Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy
Condition: Spastic Cerebral Palsy
MeSH terms: Muscle Spasticity; Paralysis; Cerebral Palsy
Study type: Interventional

Summary: 
      This study investigates the effect of integrated Botulinum Neurotoxin A (BoNT) treatment on
      morphologic muscle and tendon properties, spasticity, joint stiffness, joint range of motion,
      muscle strength, gait and gross motor function. The integrated BoNT treatment combines
      BoNT-injections with serial casting and intensive physical therapy, as previously described
      by Molenaers et al. The current study will include 30 children who are clinically scheduled
      for BoNT treatment in the medial gastrocnemius and/or the semitendinosus muscle in the
      intervention group and 30 children in a control group who will receive usual care within a
      time span of 3 months.
    

Detailed description: 
      Aim:

      This study investigates the effect of integrated Botulinum Neurotoxin A (BoNT) treatment on
      morphologic muscle and tendon properties (muscle length and muscle volume, assessed with a 3D
      ultrasound measurement), spasticity and joint stiffness (measured with an instrumented
      spasticity assessment), joint range of motion (measured through goniometry), muscle strength
      (measured using dynamometry), gait (assessed through 3D gait analysis) and gross motor
      function (assessed using clinical test batteries). The aim is twofold: (1) determine whether
      integrated BoNT treatment of the medial gastrocnemius and the semitendinosus muscle(s) leads
      to changes in the morphologic muscle and tendon properties of the medial gastrocnemius and
      the semitendinosus muscle(s), the ankle and knee range of motion, spasticity, stiffness,
      muscle strength and gait, and (2) determine the correlation between baseline morphologic
      muscle and tendon properties and the changes in the primary outcome parameters (spasticity
      and stiffness) following the BoNT-treatment.

      Design:

      The current study has a non-randomized controlled design. Because BoNT is proven an effective
      treatment to reduce spasticity and improve gross motor function, it cannot be clinically
      justified to allocate children to a non-treatment group, if a new BoNT treatment is required.
      Delayed BoNT treatment could rapidly increase musculoskeletal impairments. It is therefore
      considered unethical to temporarily withdraw BoNT treatment from patients. To compensate the
      lack of randomization accurate matching of groups is required. Children will be matched on
      diagnosis (uni/bilateral CP), GMFCS level, age and spasticity level.

      BoNT-treatment:

      All children in the intervention group will receive BoNT injections in the medial
      gastrocnemius and/or the semitendinosus muscle(s) (other muscles may also be treated as part
      of multilevel treatment). As part of the standard integrated treatment approach of the CP
      Reference Centre of the University Hospitals Leuven, the injections are followed by a period
      of bilateral stretching casts if indicated (below the knee walking casts and removable knee
      extension casts when necessary) and all children will receive intensive physical therapy and
      application of orthotic management following BoNT injections. The follow-up period for the
      current study is 8-10 weeks. During this intensive physical therapy post-BoNT, the children
      in the intervention group will work on individualized treatment goals. These goals will be
      defined based on the baseline measurements during a multidisciplinary discussion with the
      treating physician, which is scheduled prior to the BoNT treatment. The fulfillment of these
      patient-specific goals will be evaluated by the Goal Attainment Score (GAS). During the
      follow-up period, the treating physical therapist will be interviewed on a two-weekly basis
      to verify whether and to what extend the therapy is focused on the personal treatment goals.
      Assessments of morphologic muscle and tendon properties, spasticity, stiffness, joint range
      of motion, muscle strength, and gait of the participants will be performed before the BoNT
      injections, and 8-10 weeks after the injection. This period of 8-10 weeks follow-up post BoNT
      injections was found to be appropriate, since the potential effect of BoNT on gross motor
      function is expected to be optimal after 6-10 weeks.

      Study groups:

      The study will include patients who are diagnosed with spastic CP, aged between 4 and 11
      years and with Gross Motor Function Classification System (GMFCS) level I-III. The
      intervention and control group will be group-matched based on diagnosis (uni/lateral CP),
      GMFCS level, age and spasticity level.

      Overall exclusion criteria were: BoNT injections less than 6 months before inclusion, a
      treatment history that includes previous selective dorsal rhizotomy treatment or a bony
      surgery less than 2 years before inclusion, and limited cooperation that would prevent a
      proper assessment. For all enrolled children, intensive rehabilitation post BoNT injections
      had to be foreseen as the standard care. For the intervention group, 30 children with a
      clinical indication for BoNT injections in the medial gastrocnemius and/or semitendinosus
      muscle(s) will be recruited, while for the control group, 30 children without an indication
      for a specific intervention in the next 3 months will be recruited.

      For the intervention group, the baseline measures will be followed by the BoNT injections
      combined with casting and goal-oriented physical therapy (as described above), and the
      follow-up assessments will be planned 8-10 weeks post BoNT injections. Baseline and follow-up
      assessments for the intervention groups include 3D ultrasound, the instrumented spasticity
      measurement, functional strength tests, and 3D gait analysis.

      The children in the control group will also be assessed twice with an interval of 8-10 weeks.
      During the 8-10 weeks, they will continue their usual care or normal routine treatment, i.e.
      regular physiotherapy and orthotic devices. Baseline and follow-up assessments for the
      control group include 3D ultrasound, the instrumented spasticity measurement and functional
      strength tests.
    

Intervention name(s): Botulinum Toxin treatment combined with a post-BoNT intensive physical therapy period guided by individualized treatment goals.
Intervention type(s): Other
Intervention description(s): BoNT treatment combined with a follow-up period of intensive physical therapy of 8-10 weeks. During this intensive physical therapy post BoNT injections, the children in the intervention group will work on individualized treatment goals, which will be defined based on the baseline measurements during a multidisciplinary discussion with the treating physician (planned prior to the BoNT injections).
Intervention MeSH terms: Botulinum Toxins
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: We will include patients who receive BoNT injections at the lower limb in the intervention group. Patient with no indication for treatment in the next three months (besides the routine physical therapy and orthotic management) will be asked to participate in the control group. Justification for the non-randomized design is stated above.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cerebral Palsy; Spastic Cerebral Palsy; Botulinum Toxin; muscle morphology; Range of motion; Stiffness; Spasticity; Intensive physical therapy