Efficacy of repetitive transcranial magnetic stimulation for improving lower limb function in individuals with neurological disorders: A systematic review and meta-analysis of randomized sham-controlled trials
DOI:
https://doi.org/10.2340/jrm.v53.1097Keywords:
transcranial magnetic stimulation, neurological disorders, lower extremityAbstract
Objective: To determine the efficacy of repetitive transcranial magnetic stimulation vs sham stimulation on improving lower-limb functional outcomes in individuals with neurological disorders.
Data sources: PubMed, CINAHL, Embase and Scopus databases were searched from inception to 31 March 2020 to identify papers (n = 1,198). Two researchers independently reviewed studies for eligibility. Randomized clinical trials with parallel-group design, involving individuals with neurological disorders, including lower-limb functional outcome measures and published in scientific peer-reviewed journals were included.
Data extraction: Two researchers independently screened eligible papers (n = 27) for study design, clinical population characteristics, stimulation protocol and relevant outcome measures, and assessed study quality.
Data synthesis: Studies presented a moderate risk of selection, attrition and reporting bias. An overall effect of repetitive transcranial magnetic stimulation was found for outcomes: gait (effect size [95% confidence interval; 95% CI]: 0.51 [0.29; 0.74], p = 0.003) and muscle strength (0.99 [0.40; 1.58], p = 0.001) and disorders: stroke (0.20 [0.00; 0.39], p = 0.05), Parkinson’s disease (1.01 [0.65; 1.37], p = 0.02) and spinal cord injury (0.50 [0.14; 0.85], p = 0.006), compared with sham. No effect was found for outcomes: mobility and balance.
Conclusion: Supplementary repetitive transcranial magnetic stimulation may promote rehabilitation focused on ambulation and muscle strength and overall lower-limb functional recovery in individuals with stroke, Parkinson’s disease and spinal cord injury. Further evidence is needed to extrapolate these findings.
Lay abstract
Non-invasive magnetic brain stimulation can cause beneficial changes in the central nervous system of individuals with neurological disorders, which, in turn, may have a number of therapeutic qualities. This paper summarizes current knowledge about whether the technique can be used to promote recovery of leg movement function. By searching the available literature for studies on individuals with neurological disorders that have compared the effects of magnetic brain stimulation with placebo stimulation, 27 relevant studies were identified. Combined data from these studies suggested that real stimulation, compared with placebo, had positive effects specifically for recovery of walking ability and maximal leg muscle strength, as well as for improvement in overall leg movement function in individuals with stroke, Parkinson’s disease and spinal cord injury. These findings are important for patients and therapists seeking to improve rehabilitation outcomes. This research area deserves increased scientific focus.
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References
Alia C, Spalletti C, Lai S, Panarese A, Lamola G, Bertolucci F, et al. Neuroplastic changes following brain ischemia and their contribution to stroke recovery: Novel approaches in neurorehabilitation. Front Cell Neurosci 2017; 11: 1-22.
https://doi.org/10.3389/fncel.2017.00076 DOI: https://doi.org/10.3389/fncel.2017.00076
Thickbroom GW, Mastaglia FL. Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS). J Neuroeng Rehabil 2009; 6: 2-6.
https://doi.org/10.1186/1743-0003-6-4 DOI: https://doi.org/10.1186/1743-0003-6-4
Halpern R, Agarwal S, Dembek C, Borton L, Lopez-Bresnahan M. Comparison of adherence and persistence among multiple sclerosis patients treated with disease-modifying therapies: a retrospective administrative claims analysis. Patient Prefer Adherence 2011; 5: 73-84.
https://doi.org/10.2147/PPA.S15702 DOI: https://doi.org/10.2147/PPA.S15702
Straka I, Minár M, Gažová A, Valkovič P, Kyselovič J. Clinical aspects of adherence to pharmacotherapy in Parkinson disease: a PRISMA-compliant systematic review. Medicine (Baltimore) 2018; 97: e10962.
https://doi.org/10.1097/MD.0000000000010962 DOI: https://doi.org/10.1097/MD.0000000000010962
Carr J, Shepherd R. The changing face of neurological rehabilitation. Rev Bras Fisioter 2006; 10: 147-156.
https://doi.org/10.1590/S1413-35552006000200003 DOI: https://doi.org/10.1590/S1413-35552006000200003
Maizey L, Allen CPG, Dervinis M, Verbruggen F, Varnava A, Kozlov M, et al. Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Clin Neurophysiol 2013; 124: 536-544.
https://doi.org/10.1016/j.clinph.2012.07.024 DOI: https://doi.org/10.1016/j.clinph.2012.07.024
Hallett M. Transcranial magnetic stimulation and the human brain. Nature 2000; 406: 147-150.
https://doi.org/10.1038/35018000 DOI: https://doi.org/10.1038/35018000
Klomjai W, Katz R, Lackmy-Vallée A. Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS). Ann Phys Rehabil Med 2015; 58: 208-213.
https://doi.org/10.1016/j.rehab.2015.05.005 DOI: https://doi.org/10.1016/j.rehab.2015.05.005
Slotema CW, Blom JD, Hoek HW, Sommer IEC. Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry 2010; 71: 873-884.
https://doi.org/10.4088/JCP.08m04872gre DOI: https://doi.org/10.4088/JCP.08m04872gre
Giannoni-Luza S, Pacheco-Barrios K, Cardenas-Rojas A, Mejia-Pando PF, Luna-Cuadros MA, Barouh JL, et al. Non-invasive motor cortex stimulation effects on quantitative sensory testing (QST) in healthy and chronic pain subjects. Pain 2020; 161: 1955-1975.
https://doi.org/10.1097/j.pain.0000000000001893 DOI: https://doi.org/10.1097/j.pain.0000000000001893
Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM, et al. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain 2009; 10: 1205-1216.
https://doi.org/10.1016/j.jpain.2009.03.010 DOI: https://doi.org/10.1016/j.jpain.2009.03.010
Papadopoulou SL, Ploumis A, Exarchakos G, Theodorou SJ, Beris A, Fotopoulos AD. Versatility of repetitive transcranial magnetic stimulation in the treatment of poststroke dysphagia. J Neurosci Rural Pract 2018; 9: 391-396.
https://doi.org/10.4103/jnrp.jnrp_68_18 DOI: https://doi.org/10.4103/jnrp.jnrp_68_18
Naeser MA, Martin PI, Treglia E, Ho M, Kaplan E, Bashir S, et al. Research with rTMS in the treatment of aphasia. Restor Neurol Neurosci 2010; 28: 511-529.
https://doi.org/10.3233/RNN-2010-0559 DOI: https://doi.org/10.3233/RNN-2010-0559
Benninger DH, Hallett M. Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015. NeuroRehabilitation 2015; 37: 11-24.
https://doi.org/10.3233/NRE-151237 DOI: https://doi.org/10.3233/NRE-151237
van Lieshout ECC, van der Worp HB, Visser-Meily JMA, Dijkhuizen RM. Timing of repetitive transcranial magnetic stimulation onset for upper limb function after stroke: a systematic review and meta-analysis. Front Neurol 2019; 10: 1269.
https://doi.org/10.3389/fneur.2019.01269 DOI: https://doi.org/10.3389/fneur.2019.01269
Broe GA, Jorm AF, Creasey H, Grayson D, Edelbrock D, Waite LM, et al. Impact of chronic systemic and neurological disorders on disability, depression and life satisfaction. Int J Geriatr Psychiatry 1998; 13: 667-173.
https://doi.org/10.1002/(SICI)1099-1166(1998100)13:10<667::AID-GPS839>3.0.CO;2-G DOI: https://doi.org/10.1002/(SICI)1099-1166(1998100)13:10<667::AID-GPS839>3.0.CO;2-G
Putzke JD, Richards JS, Hicken BL, DeVivo MJ. Predictors of life satisfaction: A spinal cord injury cohort study. Arch Phys Med Rehabil 2002; 83: 555-561.
https://doi.org/10.1053/apmr.2002.31173 DOI: https://doi.org/10.1053/apmr.2002.31173
Soh S-E, McGinley JL, Watts JJ, Iansek R, Murphy AT, Menz HB, et al. Determinants of health-related quality of life in people with Parkinson's disease: a path analysis. Qual Life Res 2013; 22: 1543-1553.
