Pharmacological and neurosurgical management of cerebral palsy and dystonia: Clinical practice guideline update.

Dystonia, typically characterized by slow repetitive involuntary movements, stiff abnormal postures, and hypertonia, is common among individuals with cerebral palsy (CP). Dystonia can interfere with activities and have considerable impact on motor function, pain/comfort, and ease of caregiving. Although pharmacological and neurosurgical approaches are used clinically in individuals with CP and dystonia that is causing interference, evidence to support these options is limited. This clinical practice guideline update comprises 10 evidence-based recommendations on the use of pharmacological and neurosurgical interventions for individuals with CP and dystonia causing interference, developed by an international expert panel following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The recommendations are intended to help inform clinicians in their use of these management options for individuals with CP and dystonia, and to guide a shared decision-making process in selecting a management approach that is aligned with the individual's and the family's values and preferences.

Evaluating the impact of movement tracking feedback on engagement with home exercise programmes of children with cerebral palsy using a new therapy app: a protocol for a mixed-methods single-case experimental design with alternating treatments.

INTRODUCTION: Children with cerebral palsy (CP) are prescribed home exercise programmes (HEPs) to increase the frequency of movement practice, yet adherence to HEPs can be low. This paper outlines the protocol for a single-case experimental design (SCED) with alternating treatments, using a new home therapy exercise application, Bootle Boot Camp (BBCamp), offered with and without movement tracking feedback. This study will explore the impact of feedback on engagement, movement quality, lower limb function and family experiences to help understand how technology-supported HEPs should be translated and the added value, if any, of movement tracking technology. METHODS AND ANALYSIS: In this explanatory sequential mixed-methods study using a SCED, 16 children with CP (aged 6-12 years, Gross Motor Function Classification System levels I-II) will set lower limb goals and be prescribed an individualised HEP by their physiotherapist to complete using BBCamp on their home television equipped with a three-dimensional camera-computer system. Children will complete four weekly exercise sessions over 6 weeks. Children will be randomised to 1 of 16 alternating treatment schedules where BBCamp will provide or withhold feedback during the first 4 weeks. The version of BBCamp that results in the most therapeutic benefit will be continued for 2 final weeks. Goals will be re-evaluated and families interviewed. The primary outcome is adherence (proportion of prescribed exercise repetitions attempted) as a measure of behavioural engagement. Secondary outcomes are affective and cognitive engagement (smiley face ratings), exercise fidelity, lower limb function, goal achievement and participant experiences. SCED data will be analysed using visual and statistical methods. Quantitative and qualitative data will be integrated using joint displays. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Research Ethics Boards at Bloorview Research Institute and the University of Toronto. Results will be distributed through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05998239; pre-results.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

Physician Approaches to the Pharmacologic Treatment of Dystonia in Cerebral Palsy.

Objective: To determine how physicians approach pharmacologic dystonia treatment in people with CP and assess physician readiness to participate in a randomized trial comparing existing pharmacologic dystonia treatments. Methods: We administered a REDCap survey to physician members of the American Academy of Cerebral Palsy and Developmental Medicine and of the Child Neurology Society to assess which pharmacologic agents they use to treat dystonia in CP and their preferred indications and dosing. Results: Of 479 physicians surveyed, 240 (50%) responded. Respondents treated functionally limiting (95%) and generalized (57%) dystonia and most commonly used six medications: baclofen (95%), trihexyphenidyl (79%), gabapentin (67%), carbidopa/levodopa (55%), clonazepam (55%), and diazepam (54%). Baclofen was preferred in people with co-existing spasticity (81%), gabapentin was preferred in people with co-existing pain (49%), and trihexyphenidyl was avoided in people with constipation (34%) or urinary retention (42%). Preferred dosing regimens followed published regimens for dystonia, when available, but otherwise followed published regimens for other CP symptoms (spasticity and seizures). Baclofen was preferred by 64% of respondents as first line treatment, but there was no clear consensus on second or third-line medications. Most respondents (51%) were comfortable randomizing their patients to receive any of the six most commonly used medications used to treat dystonia in CP. Conclusions: This study summarizes current indications and dosing for the six most commonly used medications to treat dystonia in CP as per treating physicians in the US and Canada and also demonstrates physician support for a randomized trial comparing the effectiveness of these treatments.

NICU Language, Everyday Ethics, and Giving Better News: Optimizing Discussions about Disability with Families.

