Narcolepsy Following Yellow Fever Vaccination: A Case Report

Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.</p

Cardio-Respiratory Sleep Studies at Home:Experience in Research and Clinical Cohorts

Objective To evaluate the success rates of home cardiorespiratory polygraphy in children under investigation for sleep-disordered breathing and parent perspectives on equipment use at home. Design Prospective observational study. Setting Sheffield, Evelina London and Southampton Children's Hospitals. Patients Data are reported for 194 research participants with Down syndrome, aged 0.5-5.9 years across the three centres and 61 clinical patients aged 0.4-19.5 years from one centre, all of whom had home cardiorespiratory polygraphy including respiratory movements, nasal pressure flow, pulse oximetry, body position and motion. Main outcome measures Percentage of home cardiorespiratory studies successfully acquiring ≥4 hours of artefact-free data at the first attempt. Parental report of ease of use of equipment and preparedness to repeat home diagnostics in the future. Results 143/194 (74%; 95% CI 67% to 79%) of research participants and 50/61 (82%; 95% CI 71% to 90%) of clinical patients had successful home cardiorespiratory polygraphy at the first attempt. Some children required multiple attempts to achieve a successful study. Overall, this equated to 1.3 studies per research participant and 1.2 studies per clinical child. The median artefact-free sleep time for successful research studies was 515 min (range 261-673) and for clinical studies 442 min (range 291-583). 84% of research and 87% of clinical parents expressed willingness to repeat home cardiorespiratory polygraphy in the future. 67% of research parents found the equipment 'easy or okay' to use, while 64% of clinical parents reported it as 'easy' or 'very easy'. Conclusions Home cardiorespiratory polygraphy offers an acceptable approach to the assessment of sleep-disordered breathing in children.</p

Prevalence and predictors of obstructive sleep apnea in young children with Down syndrome

BackgroundChildren with Down syndrome (DS) are vulnerable to obstructive sleep apnoea (OSA) because of their unique craniofacial anatomy and hypotonia. Understanding the predictors of OSA in DS may enable targeted screening.MethodsChildren with DS (n = 202) aged from six months to below six years (110 boys) were recruited from three UK children's hospitals. The clinical assessment included height, weight and tonsillar size. The parents either set up cardiorespiratory polygraphy at home or chose laboratory studies. Studies with less than four hours of interpretable data were repeated where possible. American Academy of Sleep Medicine (AASM) 2012 scoring criteria were used to derive an obstructive apnoea/hypopnoea index (OAHI). Predictors of moderate to severe OSA were examined.ResultsIn total, 188/202 (93%) participants were successfully studied. Of these, 169 studies were completed at home and 19 in a sleep laboratory. Moderate to severe OSA, defined by an OAHI of &gt;5/h, was found in 14% and mild to moderate OSA (1/h≥OAHI &lt;5/h) was found in 59% of the children. Male gender and habitual snoring predicted OSA but did not have independent predictive power in the presence of the other factors. Age in months, body mass index (BMI) centile and tonsillar size did not predict OSA.ConclusionsModerate to severe OSA is common in very young children with DS. Examination of tonsillar size did not predict OSA severity. Population-based screening for OSA is recommended in these children, and domiciliary cardiorespiratory polygraphy is an acceptable screening approach. Further research is required to understand the natural history, associated morbidity, optimal screening methodology and treatment modality for OSA in these children.</p

Epilepsy-specific patient-reported outcome measures of children's health-related quality of life: A systematic review of measurement properties.

This is the final version. Available from the publisher via the DOI in this record.OBJECTIVE: To identify and appraise published evidence of the measurement properties for epilepsy-specific patient-reported outcome measures (PROMs) of children's health-related quality of life (HRQoL). METHODS: We searched multiple databases for studies evaluating the measurement properties of English-language epilepsy-specific PROMs of children's HRQoL. We assessed the methodological quality using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidance. We extracted data about the content validity, construct validity, internal consistency, test-retest reliability, proxy reliability, responsiveness, and precision, and assessed the measurement properties with reference to standardized criteria. RESULTS: We identified 27 papers that evaluated 11 PROMs. Methodological quality was variable. Construct validity, test-retest reliability, and internal consistency were more commonly assessed. Quality of Life in Childhood Epilepsy (QoLCE) questionnaires are parent-reported and evaluated more than other PROMs; QoLCE-55 has good and replicated evidence for structural and construct validity and internal consistency. Health-Related Quality of Life Measure for Children with Epilepsy (CHEQoL) has both child and parent-reported versions and good evidence of content, structural, and construct validity. SIGNIFICANCE: This review identified two leading candidate epilepsy-specific PROMs for measuring health-related quality of life in children. Establishing evidence of the responsiveness of PROMs is a priority to help the interpretation of meaningful change scores.National Institute for Health Research (NIHR

