Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Sep;75(9):1288–1293. doi: 10.1136/jnnp.2003.026021

Abnormalities of cerebral perfusion in multiple sclerosis

W Rashid 1, L Parkes 1, G Ingle 1, D Chard 1, A Toosy 1, D Altmann 1, M Symms 1, P Tofts 1, A Thompson 1, D Miller 1
PMCID: PMC1739228  PMID: 15314117

Abstract

Background: Measuring perfusion provides a potential indication of metabolic activity in brain tissue. Studies in multiple sclerosis (MS) have identified areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear.

Objectives: This study investigated perfusion changes in differing MS clinical subgroups on or off ß-interferon therapy using a non-invasive MRI technique (continuous arterial spin labelling) to investigate whether different clinical MS subtypes displayed perfusion changes and whether this could give a further insight into the pathological mechanisms involved.

Methods: Sixty patients (21 relapsing remitting, 14 secondary progressive, 12 primary progressive, 13 benign) and 34 healthy controls were compared. Statistical parametric mapping (SPM '99) was used to investigate regional variations in perfusion in both GM and WM. Global WM perfusion was derived by segmenting WM from images using T1 relaxation times.

Results: Regions of lower perfusion in predominantly GM were observed in the primary and secondary progressive cohorts, particularly in the thalamus. Increased WM perfusion was seen in relapsing remitting and secondary progressive cohorts.

Conclusions: Low GM perfusion could reflect decreased metabolism secondary to neuronal and axonal loss or dysfunction with a predilection for progressive forms of MS. Increased WM perfusion may indicate increased metabolic activity possibly due to increased cellularity and inflammation. Improved methodology and longitudinal studies may enable further investigation of regional and temporal changes, and their relationship with physical and cognitive impairment.

Full Text

The Full Text of this article is available as a PDF (102.5 KB).

