Stroke Ischemic
Conditions
Keywords
Stroke, Upper-extremity, Hemiparesis, Paired Associative Stimulaton, Rehabilitation
Brief summary
Paired associative stimulation (PAS) delivered with multi-channel deep transcranial magnetic stimulation (dTMS) may enhance motor recovery in patients with first-ever ischemic stroke. This study evaluates whether dTMS-PAS targeting both primary motor cortices (M1-M1) improves upper-extremity hemiparesis when administered at the early subacute stage (up to three weeks poststroke).
Detailed description
Unilateral ischemic stroke disrupts the activity balance between the hemispheres, which hinder brains' recovery and treatments' efficiency. The most common and pervasive acquired postischemic stroke functional disorder is hemiparesis of the upper-extremity. The limited impact of conventional rehabilitation therapies is attributed to their inability to restore the interhemispheric balance. Thus, PAS protocol, delivered using dTMS, may benefit patients by regaining the interhemispheric balance. PAS is delivered over two different cortical brain areas, and the modulation of interhemispheric balance is determined by which area is stimulated by the first pulse and which by the second. In this study, the investigators apply a dTMS-PAS protocol over the two primary motor cortices, to restore the activity balance between M1-M1, alleviate upper-extremity hemiparesis symptoms, and promote functional recovery.
Interventions
DEVICEA multi-channel device with deep TMS coil (Brainsway Ltd., Jerusalem, Israel)
Active dTMS-PAS stimulation is applied at 120% of the individual RMT of the UH. Each session consists of 600 paired pulses, delivered bilaterally over M1-M1, with an inter-pulse interval (IPI) of 10 miliseconds (ms) and an inter-stimulus interval (ISI) of 3 seconds (s), for a total duration of 30 minutes (m).
Sponsors
Soroka University Medical Center
Ben-Gurion University of the Negev
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* The diagnosis of stroke is based on computed tomography (CT) or magnetic resonance imaging (MRI). * The diagnosis of first acute ischemic stroke in unilateral hemisphere within 3 weeks after onset. * Clinically evident arm hemiparesis attributable to acute ischemic stroke. * Age of 18-85 years. * The ability to sign a informed consent.
Exclusion criteria
* Any previous stroke. * Minor stroke with non-disabling deficit or rapidly improving neurological symptoms. * Prior participation in the present study, or planned participation in another therapeutic trial, prior to the final assessment in this trial. * Current participation in another study with an investigational drug or device. * Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test. * Any intracranial surgery, intraspinal surgery, or serious head trauma (any head injury that required hospitalization) within the past 3 months prior to participation in the current study. * Presence or history of intracranial neoplasm (except small meningiomas) or arteriovenous malformation. * Intracranial aneurysm, unless surgically or endovascularlytreated more than 3 months prior to participation in the current study. * Seizure at the onset of stroke or a history of epilepsy. * Life expectancy less than 3 months. * Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease. * Other serious illness, e.g., severe hepatic, cardiac, or renal failure. * Acute myocardial infarction or complex disease that may confound treatment assessment. * Cognitive or verbal impairment that prevented understanding of or cooperation with the research study. Under the following medical conditions, treatment was stopped, and patients were excluded from the study: * Acute worsening of \> 4 points on the NIH stroke scale (NIHSS). * Acute symptoms of headache nausea and vomiting suggestive of possible sICH. * Occurrence of seizures. * Appearance of a new ventricular arrhythmia, tachycardia, fibrillation etc. or a new life-threatening supraventricular arrhythmia (e.g., rapid atrial fibrillation or supraventricular tachycardia). * Symptomatic bradycardia - heart rate less than 50 beats per min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fugl - Meyer Assessment for Upper Extremity (FMA-UE) Score | From enrollment to one year after enrollment | The FMA-UE is a standardized, clinical, stroke-specific performance scale assessing motor impairement of the upper-extremity. It includes 33 items across four domains (shoulder-arm, wrist, hand, coordination), each scored 0-2 (total range 0-66). Higher scores indicate better motor function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Action Research Arm Test (ARAT) Score | From enrollment to one year after enrollement | The ARAT is a standardized clinical measure of arm-hand functional capacity consisting of 19 items across grasp, pinch, and gross movement (score range 0-57). Higher scores indicate better function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke. |
| Jebsen-Taylor Hand Function Test (JTHFT) Time | From enrollement to one year after enrollment | The JTHFT is a standardized clinical 7-task timed assessment of functional hand performance (writing, page turning, object lifting, etc.). Each task is scored by the time required to complete it, with a maximum allowed time of 120 seconds per task. Lower total time indicates better function. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke. |
| Box and Blocks Test (BBT) Score | From enrollement to one year after enrollement | The BBT is a standardized clinical measure, assessing unilateral manual dexterity by counting the number of blocks transferred in 60 seconds. Higher values indicate greater dexterity. Normative reference values are available by age, sex, and hand dominance, allowing interpretation relative to typical performance. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke. |
| Hand-Held Dynamometry Grip Strength | From enrollement to one year after enrollment | Grip strengh is assessed using a standardized clinical hand-held dynamometer, which provides an objective numerical measure of upper-extremity muscle strength. Higher values indicate greater strength. Normative reference values are available by age, sex, and hand dominance, allowing interpretation relative to typical performance. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke. |
| Disabilities of the ARM, Shoulder, and Hand (DASH) Score | From enrollement to one year after enrollment | The DASH is a 30-item self-report questionnaire assessing upper-extremity disability (0-100%). Higher scores indicate greater disability. Assessment Schedule: Pre-treatment, Post-treatment, 2 and 12 months. |
| Resting Motor Threshold (RMT) via transcranial magnetic stimulation (TMS) | From enrollment to one year after enrollment | RMT is the minimum TMS intensity required to elicit a measurable electromyography (EMG) response in the abductor pollicis brevis. Lower thresholds indicate higher corticospinal excitability. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions. |
| Motor evoked potential (MEP) Amplitude | From enrollement to one year after enrollment | MEP amplitude (peak-to-peak EMG response) reflects corticospinal excitability following TMS. Higher amplitudes indicate greater excitability. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions. |
| MEP Latency | From enrollment to one year after enrollment | Latency is the time from TMS pulse to the initial MEP peak, reflecting conduction speed. Shorter latency indicated faster neural conduction. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke.; plus pre- and post-protocol measurements during the first two PAS sessions. |
| Interhemispheric inhibition (IHI) via PAS | From enrollment to one year after enrollment | IHI quantifies inhibitory influence from one motor cortex to the other using PAS. Greater inhibition reflects stronger interhemispheric suppression. Assessment Schedule: Pre-treatment (up to three weeks poststroke), Post-treatment (three weeks consisting of 15 sessions), 1 and 2 months post-treatment, and 6,9, and 12 months poststroke; plus pre- and post-protocol measurements during the first two PAS sessions. |
Countries
Israel
Outcome results
None listed