Neuromuscular Disorders in Pediatric Respiratory Disease.

Respiratory sequelae are a frequent cause of morbidity and mortality in children with NMD. Impaired cough strength and resulting airway clearance as well as sleep disordered breathing are the two main categories of respiratory sequelae. Routine clinical evaluation and diagnostic testing by pulmonologists is an important pillar of the multidisciplinary care required for children with NMD. Regular surveillance for respiratory disease and timely implementation of treatment including pulmonary clearance techniques as well as ventilation can prevent respiratory related morbidity including hospital admissions and improve survival. Additionally, novel disease modifying therapies for some NMDs are now available which has significantly improved the clinical trajectories of patients resulting in a paradigm shift in clinical care. Pulmonologists are 'learning' the new natural history for these diseases and adjusting clinical management accordingly.

Polysomnographic findings in children with 22q deletion & duplication syndrome: relationship to genetic diagnosis, parent-reported symptoms, and calcium levels.

PURPOSE: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome. In the current study, we assessed the relationship between parent-reported symptoms of obstructive sleep apnea (OSA) and polysomnographic (PSG) results in patients with 22q11.2DS. Additionally, we explored the relationships between genetic diagnosis, serum calcium and ferritin levels, and PSG results. METHODS: Retrospective chart review was completed for patients enrolled in our 22q Center's registry from 2015-2021. Data extracted included: patient characteristics, parent-reported sleep symptoms from the Childhood Sleep Habits Questionnaire (CSHQ), serum calcium and ferritin levels, and results from formal PSG. RESULTS: Overall, n = 89 encounters (60 unique patients) with PSG data demonstrated that there were no differences in OSA between those with deletion vs duplication, but PLMD was more common in those with deletion (35% vs 7%, p = 0.032). In a subset of n = 24 encounters with PSG and survey data in proximity, there were no significant associations between the CSHQ sleep-disordered breathing subscale and OSA presence or severity (p = 0.842). Likewise, we found no significant associations between the individual symptoms of OSA and PSG results (all p > 0.5). In those patients with available calcium (n = 44) and ferritin (n = 17) levels, we found a significant negative correlation between serum calcium and PLMS (r = -0.446, p = 0.002), but not ferritin (r = -0.067, p = 0.797) levels. CONCLUSIONS: Parent-reported symptoms do not predict the presence or severity of OSA in children with 22q11.2DS. There was a negative correlation between serum calcium, but not ferritin, and PLMS on PSG.

Images: Polysomnographic artifact in a patient with Tourette syndrome.

Patients with Tourette syndrome frequently have sleep disturbances that may require polysomnographic testing. The use of deep brain stimulators is increasing with expanding indications including children with medically intractable Tourette syndrome. It is important to understand the effect the stimulator can have on polysomnographic monitoring. Herein we present an interesting case of an adolescent with medically intractable Tourette syndrome with a deep brain stimulator implant who underwent a polysomnogram demonstrating rhythmic, monomorphic artifact. CITATION: Bindra T, Ingram DG. Images: Polysomnographic artifact in a patient with Tourette syndrome. J Clin Sleep Med. 2023;19(12):2149-2151.

Sleep Technology.

Pediatric sleep providers frequently encounter issues related to sleep technology in clinical settings. In this review article, we discuss technical issues related to standard polysomnography, research on putative complementary novel metrics derived from polysomnographic signals as well as research on home sleep apnea testing in children and consumer sleep devices. Although developments across several of these domains are exciting, it remains a rapidly evolving area. When evaluating innovative devices and home sleep testing approaches, clinicians should be mindful of accurately interpreting diagnostic agreement statistics to apply these technologies appropriately.

Sleep profiles in children with 22q deletion syndrome: a study of 100 consecutive children seen in a multidisciplinary clinic.

