The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

Variability in Newborn Screening Across Canada: Spinal Muscular Atrophy and Beyond.

BACKGROUND: Newborn screening (NBS) identifies infants with severe, early-onset diseases, enabling early diagnosis and treatment. In Canada, decisions regarding disease inclusion in NBS programs occur at the provincial level, which leads to variability in patient care. We aimed to determine whether important differences exist in NBS programs across provinces and territories. Given that spinal muscular atrophy (SMA) is the most recent disease added to NBS programs, we hypothesized that its inclusion would show interprovincial variability and be more likely in provinces already screening for a greater number of diseases. METHODS: We conducted a cross-sectional survey of all NBS labs in Canada to understand: 1) what conditions were included in their program; 2) what genetic-based testing was performed and; 3) if SMA was included. RESULTS: All NBS programs (N = 8) responded to this survey by June 2022. There was a 2.5-fold difference in the number of conditions screened (N = 14 vs N = 36) and a 9-fold difference in the number of conditions screened by gene-based testing. Only nine conditions were common to all provincial NBS programs. NBS for SMA was performed in four provinces at the time of our survey, with BC recently becoming the fifth province to add SMA to their NBS on October 1, 2022. Currently, 72% of Canadian newborns are screened for SMA at birth. CONCLUSION: Although healthcare in Canada is universal, its decentralization gives rise to regional differences in NBS programs which creates inequity in the treatment, care, and potential outcomes of affected children across provincial jurisdictions.

In utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study.

BACKGROUND: Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. METHODS: In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). RESULTS: During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association. CONCLUSIONS: In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.

Prevalence and temporal trends of cerebral palsy in children born from 2002 to 2017 in Ontario, Canada: Population-based cohort study.

AIM: To examine the prevalence and temporal trends of cerebral palsy (CP) overall and by population characteristics. METHOD: We identified 2 110 177 live births born in the province of Ontario, Canada, between 2002 and 2017 using administrative health data and estimated CP prevalence in children aged 0 to 16 years overall and by specific population characteristics. We also examined temporal trends in CP rates - overall and by characteristics - in young children (0-4 years) by their year of birth between 2002 and 2013 (n=1 587 087 live births) to allow for an equal follow-up time (4 years and 364 days) for all children. RESULTS: Overall CP prevalence among children aged 0 to 16 years was 2.52 (95% confidence interval 2.45-2.59) per 1000 live births. CP rates in ages 0 to 4 years peaked at 2.86 in 2007 births, but steadily declined afterwards to 1.94 per 1000 live births in 2013. CP rates were higher in children born preterm, small for gestational age, males, multiples, children with congenital malformations, and in children of young (<20 years), old (≥40 years), primiparous, or grand multiparous (≥4) mothers; differences by these characteristics decreased over time. We observed socioeconomic disparities in CP rates that persisted over time. INTERPRETATION: Despite the decreasing trend of CP rates overall, CP rates varied by the child and maternal characteristics over time. WHAT THIS PAPER ADDS: Overall cerebral palsy (CP) prevalence was 2.5 per 1000 live births among children born from 2002 to 2017. CP prevalence peaked in children born in 2007 then steadily decreased between 2007 and 2013. Changes in CP rates varied over time by child and maternal characteristics. Socioeconomic inequalities in CP persisted and remained stable over the study period.

Perinatal arterial ischemic stroke and periventricular venous infarction in infants with unilateral cerebral palsy.