The Neonatal Intensive Care Unit (NICU) has a language and culture that is its own. For professionals, it is a place of intense and constant attention to microdetails and cautious optimism. For parents, it is a foreign place with a new and unique language and culture. It is also the setting in which they are introduced to their child and parenthood for this child. This combination has been referred to as an emotional cauldron. The neonatal ethics literature mainly examines complex ethical dilemmas about withholding/drawing life sustaining interventions for fragile children. Rarely are everyday ethics or mundane ethics discussed. Microethics describe the mundane, discrete moments that occur between patients/families and clinicians. A key piece of these microethics is the language used to discuss patient care. Perception of prognoses, particularly around long-term neurodevelopmental outcome, is shaped with the language used. Despite this, clinicians in the NICU often have no specific training in the long-term neurodevelopment outcomes that they discuss. This paper focuses on the microethics of language used to discuss long-term neurodevelopmental outcomes, the developmental neuroscience behind language processing, and offers recommendations for more accurate and improved communication around long-term outcomes with families with critically ill neonates.

A good night's sleep: pain trajectories and sleep disturbance in children with cerebral palsy.

STUDY OBJECTIVES: Sleep quality is important during childhood and adolescence. Given the high prevalence of pain in children/youth with cerebral palsy, we aimed to measure the association between short-term pain trajectories and sleep disturbance in these individuals. METHODS: We accrued the cohort between November 2019 and October 2020 and recruited children/youth who (1) were 8-18 years old; (2) had cerebral palsy with any Gross Motor Function Classification System level; and (3) could self-report pain and sleep disturbance. We collected self-reported baseline and weekly follow-up data using electronic questionnaires completed every week for 5 weeks. Sleep disturbance at 5 weeks was the primary outcome (pediatric Patient-Reported Outcomes Measurement Information System short form, v1.0-4a). We used general linear regression to assess the association between pain intensity trajectory group and sleep disturbance controlling for confounders. RESULTS: A total of 190 individuals were eligible; 102 were enrolled and 89 were included in our final analysis. Pain trajectory groups had estimated crude mean sleep disturbance scores at 5 weeks ranging from 56.0 (95% confidence interval, 51.8, 60.8) to 61.8 (55.7, 67.9). Compared to those with stable, no/very mild pain, those in the stable, high-pain group had the greatest sleep disturbance (adjusted ß = 5.7; 95% confidence interval, 1.2, 10.2). CONCLUSIONS: Irrespective of pain trajectory, children and youth with cerebral palsy reported sleep disturbances. Those with a stable, high pain intensity in the previous 5 weeks reported the greatest sleep disturbance. The results highlight the importance of considering pain trajectories and their impact on sleep in children with cerebral palsy. CITATION: Shearer HM, Côté P, Hogg-Johnson S, Fehlings DL. A good night's sleep: pain trajectories and sleep disturbance in children with cerebral palsy. J Clin Sleep Med. 2024;20(5):719-726.

Executive functioning, ADHD symptoms and resting state functional connectivity in children with perinatal stroke.

Perinatal stroke describes a group of focal, vascular brain injuries that occur early in development, often resulting in lifelong disability. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI). Though perinatal stroke is typically considered a motor disorder, other comorbidities commonly exist including attention-deficit hyperactivity disorder (ADHD) and deficits in executive function. Rates of ADHD symptoms are higher in children with perinatal stroke and deficits in executive function may also occur but underlying mechanisms are not known. We measured resting state functional connectivity in children with perinatal stroke using previously established dorsal attention, frontoparietal, and default mode network seeds. Associations with parental ratings of executive function and ADHD symptoms were examined. A total of 120 participants aged 6-19 years [AIS N = 31; PVI N = 30; Controls N = 59] were recruited. In comparison to typically developing peers, both the AIS and PVI groups showed lower intra- and inter-hemispheric functional connectivity values in the networks investigated. Group differences in between-network connectivity were also demonstrated, showing weaker anticorrelations between task-positive (frontoparietal and dorsal attention) and task-negative (default mode) networks in stroke groups compared to controls. Both within-network and between-network functional connectivity values were highly associated with parental reports of executive function and ADHD symptoms. These results suggest that differences in functional connectivity exist both within and between networks after perinatal stroke, the degree of which is associated with ADHD symptoms and executive function.

Clinical actionability of genetic findings in cerebral palsy.

