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Effect of Botulinum Toxin on Muscles of Children With Cerebral Palsy

Not Applicable
Completed
Conditions
Cerebral Palsy
Interventions
Procedure: Muscle biopsy
Registration Number
NCT02853240
Lead Sponsor
Hospices Civils de Lyon
Brief Summary

Cerebral palsy (CP) is a group of non-progressive motor dysfunction but often changing, secondary to injury or brain abnormalities that occur in early stages of development. In children with CP, the brain injury lead to a delayed motor development in the first weeks, associated with muscular spasticity. Drug treatments include oral treatments (baclofen and tizanidine) and injectable treatments like Botox (intramuscular injection) and neurolysis with alcohol or phenol (local injection into the nerve).

Regarding botulinum toxin, there is no study questioning its effectiveness. However, no publication on the pathophysiology of human muscle of the CP child after toxin injection was found. The action of the toxin on the neuromuscular junction (NMJ) and muscle structure is unknown in children with CP.

The primary objective of this study is to describe structural abnormalities of the CP child's muscle following multiple toxin injections in terms of NMJ fragmentation and axonal sprouting.

Secondary objectives:

To evaluate the relationship between:

* The severity of the motor impairment and muscle structural abnormalities.

* The clinical measure of spasticity and muscle structural abnormalities.

* To compare the structure spastic muscles with toxin injections and spastic muscle without toxin injections

For muscles with multiple toxin injections, assessing the relationship between :

* The number of toxin injections and muscle structural abnormalities.

* The date of the first injection and muscle structural abnormalities.

* The total dose of injected toxin in the muscle and its structural abnormalities.

* The nature of the product injected in the muscle and its structural abnormalities.

This innovative study will improve the knowledge on the effects of long-term botulinum toxin injections on the muscle (and therefore its safety in usual care), on the spastic muscle NMJ of CP children, on the pathophysiology of the CP child's muscle.

All the visits all acts will be performed according to usual patient follow-up. Only a biopsy will be performed in addition, taken from an injected muscle during a planned operation. A biopsy may also be performed on a muscle without toxin injection if the act is made possible by the planned surgery. No biopsy will be made on a muscle that would not require surgery.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Age Children > 7 years and <18 years
  • With spastic cerebral palsy (all grades of the combined GMFCS
  • Having an orthopedic surgical indication already planned on the lower limbs
  • Receiving toxin injections
  • With social security coverage
  • Whose parents / holders of parental authority have signed the consent form
Read More
Exclusion Criteria
  • Patients with an evolutive CP
  • Children with a baclofen pump
  • Children who underwent neurotomy or functional dorsal rhizotomy, or alcohol or phenol injections
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Children with spastic CP receiving toxin injectionsMuscle biopsyChildren with spastic cerebral palsy receiving toxin injections
Primary Outcome Measures
NameTimeMethod
Presence of neuromuscular junctions fragmentation (both qualitative and quantitative).6 months maximum (time of surgery)

The biopsy is performed at the same time of a scheduled general anesthesia surgery (multisite surgery). The biopsy is 2 to 3 mm x 10 mm. It is a simple and quick gesture, usually practiced by surgeon

Presence of axonal sprouting (qualitative).6 months maximum (time of surgery)
Secondary Outcome Measures
NameTimeMethod
Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the delay (in months) since the first toxin injection in the muscle6 months maximum (time of surgery)
Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the brand of the injected toxin (Botox® or Dysport®).6 months maximum (time of surgery)
Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the number of toxin injections in the muscle.6 months maximum (time of surgery)
Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the total volume (IU) of injected toxin since the first injection in the muscle.6 months maximum (time of surgery)
Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to Tardieu score.6 months maximum (time of surgery)

The Tardieu Scale is bedside tool for assessing muscle spasticity in patients with neurological conditions. Tardieu scale grades from 0 to 5.

Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to patient's GMFCS grade (1 to 5).6 months maximum (time of surgery)

The Gross Motor Function Classification System (GMFCS) is a 5 level clinical classification system that describes the gross motor function of people with cerebral palsy on the basis of self-initiated movement abilities.

Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to Ashworth score.6 months maximum (time of surgery)

The Ashworth scale is bedside tool for assessing muscle spasticity in patients with neurological conditions. Ashworth grades as follows: 0, 1, 1+, 2, 3, 4.

Trial Locations

Locations (1)

Hôpital Femme Mère Enfant

🇫🇷

Bron, France

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