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Idiopathic hypersomnia (IH) is a sleep disorder characterized by highly disruptive symptoms. Like narcolepsy type 1, a well-characterized sleep disorder, individuals with IH suffer from excessive daytime sleepiness, though there is little overlap in metabolic or neural biomarkers across these two disorders. This lack of common pathophysiology, combined with the clear overlap in symptoms presents an ideal paradigm for better understanding the impact of IH on an individual's functional activity and organization, and potentially, the underlying pathophysiology. This study examines the observed functional connectivity in patients with IH, and patients with narcolepsy type 1 (NT1) against healthy control individuals. Static functional connectivity is compared, as are quasi-periodic patterns, acquired from the BOLD timecourse, for all groups. In addition to baseline data comparison, the study also included a post-nap condition, where the individuals included in this analysis napped for at least 10 minutes prior to the scanning session, to explore why individuals with IH do not feel refreshed after a nap like individuals with NT1 do. Assessing the groups' spatiotemporal patterns revealed key differences across both disorders and conditions: static connectivity revealed at baseline higher subcortical connectivity in the NT1 group. There was also observably less connectivity in the IH group both at baseline and post-nap, though none of these static analyses survived multiple comparisons correction to reach significance. The QPP results however found significant differences in the IH group in key networks, particularly the DAN/FPCN correlation is significantly different at baseline vs. post-nap, a trend not observed in either the control or NT1 groups. The DAN and FPCN are drastically altered both at baseline and post-nap when compared to the other groups, and may likely be a disorder-specific result. This study demonstrates that key networks for arousal are more heavily disrupted in IH patients, who are less affected by a nap, confirmed through both subject reporting and functional evidence through spatiotemporal patterns.

Introduction: There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants., Methods: Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2., Results: CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW., Discussion: Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships., Highlights: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The period of the year from spring to fall, when clocks in most parts of the United States are set one hour ahead of standard time, is called daylight saving time, and its beginning and ending dates and times are set by federal law. The human biological clock is regulated by the timing of light and darkness, which then dictates sleep and wake rhythms. In daily life, the timing of exposure to light is generally linked to the social clock. When the solar clock is misaligned with the social clock, desynchronization occurs between the internal circadian rhythm and the social clock. The yearly change between standard time and daylight saving time introduces this misalignment, which has been associated with risks to physical and mental health and safety, as well as risks to public health. In 2020, the American Academy of Sleep Medicine (AASM) published a position statement advocating for the elimination of seasonal time changes, suggesting that evidence best supports the adoption of year-round standard time. This updated statement cites new evidence and support for permanent standard time. It is the position of the AASM that the United States should eliminate seasonal time changes in favor of permanent standard time, which aligns best with human circadian biology. Evidence supports the distinct benefits of standard time for health and safety, while also underscoring the potential harms that result from seasonal time changes to and from daylight saving time., Citation: Rishi MA, Cheng JY, Strang AR, et al. Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement. J Clin Sleep Med . 2024;20(1):121-125., (© 2024 American Academy of Sleep Medicine.)

Restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) have been variably implicated in risk for cardiovascular disease (CVD), but there is lack of consensus on these relationships. We sought to assess subclinical CVD measures and RLS/PLMS in a large cohort to further evaluate these associations. The Emory Center for Health Discovery and Well Being cohort is composed of employed adults, with subclinical CVD measures including endothelial function (flow-mediated vasodilation), microvascular function (reactive hyperemia index, RHI), arterial stiffness (pulse wave velocity and augmentation index), and carotid intima-media thickness (cIMT). Participants were grouped based on presence ( N  = 50) or absence ( N  = 376) of RLS and subclinical CVD measures compared between groups. A subset of participants ( n  = 40) underwent ambulatory monitoring for PLMS and obstructive sleep apnea. PLMS association with subclinical CVD measures was assessed. RLS status was significantly associated with flow-mediated dilation in univariate analyses but not after controlling for potential confounders; RLS was not associated with other subclinical CVD measures. PLMS were significantly correlated with the RHI, augmentation index, and cIMT in univariate analyses; only the association between PLMS and cIMT remained significant ( p  = 0.04) after controlling for RLS status, age, apnea-hypopnea index, hyperlipidemia, and hypertension. The observed association between higher PLMS and greater cIMT suggests that PLMS may be a marker of subclinical CVD. Further work is needed to determine the relationship between PLMS and CVD risk., Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00497-7., Competing Interests: Conflict of interestThe authors declare they have no financial conflicts of interest. Dr. Trotti is a member of the Board of Directors of the American Academy of Sleep Medicine (AASM); views expressed are those of the authors and do not necessarily reflect those of the AASM or the funding source (National Institutes of Health)., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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.

