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Introduction Kleine Levin Syndrome (KLS), or recurrent hypersomnia, is a rare sleep disorder characterized by recurrent episodes of severe hyper-somnolence lasting several days to several weeks. Because the etiology is unknown, treatment is mostly supportive. Some pharmacologic agents have been attempted to treat symptoms during episodes with limited success. Report of case(s) Patient is a 17 year-old with a history attention-deficit hyperactivity disorder and generalized anxiety disorder who presented to the clinic due to recurrent episodes of severe hypersomnolence associated with derealization and cognitive dysfunction during all episodes, anxiety of being alone, and other symptoms in some episodes such as altered taste affecting appetite, and binge eating. The patient was diagnosed with KLS and tracked episodes which lasted 11-12 days (average) with recurrence every 10-17 days. Labs, 72 hour EEG, MRI and MRA were largely unremarkable. The family declined trial of Lithium. Pharmacogenetic testing showed significant gene-drug interaction with duloxetine requiring higher drug dosage for effects. After psychiatry started duloxetine, the patient experienced a 7 month period without episodes. Then episodes recurred for unclear reason while on duloxetine but with slightly less duration (6-12 days) and shorter time between episodes. Duloxetine was discontinued due to lack of mood effects. Clarithromycin was trialed next for use during episodes without changes. Episodes were tracked for several months with some predictability. Duloxetine was restarted a second time after several months, and the patient showed mild improvement in event duration down to 8-11 days for a few months. Time between episodes also shortened to 8-10 days. Anxiety was only slightly reduced between and during the episodes, though they still continued to struggle with derealization and ability to focus during episodes that effected school and work functioning. Interestingly, they also started to have more insomnia between episodes while on duloxetine. Conclusion KLS is a rare disorder with limited data on effective treatments. To date, this is the first report of a prolonged brief KLS remission with duloxetine. Norepinephrine and serotonin modulation may limit episode duration. More research is needed to determine whether duloxetine can modulate the effects of KLS. Support (if any) None

Introduction The pivotal phase 3 REST-ON trial (NCT02720744) evaluated the efficacy and safety of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation for treatment of adults with narcolepsy. In REST-ON, ON-SXB met its 3 coprimary endpoints: improvement in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement rating (% much/very much improved), and number of weekly cataplexy attacks at all doses tested (P< 0.001 vs placebo). The safety profile of ON-SXB was consistent with that of immediate-release (IR) SXB. The ongoing RESTORE trial (NCT04451668) is an open-label/switch study evaluating the safety and tolerability of ON-SXB. Methods Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive are eligible for RESTORE. Initial doses were 4.5 g/night or equivalent/closest to the previous total IR oxybate dose/night for those switching; incremental adjustments (1.5 g/week; maximum dose, 9 g/night) were allowed. Safety data for participants receiving ≥1 dose of ON-SXB as of 01 July 2022 are reported here. Results This analysis includes interim data from 180 participants (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]); mean age is 35 years [range, 16–84]). Most participants who reported an adverse event (AE; n=105 [58.3%]) had AEs that were mild (61.9%) or moderate (32.3%) in severity. Three participants had serious AEs (abscess, deep vein thrombosis, rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and all 3 participants continued in the study. Adverse drug reactions (ADRs; ie, AEs related/possibly related to study drug) were reported by 76 (42.2%) participants with 6 (3.3%) participants discontinuing ON-SXB owing to ADRs. ADRs occurring in ≥3% of participants were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%). Conclusion Interim data from the RESTORE study indicate that ON-SXB is generally well tolerated with a low rate of discontinuation owing to ADRs. If granted final FDA approval, ON-SXB will offer adults with narcolepsy a once-at-bedtime oxybate treatment option. Support (if any) Avadel Pharmaceuticals

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6 ± 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p

Introduction Restless Sleep Disorder (RSD) is characterized by frequent nocturnal movements of large muscle groups or a complaint of restless sleep by observers with associated daytime dysfunction.1 RSD, like other movement disorders of sleep, is associated with low iron stores.2 Children with RSD have increased NREM sleep instability and a propensity for parasomnia.2 No reports to date have demonstrated the use of iron therapy for parasomnia in patients with RSD. Furthermore, studies are limited in very young children with this disorder as they currently fall outside proposed diagnostic criteria.1 Report of Cases: A 2 year-old male presented to the sleep clinic with parental complaints of nightly sleep initiation and maintenance difficulty, mild snoring, restless sleep, episodes of sleepwalking and night terrors multiple times per week. Symptoms worsened over 6 months and were associated with daytime irritability and behavioral problems. Sleep quality measures assessed progress between visits: the PROMIS Sleep Disturbance (PROMIS SD) and Sleep Related Impairment (PROMIS SRI). Serum ferritin was initially 20ug/L. Polysmnogram demonstrated no significant sleep related breathing disorder, a large muscle group movement index of 14, periodic limb movement index of 3. Initial treatment included oral iron therapy, scheduled awakenings, and hypnotic dose melatonin. The sleep psychologist addressed limit setting and negative sleep associations with improved insomnia symptoms but parasomnia and restless sleep continued. The parent noted reduction in both movements and parasomnia frequency after one month of iron therapy. After a 3 month period on treatment, the parent reported complete cessation of the parasomnia, drastic reduction in restlessness, and near resolution of insomnia. Sleep quality measure PROMIS SD improved by 11, demonstrating reduced sleep disturbance. PROMIS SRI did not change. Ferritin level increased to 47ug/L. Conclusion RSD in a very young child with NREM parasomnia responded to oral iron therapy improving overall sleep quality. This case demonstrates the relationship between relative iron deficiency, RSD and associated parasomnia. Support (If Any) 1. DelRosso LM, Ferri R, Allen RP, et al. Consensus diagnostic criteria for a newly defined pediatric sleep disorder: restless sleep disorder(RSD).SleepMed.2020;75:335-340. 2. Leung W, Singh I, McWilliams S, Stockler S, Ipsiroglu OS. Iron deficiency and sleep - A scoping review. SleepMedRev.2020;51:101274

Introduction Narcolepsy is a central disorder of hypersomnia with a bimodal peak incidence at ages 15 and 35. Onset in early childhood has been reported, but rarely under the age of 5. We present a case of Narcolepsy Type 1 in a 2.5-year-old with dropping spells. Report of case(s) A 2.5-year-old African American healthy male presented with acute onset sudden drops, unsteady gait, and staring spells. These episodes lasted a few seconds, occurred multiple times a day, and were associated with eye fluttering and dysarthric speech. History was notable for increased daytime sleep/sleep attacks, disrupted nocturnal sleep with confusional arousals, nightmares and sleepwalking, weight gain and mood instability with aggressive behavior. No preceding head injury or illness. Physical examination demonstrated frequent atonic episodes with loss of deep tendon reflexes. A clinical suspicion of myoclonic/atonic epilepsy prompted video- electroencephalogram (EEG) which showed frequent bursts of generalized intermittent slowing representative of NREM 1 sleep lasting several seconds. Magnetic resonance imaging of the brain and infectious workup was unremarkable. Cerebrospinal fluid (CSF) Orexin was Conclusion This case demonstrates an unusual presentation of Narcolepsy Type 1 in a toddler initially thought to have epilepsy. Video-EEG and low CSF orexin led to the diagnosis. His age, severity of cataplexy, mood changes, and parental concerns made treatment challenging. Furthermore, this case highlights the importance of early recognition of Narcolepsy in young children to provide appropriate treatment during critical developmental stages. Support (if any)