Physiotherapeutic methods for promoting neuroplasticity in patients with multiple sclerosis.

  • Avgerou M.D
  • Evangelopoulou E.M
Keywords: Multiple sclerosis, Neuroplasticity, Physiotherapy, Rehabilitation


Multiple sclerosis (MS) is a disease of the central nervous system of autoimmune origin, characterized by inflammation, demyelination, gliosis (fibrous proliferation of the glial cells in the affected area) and finally, destruction of the neural cells (neural loss). Non pharmacological interventions for patients with MS focus primarily on physical and psychological rehabilitation.
Neuroplasticity can be defined as the ability of the brain to change, remodel and reorganize itself to obtain the ability to adapt to new situations. Although the concept of neuroplasticity is quite novel, it is one of the most important discoveries in neuroscience. The aim of the present scoping was to investigate and present the recent literature data regarding physiotherapeutic and other methods for promoting neuroplasticity in patients with multiple sclerosis.
In total, 102 relevant scientific papers (reviews, systematic reviews and original trials), published after 2010 were analyzed. The findings of the review are encouraging - a number of physiotherapeutic methods (such as therapeutic exercise or neurophysiological rehabilitation techniques, for example) appear to be effective in promoting neuroplasticity in patients with MS; on the other hand, the findings of newer and increasingly popular methods such as, for example, robotic – assisted rehabilitation are not clear.
However, as the relevant research is based on small and not always high quality clinical studies, it is clear that additional research is needed, with randomized controlled trials of sufficient statistical power in order to extract more solid scientific data.


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Author Biographies

Avgerou M.D

Postgraduate Training Program, 3rd Department of Orthopaedic Surgery,
National and Kapodistrian University of Athens, KAT General Hospital of Athens, Greece.

Evangelopoulou E.M

1st Department of Neurology, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece.


