Jenny A. Downs

Description:Background: Body position and movement during sleep is assessed for both clinical and research purposes. A diverse array of both assessment tools and classification systems are used to capture and code sleep biomechanics data. Objective: The aim of this scoping review was to identify the assessment tools and classification systems used to examine sleep biomechanics, and the strengths and limitations of current approaches. Methods: MEDLINE, EMBASE and CINAHL databases were searched from inception to July 2024, from which 73 publications were selected that assessed body position distribution and/or repositioning rate, for at least one night of sleep. Qualitative content analysis was completed to extract strengths and limitations of current approaches. Results: Nearly half (44 %) of studies assessed rate of repositioning; 26 % of studies assessed position distribution, and 30 % studies examined both rate of repositioning and position distribution. Common assessment tools were Wearable Accelerometry (26 %) and Polysomnography (22 %). The most frequent repositioning rate classification system was 90° trunk rotation (10 %) and the most frequent position distribution classification system was Supine/Left Side Lying/Right Side Lying/Prone (29 %). Strengths included richness of data set (wearable accelerometry), while limitations included cost and unfamiliar sleep environment (e.g. polysomnography). Conclusions: While different methods are needed to accommodate various research and clinical needs, a frequent challenge is the lack of detail in how sleep biomechanics are recorded and coded. Wearable sensors offer significant advantages in ease of implementation and granularity of data capture. These devices, in combination with a detailed sleep biomechanics coding system, show potential as future research tools to overcome this limitation.

Description:Objective: There is no published information on preterm children's activities and participation during middle childhood, a time when growth and development are characterised by increasing motor, reasoning, self-regulation, social and executive functioning skills. This study explored the health, activities and participation of children born very preterm during middle childhood (6-9 years) from the perspectives of their parents. Methods: This was a qualitative descriptive design. Twenty parents of 27 very preterm children born < 32 weeks gestation participated in semi-structured interviews to explore their child's health, behaviour, functioning and participation in school, at home and in the community along with environment and personal factors that influenced the child's activities and participation. Interview data were coded to each of the International Classification of Functioning in Disability (ICF-CY) domains. Results: Parents reported a broad range of health needs and participation outcomes. Parents reported challenges related to respiratory health, mental health and behaviour, sleep, nutrition and feeding. The child's participation and functioning were influenced by both personal and environmental factors including but not limited to parenting styles, education and learning support, access to health support and personal preferences and motivations. Conclusions: Preterm birth is associated with impacts on the child's health, activities and participation. This comprehensive view on the child's health and wellbeing can aid clinicians in their management of these children.

Description:Background: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is an ultrarare genetic condition causing developmental epileptic encephalopathy characterized by seizures and motor and intellectual disabilities. No disease-modifying therapies are available, and treatments focus mainly on symptom management to improve quality of life. Objective: The aim of this study was to better understand the burden of CDD based on family caregivers' perceptions. Methods: The study was a cross-sectional, web-based survey comprising 40 questions for caregivers of patients with CDD and focusing on sociodemographic and medical characteristics, disease burden, unmet needs, treatments, and support. An adapted version of the EQ-5D-5L instrument was included to measure patients' health-related quality of life as perceived by their caregivers. Results: A total of 132 caregivers, mostly from western parts of Europe, responded. The median patient age was 7.6 (IQR 2.9-12.2) years. Seizure onset occurred early, with the median onset at 2.0 (IQR 1.0-3.0) months of age. The median age at diagnosis was 1.2 (IQR 0.6-4.0) years. Epilepsy (123/132, 93.2%) and limited communication skills (111/132, 84.1%) were the most commonly reported symptoms. The highest number of different types of symptoms was reported for patients aged 5-9 years, with a median of 9.0 (IQR 7.5-10.0) symptoms. Most patients with epilepsy experienced daily seizures (81/123, 65.9%), and nearly all (119/123, 96.7%) were on antiseizure medications. A minority was on a ketogenic diet (21/123, 17.1%) or underwent vagus nerve stimulation (14/123, 11.4%). The care received was multidisciplinary. Compared to younger patients, adults had fewer medical appointments and a smaller variety of health care professionals in their care team. The EQ-5D-5L, adapted for caregivers, indicated low health-related quality of life for patients, with a median global index value of 0.18 (IQR 0.11-0.32). The most severe consequences of CDD on patients' daily lives were reported for mobility (88/132, 66.7%), self-care (120/132, 90.9%), and everyday activities (103/132, 78.0%). Caregiver burden was also substantial, with all life aspects reportedly impacted by CDD, including professional life and financial resources (median impact ratings of 9.0/10 and 7.0/10, respectively). Access to support and care varied depending on location. Caregivers outside Europe reported a longer time between the first seizure and diagnosis (26.5, IQR 3.2-47.0 months) compared to European caregivers (11.0, IQR 5.0-45.0 months). They also reported a higher impact of CDD on their financial resources (rating of 10/10) compared to European caregivers (rating of 6/10) and greater challenges in covering costs. Conclusions: The study findings provide valuable insights on symptoms and disease burden related to CDD. This burden was quantitatively characterized with the EQ-5D-5L for the first time and was perceived as substantial by family caregivers. Discrepancies between geographic regions and age groups were highlighted, especially regarding available support and access to resources and care.

