Non-Invasive Stimulation for Improving Motor Function

Study Overview
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Brief Summary
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The purpose of this study is to determine if spinal excitability is increased with a Spinal Associative Stimulation (SAS) protocol, and to determine the functional consequences of this technique on motor recovery.

Detailed Description
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Recovery of motor function continues to be a problem following Spinal Cord Injury. Non-invasive brain stimulation techniques, targeting cortical areas, have been shown to enhance the excitability in the human motor cortex, and these changes in the motor cortex may be of significance for the rehabilitation of brain injured patients. However, little is known about the adaptational changes in the excitability/plasticity of spinal neural circuits in spinal cord injury patients. The purpose of this study is to investigate the excitability of cortical and spinal inhibitory and excitatory mechanisms before and following a period of repetitive and synchronized dual peripheral nerve and brain stimulation. Repetitive, paired brain and peripheral nerve stimulation as a neuromodulatory tool, paired associative stimulation (PAS), has been well described. In this technique, stimuli are timed such that afferent and efferent volleys interact at the level of the cortex, that lead to a temporary enhancement of Motor Evoked Potential (MEP) amplitude in target muscles, and when applied repeatedly, lead to a sustained effect, outlasting the intervention period. This repetitive technique has been done in healthy subjects and patients with neurological diseases. By modifying the time between paired stimuli, the investigators will generate afferent/efferent interactions in the spinal cord. The working hypothesis of this study is that the acute facilitation of the H-reflex during Paired TMS and peripheral nerve stimulation, may be harnessed to modulate spinal excitability (sustained increase in the MEP amplitude). That is, the investigators will test if similar to PAS, a change in excitability outlasting the stimulation/intervention period may occur with afferent/efferent interactions, although at the level of the spinal cord rather than the cortex, and be useful to strengthen residual pathways after damage to the spinal cord.

Official Title
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Non-Invasive Stimulation for Improving Motor Function in Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spinal cord injury subjects with chronic lesions (> 6 months after the injury) Motor incomplete lesion, measured by the American Spinal cord Injury Association (ASIA) Impairment Scale (AIS) Traumatic cause of lesion; d) Some degree of motor function in the ankle flexor and extensors (Low extremity Motor Score - LEMS≥3). Exclusion Criteria: Motor and sensory complete lesion (AIS A); LEMS < 3; Non-traumatic cause of lesion Medically unstable condition Other concurrent neurological illness Presence of a potential TMS risk factor (detailed below) Potential TMS risk factor: Damaged skin at the site of stimulation Presence of an electrically, magnetically or mechanically activated implant An intracerebral vascular clip, or any other electrically sensitive support system Metal in any part of the body, including metal injury to the eye A history of medication-resistant epilepsy in the family Past history of seizures or unexplained spells of loss of consciousness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Thirty chronic SCI participants will given the SAS intervention and a control intervention in a randomized cross-over study, with at least one week between interventions. Each patient will be required to attend the Burke Medical Research Institute on three occasions. We will use a within-subjects design, to test changes in neurophysiologic and voluntary measures after intervention with respect to baseline.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAS20<br>The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 20ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs). | Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation<br>* Method of assessing neurophysiology and activity of the spinal cord<br>|
| Active Comparator: SAS0<br>The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 0ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs). | Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation<br>* Method of assessing neurophysiology and activity of the spinal cord<br>|
| Active Comparator: SAS50<br>The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 50ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs). | Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation<br>* Method of assessing neurophysiology and activity of the spinal cord<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in H-Reflex Threshold | Assessment of muscle reaction after stimulation of sensory fibers | Baseline compared with immediately after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower Extremity Motor Score (LEMS) | Assessment of lower extremity strength in key muscles; maximal score of 50 with 20 or less indicating participant likely has limited ambulation. | Baseline, immediately after intervention | 
| Walking Index for Spinal Cord Injury (WISCI II) | This is a functional capacity scale that rank orders ambulation in people with spinal cord injury, by evaluating the amount of physical assistance, braces or devices required to walk 10 meters. Rank scores range from 0-20. A higher score is indicative of more independent ambulation. | Baseline, immediately after intervention | 
| 10 Meter Walk Test | Measure of gait speed | Baseline, immediately after intervention | 
| Spinal Cord Independence Measure, Version 3 (SCIM III) | A disability rating scale developed to specifically address the ability of SCI patients to perform basic activities of daily living independently (including self-care, mobility, respiration and sphincter management) | Baseline, immediately after intervention | 
| Muscle Force | Amount of force recorded during maximal voluntary isometric contraction of a grip movement, recorded with a grip strength measurement device. | Baseline, immediately after intervention | 
| Anklebot | Lower extremity robotic device that provides kinematic evaluation data | Baseline, immediately after intervention |