Disorders Of Hypersomnolence Research Articles

The diagnostic value of sleep and vigilance tests in central disorders of hypersomnolence.

This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes. Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997-2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference. An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome. This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.

Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep.

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during nonrapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.

Comorbid parasomnias in narcolepsy and idiopathic hypersomnia: more REM than NREM parasomnias.

To assess the frequency, determinants, and clinical impact of clinical rapid eye movement (REM) and non-REM (NREM) parasomnias in adult patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia compared with healthy controls. Familial and past and current personal parasomnias were assessed by questionnaire and medical interviews in 710 patients (220 NT1, 199 NT2, and 221 idiopathic hypersomnia) and 595 healthy controls. Except for sleep-related eating disorder, current NREM parasomnias were rare in all patient groups and controls. Sleep-related eating disorder was more frequent in NT1 patients (7.9% vs 1.8% in NT2 patients, 2.1% in patients with idiopathic hypersomnia, and 1% in controls) and associated with disrupted nighttime sleep (odds ratio = 3.9) and nocturnal eating in full awareness (odds ratio = 6.9) but not with sex. Clinical REM sleep behavior disorder was more frequent in NT1 patients (41.4%, half being violent) than in NT2 patients (13.2%) and affected men more often than women (odds ratio = 2.4). It was associated with disrupted nighttime sleep, depressive symptoms, and antidepressant use. Frequent (> 1/week) nightmares were reported by 39% of patients with NT1, 29% with NT2, and 27.8% with idiopathic hypersomnia (vs 8.3% in controls) and were associated with depressive symptoms in narcolepsy. No parasomnia (except sleep-related hallucinations) worsened daytime sleepiness. In patients with central disorders of hypersomnolence, comorbid NREM parasomnias (except for sleep-related eating disorder) are rare and do not worsen sleepiness. In contrast, REM parasomnias are prevalent (especially in NT1) and are associated with male sex, disrupted nighttime sleep, depressive symptoms, and antidepressant use. Leu-Semenescu S, Maranci J-B, Lopez R, etal. Comorbid parasomnias in narcolepsy and idiopathic hypersomnia: more REM than NREM parasomnias. J Clin Sleep Med. 2022;18(5):1355-1364.

Neuroanatomical and Etiological Approaches to Secondary Narcolepsy

Narcolepsy is one among the disorders of central hypersomnolence characterized by excessive daytime sleepiness not related to disturbances in nocturnal sleep or misalignment in circadian rhythms. The cardinal symptom of this group of disorders is disabling daytime sleepiness, characterized by the repeated episodes of irresistible daytime sleepiness or lapses into sleep in monotonous situations, but also under unusual conditions such as eating. Narcolepsy is defined as type 1 and type 2 on the basis of the presence of cataplexy. The most pathognomonic feature of narcolepsy type 1 is cataplexy, which is characterized by sudden episodes of brief loss of muscle tone-sparing consciousness, usually triggered by strong emotions. Other nonspecific symptoms associated with rapid eye movement sleep dissociation include fragmentation of nocturnal sleep, hypnagogic or hypnopompic hallucinations, and sleep paralysis. The pathophysiology of narcolepsy type 1 is well established as the deficiency of hypocretin (orexin) signaling in the lateral hypothalamus. In narcolepsy type 2, on the other hand, hypocretin levels are not decreased, and it has been suggested that there is probably a partial deficiency in hypocretin signaling system to cause excessive daytime sleepiness but not severe enough to cause cataplexy. Instead of types 1 and 2, primary (idiopathic) narcolepsy, familial narcolepsy, secondary (symptomatic) narcolepsy, and narcolepsy plus (hereditary forms with additional neurological symptoms) forms were suggested to better classify the clinical entities. In this paper, the diagnosis of symptomatic or secondary narcolepsy is reviewed and classified based on the underlying pathophysiologic mechanisms.