Background and objectives: Single gene mutations are increasingly recognized as causes of cerebral palsy (CP) phenotypes, yet there is currently no standardized framework for measuring their clinical impact. We evaluated Pathogenic/Likely Pathogenic (P/LP) variants identified in individuals with CP to determine how frequently genetic testing results would prompt changes in care. Methods: We analyzed published P/LP variants in OMIM genes identified in clinical (n = 1,345 individuals) or research (n = 496) cohorts using exome sequencing of CP patients. We established a working group of clinical and research geneticists, developmental pediatricians, genetic counselors, and neurologists and performed a systematic review of existing literature for evidence of clinical management approaches linked to genetic disorders. Scoring rubrics were adapted, and a modified Delphi approach was used to build consensus and establish the anticipated impact on patient care. Overall clinical utility was calculated from metrics assessing outcome severity if left untreated, safety/practicality of the intervention, and anticipated intervention efficacy . Results: We found 140/1,841 (8%) of individuals in published CP cohorts had a genetic diagnosis classified as actionable , defined as prompting a change in clinical management based on knowledge related to the genetic etiology. 58/243 genes with P/LP variants were classified as actionable; 16 had treatment options targeting the primary disease mechanism , 16 had specific prevention strategies , and 26 had specific symptom management recommendations. The level of evidence was also graded according to ClinGen criteria; 44.6% of interventions had evidence class "D" or below. The potential interventions have clinical utility with 97% of outcomes being moderate-high severity if left untreated and 62% of interventions predicted to be of moderate-high efficacy . Most interventions (71%) were considered moderate-high safety/practicality . Discussion: Our findings indicate that actionable genetic findings occur in 8% of individuals referred for genetic testing with CP. Evaluation of potential efficacy , outcome severity , and intervention safety / practicality indicates moderate-high clinical utility of these genetic findings. Thus, genetic sequencing to identify these individuals for precision medicine interventions could improve outcomes and provide clinical benefit to individuals with CP. The relatively limited evidence base for most interventions underscores the need for additional research.

Understanding a videogame home intervention for children with hemiplegia: a mixed methods multi-case study.

Introduction: Access to rehabilitation therapies is a salient and growing issue for children with cerebral palsy (CP) and their families, motivating interest in home-based interventions. Bootle Blast is a low-cost, movement-tracking videogame that can be used at home to encourage upper limb (UL) functional exercise tailored to each child's abilities and therapy goals. The study objectives were to: 1) Establish the extent to which children achieve their self-directed play-time goal over a 12-week intervention, 2) Measure changes in UL motor outcomes, and 3) Explore participants' experiences of using Bootle Blast at home. Methods: Mixed methods case series study of four children with hemiplegic cerebral palsy (HCP), each with a participating parent. Participants played Bootle Blast at home for 12 weeks. Study assessments occurred at baseline, post-intervention and four week follow up. A post-intervention interview explored participants' experiences. Game-logs provided play time and progress data. Results: Three of four participants (8-13 yrs., Manual Ability Classification Level I-II) completed the intervention. One dropped out at week 6. Play-time goals were achieved in most weeks, with two of four children surpassing their overall intervention goals. Outcomes varied across the three participants, however consistent improvements were observed on the Canadian Occupational Performance Measure and the Box and Blocks Test. Inductive analysis generated four main themes: 1) Intrinsic motivators fostered play engagement, 2) Virtual play for real-world gains, 3) Therapy on demand (at home), and 4) Shifting the onus from the parent to the game. Integration of qualitative and quantitative data was important for interpreting play patterns/usage and clinical outcomes. Discussion: This mixed methods study describes a novel videogaming intervention designed for home-rehabilitation for children with HCP and provides preliminary evidence to guide future study design and research. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04009031?recrs=h&cond=Cerebral+Palsy&cntry=CA&city=Toronto&draw=2&rank=1], identifier [NCT04009031].

Uncertainties regarding cerebral palsy diagnosis: opportunities to operationalize the consensus definition.

