Cerebral Theta-Burst Stimulation Combined with Physiotherapy in Patients with Incomplete Spinal Cord Injury: A Pilot Randomized Controlled Trial
DOI:
https://doi.org/10.2340/jrm.v55.4375Keywords:
intermittent theta-burst stimulation, physiotherapy, spinal cord injury, lower extremity motor functionAbstract
Objective: To measure the effects of cerebral intermittent theta-burst stimulation with physiotherapy on lower extremity motor recovery in patients with incomplete spinal cord injury.
Design: Randomized, double-blinded, sham-controlled trial.
Subjects: Adults with incomplete spinal cord injury.
Methods: A total of 38 patients with incomplete spinal cord injury were randomized into either an intermittent theta-burst stimulation or a sham group. Both groups participated in physiotherapy 5 times per week for 9 weeks, and cerebral intermittent theta-burst stimulation or sham intermittent theta-burst stimulation was performed daily, immediately before physiotherapy. The primary outcomes were lower extremity motor score (LEMS), root-mean square (RMS), RMS of the quadriceps femoris muscle, walking speed (WS), and stride length (SL). Secondary outcomes comprised Holden Walking Ability Scale (HWAS) and modified Barthel Index (MBI). The outcomes were assessed before the intervention and 9 weeks after the start of the intervention.
Results: Nine weeks of cerebral intermittent theta-burst stimulation with physiotherapy intervention resulted in improved recovery of lower extremity motor recovery in patients with incomplete spinal cord injury. Compared with baseline, the changes in LEMS, WS, SL, RMS, HWAS, and MBI were significant in both groups after intervention. The LEMS, WS, SL, RMS, HWAS, and MBI scores were improved more in the intermittent theta-burst stimulation group than in the sham group.
Conclusion: Cerebral intermittent theta-burst stimulation with physiotherapy promotes lower extremity motor recovery in patients with incomplete spinal cord injury. However, this study included a small sample size and lacked a comparison of the treatment effects of multiple stimulation modes, the further research will be required in the future.
LAY ABSTRACT
Spinal cord injury is a serious condition caused by spinal trauma and tumours. Improving the patient’s limb function during recovery poses an important challenge. Transcranial magnetic stimulation technology is a new treatment used to improve nervous system function, which has shown promising results in treating spinal cord injuries in recent years. However, the effect of a specific type of magnetic stimulation, cerebral intermittent theta-burst stimulation, with routine physical therapy on lower extremity motor recovery in patients with incomplete spinal cord injury has not yet been explored. The results of this study suggest that 9 weeks of brain intermittent theta-burst stimulation combined with physical therapy has a positive short-term effect on lower extremity movement and recovery of daily living ability in patients with incomplete spinal cord injury, which might provide new insight into motor rehabilitation for spinal cord injury.
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References
Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG. Traumatic spinal cord injury. Nat Rev Dis Primers 2017; 3: 1-21. DOI: 10.1038/nrdp.2017.18
https://doi.org/10.1038/nrdp.2017.18 DOI: https://doi.org/10.1038/nrdp.2017.18
van Middendorp JJ, Hosman AJ, Donders AR, Pouw MH, Ditunno JF, Jr, Curt A, et al. A clinical prediction rule for ambulation outcomes after traumatic spinal cord injury: a longitudinal cohort study. Lancet 2011; 377: 1004-1010. doi:10.1016/s0140-6736(10)62276-3
https://doi.org/10.1016/S0140-6736(10)62276-3 DOI: https://doi.org/10.1016/S0140-6736(10)62276-3
Griffin JM, Bradke F. Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem. EMBO Mol Med 2020; 12: e11505. doi:10.15252/emmm.201911505
https://doi.org/10.15252/emmm.201911505 DOI: https://doi.org/10.15252/emmm.201911505