AIM: To explore clinical factors associated with perinatal arterial ischemic stroke (AIS) and periventricular venous infarction (PVI) in infants who develop unilateral cerebral palsy (CP). METHOD: This was a case-control study. Data current to 2019 was extracted from the Canadian Cerebral Palsy Registry (CCPR). Cases were infants born at term with confirmed unilateral CP. Magnetic resonance images were stratified by expert review of reports as definitive perinatal stroke (AIS or PVI). Controls with common data elements were recruited from a population-based study in Alberta. Multivariable regression analyses were performed to estimate associations expressed as odds ratios with 95% confidence intervals. RESULTS: Of 2093 cases from the CCPR, 662 had unilateral CP, of whom 299 (45%) had perinatal stroke: AIS 169 (57%) and PVI 130 (43%). Median age at diagnosis for AIS was 11.9 months (interquartile range: 6.2-25.7mo; range 0.17-104.1mo), and 58.6% were male. Median age at diagnosis for PVI was 25.3 months (interquartile range: 14.5-38mo, range 0.7-114.7mo) and 57.7% were male. Independent associations for both AIS and PVI on multivariable analysis were chorioamnionitis, illicit drug exposure, diabetes, gestational age, and maternal age. Variables associated with AIS alone were low Apgar score and prolonged rupture of membranes. Variables associated with PVI alone were small for gestational age and primigravida. INTERPRETATION: Controlled analysis of disease-specific unilateral CP may offer unique perspectives on its pathophysiology. Acute intrapartum factors are mainly associated with AIS, while in utero factors are associated with PVI.

Epilepsy in children with cerebral palsy: a data linkage study.

AIM: To compare the prevalence of epilepsy in children with cerebral palsy (CP) to peer controls and their differences in healthcare utilization. METHOD: The Quebec CP registry was linked to the provincial administrative health database. Two CP cohorts were identified from the registry (n=302, 168 males, 1y 2mo-14y) and administrative data (n=370, 221 males, 2y 2mo-14y). A control cohort (n=6040, 3340 males, 10-14y) was matched by age, sex, and region to the CP registry cohort. Administrative data algorithms were used to define epilepsy cases. Data on hospitalizations and emergency department presentations were obtained. RESULTS: Using the most sensitive epilepsy definition, prevalence was 42.05% in the CP registry, 43.24% in the CP administrative data, and 1.39% in controls. Prevalence rose with increasing Gross Motor Function Classification System level. Children with CP and epilepsy had increased number and length of hospitalizations and emergency department presentations compared to children with CP or epilepsy alone. Epilepsy accounted for approximately 5% of emergency department presentations and 10% of hospitalizations in children with epilepsy, with and without CP. INTERPRETATION: Children with CP have an increased risk of epilepsy compared to their peers. Children with CP and coexisting epilepsy represent a unique subset with complex developmental disability and increased healthcare service utilization.

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.

Global prevalence of cerebral palsy: A systematic analysis.

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence. WHAT THIS PAPER ADDS: • Birth prevalence of pre-/perinatal cerebral palsy (CP) in high-income countries (HICs) is decreasing. • Current overall CP birth prevalence for HICs is 1.6 per 1000 live births. • Trends in low- and middle-income countries (LMICs) cannot currently be measured. • Current birth prevalence in LMICs is markedly higher than in HICs. • Active surveillance of CP helps to assess the impact of medical advancements and social/economic development. • Population-based data on prevalence and trends of CP are critical to inform policy.

Informing the development of the Canadian Neurodiversity Platform: What is important to parents of children with neurodevelopmental disabilities?

BACKGROUND: A crowd-sourced Canadian platform that collects information across neurodevelopmental disabilities (NDDs) can (1) facilitate knowledge mobilization; (2) provide epidemiological data that can benefit knowledge, treatment, and advocacy; and (3) inform policy and resource allocation decisions. We obtained input from parents of children with NDDs about relevance and feasibility of questionnaire items as a first step to inform questionnaire development of a stakeholder-driven, national platform for data collection on children with NDDs. METHODS: A parent of a teenager with NDDs was a research partner on the project. Through four focus groups and using a guided discussion consensus process, 16 participants provided feedback on whether questionnaire items from existing instruments related to function and disability were feasible for parents to complete and important to include in the platform. Data were analysed using content analysis. RESULTS: Participants (1) indicated that questions about medical history, general health, body functioning, self-care, access to resources, and outcomes (e.g., quality of life) are important to include in the platform and are feasible for self-completion; (2) provided various suggestions for the questionnaire ranging from additional items to include, using non-medical language, and keeping completion time from 20 to 30 min; (3) identified incentives and knowing the purpose of the platform as strong motivators to platform participation; (4) spoke about the challenges of their caregiver experience including impact of caregiving on themselves and barriers to accessing services; and (5) highlighted the isolation experienced by their children. CONCLUSION: Through the focus groups, parent stakeholders contributed to questionnaire development and shared their caregiver experiences. Obtaining feedback from youths with NDDs and healthcare providers on the questionnaire is a next step to validating findings. Stakeholder engagement is fundamental to developing a platform that will inform research that is relevant to the needs of children with NDDs and their families.

