Exploring Cortical Remyelination in Children With Multiple Sclerosis

Study Overview
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Brief Summary
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Multiple sclerosis (MS) in children, a rare disease, follows a relapsing remitting course with a shorter interval between the first 2 clinical events and higher annualized relapse rate as compared with MS in adults. Residual deficits following clinical events are less frequent. The vast majority of children and adolescents with MS are thought to have a greater potential for myelin repair than adults. However convincing data in the literature to support this hypothesis are lacking, because until now no imaging technique has been validated to measure remyelination in vivo.

Detailed Description
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Multiple sclerosis (MS) in children, a rare disease, follows a relapsing remitting course with a shorter interval between the first 2 clinical events and higher annualized relapse rate as compared with MS in adults. Residual deficits following clinical events are less frequent. The vast majority of children and adolescents with MS are thought to have a greater potential for myelin repair than adults. However convincing data in the literature to support this hypothesis are lacking, because until now no imaging technique has been validated to measure remyelination in vivo. The investigator team has performed a first study to generate for the first time magnetization transfer ratio (MTR)-based maps of cortical myelin repair in 15 adult patients with MS. We found that patients with MS showed a high variability in cortical myelin repair, with variable index of cortical remyelination. Moreover, there was a significant correlation between the index of cortical remyelination and clinical scores. Even if childhood onset MS take longer to reach states of irreversible disability, severe disability will eventually occur at a young age. Moreover, pediatric MS could be responsible for cognitive disorders. It is therefore of crucial relevance to develop research programs designed to generate novel imaging techniques to measure the efficacy of remyelinating therapies. Multiple sclerosis (MS) in children, a rare disease, follows a relapsing remitting course with a shorter interval between the first 2 clinical events and higher annualized relapse rate as compared with MS in adults. Residual deficits following clinical events are less frequent. The vast majority of children and adolescents with MS are thought to have a greater potential for myelin repair than adults. However convincing data in the literature to support this hypothesis are lacking, because until now no imaging technique has been validated to measure remyelination in vivo. Our team has performed a first study to generate for the first time magnetization transfer ratio (MTR) - based maps of cortical myelin repair in 15 adult patients with MS. The investigator team found that patients with MS showed a high variability in cortical myelin repair, with variable index of cortical remyelination. Moreover, there was a significant correlation between the index of cortical remyelination and clinical scores. Even if childhood onset MS take longer to reach states of irreversible disability, severe disability will eventually occur at a young age. Moreover, pediatric MS could be responsible for cognitive disorders. It is therefore of crucial relevance to develop research programs designed to generate novel imaging techniques to measure the efficacy of remyelinating therapies. Finally, another extremely challenging issue in the care of children with MS is the difficulty of the transition between pediatric and adult care. Over last years, at the Pitié-Salpêtrière Hospital, the neurology team created a transition program called JUMP to improve medical, educational and psychosocial outcome for adolescent patients with MS .Taking part in the present study, young patients from 16 to 18 years old could have a direct access to the JUMP program, with the coordination of the dedicated nurses.

Official Title
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Exploring Cortical Remyelination in Children With Multiple Sclerosis

Conditions
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Children With Multiple Sclerosis

Intervention / Treatment
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* Other: MRI without injection of contrast product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: age between 12 years old and 18 years old RR-MS defined by 2017 McDonald criteria no relapse the last 4 weeks no methylprednisolone or prednisolone the last 4 weeks. affiliated to the social security system signature of the consent by the 2 holders of parental authority Volunteers: age between 12 years old and 18 years old absence of any neurological condition except headaches or psychosomatic syndrome signature of the consent by the 2 holders of parental authority Exclusion Criteria: both groups: Parental rejection Contre-indication of brain MRI: pace maker, tatoo of the face, claustrophobia…. Pregnancy, copper intrauterine device

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 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: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with MS<br>Children with MS | Other: MRI without injection of contrast product<br>* MRI without injection of contrast product<br>|
| Experimental: Volunteers<br>matched in age and sex with patients. Volunteers will perform only one brain MRI, as requested by the neurologist | Other: MRI without injection of contrast product<br>* MRI without injection of contrast product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTR-based individual indices | To investigate the association between MTR-based individual indices of cortical myelin repair in children with MS and one cognitive score (Symbol Digital Modalities Test (SDMT)) at baseline | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| indices of cortical remyelination | To investigate the association between individual indices of cortical remyelination and neurological disability | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, MS