Blackout of my nights: Contentless, timeless and selfless report from the night in patients with central hypersomnias.

At the extreme spectrum of consciousness during sleep, some patients with rare hypersomnias reported experiencing a specific night 'blackout' when sleeping, i.e., an absence of experiences or recall of them from sleep onset to offset. Thus, we explored through questionnaires the conscious experiences (dreaming experience, mind, self) during the night in 133 patients with idiopathic hypersomnia, 108 patients with narcolepsy, and 128 healthy controls. The night blackout was more frequent in idiopathic hypersomnia than in narcolepsy and control groups. Patients with idiopathic hypersomnia and frequent night amnesia had lower dream recall frequencies, and felt more often sleep as deep and mind as blank during the night. They had a higher proportion of slow wave sleep on their (retrospectively collected) sleep recordings than those without night blackout. This night blackout provides a new model for studying loss of consciousness during sleep, here as a contentless, selfless and timeless feeling upon awakening.

Hypocretin measurement: shelf age of radioimmunoassay kit, but not freezer time, influences assay variability.

The hypothalamic peptide hypocretin 1 (orexin A) may be assayed in cerebrospinal fluid to diagnose narcolepsy type 1. This testing is not commercially available, and factors contributing to assay variability have not previously been comprehensively explored. In the present study, cerebrospinal fluid hypocretin concentrations were determined in duplicate in 155 patient samples, across a range of sleep disorders. Intra-assay variability of these measures was analyzed. Inter-assay correlation between samples tested at Emory and at Stanford was high (r = 0.79, p < 0.0001). Intra-assay correlation between samples tested in duplicate in our center was also high (r = 0.88, p < 0.0001); intra-assay variability, expressed as the difference between values as a percentage of the higher value, was low at 9.4% (SD = 7.9%). Although both time the sample spent in the freezer (r = 0.16, p = 0.04) and age of the kit used for assay (t = 3.64, p = 0.0004) were significant predictors of intra-kit variability in univariate analyses, only age of kit was significant in multivariate linear regression (F = 4.93, p = 0.03). Age of radioimmunoassay kit affects intra-kit variability of measured hypocretin values, such that kits closer to expiration exhibit significantly more variability.

Decline of CSF orexin (hypocretin) levels in Prader-Willi syndrome.

Prader-Willi syndrome is a congenital neurodevelopmental disorder resulting from deletion of the paternal copies of genes within the chromosome region 15q11-q13. Patients with Prader-Willi syndrome often exhibit excessive daytime sleepiness, excessive appetite, and obesity. As is the case in narcolepsy, orexin (hypocretin) may be responsible for these symptoms. However, reports showing cerebrospinal fluid orexin levels in Prader-Willi syndrome patients have been limited. The aim of this study was to examine the relationship between the characteristic symptoms of Prader-Willi syndrome and cerebrospinal fluid orexin levels. We clinically identified 14 Prader-Willi syndrome patients and examined their cerebrospinal fluid orexin levels. A total of 12 patients with a 15q11-q13 deletion and two patients with maternal uniparental disomy of chromosome 15 were identified. A total of 37 narcoleptic patients and 14 idiopathic hypersomnia patients were recruited for comparison. Cerebrospinal fluid orexin levels (median [25-75 percentiles]) in the 14 Prader-Willi syndrome patients were intermediate (192 [161-234.5] pg/ml), higher than in the narcoleptic patients, but lower than in the idiopathic hypersomnia patients. Body mass index of the Prader-Willi syndrome patients was higher than in the narcoleptic and idiopathic hypersomnia patients. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader-Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader-Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness.

Which diagnostic findings in disorders with excessive daytime sleepiness are really helpful? A retrospective study.

Due to extensive clinical and electrophysiological overlaps, the correct diagnosis of disorders with excessive daytime sleepiness is often challenging. The aim of this study was to provide diagnostic measures that help discriminating such disorders, and to identify parameters, which don't. In this single-center study, we retrospectively identified consecutive treatment-naïve patients who suffered from excessive daytime sleepiness, and analyzed clinical and electrophysiological measures in those patients in whom a doubtless final diagnosis could be made. Of 588 patients, 287 reported subjective excessive daytime sleepiness. Obstructive sleep apnea is the only disorder that could be identified by polysomnography alone. The diagnosis of insufficient sleep syndrome relies on actigraphy as patients underestimate their sleep need and the disorder shares several clinical and electrophysiological properties with both narcolepsy type 1 and idiopathic hypersomnia. Sleep stage sequencing on MSLT appears helpful to discriminate between insufficient sleep syndrome and narcolepsy. Sleep inertia is a strong indicator for idiopathic hypersomnia. There are no distinctive electrophysiological findings for the diagnosis of restless legs syndrome. Altogether, EDS disorders are common in neurological sleep laboratories, but usually cannot be diagnosed based on PSG and MSLT findings alone. The diagnostic value of actigraphy recordings can hardly be overestimated.