Cerebral palsy in Canadian Indigenous children.

AIM: To determine whether inequities in health outcomes for Indigenous Canadians are also present in cerebral palsy (CP) by comparing CP profiles between Indigenous and non-Indigenous children. METHOD: Using the Canadian Cerebral Palsy Registry, we conducted a cross-sectional study. CP motor subtype, gross motor severity, comorbidities, perinatal adversity, preterm birth, and parental education were compared between 94 Indigenous (53 males, 41 females) and 1555 non-Indigenous (891 males, 664 females) children (all >5y). Multivariate analysis was done to analyze adverse CP factors, defined as CP gross motor severity and comorbidities. CP etiologies, either prenatal/perinatal or postnatal, were also compared. RESULTS: Indigenous children with CP have higher odds of having low parental education (odds ratio [OR] 6.15, 95% confidence interval [CI] 3.36-11.3) and comorbidities (OR 4.46, 95% CI 1.62-12.3), especially cognitive (OR 4.52, 95% CI 2.27-9.05), communication (OR 2.66, 95% CI 1.54-4.61), and feeding (OR 2.25, 95% CI 1.33-3.83) impairment. Indigenous children also have higher CP gross motor severity (p=0.03). Indigenous children are also more likely to have non-accidental head injury (n=4; OR 8.18, 95% CI 1.86-36.0) as the cause of their postnatal CP. INTERPRETATION: Indigenous populations have worse health outcomes as a result of intergenerational impacts of colonization. Our study shows that Indigenous children with CP have increased comorbidities and higher CP gross motor severity, reinforcing the need for a multidisciplinary approach to management. Furthermore, targeted prevention programs against preventable causes of CP, such as non-accidental head injury, may be beneficial. WHAT THIS PAPER ADDS: Indigenous children with cerebral palsy (CP) have more severe motor impairment and more comorbidities. Non-accidental head injury is a significant cause of postnatal CP.

Hospitalizations in School-Aged Children with Cerebral Palsy and Population-Based Controls.

OBJECTIVE: To compare hospitalizations among children with cerebral palsy (CP) and healthy controls and to identify factors associated with hospitalizations in children with CP. METHODS: This retrospective cohort study linked data from a provincial CP Registry and administrative health databases. The CP cohort was comprised of children born from 1999 to 2002. Age, sex, and region-matched controls were identified from administrative health databases. Mean differences, relative risk (RR), and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 301 children with CP were linked to administrative health data and matched to 6040 controls. Mean hospitalizations per child during the study period were higher in children with CP compared to controls (raw mean difference (RMD) 5.0 95% CI 4.7 to 5.2) with longer length of stay (RMD 2.8 95% CI 1.8 to 3.8) and number of diagnoses per hospitalization (RMD 1.6 95% CI 1.4 to 1.8). Increased risk of hospitalization was observed in non-ambulant children with CP (RR 1.12 95% CI 1.01 to 1.22) compared to ambulant children and among those with spastic tri/quadriplegic CP compared to other CP subtypes (RR 1.15, 95% CI 1.05 to 1.27). Feeding difficulties (RR 1.20 95% CI 1.13 to 1.27), cortical visual (RR 1.22 95% CI 1.13 to 1.32), cognitive (RR 1.16 95% CI 1.04 to 1.30), and communication impairment (RR 1.26 95% CI 1.10 to 1.44) were associated with increased hospitalizations. CONCLUSIONS: Children with CP face more frequent, longer hospital stays than peers, especially those with a more severe CP profile. Coordinated interdisciplinary care is needed in school-aged children with CP and medical complexity.

