The use of brain stimulation in the rehabilitation of walking disability in patients with multiple sclerosis: A randomized double-blind clinical trial study

  • Shahram Oveisgharan Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Zahra Karimi Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Siamak Abdi Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Hajir Sikaroodi Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Multiple Sclerosis, Transcranial Direct Current Stimulation, Mobility Limitation


Background: Transcranial direct current stimulation (tDCS) of the primary motor cortex of the lower limb has been exploited in the treatment of patients with stroke and spastic lower limb paresis. We examined this stimulation efficacy in the treatment of multiple sclerosis (MS)-related walking disability.

Methods: In a single-center randomized double-blind clinical trial study, 13 patients with MS and walking disability and Expanded Disability Status Scale (EDSS) score of 3 to 6 were randomized to the real and sham stimulation groups. In the real tDCS stimulation, 7 patients received anodal 2.5 mA stimulation at 1 cm anterior to the Cz point for 30-minute daily sessions in 7 consecutive days. The other group received sham stimulation with the same protocol. The primary outcome of the trial was change in the Timed 25-Foot Walk (T25-FW) from before to after the stimulation. We also assessed the Multiple Sclerosis Walking Scale-12 (MSWS-12). We employed linear mixed effects model to examine the efficacy of tDCS stimulation on changing the outcomes.

Results: On average, patients who received real tDCS stimulation walked faster after 7 sessions of stimulation [Estimate = -2.7, standard error (SE) = 1.3, P = 0.049], while walking speed of sham stimulation recipients did not change. For every session of stimulation, recipients of real tDCS stimulation spent 2.7 seconds less for walking the 25 feet. Real tDCS stimulation was not effective in improving MSWS-12 scores.

Conclusion: tDCS stimulation of the lower limb motor cortex speeded up patients with MS in walking, but without improvement in patients’ mobility in daily activities.