Sleep in children with Smith-Magenis syndrome:a case-control actigraphy study

Study Objectives: 1) To compare both actigraphy and questionnaire assessed sleep quality and timing in children with Smith-Magenis syndrome (SMS) to a chronologically age-matched typically developing (TD) group. 2) To explore associations between age, nocturnal and diurnal sleep quality and daytime behaviour.Methods: Seven nights of actigraphy data were collected from 20 children with SMS (mean age 8.70; SD 2.70) and 20 TD children. Daily parent/teacher ratings of behaviour and sleepiness were obtained. Mixed linear modelling was used to explore associations between total sleep time and daytime naps and behaviour.Results: Sleep in children with SMS was characterised by shorter total sleep time (TST), extended night waking, shorter sleep onset, more daytime naps and earlier morning waking compared to the TD group. Considerable inter-daily and inter-individual variability in sleep quality was found in the SMS group, so caution in generalising results is required. An expected inverse association between age and TST was found in the TD group, but no significant association was found for the SMS group. No between group differences in sleep hygiene practices were identified. A bidirectional negative association between TST and nap duration was found for the SMS group. In the SMS group increased afternoon sleepiness was associated with increased irritability (p=.007) and overactivity (p=.005).Conclusion: These findings evidence poor sleep quality in SMS and the need to implement evidence-based interventions in this population

Mapping epilepsy-specific patient-reported outcome measures for children to a proposed core outcome set for childhood epilepsy

Objective: To (1) map questions in epilepsy-specific patient-reported outcome measures (PROMs) of children’s health-related quality of life (HRQoL) to a proposed core outcome set (COS) for childhood epilepsy research; (2) gain insight into the acceptability of two leading candidate PROMs. Method: We identified 11 epilepsy-specific PROMs of children’s HRQoL (17 questionnaire versions) in a previous systematic review. Each item from the PROMs was mapped to 38 discrete outcomes across 10 domains of the COS: seizures, sleep, social functioning, mental health, cognition, physical functioning, behaviour, adverse events, family life and global quality of life. We consulted with three children with epilepsy and six parents of children with epilepsy in Patient Public Involvement and Engagement (PPIE) work to gain an understanding of the acceptability of the two leading PROMs from our review of measurement properties: Quality of Life in Childhood Epilepsy (QOLCE-55) and Health-Related Quality of Life Measure for Children with Epilepsy (CHEQOL). Results: Social Functioning is covered by all PROMs except DISABKIDS and G-QOLCE and Mental Health is covered by all PROMs except G-QOLCE and HARCES. Only two PROMs (ELDQOL and GEOS-YP) have items that cover the Seizure domain. QOLCE-55 includes items that cover the domains of Physical Functioning, Social Functioning, Behaviour, Mental Health and Cognition. CHEQOL parent and child versions cover the same domains as QOLCE-55 except for Physical Functioning and Behaviour, and the child version has one item that covers the discrete outcome of Overall Quality of Life and one item that covers the discrete outcome of Relationship with parents and siblings. QOLCE-55 parent version was acceptable to the parents we consulted with, and CHEQOL parent and child versions were described as acceptable to our child and parent advisory panel members. Significance: Mapping items from existing epilepsy-specific PROMs for children is an important step in operationalizing our COS for childhood epilepsy research, alongside evaluation of their measurement properties. Two leading PROMS, QOLCE-55 and CHEQOL cover a wide range of domains from our COS and would likely be used in conjunction with assessment tools selected for specific study objectives. PPIE work provided practical insights into the administration and acceptability of candidate PROMs in appropriate context. We promote our COS as a framework for selecting outcomes and PROMs for future childhood epilepsy evaluative research. Key words: Epilepsy, children, core outcome set, pediatric, patient-reported outcome measure, patient public involvement and engagement<br/