Emergency Department Use in Children with Cerebral Palsy: A Data Linkage Study.

OBJECTIVE: To describe the pattern of emergency department (ED) consultations in children with cerebral palsy (CP) compared to controls and factors predictive of ED consultations. METHODS: This retrospective cohort study linked data from the Registre de la paralysie cérébrale du Québec (REPACQ) and provincial administrative health databases. The CP cohort was comprised of children enrolled in REPACQ born between 1999 and 2002. REPACQ covers 6 of 17 Quebec health administrative regions. Region-, age-, and gender-matched controls were identified from administrative health databases in a 20:1 ratio. The primary outcome was high use of ED services (≥4 ED visits during the study period). Relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS: In total, 301 children with CP were linked to administrative data and 6040 peer controls were selected. Ninety-two percent (92%) of the CP cohort had at least one ED visit in the study period, compared to 74% among controls (RR 1.24, 95% CI 1.19-1.28). Children with CP were more likely than their peers to have high ED use (RR 1.40; 95% CI 1.30-1.52). Factors predictive of high ED use were comorbid epilepsy (RR 1.23; 95% CI 1.04-1.46) and severity of motor impairment (RR 1.14; 95% CI 0.95-1.37). CONCLUSION: Children with CP are more likely to present to the ED than their peers, resulting in increased use of ED services. Coordinated care with improved access to same-day evaluations could decrease ED use. Health system factors and barriers should be investigated to ensure optimal and appropriate use of ED services.

Complementary and Alternative Therapy Use in Children with Cerebral Palsy.

OBJECTIVE: To describe complementary and alternative medicine (CAM) use amongst children with cerebral palsy (CP) in Canada and to identify factors associated with CAM use. METHODS: We conducted a cross-sectional study, utilising data from the Canadian CP Registry. We explored the association between CAM use and regional, socioeconomic and CP phenotypic variables, and parental perception of the family-centredness of clinical care using the Measures of Process of Care-56 (MPOC-56). Chi-square analyses were performed, and odds ratios (OR) and 95% confidence intervals (CI) were obtained. Mann-Whitney U tests were used to compare MPOC-56 scores between CAM users and non-CAM users. RESULTS: The study sample consisted of 313 families of which 27% reported CAM use in the past year. Children with CP using CAM were more likely to reside in Western Canada (OR 3.3, 95% CI 1.6-6.7), live in a two-parent household (OR 3.5, 95% CI 1.5-8.4), have an ataxic/hypotonic or dyskinetic CP subtype (OR 3.0, 95% CI 1.5-6.1) and have a greater motor impairment (OR 2.8, 95% CI 1.7-4.9). MPOC-56 subscale scores were not significantly associated with CAM use. CONCLUSION: Physicians need to be aware of existing CAM therapies, the level of evidence supporting their efficacy (beneficence), their associated risks of adverse events (non-maleficence) and enable fair access to care that may be of benefit to each child.

Look Around Me: Environmental and Socio-Economic Factors Related to Community Participation for Children with Cerebral Palsy in Québec.

Aims: This study aimed at gaining a deeper understanding of the environmental and socio-economic factors affecting participation outcomes in community and leisure activities for children with disabilities, as well as the trajectories of participation for these children to promote their health and guarantee their rights are respected.Methods: A participatory action research (PAR) approach and linear regression analysis were employed to identify contextual factors associated with the community participation of children with cerebral palsy (CP) living in Quebec, Canada. Stakeholders engaged through the entire research process supported the development of questionnaires, data collection, analysis and interpretation of results.Results: Neighborhood outings were ranked among the most practiced activities by children with CP. Only in a few cases (9%) did children participate in more than two types of activities outside of school. Factors limiting children's participation were predominantly extrinsic in origin, including financial burden and lack of information about existing opportunities.Conclusions: There is a serious need for communities and local governments to inform parents about available resources, programs and policies that can support their child's participation. Rehabilitation professionals could partner with stakeholders to inform the development of public policies that target the identified barriers and promote children's integration and fulfillment.

Current Referral Practices for Diagnosis and Intervention for Children with Cerebral Palsy: A National Environmental Scan.

OBJECTIVES: To describe current physician referral practices with respect to age at referral to medical specialists for initial diagnosis of cerebral palsy (CP) and rehabilitation specialists for intervention and to identify factors associated with delayed referral. STUDY DESIGN: National environmental scan of 455 children diagnosed with CP who were born in Canada between 2008 and 2011, selected from 4 sites within the Canadian CP Registry (Edmonton, Calgary, Toronto, and Montreal). Two sources of information were used-children's medical charts and the population-based registry, which provided corresponding data for each child. Primary outcomes extracted from the charts were age at referral for diagnostic assessment, age at diagnosis, age at referral for rehabilitation services, and age at initial rehabilitation intervention. Twelve variables were explored as potential predictors. Descriptive statistics, bivariate analyses, and multiple linear regressions were conducted. RESULTS: Median age (in months) at referral for diagnostic assessment was 8 (mean: 12.7 ± 14.3), diagnosis 16 (mean: 18.9 ± 12.8), referral for rehabilitation services 10 (mean: 13.4 ± 13.5), and rehabilitation initiation 12 (mean: 15.9 ± 12.9). Lower maternal education, mild severity of motor dysfunction, type of CP, early discharge after birth, and region of residence explained between 20% and 32% of the variance in age at referral for assessment, diagnosis, referral for rehabilitation, and rehabilitation initiation. CONCLUSIONS: Findings suggest wide variability exists in the age at which young children with CP are referred to specialists for diagnosis and intervention. User-friendly tools are therefore needed to enhance early detection and referral strategies by primary care practitioners, to ensure early interventions to optimize developmental outcomes and enhance opportunities for neural repair at a younger age.

Losing a diagnosis of cerebral palsy: a comparison of variables at 2 and 5 years.

AIM: This study aims to identify characteristics at 2 years of age that differ between children with confirmed cerebral palsy (CP) and a non-CP diagnosis by 5 years of age. METHOD: This was a retrospective cohort analysis. A CP diagnosis may be considered a 'probable' diagnosis at 2 years, which is often 'confirmed' at 4 or 5 years, particularly in the context of CP registries. A total of 1683 children with a diagnosis of CP or probable CP at 2 years of age were identified from the Canadian Cerebral Palsy Registry, of whom 48 received a non-CP diagnosis at 5 years ('non-confirmed CP'). Perinatal adversity, preterm birth status, Gross Motor Function Classification System (GMFCS) level, presence of comorbidities, magnetic resonance imaging (MRI) findings, and initial CP motor type were compared between the two groups by univariate and logistic regression analyses. RESULTS: χ2 analysis and multivariate analysis both confirmed that children with a non-CP diagnosis by 5 years of age were more likely to have a normal MRI (χ2 odds ratio [OR]=7.8, 95% confidence interval [CI]=3.8-16.1; OR=5.4, 95% CI=2.4-12.5), ataxic-hypotonic (χ2 OR=10.1, 95% CI=4.9-21.2; OR=6.1, 95% CI=2.2-16.2) or dyskinetic CP (χ2 OR=2.7, 95% CI=1.2-5.9; OR=2.9, 95% CI=1.0-7.6), born at term (χ2 OR=3.7, 95% CI=1.7-8.0; OR=3.6, 95% CI=1.0-12.1), and lack perinatal adversity (χ2 OR=4.1, 95% CI=1.6-10.7; OR=3.4, 95% CI=1.0-11.7). INTERPRETATION: Normal MRI, ataxic-hypotonic or dyskinetic CP, lack of perinatal adversity, and term birth are associated with a higher odds of non-CP diagnosis by 5 years of age, thus potentially enhancing diagnostic work-up. WHAT THIS PAPER ADDS: Normal magnetic resonance imaging (MRI) at 2 years was associated with a non-cerebral palsy (CP) diagnosis by 5 years. Diagnosis of ataxic-hypotonic or dyskinetic CP motor subtype at 2 years was associated with a non-CP diagnosis by 5 years. Perinatal adversity and preterm birth were rarer with a non-CP diagnosis by 5 years.

OPORTUNIDADES DIAGNOSTICAS PERDIDAS DE PARÁLISIS CEREBRAL: UNA COMPARACIÓN DE VARIABLES A LOS 2 Y 5 AÑOS: OBJETIVO: Este estudio tiene como objetivo identificar características a los 2 años de edad que diferencian a los niños con parálisis cerebral (PC) confirmada y niños sin diagnóstico de PC a los 5 años de edad. MÉTODO: Se realizó un estudio de cohorte retrospectivo. Un diagnóstico de PC puede considerarse como "probable" a los 2 años, lo que es con frecuencia "confirmado" a los 4 o 5 años de edad, particularmente en el contexto de los registros de PC. Se identificaron un total de 1.683 niños con diagnóstico de PC o PC probable a los 2 años de edad en el Registro Canadiense de PC, de los cuales 48 recibieron un diagnóstico de no PC a los 5 años (PC no confirmado). Se compararon entre los 2 grupos: la adversidad perinatal, prematuridad, nivel de función motora en el sistema de Clasificación Motora Gruesa (GMFCS), la presencia de comorbilidades, hallazgos en imágenes de resonancia magnética nuclear (RMN), y tipo motor inicial de PC; usando un análisis univariado y de regresión logística. RESULTADOS: Tanto el análisis X2 como el multivariado confirmaron que los niños sin diagnóstico de PC a los 5 años de vida tenían más probabilidades de tener una RMN normal (X2 odds ratio [OR]= 7.8, intervalo de confianza 95 % [IC]= 3.8-16.1; OR=5.4, IC 95%= 2.4-12.5), ataxia (X2 OR=10.1, IC95%=4.9-21.2; OR=6.1, IC 95%=2.2-16.2) o PC disquinesia (X2 OR =2.7, IC 95%= 1.2-5.9; OR= 2.9, IC 95%= 1.0-7.6), nacidos a término (X2 OR=3.7, IC 95%= 1.7-8.0; OR=3.6, IC 95%=1.0-12.1), y niños sin adversidad perinatal (X2 OR=4.1, IC 95%=1.6-10.7; OR=3.4, IC 95% 1.0-11.7). INTERPRETACIÓN: La resonancia magnética normal, la PC atáxica o disquinesica, la falta de adversidad perinatal y el parto a término se asocian con una mayor probabilidad de no diagnóstico de PC a los 5 años de edad; esto refuerza el trabajo diagnóstico.

PERDENDO UM DIAGNÓSTICO DE PARALISIA CEREBRAL: UMA COMPARAÇÃO DE VARIÁVEIS AOS 2 E 5 ANOS: OBJETIVO: Este estudo visa identificar características aos 2 anos de idade que discriminem crianças com paralisia cerebral (PC) confirmada e um diagnóstico de não PC aos 5 anos de idade. MÉTODO: Esta foi uma análise de coorte retrospectiva. Um diagnóstico de PC pode ser considerado "provável" aos 2 anos, e é frequentemente confirmado aos 4 ou 5 anos, particularmente no contexto dos registros de PC. Um total de 1.683 crianças com diagnóstico de PC ou provável aos 2 anos de idade foram identificadas no Registro Canadense de Paralisia, dos quais 48 receberam um diagnóstico de não PC aos 5 anos (PC não confirmada). Adversidade perinatal, nascimento prematuro, nível I no sistema de classificação da função motora grossa (GMFCS), presença de comorbidades, achados de imagem por ressonância magnética (IRM), e tipo motor inicial de PC foram comparados entre os dois grupos por meio de análises de regressão univariada e logística. RESULTADOS: Tanto a análise de χ2 quanto a multivariada confirmaram que crianças com diagnóstico de não PC aos 5 anos de idade tinham maior probabilidade de uma IRM normal (χ2 odds ratio [OR]=7,8, intervalo de confiança [IC] 95%=3,8-16,1; OR=5,4, IC 95% =2,4-12,5), PC tipo atáxica (χ2 OR=10,1, IC 95%=4,9-21,2; OR=6,1, IC 95% =2,2-16,2) ou discinética (χ2 OR=2,7, IC 95%=1,2-5,9; OR=2,9, IC 95% =1,0-7,6), serem nascidas a termo (χ2 OR=3,7, IC 95% =1,7-8,0; OR=3,6, IC 95% =1,0-12,1), e não terem histórico de adversidade perinatal (χ2 OR=4,1, IC95% =1,6-10,7; OR=3,4, IC 95% =1,0-11,7). INTERPRETAÇÃO: IRM normal, PC tipo atáxica ou discinética, falta de adversidade perinatal, e nascimento a termo são associados com maior chance de um diagnóstico de PC não confirmado aos 5 anos de idade, o que potencialmente favorece o processo de diagnóstico.

International expert recommendations of clinical features to prompt referral for diagnostic assessment of cerebral palsy.

AIM: To establish international expert recommendations on clinical features to prompt referral for diagnostic assessment of cerebral palsy (CP). METHOD: An online Delphi survey was conducted with international experts in early identification and intervention for children with CP, to validate the results obtained in two previous consensus groups with Canadian content experts and knowledge users. We sent two rounds of questionnaires by e-mail. Participants rated their agreement using a 4-point Likert scale, along with optional open-ended questions for additional feedback. Additionally, a panel of experts and knowledge-users reviewed the results of each round and determined the content of subsequent surveys. RESULTS: Overall, there was high-level of agreement on: (1) six clinical features that should prompt referral for diagnosis; (2) two 'warning sign' features that warrant monitoring rather than immediate referral for diagnosis; and (3) five referral recommendations to other healthcare professionals to occur simultaneously with referral for diagnosis. INTERPRETATION: There was high agreement among international experts, suggesting that the features and referral recommendations proposed for primary care physicians for early detection of CP were broadly generalizable. These results will inform the content of educational tools to improve the early detection of CP in the primary care context. WHAT THIS PAPER ADDS: International experts provide strong agreement on clinical features to detect cerebral palsy. Consensus on clinical 'warning signs' to monitor over time. Referral recommendations from primary care to specialized health services are identified.

RECOMENDACIONES DE EXPERTOS INTERNACIONALES SOBRE CARACTERÍSTICAS CLÍNICAS PARA UNA DERIVACIÓN RÁPIDA PARA LA EVALUACIÓN DIAGNÓSTICA DE LA PARÁLISIS CEREBRAL: OBJETIVO: Establecer recomendaciones de expertos internacionales sobre características clínicas para iniciar derivación para la evaluación diagnóstica de la parálisis cerebral (PC). MÉTODO: Se realizó una encuesta online tipo Delphi con expertos en identificación e intervención temprana de niños con PC a fin de validar los resultados obtenidos en dos grupos de consenso realizados previamente en Canadá con expertos en contenidos y usuarios. Se enviaron dos rondas de cuestionarios por correo electrónico. Los participantes calificaron su acuerdo con un puntaje de 4 puntos en una escala Likert y con preguntas opcionales de respuesta abierta para comentarios adicionales. Además, un panel de expertos y usuarios revisaron los resultados de cada ronda y determinaron el contenido de las encuestas subsiguientes. RESULTADOS: En general, hubo un alto nivel de acuerdo sobre: ​​(1) seis características clínicas que requieren derivación rápida para el diagnóstico, (2) dos características de "señales de advertencia" que requieren monitoreo en lugar de referencia inmediata para el diagnóstico, y (3) cinco recomendaciones de referencia a otros profesionales de la salud que deben realizarse simultáneamente con la derivación para el diagnóstico. INTERPRETACIÓN: Hubo gran acuerdo entre los expertos internacionales, sugiriendo que las características y recomendaciones de referencia propuestas para los médicos de atención primaria para la detección de PC fue ampliamente generalizable. Estos resultados informarán el contenido de herramientas educativas para mejorar la detección precoz de PC en el contexto de atención primaria.

