Early identification and communication in cerebral palsy: Navigating a collaborative approach for neonatal follow-up programmes.

AIM: This article will provide a clinical case demonstrating the implementation of early identification and review the tools and findings and the diagnostic approach. We will review highlighted literature on the subject of communicating a diagnosis. While improved function is a critical goal, the process of communicating the diagnosis of CP can be challenging for both parents and providers. It aims to provide insights on the evidence supporting early identification and discusses strategies for effective communication of crucial information. METHODS: The article reviews the literature on communication of a diagnosis. RESULTS: Thirteen articles were identified relating to the communication of a diagnosis of CP and parent experience. We examine this evidence, leveraging the knowledge of an interdisciplinary team and incorporating feedback from parents. CONCLUSION: Strategies for effective communication include engagement with families, community therapy teams and all medical providers. Consistent, individualised, collaborative communication is critical. Awareness of ableism and use of balanced, value-neutral terminology is recommended.

Cerebral palsy characteristics in term-born children with and without detectable perinatal risk factors: A cross-sectional study.

AIM: To compare, in term-born children with cerebral palsy (CP), the characteristics of those who exhibit detectable risk factors for CP at birth with those who do not. METHOD: This was a cross-sectional study of term-born children using the Canadian Cerebral Palsy Registry comparing those with and without perinatal risk factors and/or neonatal symptoms for pregnancy, birth and neonatal characteristics, magnetic resonance imaging (MRI) findings, CP subtype, and impairment severity. Risk factors were quantified with a CP risk calculator. Multivariable and multinomial regressions were expressed as odds ratios (OR) and relative risk ratios. RESULTS: Of 1333 term-born children, 781 (58.6%) had complete variables for the CP risk calculator, of whom 195 (25%) had 'undetectable' newborn infant CP risk, and they did not have greater postneonatal brain injury. Focal injury on MRI was more common (OR 2.0, 95% confidence interval [CI] 1.3-3.1) than in the 'detectable' group. The 'undetectable' group had more unilateral CP (OR 1.8, 95% CI 1.3-2.6), less severe motor impairment (OR 0.76, 95% CI 0.67-0.86), and were more verbal (OR 2.3, 95% CI 1.5-3.6). INTERPRETATION: In the Canadian CP Registry, one-quarter of term-born children lacked neonatal encephalopathy, seizures, or perinatal risk factors. They were more likely to have unilateral CP, focal MRI findings, and communicate with words than children with risk factors or neonatal symptoms.

Feasibility of a home-based home videogaming intervention with a family-centered approach for children with cerebral palsy: a randomized multiple baseline single-case experimental design.

BACKGROUND: Worldwide, children with cerebral palsy (CP) living in underserved communities face barriers to accessing motor therapy services. This study assessed the implementation and effectiveness of an 8-week, upper limb (UL) home-based intervention with a movement-tracking videogame (Bootle Blast) in Costa Rican children with CP. METHODS: Children established a weekly playtime goal and two UL activities of daily living (ADLs) that they would like to improve on. A multiple-baseline, single-case experimental design, was used with the Performance Quality Rating Scale (PQRS) as the repeated measure to track changes in performance of the selected ADLs between the baseline (usual care) and intervention (Bootle Blast) phases. The Canadian Occupational Performance Measure (COPM), the Box and Blocks Test (BBT) and the Children's Hand-Use Experience Questionnaire (CHEQ) were collected before and after the intervention. Technical barriers were documented during weekly video calls with a monitoring therapist. Treatment effect size, slope changes and percentage of non-overlapping data were identified for the PQRS. Descriptive statistics summarized results for the BBT, CHEQ, videogame logs (e.g., playtime) and technical barriers. RESULTS: Fifteen children participated and 13 completed the intervention. Both participants who dropped out did so after completing baseline assessments, but before experiencing Bootle Blast. Children's mean active playtime (i.e., mini-games targeting the UL) across the 8-weeks was 377 min, while mean total time spent engaging with Bootle Blast (active + passive play time [e.g., time navigating menus, reviewing rewards]) was 728 min. In total, eight technical issues (from five children) were reported, and all but three were resolved within 48 h. Partial effectiveness was associated with the intervention. Specifically, 85% of participants improved on the PQRS and 69% achieved clinically important improvements ≥ 2 points in performance on the COPM. Children improved by 1.8 blocks on average on the BBT, while on the CHEQ, five children had a clinically important increase of 10% of the total number of UL activities performed with both hands. CONCLUSION: Bootle Blast is a feasible and effective option to facilitate access and engage children with cerebral palsy in UL home rehabilitation. Trial registration Trial registration number: NCT05403567.

