None listed
Conditions
Brief summary
After stroke, 85% of patients never regain full function in the arm and hand. Recovery from stroke requires that nerve cells in adjacent brain areas take over some of the lost function. However, this is thought to be difficult to achieve in brain areas around a stroke because of an increase in the activity of circuits that tend to ‘turn off’ or ‘inhibit’ these areas. We plan in this study to alter the activity of this circuit using external electrical stimulation delivering bursts of electrical pulses to the brain area opposite from the stroke side. This will be combined with a physiotherapy programme designed to maximise the improvement in functioning of the affected arm and hand.
Interventions
External intermittent theta burst stimulation delivering bursts of electrical pulses to the motor cortex on the opposite hemisphere from the stroke; combined with a physiotherapy rehabilitation programme designed to maximize the improvement in functioning of the affected arm and hand. Sham stimulation + rehabilitation (concurrent) to all participants for the first 3 weeks to measure the response to rehabilitation, followed by randomization into two groups as below:
a) Burst stimulation + rehabi
External intermittent theta burst stimulation delivering bursts of electrical pulses to the motor cortex on the opposite hemisphere from the stroke; combined with a physiotherapy rehabilitation programme designed to maximize the improvement in functioning of the affected arm and hand. Sham stimulation + rehabilitation (concurrent) to all participants for the first 3 weeks to measure the response to rehabilitation, followed by randomization into two groups as below: a) Burst stimulation + rehabilitation from week-4 to week-7 (4 weeks), and Sham stimulation + rehabilitation from week-8 to week-11 (4 weeks) (Group 1); or b) Sham stimulation + rehabilitation from week-4 to week-7, and Burst stimulation + rehabilitation from week-8 to week-11 (Group 2). Burst/sham stimulation will be delivered by a researcher using the STARSTIM R32 device (Neuroelectrics, Barcelona SLU, Spain). Stimulation electrodes will be placed to target the motor cortex. At initial optimization, stimulation intensity will be determined by the effect of single electrical pulses (500 µs to 1000 µs duration) on the size of motor evoked potentials (MEPs) elicited from the opposite affected cortex and measured in the paretic hand, using a single transcranial magnetic stimulation (TMS) pulse. Interstimulus intervals will be varied between 3 and 15 ms in random order and the optimal timing and intensity (up to a maximum of 1 mA) determined that reduces the amplitude of the averaged MEP by 15% or more. We have found it optimal in our animal studies to set the intensity at the minimum level that induces interhemispheric inhibition measured in this way, and that the same stimulation intensity applied during burst stimulation modulates this inhibition and improves recovery from stroke. If the intensity is unable to be determined here using this TMS procedure, a standard intensity (0.5 mA to 1 mA) will be used, based on the effect of a single pulse of the electrical stimulation recorded from scalp electrodes fitted over the opposite hemisphere. This intensity range resulted in improved motor function in our pilot implanted stimulation protocol, studied in two human participants. The initial burst stimulation pattern will consist of 50 Hz pulse triplets repeating at 5 Hz for 2 seconds in every 10 seconds, at the intensity set as above. The stimulation design can be adjusted during the trial to further optimize augmentation of participants’ rehabilitation capability. This might include burst or spike frequency adjustment, or minor subthreshold adjustments of stimulation intensity, as well as pseudorandom presentation of the proposed stimuli. Physiotherapy rehabilitation protocol: All participants will receive an intensive one-on-one physiotherapy programme for a total of 11-weeks aimed at maximising function of the affected upper limb. This will comprise: - Three (week days) x one hour intervention at the School of Physiotherapy - Home (GRASP) programme to be done daily (including weekends) - Participants will rotate around a circuit of exercises which will include: o Stretching o Strengthening individual major upper limb muscles (progressive resisted) o Functional upper limb activities (both unilateral and bilateral tasks) - Exercises will be individualised to the participant’s current ability and side affected. - The programme will be delivered by a physiotherapist specialised in neurorehabilitation. The stimulation (burst/sham) will be delivered concurrently with the physiotherapy rehabilitation programme (i.e. one-hour three-times a week)
Sponsors
Professor John Reynolds
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in the study, participants must meet all of the following inclusion criteria: 1. Capable of understanding and signing an informed consent form 2. Have a cortical or subcortical stroke at least 4 months earlier, screened by prior CT/MRI and verified by study MRI 3. Aged at least 18 years on the day of consent 4. Confirmation of intact cortical tracts by the presence of a TMS-elicited MEP recorded from the paretic upper limb. 5. Been assessed by Physiotherapy and deemed suitable (likely to be able to participate in 80% or more of the 11 weeks of three-days-a-week of physiotherapy sessions).
Exclusion criteria
To be included in the study, participants must meet none of the following exclusion criteria: 1. History of epileptic seizures 2. Participants with pacemakers/defibrillators 3. Participants who have contraindications for MRI and TMS 4. Female participants who are or intend to become pregnant 5. Participants who, in the opinion of the investigators, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved). 6. Participants who have pain, significant musculotendinous or bony restrictions of the affected upper limb, chronic disease (other than stroke) that will independently cause significant disability or weakness of the affected upper limb. 7. Any participant for whom the investigators believe, for any reason, that participation would not be an acceptable risk.
Outcome results
None listed