Continuous Theta-Burst Stimulation of the Contralesional Primary Motor Cortex for Promotion of Upper Limb Recovery After Stroke: A Randomized Controlled Trial

Jord J T Vink; Eline C C van Lieshout; Willem M Otte; Ruben P A van Eijk; Mirjam Kouwenhoven; Sebastiaan F W Neggers; H Bart van der Worp; Johanna M A Visser-Meily; Rick M Dijkhuizen

doi:10.1161/STROKEAHA.123.042924

Continuous Theta-Burst Stimulation of the Contralesional Primary Motor Cortex for Promotion of Upper Limb Recovery After Stroke: A Randomized Controlled Trial

Stroke. 2023 Aug;54(8):1962-1971. doi: 10.1161/STROKEAHA.123.042924. Epub 2023 Jun 22.

Authors

Jord J T Vink^#^{1

2

3}, Eline C C van Lieshout^#^{1

2}, Willem M Otte^{1

4}, Ruben P A van Eijk^{5

6}, Mirjam Kouwenhoven², Sebastiaan F W Neggers^{1

3}, H Bart van der Worp⁶, Johanna M A Visser-Meily^{2

7}, Rick M Dijkhuizen¹

Affiliations

¹ Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, the Netherlands (J.J.T.V., E.C.C.v.L., W.M.O., S.F.W.N., R.M.D.).
² Center of Excellence in Rehabilitation Medicine, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University and De Hoogstraat Rehabilitation, the Netherlands (J.J.T.V., E.C.C.v.L., M.K., J.M.A.V.-M.).
³ Brain Science Tools B.V., De Bilt, the Netherlands (J.J.T.V., S.F.W.N.).
⁴ Department of Pediatric Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, the Netherlands (W.M.O.).
⁵ Biostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht and Utrecht University, the Netherlands (R.P.A.v.E.).
⁶ Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, the Netherlands (R.P.A.v.E., H.B.v.d.W.).
⁷ Department of Rehabilitation, Physical Therapy Science and Sports, Brain Center, University Medical Center Utrecht and Utrecht University, the Netherlands (J.M.A.V.-M.).

^# Contributed equally.

Abstract

Background: Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery.

Methods: We performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures.

Results: We enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P=0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P=0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P=0.0494). There were no serious adverse events.

Conclusions: Ten daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center.

Registration: URL: https://trialsearch.who.int/; Unique identifier: NTR6133.

Keywords: arm; brain; ischemic stroke; rehabilitation; stroke.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Motor Cortex*
Recovery of Function / physiology
Stroke Rehabilitation*
Stroke* / complications
Stroke* / therapy
Transcranial Magnetic Stimulation
Treatment Outcome
Upper Extremity

Associated data

ClinicalTrials.gov/NTR6133