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  • Review Article
  • Published:

Neuroplasticity and functional recovery in multiple sclerosis

Abstract

The development of therapeutic strategies that promote functional recovery is a major goal of multiple sclerosis (MS) research. Neuroscientific and methodological advances have improved our understanding of the brain's recovery from damage, generating novel hypotheses about potential targets and modes of intervention, and laying the foundation for development of scientifically informed recovery-promoting strategies in interventional studies. This Review aims to encourage the transition from characterization of recovery mechanisms to development of strategies that promote recovery in MS. We discuss current evidence for functional reorganization that underlies recovery and its implications for development of new recovery-oriented strategies in MS. Promotion of functional recovery requires an improved understanding of recovery mechanisms that can be modulated by interventions and the development of robust measurements of therapeutic effects. As imaging methods can be used to measure functional and structural alterations associated with recovery, this Review discusses their use to obtain reliable markers of the effects of interventions.

Key Points

  • Evidence supports a behaviourally relevant role for neuroplasticity—which is preserved despite widespread pathology—in multiple sclerosis (MS) across all patient ages, stages and phases of the disease

  • Together with adaptive plasticity, maladaptive plasticity can occur in brain systems owing to disuse of impaired limbs and may contribute to disability

  • Interventions that drive neuroplasticity can promote functional restoration by inducing adaptive changes or by predisposing functional systems to adaptive plasticity

  • Patient-specific and disease-related factors influence both spontaneous and intervention-driven adaptive functional reorganization and how the reorganization is measured using imaging

  • Improving the interpretability of functional MRI measures is important for characterization and quantification of the effects of recovery interventions and, thereby, for development of recovery-oriented strategies

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Figure 1: Non-pharmacological modulation of brain plasticity in MS.
Figure 2: Pharmacological modulation of brain plasticity in MS.
Figure 3: Effects of disease and pharmacological interventions on generation of BOLD fMRI signal.

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Acknowledgements

V. Tomassini is supported by the MS Society Italy, the MS International Federation and the Italian Ministry of Health. D. Fuglø receives research funding from The Lundbeck Foundation Centre for Neurovascular Signalling. H. Johansen-Berg is funded by the Wellcome Trust. R. G. Wise receives research funds from the UK Medical Research Council. This Review reflects the outcome of an international workshop held in 2010 in Warwick, UK, by the MAGNIMS Network (http://www.magnims.eu/). V. Tomassini received an International Meeting Grant from the MS International Federation (http://www.msif.org/en/) in 2010 to support the organization of the workshop.

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V. Tomassini, D. Fuglø, J. J. Geurts, D. K. Jones, M. A. Rocca and R. G. Wise researched data for the article. All authors provided substantial contribution to discussion of the article content and writing of the article. V. Tomassini, P. M. Matthews, A. J. Thompson, J. J. Geurts, R. G. Wise and F. Barkhof contributed to review and/or editing of the manuscript before submission.

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Correspondence to Valentina Tomassini.

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Competing interests

P. M. Matthews is a part-time employee of GlaxoSmithKline Research and Development and holds stocks and options in GlaxoSmithKline. A. J. Thompson has received honoraria for consultancy and support for travel from BTG, Eisai, Teva, Biogen, Merck-Serono, and Novartis. The other authors declare no competing interests.

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Imaging structural repair in MS (DOC 55 kb)

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Tomassini, V., Matthews, P., Thompson, A. et al. Neuroplasticity and functional recovery in multiple sclerosis. Nat Rev Neurol 8, 635–646 (2012). https://doi.org/10.1038/nrneurol.2012.179

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