GABA A receptor-positive modulators are well-known to induce sedation, sleep, and general anesthesia. Conversely, GABA A receptor negative allosteric modulators (GABA A RNAMs) can increase arousal and induce seizures. Motivated by our studies with patients with hypersomnia, and our discovery that two GABA A RNAMs can restore the Excitation/Inhibition (E/I) balance in vitro and arousal in vivo, we chose to screen 11 compounds that have been reported to modulate arousal, to see if they shared a GABA-related mechanism. We determined modulation with both conventional and microfluidic patch clamp methods. We found that receptor activation was variably modulated by all 11 compounds: Rifampicin (RIF), Metronidazole (MET), Minocycline (MIN), Erythromycin (ERY), Ofloxacin (OFX), Chloroquine (CQ), Hydroxychloroquine sulfate (HCQ), Flumazenil (FLZ), Pentylenetetrazol (PTZ), (-)-Epigallocatechin Gallate (EGCG), and clarithromycin (CLR). The computational modeling of modulator-receptor interactions predicted drug action at canonical binding sites and novel orphan sites on the receptor. Our findings suggest that multiple avenues of investigation are now open to investigate large and brain-penetrant molecules for the treatment of patients with diminished CNS E/I balance.

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., Citation: 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. J Clin Sleep Med . 2022;18(11):2673-2680., (© 2022 American Academy of Sleep Medicine.)

Obstructive sleep apnea (OSA) may lead to serious health, safety, and financial implications-including sleepiness-related crashes and incidents-in workers who perform safety-sensitive functions in the transportation industry. Evidence and expert consensus support its identification and treatment in high-risk commercial operators. An Advanced Notice of Proposed Rulemaking regarding the diagnosis and treatment of OSA in commercial truck and rail operators was issued by the Federal Motor Carrier Safety Administration and Federal Railroad Administration, but it was later withdrawn. This reversal has led to questions about whether efforts to identify and treat OSA are warranted. In the absence of clear directives, we urge key stakeholders, including clinicians and patients, to engage in a collaborative approach to address OSA by following, at a minimum, the 2016 guidelines issued by a Medical Review Board of the Federal Motor Carrier Safety Administration, alone or in combination with 2006 guidance by a joint task force. The current standard of care demands action to mitigate the serious health and safety risks of OSA., Citation: Das AM, Chang JL, Berneking M, et al. Enhancing public health and safety by diagnosing and treating obstructive sleep apnea in the transportation industry: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2022;18(10):2467-2470., (© 2022 American Academy of Sleep Medicine.)

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., Citation: 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. J Clin Sleep Med . 2022;18(8):2041-2043., (© 2022 American Academy of Sleep Medicine.)

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., (© 2022 American Academy of Sleep Medicine.)

Citation: 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., (© 2021 American Academy of Sleep Medicine.)

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., 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)., 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)., 13: We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL)., 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)., 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)., 19: We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL)., 20: We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL)., 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., (© 2021 American Academy of Sleep Medicine.)

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., (© 2021 American Academy of Sleep Medicine.)

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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

None: 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., (© 2021 American Academy of Sleep Medicine.)

