Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data.

STUDY OBJECTIVES: To characterize the incidence of pediatric narcolepsy diagnosis, subsequent care, and potential sociodemographic disparities in a large US claims database. METHODS: Merative MarketScan insurance claims (n=12,394,902) were used to identify youth (6-17 years) newly diagnosed with narcolepsy (ICD-10 codes). Narcolepsy diagnosis and care 1-year post-diagnosis included polysomnography (PSG) with Multiple Sleep Latency Test (MSLT), pharmacological care, and clinical visits. Potential disparities were examined by insurance coverage and child race and ethnicity (Medicaid-insured only). RESULTS: The incidence of narcolepsy diagnosis was 10:100,000, primarily type 2 (69.9%). Most diagnoses occurred in adolescents with no sex differences, but higher rates in Black versus White youth with Medicaid. Two-thirds had a prior sleep disorder diagnosis and 21-36% had other co-occurring diagnoses. Only half (46.6%) had a PSG with MSLT (± 1-year post-diagnosis). Specialty care (18.9% pulmonary, 26.9% neurology) and behavioral health visits were rare (34.4%), although half were prescribed stimulant medications (51.0%). Medicaid-insured were 86% less likely than commercially insured youth to have any clinical care and 33% less likely to have a PSG with MSLT. CONCLUSIONS: Narcolepsy diagnoses occurred in 0.01% of youth, primarily during adolescence, and at higher rates for Black versus White children with Medicaid. Only half had evidence of a diagnostically required PSG with MSLT, underscoring potential misdiagnosis. Many patients had co-occurring conditions, but specialty and behavioral health care were limited. Results suggest misdiagnosis, underdiagnosis, and limited narcolepsy treatment, as well as possible insurance-related disparities. Results highlight the need to identify determinants of evidence-based pediatric narcolepsy diagnosis and management.

Energetic Demands Regulate Sleep-Wake Rhythm Circuit Development.

Sleep and feeding patterns lack a clear daily rhythm during early life. As diurnal animals mature, feeding is consolidated to the day and sleep to the night. Circadian sleep patterns begin with formation of a circuit connecting the central clock to arousal output neurons; emergence of circadian sleep also enables long-term memory (LTM). However, the cues that trigger the development of this clock-arousal circuit are unknown. Here, we identify a role for nutritional status in driving sleep-wake rhythm development in Drosophila larvae. We find that in the 2nd instar (L2) period, sleep and feeding are spread across the day; these behaviors become organized into daily patterns by L3. Forcing mature (L3) animals to adopt immature (L2) feeding strategies disrupts sleep-wake rhythms and the ability to exhibit LTM. In addition, the development of the clock (DN1a)-arousal (Dh44) circuit itself is influenced by the larval nutritional environment. Finally, we demonstrate that larval arousal Dh44 neurons act through glucose metabolic genes to drive onset of daily sleep-wake rhythms. Together, our data suggest that changes to energetic demands in developing organisms triggers the formation of sleep-circadian circuits and behaviors.

Neurofibromin 1 regulates early developmental sleep in Drosophila.

Sleep disturbances are common in neurodevelopmental disorders, but knowledge of molecular factors that govern sleep in young animals is lacking. Evidence across species, including Drosophila, suggests that juvenile sleep has distinct functions and regulatory mechanisms in comparison to sleep in maturity. In flies, manipulation of most known adult sleep regulatory genes is not associated with sleep phenotypes during early developmental (larval) stages. Here, we examine the role of the neurodevelopmental disorder-associated gene Neurofibromin 1 (Nf1) in sleep during numerous developmental periods. Mutations in Neurofibromin 1 (Nf1) are associated with sleep and circadian disorders in humans and adult flies. We find in flies that Nf1 acts to regulate sleep across the lifespan, beginning during larval stages. Nf1 is required in neurons for this function, as is signaling via the Alk pathway. These findings identify Nf1 as one of a small number of genes positioned to regulate sleep across developmental periods.