Autonomic Dysfunction in Sleep Disorders: From Neurobiological Basis to Potential Therapeutic Approaches

Sleep disorder has been portrayed as merely a common dissatisfaction with sleep quality and quantity. However, sleep disorder is actually a medical condition characterized by inconsistent sleep patterns that interfere with emotional dynamics, cognitive functioning, and even physical performance. This is consistent with sleep abnormalities being more common in patients with autonomic dysfunction than in the general population. The autonomic nervous system coordinates various visceral functions ranging from respiration to neuroendocrine secretion in order to maintain homeostasis of the body. Because the cell population and efferent signals involved in autonomic regulation are spatially adjacent to those that regulate the sleep-wake system, sleep architecture and autonomic coordination exert effects on each other, suggesting the presence of a bidirectional relationship in addition to shared pathology. The primary goal of this review is to highlight the bidirectional and shared relationship between sleep and autonomic regulation. It also introduces the effects of autonomic dysfunction on insomnia, breathing disorders, central disorders of hypersomnolence, parasomnias, and movement disorders. This information will assist clinicians in determining how neuromodulation can have the greatest therapeutic effects in patients with sleep disorders.

Sleep Disorders During Pregnancy and Postpartum: A Systematic Review

This study aimed to asses previous research results about bio-physiological alterations during pregnancy and postpartum, and make clear outlook about prevalence and related factors of sleep disorders during pregnancy and postpartum. In this review, the articles that published from 2000 to 2019 were reviewed. Related articles were searched from databases in English language. After evaluation of inclusion and exclusion criteria, articles were chosen and reviewed based on the University of York strategies. Sleep disorders in present study were classified according to the International Classification of Sleep Disorders-3. The search revealed 4449 articles, after evaluating and assessing qualified articles, finally 56 article selected to review. According to the results of this review, The prevalence of sleep disorders was almost 76%–97% in whole pregnancy. The most common sleep disorders included central disorders of hyper somnolence (waking up in the middle of the night, daytime sleepiness, sleeplessness) or insomnia, sleep-related movement disorders (restless legs syndrome), sleep related breathing disorders (obstructive sleep apnea), and parasomnia. In addition, sleep disorder may continue 3–12 months postpartum (33.2%). Sleep disorders induced by physiological processes (fetal movement, excessive weight gain, male sex of the fetus, and multiparty), health-related risks (metabolism disorders, cardiovascular diseases, and mood disorders), and physical or sexual abuse in childhood. In addition, these disorders could have maternal outcomes that can be greatest trigger to postpartum psychiatric disorders and fetal outcomes that have harmful sequences during childhood (sexual, fertility, emotional, and cognitive problems). Health care providers should evaluate the mothers’ sleep quality because sleep disorder leads to harmful consequences in fetuses and children.

Idiopathic hypersomnia: does first to approval mean first-line treatment?

Idiopathic hypersomnia is a chronic sleep–wake disorder that causes excessive daytime sleepiness, despite normal or long nocturnal sleep durations, often accompanied by pronounced sleep inertia when awakening from overnight sleep or naps. Several drugs are prescribed off-label for patients with idiopathic hypersomnia, including modafinil, sodium oxybate, and psychostimulants. 1 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: 1881-1893 Crossref PubMed Scopus (6) Google Scholar Oxybate medications are prescribed and dispensed in the USA under a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy programme and carry several so-called black box warnings for serious side-effects. In August, 2021, the FDA approved calcium, magnesium, potassium, and sodium oxybate (known as lower-sodium oxybate) for the treatment of adults with idiopathic hypersomnia. 2 US Food and Drug AdministrationFDA grants first of its kind indication for chronic sleep disorder treatment. https://www.fda.gov/news-events/press-announcements/fda-grants-first-its-kind-indication-chronic-sleep-disorder-treatmentDate: 2021 Date accessed: November 3, 2021 Google Scholar This approval is an important milestone for people living with idiopathic hypersomnia, making lower-sodium oxybate the first and only FDA-approved medication for the treatment of this disorder. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal studyLower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. Full-Text PDF

Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study

Idiopathic hypersomnia is a central hypersomnolence disorder mainly characterised by excessive daytime sleepiness, with prolonged night-time sleep and pronounced sleep inertia. Until August, 2021, no medication had regulatory approval for the treatment of idiopathic hypersomnia. This study aimed to evaluate the safety and efficacy of lower-sodium oxybate in idiopathic hypersomnia. This was a phase 3, multicentre (50 specialist sleep centres; six EU countries and the USA), placebo-controlled, double-blind, randomised withdrawal study. Participants (aged 18-75 years) with idiopathic hypersomnia (meeting criteria from the International Classification of Sleep Disorders, 2nd or 3rd editions) began lower-sodium oxybate treatment (oral solution once or twice nightly) in an open-label titration and optimisation period (10-14 weeks), followed by a 2-week, open-label, stable-dose period. After these open-label periods, participants were randomised (1:1) by means of an interactive web recognition system, stratified by participants' baseline medication use, to either placebo or lower-sodium oxybate (individually optimised dose; range 2·5-9·0 g/night) during a 2-week, double-blind, randomised withdrawal period. To maintain masking of treatment assignment, placebo and lower-sodium oxybate oral solutions were matched in volume, appearance, and taste. During the double-blind, randomised withdrawal period, participants and investigators were unaware of treatment assignments. The primary efficacy endpoint was change in Epworth Sleepiness Scale (ESS) score from the end of the stable-dose period to the end of the double-blind, randomised withdrawal period, which was assessed in the modified intention-to-treat population (defined as all participants who were randomly assigned, took at least one dose of study medication during the double blind, randomised withdrawal period, and had at least one set of post-randomisation assessments for the primary or key secondary endpoints). Adverse events were assessed in the safety population (defined as all participants who took at least one dose of study medication). This study is registered at ClinicalTrials.gov, NCT03533114, and at EU Clinical Trials, 2018-001311-79, and is complete. Between Nov 27, 2018, and March 6, 2020, 154 participants were enrolled and comprised the safety population. ESS scores decreased from a mean of 15·7 (SD 3·8) at baseline to 6·1 (4·0) by the end of the stable-dose period. After the open-label periods, 115 participants were randomly assigned either placebo (n=59) or lower-sodium oxybate (n=56) and comprised the modified intention-to-treat population. During the double-blind, randomised withdrawal period, ESS scores increased (worsened) in participants randomly assigned to placebo but remained stable in those assigned to lower-sodium oxybate (least squares mean difference -6·5; 95% CI -8·0 to -5·0; p<0·0001). Treatment-emergent adverse events included nausea (34 [22%] of 154), headache (27 [18%] of 154), dizziness (19 [12%] of 154), anxiety (17 [11%] 154), and vomiting (17 [11%] 154). No deaths were reported during the study. Lower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. Jazz Pharmaceuticals.

Pregnancy and Contraception in Central Hypersomnolence Disorders

Pregnancy and Contraception in Central Hypersomnolence Disorders

Viral and Bacterial Infections, Including COVID-19, and Central Disorders of Hypersomnolence

The article's abstract is not available.

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice.

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 hr, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Is there a relationship between the ketogenic diet and sleep disorders?

Sleep disorders are very often underestimated and, consequently, not treated with due priority. Common sleep disorders include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. The ketogenic diet (KD) is rich in fat, low in carbohydrates (CHO), and adequate in protein. The KD has shown several applications in treating medical conditions, such as epilepsy, neurodegenerative disorders, obesity with its comorbidities, and sleep disorders, with encouraging results. Therefore, the purpose of this review is to address the primary sleep disorders and their respective standard therapeutic approaches, analyse the effect of ketone bodies (KBs) on sleep homeostasis, and the effects of KD on sleep disorders and in particular on obstructive sleep apnoea (OSA) syndrome. The goal is to summarise the evidence existing up to now on the subject, to provide a starting point for further investigations.

