Spastic Myopathy in Adults With Cerebral Palsy

Official title

Clinical, Biomechanical, Histo-immunological and Radiological Characterization of the Effects of Two Gastrocnemius Stretching Programs in Adult Patients With Spastic Paresis Following Cerebral Palsy: MYOSPAS-CP, a Randomized Controlled Study

Overview

Cerebral palsy (CP) is indeed the result of a central neurological lesion, but it also involves a lesser-known muscular condition that we refer to as spastic myopathy. This condition is likely the consequence of relative immobilization and underuse of the muscles in the affected limbs and, through a vicious cycle, it in turn plays a major role in movement difficulties. Among the muscles involved are the plantar flexors, whose extensibility decreases from the earliest years of the child's life. The BIOTN research team (UR7377; Université Paris-Est Créteil; Dr M. Pradines, Prof. J.-M. Gracies, CHU Henri Mondor, Créteil), supported by the Fondation pour la Paralysie Cérébrale, is conducting a randomized controlled study aimed, on the one hand, at characterizing in these individuals the genetic, histological, radiological, mechanical, physiological, and clinical changes in the calf muscle, and on the other hand, at exploring the reversibility of these alterations by comparing the effects of two types of rehabilitation after one year. This study will provide essential insights for the development of specific and adapted rehabilitation strategies designed to improve the living conditions of individuals with cerebral palsy.

Detailed description

Cerebral palsy (CP), resulting from a perinatal central neurological lesion, leads not only to lifelong motor impairment but also to a specific muscular disorder: spastic myopathy. This condition is characterized by early and progressive structural changes including decreased passive extensibility (XV1), reduced muscle fiber diameter, decreased number of sarcomeres in series, and hypertrophy of the endomysium and perimysium. In children, impaired gastrocnemius growth-quantified by reduced medial gastrocnemius muscle volume-appears before age 3 and precedes both hyperactivity and fixed stiffness. However, the long-term consequences of decades of underuse on the mechanical, histological, and morphometric properties of the gastrocnemius in adults with IP remain insufficiently explored.

Stretching, although widely prescribed, lacks standardized parameters, and its long-term effectiveness in adults with IP has never been formally evaluated. Evidence suggests that muscular plasticity requires high-load stretching and ≥10 minutes per muscle per day. Preliminary studies using Guided Self-Rehabilitation Contracts (GSCs) demonstrated significant gains in extensibility and function, while a randomized controlled trial in adults with acquired hemiparesis showed increased fascicle length, increased muscle thickness, and improved gait speed after one year of high-load self-stretching, supporting the reversibility of molecular pathways driving contracture.

This single-blind randomized controlled trial includes 40 adults with IP, randomized to: (1) conventional physiotherapy alone, or (2) conventional physiotherapy + a one-year daily GSC-based high-load gastrocnemius self-stretching program (10 minutes/day + phasic maximal dorsiflexion efforts). Multi-scale assessments span six analytical domains: clinical measures (XV1, XV3, XA; gait speed; SF-36), in vivo tissue biomechanics (resistance torque, passive energy, fascicle length, muscle thickness), functional and neurophysiological biomechanics (agonist-antagonist recruitment during gait), MRI morphometry (volume, intramuscular fat, edema), in vitro biomechanics (compressibility, strain, rupture stress), and genetic/histological markers (satellite cells, expression profile of 57 myogenic genes). Micro-invasive biopsies of both limbs will be performed at J1 and M12.

The primary outcome is maximal barefoot 10-meter gait speed. Secondary outcomes will characterize, chronologically and mechanistically, the trajectory of spastic myopathy and the potential of long-term high-load stretching to partially reverse its pathogenic processes.

Interventions

• Behavioral Guided Self-rehabilitation Contract
  Participants randomized to the intervention arm will receive a one-year individualized program based on the Guided Self-Rehabilitation Contract (GSC) method. A physiotherapist specifically trained in GSC will supervise all 20 patients. The therapist will conduct monthly 1.5-hour home visits, supplemented as needed by intermediate webcam or telephone consultations. The GSC method aims to increase the patient's knowledge, responsibility, and active involvement in their rehabilitation. Its core ps
• Behavioral Conventional therapy group
  In this group, subjects follow their rehabilitation sessions as before their enrollment. Conventional physiotherapy will typically consist of one to three sessions per week, delivered either in a private outpatient practice or at the patient's home, depending on the medical prescription. Session duration and therapeutic content may vary, reflecting routine real-life practice. Quantitative and qualitative data regarding conventional physiotherapy will be collected for all subjects throughout the

Primary outcome measures

• Maximal ambulation speed over 10 meters [Time frame: Day 1, Month 6, Month 12]

Secondary outcome measures (12)

• Plantar flexor clinical extensibility (XV1) [Time frame: Day 1, Month 6, Month 12]
• Plantarflexor spasticity [Time frame: Day 1, Month 6, Month 12]
• Active dorsiflexion (XA) [Time frame: Day 1, Month 6, Month 12]
• LG Young modulus [Time frame: Day 1, Month 6, Month 12]
• LG fascicle length [Time frame: Day 1, Month 6, Month 12]
• LG Tickness [Time frame: Day 1, Month 6, Month 12]
• LG Muscle volume [Time frame: Day 1, Month 12]
• Intramuscular fat percentage [Time frame: Day 1, Month 12]
• LG hyperelastic behavior under compression [Time frame: Day 1, Month 12]
• LG fiber-type composition [Time frame: Day 1, Month 12]
• LG endo-/perimysial fibrosis [Time frame: Day 1, Month 12]
• LG genetic expression [Time frame: Day 1, Month 12]

Eligibility criteria

Inclusion criteria

• Hemiparesis or diparesis resulting from a cerebral lesion occurring during the perinatal period (cerebral palsy).
• Gastrocnemius extensibility XV1 < 100° (XV1, Tardieu Scale).
• Maximum barefoot walking speed (AT10) between 0.3 and 1.2 m/s.
• Written informed consent to participate in the study.

Exclusion criteria

• Botulinum toxin injections in the medial gastrocnemius within less than 3 months prior to study inclusion.
• Cognitive impairment preventing participation in the GSC program or in the study.
• Patients under legal guardianship or conservatorship.
• Known hemostasis disorders.
• Hypersensitivity to allergens.
• Presence of a metallic intraocular foreign body (accidental fragments or others), a pacemaker, a neurostimulator (pain treatment), a cochlear implant, or, more generally, any implanted electronic medical device that cannot be removed; presence of a metallic cardiac valve in the study participant.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

France · 1 center

• Maud Pradines — Créteil

Identifiers

NCT: NCT07293988 · 2020-A00041-38 · 2019-004945-33

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