Background and Objectives: Cerebral palsy (CP), the most common motor disability of childhood, is variably diagnosed. We hypothesized that child neurologists and neurodevelopmentalists, often on the frontlines of CP diagnosis in North America, harbor uncertainties regarding the practical application of the most recent CP consensus definition from 2006. Methods: We conducted a cross-sectional survey of child neurologists and neurodevelopmentalists at the 2022 Child Neurology Society Annual Meeting. Attendees were provided the 2006 CP consensus definition and asked whether they had any uncertainties about the practical application of the definition across four hypothetical clinical vignettes. Results: Of 230 attendees, 164 responded to the closing survey questions (71%). 145/164 (88%) expressed at least one uncertainty regarding the clinical application of the 2006 definition. Overwhelmingly, these areas of uncertainty focused on: 1) Age, both with regards to the minimum age of diagnosis and the maximum age of brain disturbance or motor symptom onset, (67/164, 41%), and 2) Interpretation of the term "non-progressive" (48/164, 29%). The vast majority of respondents (157/164, 96%) answered 'Yes' to the question: Do you think we should revise the 2006 consensus definition of CP? Discussion: We propose that the uncertainties we identified could be addressed by operationalizing the 2006 consensus definition to support a more uniform CP diagnosis. To address the most common CP diagnostic uncertainties we identified, we propose 3 points of clarification based on the available literature: 1) Motor symptoms/signs should be present by 2 years old; 2) CP can and should be diagnosed as early as possible, even if activity limitation is not yet present, if motor symptoms/signs can be reasonably predicted to yield activity limitation (e.g. by using standardized examination instruments, Brain MRI, and a suggestive clinical history); and 3) The clinical motor disability phenotype should be non-progressive through 5 years old. We anticipate that operationalizing the 2006 definition of CP in this manner could clarify the uncertainties we identified among child neurologists and neurodevelopmentalists and reduce the diagnostic variability that currently exists.

Motor Evoked Potential Amplitude in Motor Behavior-based Transcranial Direct Current Stimulation Studies: A Systematic Review.

Motor evoked potential amplitude (MEPamp) is frequently measured in transcranial direct current stimulation (tDCS) studies that target the primary motor cortex (M1), and a subset of these studies involve motor behavior. This systematic review explored the role of MEPamp as an indicator of neural change in M1-targeted tDCS studies involving motor behavior (i.e., motor practice and/or evaluation of motor performance) in healthy individuals, and examined the association between changes in motor performance and MEPamp. We executed our search strategy across four bibliographic databases. Twenty-two manuscripts met eligibility criteria. While anodal tDCS combined with motor practice frequently increased MEPamp, MEPamp outcomes did not necessarily align with changes in motor performance. Thus, MEPamp may not be the most appropriate indicator of neural change in tDCS studies that aim to improve motor performance.

Cognitive behavioral therapies for individuals with cerebral palsy: A scoping review.

AIM: To synthesize the evidence about the main intervention characteristics of cognitive behavioral therapies (CBTs) for individuals with cerebral palsy and identify barriers and facilitators to their success, focusing on aspects of feasibility and markers of success. METHOD: A scoping review methodology informed a literature search for papers published between 1991 and 2021. Articles were screened, reviewed, and categorized using the DistillerSR systematic review software, and critically appraised for quantitative and/or qualitative criteria. RESULTS: Out of 1265 publications identified, 14 met the inclusion criteria. Elements associated with the specific study participant characteristics (46% female; aged 6-65 years), type of CBT techniques used (third-wave [n = 6], cognitive [n = 3], cognitive and behavioral [n = 2], biofeedback training [n = 2]), and features of the study context and methodological quality (two randomized clinical trials and small sample sizes [n ≤ 12]), were identified. Most studies had psychological targets of intervention (n = 10) and secondary physiological (n = 3) or social (n = 2) objectives. Feasibility indicators were described in nearly one-third of the papers. INTERPRETATION: This study highlights the high flexibility within CBT interventions, enabling their adaptation for individuals with cerebral palsy. However, relatively little, and only low-certainty evidence was identified. More high-quality research in terms of specific CBT techniques, optimal treatment doses, and detailed population characteristics are needed.

Early Biomarkers in the Prediction of Later Functional Impairment in Term Children with Cerebral Palsy.