Hornby TG, Reisman DS, Ward IG, Scheets PL, Miller A, Haddad D, et al. Clinical Practice Guideline to improve locomotor function following chronic stroke, incomplete spinal cord injury, and brain injury. J Neurol Phys Ther 2020; 44: 49-100. doi:10.1097/npt.0000000000000303
https://doi.org/10.1097/NPT.0000000000000303 DOI: https://doi.org/10.1097/NPT.0000000000000303
Lo C, Tran Y, Anderson K, Craig A, Middleton J. Functional priorities in persons with spinal cord injury: using discrete choice experiments to determine preferences. J Neurotrauma 2016; 33: 1958-1968. doi:10.1089/neu.2016.4423
https://doi.org/10.1089/neu.2016.4423 DOI: https://doi.org/10.1089/neu.2016.4423
Xue X, Yang X, Tu H, Liu W, Kong D, Fan Z, et al. The improvement of the lower limb exoskeletons on the gait of patients with spinal cord injury: a protocol for systematic review and meta-analysis. Medicine (Baltimore) 2022; 101: e28709. doi:10.1097/MD.0000000000028709
https://doi.org/10.1097/MD.0000000000028709 DOI: https://doi.org/10.1097/MD.0000000000028709
Jendelova P. Therapeutic strategies for spinal cord injury. Int J Mol Sci 2018; 19. doi:10.3390/ijms19103200
https://doi.org/10.3390/ijms19103200 DOI: https://doi.org/10.3390/ijms19103200
Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature 2018; 563: 65-71. doi:10.1038/s41586-018-0649-2
https://doi.org/10.1038/s41586-018-0649-2 DOI: https://doi.org/10.1038/s41586-018-0649-2
Holmes D. Repairing the neural highway. Nature 2017; 552: S50-s51. doi:10.1038/d41586-017-07551-8
https://doi.org/10.1038/d41586-017-07551-8 DOI: https://doi.org/10.1038/d41586-017-07551-8
Tran AP, Warren PM, Silver J. The biology of regeneration failure and success after spinal cord injury. Physiol Rev 2018; 98: 881-917. doi:10.1152/physrev.00017.2017
https://doi.org/10.1152/physrev.00017.2017 DOI: https://doi.org/10.1152/physrev.00017.2017
Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol 2015; 126: 1071-1107. doi:10.1016/j.clinph.2015.02.001
https://doi.org/10.1016/j.clinph.2015.02.001 DOI: https://doi.org/10.1016/j.clinph.2015.02.001
Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 2014; 125: 2150-2206. doi:10.1016/j.clinph.2014.05.021
https://doi.org/10.1016/j.clinph.2014.05.021 DOI: https://doi.org/10.1016/j.clinph.2014.05.021
Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018). Clin Neurophysiol 2020; 131: 474-528. doi:10.1016/j.clinph.2019.11.002 DOI: https://doi.org/10.1016/j.clinph.2020.02.003
https://doi.org/10.1016/j.clinph.2019.11.002 DOI: https://doi.org/10.1016/j.clinph.2019.11.002
Beynel L, Powers JP, Appelbaum LG. Effects of repetitive transcranial magnetic stimulation on resting-state connectivity: a systematic review. NeuroImage 2020; 211: 116596. doi:10.1016/j.neuroimage.2020.116596
https://doi.org/10.1016/j.neuroimage.2020.116596 DOI: https://doi.org/10.1016/j.neuroimage.2020.116596
Iddings JA, Zarkou A, Field-Fote EC. Noninvasive neuromodulation and rehabilitation to promote functional restoration in persons with spinal cord injury. Curr Opin Neurol 2021; 34: 812-818. doi:10.1097/WCO.0000000000000997
https://doi.org/10.1097/WCO.0000000000000997 DOI: https://doi.org/10.1097/WCO.0000000000000997
Huang Y Z EMJ, Rounis E. Theta burst stimulation of the human motor cortex. Neuron 2005; 45: 201-206.
https://doi.org/10.1016/j.neuron.2004.12.033
Ljubisavljevic MR, Javid A, Oommen J, Parekh K, Nagelkerke N, Shehab S, et al. The effects of different repetitive transcranial magnetic stimulation (RTMS) protocols on cortical gene expression in a rat model of cerebral ischemic-reperfusion injury. PloS One 2015; 10: e0139892. doi:10.1371/journal.pone.0139892
https://doi.org/10.1371/journal.pone.0139892 DOI: https://doi.org/10.1371/journal.pone.0139892
Bonnì S, Ponzo V, Caltagirone C, Koch G. Cerebellar theta burst stimulation in stroke patients with ataxia. Functional Neurology. 2014;29:41-45. PMID: 25014048; PMCID: PMC4172246.