https://doi.org/10.1007/s11136-012-0289-1 DOI: https://doi.org/10.1007/s11136-012-0289-1
Zangen A, Roth Y, Voller B, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 2005; 116: 775-779.
https://doi.org/10.1016/j.clinph.2004.11.008 DOI: https://doi.org/10.1016/j.clinph.2004.11.008
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLoS Med 2021; e1003583
https://doi.org/10.1371/journal.pmed.1003583 DOI: https://doi.org/10.1371/journal.pmed.1003583
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol 2021; 134: 103-112.
https://doi.org/10.1016/j.jclinepi.2021.02.003 DOI: https://doi.org/10.1016/j.jclinepi.2021.02.003
WHO. Neurological disorders: public health challenges. Geneva (Switzerland). WHO Library Cataloguing 2006.
Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
https://doi.org/10.1136/bmj.d5928 DOI: https://doi.org/10.1136/bmj.d5928
Cohen J. Statistical power analysis for the behavioral sciences. New York: Academic Press; 2013.
https://doi.org/10.4324/9780203771587 DOI: https://doi.org/10.4324/9780203771587
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. 2nd edition. Chichester, UK: John Wiley & Sons; 2019.
https://doi.org/10.1002/9781119536604 DOI: https://doi.org/10.1002/9781119536604
Arias P, Vivas J, Grieve KL, Cudeiro J. Controlled trial on the effect of 10 days low-frequency repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease. Mov Disord 2010; 25: 1830-1838.
https://doi.org/10.1002/mds.23055 DOI: https://doi.org/10.1002/mds.23055
Benito J, Kumru H, Murillo N, Costa U, Medina J, Tormos JM, et al. Motor and gait improvement in patients with incomplete spinal cord injury induced by high-frequency repetitive transcranial magnetic stimulation. Top Spinal Cord Inj Rehabil 2012; 18: 106-112.
https://doi.org/10.1310/sci1802-106 DOI: https://doi.org/10.1310/sci1802-106
Benninger DH, Berman BD, Houdayer E, Pal N, Luckenbaugh DA, Schneider L, et al. Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease. Neurology 2011; 76: 601-609.
https://doi.org/10.1212/WNL.0b013e31820ce6bb DOI: https://doi.org/10.1212/WNL.0b013e31820ce6bb
Benninger DH, Iseki K, Kranick S, Luckenbaugh DA, Houdayer E, Hallett M. Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of parkinson disease. Neurorehabil Neural Repair 2012; 26: 1096-1105.
https://doi.org/10.1177/1545968312445636 DOI: https://doi.org/10.1177/1545968312445636
Chang WH, Kim YH, Bang OY, Kim ST, Park YH, Lee PKW. Long-term effects of RTMS on motor recovery in patients after subacute stroke. J Rehabil Med 2010; 42: 758-764.
https://doi.org/10.2340/16501977-0590 DOI: https://doi.org/10.2340/16501977-0590
Cohen OS, Rigbi A, Yahalom G, Warman-Alaluf N, Nitsan Z, Zangen A, et al. Repetitive deep TMS for Parkinson disease: a 3-month double-blind, randomized sham-controlled study. J Clin Neurophysiol 2018; 35: 159-165.
https://doi.org/10.1097/WNP.0000000000000455 DOI: https://doi.org/10.1097/WNP.0000000000000455
El-Tamawy MS, Shehata HS, Shalaby NM, Nawito A, Esmail EH. Can repetitive transcranial magnetic stimulation help on-freezers with Parkinson's disease? Egypt J Neurol Psychiatry Neurosurg 2013; 50: 355-360.
https://doi.org/10.1016/j.jns.2013.07.464 DOI: https://doi.org/10.1016/j.jns.2013.07.464
Forogh B, Ahadi T, Nazari M, Sajadi S, Latif LA, Akhavan Hejazi SM, et al. The effect of repetitive transcranial magnetic stimulation on postural stability after acute stroke: a clinical trial. Basic Clin Neurosci 2017; 8: 405-412.
https://doi.org/10.18869/nirp.bcn.8.5.405 DOI: https://doi.org/10.18869/nirp.bcn.8.5.405
Guan YZ, Li J, Zhang XW, Wu S, Du H, Cui LY, et al. Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: a one-year longitudinal randomized trial. CNS Neurosci Ther 2017; 23: 940-946.