AIM: To identify possible early biomarkers that could predict later functional capabilities in children at risk for cerebral palsy (CP). METHODS: Data from 869 term children with CP were extracted from the Canadian Cerebral Palsy Registry. Univariate analyses were conducted to measure the association between readily available objective early biomarkers (neonatal encephalopathy [NE], cord or first hour of life pH, magnetic resonance imaging [MRI]) and functional outcomes such as mobility and feeding status. Multivariable regressions were then modeled to study whether adding predictors would affect the strength of the observed association. RESULTS: Patients with NE have higher odds of having an assigned Gross Motor Function Classification Score level of IV to V (prevalence ratio [PR], 2.87; 95% confidence interval [CI], 2.07 to 3.97) and are more likely to require dependent tube feeding (PR, 2.09; 95% CI, 1.12 to 3.88); this was similarly seen in patients with MRI findings of deep gray matter injury, watershed injury, near-total brain injury, and/or cortical malformation (mobility status [PR, 5.13; 95% CI, 3.73 to 7.11] and feeding status [PR, 4.87; 95% CI, 2.57 to 9.75]). Patients with cord or first hour of life pH <7 were also more likely to predict dependent mobility status (PR, 2.86; 95% CI, 1.76 to 4.69), however, not significantly more likely to predict eventual dependent feeding status (PR, 1.47; 95% CI, 0.58 to 3.32). CONCLUSIONS: This retrospective cohort study demonstrates that NE, MRI findings and cord or first hour of life pH can reliably predict later CP related functioning. These associations can be used to inform and clarify early prognosis discussions between caregivers and health professionals.

Integrating Transcranial Direct Current Stimulation into an Existing Inpatient Physiotherapy Program to Enhance Motor Learning in an Adolescent with Traumatic Brain Injury: A Case Report.

PURPOSE: Describe how transcranial direct current stimulation (tDCS) was incorporated into an inpatient physiotherapy program for an adolescent with severe traumatic brain injury (TBI), detail the motor learning focus of the physiotherapy sessions, and summarize gross motor progress. METHOD: This case report describes an adolescent who received 20 minutes of anodal tDCS immediately prior to 16 physiotherapy sessions over four weeks. Potential side effects were tracked pre/post tDCS. Gross motor outcomes were measured pre-intervention, post-intervention, and three months post-intervention. Physiotherapy session content was analyzed using therapist documentation and the Motor Learning Strategies Rating Instrument. RESULTS: The youth tolerated tDCS well. The primary side effect was itchiness under the electrodes during tDCS sessions. His mobility progressed from wheelchair use pre- 'tDCS + physiotherapy' to ambulation with a walker post-intervention. His Gross Motor Function Measure score increased 33.1% points pre/post intervention. Session tasks often had several foci (e.g., skill acquisition, strength, and balance) with task focus changing as the youth progressed. Various motor learning strategies were layered within tasks to support performance and learning. CONCLUSIONS: tDCS was successfully integrated into an existing inpatient physiotherapy program for an adolescent with TBI. This protocol provides a structure for implementing, monitoring, and measuring tDCS + physiotherapy in pediatric rehabilitation.

Functional Neuroplasticity and Motor Skill Change Following Gross Motor Interventions for Children With Diplegic Cerebral Palsy.

BACKGROUND: Gross motor intervention designs for children with diplegic cerebral palsy (DCP) require an improved understanding of the children's potential for neuroplasticity. OBJECTIVE: To identify relations between functional neuroplasticity and motor skill changes following gross motor interventions for children with DCP. METHODS: There were 17 participants with DCP (ages 8-16 years; 6 females; Gross Motor Function Classification System Level I [n = 9] and II [n = 8]). Each completed a 6-week gross motor intervention program that was directed toward achievement of individualized motor/physical activity goals. Outcomes were assessed pre/post and 4 to 6 months post-intervention (follow-up). An active ankle dorsiflexion task was completed during functional magnetic resonance imaging. The ratio of motor cortical activation volume in each hemisphere was calculated using a laterality index. The Challenge was the primary gross motor skill measure. Change over time and relations among outcomes were evaluated. RESULTS: Challenge scores improved post-intervention (4.57% points [SD 4.45], P = .004) and were maintained at follow-up (0.75% [SD 6.57], P = 1.000). The laterality index for dominant ankle dorsiflexion increased (P = .033), while non-dominant change was variable (P = .534). Contralateral activation (laterality index ≥+0.75) was most common for both ankles. Challenge improvements correlated with increased ipsilateral activity (negative laterality index) during non-dominant dorsiflexion (r = -.56, P = .045). Smaller activation volume during non-dominant dorsiflexion predicted continued gross motor gains at follow-up (R2 = .30, P = .040). CONCLUSIONS: Motor cortical activation during non-dominant ankle dorsiflexion is a modest indicator of the potential for gross motor skill change. Further investigation of patterns of neuroplastic change will improve our understanding of effects. CLINICALTRIALS.GOV REGISTRY: NCT02584491 and NCT02754128.