https://doi.org/10.11138/FNeur/2014.29.1.041 DOI: https://doi.org/10.11138/FNeur/2014.29.1.041
Liao LY, Xie YJ, Chen Y, Gao Q. Cerebellar theta-burst stimulation combined with physiotherapy in subacute and chronic stroke patients: a pilot randomized controlled trial. Neurorehabil Neural Repair 2021; 35: 23-32. doi:10.1177/1545968320971735
https://doi.org/10.1177/1545968320971735 DOI: https://doi.org/10.1177/1545968320971735
Gutiérrez-Muto AM, Castilla J, Freire M, Oliviero A, Tornero J. Theta burst stimulation: technical aspects about TMS devices. Brain Stimul 2020; 13: 562-564. doi:10.1016/j.brs.2020.01.002
https://doi.org/10.1016/j.brs.2020.01.002 DOI: https://doi.org/10.1016/j.brs.2020.01.002
Philip NS, Barredo J, Aiken E, Larson V, Jones RN, Shea MT, et al. Theta-burst transcranial magnetic stimulation for posttraumatic stress disorder. Am J Psychiatry 2019; 176: 939-948. doi:10.1176/appi.ajp.2019.18101160
https://doi.org/10.1176/appi.ajp.2019.18101160 DOI: https://doi.org/10.1176/appi.ajp.2019.18101160
Solomon EA, Sperling MR, Sharan AD, Wanda PA, Levy DF, Lyalenko A, et al. Theta-burst stimulation entrains frequency-specific oscillatory responses. Brain Stimul 2021; 14: 1271-1284. doi:10.1016/j.brs.2021.08.014
https://doi.org/10.1016/j.brs.2021.08.014 DOI: https://doi.org/10.1016/j.brs.2021.08.014
Zong X, Li Y, Liu C, Qi W, Han D, Tucker L, et al. Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization. Theranostics 2020; 10: 12090-12110. doi:10.7150/thno.51573
https://doi.org/10.7150/thno.51573 DOI: https://doi.org/10.7150/thno.51573
Kirshblum S, Snider B, Rupp R, Read MS. Updates of the International Standards for Neurologic Classification of Spinal Cord Injury: 2015 and 2019. Phys Med RehabilClin N Am 2020; 31: 319-330. doi:10.1016/j.pmr.2020.03.005
https://doi.org/10.1016/j.pmr.2020.03.005 DOI: https://doi.org/10.1016/j.pmr.2020.03.005
Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron 2005; 45: 201-206. doi:10.1016/j.neuron.2004.12.033
https://doi.org/10.1016/j.neuron.2004.12.033 DOI: https://doi.org/10.1016/j.neuron.2004.12.033
Ciesla N, Dinglas V, Fan E, Kho M, Kuramoto J, Needham D. Manual muscle testing: a method of measuring extremity muscle strength applied to critically ill patients. J Vis Exp 2011; 50: 2632. doi:10.3791/2632
https://doi.org/10.3791/2632 DOI: https://doi.org/10.3791/2632
Gilmore J, Islam M, Duncan J, Natu R, Martinez-Duarte R. Assessing the importance of the root mean square (RMS) value of different waveforms to determine the strength of a dielectrophoresis trapping force. Electrophoresis 2017; 38: 2561-2564. doi:10.1002/elps.201600551
https://doi.org/10.1002/elps.201600551 DOI: https://doi.org/10.1002/elps.201600551
Maranesi E, Riccardi GR, Lattanzio F, Di Rosa M, Luzi R, Casoni E, et al. Randomised controlled trial assessing the effect of a technology-assisted gait and balance training on mobility in older people after hip fracture: study protocol. BMJ Open 2020; 10: e035508. doi:10.1136/bmjopen-2019-035508
https://doi.org/10.1136/bmjopen-2019-035508 DOI: https://doi.org/10.1136/bmjopen-2019-035508
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. doi:10.1007/s00221-016-4739-9
https://doi.org/10.1007/s00221-016-4739-9 DOI: https://doi.org/10.1007/s00221-016-4739-9
Aminalroaya R, Mirzadeh FS, Heidari K, Alizadeh-Khoei M, Sharifi F, Effatpanah M, et al. The validation study of both the modified barthel and barthel index, and their comparison based on Rasch analysis in the hospitalized acute stroke elderly. Int J Aging Hum Dev 2021; 93: 864-880. doi:10.1177/0091415020981775
