Eccentric Muscle Training, Stimulation, and Biomarkers in SCI

The investigators are studying a new rehabilitation treatment for individuals trying to recover walking after spinal cord injury (SCI). The investigators will test conditions in the blood and spinal fluid to determine the best time to start this new training program. This will include checking for certain features called biomarkers by testing participants' spinal fluid and blood and compare these features to individuals without SCI. These features will help investigators determine when to start the new training program, either right away or waiting for 3 months. The new training program uses walking downhill on a slight slope on a treadmill while muscles that are not working normally are stimulated to contract using low levels of electricity. Adding this stimulation will allow people to practice walking and other skills even though full muscle control has not recovered. This new program will be in addition to any other rehabilitation therapy and will not replace standard rehabilitation. The hope is to see if downhill training with muscle stimulation, when delivered at the most ideal time, will improve trunk and leg movement, walking, and overall function. This recovery of movement and function will be compared to people with SCI receiving standard rehabilitation alone. Certain regions of the brain and spinal cord will also be studied using MRI scans to determine if these are affected by the training and compare to individuals without SCI. The total length of the study for SCI participants will be up to 16 weeks if in the standard of care group and up to 33 weeks if in the trained group. Healthy control participants will be involved for 1-2 visits.

SCI group: Individuals 3 months (+/-2 months) after SCI will be randomized into standard of care control group or augmented rehabilitation group (DownHill training with STIMulation = dhSTIM group). The study statistician will produce the randomization schedule with varying permuted blocks of size 3 and 6. The randomization schedule will be uploaded to REDCap for randomization of subjects at the time of enrollment into the study. The dhSTIM group will have cerebrospinal fluid (CSF) and blood collected and analyzed. These will be collected for research purposes only by the study's experienced proceduralist unless it is being collected clinically within the required timeframe for the study. CSF is collected via lumbar puncture under guided fluoroscopy which is a standardized technique to collect CSF and minimizes risks. If not enough CSF is collected on the first attempt, a second attempt may be required which is not expected due to the use of guided fluoroscopy but may occur in standard practice. Based on inflammatory status relative to healthy controls, the dhSTIM group will be directed to a Go group - immediate start at \~3 months) or No Go Group - delayed start at \~6 months. All SCI groups (dhSTIM Go, dhSTIM No Go, SOC) will also continue with regular outpatient therapy. The augmented rehabilitation groups and healthy controls will undergo MRI. The dhSTIM training will be a 12-week downhill training program combined with Xcite electrical stimulation 3 times a week. Participants will walk downhill on a treadmill with a harness for body weight support and trainers assisting as needed. All SCI groups (dhSTIM Go, dhSTIM No Go, SOC) will participate in pre, post, and 4 week follow-up assessments as follows: Biomechanical analysis will include kinematics, kinetics, and electromyography (EMG) while on the treadmill. Clinical outcome measures will include: American Spinal Injury Association (ASIA) Impairment scale (AIS), International standards for neurological classification of spinal cord injury (ISNCSCI), Autonomic Standards Assessment Form, Neuromuscular Recovery Scale, Neuropathic Pain Symptom Inventory, Pain Numeric Rating Scale, Spinal Cord Injury Independence Measure (SCIM3), 6 minute walk test (MWT), 10 meter walk test (MWT). Clinical outcome measures conducted as standard measures will be collected will be accessed via medical record when available. If absent from the medical record, they will be collected by a rater blind to group assignment. Leg strength will also be measured using the Biodex system. An additional MRI scan will be obtained at the end of the 12 week training period for the dhSTIM GO and dhSTIM No Go groups. Healthy Control Group: Healthy participants from the community will volunteer for the CSF and blood collection by the study's experienced proceduralist. CSF will be collected from at least half of the healthy controls prior to enrolling participants with SCI to provide a sample of normal levels of inflammatory genes and concentration of microglia-like cells as a baseline. CSF is collected for research purposes only via lumbar puncture under guided fluoroscopy which is a standardized technique to collect CSF and minimizes risks. If not enough CSF is collected on the first attempt, a second attempt may be required which is not expected due to the use of guided fluoroscopy but may occur in standard practice. When possible, they will also participate in one MRI scan of the brain and spinal cord. Due to MRI restrictions, some healthy controls may only be able to participate in biomarkers collection, some to only participate in MRI scans and some to participate in both types of collection. Individuals for the healthy control group will be enrolled until a total of n=10 +1 for biomarkers and n=10+1 for MRI is reached. One additional individual is allocated to account for dropouts. If there no individuals are able to take part in both MRI and fluid biomarker collection, then up to n=22 healthy controls will be enrolled.

Eligibility Criteria:
INCLUSION CRITERIA:

SCI participants WITHIN 1-5 MONTHS OF THEIR INJURY:

* Discharged from inpatient rehabilitation;
* AIS A-D at neurologic level C1-T10;
* 18-85 years old.

Healthy controls:

* Adults 18-85 years old;
* no recent major musculoskeletal injury;
* no recent surgery.

EXCLUSION CRITERIA:

SCI participants:

* Use of botox in the past 3 months that reduces skeletal muscle function;
* other neurologic conditions (i.e. brain injury, stroke, HIV);
* current cancer diagnosis;
* active deep vein thrombosis and anti-coagulation therapy;
* skin wounds in regions that interfere with harness, stimulation pads or hand placement needed for training.
* pregnancy;
* ventilator-dependence;
* cognitive conditions that preclude providing informed consent.
* Implanted medical devices that are contraindicated for electrical stimulation or MRI \*(If SCI participants have conditions contraindicated for MRI they may still participate in the remainder of study activities without myelin status as an outcome measure. SCI is a rare condition therefore this is necessary in order to achieve the required sample size.)

Healthy controls:

* Implanted medical devices that are contraindicated for MRI (MRI participants only);
* neurologic conditions (i.e. brain injury, stroke, HIV);
* current cancer diagnosis;
* clotting disorders requiring anti-coagulation therapy;
* inflammatory conditions like arthritis, ulcerative colitis, lupus, etc;
* pregnancy;
* fear of needles;
* claustrophobia;
* cognitive conditions that preclude providing informed consent.