Description:Objective: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting predominantly females and associated with variants in the MECP2 gene. Recent success in clinical trials have resulted in an expanded use of the Rett Syndrome Behaviour Questionnaire (RSBQ) for clinical and research purposes. Implementation of the RSBQ as a global clinical severity scale has raised concerns about its construct validity considering its content, structure, and psychometric features. To further understand RSBQ data, we analyzed RSBQ scores available in the literature with a focus on variability and influencing factors. Methods: We identified publications reporting RSBQ total and/or subscale scores and summarized relevant study information, such as type of investigation, administration method, and descriptive data. We then analyzed means and standard deviations, calculating variance-to-mean ratios (VMR), as a measure of variability, when raw score descriptive statistics were available. Where appropriate, we compared means and VMRs by Welch t-tests. Results: Of the 14 publications identified, raw total scores from 5 observational studies and 4 clinical trials (baseline) were available. Raw subscale scores from four of the five observational studies were also available. We found a wide but comparable range of mean total scores for observational studies and clinical trials. However, VMRs were significantly higher in observational studies. Subscale scores showed either high (i.e., General Mood, Breathing Problems) or low (e.g., Hand Behaviours, Body Rocking and Expressionless Face) variability. Available data demonstrated greater variability in pediatric than adult groups and less variability when using interviews or electronic RSBQ administration compared with paper forms. Total score changes over time did not affect variability. Although certain studies offered insight into the relationship between the RSBQ and other measures, overall, data were insufficient for characterizing how RSBQ variability relates to other factors. Conclusions: Our findings on score variability support the need for more comprehensive reporting of RSBQ data, cohort characterization, and methodology; and the deployment of standardized RSBQ administration methods, such as advanced data capture systems. There is potential for use of subscales as outcome measures, subject to further psychometric validation studies, including prospective investigations testing the stability of RSBQ scores and influencing factors. Further examining the relationship between RSBQ scores and other instruments will aid in its interpretation as a clinical outcome measure.

Description:Knowledge of the natural history of CDKL5 deficiency disorder (CDD) is limited to the results of cross-sectional analysis of largely pediatric cohorts. Assessment of outcomes in adulthood is critical for clinical decision-making and future precision medicine approaches but is challenging because of the diagnostic gap and duration of follow-up that would be required for prospective studies. We aimed to delineate the natural history retrospectively from adulthood. We analyzed clinical data about an international cohort of 67 adults with CDD. We analyzed demographic, phenotypic, CDKL5 Developmental Score (CDS), and treatment data, and tested associations with genetic factors, sex, and a positive or negative history of neonatal seizures, as an early predictor of prognosis. All but one of 67 adults (55 females, median age of 24 years at last follow-up) had epilepsy, typically beginning with epileptic spasms or tonic seizures before 4 months of age. Focal-onset and non-motor seizures emerged later. Fewer than a third had been documented as having bilateral tonic-clonic seizures or status epilepticus. Seizures often improved with age, but 73% had never experienced more than 6 months of seizure-freedom. Clobazam, sodium valproate, and lamotrigine were the most frequently prescribed antiseizure medications, but no specific treatment demonstrated superiority. Common comorbidities included movement disorders, visual impairment, sleep disorders, constipation, and scoliosis. All participants had intellectual disability, 75% had not acquired speech and 45% had regressed developmentally. 16% never achieved any CDS skill, but most attained at least three, and 28% attained six or all seven. By adulthood, half of those who had achieved any CDS skill retained all their CDS skills. The skills most frequently lost were independent walking and standing. Those with a history of neonatal seizures tended to attain fewer CDS skills and were more likely to have abnormal muscle tone in adulthood, atrioventricular conduction delay, and potential complications of their illness and treatment. Individuals carrying missense variants attained more CDS skills than those with other variants and were more likely to lose skills in adulthood and develop anxiety, possibly reflecting the limited neurodevelopment of those with non-missense variants, who manifested a more multisystemic disorder. In summary, retrospective data from adulthood elucidates the evolution of symptoms, variation in developmental outcomes, and the treatment landscape in CDKL5 deficiency disorder. Presence a non-missense variants or a history of neonatal seizures indicates a more complex disorder and lower developmental trajectory. Our findings will inform management decisions, prognostication, and the design of clinical trials in CDKL5 Deficiency Disorder.