CAP': Intensive playful rehabilitation program

An urgent priority in the field of paediatric neurorehabilitation is the development of effective early motor interventions. Animal studies strongly suggest early intensive rehabilitation may have a large impact on brain and corticospinal organisation, reducing motor impairments and their mid- to long-term consequences in children with cerebral (CP).

Although most brain growth, development and organization occurs within the first 2 years of life, the majority of research into the effectiveness of intensive rehabilitation and mechanisms that underlie responses to therapy has been conducted in school-age children (i.e. > 6 years).

Furthermore the main focus of research has been on children with unilateral CP, despite the fact that bilateral CP is the most prevalent form. Studies of the effectiveness of early intensive interventions on global motor function in larger groups of children with CP, including bilateral CP are thus required.

Hand and Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the upper (UE) and lower extremities (LE) and has been shown to improve aspects of motor function of the UE and LE in school age children with unilateral2 and bilateral3 cerebral palsy across the 3 levels of the International Classification of Functioning, Disability and Health (ICF). The principles and content of HABIT-ILE can be applied to pre-school children and this method is highly promising for early rehabilitation. HABIT-ILE is a motor skill learning-based therapy carried out in a camp-setting, with structured tasks of increasing motor difficulty and functional activities that require the use of both hands whilst sustaining postural or locomotor activity of the LE. Tasks are based on games and the whole environment is set up such that the children perceive the camp as fun. For both the children with unilateral and bilateral CP, the tasks will be chosen according to individualized functional goals previously defined by the parents (e.g drinking by him/herself, walking without help, opening a box of toys, holding a book, putting off pants, playing in sitting without support, etc.).

Results of the initial assessments will be used to determine appropriate tasks for each child. Over the course of the 2 weeks, tasks will be progressed to further challenge bimanual coordination, postural control and LE function.

The primary objectives are to evaluate the effect of two weeks of early HABIT-ILE on:
- bimanual performance in pre-school children (1-4 years old) with unilateral CP (Randomized Controlled Trial 1=RCT1 N= 50 children), and on
- gross motor function of children with bilateral CP (RCT 2, N= 60 children)
in comparison with two weeks of usual motor activity including usual rehabilitation (control group).
We hypothesize that early HABIT-ILE will induce larger changes on bimanual performance and gross motor function than usual motor activity.

One of the main secondary objective is to evaluate whether the impact of HABIT-ILE is age-dependent, thus exploring what we will call in this project the window of opportunity for optimal timing of the intervention. The timing of the intervention is intentionally targeted at the period of the child’s life when CP has been confirmed, participation in intensive rehabilitation is feasible, and the window of neuroplastic potential is still open.

The other secondary objectives are to:
-Evaluate further changes in motor control and function using different tests of motor function, activity questionnaires and executive function tests
-Evaluate neuroplastic changes using brain imaging (magnetic resonance imaging, MRI) in children
-Evaluate biomechanical changes using an optoelectronic motion capture system with EMG to determine the effect of HABIT-ILE on movement pattern and quality
The children who will participate to this study will be followed in:
• Brest (34 children)
• Angers (18 children)
• Louvain (34 children)
• Pise (24 children)

In parallel, a third Randomized Controlled Trial will be carried out in a perinatal rodent model of unilateral and bilateral CP that will undergo adapted HABIT-ILE. This trial aims to evaluate mechanisms that cannot be explored in detail in children. It will assess the effects of early and late rehabilitation on functional outcomes in rats with unilateral and bilateral CP as well as white matter tract reorganisation.

Inclusion criteria will be:

children with cerebral palsy (spastic or dyskinetic), unilateral or bilateral cerebral palsy, age 1 to 4 years inclusive (corrected age if preterm birth) and ability to follow instructions and complete testing according to the age.

A pair-matched randomization will be used in order to ensure comparability. For children with unilateral CP, each child will be matched with a child with the closest profile based on age (4 categories: 1,2,3,4 yo), the affected side (right or left), and the origin of the CP (prematurity, perinatal asphyxia, stroke, others). For children with bilateral CP, each child will be matched with a child with the closest profile based on age (4 categories: 1,2,3,4 yo), the Gross Motor Function Classification System level 55 (GMFCS, 3 categories: I-II, III-IV and V) and the origin of the CP. All the efforts will be made in both RCTs to find the closest profile within the same year, same GMFCS level and same origin of CP. Group allocation (HABIT-ILE group or Control group) will be then randomly determined within each pair. However, in order to improve the monitoring of the study, the children of the control group will benefit from the HABIT-ILE treatment after the 3-month follow-up evaluation.

Methodology

In each RCT, both groups (N=25) will be assessed 3 times: T0, T+15 days and T0+90 days.
The HABIT-ILE Group (unilateral CP n = 25/bilateral CP n = 25) will benefit from 50 hours of therapy over 2 weeks (5 hours per day of treatment, 5 days per week) while the control group (unilateral CP n = 30/bilateral CP n = 30) will follow its usual activities for 2 weeks (kindergarten, nursery, usual therapy, etc.).

For the RCT 1 (Unilateral CP), the primary outcome measure will be the difference in the Assisting Hand Assessment (AHA, from 18 months to 18 years) or Mini Assisting Hand Assessment63 (Mini-AHA, from 8 to 18 months) between T0 and T0+90 days.