Gross motor change after inpatient rehabilitation for children with acquired brain injury: A 10-year retrospective review.

AIM: To estimate gross motor change in inpatient school-aged children with subacute acquired brain injury (ABI), identify factors associated with gross motor change, and describe inpatient physiotherapy focus. METHOD: This retrospective chart review involved inpatient children (5-18 years) with subacute ABI who had either two Gross Motor Function Measure (GMFM-88) assessments or one GMFM-88 with another pre/post gross motor outcome measure. Outcome change scores and Goal Attainment Scaling (GAS) T scores were calculated. Regression analyses examined factors predicting gross motor change. GAS goal areas were analysed to determine physiotherapy focus. RESULTS: Of the 546 charts screened, 266 (118 female) met study criteria. The GMFM-88 was generally administered first, followed by other measures. GMFM-88 (n = 202), Community Balance and Mobility Scale (n = 89), and Six-Minute Walk Test (6MWT) (n = 98) mean change scores were 18.03% (SD 19.34), 17.85% (SD 10.77), and 142.3 m (SD 101.8) respectively. The mean GAS T score was 55.06 (SD 11.50). Lower baseline scores and increased time between assessments were most predictive of greater GMFM-88 change (r ≥ 0.40). Twenty-five percent of GAS goals were ambulation-based. INTERPRETATION: Appropriate outcome measure selection is integral to detecting gross motor change in pediatric inpatient ABI rehabilitation. Mean change score estimates can be used to compare standard inpatient rehabilitation with new treatment approaches.

Clinical course of pain intensity in individuals with cerebral palsy: A prognostic systematic review.

AIM: To describe the clinical course of pain intensity in individuals with cerebral palsy (CP) resulting from usual care or specific interventions. METHOD: We conducted an exploratory prognostic systematic review searching electronic databases from inception to 31st December 2021. Evidence from low and moderate risk-of-bias studies was synthesized. RESULTS: We retrieved 2275 citations; 18 studies met the inclusion criteria and 10 were synthesized. The course of pain intensity in children with CP receiving usual care was stable over 15 weeks (χ2 [2]  = 1.8, p = 0.5). Children who received continuous intrathecal baclofen (CITB) reported significant pain intensity reduction (visual analogue scale [VAS] = -4.2 out of 10, 95% confidence interval [CI] = -6.3 to -2.1]) 6 months postinsertion but similar children receiving usual care had no significant change over 6 months (VAS = 1.3 out of 10, 95% CI = -1.3 to 3.6). Children receiving botulinum neurotoxin A (BoNT-A) injections had significant decreases in pain after 1 month (numeric rating scale = -6.5, 95% CI = -8.0 to -5.0). Adults with chronic pain receiving usual care reported stable pain intensity over time; pain intensity improved in ambulatory adults exercising and those treated surgically for cervical myelopathy. INTERPRETATION: The course of pain intensity in individuals with CP is unclear. Evidence suggests that children and adults receiving usual care had stable pain intensity over the short or long term. Interventions (CITB and BoNT-A in children and exercise and surgical treatment for cervical myelopathy in adults) had pain intensity reduction. Larger study samples are needed to confirm these results. WHAT THIS PAPER ADDS: Pain intensity was stable in children with cerebral palsy (CP) receiving usual care. Adults with CP and chronic pain receiving usual care had stable, persistent pain intensity. Children receiving continuous intrathecal baclofen via pump and botulinum neurotoxin A reported significantly lower pain intensities. Adults with chronic pain and dyskinetic CP and cervical myelopathy reported significantly lower pain intensity with exercise or cervical decompression. Limited high-quality evidence exists describing non-procedural pain changes in individuals with CP.

Stress, anxiety, depression, and health-related quality of life in caregivers of children with intestinal failure receiving parenteral nutrition: A cross-sectional survey study.