Tafti D, Ehsan M, Xixis KL. Multiple Sclerosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Apr 5]. Available from:
Ksiazek-Winiarek DJ, Szpakowski P, Glabinski A. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background. Neural Plast. 2015;2015:307175.
Tsunoda I, Fujinami RS. Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination. Springer Semin Immunopathol. 2002;24(2):105–25.
Dilokthornsakul P, Valuck RJ, Nair KV et al. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016 Mar 15;86(11):1014–21.
Ntranos A, Lublin F. Diagnostic Criteria, Classification and Treatment Goals in Multiple Sclerosis: The Chronicles of Time and Space. Curr Neurol Neurosci Rep. 2016;16(10):90.
Miller E, Morel A, Redlicka J et al. Pharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis. Curr Neuropharmacol. 2018;16(4):475–83.
Miller E, Kostka J, Włodarczyk T et al. Whole-body cryostimulation (cryotherapy) provides benefits for fatigue and functional status in multiple sclerosis patients. A case-control study. Acta Neurol Scand. 2016;134(6):420–6.
McKinley RA, Bridges N, Walters CM et al. Modulating the brain at work using noninvasive transcranial stimulation. Neuroimage. 2012;59(1):129–37.
Zimmermann R, Gschwandtner U, Benz N et al. Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training. Neurology. 2014 Apr 8;82(14):1219–26.
Costandi M. Neuroplasticity. MIt Press; 2016.
McDermott JJ. The Writings of William James. Random House; 2013.
Puderbaugh M, Emmady PD. Neuroplasticity. In: StatPearls [Internet]. StatPearls Publishing; 2022.
Gerstner W. From Hebb rules to spike-timing-dependent plasticity: a personal account. Frontiers in Synaptic Neuroscience. 2010;2:151.
Demarin V, Morovic S. Neuroplasticity. Periodicum biologorum. 2014;116(2):209–11.
Pascual-Leone A, Amedi A, Fregni F et al. The plastic human brain cortex. Annu Rev Neurosci. 2005;28:377–401.
Shakouri N, Branch R, Rezabeigi M. Contribution of SLA to the Brain Study: A Plausible Look. The Iranian EFL Journal June 2015 Volume 11 Issue 3. 2015;89:113.
Silver J, Schwab ME, Popovich PG. Central nervous system regenerative failure: role of oligodendrocytes, astrocytes, and microglia. Cold Spring Harb Perspect Biol. 2014;7(3):a020602.
Tricco AC, Lillie E, Zarin W et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018 Oct 2;169(7):467–73.
Peterson J, Pearce PF, Ferguson LA et al. Understanding scoping reviews: Definition, purpose, and process. J Am Assoc Nurse Pract. 2017;29(1):12–6.
Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71.
Tomassini V, Matthews PM, Thompson AJ et al. Neuroplasticity and functional recovery in multiple sclerosis. Nat Rev Neurol. 2012;8(11):635–46.
Kerschensteiner M. Neuroplasticity and its relevance for multiple sclerosis. Neurodegener Dis Manag. 2017;7(6s):31–3.
Harkany T, Keimpema E, Barabás K et al. Endocannabinoid functions controlling neuronal specification during brain development. Mol Cell Endocrinol. 2008;286(1-2 Suppl 1):S84-90.
Garnier YM, Lepers R, Stapley PJ et al. Changes in cortico-spinal excitability following uphill versus downhill treadmill exercise. Behav Brain Res. 2017;317:242–50.
Motl RW, Sandroff BM, Kwakkel G et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16(10):848–56.
Sharif K, Watad A, Bragazzi NL et al. Physical activity and autoimmune diseases: Get moving and manage the disease. Autoimmun Rev. 2018;17(1):53–72.
Feys P, Moumdjian L, Van Halewyck F et al. Effects of an individual 12-week community-located “start-to-run” program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis. Mult Scler. 2019;25(1):92–103.
Hoque M, Borich M, Sabatier M et al. Effects of downslope walking on Soleus H-reflexes and walking function in individuals with multiple sclerosis: A preliminary study. NeuroRehabilitation. 2019;44(4):587–97.
Stellmann JP, Maarouf A, Schulz KH et al. Aerobic Exercise Induces Functional and Structural Reorganization of CNS Networks in Multiple Sclerosis: A Randomized Controlled Trial. Front Hum Neurosci. 2020;14:255.
Gibson EM, Purger D, Mount CW et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science. 2014;344(6183):1252304.
Chaves AR, Devasahayam AJ, Kelly LP et al. Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study. J Neurol Phys Ther. 2020;44(2):132–44.
Chaves AR, Devasahayam AJ, Riemenschneider M et al. Walking Training Enhances Corticospinal Excitability in Progressive Multiple Sclerosis-A Pilot Study. Front Neurol. 2020;11:422.
Devasahayam AJ, Chaves AR, Lasisi WO et al. Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study. BMC Neurol. 2020;20(1):33.
Zou L, Wang H, Xiao Z et al. Tai chi for health benefits in patients with multiple sclerosis: A systematic review. PloS one. 2017;12(2):e0170212.
Liu H, Salem Y, Aggarwal S. Effects of Tai Chi on biomarkers and their implication to neurorehabilitation–a systemic review. European Journal of Integrative Medicine. 2022;50:101391.
Sandroff BM, Jones CD, Baird JF et al. Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis. Neurorehabil Neural Repair. 2020;34(7):575–88.
Tavazzi E, Cazzoli M, Pirastru A et al. Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis: A Systematic Review on MRI Markers of Functional and Structural Changes. Front Neurosci. 2021;15:707675.
Esquenazi A, Packel A. Robotic-assisted gait training and restoration. Am J Phys Med Rehabil. 2012;91(11 Suppl 3):S217-227; quiz S228-231.
Dobkin BH, Duncan PW. Should body weight-supported treadmill training and robotic-assistive steppers for locomotor training trot back to the starting gate? Neurorehabil Neural Repair. 2012;26(4):308–17.
Straudi S, Manfredini F, Lamberti N et al. The effectiveness of Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressIve MultiplE sclerosis patients (RAGTIME): study protocol for a randomized controlled trial. Trials. 2017;18(1):88.
Straudi S, Manfredini F, Lamberti N et al. Robot-assisted gait training is not superior to intensive overground walking in multiple sclerosis with severe disability (the RAGTIME study): A randomized controlled trial. Mult Scler. 2020;26(6):716–24.
Androwis GJ, Sandroff BM, Niewrzol P et al. A pilot randomized controlled trial of robotic exoskeleton-assisted exercise rehabilitation in multiple sclerosis. Mult Scler Relat Disord. 2021;51:102936.
Flachenecker P. Clinical implications of neuroplasticity - the role of rehabilitation in multiple sclerosis. Front Neurol. 2015;6:36.
Straudi S, Martinuzzi C, Pavarelli C et al. A task-oriented circuit training in multiple sclerosis: a feasibility study. BMC Neurol. 2014;14:124.
Donzé C, Massot C. Rehabilitation in multiple sclerosis in 2021. La Presse Médicale. 2021;50(2):104066.
Rocca MA, Meani A, Fumagalli S et al. Functional and structural plasticity following action observation training in multiple sclerosis. Mult Scler. 2019;25(11):1472–87.
Bonzano L, Pedullà L, Tacchino A et al. Upper limb motor training based on task-oriented exercises induces functional brain reorganization in patients with multiple sclerosis. Neuroscience. 2019 Jul 1;410:150–9.
Johnson RA, Mitchell GS. Common mechanisms of compensatory respiratory plasticity in spinal neurological disorders. Respir Physiol Neurobiol. 2013;189(2):419–28.
Huang MH, Fry D, Doyle L et al. Effects of inspiratory muscle training in advanced multiple sclerosis. Mult Scler Relat Disord. 2020;37:101492.
Martini DN, Zeeboer E, Hildebrand A et al. ADSTEP: preliminary investigation of a multicomponent walking aid program in people with multiple sclerosis. Archives of physical medicine and rehabilitation. 2018;99(10):2050–8.
Fling BW, Martini DN, Zeeboer E et al. Neuroplasticity of the sensorimotor neural network associated with walking aid training in people with multiple sclerosis. Mult Scler Relat Disord. 2019;31:1–4.
Read JL, Shortell SM. Interactive games to promote behavior change in prevention and treatment. JAMA. 2011;305(16):1704–5.
Prosperini L, Tomassini V, Castelli L et al. Exergames for balance dysfunction in neurological disability: a meta-analysis with meta-regression. J Neurol. 2021;268(9):3223–37.