For the RCT2 (Bilateral CP), the primary outcome measure will be the difference in Gross Motor Function Measure GMFM (in% of logits) between T0 and T0+90 days.

Assessments will be performed by a trained examiner totally blind to group assignment and timing of assessment ensuring a blind scoring.

In addition, a 6-month evaluation will be conducted to assess whether the 3-month results are maintained or improved over time.

HABIT-ILE is a motor skill learning-based therapy carried out in a camp-setting, with structured tasks of increasing motor difficulty and functional activities that require the use of both hands whilst sustaining postural or locomotor activity of the LE. Tasks are based on games and the whole environment is set up such that the children perceive the camp as fun. For both the children with unilateral and bilateral CP, the tasks will be chosen according to individualized functional goals previously defined by the parents (e.g drinking by him/herself, walking without help, opening a box of toys, holding a book, putting off pants, playing in sitting without support, etc.).
Results of the initial assessments (T0) will be used to determine appropriate tasks for each child. Over the course of the 2 weeks, tasks will be progressed to further challenge bimanual coordination, postural control and LE function.

The duration of activities as well as LE/postural associations will also be adapted to each child depending on his/her functional objectives, attentional ability and gross motor development. The whole process will be performed in a child-friendly, fun environment adapted to the age of the child. Eight children will undergo rehabilitation together. Some activities will be carried out in groups and others individually. Each child will have his/her own therapist (PT or OT) as well as a student therapist working with him/her.
Taking into account usual motor activity time and rest time (e.g. naps), 5 hours per day for a total of 50 hours over 2 weeks. This duration is the best compromise between current scientific evidence on dosage and the number of feasible hours in this age group.

This project began in the first quarter of 2019.

Unilateral CP: Six therapy camps took place successively in Brussels in March 2019 (18 children), in Brest in November/December 2019 (16 children) and in Pisa in October 2020 (16 children) including a total of 50 children.
Bilateral CP: a first therapy camp took place in Brussels in March 2020 and a second in September 2020 including a total of 16 children. The camps planned in Angers and Brest in 2020, due to the COVID 19 epidemic, took place in April/ May 2021 in Angers (18 children) and in June/ July 2021 in Brest (18 children). Finally the camps planned in Pisa took place in August 2021 (8 children). A total of 60 children were included in this study.
In parallel, the experimental study on rodents is still ongoing.

The first results of the study in children with unilateral CP were published in the international reference journal JAMA Pediatrics:

• The intensive HABIT-ILE therapy structured in the form of camps lasting 2 weeks and 5 hours per day significantly improves the bimanual performance evaluated by the AHA (Assisting Hand Assessment) measured 3 months after the start of the study compared to usual motor activities. Children used more frequently and more effectively boths hands to play. While the AHA score, the main endpoint of this study, is not changed in the control group, it increases significantly by about 10% in the HABIT-ILE therapy group and the difference between the 2 groups is significant at 3 months.
• The children also improved more in gross motor skills (sitting, standing, walking, climbing stairs.... ), evidence through an improvement of the Gross Motor Function Measure (GMFM 66).
• They achieved, alone, 80% of the objectives set with their parents had set at the beginning of the camp.
• Highest improvements were achieved by the youngest children (< 3 years)
  • 50 hours of therapy for toddlers were as effective as 90h in older children (> 6 years).

Unilateral CP: Six therapy camps took place successively in Brussels in March 2019 (18 children), in Brest in November/December 2019 (16 children) and in Pisa in October 2020 (16 children) including a total of 50 children.

Unilateral CP: Six therapy camps took place successively in Brussels in March 2019 (18 children), in Brest in November/December 2019 (16 children) and in Pisa in October 2020 (16 children) including a total of 50 children.

The results of the study in children with bilateral CP are expected to be published in 2025.

In parallel, the experimental study on rodents is still ongoing

This project is unique because it evaluates early HABIT-ILE in both children with unilateral and bilateral CP, in contrast with previous studies that focused on children with unilateral CP (e.g. baby-CIMT or early Action Observation therapy). The results will thus impact the whole international community of individuals with CP and their families. Moreover, the clinical and animal studies, based on the same rehabilitation and comprehensive levels of assessment (functional, neurological and biomechanical), will dramatically increase understanding of the mechanisms behind the effects of early HABIT-ILE. This is crucial for the development of guidelines for the early rehabilitation of children with CP.

With this first study "we have just proved that a 50h course of HABIT-ILE therapy brings more progress on fine motor skills than an usual rehabilitation in children with unilateral CP. And we have shown that it is probably the features of the therapy that allow this improvement compared to the usual motor activity of children,” says Pr Sylvain Brochard, coordinator of the project.

While so far, most clinical studies evaluating the effectiveness of this intensive rehabilitation have been conducted in children over the age of six and usually with unilateral cerebral palsy with excellent results, the results of this study show for the first time that it can be offered to the toddlers and that it is effective. We know that most brain growth and development occurs before the age of two and that brain plasticity is maximal at that age.

“The results of this study must change not only the current techniques of rehabilitation of children with cerebral palsy in early childhood but also the policies of rehabilitation organization.” says Dr Alain Chatelin, President of the Cerebral Palsy Foundation.