Modafinil in the treatment of idiopathic hypersomnia without long sleep time--a randomized, double-blind, placebo-controlled study.

In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo-controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug-free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep-wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non-significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.

Sleep architecture in idiopathic hypersomnia: the influence of age, sex, and body mass index.

This study aimed to progress the understanding of idiopathic hypersomnia (IH) by assessing the moderating influence of individual characteristics, such as age, sex, and body mass index (BMI) on sleep architecture. In this retrospective study, 76 IH participants (38.1 ± 11.3 years; 40 women) underwent a clinical interview, an in-laboratory polysomnography with a maximal 9-h time in bed and a multiple sleep latency test (MSLT). They were compared to 106 healthy controls (38.1 ± 14.1 years; 60 women). Multiple regressions were used to assess moderating influence of age, sex, and BMI on sleep variables. We used correlations to assess whether sleep variables were associated with Epworth Sleepiness Scale scores and mean sleep onset latency on the MSLT in IH participants. Compared to controls, IH participants had shorter sleep latency (p = 0.002), longer total sleep time (p < 0.001), more time spent in N2 sleep (p = 0.008), and showed trends for a higher sleep efficiency (p = 0.023) and more time spent in rapid eye movement (REM) sleep (p = 0.022). No significant moderating influence of age, sex, or BMI was found. More severe self-reported sleepiness in IH patients was correlated with shorter REM sleep latency and less N1 sleep in terms of proportion and duration (ps < 0.01). This study shows that, when compared to healthy controls, patients with IH had no anomalies in their sleep architecture that can explain their excessive daytime sleepiness. Moreover, there is no moderating influence of age, sex, and BMI, suggesting that the absence of major group differences is relatively robust.

Narcolepsy Severity Scale-2 and Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and consequences in Narcolepsy type 2.

STUDY OBJECTIVES: Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy type 1 and idiopathic hypersomnia (IH). We aimed: (1) to assess systematically the symptoms in patients with NT2, with self-reported questionnaires: Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), and (2) to evaluate the responsiveness of these scales to treatment. METHODS: One hundred and nine patients with NT2 (31.4 ±â€…12.2 years old, 47 untreated) diagnosed according to ICSD-3 were selected in a Reference Center for Narcolepsy. They all completed the ESS, subgroups completed the modified NSS (NSS-2, without cataplexy items) (n = 95) and IHSS (n = 76). Some patients completed the scales twice (before/during treatment): 42 ESS, 26 NSS-2, and 30 IHSS. RESULTS: Based on NSS-2, all untreated patients had sleepiness, 58% disrupted nocturnal sleep, 40% hallucinations, and 28% sleep paralysis. On IHSS, 76% reported a prolonged nocturnal sleep, and 83% sleep inertia. In the independent sample, ESS and NSS-2 scores were lower in treated patients, with same trend for IHSS scores. After treatment, ESS, NSS-2, and IHSS total scores were lower, with a mean difference of 3.7 ±â€…4.1, 5.3 ±â€…6.7, and 4.1 ±â€…6.2, respectively. The minimum clinically important difference between untreated and treated patients were 2.1 for ESS, 3.3 for NSS-2, and 3.1 for IHSS. After treatment, 61.9% of patients decreased their ESS > 2 points, 61.5% their NSS-2 > 3 points, and 53.3% their IHSS > 3 points. CONCLUSIONS: NSS-2 and IHSS correctly quantified symptoms' severity and consequences in NT2, with good performances to objectify response to medications. These tools are useful for monitoring and optimizing NT2 management, and for use in clinical trials.

Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias.

BACKGROUND: The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. METHODS: We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N-C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. RESULTS: All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N-C only 52% arose from NREM1. Within the N-C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). CONCLUSIONS: These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Polysomnographic study of nocturnal sleep in idiopathic hypersomnia without long sleep time.

