Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People With c-SCI

Study Overview
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Brief Summary
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After spinal cord injury (SCI), there is a disruption in neural circuits resulting in paralysis. There is not yet a cure for paralysis. In persons with Cervical SCI (pwC-SCI) recovery of arm-hand function is very important as it has a significant impact on the patients' level of independence and quality of life. Recovery is assumed to involve alterations in both central and peripheral motor systems. Motor training at an intensive dosage potentially provides a powerful stimulus for neurological recovery. This project exploits the peripheral and central neuroplastic effect of an early (<10 weeks after injury) and intensive (10 weeks of 12 hours in addition to usual care) upper limb motor training program (EIUMT) directed at recovery below the level of the injury in pwC-SCI within an international multi-center randomized controlled trial including 40 pwC-SCI. It has 4 objectives: to investigate 1)central neural plasticity by identifying alterations in cortical neuroplasticity and corticospinal excitability; 2)peripheral neural plasticity by identifying alteration in axonal excitability and number of motor units; 3)behavioral motor recovery of upper limb and 4)relationships between dose dimensions of motor intervention and behavioral and neurophysiological outcome measures aer EIUMT. Cutting-edge neurophysiological measures are used to provide insight in the mechanism of neuroplasticity after EIUMT and will be taken before and after EIUMT and at 6 months follow-up.

Detailed Description
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Background of the study: Paralysis or paralysis is the most common effect of spinal cord injury (SCI) on individuals. Paralysis affects the ability to walk, perform self-care, live independently and participate in work and leisure activities. In individuals with cervical spinal cord injury, arm and hand function is very important. The most promising and easily implemented intervention that could promote neurological recovery and make a lasting difference in the lives of people with spinal cord injury is early and intensive motor training aimed at recovery below the injury level. This intervention takes advantage of the early plasticity of the nervous system. By maximizing muscle activation in the first few days after injury, we can target the nervous system's unique capacity for neural plasticity where changes can occur in central and peripheral motor systems. Objective of the study: This project aims to investigate peripheral and central neuroplasticity following an early (<10 weeks after injury) and intensive (10weeks of 12 hours of additional therapy) upper extremity motor training program (EIUMT) aimed at recovery below the lesion level.This project has 4 objectives: to investigate 1) central neural plasticity (identify changes in cortical neuroplasticity and corticospinal excitability; 2) peripheral neural plasticity (identify change in axonal excitability and number of motor units); 3) clinical motor recovery of the upper limbs and 4) relationships between dose dimensions of motor intervention and clinical and neurophysiological outcome measures after EIUMT. Advanced neurophysiological measurements and clinical measurements will be taken before and after EIUMT and at 6-month follow-up. Study design: a multicenter pragmatic randomised controlled study in 2 countries Study population: 40 persons with cervical spinal cord injury (20 participants in the control and intervention groups) Inclusion criteria: Individuals are eligible to participate if they have suffered a traumatic or non-traumatic cervical spinal cord injury(with neurological level C4 or below) within the previous 10 weeks, have AIS (ASIA Impairment Scale) A lesion with motor function more than three levels below motor level (on one or both sides) or have AIS C or AIS D lesion (as defined by the International Standards for the Neurological Classification of spinal cord injury), are older than 16 years of age, have received permission to begin rehabilitation and are likely to remain an inpatient for the next 10 weeks. Exclusion criteria: Participants will be excluded if they have a significant medical or physical condition or psychiatric illness that could prevent the person from participating in the study, or would place the person at unacceptable risk if they were to participate. Intervention: The intervention group receives 12 hours of motor training each week. This involves active and targeted motor training of all affected muscles below the injury level in the context of functional activities. The control group receives only standard rehabilitation and care. Primary study parameters/outcome of the study: Central plasticity via: Single pulse TMS (transcranial magnetic stimulation) (cortical mapping and rest motor threshold) 10 weeks after randomisation Secundary study parameters/outcome of the study: Clinical Measures: Upper Extremity Motor Score, Spinal Cord Independence Measure (SClM-zelfzorg); Van Lieshout Test (VLT);Grades redefined assessment of strength sensibility and Prehension (GRASSP); Hand-Held Dynamometry; accelerometry (session density: active therapy time/session length); perceived difficulty and exertion) Central plasticity: Paired pulse TMS: (SICI (short interval intracortical inhibition); LICI (long interval intracortical inhibition); SICF (short interval intracortical inhibition); peripheral plasticity: NET (Nerve excitability testing) en MScanFit MUNE(Compound muscle action potential (CMAP).

Official Title
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Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People With Cervical Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Other: experimental group: intensive motor training
* Other: usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic or non-traumatic C-SCI below C4 in the preceding 10 weeks; age over 16 years; have an incomplete SCI or an AIS A SCI with zones of partial motor paralysis (as defined by the International Standards for the Neurological Classification of SCI (ISNCI) and medically stable. Exclusion Criteria: SCI with ASIA Impairment Scale (AIS) A without zones of partial preservation (decided based on former studies [58]) and expertise of the team; SCI with any significant medical condition that could prevent the person from participating. In order to ensure TMS measurement can be performed, patients will only be included for this measure if they have a positive response to motor evoked potential measurement (MEP+) [59] and will be excluded in the presence of contraindications for TMS application such as epilepsy, metal implants in the brain,defibrillator, pacemaker and pregnancy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intensive upper limb training<br>The intervention group receives 12 hours of motor training each week upon usual care during 10 weeks. This involves active and targeted motor training of all affected muscles below the injury level in the context of functional activities. | Other: experimental group: intensive motor training<br>* Intervention group: receive an extra 12 hours of motor training each week (distributed over the week) for 10 weeks. It will involve active and targeted motor training of all affected muscles of the upper limb below the level of the injury within the context of practice of functional activities. Interventions will be goal directed and individualized to the needs of each participant with a focus on training that addresses each person's specific motor problem, promoting motor learning as well as stimulating neural plasticity. All patients will continue to receive usual physiotherapy and usual rehabilitation.<br>|
| Other: usual care<br>The control group receives only standard rehabilitation and care | Other: usual care<br>* usual rehabilitation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in single pulse TMS: mapping | to evaluate changes in cortical reorganisation | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in single pulse TMS: resting motor threshold | to asses changes in cortical reactivity | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes SICI | to evaluatie changes in Short interval intracortical inhibition | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes SICF | short-interval intracortical facilitation | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in LICI | long-interval intracortical inhibition | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in MscanFit MUNE | Compound muscle action potential (CMAP) scans will be recorded | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in NET (Nerve excitability testing) | Strength duration time constant (SDTC), threshold electrotonus (TE), I/V relationship (I/V) and recovery cycles (RC) will be measured. | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in behavioral measures: Upper extremity motor score | score on 50 | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in Spinal Cord independence Measures | questionaire: self-care score | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in Van Lieshout Test | basis upper extremity skills | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in GRASSP | Grades redefined assessment of strength sensibility and Prehension | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 
| changes in hand held dynamometry | strength in hand | before intervention; at 10 weeks (after intervention) and at 6 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord rehabilitation, therapy dose, neural plasticity, motor recovery, upper limb training