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Obstructive sleep apnea (OSA) remains a highly prevalent disorder that can lead to multiple adverse outcomes when undiagnosed and/or when left untreated. There continue to be gaps and variations in the provision of care for the adult patient population with OSA, which emphasizes the importance of the measure maintenance initiative for The Quality Measures for the Care of Adult Patients with Obstructive Sleep Apnea (originally developed in 2015). The American Academy of Sleep Medicine (AASM) convened the Quality Measures Task Force in 2018 to review the current medical literature, other existing quality measures focused on the same patient population, and any performance data or data in the medical literature that show gaps or variations in care, to inform potential revisions to the quality measure set. These revised quality measures will be implemented in the AASM Sleep Clinical Data Registry (Sleep CDR) to capture performance data and encourage continuous improvement in outcomes associated with diagnosing and managing OSA in the adult population.Lloyd R, Morgenthaler TI, Donald R, et al. Quality measures for the care of adult patients with obstructive sleep apnea: 2022 update after measure maintenance.

Although many people suffer from sleep disorders, most are undiagnosed, leading to impairments in health. The existing polysomnography method is not easily accessible; it's costly, burdensome to patients, and requires specialized facilities and personnel. Here, we report an at-home portable system that includes wireless sleep sensors and wearable electronics with embedded machine learning. We also show its application for assessing sleep quality and detecting sleep apnea with multiple patients. Unlike the conventional system using numerous bulky sensors, the soft, all-integrated wearable platform offers natural sleep wherever the user prefers. In a clinical study, the face-mounted patches that detect brain, eye, and muscle signals show comparable performance with polysomnography. When comparing healthy controls to sleep apnea patients, the wearable system can detect obstructive sleep apnea with an accuracy of 88.5%. Furthermore, deep learning offers automated sleep scoring, demonstrating portability, and point-of-care usability. At-home wearable electronics could ensure a promising future supporting portable sleep monitoring and home healthcare.

STUDY OBJECTIVES: The central disorders of hypersomnolence (CDH) manifest with daytime sleepiness, often accompanied by cognitive symptoms. Objective tests characterizing cognitive dysfunction may have diagnostic utility. Further, because some people with CDH report worsening cognition upon awakening, cognitive testing before and after napping may provide additional diagnostic information. METHODS: Patients with CDH with idiopathic hypersomnia (n = 76), narcolepsy type 1 (n = 19), narcolepsy type 2 (n = 22), and self-reported excessive daytime sleepiness not meeting current diagnostic criteria (n = 76) and nonsleepy controls (n = 33) underwent testing with the Psychomotor Vigilance Test (PVT), a 10-minute reaction-time test. A subset of participants underwent repeat testing during a Multiple Sleep Latency Test, before and immediately after naps 2 and 4. RESULTS: Most PVT metrics were significantly better in controls than in patients with CDH. Minimal group differences in PVT performance were observed by CDH diagnosis. PVT performance was weakly correlated to Epworth Sleepiness Scale and Multiple Sleep Latency Test mean sleep latency in the CDH group. Before and after naps, PVT metrics were minimally different for controls, while PVT performance generally worsened following naps in the CDH group, with significant worsening compared with controls for nap 2 mean, median, lapses, and fastest 10% of responses and nap 4 lapses and slowest 10% of responses. Change in performance did not differ based on CDH diagnostic group for any metric on either nap. CONCLUSIONS: The PVT, at baseline and following a short nap, may provide adjunctive diagnostic utility in separating individuals with CDH from controls. CITATION: Trotti LM, Saini P, Bremer E, et al. The Psychomotor Vigilance Test as a measure of alertness and sleep inertia in people with central disorders of hypersomnolence. J Clin Sleep Med. 2022;18(5):1395–1403.

This position statement provides guidance for age and weight considerations for using continuous positive airway pressure therapy in pediatric populations. The American Academy of Sleep Medicine commissioned a task force of experts in pediatric sleep medicine to review the medical literature and develop a position statement based on a thorough review of these studies and their clinical expertise. The American Academy of Sleep Medicine Board of Directors approved the final position statement. It is the position of the American Academy of Sleep Medicine that continuous positive airway pressure can be safe and effective for the treatment of obstructive sleep apnea for pediatric patients, even in children of younger ages and lower weights, when managed by a clinician with expertise in evaluating and treating pediatric obstructive sleep apnea. The clinician must make the ultimate judgment regarding any specific care in light of the individual circumstances presented by the patient, accessible treatment options, patient/parental preference, and resources.Amos L, Afolabi-Brown O, Gault D, et al. Age and weight considerations for the use of continuous positive airway pressure therapy in pediatric populations: an American Academy of Sleep Medicine position statement.

Sleep is a biological necessity, and insufficient sleep and untreated sleep disorders are detrimental for health, well-being, and public safety. Healthy People 2030 includes several sleep-related objectives with the goal to improve health, productivity, well-being, quality of life, and safety by helping people get enough sleep. In addition to adequate sleep duration, healthy sleep requires good quality, appropriate timing, regularity, and the absence of sleep disorders. It is the position of the American Academy of Sleep Medicine (AASM) that sleep is essential to health. There is a significant need for greater emphasis on sleep health in education, clinical practice, inpatient and long-term care, public health promotion, and the workplace. More sleep and circadian research is needed to further elucidate the importance of sleep for public health and the contributions of insufficient sleep to health disparities. CITATION: Ramar K, Malhotra RK, Carden KA, et al. Sleep is essential to health: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2021;17(10):2115–2119.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. RESULTS: The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895–1945.