P003 The impact of forced wake from overnight polysomnography on multiple sleep latency test results

Abstract Introduction The multiple sleep latency test (MSLT) is used to diagnose disorders of hypersomnolence. Although internationally-recognised protocols do not stipulate whether patients should be woken from the preceding overnight polysomnography (PSG), many labs wake their patients for logistic reasons. This study analyses the impact on PSG and MSLT parameters of forced wake (FW) from the overnight PSG compared with unrestricted sleep (US). Methods 400 consecutive patients (FW=200; US=200) undergoing PSG/MSLT were included and the following parameters were compared: Epworth Sleepiness Scale (ESS), Morningness-Eveningness Questionnaire score (MEQ), PSG total sleep time (TST), wake-up time from the PSG, overall MSLT sleep latency (MSL), individual nap latencies (SLNap 1–4), number of MSLT naps with sleep-onset REM periods (#SOREMP), and percentage of MSLTs with overall MSL&amp;lt;8 minutes (%MSLT&amp;lt;8). Results The 2 groups were well-matched for ESS and MEQ. The FW group had more males (49% vs 39%). When compared to FW, patients with US had longer TST (+38 minutes; p=&amp;lt;0.0001), later wake-up time (+52 minutes; p&amp;lt;0.0001), longer MSL (+1.9 minutes; p=0.0049), 50% fewer #SOREMP (p=0.0224), and 16% fewer %MSLT&amp;lt;8 (p=0.0018). SLNap1 increased by 1.5 minutes (p=0.0623), SLNap2 increased by 2.0 minutes (p=0.0067), SLNap3 increased by 0.75minutes (p=0.0533) and SLNap4 increased by 2.5 minutes (p=0.0059). Discussion Allowing patients to have unrestricted sleep on the night prior to the MSLT resulted in significantly longer TST, longer sleep latencies during the MSLT, fewer SOREMP and fewer tests with MSL&amp;lt;8 minutes. International protocols should stipulate unrestricted sleep on the PSG prior to the MSLT to improve diagnostic accuracy.

Diagnostics of hypersomnolence disorders in patients with acute ischemic stroke – Condition and perspectives

Diagnostics of hypersomnolence disorders in patients with acute ischemic stroke – Condition and perspectives

Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency.

To evaluate the clinical utility of actigraphy as compared with sleep questionnaires prior to the Multiple Sleep Latency Test (MSLT) in a sleep disorders clinic population. Twenty-eight clinically referred participants (mean age: 42.3 ± 18.8 years) completed the study protocol. On day 1, participants completed the following questionnaires: Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale (affect, vigor), Patient Health Questionnaire, and Multidimensional Fatigue Symptom Inventory-Short Form. On days 1-8, participants wore an actigraph and completed a sleep diary to assess mean nighttime and mean daytime total sleep time and sleep efficiency or sleep percentage. On day 9, participants repeated the ESS and completed an MSLT. Correlations assessed mean MSLT sleep-onset latency (MSLT-SOL) vs actigraphy, sleep diary, and questionnaires. Chi-square analyses assessed abnormal MSLT-SOL (≤ 8 minutes) or daytime sleepiness (ESS ≥ 10) and referral question (ie, sleep-disordered breathing vs hypersomnolence disorder). Mean MSLT-SOL was correlated with nighttime total sleep time assessed via both actigraphy and diary, but not with questionnaires. Significant correlations emerged for ESS score on day 1 vs 9, actigraphy vs sleep diary mean nighttime total sleep time, and PSQI vs mean sleep diary sleep efficiency. There was no significant relationship between mean MSLT-SOL and referral question. Our finding that total sleep time measured by actigraphy was associated with MSLT-SOL suggests it is useful in informing the interpretation of MSLT findings; however, it does not appear to be a viable substitute for MSLT for the measurement of objective sleepiness in clinical settings. Kelly MR, Zeidler MR, DeCruz S, et al. Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency. J Clin Sleep Med. 2022;18(1):161-170.

