Promoting Neuroplastic Mechanisms With Modeling-based Optimization of a Novel Robot-asisted Walking Rehabilitation Therapy

Assessment of Corticospinal pathway conduction using Motor Evoked Potentials (MEPs) with Transcranial Magnetic Stimulation (TMS)

Parameters of corticospinal pathway conduction are assessed. Transcranial Magnetic Stimulation (TMS) is applied to the primary motor cortex to elicit neural responses recorded from the rectus femoris, tibialis anterior and abductor hallucis muscles using surface electromyography (EMG). Participants receive five pulses at each stimulation intensity (40%, 50%, 60%, 70%, 80%), as well as three 3 additional pulses at 100% of the maximum device output. Motor evoked potentials recorded by EMG are analyzed for presence or absence, amplitude, and latency.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Assessment of Proximal motor conduction with M and F waves recorded in the abductor hallucis muscle.

The stimulator is placed on the posterior aspect of the medial malleolus over the posterior tibial nerve, and muscle responses are recorded from the abductor hallucis. The stimlation intensity at wich the M-wave amplitude no longer increases is determined, and three stimuli are recorded. For F-wave assessment, the stimulation intensity is increased to 130% of the M-wave intensity, and twenty stimuli are recorded. The presence or absence of the F wave is used to assess proximal motor conduction.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Spasticity as assessed by the Modified Ashworth Scale (MAS)

The Modified Ashworth Scale (MAS) measures spasticity in patients with neurological disorders of the central nervous system. Spasticity is defined as an increase in muscle tone that is dependent on the speed of movement. The MAS is a modified version of Ashworth Scale and provides a spasticity score ranging from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Assessment of walking speed using the 10-Meter Walk Test (10MWT)

The 10-Meter Walk Test assesses walking speed in patients with spinal cord injury along a 10-meter corridor. Participants may use assistive devices as needed. The first 2 meters are used to reach a steady walking speed, and the final 2 meters are used for slowing down; time is recorded over the central 6 meters.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Walking ability, fall risk, mobility, and balance as assessed by the Timed Up and Go (TUG) test.

The test starts with the participant seated in a chair. It measures the time required to stand up from the chair, walk to and around a cone located 3 meters away, and sit back down in the same chair. Timing starts at the therapist's signal and finishes when the participant's buttocks touch the chair. Participants may use assistive devices if needed; however, they may only use them for walking and not for standing up.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Walking ability as assessed by the Walking Index for Spinal Cord Injury II (WISCI-II)

The Walking Index for Spinal Cord Injury II (WISCI-II) measures the need for assistance and devices for walking after a spinal cord injury. The scale consists of 21 items scored from 0 to 20, where 0 indicates inability to walk and 20 indicates the ability to walk 10 meters without assistance, orthoses, or walking devices. Walking devices include parallel bars, walkers, crutches, and canes. Orthoses include long leg braces, short leg braces, and knee braces with the knee locked or unlocked. Assistance refers to the need for support from one or two persons. The assessment is based on the ability to walk a distance of 10 meters.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Functional assessment of specific areas in patients with spinal cord injury using the Spinal Cord Independence Measure III (SCIM-III) score

SCIM III is functional assessment tool designed for patients with spinal cord injury. It includes three functional domains: self-care (subscore 0-20), respiration and sphincter management (subscore 0-40) and mobility (subscore 0-40). The total score ranges from 0 to 100. Self-care area consist of six items, including feeding, bathing, dressing, and grooming. The respiration and sphincter management domain include four items: respiration, bladder management, bowel management and the use of the toilet. The mobility domain include nine items, divided into tasks performed in the room and toilet, and tasks performed indoors and outdoors. Administration of the assessment takes up to 60 minutes, including observation and patient interview.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Muscle strength assessed by maximum voluntary isometric contraction (MVIC) using a hand-held dynamometer.

