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Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis

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Abstract

Patients with multiple sclerosis (MS) activate a more diffuse cortical network than do healthy subjects when they perform motor tasks. This brain functional reorganisation might contribute to the limiting of disability, but it is unclear whether there is a loss of regional activation in more advanced disease. The aim of this study was to assess whether functional reorganisation diminishes in more disabled patients with primary progressive (PP) MS. The differences in the fMRI response to active and passive movements of the dominant ankle of 13 patients and 16 controls were assessed. The relationships between functional activation and disability and brain lesion load and atrophy were investigated.

Patients showed greater fMRI activation than controls with passive movements in the superior temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and passive movements in the ipsilateral inferior frontal gyrus was lower in patients with greater disability and greater brain T2 lesion load, respectively. Furthermore, the fMRI activation with active movements in the contralateral cerebellum was lower in patients with worse mobility.

The increased activity with passive movements in regions that participate in sensori–motor integration, such as the putamen, reflects true functional reorganisation, since passive movements induce brain activation through sensory afferents only. The inverse correlation between the fMRI response in regions that are associated with motor control, and clinical or MRI measures of disease progression, suggests that there is a loss of distributed activation in more disabled patients. This may inform future treatment strategies.

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References

  1. Filippi M, Rocca MA (2003) Disturbed function and plasticity in multiple sclerosis as gleaned from functional magnetic resonance imaging. Curr Opin Neurol 16:275–282

    Article  PubMed  Google Scholar 

  2. Audoin B, Ibarrola D, Ranjeva JP, Confort– Gouny S, Malikova I, Ali–Cherif A, Pelletier J, Cozzone P (2003) Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp 20:51–58

    Article  PubMed  Google Scholar 

  3. Pantano P, Mainero C, Iannetti GD, Caramia F, Di Legge S, Piattella MC, Pozzilli C, Bozzao L, Lenzi GL (2002) Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis. Neuroimage 17:1837–1843

    Article  PubMed  Google Scholar 

  4. Lee M, Reddy H, Johansen–Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM (2000) The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neurol 47:606–613

    Article  PubMed  CAS  Google Scholar 

  5. Reddy H, Narayanan S, Arnoutelis R, Jenkinson M, Antel J, Matthews PM, Arnold DL (2000) Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain 123:2314–2320

    Article  PubMed  Google Scholar 

  6. Rocca MA, Gavazzi C, Mezzapesa DM, Falini A, Colombo B, Mascalchi M, Scotti G, Comi G, Filippi M (2003) A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis. Neuroimage 19:1770–1777

    Article  PubMed  Google Scholar 

  7. Rocca MA, Falini A, Colombo B, Scotti G, Comi G, Filippi M (2002) Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol 51:330–339

    Article  PubMed  Google Scholar 

  8. Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G (2002) Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 15:537–546

    Article  PubMed  CAS  Google Scholar 

  9. Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH, Polman CH, Stevenson VL, McDonald WI (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47:831–835

    Article  PubMed  CAS  Google Scholar 

  10. Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DP, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62

    Article  PubMed  CAS  Google Scholar 

  11. Wolinsky JS (2003) The diagnosis of primary progressive multiple sclerosis. J Neurol Sci 206:145–152

    Article  PubMed  Google Scholar 

  12. Reddy H, Narayanan S, Woolrich M, Mitsumori T, Lapierre Y, Arnold DL, Matthews PM (2002) Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. Brain 125:2646–2657

    Article  PubMed  CAS  Google Scholar 

  13. Penfield W, Rasmusseun T (1950) The cerebral cortex of man. New York: Macmillan

    Google Scholar 

  14. Dobkin BH, Firestine A, West M, Saremi K, Woods R (2004) Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation. Neuroimage 23:370–381

    Article  PubMed  Google Scholar 

  15. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

    PubMed  CAS  Google Scholar 

  16. Schwid SR, Goodman AD, Mattson DH, Mihai C, Donohoe KM, Petrie MD, Scheid EA, Dudman JT, McDermott MP (1997) The measurement of ambulatory impairment in multiple sclerosis. Neurology 49:1419–1424

    PubMed  CAS  Google Scholar 

  17. Bohannon RW, Smith MB (1987) Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67:206–207

    PubMed  CAS  Google Scholar 

  18. Raczkowski D, Kalat JW, Nebes R (1974) Reliability and validity of some handedness questionnaire items. Neuropsychologia 12:43–47

    Article  PubMed  CAS  Google Scholar 

  19. Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: A general linear approach. Hum Brain Mapp 2:189–210

    Article  Google Scholar 

  20. Worsley KJ, Friston KJ (1995) Analysis of fMRI time–series revisited – again. Neuroimage 2:173–181

    Article  PubMed  CAS  Google Scholar 

  21. Friston KJ, Holmes AP, Worsley KJ (1999) How many subjects constitute a study? Neuroimage 10:1–5

    Article  PubMed  CAS  Google Scholar 

  22. Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC (1996) A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp 4:58–73

    Article  Google Scholar 

  23. Sahyoun C, Floyer–Lea A, Johansen– Berg H, Matthews PM (2004) Towards an understanding of gait control: brain activation during the anticipation, preparation and execution of foot movements. Neuroimage 21:568–575

    Article  PubMed  CAS  Google Scholar 

  24. Rocca MA, Matthews PM, Caputo D, Ghezzi A, Falini A, Scotti G, Comi G, Filippi M (2002) Evidence for widespread movement–associated functional MRI changes in patients with PPMS. Neurology 58:866–872