Diagnostic value of actigraphy in hypersomnolence disorders

ObjectiveDifferentiating between the central hypersomnias presents a challenge to the diagnosis of patients with hypersomnolence. Actitigraphy may support efforts to distinguish them.We aimed to evaluate: 1) the ability of actigraphy to quantify sleep continuity measures in comparison with polysomnography in patients with hypersomnolence; 2) whether actigraphy can distinguish patients with hypersomnolence with normal hypocretin-1 in cerebrospinal fluid from patients with narcolepsy type 1 and from sleep-healthy controls; and 3) the distinct activity profiles and circadian rhythms of patients with narcolepsy type 1, patients with hypersomnolence with normal hypocretin-1 in cerebrospinal fluid, and sleep-healthy controls. MethodPolysomnography, multiple sleep latency tests and actigraphy were conducted in 14 patients with narcolepsy type 1, 29 patients with hypersomnolence with normal hypocretin-1 in cerebrospinal fluid and 15 sleep-healthy controls. ResultsActigraphy quantified several sleep continuity measures consistently with polysomnography in all the patients. Actigraphy distinguished patients with hypersomnolence with normal hypocretin-1 in cerebrospinal fluid from patients with narcolepsy type 1 and sleep-healthy controls. Patients with narcolepsy type 1 had poor sleep quality and altered circadian rest-activity rhythm compared with controls. ConclusionActigraphy is an adequate tool for establishing the amount of night sleep and supports the differential diagnosis of patients with hypersomnolence.

The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample of patients with sleep disorders.

The Hypersomnia Severity Index (HSI) was designed to assess the severity and impairment of hypersomnolence and has been validated in persons with psychiatric disorders. Little is known about its psychometric properties in clinical samples of patients with sleep disorders. One hundred fifty-eight patients (aged 44.1 ± 16.4 years, 29.1% male, 19.6% racial/ethnic minority) evaluated at the Behavioral Sleep Medicine program of the Penn State Health Sleep Research and Treatment Center completed the HSI and other patient-reported outcomes. We examined the HSI's reliability and factorial, construct, and criterion validity. The HSI showed satisfactory internal consistency (α = 0.79). A 2-factor structure, reflecting symptoms (HSI-S) and impairment, explained 56.2% of the variance. Convergent validity with the Epworth Sleepiness Scale was optimal (r = .65) but greater for HSI-S (r = .69) than for impairment (r = .39). Divergent validity was optimal for HSI-S against unrelated measures of sleep effort, reactivity, and incompatible behaviors (r ≤ .02). Construct validity showed higher scores in patients with central disorders of hypersomnolence and lower scores in patients with chronic insomnia disorder compared to those with other sleep disorders; however, these divergent scores were primarily driven by HSI-S rather than impairment. Criterion validity showed that an HSI-S cutoff score ≥ 8 provided the best balance in sensitivity/specificity (0.82/0.78) to identify central disorders of hypersomnolence (area under the curve, 0.85). The HSI shows satisfactory indices of reliability and validity in a clinical patient sample. Its construct and criterion validity are supported by its divergent association with other patient-reported outcomes and central disorders of hypersomnolence vs chronic insomnia disorder diagnoses and the adequate sensitivity/specificity of its HSI-S cutoff score to reliably identify central disorders of hypersomnolence. Fernandez-Mendoza J, Puzino K, Amatrudo G, etal. The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample with sleep disorders. J Clin Sleep Med. 2021;17(11):2249-2256.

022 Cytokines as correlates of reported symptoms in disorders of hypersomnolence

Abstract 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&amp;lt;0.01) in patients but not controls. In controls, hours slept per week positively correlated with G-CSF (p=0.05), but this was not true in patients with EDS, IH, or NT2. IL-8 level was negatively correlated with reported sleep inertia in sleepy patients (p=0.05), but not controls. 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

499 Utilization of Diagnostic Sleep Testing Prior to Idiopathic Hypersomnia Diagnosis Among US Adults: A Real-World Claims Analysis