STUDY OBJECTIVES: While previous studies have suggested a high prevalence of sleep disorders in children with 22q deletion syndrome (22qDS), they were limited by potential selection bias. In the current investigation, we assessed sleep characteristics in 100 consecutive children presenting to a 22qDS multidisciplinary clinic. METHODS: An observational retrospective case series of consecutive children presenting to 22qDS multidisciplinary clinic was performed. Children aged 2 to 17 years of age were included, and data were abstracted including sleep characteristics (sleep history, Childhood Sleep Habits Questionnaire [CSHQ], and free response questions), comorbid medical conditions, and demographics. RESULTS: Overall, 100 children were included in analysis, 85% of whom had scores on the CSHQ consistent with clinically meaningful sleep disorder. Sleep problems were common in all domains of the CSHQ, including daytime sleepiness (66%), sleep-onset delay (54%), parasomnias (52%), night wakings (52%), sleep-disordered breathing (49%), sleep duration (45%), bedtime resistance (38%), and sleep anxiety (33%). Overall CSHQ score was significantly associated with daytime behavioral problems and speech delay [F(2,97) = 10.4, P < .001, adjusted R2 = 0.16]. The most common interventions reported to be helpful for sleep by parents were behavioral (routine, bedtime story), environmental (light avoidance at night, calming music), and pharmacologic (melatonin, clonidine). CONCLUSIONS: These data confirm a high prevalence of sleep disorders in a large, unselected sample of children with 22qDS, and suggest an important relationship between sleep dysfunction and daytime behavioral challenges. Our findings highlight the potential role for multimodal treatment approaches including behavioral, environmental, and pharmacologic interventions. CITATION: Ingram DG, Raje N, Arganbright JM. Sleep profiles in children with 22q deletion syndrome: a study of 100 consecutive children seen in a multidisciplinary clinic. J Clin Sleep Med. 2023;19(1):27-34.

Sleep Disorders in Children with Prader Willi Syndrome: Current Perspectives.

Children with Prader-Willi syndrome (PWS) face a multitude of potential health challenges including life-threatening obesity, endocrinopathies, behavioral and emotional dysregulation, developmental delays, and sleep disorders. In the current perspective piece, we provide a focused review of the condition's etiology and clinical findings, as well as a more in-depth discussion of sleep disorders frequently associated with PWS. In particular, we highlight and discuss difficult clinical scenarios frequently encountered by the pediatric sleep physician caring for this patient population, including diagnosis and treatment of complex sleep-related breathing disorders, considerations for sleep apnea surgery, the interplay between growth hormone and sleep apnea, diagnostic challenges in hypersomnia/narcolepsy, and current and emerging therapies for hypersomnia/narcolepsy. Overall, although there are many areas that need further research, sleep disorders remain a fruitful target for improving quality of life of children with PWS and their families.

Intravenous iron therapy in the pediatric sleep clinic: a single institution experience.

STUDY OBJECTIVES: Initial reports of intravenous (IV) iron administration have been promising for children with restless legs syndrome, periodic limb movement disorder, and restless sleep disorder. The aim of the current study was to evaluate further the clinical response to IV iron supplementation in children seen in a pediatric sleep clinic. METHODS: We performed a retrospective chart review of children cared for in a single pediatric sleep clinic who also underwent IV iron infusion. Pre and post IV data regarding their sleep symptoms and ferritin levels were abstracted. RESULTS: Overall, 63 pediatric sleep patients underwent IV iron infusion, mostly with ferric carboxymaltose (n = 60), for restless legs syndrome (n = 30), periodic limb movement disorder (n = 22), and restless sleep disorder (n = 17). Of the 59 patients with clinical follow-up, 39 (73%) noted improvement in at least 1 symptom, and 14 (26%) did not notice improvement or noticed worsening symptoms. Of the 59 patients with preinfusion and postinfusion labs, the average ferritin level increased from 21.7 (13.3) to 147.9 (120.9) µg/L, P < .001. Comparing patients who experienced clinical improvement vs those who did not, there were no statistically significant differences in change in ferritin levels (P = .278), sex (P = .452), or age (P = .391). Ferritin change with infusion according to diagnostic subgroups (restless legs syndrome/periodic limb movement disorder/restless sleep disorder) was examined, and no significant differences were noted (F(2,56) = 0.852, P = .432). In terms of immediate adverse reactions to the IV infusion, 7 (11%) experienced at least 1 side effect, with the most common being behavior change (n = 6) or gastrointestinal discomfort (n = 4); no episodes of anaphylaxis or extravasation were noted. CONCLUSIONS: These data provide additional support for the efficacy and safety of IV iron for pediatric restless legs syndrome, periodic limb movement disorder, and restless sleep disorder recalcitrant to oral iron. CITATION: Ingram DG, Al-Shawwa B, DelRosso LM, Sharma M. Intravenous iron therapy in the pediatric sleep clinic: a single institution experience. J Clin Sleep Med. 2022;18(11):2545-2551.

Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance.

The relation between iron deficiency and restless legs syndrome has been widely described and investigated in both adults and children. However, the diagnosis of restless legs syndrome relies on patients voicing their symptoms, which is very difficult for patients younger than age 5 years. Frequently, we evaluate children between ages 2 and 4 years whom parents describe as "restless sleepers," "difficult to settle down," or having "frequent awakening" or "bedtime resistance." Parents are concerned that their child's poor sleep quality is leading to daytime dysfunction such as increased sleepiness, behavioral outbursts, or hyperactivity. Many of these children are diagnosed with behavioral insomnia of childhood, and behavior modification therapy is recommended with variable degrees of success. Herein, we describe a 2-year-old with similar symptoms of restless sleep, bedtime resistance, and daytime sleepiness who was found to have an underlying iron deficiency without anemia that was treated successfully with iron infusion. We highlight the importance of evaluating for underlying iron deficiency even without anemia in patients with restless sleep and associated poor daytime behavior. We also describe some common challenges associated with iron therapy and clarify iron therapeutic targets. CITATION: Al-Shawwa B, Sharma M, Ingram DG. Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance. J Clin Sleep Med. 2022;18(2):677-680.

Sleep Challenges and Interventions in Children With Visual Impairment.

PURPOSE: To examine sleep patterns in a large and heterogeneous group of children with visual impairment. METHODS: A cross-sectional survey of parents of children with visual impairment was offered via the National Federation of the Blind and the National Organization for Albinism and Hypopigmentation. RESULTS: Complete survey results were available for 72 participants, aged 1 to 16 years. Parents of 52 (72%) children reported that their child had cycles of good sleep and bad sleep, and 50 (69%) reported that their child's sleep patterns caused significant stress for them or their family. Scores on the Childhood Sleep Habits Questionnaire (CSHQ) increased (> 41) in 64 (89%) children, indicating a likely clinically significant sleep problem. When compared to normative data from children aged 4 to 10 years, children in the current sample scored higher (more sleep problems) on all eight subscales on the CSHQ. The presence of comorbid developmental delay was most strongly associated with sleep problems. Supplemental melatonin and improving daytime and nighttime schedules or routines were reported as the most helpful for sleep. Many families reported a need for further information regarding melatonin use as a supplement. CONCLUSIONS: A high proportion of children with visual impairment experience clinically meaningful sleep problems, regardless of degree of light perception or visual acuity. There is a strong need for increased awareness and screening for sleep problems in this population. Potential treatment modalities, including supplemental melatonin, should be discussed with families. [J Pediatr Ophthalmol & Strabismus. 2022;59(2):77-86.].

Enuresis and sleep fellowship education.

PURPOSE: Enuresis is a common sleep-related concern in school aged children that gradually decreases into adulthood. We performed a survey of sleep providers in order to assess their comfort level in managing patients with enuresis. METHODS: Survey participants were recruited via the Pedsleep listserv and sleep medicine program directors in the USA on basecamp application. The Pedsleep list includes a mixture of physicians, psychologists, and other sleep providers/researchers. RESULTS: Forty-two sleep providers completed the survey. Forty (95%) were board certified in sleep medicine, and 32 (76%) were board certified in pediatrics. Practice patterns for management of enuresis varied among respondents, with 69% who evaluate for possible contributions from other sleep disorders such as obstructive sleep apnea then refer for additional management. Nineteen (45%) respondents felt that they received inadequate or very inadequate training during their sleep fellowship for management of enuresis. While 83% of respondents worked in an academic medical center setting, none of their respective sleep clinics were the primary managing clinic at their own situation. Participants who endorsed their training as adequate/very adequate were significantly more likely to feel comfortable/very comfortable managing enuresis (90% vs 37.5%, p = 0.009). CONCLUSIONS: A large percentage of sleep providers are lacking essential training to manage enuresis patients. These results suggest the need for additional educational initiatives in this area.

