Stroke
Conditions
Keywords
sensory impairment, sensory deficit, upper limb, transcranial magnetic stimulation, brain stimulation, rehabilitation
Brief summary
Stroke affects over 795,000 Americans every year and has an enormous impact on the well-being of American Veterans with 6,000 new stroke admissions every year. Many of these stroke survivors are living with disabilities that limit their everyday function. One of the major consequences of stroke is loss of sensation which manifests as inability to perceive touch, temperature, pain or limb movement. Lack of sensation hinders full functional recovery. Current treatments for sensory loss produce only limited improvements and do not achieve full recovery. Therefore, it is critical to develop new therapies to re-train sensory function. The investigators propose to evaluate a novel non-invasive brain stimulation treatment called repetitive Transcranial Magnetic Stimulation (rTMS). The effects of this technique on motor deficits following stroke have been studied, however rTMS for the treatment of sensory loss has not been examined to date. The investigators' study will examine for the first time if rTMS of a sensory brain region can improve sensory function in chronic stroke survivors.
Detailed description
Sensory deficits are present in the majority of stroke survivors. Inability to feel movement, touch or pain impairs the investigators' ability to interact with environment and diminished the quality of life. These sensory deficits significantly impair functional activity and slow down recovery during rehabilitation. Currently available sensory rehabilitation techniques can only partially restore sensory function. The main objective of this study is to test a novel approach to improve sensory function after stroke using non-invasive brain stimulation. This pilot study will measure an immediate effect of different repetitive Transcranial Magnetic Stimulation (rTMS) paradigms in a crossover single session design. The effect of intervention is measured with clinical measures of sensory and motor function and with neurophysiological assessment of sensory pathways. If the concept is demonstrated in this pilot study, then following the lead of other investigations of this type, this pilot will provide the foundation to test the efficacy of a long-term multi-session intervention of combined rTMS and peripherally directed therapy.
Interventions
OTHERrepetitive transcranial magnetic stimulation (rTMS)
3 types of interventions on different sessions * session 1 - High frequency rTMS targeting contralesional sensory cortex * session 2 - Low frequency rTMS * session 3 - sham rTMS
OTHERperipheral sensory stimulation
peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Medically stable at least 6 months after first ever stroke. * Sufficient endurance to participate in the study. * Cognition sufficiently intact to give valid informed consent to participate. * Age \> 18years. * Ability to follow 2 stage commands. * Impaired but not absent ability to feel touch, vibration and movement of the affected arm.
Exclusion criteria
* Acute or progressive cardiac, renal, respiratory, neurological disorders or malignancy. * Any psychiatric diagnosis or active psychological condition. * History of substance abuse within the last 6 months * More than one ischemic stroke or stroke affecting both sides. * Claustrophobia, or inability to operate the MRI patient call button. * Pregnancy or pregnancy planning during the study period. * Lower motor neuron damage or radiculopathy * Contraindications for rTMS according to the TMS-use guidelines (Rossi et al 2009). * Inability to understand English. * Significant neglect for those with left-sided deficits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Two-point Discrimination | up to 1 hour after intervention | Baseline measure is collected immediately before the intervention. There are two data collections following each intervention, one datacollection is immediately after the intervention and the second one is at 1 hour after intervention. Two-point discrimination was measured with Disk-Criminator disks (Baltimore, MD) by determining the subjects' ability to perceive two points on the disk as two separate points rather than as a single point. The distances between the two points ranged between 2 and 15 mm. One and two sensory points were presented in a pseudo-random order to subjects' 4th digit volar fingertip surface. A threshold is determined when seventy percent accuracy is exhibited for identifying the difference between single versus double point stimulation. |
| Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | up to 1 hour after intervention | Baseline measure is collected immediately before the intervention. Following each intervention, data is collected immediately after each intervention and at 1 hour after intervention. SEPs were recorded with a Cadwell Sierra Wave (Cadwell, Kennewick, WA) (LSCDVAMC) or with Powerlab 4/25T (AD Instruments Inc. Colorado Springs, CO) and a Grass Stimulator (Natus Neurology, Middleton, WI) (CC)44. The recording electrodes (1 cm diameter, gold cup electrodes filled with conductive paste) were placed 2 cm posterior to C3 & C4 (10-20 international system of EEG electrode placement) and the reference electrode at Fz (Figure 1). Stimulus was applied to the median nerve at the wrist. Ground electrodes were placed at the lateral epicondyle of the stimulated arm. The evoked response from 500 stimuli were recorded and averaged for a single trial. Three SEP trials were recorded then analyzed. Latencies (in milliseconds) were determined for N20. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stroke Cohort Each subject is provided with three different brain stimulation interventions in a single arm, single session crossover design study
repetitive transcranial magnetic stimulation (rTMS): 3 types of interventions on different sessions
* session 1 - High frequency rTMS targeting contralesional sensory cortex
* session 2 - Low frequency rTMS
* session 3 - sham rTMS
peripheral sensory stimulation: peripheral sensory electrical stimulation and vibration of the stroke-affected hand administered concurrently with each rTMS | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Stroke Cohort |
|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
| two point discrimination | 12.5 mm STANDARD_DEVIATION 5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency
Baseline measure is collected immediately before the intervention. Following each intervention, data is collected immediately after each intervention and at 1 hour after intervention. SEPs were recorded with a Cadwell Sierra Wave (Cadwell, Kennewick, WA) (LSCDVAMC) or with Powerlab 4/25T (AD Instruments Inc. Colorado Springs, CO) and a Grass Stimulator (Natus Neurology, Middleton, WI) (CC)44. The recording electrodes (1 cm diameter, gold cup electrodes filled with conductive paste) were placed 2 cm posterior to C3 & C4 (10-20 international system of EEG electrode placement) and the reference electrode at Fz (Figure 1). Stimulus was applied to the median nerve at the wrist. Ground electrodes were placed at the lateral epicondyle of the stimulated arm. The evoked response from 500 stimuli were recorded and averaged for a single trial. Three SEP trials were recorded then analyzed. Latencies (in milliseconds) were determined for N20.
Time frame: up to 1 hour after intervention
Population: stroke cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Frequency rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | Immediately post-intervention | -1.1 msec | Standard Deviation 2.3 |
| High Frequency rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | One hour post-intervention | 0.1 msec | Standard Deviation 2 |
| Low Frequency rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | Immediately post-intervention | 0.1 msec | Standard Deviation 2.2 |
| Low Frequency rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | One hour post-intervention | -1.8 msec | Standard Deviation 5.8 |
| Sham rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | Immediately post-intervention | 0.7 msec | Standard Deviation 3 |
| Sham rTMS | Change From Baseline in N20 Somatosensory Evoked Potential(SSEP) Peak Latency | One hour post-intervention | 1.2 msec | Standard Deviation 2.5 |
Primary
Change From Baseline in Two-point Discrimination
Baseline measure is collected immediately before the intervention. There are two data collections following each intervention, one datacollection is immediately after the intervention and the second one is at 1 hour after intervention. Two-point discrimination was measured with Disk-Criminator disks (Baltimore, MD) by determining the subjects' ability to perceive two points on the disk as two separate points rather than as a single point. The distances between the two points ranged between 2 and 15 mm. One and two sensory points were presented in a pseudo-random order to subjects' 4th digit volar fingertip surface. A threshold is determined when seventy percent accuracy is exhibited for identifying the difference between single versus double point stimulation.
Time frame: up to 1 hour after intervention
Population: stroke cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Frequency rTMS | Change From Baseline in Two-point Discrimination | Immediately post-intervention | -0.7 mm | Standard Deviation 2.7 |
| High Frequency rTMS | Change From Baseline in Two-point Discrimination | One hour post-intervention | -1.7 mm | Standard Deviation 3.5 |
| Low Frequency rTMS | Change From Baseline in Two-point Discrimination | One hour post-intervention | -0.3 mm | Standard Deviation 1.2 |
| Low Frequency rTMS | Change From Baseline in Two-point Discrimination | Immediately post-intervention | -0.5 mm | Standard Deviation 1.8 |
| Sham rTMS | Change From Baseline in Two-point Discrimination | One hour post-intervention | 0.1 mm | Standard Deviation 2.1 |
| Sham rTMS | Change From Baseline in Two-point Discrimination | Immediately post-intervention | -0.1 mm | Standard Deviation 1.3 |