Efficacy of baby-CIMT: study protocol for a randomised controlled trial on infants below age 12 months, with clinical signs of unilateral CP

BACKGROUND: Infants with unilateral brain lesions are at high risk of developing unilateral cerebral palsy (CP). Given the great plasticity of the young brain, possible interventions for infants at risk of unilateral CP deserve exploration. Constraint-induced movement therapy (CIMT) is known to be effective for older children with unilateral CP but is not systematically used for infants. The development of CIMT for infants (baby-CIMT) is described here, as is the methodology of an RCT comparing the effects on manual ability development of baby-CIMT versus baby-massage. The main hypothesis is that infants receiving baby-CIMT will develop manual ability in the involved hand faster than will infants receiving baby-massage in the first year of life. METHOD AND DESIGN: The study will be a randomised, controlled, prospective parallel-group trial. Invited infants will be to be randomised to either the baby-CIMT or the baby-massage group if they: 1) are at risk of developing unilateral CP due to a known neonatal event affecting the brain or 2) have been referred to Astrid Lindgren Children’s Hospital due to asymmetric hand function. The inclusion criteria are age 3–8 months and established asymmetric hand use. Infants in both groups will receive two 6-weeks training periods separated by a 6-week pause, for 12 weeks in total of treatment. The primary outcome measure will be the new Hand Assessment for Infants (HAI) for evaluating manual ability. In addition, the Parenting Sense of Competence scale and Alberta Infant Motor Scale will be used. Clinical neuroimaging will be utilized to characterise the brain lesion type. To compare outcomes between treatment groups generalised linear models will be used. DISCUSSION: The model of early intensive intervention for hand function, baby-CIMT evaluated by the Hand Assessment for Infants (HAI) will have the potential to significantly increase our understanding of how early intervention of upper limb function in infants at risk of developing unilateral CP can be performed and measured. TRIAL REGISTRATION: SFO-V4072/2012, 05/22/201

To Explore the Validity of Change Scores of the Children's Hand-use Experience Questionnaire (CHEQ) in Children with Unilateral Cerebral Palsy

© 2018 The Author(s). Aims: To explore the validity of change scores of the Children's Hand-use Experience Questionnaire (CHEQ). Methods: Analysis of the CHEQ included 44 children (15 girls) between 6–16 years (median 9.0; IQR 8–11) with unilateral cerebral palsy, with baseline and post- (two-week intensive) intervention assessments using the Goal Attainment Scale (GAS) as external anchor for change. Hypotheses on the magnitude of expected change were formulated and correlation coefficients and effect sizes calculated. Receiver operating curve analysis was performed and the area under the curve (AUC) calculated to investigate the ability of CHEQ to discriminate between improvement and non-improvement according to GAS. Results: All hypotheses about the magnitude of change were confirmed supporting longitudinal validity of CHEQ scales to measure change in the perception of bimanual performance. AUCs for the Grasp efficacy and the Time utilization were slightly below, and for the Feeling bothered slightly above the threshold. The latter one accurately discriminating between children that improved and did not improve according to the GAS. Conclusions: Evidence was found that CHEQ scales capture change in bimanual performance but with limited accuracy for two out of three scales. The validity of CHEQ change scores needs to be further explored in a wider population

Predictive validity of the Hand Assessment for Infants in infants at risk of unilateral cerebral palsy

Aim: To evaluate the sensitivity, specificity, and predictive value of the Hand Assessment for Infants (HAI) in identifying infants at risk of being diagnosed with unilateral cerebral palsy(CP), and to determine cut-off values for this purpose. Method: A convenience sample of 203 infants (106 females, 97 males) was assessed by the HAI at 3, 6, 9, and 12 months. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using receiver operating characteristic curve analysis. Cut-off values were derived for different ages. The clinical outcome (unilateral CP yes/no) at 24 months or more served as an external criterion to investigate the predictive validity of HAI. Results: Half of the infants developed unilateral CP. The area under the curve ranged from0.77 (95% CI [confidence interval] 0.63–0.91) to 0.95 (95% CI 0.90–1.00) across HAI scales and age intervals. Likewise, sensitivity ranged from 63% to 93%, specificity from 62% to 91%, and accuracy from 73% to 94%. Interpretation: HAI scores demonstrated overall accuracy that ranged from very good to excellent in predicting unilateral CP in infants at risk aged between 3.5 and 12 months. This accuracy increased with age at assessment and the earliest possible prediction was at3.5 months of age, when appropriate HAI cut-off values for different ages were applied

