Neuromodulation to Enhance Motor Function in HSP

10MWT assesses walking speed over a 10-meter walkway at a comfortable and maximum safe pace. Timing occurs between 2 and 8 meters to exclude acceleration/deceleration, with two trials averaged per speed. Assistive devices are allowed

6MWT evaluates walking endurance by measuring the total distance walked over six minutes. Patients are instructed to walk as far as possible at their own pace, with rests allowed if needed. The total distance reflects functional capacity and stamina, which are often affected in HSP due to progressive spasticity and weakness.

measures muscle spasticity by assessing resistance to passive muscle stretch through the range of motion and grades the muscle tone on a 0-4 scale based on the resistance felt.

MAS 0-4 scale:

0: No increased muscle tone

1: Slight increase in tone; catch and release at the end of the range

1+ : Slight increase; catch followed by minimal resistance through < half the range

2: More marked increase through most of the range, but the limb still moves easily

3: Considerable increase in tone; passive movement is difficult

4: Limb is rigid in flexion or extension

The Spastic Paraplegia Rating Scale (SPRS) is a validated clinical outcome measure used to assess disease severity in individuals with spastic paraplegia. The scale consists of 13 items evaluating gait, spasticity, muscle strength, coordination, and functional impairment. Each item is scored to yield a total score ranging from 0 to 52, where a score of 0 indicates no neurological disability and higher scores reflect increasing severity of impairment, with 52 representing the most severe disease manifestation.

HSP-SNAP is a questionnaire used to assess the self-perception of individuals diagnosed with hereditary spastic paraplegia (HSP).

HSP-SNAP includes 12 questions, with 2 items dedicated to each symptom dimension (stiffness, weakness, imbalance, reduced endurance, fatigue, and pain). Each pair of items for a given dimension includes both positive and negative responses to prevent automatic answers. The HSP-SNAP employs a 5-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). To account for both positive and negative items, scoring is as follows: for items with a positive tone, the score is calculated as "patient's score minus 1" (pt score-1); for negative items, the score is "5 minus the patient's score" (5-pt score). The overall score is the sum of all item scores, ranging from 0 to 48. A higher score indicates better well-being and milder symptoms.

3D Gait Analysis will be performed using a 14-camera motion capture system, a wireless Electromyography (EMG) system, and 3 in-ground force plates. We will track walking speed using timing gates. Wireless EMG sensors will be placed on the vastus lateralis, rectus femoris, and vastus medialis to assess muscle activation during the gait trials. The outcomes will include joint kinematics (hip, knee, and ankle,).

Participants will be asked to perform a sit-to-stand task, whereby they will be told to stand up and sit down on a stool at their own self-selected pace. Sit-to-Stand performance, measured as the time and kinematic characteristics of sit-to-stand transition (average of two trials) obtained using motion capture analysis.

Bilateral isometric knee strength will be obtained with three, 5-sec maximal voluntary isometric contractions (MVIC) separated by one-minute rest. Knee strength, measured as peak knee extensor torque obtained using isokinetic dynamometry (Biodex), expressed in Newton-meters (Nm), with higher values indicating greater muscle strength.

Knee pain during knee strength test is recorded on an 11-point visual analog scale (0=no pain and 10 most pain possible).

The Neurogenic Bladder Symptom Score (NBSS) is a validated, disease-specific patient-reported outcome measure designed to assess lower urinary tract symptoms in individuals with neurogenic bladder. The questionnaire evaluates symptom severity across three domains, including incontinence, storage and voiding symptoms, and bladder-related consequences, as well as a global quality-of-life item. Individual items are scored on ordinal response scales, and summed to generate a total score ranging from 0 to 74, with higher scores indicating greater urinary symptom severity and impact on daily functioning.

The Neurogenic Bowel Dysfunction Score (NBDS) is a validated clinical questionnaire used to assess the severity and impact of bowel dysfunction in individuals with neurological conditions, including spinal cord injury. The instrument evaluates multiple domains of bowel function, including frequency of defecation, constipation, fecal incontinence, use of medication or mechanical assistance, and impact on quality of life. Individual item scores are summed to yield a total score ranging from 0 to 47, with higher scores indicating more severe bowel dysfunction and greater impact on daily living.

Approximately 10 mL of venous blood samples will be collected and processed for metabolomic/lipid profiling and biomarker assays