Epidural Spinal Cord Stimulation for Restoring Walking in Spinal Cord Injury

The incidence, severity, and relationship to the intervention of all AEs . All AEs will be defined, recorded, and graded according to the International Council for Harmonisation Good Clinical Practice guidelines. Serious adverse events will be reported specifically based on established criteria. This assessment will comprehensively cover all safety concerns related to the surgical procedure (epidural stimulator implantation), the electrical stimulation itself (across various parameter sets).

The WISCI II evaluates walking ability in spinal cord injury patients. It has 21 levels (0-20), with scores based on mobility aids and assistance needed. A score of 0 means no walking; 20 indicates independent walking without aids.

SCIM III is a disease-specific, validated assessment tool designed to evaluate the functional independence of individuals with spinal cord injury in performing essential activities of daily living, self-care, mobility, and respiration/management. It is tailored to reflect the unique challenges and priorities of the SCI population.

The SCIM III consists of 19 items across three subscales:

Self-care subscale (0-20 points): Includes feeding, grooming, bathing, and dressing.

Respiration and sphincter management subscale (0-40 points): Covers respiration, bladder management, and bowel management.

Mobility subscale (0-40 points): Assesses mobility in room and toilet, indoors and outdoors mobility, and stair management.

The total score ranges from 0 to 100 points, with higher scores indicating greater functional independence.

ISNCSCI is the most authoritative and widely used standard for evaluating neurological function after spinal cord injury, comprising:

Motor Scores:

Range:

Upper limbs (C5-T1): 0-25 per limb (total 0-50) Lower limbs (L2-S1): 0-25 per limb (total 0-50) Total motor score: 0-100 points Higher scores indicate better motor function

Sensory Scores:

Light touch:

0-2 points per dermatome (C2-S4/5) Total: 0-112 points

Pinprick:

0-2 points per dermatome (C2-S4/5) Total: 0-112 points Interpretation: Higher scores indicate better sensory preservation Neurological Level of Injury: determined by the most caudal segment

ASIA Impairment Scale (AIS) Grading:

A = Complete (no motor/sensory function in S4-S5) B = Sensory incomplete C = Motor incomplete (<50% key muscles strength ≥3/5 grade) D = Motor incomplete (≥50% key muscles strength ≥3/5 grade) E = Normal

The Functional Independence Measure (FIM) is a widely used assessment tool designed to evaluate a person's functional status and level of independence in daily living activities, particularly among individuals with disabilities.

FIM items are scored based on the level of assistance required to complete a task, ranging from 1 to 7 points per item.

The FIM consists of 18 items across two domains: Motor domain (13 items): Includes activities such as eating, grooming, bathing, dressing, toileting, transfers (bed/chair, toilet, tub/shower), walking, and stair climbing. Cognitive domain (5 items): Covers communication (comprehension and expression) and social cognition (memory, problem-solving, and social interaction).

The total score ranges from 18 to 126 points:

≤ 35 points: Severe dependence 36-89 points: Moderate dependence 90-119 points: Mild dependence 120-126 points: Functional independence

10mWT is a widely used, objective performance-based assessment tool designed to evaluate short-distance walking speed and functional mobility in individuals with neurological impairments, including spinal cord injury.

The time taken to walk the middle 6 meters is recorded in seconds.

The 6min-WT is a widely used, objective performance-based assessment tool designed to evaluate submaximal exercise capacity, functional endurance, and walking distance in individuals with chronic cardiopulmonary or neurological conditions, including spinal cord injury.

The participant is instructed to walk back and forth as far as possible within the 6-minute time period, at a self-selected pace that can be sustained throughout the test.

MAS is a clinical tool used to assess muscle spasticity by grading resistance during passive movement. It scores from 0 (no tone increase) to 4 (rigid joint), with intermediate grades: 1 (slight resistance), 1+ (mild resistance through ≤50% ROM), 2 (marked resistance), and 3 (considerable resistance). Higher MAS scores (max=4) indicate worse outcomes, reflecting more severe spasticity that impairs mobility.

The Penn Scale is a specific assessment tool for measuring muscle spasticity. Scores range from 0 (no spasticity) to 4 (severe, rigid spasticity), with higher scores indicating more intense muscle stiffness and involuntary contractions.

The VAS Pain Score is a self-reported measure of pain intensity. It consists of a 10-cm horizontal line, anchored by "no pain" (0) on one end and "worst pain imaginable" (10) on the other. Patients mark the line to represent their current pain level, and the score is determined by measuring the distance from "no pain." It provides a simple, quick method to quantify subjective pain experiences, monitor fluctuations, and guide pain management strategies.

EMG is a non-invasive electrophysiological assessment tool designed to quantify the electrical activity and activation patterns of lower-limb muscles during specific volitional or task-related motor attempts.

EMG recordings are obtained using surface electrodes placed over key lower-lild muscles. The root mean square amplitude of the signal during defined task epochs is measured in microvolts. Changes in EMG amplitude and temporal coordination provide an objective measure of muscle recruitment efficacy, spinal motor pool excitability, and the recovery of coordinated motor output following neuromodulation and rehabilitation.

MEPs are neurophysiological responses elicited by transcranial magnetic stimulation, designed to assess the integrity and conductivity of the corticospinal tract.

MEP latency and peak-to-peak amplitude are recorded from target lower-limb muscles using surface EMG. Latency reflects conduction time along the central motor pathway, while amplitude correlates with the number of synchronously activated motor units and the excitability of spinal motoneurons. Changes in these parameters serve as quantitative biomarkers for the functional reorganization and strengthening of descending supraspinal control after intervention.

SEPs are neurophysiological responses elicited by electrical stimulation of peripheral nerves, designed to evaluate the integrity of the dorsal column-medial lemniscus sensory pathway.

SEP latency and amplitude are recorded over the scalp following tibial nerve stimulation. Prolonged latency or reduced amplitude indicates impaired conduction within the ascending sensory tracts. Serial measurements provide an objective assessment of the recovery or reorganization of afferent sensory input to the cortex, complementing clinical sensory examinations.

Spinal ¹⁸F-FDG PET-CT is a molecular imaging modality designed to quantify regional glucose metabolism, serving as an indicator of neuronal and glial metabolic activity.

The standardized uptake value ratio is calculated for defined spinal cord segments relative to a reference region. Changes in FDG uptake reflect alterations in synaptic activity, inflammation, or tissue repair processes. This measure provides a unique in vivo biomarker for assessing metabolis neuroplasticity and the longitudinal changes in spinal cord circuitry activity in response to epidural stimulation and rehabilitation.