INTRODUCTION: This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS: The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength (“strong” or “conditional”). A “strong” recommendation (ie, “We recommend…”) is one that clinicians should follow under most circumstances. A “conditional” recommendation (ie, “We suggest…”) is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient’s values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment. ADULT PATIENTS WITH NARCOLEPSY: 1. We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG); 2. We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG); 3. We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG); 4. We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG); 5. We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL); 6. We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL); 7. We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL). ADULT PATIENTS WITH IDIOPATHIC HYPERSOMNIA: 8. We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG); 9. We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL); 10. We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL); 11. We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL); 12. We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). ADULT PATIENTS WITH KLEINE-LEVIN SYNDROME: 13. We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL). ADULT PATIENTS WITH HYPERSOMNIA DUE TO MEDICAL CONDITIONS: HYPERSOMNIA SECONDARY TO ALPHA-SYNUCLEINOPATHIES: 14. We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL); 15. We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson’s disease in adults. (CONDITIONAL); 16. We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson’s disease in adults. (CONDITIONAL). POSTTRAUMATIC HYPERSOMNIA: 17. We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL); 18. We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). ADULT PATIENTS WITH GENETIC DISORDERS ASSOCIATED WITH PRIMARY CENTRAL NERVOUS SYSTEM SOMNOLENCE: 19. We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL). ADULT PATIENTS WITH HYPERSOMNIA SECONDARY TO BRAIN TUMORS, INFECTIONS, OR OTHER CENTRAL NERVOUS SYSTEM LESIONS: 20. We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL). PEDIATRIC PATIENTS WITH NARCOLEPSY: 21. We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL); 22. We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). CITATION: Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881–1893.

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls ( n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men ( r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs while at rest, relief upon movement or getting up to walk, and worsened symptom severity at night. RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency. Genetic predisposition with a family history is common. The pathogenesis of RLS remains unclear but is likely to involve central nervous system dopaminergic dysfunction, as well as other, undefined contributing mechanisms. Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms, especially when augmentation develops. Augmentation is characterized by more intense symptom severity, earlier symptom occurrence, and often, symptom spread from the legs to the arms or other body regions. Some people with RLS have adequate symptom control with non-pharmacological measures such as massage or temperate baths. First-line management options include iron-replacement therapy in those with evidence for reduced body-iron stores or, alternatively, with prescribed gabapentin or pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine. Second-line therapies include intravenous iron infusion in those who are intolerant of oral iron and/or those having augmentation with intense, severe RLS symptoms, and opioids including tramadol, oxycodone, and methadone. RLS significantly impacts patients’ quality of life and remains a therapeutic area sorely in need of innovation and a further pipeline of new, biologically informed therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01019-4.

Objective/background Knowledge of idiopathic hypersomnia symptomatology derives from clinical case series. Web-based registries provide complementary information by allowing larger sample sizes, with greater geographic and social diversity. Patients/methods Data were obtained from the Hypersomnia Foundation's online registry. Common clinical features of idiopathic hypersomnia and other central disorders of hypersomnolence were queried, for the last thirty days and when symptoms were most severe. Symptoms were compared between idiopathic hypersomnia participants with and without long sleep durations and between participants with idiopathic hypersomnia and those with either form of narcolepsy. Frequency of medication use and residual symptoms on medication were evaluated. Results Five-hundred sixty-three registry respondents were included, with idiopathic hypersomnia (n = 468), narcolepsy type 2 (n = 44), and narcolepsy type 1 (n = 51). “Brain fog,” poor memory, and sleep drunkenness were all present in most idiopathic hypersomnia respondents, with brain fog and sleep drunkenness more commonly endorsed by those with long sleep durations. Eighty-two percent of participants with idiopathic hypersomnia were currently treated with medication, most commonly traditional psychostimulants such as amphetamine salts. Among treated patients, symptoms improved while on medication, but substantial residual hypersomnia symptoms remained. Participants with narcolepsy type 1 were more likely than those with idiopathic hypersomnia to endorse intentional and unintentional daytime naps and automatic behaviors. Conclusions Symptoms of idiopathic hypersomnia extend well beyond excessive daytime sleepiness, and these symptoms frequently persist despite treatment. These findings highlight the importance of online registries in identifying gaps in the use and effectiveness of current treatments.

Despite its high frequency in narcolepsy type 1(NT1), disrupted nocturnal sleep (DNS) remains understudied, and its determinants have been poorly assessed. We aimed to determine the clinical, polysomnographic (PSG), and biological variables associated with DNS in a large sample of patients with NT1, and to evaluate the effect of medication on DNS and its severity.Two hundred and forty-eight consecutive adult patients with NT1 (145 untreated, 103 treated) were included at the National Reference Center for Narcolepsy-France; 51 drug-free patients were reevaluated during treatment. DNS, assessed with the Narcolepsy Severity Scale (NSS), was categorized in four levels (absent, mild, moderate, severe). Clinical characteristics, validated questionnaires, PSG parameters (sleep fragmentation markers: sleep (SB) and wake bouts (WB), transitions), objective sleepiness, and orexin-A levels were assessed.In drug-free patients, DNS severity was associated with higher scores on NSS, higher sleepiness, anxiety/depressive symptoms, autonomic dysfunction, worse quality of life (QoL). Patients with moderate/severe DNS (59%) had increased sleep onset REM periods, lower sleep efficiency, longer wake after sleep onset, more N1, SB, WB, sleep instability, transitions. In treated patients, DNS was associated with the same clinical data, and antidepressant use; but only with longer REM sleep latency on PSG. During treatment, sleepiness, NSS scores, depressive symptoms decreased, as well as total sleep time, WB, SB, transitions. DNS improved in 55% of patients, without predictors except more baseline anxiety.DNS complaint is frequent in NT1, associated with disease severity based on NSS, several PSG parameters, and objective sleepiness in untreated and treated conditions. DNS improves with treatment. We advocate the systematic assessment of this symptom and its inclusion in NT1 management strategy.