https://doi.org/10.1111/cns.12762 DOI: https://doi.org/10.1111/cns.12762
Hamada M, Ugawa Y, Tsuji S. High-frequency rTMS over the supplementary motor area improves bradykinesia in Parkinson's disease: subanalysis of double-blind sham-controlled study. J Neurol Sci 2009; 287: 143-146.
https://doi.org/10.1016/j.jns.2009.08.007 DOI: https://doi.org/10.1016/j.jns.2009.08.007
Huang YZ, Lin LF, Chang KH, Hu CJ, Liou TH, Lin YN. Priming with 1-Hz repetitive transcranial magnetic stimulation over contralesional leg motor cortex does not increase the rate of regaining ambulation within 3 months of stroke: a randomized controlled trial. Am J Phys Med Rehabil 2018; 97: 339-345.
https://doi.org/10.1097/PHM.0000000000000850 DOI: https://doi.org/10.1097/PHM.0000000000000850
Ji S-G, Cha H-G, Kim K-J, Kim M-K. Effects of motor imagery practice in conjunction with repetitive transcranial magnetic stimulation on stroke patients. J Magn 2014; 19: 181-184.
https://doi.org/10.4283/JMAG.2014.19.2.181 DOI: https://doi.org/10.4283/JMAG.2014.19.2.181
Ji S-G, Kim M-K. The effects of repetitive transcranial magnetic stimulation on the gait of acute stroke patients. J Magn 2015; 20: 129-132.
https://doi.org/10.4283/JMAG.2015.20.2.129 DOI: https://doi.org/10.4283/JMAG.2015.20.2.129
Khedr EM, Farweez HM, Islam H. Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson's disease patients. Eur J Neurol 2003; 10: 567-572.
https://doi.org/10.1046/j.1468-1331.2003.00649.x DOI: https://doi.org/10.1046/j.1468-1331.2003.00649.x
Kim WS, Jung SH, Oh MK, Min YS, Lim JY, Paik NJ. Effect of repetitive transcranial magnetic stimulation over the cerebellum on patients with ataxia after posterior circulation stroke: a pilot study. J Rehabil Med 2014; 46: 418-423.
https://doi.org/10.2340/16501977-1802 DOI: https://doi.org/10.2340/16501977-1802
Kumru H, Benito-Penalva J, Valls-Sole J, Murillo N, Tormos JM, Flores C, et al. Placebo-controlled study of rTMS combined with Lokomat® gait training for treatment in subjects with motor incomplete spinal cord injury. Exp Brain Res 2016; 234: 3447-3455.
https://doi.org/10.1007/s00221-016-4739-9 DOI: https://doi.org/10.1007/s00221-016-4739-9
Lin YN, Hu CJ, Chi JY, Lin LF, Yen TH, Lin YK, et al. Effects of repetitive transcranial magnetic stimulation of the unaffected hemisphere leg motor area in patients with subacute stroke and substantial leg impairment: a pilot study. J Rehabil Med 2015; 47: 305-310.
https://doi.org/10.2340/16501977-1943 DOI: https://doi.org/10.2340/16501977-1943
Lin LF, Chang KH, Huang YZ, Lai CH, Liou TH, Lin YN. Simultaneous stimulation in bilateral leg motor areas with intermittent theta burst stimulation to improve functional performance after stroke: a feasibility pilot study. Eur J Phys Rehabil Med 2019; 55: 162-168.
https://doi.org/10.23736/S1973-9087.18.05245-0 DOI: https://doi.org/10.23736/S1973-9087.18.05245-0
Lomarev MP, Kanchana S, Bara-Jimenez W, Iyer M, Wassermann EM, Hallett M. Placebo-controlled study of rTMS for the treatment of Parkinson's disease. Mov Disord 2006; 21: 325-331.
https://doi.org/10.1002/mds.20713 DOI: https://doi.org/10.1002/mds.20713
Ma J, Gao L, Mi T, Sun J, Chan P, Wu T. Repetitive transcranial magnetic stimulation does not improve the sequence effect in freezing of gait. Parkinsons Dis 2019; 2196195.