Eight muscles of each lower limb (gluteus medius, rectus femoris, vastus lateralis, biceps femoris, semitendinosus, tibialis anterior, soleus, and medial gastrocnemius) will be monitored using electromyography (EMG). Isometric force exerted against the hand-held dynamometer will be measured during knee flexion and extension, hip abduction, and ankle plantarflexion and dorsiflexion. Maximum contraction will be maintained for 3-5 seconds, and the peak force achieved during this period will be recorded in newtons. Three repetitions of each movement will be performed, and the mean value will be calculated. Participants will be positioned sitting for knee flexion and extension and supine for hip abduction and ankle plantarflexion and dorsiflexion. The distance between the joint involved and the point at which resistance is exerted will be recorded.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Assessing muscle activation during maximum voluntary isometric contraction (MVIC) using surface electromyography (EMG).

This procedure will be used to normalize EMG signals recorded during three-dimensional gait analysis. Activation of eight muscles of each lower limb (gluteus medius, rectus femoris, vastus lateralis, biceps femoris, semitendinosus, tibialis anterior, soleus, and medial gastrocnemius) will be recorded using surface EMG. Isometric force exerted against the hand-held dynamometer and the muscle activation derived from the contraction will be measured during knee flexion and extension, hip abduction, and ankle plantarflexion and dorsiflexion. Maximum contraction will be maintained for 3-5 seconds. Three repetitions of each movement will be performed, and the mean value will be calculated. Participants will be positioned sitting for knee flexion and extension and supine for hip abduction and ankle plantarflexion and dorsiflexion. The distance between the joint involved and the point at which resistance is exerted will be recorded.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Pain intensity assessed using the Visual Analogue Scale (VAS) after Lokomat sessions, the 10-meter walk test (10MWT), and the Timed Up and Go (TUG) test.

Participants will mark their perceived pain intensity on a 10-centimeter line, anchored at 0 (no pain) and 10 (worst imaginable pain). The distance from the zero point will be measured in centimeters to determine the pain score.

Time frame: After each Lokomat session (5 days/week for 8 weeks) and after the 10-meter walk test (10MWT) and Timed Up and Go (TUG) test at Baseline (Week 0), Mid-intervention (Week 4), Post-intervention (Week 8), and at follow-up 4 weeks after the intervention.

Perceived effort, exertion, breathlessness, and fatigue assessed using the modified Borg scale after Lokomat sessions, the 10-meter walk test (10MWT), and the Timed Up and Go (TUG) test.

The modified Borg scale is an 11-point scale ranging from 0 (nothing at all) to 10 (very, very hard), measuring patient-perceived fatigue during physical activity or exercise.

Time frame: After each Lokomat session (5 days/week for 8 weeks) and after the 10-meter walk test (10MWT) and Timed Up and Go (TUG) test at Baseline (Week 0), Mid-intervention (Week 4), Post-intervention (Week 8), and at follow-up 4 weeks after the intervention.

Biomechanical gait parameters, including kinematics, assessed using three-dimensional gait analysis (3DGA) with a motion capture system during walking on a 10-meter corridor.

Participants will be instrumented with passive markers according to the Vicon Plug-in Gait model, with additional markers on the foot. They will walk barefoot in a 10-meter corridor, unless an orthosis requires wearing shoes, while the system records each trial. Participants will also perform a sit-to-stand movement. Assistive devices may be used as needed. The resulting recordings will be processed using Vicon software, and the data will be prepared for subsequent analysis.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Kinetic gait parameters, including ground reaction forces, assessed using a motion capture system and force platforms during walking on a 10-meter corridor.

Participants will be instrumented with passive markers according to the Vicon Plug-in Gait model, with additional markers on the foot. They will walk in a 10-meter corridor with two force platforms embedded in the middle, which will record ground reaction forces, while the Vicon motion capture system records each trial. Participants will walk barefoot unless an orthosis requires wearing shoes. They will also perform a sit-to-stand movement. Assistive devices may be used as needed. The resulting recordings will be processed using Vicon software, and the data will be prepared for subsequent analysis.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Lower limb muscle activity during three-dimensional gait analysis as assessed by surface elecgromyography

Participants are instrumented with passive reflective markers according to the Vicon Plug-in Gait model, with additional markers placed on the foot. Participants walk along a 10-meter corridor while the Vicon motion capture system records each trial. Participants walk barefoot unless an orthosis requiring shoes is used. Surface electromyography electrodes are placed on eight muscles of each lower limb (gluteus medius, rectus femoris, vastus lateralis, biceps femoris, semitendinosus, tibialis anterior, soleus, and medial gastrocnemius) following SENIAM recommendations. A sit-to-stand movement is also performed. Participants may use assistive devices as needed.