The scent of lavender has been purported to promote sleep in patients with neurodegenerative disease, but an obvious paradox is how, given the widely recognized deficits in olfaction observed in such patients, such an effect could occur. In this study we examined the ability of Parkinson’s Disease patients to discriminate lavender from rose in a forced-choice discrimination task. Results indicated that most Parkinson’s patients could not discriminate lavender above chance, although about a third were able to do so. This preserved ability was unrelated to disease severity or years with diagnosis. It was unrelated to age- and sex-adjusted performance on a standardized test of olfaction (University of Pennsylvania Smell Identification Test). These results were compatible with lavender’s potential impact via trigeminal afferents and leave open the possibility that lavender could indeed impact sleep in some patients with neurodegenerative disease.

Many questionnaires have been proposed to collect data related to dream enactment. These are typically validated by reference to objective measurements of polysomnography, which incorporate physiologic recording of muscle activity during sleep. Another approach to such questionnaire validation would be the direct behavioral observations of patients' sleep. In the course of an ongoing study, we examined the association between sleep technologists' observations of dream enactment on two consecutive sleep laboratory nights and patients' and bedpartners' responses on the University of Michigan REM Behavior Disorder Questionnaire (UMRBDQ). Results suggested good correspondence between laboratory-based observations and questionnaire responses that did not appear to be impacted by whether the patient or the bedpartner completed the questionnaire. These results suggest utility of the UMRBDQ to identify individuals who have dream enactment during sleep.

Purpose of review This article discusses the central disorders of hypersomnolence, a group of disorders resulting in pathologic daytime sleepiness, particularly narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, and Kleine-Levin syndrome. Disease features, diagnostic testing, epidemiology, pathophysiology, and treatment are reviewed. Recent findings Increasing evidence implicates autoimmunity in narcolepsy type 1, including a strong association with human leukocyte antigen-DQB1*06:02, association with a polymorphism in the T-cell receptor alpha locus in genome-wide association, and the identification of autoreactive T cells in patients with this type of narcolepsy. In contrast, the cause or causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Multiple treatment options exist, including two medications approved for the treatment of narcolepsy by the US Food and Drug Administration (FDA) in 2019. These include solriamfetol, a dopamine- and norepinephrine-reuptake inhibitor, and pitolisant, an H3-inverse agonist/antagonist that increases histaminergic neurotransmission. Summary The central disorders of hypersomnolence all cause severe sleepiness but can be differentiated based on ancillary symptoms, diagnostic testing, and pathophysiology. It is important that these disorders are identified because multiple treatments are available to improve functioning and quality of life.

Background Insomnia is one of the most common nonmotor features of Parkinson's disease (PD). However, there are few practical guidelines for providers on how to best evaluate and treat this problem. Methods and Findings This review was developed to provide clinicians with a pragmatic approach to assessing and managing insomnia in PD. Recommendations were based on literature review and expert opinion. We addressed the following topics in this review: prevalence of insomnia in PD, sleep–wake mechanisms, theoretical models of insomnia, risk factors, assessment, pharmacologic and nonpharmacologic treatments. Insomnia treatment choices may be guided by PD severity, comorbidities, and patient preference. However, there is limited evidence supporting pharmacotherapy and nonpharmacologic treatments of insomnia in PD. Conclusions We provide a pragmatic algorithm for evaluating and treating insomnia in PD based on the literature and our clinical experience. We propose personalized insomnia treatment approaches based on age and other issues. Gaps in the existing literature and future directions in the treatment of insomnia in PD are also highlighted.

Background/Objective Restless legs syndrome (RLS) is a neurological disorder with a strong genetic susceptibility. A painful RLS sub-phenotype has been described previously but the neurobiological basis for this phenotypic variant remains unknown. This study investigated whether any of the six initially discovered genomic loci associating with RLS (BTBD9, MEIS1, PTPRD, MAP2K5/SKOR1, TOX3, and an intergenic region on chromosome 2), were more strongly associated with complaints of painful versus non-painful RLS. Methods RLS patients (N = 199; Age = 53.1 ± 16.8; 100% Caucasians; 57% women) diagnosed clinically were genotyped for known variants associating with RLS. Definition of painful RLS required that subjects selected “painful” from a list of 14 adjectives to describe their RLS sensory experience and answered positively to a separate question that queried specifically as to whether they perceived their RLS sensations as painful. Genotype association tests employed logistic regression analyses with assumption of an additive genetic model. Analyses were performed using PLINK software v1.07. Results We identified two RLS patient subgroups: a painful (n = 41) and non-painful (n = 158). Among 10 tested SNPs, only rs3104767 (related to the TOX3 gene locus) was more associated with painful RLS. The minor allele T of SNP rs3104767 was associated with an increased risk of RLS being perceived as painful with an OR of 1.67 [CI = (1.01–2.74); p = 0.049]. Notably, this minor T allele associated with pain sensation in RLS patients in this study was the non-risk allele for RLS in the original RLS genome wide association study, but a similar trend was observed in a recent Parkinson disease sample study. Conclusion This study might suggest the TOX3 gene variant as a potential genetic substrate for the painful RLS sub-phenotype. This was an exploratory small study and correction for multiple comparisons would have rendered the results not significant. Therefore, the above findings require replication in larger clinical as well as population-based samples of RLS subjects.

