Document Type: Original Research


1 PhD, Department of Physiotherapy, School of Rehabilitation Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 PhD, Student Research Committee, School of Rehabilitation Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 PhD, Rehabilitation Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 MD, Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 MD, Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

6 PhD, Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


Background: Repetitive transcranial magnetic stimulation (rTMS) is a novel technique that may improve recovery in patients with stoke, but the role of rTMS as an applied and practical treatment modality for stroke rehabilitation has not been established yet.
Objective: This study was conducted to determine the effects of a rehabilitation program (RP) in conjunction with rTMS on functional indices of the paretic upper limb in the subacute phase of stroke.
Material and Methods: In this experimental study, twenty patients in the subacute phase of stroke were randomly assigned into two groups: The high frequency rTMS (HF-rTMS) in conjunction with RP (experimental group), and the RP group (control group). The experimental group received 10 sessions of 20 Hz rTMS on the affected primary motor cortex and the other group received 10 sessions of RP. In experimental group, RP for the paretic hand was conducted following rTMS session. Box and block test (BBT), Fugl-Meyer Motor Assessment for upper limb (FMA-UL), grip strength and pinch strength were used to assess motor function before the first session and after the last session of treatment.
Results: Significant improvement in BBT, FMA-UL, grip strength and pinch strength was observed in both groups. Improvement of BBT and grip strength was significantly greater in the experimental group rather than the control group (p <0.05). FMA-UL score and the pinch strength were greater in the experimental group, although the differences were not statistically significant.
Conclusion: HF-rTMS in conjunction with RP is effective to improve the function of upper limb. It seems HF-rTMS is a novel feasible and safe technique for hemiparesis patients in the subacute phase of stroke.


  1. Guo Z, Jin Y, Peng H, Xing G, Liao X, Wang Y, et al. Ipsilesional High Frequency Repetitive Transcranial Magnetic Stimulation Add-On Therapy Improved Diffusion Parameters of Stroke Patients with Motor Dysfunction: A Preliminary DTI Study. Neural Plast. 2016;2016:6238575. doi: 10.1155/2016/6238575. PubMed PMID: 27840742. PubMed PMCID: PMC5093297.
  2. Buma FE, Lindeman E, Ramsey NF, Kwakkel G. Functional neuroimaging studies of early upper limb recovery after stroke: a systematic review of the literature. Neurorehabil Neural Repair. 2010;24:589-608. doi: 10.1177/1545968310364058. PubMed PMID: 20439501.
  3. Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8:741-54. doi: 10.1016/S1474-4422(09)70150-4. PubMed PMID: 19608100.
  4. Urton ML, Kohia M, Davis J, Neill MR. Systematic literature review of treatment interventions for upper extremity hemiparesis following stroke. Occup Ther Int. 2007;14:11-27. doi: 10.1002/oti.220. PubMed PMID: 17623376.
  5. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain. 1951;74:443-80. PubMed PMID: 14895765.
  6. Nakayama H, Jorgensen HS, Raaschou HO, Olsen TS. Recovery of upper extremity function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1994;75:394-8. PubMed PMID: 8172497.
  7. Stig Jørgense H, Nakayama H, Otto Raaschou H, Møller Pedersen P, Houth J, Skyhøj Olsen T. Functional and neurological outcome of stroke and the relation to stroke severity and type, stroke unit treatment, body temperature, age, and other risk factors: The Copenhagen Stroke Study. Top Stroke Rehabil. 2000;6:1-19. doi: 10.1310/bt7j-2n6u-vd53-e1qu.
  8. Wade DT, Langton-Hewer R, Wood VA, Skilbeck CE, Ismail HM. The hemiplegic arm after stroke: measurement and recovery. J Neurol Neurosurg Psychiatry. 1983;46:521-4. PubMed PMID: 6875585. PubMed PMCID: PMC1027442.
  9. Broeks JG, Lankhorst GJ, Rumping K, Prevo AJ. The long-term outcome of arm function after stroke: results of a follow-up study. Disabil Rehabil. 1999;21:357-64. PubMed PMID: 10503976.
  10. Calautti C, Baron JC. Functional neuroimaging studies of motor recovery after stroke in adults: a review. Stroke. 2003;34:1553-66. doi: 10.1161/01.STR.0000071761.36075.A6. PubMed PMID: 12738893.
  11. Johansen-Berg H, Dawes H, Guy C, Smith SM, Wade DT, Matthews PM. Correlation between motor improvements and altered fMRI activity after rehabilitative therapy. Brain. 2002;125:2731-42. PubMed PMID: 12429600.
  12. Liepert J, Bauder H, Wolfgang HR, Miltner WH, Taub E, Weiller C. Treatment-induced cortical reorganization after stroke in humans. Stroke. 2000;31:1210-6. PubMed PMID: 10835434.
  13. Kamble N, Netravathi M, Pal PK. Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) in movement disorders: a review. Parkinsonism Relat Disord. 2014;20:695-707. doi: 10.1016/j.parkreldis.2014.03.018. PubMed PMID: 24726453.
  14. Gupta M, Rajak B, Bhatia D, Mukherjee A. Transcranial magnetic stimulation therapy in spastic cerebral palsy children improves motor activity. J Neuroinfect Dis. 2016;7:2.
  15. 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. doi: 10.1177/1545968312451915. PubMed PMID: 22785003.
  16. Kimberley TJ, Schmidt RL, Chen M, Dykstra DD, Buetefisch CM. Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia. Front Hum Neurosci. 2015;9:385. doi: 10.3389/fnhum.2015.00385. PubMed PMID: 26217209.PubMed PMCID: PMC4496570.
  17. Kubis N. Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery. Front Neural Circuits. 2016;10:56. doi: 10.3389/fncir.2016.00056. PubMed PMID: 27512367. PubMed PMCID: PMC4961863.
  18. Takeuchi N. Overview of non-invasive brain stimulation for motor recovery after stroke. Int J Phys Med Rehabil. 2013;1:2. doi: 10.4172/2329-9096.1000114.
  19. Dimyan MA, Cohen LG. Contribution of transcranial magnetic stimulation to the understanding of functional recovery mechanisms after stroke. Neurorehabil Neural Repair. 2010;24:125-35. doi: 10.1177/1545968309345270. PubMed PMID: 19767591. PubMed PMCID: PMC2945387.
  20. Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol. 2006;117:2584-96. doi: 10.1016/j.clinph.2006.06.712. PubMed PMID: 16890483.
  21. Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004;55:400-9. doi: 10.1002/ana.10848. PubMed PMID: 14991818.
  22. Hsu WY, Cheng CH, Liao KK, Lee IH, Lin YY. Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke. 2012;43:1849-57. doi: 10.1161/STROKEAHA.111.649756. PubMed PMID: 22713491.
  23. Munoz Maniega S, Cvoro V, Chappell FM, Armitage PA, Marshall I, Bastin ME, et al. Changes in NAA and lactate following ischemic stroke: a serial MR spectroscopic imaging study. Neurology. 2008;71:1993-9. doi: 10.1212/01.wnl.0000336970.85817.4a. PubMed PMID: 19064881.
  24. Cramer SC. Repairing the human brain after stroke. II. Restorative therapies. Ann Neurol. 2008;63:549-60. doi: 10.1002/ana.21412. PubMed PMID: 18481291.
  25. Kim C, Choi HE, Jung H, Lee BJ, Lee KH, Lim YJ. Comparison of the Effects of 1 Hz and 20 Hz rTMS on Motor Recovery in Subacute Stroke Patients. Ann Rehabil Med. 2014;38:585-91. doi: 10.5535/arm.2014.38.5.585. PubMed PMID: 25379487.PubMed PMCID: PMC4221386.
  26. Desrosiers J, Bravo G, Hebert R, Dutil E, Mercier L. Validation of the Box and Block Test as a measure of dexterity of elderly people: reliability, validity, and norms studies. Arch Phys Med Rehabil. 1994;75:751-5. PubMed PMID: 8024419.
  27. Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985;39:386-91. PubMed PMID: 3160243.
  28. Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther. 1983;63:1606-10. PubMed PMID: 6622535.
  29. Sullivan KJ, Tilson JK, Cen SY, Rose DK, Hershberg J, Correa A, et al. Fugl-Meyer assessment of sensorimotor function after stroke: standardized training procedure for clinical practice and clinical trials. Stroke. 2011;42:427-32. doi: 10.1161/STROKEAHA.110.592766. PubMed PMID: 21164120.
  30. Gladstone DJ, Danells CJ, Black SE. The fugl-meyer assessment of motor recovery after stroke: a critical review of its measurement properties. Neurorehabil Neural Repair. 2002;16:232-40. doi: 10.1177/154596802401105171. PubMed PMID: 12234086.
  31. Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998;108:1-16. PubMed PMID: 9474057.
  32. Yozbatiran N, Alonso-Alonso M, See J, Demirtas-Tatlidede A, Luu D, Motiwala RR, et al. Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke. Stroke. 2009;40:309-12. doi: 10.1161/STROKEAHA.108.522144. PubMed PMID: 18845801. PubMed PMCID: PMC3366156.
  33. Kim YH, You SH, Ko MH, Park JW, Lee KH, Jang SH, et al. Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke. 2006;37:1471-6. doi: 10.1161/01.STR.0000221233.55497.51. PubMed PMID: 16675743.
  34. Ji S-G, Cha H-G, Kim M-K. Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation combined with mirror therapy. Journal of Magnetics. 2014;19:28-31. doi: 10.4283/jmag.2014.19.1.028.
  35. Rajak B, Gupta M, Bhatia D, Mukherjee A. Effect of repetitive Transcranial Magnetic Stimulation on hand function of spastic cerebral palsy children. J Neurol Disord. 2017;5:2. doi: 10.4172/2329-6895.1000339.
  36. Niimi M, Hashimoto K, Kakuda W, Miyano S, Momosaki R, Ishima T, et al. Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke. PLoS One. 2016;11:e0152241. doi: 10.1371/journal.pone.0152241. PubMed PMID: 27007747.PubMed PMCID: PMC4805302.
  37. Zhang X, Mei Y, Liu C, Yu S. Effect of transcranial magnetic stimulation on the expression of c-Fos and brain-derived neurotrophic factor of the cerebral cortex in rats with cerebral infarct. J Huazhong Univ Sci Technolog Med Sci. 2007;27:415-8. doi: 10.1007/s11596-007-0416-3. PubMed PMID: 17828499.
  38. Baba T, Kameda M, Yasuhara T, Morimoto T, Kondo A, Shingo T, et al. Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/Akt signaling pathway. Stroke. 2009;40:e598-e605. doi: 10.1161/strokeaha.109.563627.
  39. Gao F, Wang S, Guo Y, Wang J, Lou M, Wu J, et al. Protective effects of repetitive transcranial magnetic stimulation in a rat model of transient cerebral ischaemia: a microPET study. Eur J Nucl Med Mol Imaging. 2010;37:954-61. doi: 10.1007/s00259-009-1342-3. PubMed PMID: 20107794.
  40. Yoon KJ, Lee YT, Han TR. Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity or anti-apoptosis? Exp Brain Res. 2011;214:549-56. doi: 10.1007/s00221-011-2853-2. PubMed PMID: 21904929.
  41. Ogiue-Ikeda M, Kawato S, Ueno S. Acquisition of ischemic tolerance by repetitive transcranial magnetic stimulation in the rat hippocampus. Brain Res. 2005;1037:7-11. doi: 10.1016/j.brainres.2004.10.063. PubMed PMID: 15777747.
  42. Khedr EM, Etraby AE, Hemeda M, Nasef AM, Razek AA. Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke. Acta Neurol Scand. 2010;121:30-7. doi: 10.1111/j.1600-0404.2009.01195.x. PubMed PMID: 19678808.
  43. Greenough WT, Larson JR, Withers GS. Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. Behav Neural Biol. 1985;44:301-14. PubMed PMID: 2415103.
  44. Jones TA, Chu CJ, Grande LA, Gregory AD. Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J Neurosci. 1999;19:10153-63. PubMed PMID: 10559423.
  45. Kleim JA, Vij K, Ballard DH, Greenough WT. Learning-dependent synaptic modifications in the cerebellar cortex of the adult rat persist for at least four weeks. J Neurosci. 1997;17:717-21. PubMed PMID: 8987793.
  46. Biernaskie J, Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci. 2001;21:5272-80. PubMed PMID: 11438602.
  47. Stroemer RP, Kent TA, Hulsebosch CE. Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke. 1995;26:2135-44. PubMed PMID: 7482662.
  48. Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol. 2006;59:735-42. doi: 10.1002/ana.20845. PubMed PMID: 16634041.
  49. Dobkin BH. Training and exercise to drive poststroke recovery. Nat Clin Pract Neurol. 2008;4:76-85. doi: 10.1038/ncpneuro0709. PubMed PMID: 18256679. PubMed PMCID: PMC4099052.