BACKGROUND: Improved survival rates for children with intestinal failure (IF) have resulted in an increased population of children receiving long-term parenteral nutrition (PN). Our objective was to determine burden on caregivers of children with IF receiving long-term PN. METHODS: We performed a cross-sectional study of caregivers of children with IF receiving long-term PN in our intestinal rehabilitation program. A healthy comparison group matched on age of the child was enrolled. All participants completed standardized questionnaires, including the Parental Stress Index - Short Form (PSI-SF), Hospital Anxiety and Depression Scale (HADS), and PedsQL Family Impact Module (PedsQL FIM). Univariate analysis was completed using a Student t test and chi-square, with an alpha value of <0.05 considered significant. RESULTS: Thirty-eight caregivers of children with IF and 29 caregivers of healthy children consented, with response rates of 89% and 96.5%, respectively. Our study demonstrated increased stress for caregivers compared with comparison parents (PSI-SF total score of 83 [SD = 26.8] vs 62.9 [SD = 13.5]; P < 0.01). Caregivers had increased anxiety (HADS anxiety score of 9.3 [SD = 4.8] vs 6.7 [SD = 3.2]; P = 0.02) and higher depression scores (HADS depression score of 6.3 [SD = 4.3] vs 4.1 [SD = 2.6]; P = 0.02) compared with the comparison group. Caregivers of children with IF demonstrated decreased health-related quality of life (HRQoL) (reduced PedsQL FIM total score of 50.6 [SD = 18.2] vs 84.1 [SD = 20.5]; P < 0.01). CONCLUSIONS: Our results demonstrated significant burden of care in caregivers of children with IF receiving long-term PN, with elevated stress, anxiety, and depression and decreased HRQoL.

Chronic Iron Deficiency and Cognitive Function in Early Childhood.

BACKGROUND AND OBJECTIVES: A landmark longitudinal study, conducted in Costa Rica in the 1980s, found that children with chronic iron deficiency compared with good iron status in infancy had 8 to 9 points lower cognitive scores, up to 19 years of age. Our objective was to examine this association in a contemporary, high-resource setting. METHODS: This was a prospective observational study of children aged 12 to 40 months screened with hemoglobin and serum ferritin. All parents received diet advice; children received oral iron according to iron status. After 4 months, children were grouped as: chronic iron deficiency (iron deficiency anemia at baseline or persistent nonanemic iron deficiency) or iron sufficiency (IS) (IS at baseline or resolved nonanemic iron deficiency). Outcomes measured at 4 and 12 months included the Early Learning Composite (from the Mullen Scales of Early Learning) and serum ferritin. RESULTS: Of 1478 children screened, 116 were included (41 chronic, 75 sufficient). Using multivariable analyses, the mean between-group differences in the Early Learning Composite at 4 months was -6.4 points (95% confidence interval [CI]: -12.4 to -0.3, P = .04) and at 12 months was -7.4 points (95% CI: -14.0 to -0.8, P = .03). The mean between-group differences in serum ferritin at 4 months was 14.3 µg/L (95% CI: 1.3-27.4, P = .03) and was not significantly different at 12 months. CONCLUSIONS: Children with chronic iron deficiency, compared with children with IS, demonstrated improved iron status, but cognitive scores 6 to 7 points lower 4 and 12 months after intervention. Future research may examine outcomes of a screening strategy on the basis of early detection of iron deficiency using serum ferritin.

Stability of the Gross Motor Function Classification System over time in children with cerebral palsy.

AIM: To assess the stability of the Gross Motor Functional Classification System (GMFCS) in children with cerebral palsy (CP) from time of preliminary diagnosis (~2 years of age) to time of diagnosis (~5 years of age), and to examine factors associated with reclassification. METHOD: We conducted a longitudinal study using a sample from the Canadian CP Registry. Stability was analysed by using the percentage of agreement between timepoints and a weighted prevalence and bias adjusted kappa statistic. Univariate and multivariate logistic regressions were performed to identify variables associated with reclassification. RESULTS: The study included 1670 children (857 males, 713 females) with a mean age of 11 years 4 months (SD 4 years, range 3 years 5 months-20 years 1 month) at time of data extraction (3rd September 2019), of which 1435 (85.9%) maintained a stable GMFCS, with a weighted kappa of 0.91 (95% confidence interval 0.89-0.92). Univariate logistic regression showed that initial GMFCS level, CP subtype, and the presence of cognitive impairment were associated with the likelihood of change in the GMFCS level (p < 0.1). In the multivariate analysis, however, the likelihood was associated with initial GMFCS level only (odds ratio 7.10-8.88, p < 0.00). INTERPRETATION: The GMFCS has good stability in early childhood. For the majority of children, it is predictive of their long-term motor function. WHAT THIS PAPER ADDS: The Gross Motor Function Classification System (GMFCS) rating in early childhood is stable over time. There is no directionality in the reclassification of the GMFCS. The initial GMFCS level was related to the likelihood of change in follow-up GMFCS level.