https://doi.org/10.1155/2019/2196195 DOI: https://doi.org/10.1155/2019/2196195
Mi TM, Garg S, Ba F, Liu AP, Wu T, Gao LL, et al. High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial. Park Relat Disord 2019; 68: 85-90.
https://doi.org/10.1016/j.parkreldis.2019.10.009 DOI: https://doi.org/10.1016/j.parkreldis.2019.10.009
Mori F, Codecà 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: 295-300.
https://doi.org/10.1111/j.1468-1331.2009.02806.x DOI: https://doi.org/10.1111/j.1468-1331.2009.02806.x
Sasaki N, Abo M, Hara T, Yamada N, Niimi M, Kakuda W. High-frequency rTMS on leg motor area in the early phase of stroke. Acta Neurol Belg 2017; 117: 189-194.
https://doi.org/10.1007/s13760-016-0687-1 DOI: https://doi.org/10.1007/s13760-016-0687-1
Wang RY, Tseng HY, Liao KK, Wang CJ, Lai KL, Yang YR. RTMS combined with task-oriented training to improve symmetry of interhemispheric corticomotor excitability and gait performance after stroke: a randomized trial. Neurorehabil Neural Repair 2012; 26: 222-230.
https://doi.org/10.1177/1545968311423265 DOI: https://doi.org/10.1177/1545968311423265
Wang RY, Wang FY, Huang SF, Yang YR. High-frequency repetitive transcranial magnetic stimulation enhanced treadmill training effects on gait performance in individuals with chronic stroke: a double-blinded randomized controlled pilot trial. Gait Posture 2019; 68: 382-387.
https://doi.org/10.1016/j.gaitpost.2018.12.023 DOI: https://doi.org/10.1016/j.gaitpost.2018.12.023
Yang YR, Tseng CY, Chiou SY, Liao KK, Cheng SJ, Lai KL, et al. Combination of rTMS and treadmill training modulates corticomotor inhibition and improves walking in parkinson disease: a randomized trial. Neurorehabil Neural Repair 2013; 27: 79-86.
https://doi.org/10.1177/1545968312451915 DOI: https://doi.org/10.1177/1545968312451915
Zanette G, Forgione A, Manganotti P, Fiaschi A, Tamburin S. The effect of repetitive transcranial magnetic stimulation on motor performance, fatigue and quality of life in amyotrophic lateral sclerosis. J Neurol Sci 2008; 270: 18-22.
https://doi.org/10.1016/j.jns.2008.01.011 DOI: https://doi.org/10.1016/j.jns.2008.01.011
Tung YC, Lai CH, Liao C De, Huang SW, Liou TH, Chen HC. Repetitive transcranial magnetic stimulation of lower limb motor function in patients with stroke: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil 2019; 33: 1102-1012.
https://doi.org/10.1177/0269215519835889 DOI: https://doi.org/10.1177/0269215519835889
Xie YJ, Gao Q, He CQ, Bian R. Effect of repetitive transcranial magnetic stimulation on gait and freezing of gait in Parkinson disease: a systematic review and meta-analysis. Arch Phys Med Rehabil 2020; 101: 130-140.
https://doi.org/10.1016/j.apmr.2019.07.013 DOI: https://doi.org/10.1016/j.apmr.2019.07.013
Hoogendam JM, Ramakers GMJ, Di Lazzaro V. Physiology of repetitive transcranial magnetic stimulation of the human brain. Brain Stimul 2010; 3: 95-118.
https://doi.org/10.1016/j.brs.2009.10.005 DOI: https://doi.org/10.1016/j.brs.2009.10.005
Bailey NW, Hoy KE, Rogasch NC, Thomson RH, McQueen S, Elliot D, et al. Differentiating responders and non-responders to rTMS treatment for depression after one week using resting EEG connectivity measures. J Affect Disord 2019; 242: 68-79.
https://doi.org/10.1016/j.jad.2018.08.058 DOI: https://doi.org/10.1016/j.jad.2018.08.058
He R, Fan J, Wang H, Zhong Y, Ma J. Differentiating responders and non-responders to rTMS treatment for disorder of consciousness using EEG after-effects. Front Neurol 2020; 11: 583268.
https://doi.org/10.3389/fneur.2020.583268 DOI: https://doi.org/10.3389/fneur.2020.583268
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