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

The state of the evidence for intensive upper limb therapy approaches for children with unilateral cerebral palsy

Children with unilateral cerebral palsy experience difficulties with unimanual and bimanual upper limb function, impacting independence in daily life. Targeted upper limb therapies such as constraint-induced movement therapy, bimanual training, and combined approaches have emerged in the last decade. This article reviews the scientific rationale underpinning these treatments and current evidence to improve upper limb outcomes and goal attainment. Intensive models of therapy achieved modest to strong effects to improve upper limb function compared to usual care. Dose-matched comparisons of bimanual and unimanual training demonstrated similar gains in upper limb outcomes. The optimum timing, dose and impact of repeat episodes of intensive upper limb therapies require further investigation. Characteristics of children who achieve clinically meaningful outcomes remain unclear. Key components of intervention include collaborative goal setting with families and intensive repetitive, incrementally challenging, task practice. Choice of treatment approach should be governed by child/family goals and preferences, individual, and contextual factors

Genetic Variation in the Dopamine System Influences Intervention Outcome in Children with Cerebral Palsy

Background: There is large variation in treatment responses in children with cerebral palsy. Experimental and clinical results suggest that dopamine neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are involved in motor learning and plasticity, which are key factors in modern habilitation success. We examined whether naturally occurring variations in dopamine and BDNF genes influenced the treatment outcomes. Methods: Thirty-three children (18–60 months of age) with spastic unilateral cerebral palsy were enrolled in the study. Each child had participated in a training programme consisting of active training of the involved hand for 2 h every day during a 2-month training period. The training outcome was measured using Assisting Hand Assessment before and after the training period. Saliva was collected for genotyping of COMT, DAT, DRD1, DRD2, DRD3, and BDNF. Regression analyses were used to examine associations between genetic variation and training outcome. Findings: There was a statistically significant association between variation in dopamine genes and treatment outcome. Children with a high polygenic dopamine gene score including polymorphisms of five dopamine genes (COMT, DAT, DRD1, DRD2, and DRD3), and reflecting higher endogenous dopaminergic neurotransmission, had the greatest functional outcome gains after intervention. Interpretation: Naturally occurring genetic variation in the dopamine system can influence treatment outcomes in children with cerebral palsy. A polygenic dopamine score might be valid for treatment outcome prediction and for designing individually tailored interventions for children with cerebral palsy

General movements and magnetic resonance imaging in the prediction of neuromotor outcome in children born extremely preterm

BACKGROUND: Extremely preterm (EPT) birth is a major risk factor for brain injury and neurodevelopmental impairment. Reliable tools for early prediction of outcome are warranted. AIM: To investigate the predictive value of general movements (GMs) at "fidgety age" for neurological outcome at age 30months in EPT infants, both in comparison and in combination with structural magnetic resonance imaging (MRI) at term equivalent age (TEA). STUDY DESIGN: Fifty-three infants born <27weeks of gestation were included prospectively. MRI was performed at TEA and images were evaluated for white and grey matter abnormalities. GMs were assessed at age 3months corrected ("fidgety age"). OUTCOME MEASURES: Neuromotor outcome was assessed at age 30months corrected. Children were classified as having a normal neurological status, unspecific signs, or cerebral palsy (CP). RESULTS: Abnormal GMs were a common finding, seen in 32% (17/53) of infants. Of these, six infants (11%) had definitely abnormal GMs. Four infants (8%) had a diagnosis of CP at follow up. Definitely abnormal GMs were significantly associated to CP at 30months (Fisher's Exact test p=0.03, sensitivity 50%, specificity 92%). Moderate-severe white matter abnormalities on MRI were more strongly associated with CP (Fisher's Exact test p<0.001, sensitivity 100%, specificity 98%) than GMs. Combining GMs with MRI-findings at TEA increased the predictive specificity to 100% (Fisher's Exact test, p=0.005), whereas sensitivity remained unchanged. CONCLUSIONS: The presence of definitely abnormal GMs was predictive of CP: prediction was significantly enhanced when the GMs assessment was combined with findings from MRI obtained at TEA