    PubMed  CAS  Google Scholar 

  25. Rorden C, Brett M (2000) Stereotaxic display of brain lesions. Behav Neurol 12:191–200

    PubMed  Google Scholar 

  26. Plummer DL (1992) Dispimage: a display and analysis tool for medical images. Rev Neuroradiol 5:489–495

    Google Scholar 

  27. Chard DT, Parker GJ, Griffin CM, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM–based segmentation methodology. J Magn Reson Imaging 15:259–267

    Article  PubMed  Google Scholar 

  28. Rocca MA, Pagani E, Ghezzi A, Falini A, Zaffaroni M, Colombo B, Scotti G, Comi G, Filippi M (2003) Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain. Neuroimage 19:826–836

    Article  PubMed  Google Scholar 

  29. Reddy H, Narayanan S, Matthews PM, Hoge RD, Pike GB, Duquette P, Antel J, Arnold DL (2000) Relating axonal injury to functional recovery in MS. Neurology 54:236–239

    PubMed  CAS  Google Scholar 

  30. Filippi M, Rocca MA, Mezzapesa DM, Ghezzi A, Falini A, Martinelli V, Scotti G, Comi G (2004) Simple and complex movement–associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Hum Brain Mapp 21:108–117

    Article  PubMed  Google Scholar 

  31. Yeterian EH, Pandya DN (1998) Corticostriatal connections of the superior temporal region in rhesus monkeys. J Comp Neurol 399:384–402

    Article  PubMed  CAS  Google Scholar 

  32. Ward NS, Frackowiak RS (2003) Agerelated changes in the neural correlates of motor performance. Brain 126:873–888

    Article  PubMed  CAS  Google Scholar 

  33. Weiller C, Juptner M, Fellows S, Rijntjes M, Leonhardt G, Kiebel S, Muller S, Diener HC, Thilmann AF (1996) Brain representation of active and passive movements. Neuroimage 4:105–110

    Article  PubMed  CAS  Google Scholar 

  34. Gerardin E, Lehericy S, Pochon JB, Tezenas du MS, Mangin JF, Poupon F, Agid Y, Le Bihan D, Marsault C (2003) Foot, hand, face and eye representation in the human striatum. Cereb Cortex 13:162–169

    Article  PubMed  Google Scholar 

  35. Ciccarelli O, Toosy AT, Marsden JF, Wheeler–Kingshott CM, Sahyoun C, Matthews PM, Miller DH, Thompson AJ (2005) Identifying brain regions for integrative sensorimotor processing with ankle movements. Exp Brain Res 166:31–42

    Article  PubMed  CAS  Google Scholar 

  36. Abbruzzese G, Berardelli A (2003) Sensorimotor integration in movement disorders. Mov Disord 18:231–240

    Article  PubMed  Google Scholar 

  37. Rizzolatti G, Luppino G (2001) The cortical motor system. Neuron 31:889–901

    Article  PubMed  CAS  Google Scholar 

  38. Filippi M, Rocca MA, Mezzapesa DM, Falini A, Colombo B, Scotti G, Comi G (2004) A functional MRI study of cortical activations associated with object manipulation in patients with MS. Neuroimage 21:1147–1154

    Article  PubMed  Google Scholar 

  39. Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2003) Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 18:847–855

    Article  PubMed  Google Scholar 

  40. Okabe S, Hanajima R, Ohnishi T, Nishikawa M, Imabayashi E, Takano H, Kawachi T, Matsuda H, Shiio Y, Iwata NK, Furubayashi T, Terao Y, Ugawa Y (2003) Functional connectivity revealed by single–photon emission computed tomography (SPECT) during repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. Clin Neurophysiol 114:450–457

    Article  PubMed  Google Scholar 

  41. Pantano P, Mainero C, Lenzi D, Caramia F, Iannetti GD, Piattella MC, Pestalozza I, Di Legge S, Bozzao L, Pozzilli C (2005) A longitudinal fMRI study on motor activity in patients with multiple sclerosis. Brain 128:2146–2153

    Article  PubMed  Google Scholar 

  42. Filippi M, Rocca MA (2004) Cortical reorganisation in patients with MS. J Neurol Neurosurg Psychiatry 75:1087–1089

    Article  PubMed  CAS  Google Scholar 

  43. Rocca MA, Colombo B, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2005) Cortical adaptation in patients with MS: a cross–sectional functional MRI study of disease phenotypes. Lancet Neurol 4:618–626

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Headache, Brain Injury and Neurorehabilitation, Institute of Neurology, University College London, London, WC1N 3BG, UK

    O. Ciccarelli, A. T. Toosy & A. J. Thompson

  2. Centre for Functional Magnetic Resonance, Imaging of the Brain, Dept. of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK

    O. Ciccarelli & P. M. Matthews

  3. MRC Human Movement Group, Sobell Department for Motor, Neurophysiology and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK

    J. F. Marsden

  4. Department of Neuroinflammation, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

    C. M. Wheeler-Kingshott & D. H. Miller

Authors
  1. O. Ciccarelli
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  2. A. T. Toosy
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  3. J. F. Marsden
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  4. C. M. Wheeler-Kingshott
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  5. D. H. Miller
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  6. P. M. Matthews
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  7. A. J. Thompson
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Correspondence to O. Ciccarelli.

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Ciccarelli, O., Toosy, A.T., Marsden, J.F. et al. Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis. J Neurol 253, 882–891 (2006). https://doi.org/10.1007/s00415-006-0125-z

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  • DOI: https://doi.org/10.1007/s00415-006-0125-z

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