Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation

Study Overview
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Brief Summary
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The aim of our study is to evaluate the correlation between quantified fibro-adipous infiltration of muscles on MRI assessed by MERCURI Score and the functional abilities (deficiencies, activity limitations and social participation of pediatric patients with arthrogryposis.

Detailed Description
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Arthrogryposis multiplex congenita (AMC) is a group of rare diseases characterized by joint contractures at two or more distinct joint levels at birth. More than 400 causes are currently known. The prevalence is estimated at 1/3000 to 1/2000. Joint limitations are not progressive, but the functional consequences have a lifelong impact on patients. Correlations between fibro-adipous infiltration and muscular deficits have already been studied in other neuromuscular diseases such as Pompe disease or Duchenne muscular dystrophy. These studies concluded on a good correlation between disease progression and severity, muscle strength, and fatty infiltration assessed by Mercuri score. The investigators concluded that muscular MRI can be used as a non-invasive biomarker and a tool to follow the progression of neuromuscular disease and help evaluate the potential effects of therapies. The aim of this project is to define whether MRI could also be used as a tool, through the assessment of muscle fatty infiltration, to help predict the functional abilities of our patients with AMC, and more specifically the two most frequent types, Amyoplasia and distal arthrogryposis. The investigators will analyze fatty infiltration measured by muscle MRI and quantify it using the MERCURI score which was developed by Mercuri et al. (Mercuri et al. 2002) as a semi-quantitative score to quantify fibro-adipose muscle infiltration on muscle MRI. The investigators will evaluate musculoskeletal deficiencies and limitations of activity from data obtained from patients followed in our AMC reference center at the University Hospital Grenoble Alpes (CHUGA). The investigators will include data from 220 children, 97 of whom have had a complete check-up including a muscle MRI. The investigators will study the existence of a correlation between this score and the deficiencies and limitations of activity. The investigators will then evaluate the potential predictive role of fatty infiltration measured on MRI in the functional abilities of the patients. This characterization will help to better determine and anticipate the functional capacities of our patients from the beginning of their treatment to improve their functional prognosis. This initial work could enhance the reflection on the biomechanical modeling of joints and key functions such as standing and the acquisition of walking, in order to pave the way for rehabilitation and compensation methods that are better adapted to patient's needs.

Official Title
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Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation

Conditions
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Arthrogryposis Multiplex Congenita, AMC-Arthrogryposis Multiplex Congenita, Pediatric ALL

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age < 18 at the first clinical evaluation or follow up exclusively in CHUGA pediatric rehabilitation unit Clinical or molecular diagnosis of AMC established by geneticists at CHUGA functional evaluation during consultation and follow-up in CHUGA pediatric rehabilitation unit Muscle MRI of upper limbs, lower limbs and trunk performed at CHUGA pediatric radiology unit Exclusion Criteria: Contra indication MRI. MRI non exploitable. Patient under guardianship or deprived of liberty

Ages Eligible for Study
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Minimum Age: 0 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 Amyoplasia<br>Patients with diagnosis of Amyoplasia | Other: No intervention<br>* No intervention<br>|
| Group 2 Distal Arthrogryposis<br>Patients with diagnosis of Distal Arthrogryposis | Other: No intervention<br>* No intervention<br>|
| Group 3 Other<br>Patients with diagnosis of other form of AMC | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mercuri Scores of upper limbs, trunk, and lower limbs evaluated on muscle MRI T1 | The degree of fatty muscle infiltration was assessed on muscular MRI and quantified by Mercuri score, each muscle was staged as follows: 1. Normal appearance, 2. Mild involvement (30-60% fatty infiltration). 3. Moderate involvement (>60% fatty infiltration). 4. Severe involvement (complete infiltration). The degree of muscle fat infiltration was assessed with at least 2 visible slices, and performed by two independent operators. In case of divergent assessments, a consensus was reached after discussion. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular weakness | Muscular weakness assessed by function (flexion, extension etc.) and not by each muscle, using the Medical Research Council (MRC) scale (from 0 to 5). The quotation was as follows: 0, no contraction; 1, flicker or trace of contraction; 2, active movement possible only with gravity eliminated; 3, active movement against gravity in the whole range of motion; 4, active movement against gravity and resistance; 5, quasi-normal strength) Evaluated by physiotherapists, occupational therapists and physician during evaluation. | through study completion, an average of 1 year | 
| Passive range of motion (PROM) | Evaluated by physiotherapists; the range of motion of each movement in degrees was normalized with respect to the normal maximal movement, expressed as percentages | through study completion, an average of 1 year | 
| Reaching score | Reaching capacity was assessed by ad hoc test. Patients were instructed to successively touch some body targets with upper limbs : mouth, head, forehead, neck, back, stomach, gluteal region, opposite shoulders, ipsilateral shoulders, knee, feet, Beggar's pose, position of the oath, and Zenith Pose. Each gesture was marked yes if successful or no if not. Responses were transformed into a binary variable with yes being worth 1 and no being worth 0 to allow for statistical correlations afterwards. The total score was calculated on both sides averaged and ranged from 0 to 14 points | through study completion, an average of 1 year | 
| Ambulatory status | Ambulatory statuses were gathered by the teams during the check-ups as well as the age of acquisition of walking if available and the use or not of technical aids | through study completion, an average of 1 year | 
| School status | Type of schooling (mainstream education, adapted schooling, presence of a carer) | through study completion, an average of 1 year | 
| Activity limitation | Gathered evaluating living habits and essential acts of daily life such as element of the Functional Independence Measure (FIM) : feeding, dressing, potty training, toileting, schooling, transfers, locomotion, and also existence of leisure, hobby, presence of human or technical helps. | through study completion, an average of 1 year | 
| Surgery History | Surgical history for each patient | through study completion, an average of 1 year | 
| Human and technical Help | use of a technical aid (manual or electric wheelchair ...), or humain for daily life activities | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthrogryposis Multiplex Congenita, Pediatric, Mercuri Score, MRI, Fibro-adipous infiltration, Functional capacity, Rehabilitation, Retrospective observational study