Background: The association between restless legs syndrome (RLS) and Parkinson’s disease (PD) remains controversial, with epidemiologic and descriptive evidence suggesting some potential overlap while mechanistic/genetic studies suggesting relative independence of the conditions. Objective: To examine a known, objectively measured endophenotype for RLS, periodic leg movements (PLMS) in sleep, in patients with PD and relate that objective finding to restless legs symptoms. Methods: We performed polysomnography for one (n = 8) or two (n = 67) consecutive nights in 75 PD patients and examined the association of PLMS with restless legs symptoms. Results: We found no association between restless legs symptoms and PLMS in PD. Prevalence of both was similar to data reported previously in other PD samples. Conclusion: We interpret these results as suggesting that restless legs symptoms in PD patients may represent a different phenomenon and pathophysiology than RLS in the non-PD population.

PURPOSE OF REVIEW: The pathophysiology of idiopathic hypersomnia remains unclear, but some of its clinical features suggest the possibility of circadian dysfunction. This review will provide an overview of recent studies of circadian biology that have begun to elucidate the potential role of circadian rhythm dysfunction in idiopathic hypersomnia. RECENT FINDINGS: Clinically, people with idiopathic hypersomnia tend to have both a late chronotype and prominent sleep inertia or sleep drunkenness. Melatonin and cortisol profiles in people with IH confirm this tendency toward phase delay. More recently, it has been suggested that the night phase as defined by melatonin profile or period length as defined by BMA1 in dermal fibroblasts may also be prolonged in people with IH. Additionally, amplitude of melatonin rhythm and circadian gene expression, particularly BMAL1, PER1, and PER2, may be impaired in this disease. SUMMARY: Clinical features, melatonin profiles, and circadian gene expression all suggest abnormalities of the circadian system may be a contributor to the pathogenesis of IH.

Introduction Questionnaires that inquire about REM sleep behavior disorder are typically validated by reference to polysomnographic findings of REM sleep without atonia. We sought validation for such a questionnaire by examining observed REM-based dream enactment over two nights in a sleep laboratory. Methods Participants with alpha-synucleinopathic disease underwent two consecutive nights of polysomnography attended by a single sleep technologist who was instructed to observe for and document any abnormal behaviors occurring out of sleep. We evaluated University of Michigan REM Behavior Disorder Questionnaire responses completed by either the participant or bed-partner prior to polysomnographic recording and analyzed associations between questionnaire responses and observational data in the sleep laboratory. We subsequently cross-validated the technologist’s observations with hypnogram tracings from nights when dream enactment was observed to determine whether the timing of observed behavior aligned with the timing of REM sleep. Results We studied 92 participants [idiopathic Parkinson’s disease, n = 67; Dementia with Lewy bodies, n = 14; Multiple Systems Atrophy, n = 3; Idiopathic REM sleep behavior disorder, n = 8]. Of 92 participants studied, 30 (32.61%) exhibited dream enactment during REM sleep observed on either night of polysomnographic recording (11 on both nights, 19 on one night). There was a statistically significant difference (p = 0.041 by 2-tailed test) in mean questionnaire scores between participants with observed dream enactment during REM sleep (mean score 0.43; [95% CI mean 0.34-0.52]) and those without dream enactment on either night (mean score 0.32; [95% CI mean 0.26-0.38]). When limiting the sample to participants whose questionnaire responses were derived from the bed-partner (n = 74), the difference approached, but did not reach, statistical significance (p = 0.066). Conclusion These data provide further validation of the University of Michigan REM Behavior Disorder Questionnaire as a useful tool in evaluating REM-based dream enactment behavior in patients with alpha-synucleinopathic disease. Support (If Any)

Introduction Narcolepsy type 1 is caused by destruction of hypocretin-producing neurons, likely via a T-cell mediated autoimmune process, and clinically identified either by CSF hypocretin deficiency or the presence of cataplexy. Individuals with narcolepsy type 1 have an underlying genetic predisposition attributed to the HLA DQB1*0602 gene. This genetic variant has been linked to increased propensity for sleepiness even in healthy adults. Relatives of patients with narcolepsy type 1 appear to be at increased risk for other disorders of hypersomnolence such as idiopathic hypersomnia. Here we describe three siblings, all positive for HLA DQB1*0602, who presented with distinct clinical features diagnostic for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. Report of Cases: A 15-year-old female was diagnosed with narcolepsy type 1 based on typical cataplexy, excessive daytime sleepiness, and mean sleep latency of 2 min with 2 SOREMPs on MSLT. Lumbar puncture (LP) performed 5 years after symptom onset showed low CSF hypocretin (9.3 pg/mL). Her older brother presented at age 21 with excessive sleepiness, somewhat atypical cataplexy, hypnagogic hallucinations, and sleep paralysis. MSLT showed mean sleep latency of 6 min with 5 SOREMPs. Despite the presence of cataplexy, LP performed 2 years after symptom onset showed normal CSF hypocretin (296.5 pg/mL) and he was diagnosed with narcolepsy type 2. Their younger sister presented at age 19 with progressive daytime sleepiness. PSG/MSLT showed mild OSA (RDI 9.2) and mean sleep latency of 6.5 min without SOREMPs. She does not have cataplexy, hypnagogic hallucinations, or sleep paralysis. The current findings are most consistent with idiopathic hypersomnia, although an LP to evaluate for hypocretin deficiency is an important next step. Similarly, a repeat LP in the brother might demonstrate change in hypocretin over time. Conclusion These cases may support a familial link between narcolepsy type 1, type 2, and idiopathic hypersomnia. The discordant hypocretin and cataplexy statuses of these siblings implies a mechanism for excessive sleepiness beyond hypocretin deficiency, possibly mediated by HLA DQB1*0602. Identifying the mechanisms of familial aggregation of sleepiness in the central disorders of hypersomnolence may shed light on the pathophysiology of these distinct disorders. Support (If Any)