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., Competing Interests: Dr. Lynn Marie Trotti reports grants from NINDS/NIH during the conduction of this study and personal fees from Medscape and Oakstone for providing CME lectures. Dr. Donald L. Bliwise reports grants from the Alzheimer's Association during the conduction of this study and personal fees from Merck, Ferring, Eisai, and Jazz outside of the submitted work. Dr. Glenda L. Keating has no conflict of interests to declare. Dr. David B. Rye reports grants from NIH/NINDS during the conduction of this study and personal fees from Jazz, Harmony, and Eisai outside of the submitted work. In addition, Dr. David B. Rye has a patent (US9616070B2) issued and licensed to Balance Therapeutics and a patent (US10029-053W01) pending and licensed to Balance Therapeutics and Expansion Therapeutics. Dr. William T. Hu reports grant funding from NINDS/NIH during the conduction of this study and grants from Fujirebio US, personal fees from ViveBio LLC, Roche Diagnostics, and AARP, and nonfinancial support from Advanced Brain Monitoring outside of the submitted work. In addition, Dr. William T. Hu has a patent (US9618522B2) issued., (Copyright © 2021 by S. Karger AG, Basel.)

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.

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.

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., (© 2020 American Academy of Sleep Medicine.)

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.

Study Objectives: We aimed to quantify the symptoms of autonomic nervous system dysfunction in a large online cohort of patients with idiopathic hypersomnia, and to determine how the severity of these symptoms interacts with sleepiness, fatigue, and quality of life., Methods: One hundred thirty-eight patients with idiopathic hypersomnia and 81 age- and sex-matched controls were recruited through the website of the Hypersomnia Foundation, a US-based patient advocacy group. Twenty-four patients with confirmed idiopathic hypersomnia were selected by the study investigators as a comparison group. All participants completed a battery of online sleep, autonomic, and quality of life questionnaires including the composite autonomic symptom score-31 (COMPASS-31)., Results: Online and confirmed patients reported significantly higher COMPASS-31 scores (median [interquartile range]) (43.6 [33.6-52.7] and 32.9 [21.7-46.8] vs 17.6 [11.7-27.9], P < .001), with the greatest symptom burden in the orthostatic and vasomotor domains. Online and confirmed patients reported more sleepiness (Epworth sleepiness scale), whereas only online patients reported more fatigue (Chalder fatigue scale). Both the Epworth sleepiness scale and Chalder fatigue scale positively correlated with COMPASS-31 scores. Patients reported lower quality of life as reflected by lower scores across all domains of the RAND 36-item health survey, which was negatively correlated with COMPASS-31 scores., Conclusions: Symptoms of autonomic nervous system dysfunction are common in idiopathic hypersomnia. In addition, autonomic nervous system symptom burden was positively correlated with sleepiness and negatively correlated with quality of life., (© 2020 American Academy of Sleep Medicine.)

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 iron 59 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.

