI] [PubMed] [Google Scholar]
  14. McDonnell G. V., Cabrera-Gomez J., Calne D. B., Li D. K. B., Oger J. Clinical presentation of primary progressive multiple sclerosis 10 years after the incidental finding of typical magnetic resonance imaging brain lesions: the subclinical stage of primary progressive multiple sclerosis may last 10 years. Mult Scler. 2003 Mar;9(2):204–209. doi: 10.1191/1352458503ms890cr. [DOI] [PubMed] [Google Scholar]
  15. Miller D. H., Rudge P., Johnson G., Kendall B. E., Macmanus D. G., Moseley I. F., Barnes D., McDonald W. I. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain. 1988 Aug;111(Pt 4):927–939. doi: 10.1093/brain/111.4.927. [DOI] [PubMed] [Google Scholar]
  16. Revesz T., Kidd D., Thompson A. J., Barnard R. O., McDonald W. I. A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain. 1994 Aug;117(Pt 4):759–765. doi: 10.1093/brain/117.4.759. [DOI] [PubMed] [Google Scholar]
  17. Rudick R. A. Disease-modifying drugs for relapsing-remitting multiple sclerosis and future directions for multiple sclerosis therapeutics. Arch Neurol. 1999 Sep;56(9):1079–1084. doi: 10.1001/archneur.56.9.1079. [DOI] [PubMed] [Google Scholar]
  18. Silver N. C., Good C. D., Barker G. J., MacManus D. G., Thompson A. J., Moseley I. F., McDonald W. I., Miller D. H. Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging. Brain. 1997 Jul;120(Pt 7):1149–1161. doi: 10.1093/brain/120.7.1149. [DOI] [PubMed] [Google Scholar]
  19. Silver N. C., Good C. D., Sormani M. P., MacManus D. G., Thompson A. J., Filippi M., Miller D. H. A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis. J Neurol. 2001 Mar;248(3):215–224. doi: 10.1007/s004150170229. [DOI] [PubMed] [Google Scholar]
  20. Thompson A. J., Kermode A. G., Wicks D., MacManus D. G., Kendall B. E., Kingsley D. P., McDonald W. I. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol. 1991 Jan;29(1):53–62. doi: 10.1002/ana.410290111. [DOI] [PubMed] [Google Scholar]
  21. Thompson A. J., Montalban X., Barkhof F., Brochet B., Filippi M., Miller D. H., Polman C. H., Stevenson V. L., McDonald W. I. Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol. 2000 Jun;47(6):831–835. [PubMed] [Google Scholar]
  22. Thompson A. J., Polman C. H., Miller D. H., McDonald W. I., Brochet B., Filippi M Montalban X., De Sá J. Primary progressive multiple sclerosis. Brain. 1997 Jun;120(Pt 6):1085–1096. doi: 10.1093/brain/120.6.1085. [DOI] [PubMed] [Google Scholar]
  23. Wolinsky Jerry S., PROMiSe Study Group The diagnosis of primary progressive multiple sclerosis. J Neurol Sci. 2003 Feb 15;206(2):145–152. doi: 10.1016/s0022-510x(02)00346-5. [DOI] [PubMed] [Google Scholar]
  24. van Waesberghe J. H., van Walderveen M. A., Castelijns J. A., Scheltens P., Lycklama à Nijeholt G. J., Polman C. H., Barkhof F. Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. AJNR Am J Neuroradiol. 1998 Apr;19(4):675–683. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES