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Respiratory illness is the leading cause of mortality in children with cerebral palsy (CP). Although risk factors for developing chronic respiratory illness have been identified, comprehensive clinical care recommendations for the prevention and management of respiratory illness do not currently exist. We invited over 200 clinicians and researchers from multiple disciplines with expertise in the management of respiratory illness in children with CP to develop care recommendations using a modified Delphi method on the basis of the RAND Corporation–University of California Los Angeles Appropriateness Method. These recommendations are intended for use by the wide range of practitioners who care for individuals living with CP. They provide a framework for recognizing multifactorial primary and secondary potentially modifiable risk factors and for providing coordinated multidisciplinary care. We describe the methods used to generate the consensus recommendations, and the overall perspective on assessment, prevention, and treatment of respiratory illness in children with CP. What this paper adds The first consensus statement for preventing and managing respiratory disease in cerebral palsy (CP).Risk factors for respiratory disease in CP should be identified early.Individuals with CP at risk of respiratory disease require regular assessment of risk factors.Effective partnerships between multidisciplinary teams, individuals with CP, and families are essential.Treatment of respiratory disease in individuals with CP must be proactive., What this paper adds The first consensus statement for preventing and managing respiratory disease in cerebral palsy (CP).Risk factors for respiratory disease in CP should be identified early.Individuals with CP at risk of respiratory disease require regular assessment of risk factors.Effective partnerships between multidisciplinary teams, individuals with CP, and families are essential.Treatment of respiratory disease in individuals with CP must be proactive. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the abstract to view the translations. Editor's Choice Many individuals with cerebral palsy (CP) have a risk of developing respiratory problems, including infections and long‐term lung damage. This may affect many aspects of functioning, quality of life, and life expectancy. Assessment, prevention, and management are complex. Yet, the topic is insufficiently addressed in both clinical practice and research. My Editor's Choice for the February issue is this useful evidence‐based, expert‐ and consumer‐informed consensus statement, produced on the one hand for health professionals and on the other hand for young people with CP, their family, and caregivers, in order to implement and follow up optimal prevention and management of respiratory disease in this group.

Background Respiratory disease is a leading cause of hospitalizations and deaths in young people with cerebral palsy (CP). It is insidious and multifactorial. Clinical management can be complex. This systematic review describes effects of interventions for the prevention and management of respiratory disease in young people with CP. Methods Nine databases (Cochrane, CINAHL, Embase, EMCare, MEDLINE, PEDro, OpenGrey, ScienceDirect, and SpeechBITE) were searched. Eligibility criteria were as follows: the population included at least 50% individuals with CP aged under 26 years, the intervention was for chronic respiratory illness, the outcomes were any measurable indicators of respiratory health or morbidity; the study design could be any original study reporting effects of an intervention on measurable outcomes, and the study was published January 1998 or later. The American Academy for Cerebral Palsy and Developmental Medicine methodology guided study appraisal and synthesis. The review was registered with PROSPERO (reference number CRD42018086314). Results The search yielded 3,347 papers; 37 papers (reporting 34 studies) of these met the eligibility criteria. They included 582 participants with CP (ranging from 1 to 77 across studies) with ages from 5 months to 25 years. Interventions were diverse and included: airway clearance techniques, exercise, positioning, mealtime management, salivary management, upper airway interventions, antibiotics, gastro-intestinal interventions, and spinal surgery. There were no interventions aimed at prevention of respiratory disease in this population. Research designs were classified as Levels 2 (n = 3), 3 (n = 2), 4 (n = 25), and 5 (n = 4). Conclusions Evidence for most respiratory interventions for young people with CP is absent or weak. No controlled trials demonstrated significant effects on respiratory morbidity, owing to their scarcity, weak designs, and inadequate power. There is an urgent need for well-designed prospective controlled studies investigating prevention and management of respiratory disease in young people with CP.

