Description

Background and Rationale

Spinal cord injury (SCI) can result in long-term impairments in voluntary motor control, muscle strength, mobility, balance, and functional independence. Although neurological recovery may be limited following chronic SCI, emerging research suggests that spinal neural networks below the level of injury may retain the capacity for functional activation through neuromodulation and activity-dependent rehabilitation.

Transcutaneous spinal cord stimulation (TSS) is a noninvasive neuromodulation technique that delivers electrical stimulation through electrodes placed on the skin overlying the spinal cord. This approach is intended to increase spinal network excitability and facilitate voluntary motor activation during functional rehabilitation.

Dalfampridine (4-aminopyridine or 4-AP) is a potassium channel blocker that may enhance neural conduction by prolonging action potentials. Dalfampridine is approved by the U.S. Food and Drug Administration (FDA) to improve walking in individuals with multiple sclerosis and has also been investigated for potential motor function benefits following spinal cord injury.

Combining spinal neuromodulation, pharmacologic augmentation, and intensive task-specific rehabilitation may support motor activation and activity-dependent neuroplasticity. However, the feasibility, safety, and preliminary functional outcomes of this combined approach in individuals with chronic SCI require further investigation.

Study Objectives

The primary objective of this study is to evaluate the safety and feasibility of combining transcutaneous spinal cord stimulation, physician-prescribed dalfampridine, and intensive rehabilitation in adults with chronic spinal cord injury.

Feasibility will be assessed through participant recruitment, treatment attendance, intervention tolerability, and completion of the rehabilitation program. Safety will be evaluated through monitoring and documentation of adverse events.

Secondary exploratory objectives will assess preliminary changes in upper extremity motor function, hand dexterity, lower extremity function, walking ability, balance, and functional mobility.

Study Design and Participants

This study is a prospective, single-arm pilot feasibility study conducted at TRYAbility NeuroRecovery Center in Downers Grove, Illinois.

Eight adults between 18 and 75 years of age with chronic spinal cord injury, defined as at least 12 months following injury, will be recruited.

Eligible participants must be medically stable, capable of providing informed consent, and receiving dalfampridine prescribed by their treating physician as part of routine medical care.

All enrolled participants will undergo a 12-week intervention program consisting of approximately three rehabilitation visits per week.

The study does not include randomization, a control group, or blinding. Outcomes will be evaluated using repeated assessments within participants over the intervention period.

Intervention Protocol

The intervention combines noninvasive transcutaneous spinal cord stimulation using the ANEUVO ExaStim Stimulation System with intensive, task-specific physical and occupational therapy.

Participants will complete approximately three treatment visits per week for 12 weeks. Each visit will include 60 minutes of occupational therapy and 60 minutes of physical therapy.

Transcutaneous Spinal Cord Stimulation

Transcutaneous spinal stimulation will be administered during rehabilitation sessions using the ANEUVO ExaStim Stimulation System.

Stimulation electrodes will be positioned over cervical spinal segments C5-C7 and thoracic/lumbar segments T11-L1, with abdominal reference electrodes.

Stimulation parameters will be individualized according to motor responses and participant tolerance. The protocol specifies biphasic rectangular pulses, pulse widths of 500-2000 microseconds, and frequencies ranging from 0-100 Hz.

Stimulation intensity will be adjusted to produce visible motor activation without discomfort. Stimulation will be delivered during physical and occupational therapy activities to facilitate motor engagement during functional training.

Pharmacologic Component

Participants will be receiving dalfampridine (4-aminopyridine) prescribed by their treating physicians as part of routine clinical care.

When applicable, rehabilitation sessions will be scheduled approximately 60 minutes after participants self-administer their prescribed medication.

The research team will not prescribe, dispense, administer, or modify dalfampridine dosing. Medication management will remain under the supervision of each participant's treating physician.

Medication timing relative to rehabilitation sessions will be documented.

Occupational Therapy

Occupational therapy will focus on upper extremity motor function, strengthening, coordination, and fine motor performance.

Treatment activities will include upper extremity aerobic priming using cycling or ergometry, progressive resistance exercises targeting the shoulder, elbow, wrist, and hand, and task-specific training involving grasp, pinch, object manipulation, and dexterity.

Physical Therapy

Physical therapy will focus on lower extremity strength, postural control, balance, mobility, and gait-related function.

Interventions will include lower extremity aerobic priming, cycling or stepping activities, progressive resistance exercises, sit-to-stand training, transfer practice, postural control activities, and individualized gait and balance training.

Treatment activities will be modified according to each participant's neurological impairment, functional capacity, and rehabilitation goals.

Outcome Assessments

Standardized clinical assessments will be performed at three time points:

Baseline, before beginning the intervention

Week 6, at the midpoint of the intervention

Week 12, following completion of the intervention

The primary study outcomes will focus on feasibility and safety, including recruitment, attendance, tolerability, and adverse events.

Secondary exploratory outcomes will evaluate changes in neurological and functional performance using standardized assessments, including:

Upper Extremity Motor Score (UEMS)

Capabilities of Upper Extremity Test (CUE-T)

10-Meter Walk Test (10MWT)

6-Minute Walk Test (6MWT)

Timed Up and Go (TUG)

Walking Index for Spinal Cord Injury (WISCI)

These measures will be used to examine preliminary changes in upper extremity motor performance, walking speed, walking endurance, functional mobility, and walking ability.

Safety Monitoring

Participants will be monitored throughout the study for adverse events associated with spinal stimulation, physical activity, and prescribed medication use.

Potential stimulation-related adverse events include skin irritation, discomfort, and temporary muscle fatigue. Rehabilitation-related risks may include muscle soreness, fatigue, and musculoskeletal strain.

Potential medication-related adverse events include dizziness, headache, insomnia, nausea, and seizure activity.

Trained clinicians will monitor participant tolerance and adjust stimulation parameters and exercise intensity as needed. Skin integrity and vital signs will be assessed before and after treatment sessions.

All adverse events will be documented and categorized according to severity and potential relationship to study procedures. Serious adverse events will be reported to the Institutional Review Board according to the study protocol.

Data Analysis

Descriptive statistics will summarize participant characteristics, treatment attendance, feasibility measures, and adverse events.

Changes in functional outcomes will be examined across baseline, week 6, and week 12 using repeated-measures analyses.

Mean change scores, standard deviations, and estimated effect sizes will be calculated to characterize preliminary treatment responses.

Given the small sample size and absence of a control group, findings will be considered exploratory and will not be used to establish definitive treatment efficacy.

Expected Contribution

This pilot study is intended to generate preliminary information regarding the safety, feasibility, and potential functional benefits of combining transcutaneous spinal cord stimulation, physician-prescribed dalfampridine, and intensive rehabilitation in adults with chronic spinal cord injury.

The findings may help inform the design of future larger-scale controlled clinical trials investigating combined neuromodulation and rehabilitation strategies for motor recovery following spinal cord injury.