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Brief Summary

The focus of this study is to understand and define the mechanisms of the altered muscle development and growth on a microscopic level within a long-term perspective in children with cerebral palsy and to relate these findings to muscle macroscopic properties defined by muscle imaging, to neuromuscular symptoms and to treatment. This study aims to (1) evaluate intrinsic microscopic muscle properties of young growing children with CP, and (2) to evaluate these muscle properties in relation to macroscopic properties, neuromuscular symptoms and to treatment. Improved understanding of changes in microscopic muscle properties, and how they relate to macroscopic properties and to the neuromuscular symptoms as well as how they are influenced by treatment, has the potential to delineate CP phenotypes prone to intervention and to optimize treatment protocols or develop new treatments, leading to new avenues for improving function in CP. The method to study microscopic muscle properties involves analysis of muscle biopsies (histological / immunohistochemistry analysis, SC and IC culture, gene expression). Biopsies will be collected using the minimally invasive percutaneous needle microbiopsy technique, suitable for collecting repeated samples over time in the same individual while still leading to sufficient tissue of good quality for subsequent analysis1,2. For the children with CP, the local hospital's tradition of applying general anesthesia for delivering BTX injections will be exploited to collect the muscle samples prior to the BTX session and the one-year follow-up, or general anesthesia planned for orthopedic surgery or diagnostic imaging such as MRI, etc. For the collection of the samples 3 months before the BTX session, as well as 3 months and 6 months after BTX injections, the common approach for microbiospy collection will be applied, with local sedation on the skin (Rapydan©) and fascia (Xylocaine©) and local anesthesia by using Kalinox© (nitrous oxide in oxygen) under supervision of the University Hospital PROSA team. Biopsies of TD muscles will be collected in children with no history of neurological disorder, nor musculoskeletal problems at the level of the gastrocnemius or semitendinosus, at the time of upper limb orthopedic or trauma surgery and thus always under general anesthesia. Ultrasound guided percutaneous muscle biopsy has been performed in children (2 months-18 years)3,4 and has proven to be safe and well-tolerated. A pilot study (S61110) was conducted to confirm that the microbiopsy technique is suitable for the analysis of microscopic muscle properties and is well-tolerated in children with CP. Two specific research goals are planned, with hypotheses emerging from literature.

Outcome Measures

Primary Outcomes (9)

Muscle fiber size
Cross sectional area in µm of the fiber. Muscle fiber size will be assessed on cryosection stained with an antibody cocktail specific to laminin, myosin heavy chain (MHC)-I, MHC-IIA, MHC-IIB, MHC-embryonal and immunofluorescent detection will be done using appropriate secondary antibodies.
Through a study participation of 1,2 years depending on the trajectory: 1 evaluation moment at baseline, 1 follow-up 1,2 years after, or 5 evaluations: 3 months pre, baseline, 3 months after, 6 months after and 1,2 years after baseline
Muscle fibre type proportion
For each muscle, muscle fiber proportion will be assessed on cryosection stained with an antibody cocktail specific to laminin, myosin heavy chain (MHC)-I, MHC-IIA, MHC-IIB, MHC-embryonal and immunofluorescent detection will be done using appropriate secondary antibodies.
Through a study participation of 1,2 years depending on the trajectory: 1 evaluation moment at baseline, 1 follow-up 1,2 years after, or 5 evaluations: 3 months pre, baseline, 3 months after, 6 months after and 1,2 years after baseline
Capillary density
Capillaries /mm2 fiber and capillary to fiber ratio. Capillaries will be detected in-situ. Capillaries will be assessed using CD31 staining.

Secondary Outcomes (3)

Overall changes in collagen content
Through a study participation of 1,2 years depending on the trajectory: 1 evaluation moment at baseline, 1 follow-up 1,2 years after, or 5 evaluations: 3 months pre, baseline, 3 months after, 6 months after and 1,2 years after baseline
Overall change in muscle composition of the medial gastrocnemius muscle and the semitendinosus muscle by means of echo-intensity
Through a study participation of 1,2 years depending on the trajectory: 1 evaluation moment at baseline, 1 follow-up 1,2 years after, or 5 evaluations: 3 months pre, baseline, 3 months after, 6 months after and 1,2 years after baseline
Overall change in muscle tendon length of the medial gastrocnemius muscle and the semitendinosus muscle
Through a study participation of 1,2 years depending on the trajectory: 1 evaluation moment at baseline, 1 follow-up 1,2 years after, or 5 evaluations: 3 months pre, baseline, 3 months after, 6 months after and 1,2 years after baseline

Study Arms (4)

Children with spastic cerebral palsy

Children between 2 and 9 years old.

Typical developing children

Children between 2 and 9 years old.

Adolescents and adults with HSP

Adolescents between 12 and 18 years of age and adults.

Typically developing adolescents and adults

Age- and gender- matched with the recruited HSP patients

Eligibility Criteria

Age2 Years - 9 Years

Sexall

Healthy VolunteersYes

Age GroupsChild (0-17)

Sampling MethodNon-Probability Sample

Study Population

Children with spastic cerebral palsy, who have routine follow-up care at the CP reference center of the University Hospitals Leuven.

You may qualify if:

Children (boys/girls) diagnosed with predominantly spastic type of CP

Biospecimen

Retention: SAMPLES WITH DNA

Sonographically guided percutaneous needle micro-biopsies will be collected at the Medial Gastrocnemius and the Semitendinosus. Per biopsy, four muscle samples of +/- 20 mg will be collected per muscle on one location of the muscle, and useable for both histological and cell culture analysis.

3D-Microscopic Muscle Architecture in Cerebral Palsy

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (9)

Secondary Outcomes (3)

Study Arms (4)

Children with spastic cerebral palsy

Typical developing children

Adolescents and adults with HSP

Typically developing adolescents and adults

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Biospecimen

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations

3D-Microscopic Muscle Architecture in Cerebral Palsy

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (9)

Secondary Outcomes (3)

Study Arms (4)

Children with spastic cerebral palsy

Typical developing children

Adolescents and adults with HSP

Typically developing adolescents and adults

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Biospecimen

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Central Study Contacts

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations