Automated, quantitative measures of grey and white matter lesion burden correlates with motor and cognitive function in children with unilateral cerebral palsy

AbstractWhite and grey matter lesions are the most prevalent type of injury observable in the Magnetic Resonance Images (MRIs) of children with cerebral palsy (CP). Previous studies investigating the impact of lesions in children with CP have been qualitative, limited by the lack of automated segmentation approaches in this setting. As a result, the quantitative relationship between lesion burden has yet to be established. In this study, we perform automatic lesion segmentation on a large cohort of data (107 children with unilateral CP and 18 healthy children) with a new, validated method for segmenting both white matter (WM) and grey matter (GM) lesions. The method has better accuracy (94%) than the best current methods (73%), and only requires standard structural MRI sequences. Anatomical lesion burdens most predictive of clinical scores of motor, cognitive, visual and communicative function were identified using the Least Absolute Shrinkage and Selection operator (LASSO). The improved segmentations enabled identification of significant correlations between regional lesion burden and clinical performance, which conform to known structure-function relationships. Model performance was validated in an independent test set, with significant correlations observed for both WM and GM regional lesion burden with motor function (p<0.008), and between WM and GM lesions alone with cognitive and visual function respectively (p<0.008). The significant correlation of GM lesions with functional outcome highlights the serious implications GM lesions, in addition to WM lesions, have for prognosis, and the utility of structural MRI alone for quantifying lesion burden and planning therapy interventions

Early detection of Australian Aboriginal and Torres Strait Islander infants at high risk of adverse neurodevelopmental outcomes at 12 months corrected age:LEAP-CP prospective cohort study protocol

INTRODUCTION: Neurodevelopmental disorders (NDD), including cerebral palsy (CP), autism spectrum disorder (ASD) and foetal alcohol spectrum disorder (FASD), are characterised by impaired development of the early central nervous system, impacting cognitive and/or physical function. Early detection of NDD enables infants to be fast-tracked to early intervention services, optimising outcomes. Aboriginal and Torres Strait Islander infants may experience early life factors increasing their risk of neurodevelopmental vulnerability, which persist into later childhood, further compounding the health inequities experienced by First Nations peoples in Australia. The LEAP-CP prospective cohort study will investigate the efficacy of early screening programmes, implemented in Queensland, Australia to earlier identify Aboriginal and Torres Strait Islander infants who are ‘at risk’ of adverse neurodevelopmental outcomes (NDO) or NDD. Diagnostic accuracy and feasibility of early detection tools for identifying infants ‘at risk’ of a later diagnosis of adverse NDO or NDD will be determined. METHODS AND ANALYSIS: Aboriginal and/or Torres Strait Islander infants born in Queensland, Australia (birth years 2020–2022) will be invited to participate. Infants aged <9 months corrected age (CA) will undergo screening using the (1) General Movements Assessment (GMA); (2) Hammersmith Infant Neurological Examination (HINE); (3) Rapid Neurodevelopmental Assessment (RNDA) and (4) Ages and Stages Questionnaire-Aboriginal adaptation (ASQ-TRAK). Developmental outcomes at 12 months CA will be determined for: (1) neurological (HINE); (2) motor (Peabody Developmental Motor Scales 2); (3) cognitive and communication (Bayley Scales of Infant Development III); (4) functional capabilities (Paediatric Evaluation of Disability Inventory-Computer Adaptive Test) and (5) behaviour (Infant Toddler Social and Emotional Assessment). Infants will be classified as typically developing or ‘at risk’ of an adverse NDO and/or specific NDD based on symptomology using developmental and diagnostic outcomes for (1) CP (2) ASD and (3) FASD. The effects of perinatal, social and environmental factors, caregiver mental health and clinical neuroimaging on NDOs will be investigated. ETHICS AND DISSEMINATION: Ethics approval has been granted by appropriate Queensland ethics committees; Far North Queensland Health Research Ethics Committee (HREC/2019/QCH/50533 (Sep ver 2)-1370), the Townsville HHS Human Research Ethics Committee (HREC/QTHS/56008), the University of Queensland Medical Research Ethics Committee (2020000185/HREC/2019/QCH/50533) and the Children’s Health Queensland HHS Human Research Ethics Committee (HREC/20/QCHQ/63906) with governance and support from local First Nations communities. Findings from this study will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12619000969167