RECOMENDAÇÕES DE ESPECIALISTAS INTERNACIONAIS SOBRE ASPECTOS CLÍNICOS DISPARADORES DE ENCAMINHAMENTO PARA AVALIAÇÃO DIAGNÓSTICA EM PARALISIA CEREBRAL: OBJETIVO: Estabelecer recomendações de especialistas internacionais sobre os aspectos clínicos disparadores de encaminhamento para avaliação diagnóstica em paralisia cerebral (PC). MÉTODO: Um levantamento online internacional do tipo Delphi foi realizado com especialistas em identificação e intervenção precoce para crianças com PC, para validar os resultados obtidos em dois consensos prévios com especialistas no conteúdo e usuários canadenses. Enviamos duas rodadas de questionários por email. Os participantes pontuaram sua concordância usando uma escala Likert de 4 pontos, junto com questões abertas opcionais para informações adicionais. Além disso, um painel de especialistas e usuários revisaram os resultados de cada rodada, e determinaram o conteúdo das pesquisas subsequentes. RESULTADOS: Em geral, houve alto nível de concordância em: 1) seis aspectos clínicos que devem disparar encaminhamento para diagnóstico. 2) dois 'sinais de alerta' que merecem monitoramento mas não encaminhamento imediato para diagnóstico, e 3) cinco recomendações de encaminhamento para outros profissionais da saúde simultaneamente ao encaminhamento para diagnóstico. INTERPRETAÇÃO: Houve alta concordância entre especialistas internacionais, sugerindo que os aspectos e recomendações para encaminhamento propostos para médicos na atenção básica para a identificação precoce da PC foram amplamente generalizáveis. Estes resultados informarão o conteúdo de ferramentas educacionais para melhorar a detecção precoce de PC no contexto da atenção básica.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

Use of consensus methods to determine the early clinical signs of cerebral palsy.

OBJECTIVES: To develop expert-informed content regarding the early motor attributes of cerebral palsy (CP) that should prompt physician referral for diagnostic assessment of CP, as well as concurrent referral recommendations. This content will be used in the creation of knowledge translation (KT) tools for primary care practitioners and parents. METHODS: Two nominal group processes were conducted with relevant stakeholders, representing Canadian 'content experts' and 'knowledge-users', using an integrated KT approach. RESULTS: Six attributes were identified that should prompt referral for diagnosis. If the child demonstrates: Early handedness <12 months; stiffness or tightness in the legs between 6 and 12 months; persistent fisting of the hands >4 months; persistent head-lag >4 months; inability to sit without support >9 months; any asymmetry in posture or movement. Five referral recommendations were agreed upon: Motor intervention specialist (physical therapy and/or occupational therapy) for ALL; speech-language pathology IF there is a communication delay; audiology IF there is parental or healthcare professional concern regarding a communication delay; functional vision specialist (e.g., optometrist or occupational therapist) IF there is a vision concern (e.g., not fixating, following, or tracking); feeding specialist (e.g., occupational therapist, speech-language pathologist) IF there are feeding difficulties (e.g., poor sucking, poor swallowing, choking, and/or not gaining weight). CONCLUSION: Rigorous consensus methods provided the initial evidence necessary to inform the content of tools to assist primary care providers in the early detection of CP. Results will be validated through a Delphi process with international experts, and user-friendly formats of this KT tool will be developed collaboratively with stakeholders.

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

OBJECTIVE: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population. METHODS: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended. RESULTS: Fifteen class I-III studies on migraine prevention in children in adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine and flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency. Recommendations The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency, and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments.