Neuromodulation to Improve Respiratory Function in Cervical Spinal Cord Injury

There are five main phases to this study. The first phase is baseline testing, second phase is temporary implant, third phase is post-temporary implant mapping/treatment, fourth phase is permanent implant, and fifth phase is post-permanent implant treatment.

Phase 1. Screening and Baseline testing/training (up to 6 months, UCLA Semel Institute for Neuroscience and Human Behavior), the purpose of which is to ensure that each subject begins with the full benefits achievable by standard rehabilitative respiratory therapy and has stable baseline of function before they begin epidural stimulation. 12 subjects will undergo this phase. Maximum inspiratory and expiratory pressure, resting spontaneous respiratory activity, and respiratory muscle EMG will be measured during this phase. Subjects on ventilator assist mode (unless or until they can sustain adequate respiration on their own) will be monitored via pneumotachometer for respiratory frequency changes. Additionally, subjects will undergo motor and sensory testing. The subjects must show stable respiratory function before implantation, therefore if a subject is showing small improvements at 3 months the subject will continue training until they have reached their maximal effect from training (up to 6 months). Subjects that show stable baseline at 3 months will proceed to Phase 2. If a subject's health worsens, including non-respiratory functioning, subject will be assessed by appropriate physician and testing will be held until subject's health has improved and maintains stable for at least 2 months. Subjects will obtain preoperative clearance and general anesthesia clearance in preparation for Phase 2.

Phase 2. Temporary Implant (1 day, 24 hours overnight stay, UCLA Medical Center, Santa Monica). Subjects will undergo temporary stimulator implant surgery. CT scan may be collected prior for surgical planning if needed by PI. Up to 9 subjects with most connectivity and evidence of response to baseline testing will undergo this phase from the pool of 12 subjects in Phase 1 above. The electrode that will be used will be the same one that will be applied in subsequent permanent trial Phase 4, however a temporary connector will be placed to an external battery source and no permanent battery will be implanted. Connectivity of subject will be based on motor evoked potentials and somatosensory evoked potentials done during baseline testing and evaluated by a clinical neurophysiologist

Phase 3. Post-temporary implant mapping/treatment. Respiratory ability will be assessed. Respiratory rehabilitation regimen with the stimulator will be used to re-enable respiratory function. The length of time of this phase will be dependent on the participant's response (as explained below) to the implant. The paddle will remain implanted until a comprehensive assessment of the participant's respiratory response is conducted by PI. Should the participant fail to exhibit a measurable respiratory response, the explantation of the paddle electrodes may be performed by the PI, provided that it is deemed safe to proceed. Extent and amplitude of evoked responses and motor pools activated from electrode pairs will be analyzed through EMG obtained. Response to the temporary stimulator implant will be based on tidal volume and spontaneous respiratory rate and respiratory muscle EMG. The same 9 subjects from Phase 2 will undergo this phase. Maximum inspiratory and expiratory pressure, and respiratory muscle EMG measurements will also be collected during this Phase.

Phase 4. Permanent implant procedure (1 day, 24 hours overnight stay, UCLA Medical Center, Santa Monica). Subjects will undergo stimulator implant surgery. Up to 6 subjects with most connectivity and evidence of response to baseline testing will undergo this phase from the pool of 9 subjects in Phase 3 above. The functional respiratory circuit connectivity of the subject will be based on implanted spinal cord stimulator-induced spinal evoked respiratory muscle potential changes. Response to stimulator implant-induced respiratory facilitation will be evaluated based on intraoperative minute ventilation, tidal volume, and respiratory muscle EMG before and after the spinal stimulation. Subjects will be monitored overnight following surgery as a pre-cautionary measure. Ventilated subjects undergoing surgery are not at an increased risk over non-ventilated subjects.