Randomized controlled trial of a web-based mult-imodal therapy program for executive functioning in children and adolescents with unilateral cerebral palsy

Purpose state: Determine the efficacy of Move-it-to-improve-it (Mitii™), a multi-modal web-based program, in improving Executive Function (EF) in children with unilateral cerebral palsy (UCP). Method: Participants (n=102) were matched in pairs then randomised to: intervention (Mitii™ for 20 weeks; n=51; 26 males; mean age=11 years 8 months (SD=2y4m); Full Scale IQ=84.65 (SD=15.19); 28 left UCP; GMFCS-E&R (I=20, II=31) or waitlist control (n=50; 25 males; mean age=11y10m (SD=2y5m); Full Scale IQ=80.75 (SD=19.81); 20 left UCP; GMFCS-E&R (I=25, II=25). Mitii™ targeted working memory (WM), visual processing (VP), upper limb co-ordination and physical activity. EF capacity was assessed: attentional control (DSB; WISC-IV); cognitive flexibility (inhibition and number-letter sequencing DKEFS); goal setting (D-KEFs Tower Test); and information processing (WISC-IV Symbol Search and Coding). EF performance was assessed via parent report (BRIEF). Groups were compared at 20 weeks using linear regression (SPSS 21). Results: There were no significant between group differences in attentional control (DSB; p=0.20;CI=-0.40,1.87); cognitive flexibility (Inhibition, p=0.34;CI=-0.73,2.11; number/letter sequencing, p=0.17; CI=-0.55,2.94); problem solving (Tower; p=0.28; CI=-0.61,2.09), information processing (Symbol; p=0.08; CI=-0.16, 2.75; Coding; p=0.07; CI=-0.12,2.52) or EF performance (p=0.13; CI=-10.04,1.38). Conclusion: In a large RCT, Mitii TM did not lead to significant improvements on measures of EF or parent ratings of EF performance in children with UCP

Early brain morphometrics from neonatal MRI predict motor and cognitive outcomes at 2-years corrected age in very preterm infants

Infants born very preterm face a range of neurodevelopmental challenges in cognitive, language, behavioural and/or motor domains. Early accurate identification of those at risk of adverse neurodevelopmental outcomes, through clinical assessment and Magnetic Resonance Imaging (MRI), enables prognostication of outcomes and the initiation of targeted early interventions. This study utilises a prospective cohort of 181 infants born <31 weeks gestation, who had 3T MRIs acquired at 29-35 weeks postmenstrual age and a comprehensive neurodevelopmental evaluation at 2 years corrected age (CA). Cognitive, language and motor outcomes were assessed using the Bayley Scales of Infant and Toddler Development – Third Edition and functional motor outcomes using the Neuro-sensory Motor Developmental Assessment. By leveraging advanced structural MRI pre-processing steps to standardise the data, and the state-of-the-art developing Human Connectome Pipeline, early MRI biomarkers of neurodevelopmental outcomes were identified. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression, significant associations between brain structure on early MRIs with 2-year outcomes were obtained (r = 0.51 and 0.48 for motor and cognitive outcomes respectively) on an independent 25% of the data. Additionally, important brain biomarkers from early MRIs were identified, including cortical grey matter volumes, as well as cortical thickness and sulcal depth across the entire cortex. Adverse outcome on the Bayley-III motor and cognitive composite scores were accurately predicted, with an Area Under the Curve of 0.86 for both scores. These associations between 2-year outcomes and patient prognosis and early neonatal MRI measures demonstrate the utility of imaging prior to term equivalent age for providing earlier commencement of targeted interventions for infants born preterm