1. Conradsson D, Ytterberg C, von KL, Johansson S. Changes in disability in people with multiple sclerosis: A 10-year prospective study. J Neurol 2018; 265(1): 119-26.
2. Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, et al. The natural history of multiple sclerosis: A geographically based study 10: Relapses and long-term disability. Brain 2010; 133(Pt 7): 1914-29.
3. Heesen C, Bohm J, Reich C, Kasper J, Goebel M, Gold SM. Patient perception of bodily functions in multiple sclerosis: Gait and visual function are the most valuable. Mult Scler 2008; 14(7): 988-91.
4. Sutliff MH. Contribution of impaired mobility to patient burden in multiple sclerosis. Curr Med Res Opin 2010; 26(1): 109-19.
5. Weiss S, Mori F, Rossi S, Centonze D. Disability in multiple sclerosis: when synaptic long-term potentiation fails. Neurosci Biobehav Rev 2014; 43: 88-99.
6. Cooke SF, Bliss TV. Plasticity in the human central nervous system. Brain 2006; 129(Pt 7): 1659-73.
7. Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology 2007; 68(13): 1045-50.
8. Mori F, Codeca C, Kusayanagi H, Monteleone F, Boffa L, Rimano A, et al. Effects of intermittent theta burst stimulation on spasticity in patients with multiple sclerosis. Eur J Neurol 2010; 17(2): 295-300.
9. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist 2011; 17(1): 37-53.
10. Mori F, Codeca C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, et al. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain 2010; 11(5): 436-42.
11. Mori F, Nicoletti CG, Kusayanagi H, Foti C, Restivo DA, Marciani MG, et al. Transcranial direct current stimulation ameliorates tactile sensory deficit in multiple sclerosis. Brain Stimul 2013; 6(4): 654-9.
12. Ferrucci R, Vergari M, Cogiamanian F, Bocci T, Ciocca M, Tomasini E, et al. Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis. NeuroRehabilitation 2014; 34(1): 121-7.
13. Oveisgharan S, Organji H, Ghorbani A. Enhancement of motor recovery through left dorsolateral prefrontal cortex stimulation after acute ischemic stroke. J Stroke Cerebrovasc Dis 2018; 27(1): 185-91.
14. Li Y, Fan J, Yang J, He C, Li S. Effects of transcranial direct current stimulation on walking ability after stroke: A systematic review and meta-analysis. Restor Neurol Neurosci 2018; 36(1): 59-71.
15. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69(2): 292-302.
16. Arifin WN. Random sampling and allocation using SPSS. Education in Medicine Journal 2012; 4(1): e129-e143.
17. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987; 67(2): 206-7.
18. Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ. Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology 2003; 60(1): 31-6.
19. Nakhostin AN, Naghdi S, Mohammadi R, Hasson S. Multiple Sclerosis Walking Scale-12, translation, adaptation and validation for the Persian language population. Gait Posture 2015; 41(2): 420-4.
20. Rooney S, Wood L, Moffat F, Paul L. Prevalence of fatigue and its association with clinical features in progressive and non-progressive forms of Multiple Sclerosis. Mult Scler Relat Disord 2019; 28: 276-82.
21. Azimian M, Shahvarughi Farahani A, Dadkhah A, Fallahpour M, Karimlu M. Fatigue Severity Scale: The psychometric properties of the Persian-version in patients with multiple sclerosis. Research Journal of Biological Sciences 2009; 4(9): 974-7.
22. Eskandarieh S, Heydarpour P, Elhami SR, Sahraian MA. Prevalence and Incidence of Multiple Sclerosis in Tehran, Iran. Iran J Public Health 2017; 46(5): 699-704.
23. Kingwell E, van der Kop M, Zhao Y, Shirani A, Zhu F, Oger J, et al. Relative mortality and survival in multiple sclerosis: Findings from British Columbia, Canada. J Neurol Neurosurg Psychiatry 2012; 83(1): 61-6.
24. Lunde HMB, Assmus J, Myhr KM, Bo L, Grytten N. Survival and cause of death in multiple sclerosis: A 60-year longitudinal population study. J Neurol Neurosurg Psychiatry 2017; 88(8): 621-5.
25. Iodice R, Dubbioso R, Ruggiero L, Santoro L, Manganelli F. Anodal transcranial direct current stimulation of motor cortex does not ameliorate spasticity in multiple sclerosis. Restor Neurol Neurosci 2015; 33(4): 487-92.
26. Jor'dan AJ, Poole VN, Iloputaife I, Milberg W, Manor B, Esterman M, et al. Executive network activation is linked to walking speed in older adults: Functional MRI and TCD ultrasound evidence from the MOBILIZE Boston Study. J Gerontol A Biol Sci Med Sci 2017; 72(12): 1669-75.
27. Picelli A, Chemello E, Castellazzi P, Filippetti M, Brugnera A, Gandolfi M, et al. Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: A pilot, single blind, randomized controlled trial. Restor Neurol Neurosci 2018; 36(2): 161-71.
28. Zecca C, Riccitelli GC, Disanto G, Singh A, Digesu GA, Panicari L, et al. Urinary incontinence in multiple sclerosis: Prevalence, severity and impact on patients' quality of life. Eur J Neurol 2016; 23(7): 1228-34.
29. Johnsen NV, Osborn DJ, Dmochowski RR. The role of electrical stimulation techniques in the management of the male patient with urgency incontinence. Curr Opin Urol 2014; 24(6): 560-5.
30. Sangelaji B, Kordi M, Banihashemi F, Nabavi SM, Khodadadeh S, Dastoorpoor M. A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: A randomized clinical trial. Iran J Neurol 2016; 15(3): 111-20.
How to Cite
Oveisgharan S, Karimi Z, Abdi S, Sikaroodi H. The use of brain stimulation in the rehabilitation of walking disability in patients with multiple sclerosis: A randomized double-blind clinical trial study. Curr J Neurol. 18(2):57-63.
Original Article(s)