Abstract Introduction A retrospective analysis was conducted to characterize diagnostic sleep testing during the 12 months before diagnosis of idiopathic hypersomnia (IH), a hypersomnolence disorder with no approved treatments. Methods IBM® MarketScan® claims data were analyzed (1/1/14–9/30/19) to identify adults with newly diagnosed IH, defined as ≥2 claims with an IH diagnosis code ≥1 day and ≤180 days apart, and without an IH diagnosis ≤12 months before cohort entry. Demographics, diagnosing physician specialty, and diagnostic sleep disorder testing (identified via claims with procedure codes for multiple sleep latency test/maintenance of wakefulness test [MSLT/MWT], home sleep test, and polysomnography) were summarized. Analyses were performed on patients with IH diagnosis codes recorded in any position on the claims (“overall IH”) and in the primary position (“primary IH”) to understand the effects of applying a more specific definition of IH. Results Of 32,948,986 eligible people, 4,980 (0.015%) newly diagnosed IH patients were identified. Mean age was 43 years and 67% were female; those with primary IH (n=2,205; 44% of overall IH) were younger (mean age, 39 years) and more likely to be female (73%). Long sleep time was documented for 69% of the overall IH group and 67% of the primary IH group. The top 3 diagnosing physicians’ specialties were similar for overall IH/primary IH: pulmonology (23%/26%), neurology (14%/16%), and internal medicine (11%/10%). Few patients (9% overall IH; 7% with primary IH) were diagnosed in family practice. Any sleep testing was performed in 44% of overall IH and 53% of primary IH patients. Polysomnography and MSLT/MWT, the most frequently used sleep tests, were less common in overall IH (39% and 22%) than in primary IH (48% and 32%). Conclusion IH patients were typically diagnosed by specialists, outside of general medical practice. The most common diagnosing physicians were pulmonologists and neurologists for both the overall and primary IH groups. Objective sleep testing was more frequently documented in diagnosis of primary IH but utilization was low regardless of the definition of IH diagnosis. Further research is needed to investigate the utilization of sleep testing by clinicians for diagnosing IH. Support (if any) Jazz Pharmaceuticals

512 Confirmatory Factor Analysis of the Sleep Inertia Questionnaire in a Clinical Sample with Sleep Disorders

Abstract Introduction The Sleep Inertia Questionnaire (SIQ) was developed and validated in patients with mood disorders to evaluate difficulties with becoming fully awake after nighttime sleep or daytime naps in a multidimensional manner. However, few data are available regarding its psychometric properties in clinical samples with sleep disorders. Methods 211 patients (43.0±16.4 years old, 68% female, 17% minority) evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Health Sleep Research &amp; Treatment Center completed the SIQ. All patients were diagnosed using ICSD-3 criteria, with 111 receiving a diagnosis of chronic insomnia disorder (CID), 48 of a central disorder of hypersomnolence (CDH), and 52 of other sleep disorders (OSD). Structural equation modelling was used to conduct confirmatory factor analysis (CFA) of the SIQ. Results CFA supported four SIQ dimensions of “physiological”, “cognitive”, “emotional” and “response to” (RSI) sleep inertia with adequate goodness-of-fit (TLI=0.90, CFI=0.91, GFI=0.85, RMSEA=0.08). Internal consistency was high (α=0.94), including that of its dimensions (physiological α=0.89, cognitive α=0.94, emotional α=0.67, RSI α=0.78). Dimension inter-correlations were moderate to high (r=0.42–0.93, p&amp;lt;0.01), indicating good construct validity. Convergent validity showed moderate correlations with Epworth sleepiness scale (ESS) scores (r=0.38) and large correlations with Flinders fatigue scale (FFS) scores (r=0.65). Criterion validity showed significantly (p&amp;lt;0.01) higher scores in subjects with CDH (69.0±16.6) as compared to those with CID (54.4±18.3) or OSD (58.5±20.0). A SIQ cut-off score ≥57.5 provided a sensitivity/specificity of 0.77/0.65, while a cut-off score ≥61.5 provided a sensitivity/specificity of 0.71/0.70 to identify CDH vs. ESS&amp;lt;10 (AUC=0.76). Conclusion The SIQ shows satisfactory indices of reliability and construct validity in a clinically-diverse sleep disorders sample. Its criterion validity is supported by its divergent association with hypersomnia vs. insomnia disorders, as well as its adequate sensitivity/specificity to identify patients with CDH. The SIQ can help clinicians easily assess the complex dimensionality of sleep inertia and target behavioral sleep treatments. Future studies should confirm the best SIQ cut-off score by including good sleeping controls, while clinical studies should determine its minimal clinically important difference after pharmacological or behavioral treatments. Support (if any):