A randomized trial of Baby Triple P for Preterm Infants: child outcomes at 2\ua0years of corrected age

To determine the efficacy of a hospital-based intervention that transitions into existing community support, in enhancing developmental outcomes at 2\ua0years of corrected age in infants born at less than 32\ua0weeks.In total, 323 families of 384 infants bor

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy International Clinical Practice Guideline Based on Systematic Reviews:International Clinical Practice Guideline Based on Systematic Reviews

IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). CONCLUSIONS AND RELEVANCE: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline

Improving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems

INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia

Background: Congenital hemiplegia is the most common form of cerebral palsy (CP) accounting for 1 in 1300 live births. These children have limitations in capacity to use the impaired upper limb and bimanual coordination deficits which impact on daily activities and participation in home, school and community life. There are currently two diverse intensive therapy approaches. Traditional therapy has adopted a bimanual approach (BIM training) and recently, constraint induced movement therapy (CIMT) has emerged as a promising unimanual approach. Uncertainty remains about the efficacy of these interventions and characteristics of best responders. This study aims to compare the efficacy of CIMT to BIM training to improve outcomes across the ICF for school children with congenital hemiplegia

Functional progressive resistance training improves muscle strength but not walking ability in children with cerebral palsy

Summary of: Scholtes VA et al (2012) Effectiveness of functional progressive resistance exercise training on walking ability in children with cerebral palsy: a randomized controlled trial. Res Dev Disabil 33: 181-188. [Prepared by Nora Shields, CAP Editor.]. Question: Does functional progressive resistance exercise (PRE) improve walking ability and participation in school-aged children with cerebral palsy (CP)? Design: Randomised, controlled trial with concealed allocation and blinded outcome assessment. Setting: Three special schools for children with physical disability in the Netherlands. Participants: Ambulatory children (Gross Motor Function Classification System 1-3) with spastic unilateral or bilateral cerebral palsy aged 6-13 years. Botulinum toxin injections in the previous three months or orthopaedic surgery in the previous six months were exclusion criteria. Randomisation of 51 participants allocated 26 to the functional PRE group and 25 to a usual care group. Interventions: The intervention group participated in a 12-week functional PRE program, three times a week for 60 minutes in groups of 4 or 5. The program comprised four exercises: one using a leg press machine and three functional exercises (sit-to-stand, lateral step-up, half knee-rise) using body weight and a weighted vest to provide resistance. Participants completed 3 sets of 8 repetitions for each exercise. Intensity was increased progressively based on repeated estimation of 8 RM (repetition maximum). The control group received conventional physiotherapy 1-3 sessions a week. Outcome measures: The primary outcomes were walking ability (timed 10. m walk, 1-minute fast walk test, timed stair test) and participation (intensity scores of 17 items of Children's Assessment of Participation and Enjoyment questionnaire recalculated on a 0-100 scale) measured at baseline, after 6 and 12 weeks training, and 6 weeks after the intervention. Secondary outcome measures were anaerobic muscle power, muscle strength, spasticity and range of movement (ROM). Results: 49 participants completed the study. At the end of the intervention period, there was no difference between the groups for comfortable (-0.04, 95% CI -0.18 to 0.1. m/s) or fast walking speed (0.04, 95% CI -0.04 to 0.12. m/s), timed stair test (0.8, 95% CI -2.6 to 4.3. s) or participation (-1, 95% CI -11 to 9). Muscle strength improved significantly more in the intervention group than the control group immediately after the intervention by 1.3. N/kg (95% CI 0.6 to 2.5) for total isometric muscle strength and by 14% BW (95% CI 2 to 26) for 6 RM leg press. Knee flexion range had decreased in the intervention group by 15° (95% CI -29 to -1) compared to the control group 6 weeks after training stopped. The groups did not significantly differ on anaerobic muscle power, spasticity or other ROM outcomes. Conclusion: A 12-week functional PRE program improved muscle strength, but did not improve functional walking activity in school-aged ambulatory children with CP