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., (© 2020 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Background: Restless legs syndrome (RLS) is a common neurologic disorder that is associated with peripheral iron deficiency in a subgroup of patients. It is unclear whether iron therapy is effective treatment for RLS., Objectives: To evaluate the efficacy and safety of oral or parenteral iron for the treatment of restless legs syndrome (RLS) when compared with placebo or other therapies., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycNFO, and CINAHL for the time period January 1995 to September 2017. We searched reference lists for additional published studies. We searched Clinicaltrials.gov and other clinical trial registries (September 2017) for ongoing or unpublished studies., Selection Criteria: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment, in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria., Data Collection and Analysis: Two review authors independently extracted data and assessed trial quality, with discussion to reach consensus in the case of any disagreement. The primary outcome considered in this review was restlessness or unpleasant sensations, as experienced subjectively by the patient. We combined treatment/control differences in the outcomes across studies using random-effects meta-analyses. We analysed continuous data using mean differences (MDs) where possible and performed standardised mean difference (SMD) analyses when different measurements were used across studies. We calculated risk ratios (RRs) for dichotomous data using the Mantel-Haenszel method and 95% confidence intervals (CIs). We analysed study heterogeneity using the I 2 statistic. We used standard methodological procedures expected by Cochrane. We performed GRADE analysis using GRADEpro., Main Results: We identified and included 10 studies (428 total participants, followed for 2-16 weeks) in this review. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the International Restless Legs Scale (IRLS) (range, 0 to 40) in eight trials and a different RLS symptom scale in a ninth trial. Nine studies compared iron to placebo and one study compared iron to a dopamine agonist (pramipexole). The possibility for bias among the trials was variable. Three studies had a single element with high risk of bias, which was lack of blinding in two and incomplete outcome data in one. All studies had at least one feature resulting in unclear risk of bias.Combining data from the seven trials using the IRLS to compare iron and placebo, use of iron resulted in greater improvement in IRLS scores (MD -3.78, 95% CI -6.25 to -1.31; I 2 = 66%, 7 studies, 345 participants) measured 2 to 12 weeks after treatment. Including an eighth study, which measured restlessness using a different scale, use of iron remained beneficial compared to placebo (SMD -0.74, 95% CI -1.26 to -0.23; I 2 = 80%, 8 studies, 370 participants). The GRADE assessment of certainty for this outcome was moderate.The single study comparing iron to a dopamine agonist (pramipexole) found a similar reduction in RLS severity in the two groups (MD -0.40, 95% CI -5.93 to 5.13, 30 participants).Assessment of secondary outcomes was limited by small numbers of trials assessing each outcome. Iron did not improve quality of life as a dichotomous measure (RR 2.01, 95% CI 0.54 to 7.45; I 2 =54%, 2 studies, 39 participants), but did improve quality of life measured on continuous scales (SMD 0.51, 95% CI 0.15 to 0.87; I 2 = 0%, 3 studies, 128 participants), compared to placebo. Subjective sleep quality was no different between iron and placebo groups (SMD 0.19, 95% CI -0.18 to 0.56; I 2 = 9%, 3 studies, 128 participants), nor was objective sleep quality, as measured by change in sleep efficiency in a single study (-35.5 +/- 92.0 versus -41.4 +/- 98.2, 18 participants). Periodic limb movements of sleep were not significantly reduced with iron compared to placebo ( SMD -0.19, 95% CI -0.70 to 0.32; I 2 = 0%, 2 studies, 60 participants). Iron did not improve sleepiness compared to placebo, as measured on the Epworth Sleepiness Scale (data not provided, 1 study, 60 participants) but did improve the daytime tiredness item of the RLS-6 compared to placebo (least squares mean difference -1.5, 95% CI -2.5 to -0.6; 1 study, 110 participants). The GRADE rating for secondary outcomes ranged from low to very low.Prespecified subgroup analyses showed more improvement with iron in those trials studying participants on dialysis. The use of low serum ferritin levels as an inclusion criteria and the use or oral versus intravenous iron did not show significant subgroup differences.Iron did not result in significantly more adverse events than placebo (RR 1.48, 95% CI 0.97 to 2.25; I 2 =45%, 6 studies, 298 participants). A single study reported that people treated with iron therapy experienced fewer adverse events than the active comparator pramipexole., Authors' Conclusions: Iron therapy probably improves restlessness and RLS severity in comparison to placebo. Iron therapy may not increase the risk of side effects in comparison to placebo. We are uncertain whether iron therapy improves quality of life in comparison to placebo. Iron therapy may make little or no difference to pramipexole in restlessness and RLS severity, as well as in the risk of adverse events. The effect on secondary outcomes such as quality of life, daytime functioning, and sleep quality, the optimal timing and formulation of administration, and patient characteristics predicting response require additional study.