Cerebral palsy (CP) is the most common cause of disability in childhood. Respiratory illness is the most common cause of mortality, morbidity, and poor quality of life in the most severely affected children. Respiratory illness is caused by multiple and combined factors. This review describes these factors and discusses assessments and treatments. Oropharyngeal dysphagia causes pulmonary aspiration of food, drink, and saliva. Speech pathology assessments evaluate safety and adequacy of nutritional intake. Management is holistic and may include dental care, and interventions to improve nutritional intake, and ease, and efficiency of feeding. Behavioral, medical, and surgical approaches to drooling aim to reduce salivary aspiration. Gastrointestinal dysfunction, leading to aspiration from reflux, should be assessed objectively, and may be managed by lifestyle changes, medications, or surgical interventions. The motor disorder that defines cerebral palsy may impair fitness, breathing mechanics, effective coughing, and cause scoliosis in individuals with severe impairments; therefore, interventions should maximize physical, musculoskeletal functions. Airway clearance techniques help to clear secretions. Upper airway obstruction may be treated with medications and/or surgery. Malnutrition leads to poor general health and susceptibility to infection, and improved nutritional intake may improve not only respiratory health but also constipation, gastroesophageal reflux, and participation in activities. There is some evidence that children with CP carry pathogenic bacteria. Prophylactic antibiotics may be considered for children with recurrent exacerbations. Uncontrolled seizures place children with CP at risk of respiratory illness by increasing their risk of salivary aspiration; therefore optimal control of epilepsy may reduce respiratory illness. Respiratory illnesses in children with CP are sometimes diagnosed as asthma; a short trial of asthma medications may be considered, but should be discontinued if ineffective. Overall, management of respiratory illness in children with CP is complex and needs well-coordinated multidisciplinary teams who communicate clearly with families. Regular immunizations, including annual influenza vaccination, should be encouraged, as well as good oral hygiene. Treatments should aim to improve quality of life for children and families and reduce burden of care for carers.

Contains fulltext : 220941.pdf (Publisher’s version ) (Closed access) PURPOSE: TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. METHODS: Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. RESULTS: We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. CONCLUSION: We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders.

Contains fulltext : 218155.pdf (Publisher’s version ) (Closed access) PURPOSE: To delineate the genotype-phenotype correlation in individuals with likely pathogenic variants in the CLTC gene. METHODS: We describe 13 individuals with de novo CLTC variants. Causality of variants was determined by using the tolerance landscape of CLTC and computer-assisted molecular modeling where applicable. Phenotypic abnormalities observed in the individuals identified with missense and in-frame variants were compared with those with nonsense or frameshift variants in CLTC. RESULTS: All de novo variants were judged to be causal. Combining our data with that of 14 previously reported affected individuals (n = 27), all had intellectual disability (ID), ranging from mild to moderate/severe, with or without additional neurologic, behavioral, craniofacial, ophthalmologic, and gastrointestinal features. Microcephaly, hypoplasia of the corpus callosum, and epilepsy were more frequently observed in individuals with missense and in-frame variants than in those with nonsense and frameshift variants. However, this difference was not significant. CONCLUSIONS: The wide phenotypic variability associated with likely pathogenic CLTC variants seems to be associated with allelic heterogeneity. The detailed clinical characterization of a larger cohort of individuals with pathogenic CLTC variants is warranted to support the hypothesis that missense and in-frame variants exert a dominant-negative effect, whereas the nonsense and frameshift variants would result in haploinsufficiency.

Aim To determine the prevalence of long‐term mechanical insufflation‐exsufflation (MI‐E) and concomitant mechanical ventilation in children with neurological conditions, with reported reasons behind the initiation of treatment. Method This was a population‐based, cross‐sectional study using Norwegian national registries and a questionnaire. Results In total, 114 of 19 264 children with a neurological condition had an MI‐E device. Seventy‐three of 103 eligible children (31 females, 42 males), median (min–max) age of 10 years 1 month (1y 5mo–17y 10mo), reported their MI‐E treatment initiation. Overall, 76% reported airway clearance as the main reason to start long‐term MI‐E. A prophylactic use was mainly reported by children with neuromuscular disorders (NMDs). Prevalence and age at initiation differed by diagnosis. In spinal muscular atrophy and muscular dystrophies, MI‐E use was reported in 34% and 7% of children, of whom 83% and 57% respectively received ventilator support. One‐third of the MI‐E users were children with central nervous system (CNS) conditions, such as cerebral palsy and degenerative disorders, and ventilator support was provided in 31%. The overall use of concomitant ventilatory support among the long‐term MI‐E users was 56%. Interpretation The prevalence of MI‐E in a neuropaediatric population was 6 per 1000, with two‐thirds having NMDs and one‐third having conditions of the CNS. The decision to initiate MI‐E in children with neurological conditions relies on clinical judgment. What this paper adds The prevalence and age at initiation of mechanical insufflation/exsufflation (MI‐E) differed between diagnoses.MI‐E was most commonly used in spinal muscular atrophy, where it generally coincided with ventilatory support.One‐third of MI‐E devices were given to children with central nervous system conditions, and one‐third also received ventilatory support., What this paper adds The prevalence and age at initiation of mechanical insufflation/exsufflation (MI‐E) differed between diagnoses.MI‐E was most commonly used in spinal muscular atrophy, where it generally coincided with ventilatory support.One‐third of MI‐E devices were given to children with central nervous system conditions, and one‐third also received ventilatory support. This article is commented on by Langdon and Cooper on pages 494–495 of this issue.

Background Changing medical care has resulted in growing numbers of Children with Medical Complexity (CMC). CMC have high care needs, often unmet by traditional healthcare models. In response to this need, the Complex Care Service (CCS) at The Royal Children’s Hospital (RCH) in Melbourne was created. While there was preliminary pilot data on the level of parent satisfaction with the service, we did not have sufficient knowledge of the value and importance of the various components of the service or parent satisfaction as the service expanded. Aim The aim of this study was to determine 1) what caregivers value most about the CCS service at the RCH and 2) explore caregiver perceptions of care. Methods All caregivers of children who were enrolled in the CCS at RCH in April 2017 (n = 103) were invited to participate. A purposefully designed survey explored their perceptions of care and included questions regarding: the extent to which the CCS improved patient quality of care; the extent to which the CCS components added value to patient care; satisfaction with the CCS; and likelihood of recommending the service to other families. Participants were invited to answer open ended questions about what the CCS did well, and what could be improved, and were invited to provide general comments. Results Responses were received from 53 families (51%). We found that 24 hour phone advice; coordination of appointments; a key contact; and access to timely information, are the most important components of a service for CMC for caregivers. Overall, levels of satisfaction with the RCH service were high - over 90% of caregivers indicated that they were very/somewhat satisfied with care. Further, over 90% of participants perceived that the CCS improved their child’s quality of care. Coordination, communication, family centred care, quality care and access were emergent themes in comments. Conclusion This study provides important information for the design and operation of services for CMC in hospitals throughout Australia and further afield. Our findings highlight the importance of the key contact and family centred care This has implications for practice, as maintaining the quality of the service as it expands and is implemented more widely is a major sustainability challenge. It is crucial that we have a detailed understanding of what elements are required to support effective care coordination, to achieve successful implementation on a large scale.

We report a case of prophylactic management with methylene blue (MB) in an almost 4-year-old male with congenital methemoglobinemia type II. He has a CYB5R3 compound heterozygote mutation, causing a cytochrome-b(5) reductase deficiency. Since the MB treatment regimen has commenced, his methemoglobin level has been significantly lower. He has shown modest behavioral improvements (as assessed on the Achenbach behavior report scales). There have been no iatrogenic side effects. These findings are encouraging for symptomatic improvement with regular prophylactic MB treatment but represent a single case report, which must be interpreted with caution.

OBJECTIVE: The goal of this study was to describe the prevalence, syndromes, and evolution of seizure disorders in children with cerebral palsy (CP) due to white matter injury (WMI). METHODS: For this population-based cohort study, brain MRI scans and medical records were reviewed in children in the Victorian Cerebral Palsy Register born between 1999 and 2006 recorded as having WMI. Children were excluded if they had features of an undiagnosed syndrome, associated cortical malformation or injury, or no medical contact in the preceding year. Included were 166 children with CP and isolated WMI due to presumed vascular insufficiency or hemorrhage; 87 were born preterm. Seizure and CP details were obtained from medical records and interviews, and EEG recordings were reviewed. RESULTS: Forty-one children (25%) had seizures beyond the neonatal period. Four children had West syndrome, which resolved with treatment. Thirteen children had febrile seizures that they outgrew. Thirty children had focal epilepsy with seizure manifestations and EEG discharges typical of early-onset childhood occipital epilepsy or childhood epilepsy with centrotemporal spikes; 23 have outgrown these seizures. Two children had idiopathic generalized epilepsy; it was ongoing in 1 child. Fourteen children had evolution from 1 epileptic syndrome to another. At last follow-up (median age, 12.7 years; minimum age, 9.7 years), 80% had not had a seizure for >2 years. CONCLUSIONS: The electroclinical features of seizure disorders associated with CP and WMI are those of the age-limited, epileptic syndromes of childhood, with favorable outcome in the majority. The findings have important implications for counseling and drug treatment.

We measured the mortality rate and the rate of Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet Syndrome (DS). We studied a cohort of 100 consecutively recruited, unrelated patients with DS; 87 had SCN1A mutations. Living cases had a median follow-up of 17 years. Seventeen patients died, at a median age of seven years (inter-quartile range 3-11 years) with causes of death: 10 SUDEP, four status epilepticus, two drowning and one asphyxia. The SUDEP classification included three Definite, one Definite Plus and six Probable. The Dravet-specific mortality rate/1000-person-years was 15.84 (98% CI 9.01-27.85). The Dravet-specific SUDEP rate was 9.32/1000-person-years (98% CI 4.46-19.45). The Dravet-specific SUDEP rate is the only documented syndrome-specific SUDEP rate. SUDEP in DS occurs mainly in childhood. It is also the highest SUDEP rate, considerably higher than the recent 5.1 SUDEP rate/1000-person-years for adults with refractory epilepsy.