https://doi.org/10.1177/0091415020981775 DOI: https://doi.org/10.1177/0091415020981775
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. doi:10.1310/sci1802-106
https://doi.org/10.1310/sci1802-106 DOI: https://doi.org/10.1310/sci1802-106
Xu L, Gu H, Zhang Y. Research hotspots of the rehabilitation medicine use of sEMG in recent 12 years: a bibliometric analysis. J Pain Res 2022; 15: 1365-1377. doi:10.2147/JPR.S364977
https://doi.org/10.2147/JPR.S364977 DOI: https://doi.org/10.2147/JPR.S364977
Feng XJ, Huang YT, Huang YZ, Kuo CW, Peng CW, Rotenberg A, et al. Early transcranial direct current stimulation treatment exerts neuroprotective effects on 6-OHDA-induced Parkinsonism in rats. Brain Stimul 2020; 13: 655-663. doi:10.1016/j.brs.2020.02.002
https://doi.org/10.1016/j.brs.2020.02.002 DOI: https://doi.org/10.1016/j.brs.2020.02.002
Delarue Q, Chalfouh C, Guérout N. Spinal cord injury: can we repair spinal cord non-invasively by using magnetic stimulation? Neural Regen Res 2021; 16: 2429-2430. doi:10.4103/1673-5374.313033
https://doi.org/10.4103/1673-5374.313033 DOI: https://doi.org/10.4103/1673-5374.313033
Potter-Baker KA, Janini DP, Lin YL, Sankarasubramanian V, Cunningham DA, Varnerin NM, et al. Transcranial direct current stimulation (tDCS) paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: A pilot study. J Spinal Cord Med 2018; 41: 503-517. doi:10.1080/10790268.2017.1361562
https://doi.org/10.1080/10790268.2017.1361562 DOI: https://doi.org/10.1080/10790268.2017.1361562
Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med 2018; 379: 1244-1250. doi:10.1056/NEJMoa1803588
https://doi.org/10.1056/NEJMoa1803588 DOI: https://doi.org/10.1056/NEJMoa1803588
Krogh S, Aagaard P, Jønsson AB, Figlewski K, Kasch H. Effects of repetitive transcranial magnetic stimulation on recovery in lower limb muscle strength and gait function following spinal cord injury: a randomized controlled trial. Spinal Cord 2022; 60: 135-141. doi:10.1038/s41393-021-00703-8
https://doi.org/10.1038/s41393-021-00703-8 DOI: https://doi.org/10.1038/s41393-021-00703-8
Venkatesh K, Ghosh SK, Mullick M, Manivasagam G, Sen D. Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications. Cell Tissue Res 2019; 377: 125-151. doi:10.1007/s00441-019-03039-1
https://doi.org/10.1007/s00441-019-03039-1 DOI: https://doi.org/10.1007/s00441-019-03039-1
Holmes D. Spinal-cord injury: spurring regrowth. Nature 2017; 552: S49. doi:10.1038/d41586-017-07550-9
https://doi.org/10.1038/d41586-017-07550-9 DOI: https://doi.org/10.1038/d41586-017-07550-9
Jo HJ, Perez MA. Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury. Brain 2020; 143: 1368-1382. doi:10.1093/brain/awaa052
https://doi.org/10.1093/brain/awaa052 DOI: https://doi.org/10.1093/brain/awaa052
Tazoe T, Perez MA. Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury. Arch Phys Med Rehabil 2015; 96: S145-155. doi:10.1016/j.apmr.2014.07.418
https://doi.org/10.1016/j.apmr.2014.07.418 DOI: https://doi.org/10.1016/j.apmr.2014.07.418
Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: a systematic review and meta-analysis. Neuroscience and biobehavioral reviews 2016; 63: 43-64. doi:10.1016/j.neubiorev.2016.01.008
https://doi.org/10.1016/j.neubiorev.2016.01.008 DOI: https://doi.org/10.1016/j.neubiorev.2016.01.008
Huang Y, Liu AA, Lafon B, Friedman D, Dayan M, Wang X, et al. Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. eLife 2017; 6: 18834. doi:10.7554/eLife.18834
https://doi.org/10.7554/eLife.18834 DOI: https://doi.org/10.7554/eLife.18834
de Araújo AVL, Barbosa VRN, Galdino GS, Fregni F, Massetti T, Fontes SL, et al. Effects of high-frequency transcranial magnetic stimulation on functional performance in individuals with incomplete spinal cord injury: study protocol for a randomized controlled trial. Trials 2017; 18: 522. doi:10.1186/s13063-017-2280-1
https://doi.org/10.1186/s13063-017-2280-1 DOI: https://doi.org/10.1186/s13063-017-2280-1
Ardestani MM, Henderson CE, Salehi SH, Mahtani GB, Schmit BD, Hornby TG. Kinematic and neuromuscular adaptations in incomplete spinal cord injury after high- versus low-intensity locomotor training. J Neurotrauma 2019; 36: 2036-2044. doi:10.1089/neu.2018.5900
https://doi.org/10.1089/neu.2018.5900 DOI: https://doi.org/10.1089/neu.2018.5900
Amer A, Xia J, Smith M, Martin JH. Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP. Proc Nat Acad Sci U S A 2021; 118. doi:10.1073/pnas.2113192118
https://doi.org/10.1073/pnas.2113192118 DOI: https://doi.org/10.1073/pnas.2113192118
Kumru H, Murillo N, Samso JV, Valls-Sole J, Edwards D, Pelayo R, et al. Reduction of spasticity with repetitive transcranial magnetic stimulation in patients with spinal cord injury. Neurorehabil Neural Repair 2010; 24: 435-441. doi:10.1177/1545968309356095
https://doi.org/10.1177/1545968309356095 DOI: https://doi.org/10.1177/1545968309356095
Courtine G HJ, Van Den Brand R. Response to comment on "restoring voluntary control of locomotion after paralyzing spinal cord injury". Science 2012; 338: 328-328.
https://doi.org/10.1126/science.1226274 DOI: https://doi.org/10.1126/science.1226274
Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Natu Neurosci 2004; 7: 269-277. doi:10.1038/nn1195
https://doi.org/10.1038/nn1195 DOI: https://doi.org/10.1038/nn1195
Kakulas BA. Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord 2004; 42: 549-563. doi:10.1038/sj.sc.3101670
https://doi.org/10.1038/sj.sc.3101670 DOI: https://doi.org/10.1038/sj.sc.3101670
GBD 2016 Dementia Collaborators Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18: 459-480. doi:10.1016/s1474-4422(18)30499-x
https://doi.org/10.1016/S1474-4422(18)30499-X DOI: https://doi.org/10.1016/S1474-4422(18)30499-X
Nelson LD, Temkin NR, Dikmen S, Barber J, Giacino JT, Yuh E, et al. Recovery after mild traumatic brain injury in patients presenting to US Level I Trauma Centers: a Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. JAMA neurology 2019; 76: 1049-1059. doi:10.1001/jamaneurol.2019.1313
https://doi.org/10.1001/jamaneurol.2019.1313 DOI: https://doi.org/10.1001/jamaneurol.2019.1313
Diaz-Ríos M, Guertin PA, Rivera-Oliver M. Neuromodulation of spinal locomotor networks in rodents. Curr Pharm Des 2017; 23: 1741-1752. doi:10.2174/1381612823666170124111729
https://doi.org/10.2174/1381612823666170124111729 DOI: https://doi.org/10.2174/1381612823666170124111729
Hayes SC, White M, Wilcox CRJ, White HSF, Vanicek N. Biomechanical differences between able-bodied and spinal cord injured individuals walking in an overground robotic exoskeleton. PloS One 2022; 17: e0262915. doi:10.1371/journal.pone.0262915
https://doi.org/10.1371/journal.pone.0262915 DOI: https://doi.org/10.1371/journal.pone.0262915
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