The challenges in scoring hypopneas in children: is pulse wave amplitude drop the answer?

BACKGROUND: Identifying electroencephalogram (EEG) cortical arousals are crucial in scoring hypopneas and respiratory efforts related arousals (RERAs) during a polysomnogram. As children have high arousal threshold, many of the flow limited breaths or hypopneas may not be associated with visual EEG arousals, hence this may lead to potential underestimation of the degree of sleep disordered breathing. Pulse wave amplitude (PWA) is a signal obtained from finger photoplethysmography which correlates directly to finger blood flow. The drop in PWA has been shown to be a sensitive marker for subcortical/autonomic and cortical arousals. Our aim was to use the drop in PWA as a surrogate for arousals to guide scoring of respiratory events in pediatric patients. METHODS: Ten polysomnograms for patients between the ages of 5-15 years who had obstructive apnea-hypopnea indices between 1 and 5 events/hour were identified. Patients with syndromes were excluded. A drop in PWA signal of at least 30% that lasted for 3 s was needed to identify subcortical/autonomic arousals. Arousals were rescored based on this criteria and subsequently respiratory events were rescored. Paired t-tests were employed to compare PSG indices scored with or without PWA incorporation. RESULTS: The sample of 10 children included 2 females, and the average age was 9.8 ± 3.1 years. Overall, polysomnography revealed an average total sleep time of 464.1 ± 25 min, sleep efficiency of 92% +/-4.2, sleep latency of 19.6 ± 17.0 min, rapid eye movement (REM) latency 143 ± 66 min, N1 3.9% +/-2.0, N2 50.3% +/-12.0, N3 28.2% +/-9.1, REM 16.7% +/-4.0, and wakefulness after sleep onset (WASO) 18.1 ± 7.5 min. Including arousals from PWA changes, respiratory indices significantly increased including total AHI (2.3 ± 0.7 vs 5.7 ± 2.1, p < 0.001), obstructive AHI (1.45 ± 0.7 vs 4.8 ± 1.8, p < 0.001), and RDI (2.36 ± 0.7 vs 7.6 ± 2.0, p < 0.001). Likewise, total arousal index was significantly higher (8.7 ± 2.3 vs 29.4 ± 6.5, p < 0.001). CONCLUSIONS: The drop in pulse wave amplitude signal is a useful marker to guide scoring arousals that are not otherwise easily identified in pediatric polysomnography and subsequently helped in scoring respiratory events that otherwise would not be scored. Further studies are needed to delineate if such methodology would affect clinical outcome.

Innovating and adapting in pediatric pulmonology and sleep medicine during the COVID-19 pandemic: ATS pediatric assembly web committee consensus statement for initial COVID-19 virtual response.

Coronavirus disease 2019 (COVID-19) has been an unprecedented and continuously evolving healthcare crisis. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread rapidly and initially little was known about the virus or the clinical course for infected children. In the United States of America, the medical response has been regionalized, based on variation in community transmission of the virus and localized outbreaks. Pediatric pulmonary and sleep divisions evolved in response to administrative and clinical challenges. As the workforce transitioned to working remotely, video conferencing technology and multicenter collaborative efforts were implemented to create clinical protocols. The COVID-19 pandemic challenges the framework of current medical practice but also highlights the dynamic and cooperative nature of pediatric pulmonology and sleep medicine. Our response to this pandemic has laid the groundwork for future challenges.

Small sleepers, big data: leveraging big data to explore sleep-disordered breathing in infants and young children.