Introduction: The importance of obstructive sleep apnea in patients undergoing surgery with general anesthesia is well-defined, but the surgical and anesthetic implications of other sleep disorders are less clear. We sought to evaluate response to surgery with general anesthesia in patients with central disorders of hypersomnolence or restless legs syndrome. Methods: We surveyed patients on their most recent surgical procedure with general anesthesia, querying about procedure, recovery, and any changes in sleep disorder symptomatology following the procedure. Results: Forty-five patients with restless legs syndrome and 57 patients with central disorders of hypersomnolence (15 narcolepsy type 2, 1 narcolepsy type 1, 30 idiopathic hypersomnia, 1 Kleine-Levin syndrome, and 10 subjective sleepiness) completed the survey, with response rates of 45.5 and 53.8%, respectively. While patients in both groups were equally likely to report surgical complications and difficulty awakening from anesthesia, hypersomnolent patients were more likely to report worsened sleepiness (40% of the hypersomnolent group vs. 11% of the RLS group, p = 0.001) and worsening of their sleep disorder symptoms (40% of the hypersomnolent group vs. 9% of the RLS group, p = 0.0001). Conclusion: Patients with sleep disorders other than sleep apnea frequently report surgical or anesthetic complications. Patients with hypersomnolence disorders commonly perceive that their sleep disorder worsened following a procedure; whether this might be related to long term effects of general anesthesia in a particularly vulnerable clinical population requires further study.

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., (© 2018 American Academy of Sleep Medicine)

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.

Lithium is a mood stabilizer rarely associated with drug-induced parkinsonism (DIP). We present a case of an elderly woman with bipolar disorder who developed parkinsonian symptoms after chronic lithium administration despite therapeutic serum levels. Upon evaluation, classic parkinsonian signs of muscle rigidity, tremor, bradykinesia, freezing of gait, and cognitive decline were observed. Initially, she was diagnosed with Parkinson's disease (PD); however, DaTscan SPECT imaging clarified the diagnosis as DIP. As the daily lithium dosage was reduced, the patient's motor symptoms improved. This report emphasizes close monitoring of lithium levels in geriatric populations and the need to consider lithium-induced parkinsonism when PD symptoms appear in chronic lithium users.

Study Objectives: Patients with central disorders of hypersomnolence sometimes do not achieve satisfactory symptom control with currently available wake-promoting medications. Based on the finding that the cerebrospinal fluid from some patients with hypersomnolence demonstrates potentiation of gamma-aminobutyric acid (GABA)-A receptors in excess of that of controls, a finding that reverses with flumazenil, we initiated prescribing compounded flumazenil to carefully selected, treatment-refractory hypersomnolent patients., Methods: This retrospective chart review evaluated the first 153 consecutive patients treated with transdermal and/or sublingual flumazenil by physicians at our center from 2013 through January 2015., Results: Patients were 35.5 y old (± 14.4) and 92 (60.1%) were women. Mean Epworth Sleepiness Scale scores prior to flumazenil were 15.1 (± 4.5) despite prior or current treatment with traditional wake-promoting therapies. Symptomatic benefit was noted by 96 patients (62.8%), with a mean reduction in Epworth Sleepiness Scale score of 4.7 points (± 4.7) among responders. Of these, 59 remained on flumazenil chronically, for a mean of 7.8 mo (± 6.9 mo). Female sex and presence of reported sleep inertia differentiated flumazenil responders from nonresponders. Adverse events were common, but often did not result in treatment discontinuation. Serious adverse events included a transient ischemic attack and a lupus vasculopathy, although whether these events occurred because of flumazenil administration is unknown., Conclusions: This chart review demonstrates that sublingual and transdermal flumazenil provided sustained clinical benefit to 39% of patients with treatment-refractory hypersomnolence. Prospective, controlled studies of this GABA-A receptor antagonist for the treatment of hypersomnolence are needed., Commentary: A commentary on this article appears in this issue on page 1321., (© 2016 American Academy of Sleep Medicine)