Early Biomarkers in the Prediction of Later Functional Impairment in Preterm Children With Cerebral Palsy.

BACKGROUND: To identify early biomarkers that could predict later functional capabilities in preterm children with later cerebral palsy (CP). METHODS: Data from 968 preterm children with later CP were extracted from the Canadian Cerebral Palsy Registry. One hundred eighty-two infants were born before 27 weeks of gestation, 461 infants were born between 27 and 33 weeks, and 325 infants were born between 34 and 37 weeks. Univariate and chi-square analyses were conducted to measure the association between early objective biomarkers and later mobility status defined as Gross Motor Function Classification System (GMFCS) levels IV and V as well as tube feeding dependence. RESULTS: Univariate analysis suggested no significant association between GMFCS levels IV and V or impaired feeding status and bilateral white matter injury on magnetic resonance imaging, high-grade intraventricular hemorrhage on head ultrasound, chorioamnionitis, a birth weight of 1000 to 1500 g or <1000 g, as well as an Apgar score of ≤5 at five minutes of life. Similar results were found for gestational age <28 weeks at birth. Only a significant association between GMFCS levels IV and V and a cord or first hour of life pH of ≤7 was reported (mobility status: odds ratio [OR] 1.95, 95% confidence interval [CI] 1.09 to 3.57) and feeding status: OR 2.23, CI 0.97 to 4.65)]. CONCLUSIONS: Prediction of functional outcomes based on specific early biomarkers appears hard to obtain in children with CP born preterm in contrast to those born at term. The complications and causal pathways inherent to prematurity may contribute to making prognostication less determinant.

Uncertainties Regarding Cerebral Palsy Diagnosis: Opportunities to Clarify the Consensus Definition.

Background and Objectives: We have established that physicians, including neurologists, variably diagnose cerebral palsy (CP) when using the most recent CP definition from 2006. We also know that child neurologists and neurodevelopmentalists view themselves to be optimally suited to diagnose CP based on their training backgrounds. Therefore, to reduce variability in CP diagnosis, our objective was to elucidate uncertainties child neurologists and neurodevelopmentalists may have regarding practical application of the 2006 definition. Methods: We conducted a cross-sectional survey of child neurologists and neurodevelopmentalists built into a discussion seminar at the 2022 Child Neurology Society (CNS) Annual Meeting, the largest professional meeting of these specialists in North America. Seminar attendees were provided the 2006 definition and asked whether they had any uncertainties about the practical application of the definition across 4 hypothetical clinical vignettes. A group of national and international CP leaders then processed these data through iterative discussions to develop recommendations for clarifying the 2006 definition. Results: The seminar was attended by 50% of all conference attendees claiming CME (202/401). Of the 164 closing survey respondents, 145 (88%) expressed uncertainty regarding the clinical application of the 2006 definition. These uncertainties focused on 1) age, both regarding the minimum and maximum ages of brain disturbance or motor symptom onset (67/164, 41%), and 2) interpretation of the term "nonprogressive" (48/164, 29%). Almost all respondents (157/164, 96%) felt that we should revise the 2006 consensus definition of CP. Discussion: To address the most common CP diagnostic uncertainties we identified, we collectively propose 4 points of clarification to the 2006 definition: 1) motor symptoms/signs should be present by 2 years old; 2) CP can and should be diagnosed as early as possible; 3) the clinical motor disability phenotype should be nonprogressive through 5 years old; and 4) a CP diagnosis should be re-evaluated if motor disability is progressive or absent by 5 years old. We anticipate that clarifying the 2006 definition of CP in this manner could address the uncertainties we identified among child neurologists and neurodevelopmentalists and reduce the diagnostic variability that currently exists.

Designing strategies to support Implementation of iNtensive Therapy for Early Reach through PLAY (INTERPLAY) for young children with cerebral palsy: a study protocol.

BACKGROUND: Intensive manual therapy is important for improving lifelong upper limb motor outcomes for infants and toddlers with cerebral palsy. This play-based therapy is delivered by caregivers who are coached by occupational therapists. However, access to this therapy is very limited for Canadian children with cerebral palsy younger than two years old. This project aims to first identify barriers and facilitators and then design implementation strategies to support early intensive manual therapy delivery for infants and toddlers with cerebral palsy across Canada. METHODS: A mixed-methods sequential explanatory design will be used with four consecutive phases. The updated Consolidated Framework for Implementation Research will guide the study. Quantitative data will be collected from a survey in Phase One. Participants will be recruited from three groups: (1) Caregivers of children with cerebral palsy six years old and younger who are eligible for manual therapy; (2) occupational therapists who treat children with cerebral palsy; and (3) healthcare administrators or people responsible for managing pediatric occupational therapy programs. In Phase Two, quantitative data from the survey will be used to map to implementation strategies known to be effective at addressing the identified modifiable barriers and facilitators. Phase Three will collect qualitative data from semi-structured interviews for the purpose of explaining Phase One quantitative findings in greater depth, and for understanding the appropriateness of strategies identified in Phase Two. The participant recruitment strategy and interview guide content for Phase Three will be informed by results of Phase One. Phase Four will use a modified nominal group technique to refine and prioritize an implementation strategy toolbox. Results will be widely disseminated to knowledge users to provide them with tailorable strategies to increase delivery of early intensive manual interventions. DISCUSSION: This study will provide a comprehensive understanding of the barriers and facilitators to implementation of early intensive manual therapy for young children with cerebral palsy in Canada. A toolbox of evidence-based and tailorable implementation strategies will be disseminated nationally to support uptake of early intensive manual therapy into clinical practice for young children with cerebral palsy.

Evolving understanding of CP phenotypes: the importance of dystonia.

Cerebral palsy (CP) is the core neurodevelopmental disorder affecting movement. Several distinct movement disorders can occur in people with cerebral palsy. Dystonia is a movement disorder that causes non-velocity-dependent hypertonia and/or abnormal, often repetitive, twisting movements, and/or postures. Dystonia occurs more frequently in patients with CP than has been recognized previously, and is treated differently than other aspects of CP. Dystonia is an important cause of chronic pain, hospitalization, and musculoskeletal complications. We describe recent advances in dystonia diagnosis in patients with cerebral palsy and highlight focus areas for ongoing research and clinical care. IMPACT: Dystonia is a movement disorder that is more common in people with cerebral palsy (CP) than previously thought. Dystonia contributes to hospitalization, chronic pain, and complications in CP patients. People with dystonic CP require different tools to diagnose and treat their condition. We summarize current state of the art in dystonia in CP and identify areas of focus for future work.

Family expectations and demand for home-based videogaming therapy in children with cerebral palsy in Costa Rica: a mixed methods study.

