Early Detection and Neuro-restorative Rehabilitation for Children with Cerebral Palsy

In the next 30 minutes another child with Cerebral Palsy (CP) will be born, however on average their parents will not have a confirmed diagnosis until the child is 19 months old and most of their window of neuroplasticity will be closed. Two international Clinical Practice Guidelines have recommended very early detection in the first 5 months of life and that children commence early neurorehabilitation for children at high risk of Cerebral Palsy (CP). They provided a strong recommendation for use of General Movement’s Assessment at fidgety age (Se 98%, Sp 90%) and structural MRI at term to detect CP in infants (to classify infants as “high risk of a later diagnosis of CP”) followed by the Hammersmith Infant Neurological Exam (HINE, Se 90%). In our systematic review Structural MRI performed at term corrected age (in preterm infants) was a strong predictor of CP, with sensitivity ranging in individual studies from 86 to 100% and specificity ranging from 89 to 97% (Bosanquet et al. 2013). Newer advanced brain imaging techniques such as diffusion imaging offer new opportunities to quantify networks for brain integrity using connectomes (Panneck et al. 2014, Saha 2020).

So what intervention should we be referring to after early detection at 12 weeks post term. Interventions need to promote early development of the visual system (VISIBLE, Guzzetta), early upper limb development (Boyd REACH) with child active goal directed early neurorehabilition and an enriched environment provide potential for early neuroplasticity (GAME Morgan). Interventions to promote brain reorganisation in response to Baby CIMT are safe and feasible (Eliasson, Baby CIMT) and infant friendly Bimanal training leads to equal improvements in hand skills (Greaves Baby BIM, REACH Boyd 2017). Parent training of motor abilities currently adopts a coaching model to enhance Parent Engagement (Scott 2022). Parenting interventions provide an enriched environment and the additional of Acceptance and Commitment therapy (ACT) provides additional benefits above and beyond established parenting interventions (Whittingham, et al., 2014; 2022). Two international clinical practice guidelines have been published to highlight the state of the science for early detection and early intervention for children with CP (Novak et al. 2017, Morgan et al. 2020). Our current plan is to develop a toolbox of clinical, HD EEG, MRI, genomic and microbiome biomarkers to identify infants at high chance of CP and other adverse neurodevelopmental outcomes (Autism, FASD) in the few months of life in order to fast-track families to evidence based early interventions.

Our research on the efficacy for activity-based therapies has implications for the dose, context and density of optimal upper limb intervention for children with Unilateral Cerebral Palsy (UCP) (Sakzewski et al. 2013). The essential elements of effective activity and Participation focused interventions include: (1) intensive activity based task-practice with repetition; (2) progressive incremental increase in difficulty and; (3) goal directed approaches to enhance motivation and engagement in therapy (4) engagement of families using a home based coaching model that is (5) in context. Lessons have been learnt from our research of neurorestorative rehabilitation in school age children and their families (Jackman 2022) that have impacted our current clinical trials of early intervention for infants identified early with Cerebral Palsy.

References:

1. Bosanquet M, Copeland L, Ware R, Boyd RN. A systematic review of tests to predict cerebral palsy in young children. Developmental Medicine & Child Neurology. 2013;55(5):418-426.

2. Novak, I., Morgan, C., Adde, L., Blackman, J., Boyd, R. N., et al. (2017a). Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy Advances in Diagnosis and Treatment. JAMA Pediatrics, 171(9), 897-907.

3. Morgan, Fetters, L., …. Boyd, R. N., …Novak, I. (2021). Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International CPG Based on Systematic Reviews. JAMA Pediatrics, 175(8), 846–858.

4. Pannek K, Scheck SM, Colditz PB, Boyd RN, Rose SE. Magnetic resonance diffusion tractography of the preterm infant brain: a systematic review. Developmental Medicine & Child Neurology. (2014) 56 2 113 – 124.

5. George, J. M., Fiori, S., …Boyd RN (2018). Validation of an MRI Brain Injury & Growth Scoring System in Very Preterm Infants Scanned at 29-to 35-Week Postmenstrual Age. Am J of Neuroradiology,vol 38, pg 1435, 2017, 39(1), E8.

6. Saha, S., Pagnozzi, A., .. . . .Boyd RN, Pannek, K. (2020). Predicting motor outcome in preterm infants from very early brain diffusion MRI using a deep learning convolutional neural network (CNN) model. Neuroimage, 215, 116807.

7. Pagnozzi, A. M., Dowson, N., … Boyd, R. N., & Rose, S. (2017). Identifying relevant biomarkers of brain injury from structural MRI: Validation using automated approaches in children with unilateral cerebral palsy. PLOS One, 12(8).

8. Boyd, R. N., Ziviani, J., Sakzewski, L., Novak, I., et al. (2017). REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia. BMJ Open, 7(9).

9. Whittingham, K., Sanders, M., McKinlay, L., & Boyd, R. N. (2014). Interventions to reduce behavioral problems in children with cerebral palsy: an RCT. Pediatrics (2014) 133 5 e1249 - e1257.

10. Whittingham, Koa, Sheffield, …Boyd, Roslyn N. (2022). Parenting Acceptance and Commitment Therapy: An RCT of an online course with families of children with CP. Behaviour Research and Therapy, 155 104129, 104129.

11. Colditz PB, Boyd RN, , …Sanders MR. A Randomized Trial of Baby Triple P for Preterm Infants: Child Outcomes at 2 Years of Corrected Age. J Pediatr. 2019 Mar 8. pii: S0022-3476(19)30052-6. doi: 10.1016/j.jpeds.2019.01.024.

12. Sakzewski L, Boyd RN. Efficacy Upper Limb Therapies for Unilateral CP: Meta-analysis. Pediatrics 2014;133:e175-204.

13. Reedman SE, Boyd RN, Trost SG, Elliott C, Sakzewski L. Efficacy of Participation-Focused Therapy on Performance of Physical Activity Participation Goals and Habitual Physical Activity in Children with CP: an RCT.Arch Phys Med Rehabil. 2019 Apr;100(4):676-686.

14. Jackman, Michelle, Sakzewski, Leanne, Morgan, Catherine, Boyd, Roslyn N… Novak, Iona (2022). Interventions to improve physical function for children and young people with cerebral palsy: international clinical practice guideline. Developmental Medicine and Child Neurology, 64 (5), 536-549.