None listed
Conditions
Brief summary
As we know, stroke affects about 9000 people each year in New Zealand, with a disproportionate ratio affecting the Maori and Pacific people. About 85% of these people often don't regain their upper limb function and one can imagine that this affects activities of daily living and hence quality of life. It has been suggested in physiological studies that there is enhanced interhemispheric inhibition between the neural circuits of the motor cortex. This makes recovery after stroke difficult and potentially explains why some patients never regain complete upper limb function. In rat models, it has shown that intermittent burst stimulation significantly improves forelimb function in rats after stroke; this has shown promise for us to do a translational study with human beings. The i-START trial aims to recruit up to 10 participants that will be implanted with the electrodes and another 10 participants as the control group. For the patients who meet the inclusion criteria, they will have resting state EEG and the integrity of the descending motor pathways assessed from motor-evoked potentials (MEPs) elicited in the affected limb using single-pulse transcranial magnetic stimulation (TMS). Following that, they will have a structured assessment of their upper limb function by the physiotherapists. If all the assessments are acceptable, they will undergo a functional MRI and tractography imaging for surgical planning. For the group receiving implanted stimulators, they will be either randomised to an immediate or delayed start, where the stimulator will either be switched on immediately or left off until 6 weeks after implantation has elapsed. Both the implanted and non-implanted group will undergo an intense physiotherapy session each day for the next 12 weeks. Both groups will be assessed at week 6, 12 and 26 to determine the acceptability of retaining the stimulators as well their upper limb function.
Interventions
The cohort of stroke patients will be identified and will have had a cortical/subcortical stroke proven on imaging (CT/MRI). Those eligible for surgery will undergo a further MRI Stealth and tractography scan to determine preservation of motor tracts and for surgical planning. They will also undergo transcranial magnetic stimulation (TMS) to determine presence of Motor Evoked Potentials (MEPs). The eligible participants and those who consent to the surgical procedure will then undergo implantati
The cohort of stroke patients will be identified and will have had a cortical/subcortical stroke proven on imaging (CT/MRI). Those eligible for surgery will undergo a further MRI Stealth and tractography scan to determine preservation of motor tracts and for surgical planning. They will also undergo transcranial magnetic stimulation (TMS) to determine presence of Motor Evoked Potentials (MEPs). The eligible participants and those who consent to the surgical procedure will then undergo implantation of the stimulators on the contralateral side of the lesion on the motor cortex extradurally. This will involve the patient being anaesthetised under general anaesthesia (GA), being positioned and with the use of the MRI STEALTH neuronavigation system to identify the contralateral motor cortex to the stroke side. One burr hole will be performed at the site identified followed by a small trepanation of the skull. Two (2) Lamitrode 44 electrodes (St Jude Medical, Neurodivision, Plano, Tx, USA) will be placed on the dura overlying the motor cortex as demonstrated by the MRI. We will then do a subcutaneous tunnelling of the electrode lead behind the ear to mid thorax, connect an extension lead of 60cm (St Jude Medical) and tunnelling that further to exit at the right or left abdominal fossa which will be connected to an external pulse generator. This operation is estimated to take about 60 to 90 minutes. They will then stay in the High Dependency Unit overnight for observations and have intravenous antibiotics for 24 hours post surgery. A postoperative STEALTH CT scan will also be performed to exclude any extradural hematoma and to fuse lead placement with the preoperative tractography data. The patients will then have their stimulation intensity identified via a recording of a motor-evoked potential (MEP) elicited in the unaffected upper limb from the external pulse generator pulses. The intensity will be set as midway point between the field potential and active motor thresholds. After approximately 10 days and following the initial setting of stimulation intensity as stated before, the external pulse generator and the extension lead will be removed. The remaining electrode lead (in the mid thorax) will then be connected to the Proclaim Internal Pulse Generator (IPG) (St Jude Medical). This procedure will be done under local anaesthetic and will take about 15 minutes. The IPG will then be programmed to reflect the established stimulation intensity. This system/implant will remain in-situ indefinitely as there are no long-term risks from leaving the electrodes implanted. Following this, both implanted and non-implanted groups will undergo intense physiotherapy sessions for the next 12 weeks. In the implanted group, one group will be randomised to have an immediate start (day 3) and the other group will have a delayed start i.e. starting at day 45. During and after this period of physiotherapy, they will assessed on their upper limb motor function. The physiotherapy sessions will consist of: - daily (week days) x one hour intervention at the School of Physiotherapy - home (GRASP) programme to be done daily (including weekends) {Graded Repetitive Arm Supplementary Programme (GRASP) is a programme designed to improve upper limb function in post-stroke patients. It comes with a manual that will be distributed and taught to the patients to allow them to do the exercises-range of motion, strengthening, weigh-bearing, functional tasks and fine motor skills, at home to supplement the intense physiotherapy sessions. They are encouraged to spend at least half an hour each day doing those exercises at home) - participants will rotate around a circuit of exercises which will include: stretching, strengthening individual major upper limb muscles (progressive resisted), functional upper limb activities (both unilateral and bilateral tasks) Exercises will be individualised to the participant's current ability and side affected. The programme is designed by Professor Leigh Hale (Head of Physiotherapy) and will be delivered by final year undergraduate physiotherapy students under the supervision of a School of Physiotherapy neurorehabilitation clinical educator/supervisor. Depending on when the participants are available, the participants can either attend as a group or individually-this will not change their exercises as they will be individualised exercises. All patients will be given an exercise book as a log book to determine their attendance and exercises performed at home.
Sponsors
Ministry of Business, Innovation and Employment
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged at least 18 years on the day of consent 2. capable of understanding and signing an informed consent form 3. have a cortical or subcortical stroke at least 4 months earlier, screened by prior CT/MRI and verified by study MRI 4. been assessed by physiotherapy and deemed suitable (UEFM 20 to 50-moderate to mild upper limb function; Motor Assessment Scale: 2/6 on the Upper Arm Function scale; likely to be able to participate in 80% or more of the 12 weeks of daily physiotherapy post-surgery sessions) 5. suitable and fit for surgery
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 8. patients in whom any anticoagulation treatment cannot be transiently stopped in the preoperative period, analogous to what is done in the routine brain surgery (5 to 10 days stop before the surgery, and 2 days postoperatively, depending on the medication use)
Outcome results
None listed