Background Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. Objectives To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. Search methods We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. Selection criteria Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. Main results We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. Authors' conclusions Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

The COVID-19 pandemic led to widespread use of telemedicine and highlighted its importance in improving access to sleep care and advocating for sleep health. This update incorporates the lessons learned from such widespread utilization of telehealth to build on the American Academy of Sleep Medicine’s 2015 position paper on the use of telemedicine for diagnosing and treating sleep disorders. Important key factors in this update include an emphasis on quality and value, privacy and safety, health advocacy through sleep telemedicine, and future directions. CITATION: Shamim-Uzzaman QA, Bae CJ, Ehsan Z, et al. The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update. J Clin Sleep Med. 2021;17(5):1103–1107.

The central disorders of hypersomnolence (CDH) are lifelong conditions that cause an irrepressible need for sleep during waking hours. Some of these disorders are due to medications or other conditions, but narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) occur as primary conditions. In each disorder excessive daytime sleepiness (EDS) may be accompanied by ancillary features such as sleep paralysis, hypnagogic/hypnopompic hallucinations, sleep drunkenness, or, in the case of NT1, cataplexy. Polysomnography and a multiple sleep latency test are used for diagnosis. Diagnostic lumbar puncture may be performed to differentiate NT1 from NT2. Although the mainstay of treatment for CDH is currently pharmacotherapy, management may also involve behavioral approaches such as sleep and nap scheduling, dietary modifications, and cognitive-behavioral therapy. Pharmacologic treatment can include traditional medications such as modafinil, methylphenidate, or sodium oxybate. Novel therapeutic agents such as pitolisant, clarithromycin, flumazenil, and melatonin may be useful in relieving EDS and associated symptoms.

Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/d over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient’s global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire. Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea–hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (−2.8; 95% confidence interval, −4.0 to −1.5; P

Objective The purpose of this study was to enhance our understanding of clinical trends in sleep and rapid eye movement (REM) propensity on the multiple sleep latency test (MSLT). Demographic variables of interest included early childhood/advanced age, gender, race, and REM-suppressant use. Methods Nocturnal sleep studies and 5-nap MSLTs were retrieved from a large repository of deidentified studies from various US sleep clinics between 2007 and 2015. Studies were signal processed, human-edited, and underwent rigorous quality assurance for inclusion. Results The final sample consisted of N = 2498 MSLTs (24.2% Black; 34.2% Men; Age 4–89). In adults (age ≥ 21), sleep propensity modestly decreased across nap (90% at nap 1 to 80% at nap 5; p Conclusions MSLT outcomes vary greatly across age, gender, and use of psychotropic medication. Demographic variance should be considered when interpreting MSLT results. Robust age effect question the appropriateness of the MSLT as currently designed and implemented for children and older adults.

Introduction The International Restless Legs Study Group (IRLSSG) has developed the IRLS (International Restless Legs Syndrome Severity Scale) and validated it as a clinician/researcher administered scale to be used when both patient and examiner are present. The IRLSSG recognized the need for a self-completing scale that can be used economically in clinical practice and in large population-based studies. In this study the validity and the reliability of the IRLS as a self-administered scale (sIRLS) is assessed. Methods Established RLS patients were recruited by eight centers in four countries and consented to participate in this study. The validity of the sIRLS was assessed by patients completing the sIRLS before a clinician administered the IRLS. The reliability of the sIRLS was assessed by patients completing the sIRLS again, two weeks after the first one, provided no change had occurred. Results Overall, 173 patients were recruited and 164 of them were included in the analyses. The sIRLS showed satisfactory scaling assumptions and no relevant floor or ceiling effect. One factor explained 61.3% of the variance. Cronbach's alpha was 0.93 and the item homogeneity index was 0.59. Intraclass correlation coefficient between the sIRLS and the IRLS was 0.94. The sIRLS standard error of measurement was 3.61 (½ SD at baseline = 4.11). The results mostly overlapped those of the IRLS analyzed in parallel. Discussion The sIRLS is a reliable, valid and precise instrument that showed tight association with the IRLS. These findings support the use of the sIRLS for self-evaluation of RLS severity. The responses obtained on the sIRLS and the IRLS scale varied slightly. Therefore, we recommend that either the sIRLS or the IRLS scale be used as the only scale for serial measures over time.