PURPOSE: To understand the expectations and demand for a movement-tracking videogame (Bootle Blast) for home-based, upper limb (UL) rehabilitation among Costa Rican children with cerebral palsy (CP). METHODS: Data were collected via telephone screening (demand) and child-parent dyads Zoom interviews (expectations). Descriptive statistics and data transformation were used to report on demand success criteria (i.e., recruitment rate, having an appropriate screen and space to play, setting a weekly play time goal (PTG) ≥45 min, identifying one UL therapy goal). The DEPICT model for collaborative qualitative analysis was used in the thematic analysis of interview data. RESULTS: Fifteen dyads participated (1.6 ± 1 recruited/month). All had a flat-screen TV in a suitable location to play, were able to set a UL therapy goal, and established PTGs ranging from 45-120 min per week. Identified themes were: 1) Socio-cultural factors heighten demand, 2) Feelings of hope prevail for the intervention, and 3) Collaborative goal setting supports realistic expectations for Bootle Blast. CONCLUSIONS: Dyads had positive and realistic expectations about implementing the proposed videogaming intervention. This study provides insights on tailoring a family-centered, therapy gaming intervention to improve access to motor rehabilitation for children with CP in rural/remote settings and low-middle income countries.

Costa Rican children have limited access to upper limb rehabilitation due to a combination of economic barriers, societal factors and the family context.Costa Rican children with cerebral palsy and their families expected home-based therapy gaming to be adaptable to their routines and aligned with their interests.Families perceived therapy gaming interventions as a promising path to access, participation, and enjoyment of at home upper limb motor therapy.

Association of Gestational Age at Birth and Changes on MRI With Prevalence and Spectrum of Comorbidities in Children With Cerebral Palsy.

BACKGROUND AND OBJECTIVES: For individuals with cerebral palsy (CP) and caregivers, comorbidities may be a greater challenge than neuromotor impairment. Clinicians may make assumptions regarding risk of comorbidities based simply on term vs preterm birth, but this has not been well examined. To better understand factors affecting comorbidity pattern, we investigated the relationship between gestational age (GA) and imaging pattern on the presence of specific comorbidities. METHODS: This is a cross-sectional study of data extracted from the Canadian Cerebral Palsy Registry of children with CP. Multivariable analysis was used to evaluate the relationship between brain injury, GA, and comorbidities. Comorbidities included in the analysis were communication, cognitive, visual, and auditory impairment, seizures in the past year, and gavage feeding. Each comorbidity was assessed as a separate nonexclusive outcome, with GA, MRI pattern, birth weight, postneonatal insult, 5-minute Apgar score, and male sex considered as potential modifiers. RESULTS: The only comorbidity affected by GA on multivariable analysis was seizures within the past year that were more prevalent in term children (odds ratio [OR] 1.1 95% CI 1.0-1.2) and was also affected by Apgar score (OR 0.9 95% CI 0.85-0.94), but not MRI pattern. MRI pattern appeared important for communication impairment (deep gray OR 4.2 95% CI 1.8-10.0; total brain injury OR 8.5, 95% CI 3.2-22.6; malformation OR 2.7, 95% CI 1.3-5.7) and cognitive impairment (deep gray OR 5.6, 95% CI 2.4-13.2; total brain injury OR 10.1, 95% CI 4.0-25.3; malformation OR 3.3, 95% CI 1.6-6.8; watershed OR 3.6, 95% CI 1.4-8.9). Focal injury compared with normal MRI was associated with reduced odds of visual impairment (OR 0.24, 95% CI 0.12-0.48), auditory impairment (OR 0.2195% CI 0.10-0.46) and communication impairment (OR 0.46, 95% CI 0.26-0.82), and overall number of comorbidities (coefficient -0.73, 95% CI -1.2 to -0.31). The number of comorbidities was increased by total brain injury pattern (coefficient 0.65, 95% CI 0.15-1.13) and reduced by focal brain injury (coefficient -0.73, 95% CI -1.2 to -0.31) and increasing 5-minute Apgar score (coefficient -0.11, 95% CI -0.16 to -0.07). DISCUSSION: In those with brain injuries sufficient to cause CP, development of additional comorbidities is less affected by GA at birth and more related to the underlying cause of CP as reflected by MRI patterns.

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.

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.