STUDY OBJECTIVES: Infants represent an understudied minority in sleep-disordered breathing (SDB) research and yet the disease can have a significant impact on health over the formative years of neurocognitive development that follow. Herein we report data on SDB in this population using a big data approach. METHODS: Data were abstracted using the Cerner Health Facts database. Demographics, sleep diagnoses, comorbid medication conditions, healthcare utilization, and economic outcomes are reported. RESULTS: In a cohort of 68.7 million unique patients, over a 9-year period, there were 9,773 infants and young children with a diagnosis of SDB (obstructive sleep apnea [OSA], nonobstructive sleep apnea, and "other" sleep apnea) who met inclusion criteria, encompassing 17,574 encounters, and a total of 27,290 diagnoses across 62 U.S. health systems, 172 facilities, and 3 patient encounter types (inpatient, clinic, and outpatient). Thirty-nine percent were female. Thirty-nine percent were ≤1 year of age (6,429 infants), 50% were 1-2 years of age, and 11% were 2 years of age. The most common comorbid diagnoses were micrognathia, congenital airway abnormalities, gastroesophageal reflux, chronic tonsillitis/adenoiditis, and anomalies of the respiratory system. Payor mix was dominated by government-funded entities. CONCLUSIONS: We have used a novel resource, large-scale aggregate, de-identified EHR data, to examine SDB. In this population, SDB is multifactorial, closely linked to comorbid medical conditions and may contribute to a significant burden of healthcare costs. Further research focusing on infants at highest risk for SDB can help target resources and facilitate personalized management.

Perceived challenges in pediatric narcolepsy: a survey of parents, youth, and sleep physicians.

STUDY OBJECTIVES: To clarify the most common and problematic symptoms, psychosocial challenges, and comorbidities among youth with narcolepsy based on input from key stakeholders. METHODS: A nationwide cross-sectional survey of youth with narcolepsy, parents, and sleep physicians. RESULTS: Overall, 116 parents, 35 youth, and 30 providers completed the entire survey. Symptoms that were rated as most common and problematic by both parents and youth were (in descending order) as follows: daytime sleepiness, disturbed nighttime sleep, mood challenges, cataplexy, sleep-related hallucinations, and sleep paralysis. Most of the 18 queried psychosocial concerns were identified as substantial challenges by both adults and youth, including difficulty focusing and memory, school, worry and anxiety, diet and nutrition, lack of motivation, mood problems, and relationship problems. In contrast, while physicians did recognize some of these challenges, they rated medication side effects and driver's license issues as relatively greater challenges. CONCLUSIONS: These data highlight the high prevalence of psychosocial challenges, discordance between physician and family ratings of challenges, and a high rate of medical comorbidities in youth with narcolepsy and support the application of a biopsychosocial framework in the assessment and treatment of pediatric narcolepsy.

Treatment and care delivery in pediatric narcolepsy: a survey of parents, youth, and sleep physicians.

STUDY OBJECTIVES: To describe the most commonly used treatments in pediatric narcolepsy and their perceived effectiveness, as well as to elicit key stakeholder perspectives on the most optimal manner in which care ought to be delivered to youth with narcolepsy. METHODS: A cross-sectional survey of youth with narcolepsy, parents, and sleep physicians. RESULTS: Complete survey results were available for 35 youth with narcolepsy, 116 parents, and 30 sleep physicians. Overall there was general agreement among family and physicians regarding most effective treatments, including both pharmacologic (stimulants, sodium oxybate, and modafinil/armodafinil) and nonpharmacologic (sleep schedule, exercise, diet) approaches. There was a stronger interested in cannabidiol oil (CBD) from families compared to physicians. Both families and physicians also endorsed a need for multispecialty care, ideally delivered in a same day setting and including specialists in mental health, social work, and nutrition. Quality measures were felt to be important but are not currently tracked by most sleep physicians. Qualitative responses highlight the value families place on providers who listen well and remain open-minded. CONCLUSIONS: Our results suggest strong support by key stakeholders for an interdisciplinary approach to care for youth with narcolepsy.