Abstract: The American Academy of Sleep Medicine (AASM) commissioned several Workgroups to develop quality measures for the care of patients with common sleep disorders, including adults with restless legs syndrome (RLS). Using the AASM process for quality measure development, the RLS Work-group developed three target outcomes for RLS management, including improving the accuracy of diagnosis, reducing symptom severity, and minimizing treatment complications. Seven processes were developed to support these outcomes. To achieve the outcome of improving accuracy of diagnosis, the use of accepted diagnostic criteria and assessment of iron stores are recommended. To realize the outcome of decreasing symptom severity, routine assessment of severity and provision of evidence-based treatment are recommended. To support the outcome of minimizing treatment complications, counseling about potential side effects and assessing for augmentation and impulse control disorders, when indicated, are recommended. Further research is needed to validate optimal practice processes to achieve best outcomes in adult patients with RLS., (© 2015 American Academy of Sleep Medicine.)

Sleep disorders are common in patients with Parkinson's disease (PD), and preliminary work has suggested viable treatment options for many of these disorders. For rapid eye movement sleep behavior disorder, melatonin and clonazepam are most commonly used, while rivastigmine might be a useful option in patients whose behaviors are refractory to the former. Optimal treatments for insomnia in PD have yet to be determined, but preliminary evidence suggests that cognitive-behavioral therapy, light therapy, eszopiclone, donepezil, and melatonin might be beneficial. Use of the wake-promoting agent modafinil results in significant improvement in subjective measures of excessive daytime sleepiness, but not of fatigue. Optimal treatment of restless legs syndrome and obstructive sleep apnea in PD are not yet established, although a trial of continuous positive airway pressure for sleep apnea was recently completed in PD patients. In those patients with early morning motor dysfunction and disrupted sleep, the rotigotine patch provides significant benefit.

Background: The prevalence of optic nerve and retinal vascular changes within the obstructive sleep apnea (OSA) population are not well-known, although it has been postulated that optic nerve ischemic changes and findings related to an elevated intracranial pressure may be more common in OSA patients. We prospectively evaluated the ocular fundus in unselected patients undergoing overnight diagnostic polysomnography (PSG)., Methods: Demographic data, medical/ocular history, and nonmydriatic fundus photographs were prospectively collected in patients undergoing PSG at our institution and reviewed for the presence of optic disc edema for which our study was appropriately powered a priori. Retinal vascular changes were also evaluated. OSA was defined using the measures of both sleep-disordered breathing and hypoxia., Results: Of 250 patients evaluated in the sleep center, fundus photographs were performed on 215 patients, among whom 127 patients (59%) had an apnea/hypopnea index (AHI) ≥ 15 events per hour, including 36 with severe OSA. Those with AHI <15 served as the comparison group. None of the patients had optic disc edema (95% confidence interval [CI]: 0%-3%). There was no difference in rates of glaucomatous appearance or pallor of the optic disc among the groups. Retinal arteriolar changes were more common in severe OSA patients (odds ratio: 1.09 per 5 unit increase in AHI; 95% CI, 1.02-1.16; P = 0.01), even after controlling for mean arterial blood pressure., Conclusions: We did not find an increased prevalence of optic disc edema or other optic neuropathies in our OSA population. However, retinal vascular changes were more common in patients with severe OSA, independent of blood pressure.

Study Objectives: Differentiation of narcolepsy without cataplexy from idiopathic hypersomnia relies entirely upon the multiple sleep latency test (MSLT). However, the test-retest reliability for these central nervous system hypersomnias has never been determined., Methods: Patients with narcolepsy without cataplexy, idiopathic hypersomnia, and physiologic hypersomnia who underwent two diagnostic multiple sleep latency tests were identified retrospectively. Correlations between the mean sleep latencies on the two studies were evaluated, and we probed for demographic and clinical features associated with reproducibility versus change in diagnosis., Results: Thirty-six patients (58% women, mean age 34 years) were included. Inter -test interval was 4.2 ± 3.8 years (range 2.5 months to 16.9 years). Mean sleep latencies on the first and second tests were 5.5 (± 3.7 SD) and 7.3 (± 3.9) minutes, respectively, with no significant correlation (r = 0.17, p = 0.31). A change in diagnosis occurred in 53% of patients, and was accounted for by a difference in the mean sleep latency (N = 15, 42%) or the number of sleep onset REM periods (N = 11, 31%). The only feature predictive of a diagnosis change was a history of hypnagogic or hypnopompic hallucinations., Conclusions: The multiple sleep latency test demonstrates poor test-retest reliability in a clinical population of patients with central nervous system hypersomnia evaluated in a tertiary referral center. Alternative diagnostic tools are needed.