Study Objectives Daytime sleepiness is a manifestation of multiple sleep and neurologic disorders. Few studies have assessed patterns of regional brain metabolism across different disorders of excessive daytime sleepiness. One such disorder, idiopathic hypersomnia (IH), is particularly understudied. Methods People with IH, narcolepsy (NT1), and non-sleepy controls underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) with electroencephalography (EEG). Participants were instructed to resist sleep and were awoken if sleep occurred. Voxel-wise parametric analysis identified clusters that significantly differed between each pair of groups, with a minimum cluster size of 100 voxels at a cluster detection threshold of p < 0.005. Correlations between glucose metabolism and sleep characteristics were evaluated. Results Participants (77% women) had IH (n = 16), NT1 (n = 14), or were non-sleepy controls (n = 9), whose average age was 33.8 (±10.7) years. Compared to controls, NT1 participants demonstrated hypermetabolism in fusiform gyrus, middle occipital gyrus, superior and middle temporal gyri, insula, cuneus, precuneus, pre- and post-central gyri, and culmen. Compared to controls, IH participants also demonstrated hypermetabolism in precuneus, inferior parietal lobule, superior and middle temporal gyri, and culmen. Additionally, IH participants demonstrated altered metabolism of the posterior cingulate. Most participants fell asleep. Minutes of N1 during uptake was significantly negatively correlated with metabolism of the middle temporal gyrus. Conclusion NT1 and IH demonstrate somewhat overlapping, but distinct, patterns of regional metabolism.

Funder: Scottish Government; doi: https://doi.org/10.13039/100012095, Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.

Introduction Cytokines are known for their role in inflammation, and more recently in sleepiness and fatigue. There is a paucity of data regarding cytokines in Idiopathic Hypersomnia (IH) and Narcolepsy Type 2 (NT2) as defined by the International Classifications of Sleep Disorders-Third Edition. Additionally the heterogenous cohort of patients with excessive daytime sleepiness (EDS), but do not meet criteria for a sleep disorder, has not been studied separately from IH patients. Methods The study cohort was a convenience sample evaluated at a single tertiary-care sleep center between 2016 and 2019. Diagnoses were IH, NT2, EDS, and controls (based on sleep laboratory testing). The following cytokines were measured using the Mesoscale U-PLEX biomarker assay: G-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, and TNF-α. Demographic data and survey data pertaining to sleepiness, depression, and sleep inertia were available for all. Results The study cohort consisted of 22 controls, 26 patients with EDS, 51 patients with IH, and 12 patients with NT2. There were no significant differences between diagnosis and any cytokine. Pearson correlations showed significant negative correlations between G-CSF concentrations with depression (p=0.05) and sleep inertia (p Conclusion Though differences in cytokines levels between diagnostic groups did not reach significance, several cytokines correlated with severity of reported symptoms in disorders of hypersomnolence. G-CSF and IL-8 may serve as a biomarker for symptoms of depression and sleep inertia in sleepiness disorders, and thus could be a targeted for therapies. Support (if any) Hypersomnia Foundation Grant

There are numerous disorders of known or presumed neurologic origin that result in excessive daytime sleepiness, collectively known as the central disorders of hypersomnolence. These include narcolepsy types 1 and 2, idiopathic hypersomnia, Kleine–Levin syndrome, and hypersomnia due to or associated with medical disease, neurologic disease, psychiatric disease, medications or substances, and insufficient sleep durations. This chapter focuses on the treatment of nonnarcoleptic hypersomnia syndromes, from those that are commonly encountered in neurologic practice, such as hypersomnia due to Parkinson’s disease, to those that are exceedingly rare but present with dramatic manifestations, such as Kleine–Levin syndrome. The level of evidence for the treatment of sleepiness in these disorders is generally lower than in the well-characterized syndrome of narcolepsy, but available clinical and randomized, controlled trial data can provide guidance for the management of each of these disorders. Treatments vary by diagnosis but may include modafinil/armodafinil, traditional psychostimulants, solriamfetol, pitolisant, clarithromycin, flumazenil, sodium oxybate, melatonin, methylprednisolone, and lithium. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00919-1) contains supplementary material, which is available to authorized users.

Restless legs syndrome (RLS) is a common disorder. The population prevalence is 1.5% to 2.7% in a subgroup of patients having more severe RLS with symptoms occurring 2 or more times a week and causing at least moderate distress. It is important for primary care physicians to be familiar with the disorder and its management. Much has changed in the management of RLS since our previous revised algorithm was published in 2013. This updated algorithm was written by members of the Scientific and Medical Advisory Board of the RLS Foundation based on scientific evidence and expert opinion. A literature search was performed using PubMed identifying all articles on RLS from 2012 to 2020. The management of RLS is considered under the following headings: General Considerations; Intermittent RLS; Chronic Persistent RLS; Refractory RLS; Special Circumstances; and Alternative, Investigative, and Potential Future Therapies. Nonpharmacologic approaches, including mental alerting activities, avoidance of substances or medications that may exacerbate RLS, and oral and intravenous iron supplementation, are outlined. The choice of an alpha2-delta ligand as first-line therapy for chronic persistent RLS with dopamine agonists as a second-line option is explained. We discuss the available drugs, the factors determining which to use, and their adverse effects. We define refractory RLS and describe management approaches, including combination therapy and the use of high-potency opioids. Treatment of RLS in pregnancy and childhood is discussed.

STUDY OBJECTIVES: In this study we investigated the clinical correlates of restless legs syndrome in children with autism and report on our experiences with response to treatment. METHODS: A retrospective chart review of children seen in our sleep center from 2016–2019 was performed to identify children with autism and chronic insomnia. Patients underwent clinical assessments for restless legs symptomatology. Overnight polysomnogram, serum ferritin testing, and response to clinical treatment data were collected. RESULTS: A total of 103 children with autism and chronic insomnia were identified (age range 2–19 years). Of these, 41 children (39%) were diagnosed with restless legs syndrome. The diagnosis of restless legs syndrome was associated with significantly lower serum ferritin levels (mean 29 ± 18.62 ng/mL vs non–restless legs syndrome 56.7 ± 17.59, P < .001) and higher periodic limb movements of sleep on polysomnogram (8.12 ± 6.6 vs non–restless legs syndrome 0.06 ± 0.17). The presence of leg kicking, body rocking, or any symptoms involving the legs was highly correlated with the diagnosis of restless legs syndrome. Positive treatment response was noted in nearly all treated patients, including those treated with oral iron supplementation alone (25 children, 23 responders), gabapentin alone (12 children, all responders), and combination therapy (3 children, all responders). CONCLUSIONS: Our findings suggest restless legs syndrome may represent an under-recognized cause of insomnia in children with autism. Initial assessment should include a thorough query of behaviors related to nocturnal motor complaints, because restless legs syndrome may be a treatable cause of sleep disruption. CITATION: Kanney ML, Durmer JS, Trotti LM, Leu R. Rethinking bedtime resistance in children with autism: is restless legs syndrome to blame? J Clin Sleep Med. 2020;16(12):2029–2035.

The classification of the central disorders of hypersomnolence has undergone multiple iterations in an attempt to capture biologically meaningful disease entities in the absence of known pathophysiology. Accumulating data suggests that further refinements may be necessary. At the 7th International Symposium on Narcolepsy, a group of clinician-scientists evaluated data in support of keeping or changing classifications, and as a result suggest several changes. First, idiopathic hypersomnia with long sleep durations appears to be an identifiable and meaningful disease subtype. Second, idiopathic hypersomnia without long sleep time and narcolepsy without cataplexy share substantial phenotypic overlap and cannot reliably be distinguished with current testing, and so combining them into a single disease entity seems warranted at present. Moving forward, it is critical to phenotype patients across a wide variety of clinical and biological features, to aid in future refinements of disease classification.

Background Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron’s involvement in erythropoiesis drives clinical practice, the guidelines informing interventional strategies for iron repletion in neurological disorders are poorly defined. The objective of this study was to determine if peripheral iron status is communicated to the brain. Methods We used a bi-chamber cell culture model of the blood–brain-barrier to determine transcytosis of iron delivered by transferrin as a metric of iron transport. In the apical chamber (representative of the blood) we placed transferrin complexed with iron59 and in the basal chamber (representative of the brain) we placed human cerebrospinal fluid. Cerebrospinal fluid (CSF) samples (N = 24) were collected via lumbar puncture. The integrity of the tight junctions were monitored throughout the experiments using RITC-Dextran. Results We demonstrate that iron transport correlates positively with plasma hemoglobin concentrations but not serum ferritin levels. Conclusions The clinical ramifications of these findings are several- fold. They suggest that erythropoietic demands for iron take precedence over brain requirements, and that the metric traditionally considered to be the most specific test reflecting total body iron stores and relied upon to inform treatment decisions–i.e., serum ferritin–may not be the preferred peripheral indicator when attempting to promote brain iron uptake. The future direction of this line of investigation is to identify the factor(s) in the CSF that influence iron transport at the level of the BBB.

Study Objectives: To examine repeatability of Multiple Sleep Latency Test (MSLT) results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3). Methods: Repeatability of the MSLT was retrospectively evaluated in NT1 (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had documented HLA-DQB1. 06:02 status and/or hypocretin-1 levels from cerebrospinal fluid. All subjects had undergone 2 MSLTs (≥ 1 meeting ICSD-3 criteria for narcolepsy). Repeatability was explored in children versus adults and in those on versus not on medication(s). Subsample and multivariate analysis were performed. Results: Both MSLTs in unmedicated patients were positive for narcolepsy in 78%, 18%, and 7% of NT1, NT2, and controls, respectively. NT2 cases changed to idiopathic hypersomnia or to a negative MSLT 26% and 57% of the time, respectively. Although NT1 cases were 10 to 14 times more likely to demonstrate a second positive MSLT compared to NT2 cases (P < 10-5) and controls (P < 10-4), respectively, NT2 cases were not significantly different from controls (P = .64). Medication use (P = .009) but not adult versus children status (P = .85) significantly decreased the likelihood of a repeat positive MSLT. Conclusions: In a clinical setting, a positive MSLT for narcolepsy is a more reproducible and stable feature in NT1 than NT2. The retrospective design of this study hinders interpretation of these data, as there are many different, and possibly opposing, reasons to repeat a MSLT in NT1 versus NT2 (ie, ascertainment bias). Additional systematic MSLT repeatability studies independent of confounds are ideally needed to confirm these findings.

Citation:Trotti LM. Twice is nice? Test-retest reliability of the Multiple Sleep Latency Test in the central disorders of hypersomnolence. J Clin Sleep Med. 2020;16(suppl_1):17S–18S.

