Botulinum Neurotoxin for Children With CP: a Delicate Balance Between Clinical Benefits and Muscular Harm

Botulinum Neurotoxin for Children With Cerebral Palsy: a Delicate Balance Between Clinical Benefits and Muscular Harm

A cross-sectional design study will be carried out to explore the morphological muscle properties and alterations in muscle composition on a macroscopic level in children with spastic cerebral palsy (CP). Muscle composition will be assessed using quantitative Magnetic Resonance Imaging (qMRI) and shear wave elastography (SWE), while macroscopic muscle size properties will be evaluated through 'Three-dimensional freehand ultrasound (3DfUS).

Background: Altered muscle composition, including increased fat infiltration and collagen content, is a key factor in impaired muscle function in cerebral palsy (CP). However, quantitative data on muscle composition in CP is limited. Traditional methods like ultrasound can only indirectly assess these changes through echo-intensity, while invasive muscle biopsies are impractical for children. Recent advancements in quantitative Magnetic Resonance Imaging (qMRI) and shear wave elastography (SWE) provide non-invasive alternatives. The qMRI Dixon sequence can assess fat infiltration, while the T1ρ sequence can estimate collagen content. SWE can measure passive muscle stiffness as a surrogate marker for collagen. Combining these techniques allows for a comprehensive evaluation of muscle composition and its impact on muscle function in CP. Next to muscle composition, children with CP also exhibit muscle size deficits compared to typically developing (TD) children. More specifically, when accounting for the effect of natural muscle growth, normalized muscle volume was found to be reduced, which could be attributed to a reduction in normalized cross-sectional area and normalized muscle belly length. Because muscle morphology (or muscle size) can be estimated using accessible ultrasonography techniques, alterations in muscle size have been well-described in growing children with CP. However, since muscle composition can only be estimated through more advanced, recent muscle imaging techniques, its alteration in CP remains underexplored.

Aim: To comprehensively describe the alterations in intrinsic muscle properties, the evaluation of altered muscle morphology (or muscle size) will be complemented with the description of alterations in muscle composition. Unlike muscle size, which increases with age, muscle composition remains relatively stable in typically developing children. Since comprehensive assessment of muscle composition requires MRI, a less practical tool compared to ultrasonography, the study will adopt a cross-sectional descriptive design. We aim to create an integrated dataset of muscle composition combined with muscle size, passive muscle stiffness and clinical assessments for CP and TD children that are equally distributed over pre-school, grade-school and teen-aged.

Methods/design: Children with CP who participated in previous studies within this project will be invited to join the current study. 34 children with CP participants will be recruited to reach the target sample size . The CP group will be evenly divided between those who are botulinum neurotoxin (BTX) naïve and those who have received BTX treatment. Only children with a Gross Motor Function Classification System (GMFCS) level of I, II, or III will be included. In total, 34 children with CP and 17 age-matched typically developing (TD) children will be enrolled in the study.

Participants will be evaluated at the University Hospitals Leuven (UZ Leuven) at campus Gasthuisberg or campus Pellenberg. Data will be collected during a hospital visit and every participant will undergo at least a 3DfUS and SWE measurement of the medial gastrocnemius. Other information that will be collected out of the available medical records includes the results of the structural brain MRI, the use of medication, treatment details (physiotherapy, orthotics and/or orthopedic interventions), anthropometric measures (body weight and length and leg lengths), data of a standard clinical examination (joint range of motion, spasticity, and muscle selectivity and strength).

- Children with spastic cerebral palsy

Inclusion criteria:

• Children (boys/girls) with congenital brain lesion, confirmed with neuro-imaging such as MRI
• At high-risk for CP or diagnosed spastic type of CP
• (Suspected) Gross Motor Function Classification Scale (GMFCS) Level I-III
• Uni or bilateral involvement
• Aged between 2-16 years

Exclusion criteria:

• Presence of dyskinesia or ataxia

• Severe co-morbidities (cognitive problems)

• BTX treatment in the gastrocnemius in the past 10 months

• Previous surgery at the investigated muscles.

• Previous orthopedic or neurosurgery

• Severe ankle deformities

• Weight for height values >2SD or <-2SD from mean

  • Typically developing children

Inclusion criteria:

• Aged between 2-16 years

Exclusion criteria:

• History of neurological, orthopedic or muscular problems
• Involvement in an elite or high-performance sporting program (Children performing the same sports for > 5 hours/week will be excluded)