Selected References

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

  1. Allen I. V., Glover G., Anderson R. Abnormalities in the macroscopically normal white matter in cases of mild or spinal multiple sclerosis (MS). Acta Neuropathol Suppl. 1981;7:176–178. doi: 10.1007/978-3-642-81553-9_53. [DOI] [PubMed] [Google Scholar]
  2. Alsop D. C., Detre J. A. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow. J Cereb Blood Flow Metab. 1996 Nov;16(6):1236–1249. doi: 10.1097/00004647-199611000-00019. [DOI] [PubMed] [Google Scholar]
  3. Arnold D. L., Matthews P. M., Francis G., Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr;14(1):154–159. doi: 10.1002/mrm.1910140115. [DOI] [PubMed] [Google Scholar]
  4. Banati R. B., Newcombe J., Gunn R. N., Cagnin A., Turkheimer F., Heppner F., Price G., Wegner F., Giovannoni G., Miller D. H. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain. 2000 Nov;123(Pt 11):2321–2337. doi: 10.1093/brain/123.11.2321. [DOI] [PubMed] [Google Scholar]
  5. Blinkenberg M., Rune K., Jensen C. V., Ravnborg M., Kyllingsbaek S., Holm S., Paulson O. B., Sørensen P. S. Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS. Neurology. 2000 Feb 8;54(3):558–564. doi: 10.1212/wnl.54.3.558. [DOI] [PubMed] [Google Scholar]
  6. Brooks D. J., Leenders K. L., Head G., Marshall J., Legg N. J., Jones T. Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1984 Nov;47(11):1182–1191. doi: 10.1136/jnnp.47.11.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brück W., Lucchinetti C., Lassmann H. The pathology of primary progressive multiple sclerosis. Mult Scler. 2002 Apr;8(2):93–97. doi: 10.1191/1352458502ms785rr. [DOI] [PubMed] [Google Scholar]
  8. Cifelli Alberto, Arridge Marzena, Jezzard Peter, Esiri Margaret M., Palace Jacqueline, Matthews Paul M. Thalamic neurodegeneration in multiple sclerosis. Ann Neurol. 2002 Nov;52(5):650–653. doi: 10.1002/ana.10326. [DOI] [PubMed] [Google Scholar]
  9. De Stefano Nicola, Iannucci Giuseppe, Sormani Maria P., Guidi Leonello, Bartolozzi Maria L., Comi Giancarlo, Federico Antonio, Filippi Massimo. MR correlates of cerebral atrophy in patients with multiple sclerosis. J Neurol. 2002 Aug;249(8):1072–1077. doi: 10.1007/s00415-002-0790-5. [DOI] [PubMed] [Google Scholar]
  10. Debruyne J. C., Versijpt J., Van Laere K. J., De Vos F., Keppens J., Strijckmans K., Achten E., Slegers G., Dierckx R. A., Korf J. PET visualization of microglia in multiple sclerosis patients using [11C]PK11195. Eur J Neurol. 2003 May;10(3):257–264. doi: 10.1046/j.1468-1331.2003.00571.x. [DOI] [PubMed] [Google Scholar]
  11. Detre J. A., Leigh J. S., Williams D. S., Koretsky A. P. Perfusion imaging. Magn Reson Med. 1992 Jan;23(1):37–45. doi: 10.1002/mrm.1910230106. [DOI] [PubMed] [Google Scholar]
  12. Evangelou N., Esiri M. M., Smith S., Palace J., Matthews P. M. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol. 2000 Mar;47(3):391–395. [PubMed] [Google Scholar]
  13. Filippi M., Gawne-Cain M. L., Gasperini C., vanWaesberghe J. H., Grimaud J., Barkhof F., Sormani M. P., Miller D. H. Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis. Neurology. 1998 Jan;50(1):238–244. doi: 10.1212/wnl.50.1.238. [DOI] [PubMed] [Google Scholar]
  14. Fu L., Matthews P. M., De Stefano N., Worsley K. J., Narayanan S., Francis G. S., Antel J. P., Wolfson C., Arnold D. L. Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain. 1998 Jan;121(Pt 1):103–113. doi: 10.1093/brain/121.1.103. [DOI] [PubMed] [Google Scholar]
  15. Haselhorst R., Kappos L., Bilecen D., Scheffler K., Möri D., Radü E. W., Seelig J. Dynamic susceptibility contrast MR imaging of plaque development in multiple sclerosis: application of an extended blood-brain barrier leakage correction. J Magn Reson Imaging. 2000 May;11(5):495–505. doi: 10.1002/(sici)1522-2586(200005)11:5<495::aid-jmri5>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  16. Keir S. L., Wardlaw J. M. Systematic review of diffusion and perfusion imaging in acute ischemic stroke. Stroke. 2000 Nov;31(11):2723–2731. doi: 10.1161/01.str.31.11.2723. [DOI] [PubMed] [Google Scholar]
  17. Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–1452. doi: 10.1212/wnl.33.11.1444. [DOI] [PubMed] [Google Scholar]
  18. Lassmann H. Neuropathology in multiple sclerosis: new concepts. Mult Scler. 1998 Jun;4(3):93–98. doi: 10.1177/135245859800400301. [DOI] [PubMed] [Google Scholar]
  19. Leenders K. L., Perani D., Lammertsma A. A., Heather J. D., Buckingham P., Healy M. J., Gibbs J. M., Wise R. J., Hatazawa J., Herold S. Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain. 1990 Feb;113(Pt 1):27–47. doi: 10.1093/brain/113.1.27. [DOI] [PubMed] [Google Scholar]
  20. Li D. K., Paty D. W. 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 Aug;46(2):197–206. doi: 10.1002/1531-8249(199908)46:2<197::aid-ana9>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  21. Lojkowska Wanda, Ryglewicz Danuta, Jedrzejczak Tomasz, Sienkiewicz-Jarosz Halina, Minc Slawomira, Jakubowska Teresa, Kozlowicz-Gudzinska Izabela. SPECT as a diagnostic test in the investigation of dementia. J Neurol Sci. 2002 Nov 15;203-204:215–219. doi: 10.1016/s0022-510x(02)00294-0. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Lublin F. D., Reingold S. C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907–911. doi: 10.1212/wnl.46.4.907. [DOI] [PubMed] [Google Scholar]
  24. Lycke J., Wikkelsö C., Bergh A. C., Jacobsson L., Andersen O. Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime. Eur Neurol. 1993;33(2):163–167. doi: 10.1159/000116926. [DOI] [PubMed] [Google Scholar]
  25. Matthews P. M., Pioro E., Narayanan S., De Stefano N., Fu L., Francis G., Antel J., Wolfson C., Arnold D. L. Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. Brain. 1996 Jun;119(Pt 3):715–722. doi: 10.1093/brain/119.3.715. [DOI] [PubMed] [Google Scholar]
  26. Miller D. H., Johnson G., Tofts P. S., MacManus D., McDonald W. I. Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease. Magn Reson Med. 1989 Sep;11(3):331–336. doi: 10.1002/mrm.1910110307. [DOI] [PubMed] [Google Scholar]
  27. Parkes Laura M., Tofts Paul S. Improved accuracy of human cerebral blood perfusion measurements using arterial spin labeling: accounting for capillary water permeability. Magn Reson Med. 2002 Jul;48(1):27–41. doi: 10.1002/mrm.10180. [DOI] [PubMed] [Google Scholar]
  28. Pasquier Jacques, Michel Bernard F., Brenot-Rossi Isabelle, Hassan-Sebbag Nathalie, Sauvan Richard, Gastaut Jean Louis. Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies. Eur J Nucl Med Mol Imaging. 2002 Jul 31;29(10):1342–1348. doi: 10.1007/s00259-002-0919-x. [DOI] [PubMed] [Google Scholar]
  29. Paulesu E., Perani D., Fazio F., Comi G., Pozzilli C., Martinelli V., Filippi M., Bettinardi V., Sirabian G., Passafiume D. Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study. Neuroimage. 1996 Oct;4(2):87–96. doi: 10.1006/nimg.1996.0032. [DOI] [PubMed] [Google Scholar]
  30. Poser C. M., Paty D. W., Scheinberg L., McDonald W. I., Davis F. A., Ebers G. C., Johnson K. P., Sibley W. A., Silberberg D. H., Tourtellotte W. W. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar;13(3):227–231. doi: 10.1002/ana.410130302. [DOI] [PubMed] [Google Scholar]
  31. Pozzilli C., Passafiume D., Bernardi S., Pantano P., Incoccia C., Bastianello S., Bozzao L., Lenzi G. L., Fieschi C. SPECT, MRI and cognitive functions in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1991 Feb;54(2):110–115. doi: 10.1136/jnnp.54.2.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sellebjerg F., Jensen C. V., Larsson H. B. W., Frederiksen J. L. Gadolinium-enhanced magnetic resonance imaging predicts response to methylprednisolone in multiple sclerosis. Mult Scler. 2003 Feb;9(1):102–107. doi: 10.1191/1352458503ms880sr. [DOI] [PubMed] [Google Scholar]
  33. Steen R. G., Gronemeyer S. A., Kingsley P. B., Reddick W. E., Langston J. S., Taylor J. S. Precise and accurate measurement of proton T1 in human brain in vivo: validation and preliminary clinical application. J Magn Reson Imaging. 1994 Sep-Oct;4(5):681–691. doi: 10.1002/jmri.1880040511. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Thompson A. J., Miller D., Youl B., MacManus D., Moore S., Kingsley D., Kendall B., Feinstein A., McDonald W. I. Serial gadolinium-enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. Neurology. 1992 Jan;42(1):60–63. doi: 10.1212/wnl.42.1.60. [DOI] [PubMed] [Google Scholar]
  36. Tofts P. S., Kermode A. G. Blood brain barrier permeability in multiple sclerosis using labelled DTPA with PET, CT and MRI. J Neurol Neurosurg Psychiatry. 1989 Aug;52(8):1019–1020. doi: 10.1136/jnnp.52.8.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trapp B. D., Peterson J., Ransohoff R. M., Rudick R., Mörk S., Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29;338(5):278–285. doi: 10.1056/NEJM199801293380502. [DOI] [PubMed] [Google Scholar]
  38. Trapp B. D., Ransohoff R., Rudick R. Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol. 1999 Jun;12(3):295–302. doi: 10.1097/00019052-199906000-00008. [DOI] [PubMed] [Google Scholar]
  39. Varrone Andrea, Pappatà Sabina, Caracò Corradina, Soricelli Andrea, Milan Graziella, Quarantelli Mario, Alfano Bruno, Postiglione Alfredo, Salvatore Marco. Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks. Eur J Nucl Med Mol Imaging. 2002 Aug 28;29(11):1447–1454. doi: 10.1007/s00259-002-0883-5. [DOI] [PubMed] [Google Scholar]
  40. Vymazal J., Righini A., Brooks R. A., Canesi M., Mariani C., Leonardi M., Pezzoli G. T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology. 1999 May;211(2):489–495. doi: 10.1148/radiology.211.2.r99ma53489. [DOI] [PubMed] [Google Scholar]

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

RESOURCES