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, post-intervention at Week 8, and follow-up 4 weeks after completion of the intervention (Week 12).

Maximum voluntary isometric torque (MVIT) as assessed by the Lokomat L-FORCE tool.

The Lokomat L-FORCE tool assesses maximum voluntary isometric torque (MVIT) during hip and knee flexion and extension. Torque is measured in Newton-meters (Nm). During testing, the exoskeleton is maintained in a fixed position, and participants are instructed to perform maximal voluntary isometric contractions against the device resistance. The assessment sequence includes right hip flexion, right hip extension, left hip flexion, left hip extension, right knee flexion, right knee extension, left knee flexion, and left knee extension.

Time frame: Once weekly, after a Lokomat session, during the 2-month intervention.

Joint stiffness at three angular velocities as assessed by the Lokomat L-STIFF tool.

The Lokomat L-STIFF tool assesses joint stiffness during passive hip and knee flexion and extension at three angular velocities (30°/s, 60°/s, and 120°/s). Stiffness is measured in Newton-meters per degree (Nm/°). During testing, participants remain relaxed while the Lokomat passively moves each joint individually at the specified velocities.

Time frame: Once weekly, after a Lokomat session, during the 2-month intervention.

User experience as assessed by an adapted version of the Usability Metric for User Experience (UMUX) questionnaire.

The Usability Metric for User Experience (UMUX) is a self-administered questionnaire designed to assess perceived usability and user satisfaction with the intervention. The adapted version used in this study consists of 10 items. Each item is rated on a 7-point Likert scale ranging from 1 ("completely disagree") to 7 ("completely agree"), where 4 represents "neither agree nor disagree."

Time frame: Baseline (Week 0), during the 2-month Lokomat intervention at Week 4, and post-intervention at Week 8.

Walking speed during gait training with the Lokomat system (km/h).

The Lokomat system will automatically record gait training parameters modified by the physiotherapist during each session. Walking speed will be documented in kilometers per hour (km/h). The programmable speed range is from 1.0 to 3.2 km/h.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.

Body Weight Support (BWS) during gait training with the Lokomat system (kg).

The Lokomat system will automatically record gait training parameters modified by the physiotherapist during each session. Body Weight Support (BWS) will be documented in kilograms (kg). The system allows adjustable unloading of the participant's body weight, with a programmable support range from 0 to 75 kg.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.

Guidance Force recorded by the Lokomat system during gait training (%)

The Lokomat system will automatically record training parameters modified by the physiotherapist during each session, including Guidance Force expressed as a percentage (%), with a programmable range from 0% to 100%. This parameter reflects the degree of movement guidance provided by the exoskeleton. A value of 100% represents complete control of the exoskeleton's movements. Values below 80% indicate reduced robotic assistance and greater freedom of movement and active participation by the participant, whereas values below 20% correspond to minimal robotic guidance, and may be considered free movement.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.

Range of motion recorded by the Lokomat system for hips and knees (degrees)

The Lokomat system will automatically record training parameters modified by the physiotherapist during each session, including the range of motion (ROM) of the hips and knees of the exoskeleton. * Hip ROM ranges from 0° to 64°, with an adjustable variation of ±5° to adapt the movement to the participant. This parameter modifies flexion (negative values) and extension (positive values). * Knee ROM ranges from 0° to 85°, with an adjustable variation of 0° to 8°, applied to flexion. The system can assess the desired movement (predetermined by the programmed parameters) and the actual movement performed by the participant. All measurements are recorded in degrees.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.

Duration of gait training sessions recorded by the Lokomat system (minutes and seconds)

The Lokomat system will automatically record training parameters modified by the physiotherapist during each session, including session duration. Each session is planned to last 30 minutes; however, actual session duration may vary due to technical issues or other factors. Duration is recorded in minutes and seconds.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.

Distance covered during gait training sessions recorded by the Lokomat system (meters)

The Lokomat system will automatically record training parameters modified by the physiotherapist during each session, including the distance covered. Distance is measured in meters and depends on the duration of the session and the programmed walking speed.

Time frame: During each Lokomat session, conducted 5 times per week (Monday through Friday) for 4 consecutive weeks.