Efficacy of rTMS and VCT on Upper Limb Function in Patients With Stroke

Efficacy of Repetitive Transcranial Magnetic Stimulation and Virtual Cycling Training on Upper Limb Function in Patients With Stroke

Stroke is the major cause of motor impairment and physical disabilities in the adult population. Spasticity and loss of dexterity are the common problems in stroke. Recently, current interventions, such as cycling training, virtual reality (VR) and repetitive transcranial magnetic stimulation (rTMS), were used for the treatment of upper extremity (UE) dysfunction in patients with stroke. However, few studies investigated the effects of the combinations of different treatment strategies using by integrating brain imaging and motor control studies. This project proposes different novel treatment strategies in the treatment of UE dysfunction in patients with stroke: combined inhibitory/facilitatory rTMS, VR-based cycling training (VCT), and combined rTMS and VCT. We hypothesize that the treatment effect of the combined protocol (optimal rTMS protocol and VCT) is more effective than single treatment due to integration of central and peripheral effects. Different treatment protocols will induce different changes in the brain reorganization and motor control, which further improve motor function, activity, participation, and health related quality of life (HRQOL).

This study aims to 1. identify the immediate effects of different treatment protocols in for UE training in these patients through brain image, motor control and clinical measures; 2. to determine the maintaining therapeutic effects; 3. to elucidate the most optimal treatment protocols; 4. to determine the neuro-motor control mechanism underlying clinical improvement; 5. to determine the clinimetric properties of the brain imaging and motor control measure that are responsive and valid for detecting changes after treatment protocol intervention, and 6. to identify clinical predictors influencing the outcome for treatment protocols. The research will offer valuable motor control biomarkers for outcome prediction and targeting patients who benefit from new protocols. This project is significant for the translational and evidence-based medicine on stroke neurorehabilitation.

repetitive transcranial magnetic stimulation, stroke, optimal treatment protocol, VR-based cycling training (VCT), randomized controlled trial, motor control, clinical predictors

In intermittent theta burst stimulation (iTBS group), they received iTBS (80% of active motor threshold) on affected hemisphere.

In continuous theta burst stimulation (cTBS group), they received cTBS (80% of active motor threshold) on unaffected hemisphere.

Continuous theta burst stimulation (cTBS group) at first followed by intermittent theta burst stimulation (iTBS group).

VCT group received the VCT training in addition to traditional rehabilitation. Each UE VCT session involved upper limb cycling training followed by UE training in addition to home program. The cycling program consisted of a warm-up exercise, twenty repetitions of hand push-up movements in the sitting position, UE cycling, and a cool-down exercise.

VCT+optimal rTMS group received the VCT training and optimal rTMS in addition to traditional rehabilitation.

In intermittent theta burst stimulation pattern (iTBS) will intermittently give a 2 s train of TBS every 10s repeated 2 times for a total of 40 times (low pulse: 1200 pulses in total) Other Names: intermittent theta burst stimulation

In continuous burst stimulation pattern (cTBS) will intermittently give a cTBS treatment consists of a continuous train of TBS for 40 seconds repeated for 2 times(low pulse: 1200 pulses in total). Other Names: continuous burst stimulation

In iTBS+cTBS pattern, continuous cTBS will be followed by intermittent iTBS (low pulse; 1200 pulses in total)

In sham burst stimulation pattern (sham TBS) will intermittently give a sham TBS treatment consists of a continuous train of TBS for 40 seconds(almost no pulse: 1200 pulses in total). Other Names: sham theta burst stimulation

The UE VCT programs were conducted three times per week, for 12 weeks. Each UE VCT session involved upper limb cycling training followed by UE training in addition to home program. The cycling program consisted of a warm-up exercise, twenty repetitions of hand push-up movements in the sitting position, UE cycling, and a cool-down exercise. The warm-up and cool-down exercises involved stretching and relaxing the head, neck, and the upper and lower body. Other Names: The upper extremity programs virtual cycling training program

In VCT+optimal rTMS group, VCT will be combined with optimal rTMS, which has the best outcome in phase 1.

Change from baseline of mechanical measurement for stroke after 3 weeks treatment and 3 months follow-up

Brunnstrom stage classification(by severity from stage 1 to stage 6), Modified Ashworth Scale (tension of upper limb from min(0) to max (4)) and National Institute of Health Stroke Scale (severity from min(0) to max(4))

Change from baseline of Muscle tone measurement for stroke after 3 weeks treatment and 3 months follow-up

Change from baseline of Muscle strength measurement for stroke after 3 weeks treatment and 3 months follow-up

Change from baseline of body composition for stroke in after 3 weeks treatment and 3 months follow-up

Inclusion Criteria: first stroke chronic stroke (onset > 3 months) unilateral cerebral lesion with hemiparesis or hemiplegia age of 20-80 years no epileptic spikes on the EEG Exclusion Criteria: brain stem or cerebellum stroke epilepsy aneurysm arteriovenous malformation psychiatric disease degenerative disease severe cognitive and communicative impairment or aphasia severe medical disease active medical problems metal implant in the body pregnancy poor cooperation with assessments

Chen YH, Chen CL, Huang YZ, Chen HC, Chen CY, Wu CY, Lin KC. Augmented efficacy of intermittent theta burst stimulation on the virtual reality-based cycling training for upper limb function in patients with stroke: a double-blinded, randomized controlled trial. J Neuroeng Rehabil. 2021 May 31;18(1):91. doi: 10.1186/s12984-021-00885-5.