Introduction Sleep apnea and stroke have long been shown to be linked, with sleep apnea increasing the risk for stroke and stroke leading to sleep apnea. When the latter occurs, it can present as central sleep apnea (CSA), often in the form of Cheyne-Stokes breathing (CSB), and has been shown to resolve over time. We present a patient with persistent CSA after severe hemorrhagic stroke secondary to rupture of a temporal/thalamic arteriovenous malformation (AVM). Report of case(s) A 33-year-old man with a history of obstructive sleep apnea (OSA) presented to our clinic for re-evaluation of his disease. He was diagnosed with OSA in 2006 at which time he was 270 pounds with a body mass index (BMI) of 36.7, thus the OSA was thought to be secondary to obesity. When he presented to our clinic 10 years later, he had lost approximately 80 pounds after suffering multiple strokes. In 2014, he had a left temporal lobe hemorrhage due to rupture of a left temporal/thalamic AVM and required decompressive hemicraniectomy. In 2015, he had a re-bleed of this AVM, with new hemorrhage extending inferiorly into the left cerebral peduncle and pons, and superiorly into the left parietal periventricular white matter anteriorly along the optic tract. Ultimately, he was treated with stereotactic radiotherapy to the AVM nidus with no residual AVM. However, he has chronic encephalomalacia of the left basal ganglia, thalamus, temporal, parietal, and occipital lobes with extension into the left cerebral peduncle and changes consistent with radiation necrosis. His residual symptoms are aphasia and right-sided hemiplegia and although his snoring resolved with weight loss, his mother noticed pauses in his breathing overnight. A repeat sleep study done in 2016 showed 27 central apneas and 0 obstructive apneas with an AHI of 5.4 events/hour. He was subsequently studied on ASV with residual AHI of 0.4 events/hour. Conclusion Although patients with OSA may be at higher risk for stroke, it is important to re-evaluate their sleep apnea after such an event to ensure appropriate diagnosis and treatment going forward. Support (if any)

The transition from sleep to wake is marked by sleep inertia, a distinct state that is measurably different from wakefulness and manifests as performance impairments and sleepiness. Although the precise substrate of sleep inertia is unknown, electroencephalographic, evoked potential, and neuroimaging studies suggest the persistence of some features of sleep beyond the point of awakening. Forced desynchrony studies have demonstrated that sleep inertia impacts cognition differently than do homeostatic and circadian drives and that sleep inertia is most intense during awakenings from the biological night. Recovery sleep after sleep deprivation also amplifies sleep inertia, although the effects of deep sleep vary based on task and timing. In patients with hypersomnolence disorders, especially but not exclusively idiopathic hypersomnia, a more pronounced period of confusion and sleepiness upon awakening, known as “sleep drunkenness”, is common and problematic. Optimal treatment of sleep drunkenness is unknown, although several medications have been used with benefit in small case series. Difficulty with awakening is also commonly endorsed by individuals with mood disorders, disproportionately to the general population. This may represent an important treatment target, but evidence-based treatment guidance is not yet available.

This article provides an update on six sleep-related movement disorders: restless legs syndrome (RLS), periodic limb movement disorder, sleep-related leg cramps, bruxism, rhythmic movement disorder, and propriospinal myoclonus, with an emphasis on RLS.RLS is a common sensorimotor disorder that impairs quality of life. RLS is frequently comorbid to neurologic, psychiatric, vascular, and inflammatory diseases. Accumulating evidence implicates the pathophysiology of RLS as a state of dopamine dysfunction and iron deficiency that occurs on a background of genetic susceptibility conferred by 6 gene polymorphisms. Multiple treatments approved by the US Food and Drug Administration (FDA) are available. Dopamine agonists and α2δ calcium channel ligands are considered first-line treatments, but these treatments have very different side effect profiles that should be taken into consideration.Sleep-related movement disorders are frequently encountered in clinical practice. For some disorders, particularly RLS and periodic limb movement disorder, our understanding of biology, epidemiology, and treatment is advanced. For others, much work is needed to determine optimal treatment strategies.

Background Providing high-quality care for patients with Parkinson's disease (PD) involves addressing both motor and nonmotor features. We describe the implementation and evaluation of a 2-day, interdisciplinary Comprehensive Care Clinic (CCC) for patients with PD. Methods Patients who attended the CCC between January 2010 and July 2013 were matched by sex and age with patients who were evaluated in specialist care during the same time frame. Provider documentation of the American Academy of Neurology (AAN) quality measures for PD and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were compared between specialist and CCC visits at baseline and at 12 months. Results Ninety-five patients participated in the CCC (60% men; 75% white; mean age, 68 years; age range, 38–97 years). Of these, 29 patients were matched to specialist care patients based on the availability of 12-month follow-up data. Both groups were similar with respect to race, marital status, years with PD, and baseline UPDRS motor scores. On average, patients who received CCC care met 10 of 10 AAN quality measures, whereas those who received specialist care met only 5 of 10 quality measures (P < 0.001) over 12 months. At 12-months, there were no significant differences in UPDRS motor scores between the groups (P = 0.5). Conclusions According to the AAN quality measures, the CCC provided higher quality care than the gold standard of specialty care. A randomized controlled trial of the CCC model is warranted to determine its impact on patient-centered outcomes and to assess whether the standard model of care should be altered.

The hypothalamic peptide hypocretin 1 (orexin A) may be assayed in cerebrospinal fluid to diagnose narcolepsy type 1. This testing is not commercially available, and factors contributing to assay variability have not previously been comprehensively explored. In the present study, cerebrospinal fluid hypocretin concentrations were determined in duplicate in 155 patient samples, across a range of sleep disorders. Intra-assay variability of these measures was analyzed. Inter-assay correlation between samples tested at Emory and at Stanford was high (r = 0.79, p