No accepted clinical therapies exist for repair of motor pathways following spinal cord injury (SCI) in humans, leaving permanent disability and devastating personal and socioeconomic cost. A robust neural repair strategy has been demonstrated in preclinical studies, that is ready for translation to recovery of hand and arm function in human SCI, comprising daily transcranial magnetic stimulation treatment at the inpatient rehabilitation facility. This study will establish clinical effect size of the intervention, as well as safety and feasibility necessary for a subsequent controlled efficacy trial and inform preclinical studies for dosing optimization.

The objective of this proposal is to begin translating findings from pre-clinical studies to human motor deficits following cervical SCI (cervSCI). This HF-rTMS treatment protocol has not been previously assessed in human SCI and is qualitatively different from rTMS protocols reported to transiently modulate excitability of existing pathways, previously demonstrated in the literature. The protocol involves a daily stimulation of ~10 mins bilateral HF-rTMS for 2 weeks. SCI participants will be studied in a United States inpatient setting for this phase I study.

Given the findings in the pre-clinical model of robust axonal sprouting and functional synapse formation close to the damaged tissue using the above stimulation parameters, the transcranial magnetic stimulation treatment will target the hand-forearm region of the primary motor cortex, bilaterally. The aim is to include the cortical representation of affected muscles adjacent to the neurological level of injury. This zone often contains a mix of clinically and neurophysiologically intact, weakly innervated and denervated corticospinal pathways. Under standard sub-acute rehabilitation care, recovery of up to 1 neurological level of injury (NLI) is often the case, but improvement of 2 or more levels is far less common (<30% of patients). To examine the feasibility and safety of this novel intervention is the principal aim of the study. The associated potential clinical and neurophysiological changes will also be evaluated. These preliminary data will be used to power a subsequent efficacy trial to test the hypothesis that rTMS induced corticospinal augmentation will result in greater than typical extension of the NLI in human SCI, assessed up to the stable recovery phase at 6 months post-injury.

Inclusion Criteria:

1. Post traumatic or non-traumatic cervical spinal cord injury (SCI) with residual upper-extremity paralysis
2. Time post-injury less than six weeks
3. Neurological Level of Injury (NLI) C4-C6
4. ASIA Impairment Scale (AIS) A-D
5. Sensory and motor zone of partial preservation (ZPP, clinically complete or incomplete)
6. Age 18 to 80 years old

Exclusion Criteria:

1. Ventilator dependence;
2. Concurrent neurological condition affecting sensory or motor pathways or otherwise limiting ability to participate in the study;
3. Evidence of trauma-related brain injury;
4. Contraindications for TMS or history of seizure or seizure risk;
5. Spinal instability;
6. Uncontrolled autonomic dysreflexia;
7. Severe muscular or skeletal or neuropathic pain;
8. Known or suspected pregnancy;
9. Medically unstable or any reason the physician may deem as inappropriate for the participant to enroll or continue in the study.

Upon completion of the study, data will be deidentified and shared within the supplementary material of published scientific papers or per the journal recommendations. We may also share the full range of available individual participant data with the members of the scientific community upon reasonable request and at the discretion of the PI.

Data will become available upon publication of results and may be shared indefinitely.

IPD and any additional supporting information will be shared with members of the scientific and medical communities for analyses related to the use of rTMS to improve upper extremity motor function following neurological insult. The mechanism for data sharing will be decided on a case by case basis; the study PI will review all data sharing request.

Patients will be equally randomized to either the Active rTMS or Sham rTMS group following the Baseline Assessment. Device will be set up to active/sham mode prior to intervention using a unique patient and intervention code by an unblinded study team member. Subjects, outcome assessors and staff administering rTMS intervention (care provider) will be blinded to the device setting (Active/Sham).