Working memory is essential to higher order cognition (e.g. fluid intelligence) and to performance of daily activities. Though working memory capacity was traditionally thought to be inflexible, recent studies report that working memory capacity can be trained and that offline processes occurring during sleep may facilitate improvements in working memory performance. We utilized a 48-h in-laboratory protocol consisting of repeated digit span forward (short-term attention measure) and digit span backward (working memory measure) tests and overnight polysomnography to investigate the specific sleep-dependent processes that may facilitate working memory performance improvements in the synucleinopathies. We found that digit span backward performance improved following a nocturnal sleep interval in patients with Parkinson's disease on dopaminergic medication, but not in those not taking dopaminergic medication and not in patients with dementia with Lewy bodies. Furthermore, the improvements in patients with Parkinson's disease on dopaminergic medication were positively correlated with the amount of slow-wave sleep that patients obtained between training sessions and negatively correlated with severity of nocturnal oxygen desaturation. The translational implication is that working memory capacity is potentially modifiable in patients with Parkinson's disease but that sleep disturbances may first need to be corrected.

Background: Restless legs syndrome (RLS) is a common neurologic syndrome and is associated with iron deficiency in many patients. It is unclear whether iron therapy is effective treatment for RLS., Objectives: The objective of this review was to assess the effects of iron supplementation (oral or intravenous) for patients with RLS., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Jan 1995 to April 2011); EMBASE (Jan 1995 to April 2011); PsycINFO (Jan 1995 to April 2011); and CINAHL (Jan 1995 to April 2011). Corresponding authors of included trials and additional members of the International Restless Legs Syndrome Study Group were contacted to locate additional published or unpublished trials., Selection Criteria: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria., Data Collection and Analysis: Two review authors extracted data and at least two authors assessed trial quality. We contacted trial authors for missing data., Main Results: Six studies (192 total subjects) were identified and included in this analysis. The quality of trials was variable. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the IRLS severity scale in four trials and another RLS symptom scale in a fifth trial. Combining data from the four trials using the IRLS severity scale, there was no clear benefit from iron therapy (mean difference in IRLS severity scores of -3.79, 95% CI: -7.68 to 0.10, p = 0.06). However, the fifth trial did find iron therapy to be beneficial (median decrease of 3 points in the iron group and no change in the placebo group on a 10 point scale of RLS symptoms, p = 0.01). Quality of life was improved in the iron group relative to placebo in some studies but not others. Changes in periodic limb movements were not different between groups (measured in two studies). Objective sleep quality, subjective sleep quality and daytime functioning were not different between treatment groups in the studies that assessed them. The single study of subjects with end stage renal disease did show a benefit of therapy. Most trials did not require subjects to have co-morbid iron deficiency and several excluded patients with severe anemia. The single study that was limited to iron deficient subjects did not show clear benefit of iron supplementation on RLS symptoms. There was no clear superiority of oral or intravenous delivery of iron. Iron therapy did not result in significantly more side effects than placebo (RR 1.39, 95% CI 0.85 to 2.27)., Authors' Conclusions: There is insufficient evidence to determine whether iron therapy is beneficial for the treatment of RLS. Further research to determine whether some or all types of RLS patients may benefit from iron therapy, as well as the best route of iron administration, is needed.