Study of the Biological Function of Muscle Satellite Cells From Patients With Obstetric Brachial Plexus Palsy

Study Overview
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Brief Summary
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The purpose of this prospective work is to study the consequences of obstetrical brachial plexus paralysis on the rotator muscles of the shoulder. The hypothesis is that shoulder stiffness of these children is due to an impairment of the shoulder rotator muscles. The investigators want to test the regenerative capacities of these muscles. The development of a cellular model of this pathology will allow to test new therapeutic perspectives and to validate our hypothesis.

Detailed Description
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During delivery, there can be a lesion of the nerve roots of the brachial plexus (cervical C5-C8 and/or thoracic T1 roots). The newborn presents at birth a paralysis of the arm (Obstetrical Brachial Plexus Paralysis: OBPP). One third of children with OBPP will have sequelae despite daily rehabilitation. The most frequent disability is shoulder stiffness. The current hypothesis is that this stiffness is due to a permanent imbalance between the affected shoulder muscles (lateral rotators) and the muscles less affected by the paralysis (medial rotators). Because of this imbalance, the injured shoulder is spontaneously positioned in medial rotation. This position would lead to retractions at the front of the joint despite rehabilitation. In case of incomplete recovery, growth disorders of the shoulder joint (dysplasia) appear as well as a functional handicap. The management, from the age of 2 years, in case of shoulder stiffness and dysplasia, is surgery (arthrolysis) to regain mobility. During this operation, a muscle transfer can also be performed to strengthen the lateral rotator muscles. However, despite surgery, mobility deficits often recur within a few years. To understand the origin of the lateral and medial rotation deficits, the investigators conducted an anatomopathological study of the rotator muscles in these children. The preliminary results show a significant damage of the rotator muscles with the presence of fibrosis which could explain the rotational stiffness and the functional impairment. To better understand the pathophysiological mechanisms, the investigatorswill set up an OBPP model in cell culture to understand the regenerative capacities and to test new pharmacological approaches.

Official Title
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Study of the Biological Function of Muscle Satellite Cells From Patients With Obstetric Brachial Plexus Palsy Satellite Cell Obstetrical PlExus (SCOPE)

Conditions
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Obstetrical Brachial Plexus Palsy

Intervention / Treatment
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* Procedure: Muscle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OBPP children with a planned shoulder surgery (arthrolysis and/or muscle transfer). Exclusion Criteria: other neurological disorders, post-traumatic shoulder stiffness

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OBPP children<br>OBPP children operated on to treat shoulder stiffness. | Procedure: Muscle biopsy<br>* Peroperative muscle biopsy will be performed during a planned shoulder surgery (arthrolysis and/or muscle transfer)<br>* Other names: Shoulder muscle transfer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of muscle regeneration capacity: proliferation capacity | Proliferation capacity of satellite cells assessed by immunofluorescence: percentage of Pax 7 positive cells/total desmin positive cells | 30 days | 
| assessment of muscle regeneration capacity: differenciation capacity | Differentiation capacity of satellite cells assessed by histology: fusion index (number of nuclei in a myotubule compared to total number of nuclei in the sample) in percentage | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of botulinum toxin on the proliferation potential of satellite cells: proliferation capacity | Proliferation capacity of satellite cells assessed by immunofluorescence: percentage of Pax 7 positive cells/total desmin positive cells. | 30 days | 
| Effect of botulinum toxin on the proliferation potential of satellite cells: differentiation capacity | Differentiation capacity of satellite cells assessed by histology: fusion index (number of nuclei in a myotubule compared to total number of nuclei in the sample) in percentage | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brachial plexus, Neonatal brachial plexus palsy, Denervation, Muscle atrophy, Muscle regeneration, Botulinum toxin, Satellite cell, Primary human muscle cell culture