We investigated nocturnal sleep abnormalities in 19 patients with idiopathic hypersomnia without long sleep time (IH) in comparison with two age- and sex- matched control groups of 13 normal subjects (C) and of 17 patients with narcolepsy with cataplexy (NC), the latter considered as the extreme of excessive daytime sleepiness (EDS). Sleep macro- and micro- (i.e. cyclic alternating pattern, CAP) structure as well as quantitative analysis of EEG, of periodic leg movements during sleep (PLMS), and of muscle tone during REM sleep were compared across groups. IH and NC patients slept more than C subjects, but IH showed the highest levels of sleep fragmentation (e.g. awakenings), associated with a CAP rate higher than NC during lighter sleep stages and lower than C during slow wave sleep respectively, and with the highest relative amount of A3 and the lowest of A1 subtypes. IH showed a delta power in between C and NC groups, whereas muscle tone and PLMS had normal characteristics. A peculiar profile of microstructural sleep abnormalities may contribute to sleep fragmentation and, possibly, EDS in IH.

Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness.

Patients with idiopathic hypersomnia never feel fully alert despite a normal or long sleep night. The spectrum of the symptoms is insufficiently studied. We interviewed 62 consecutive patients with idiopathic hypersomnia (with a mean sleep latency lower than 8 min or a sleep time longer than 11 h) and 50 healthy controls using a questionnaire on sleep, awakening, sleepiness, alertness and cognitive, psychological and functional problems during daily life conditions. Patients slept 3 h more on weekends, holidays and in the sleep unit than on working days. In the morning, the patients needed somebody to wake them, or to be stressed, while routine, light, alarm clocks and motivation were inefficient. Three-quarters of the patients did not feel refreshed after short naps. During the daytime, their alertness was modulated by the same external conditions as controls, but they felt more sedated in darkness, in a quiet environment, when listening to music or conversation. Being hyperactive helped them more than controls to resist sleepiness. They were more frequently evening-type and more alert in the evening than in the morning. The patients were able to focus only for 1 h (versus 4 h in the controls). They complained of attention and memory deficit. Half of them had problems regulating their body temperature and were near-sighted. Mental fatigability, dependence on other people for awakening them, and a reduced benefit from usually alerting conditions (except being hyperactive or stressed) seem to be more specific of the daily problems of patients with idiopathic hypersomnia than daytime sleepiness.

Insulinoma presenting as idiopathic hypersomnia.

We report the case of a 32-year-old woman with a history of increased sleep need and difficulty waking up; the diagnosis of idiopathic hypersomnia was hypothesized. During ambulatory polysomnography (PSG), the patient presented an episode characterized by loss of consciousness and jerking of the four limbs. A video-PSG monitoring was performed and the patient showed unresponsiveness and drowsiness at 7 a.m. During the episode, EEG showed theta-delta diffuse activity, and blood glucose level was 32 mg dl(-1). The diagnosis of insulinoma was then assumed; CT scan showed a hypodense mass into the pancreatic tail, and a partial pancreasectomy was performed. The described symptoms disappeared, and 5 years later the findings of a complete clinical and neurophysiological examination were negative. The clinical picture of insulinoma presenting with paroxysmal disorders has been previously described; however, whereas hypersomnia is uncommon, in the current case it represents the main symptom. Clinicians should keep in mind that neuroglycopenia should be considered in the differential diagnosis of patients with hypersomnia, particularly if the clinical scenario does not conform to standard criteria.

Automatic detection of microsleep episodes with feature-based machine learning.

STUDY OBJECTIVES: Microsleep episodes (MSEs) are brief episodes of sleep, mostly defined to be shorter than 15 s. In the electroencephalogram (EEG), MSEs are mainly characterized by a slowing in frequency. The identification of early signs of sleepiness and sleep (e.g. MSEs) is of considerable clinical and practical relevance. Under laboratory conditions, the maintenance of wakefulness test (MWT) is often used for assessing vigilance. METHODS: We analyzed MWT recordings of 76 patients referred to the Sleep-Wake-Epilepsy-Center. MSEs were scored by experts defined by the occurrence of theta dominance on ≥1 occipital derivation lasting 1-15 s, whereas the eyes were at least 80% closed. We calculated spectrograms using an autoregressive model of order 16 of 1 s epochs moved in 200 ms steps in order to visualize oscillatory activity and derived seven features per derivation: power in delta, theta, alpha and beta bands, ratio theta/(alpha + beta), quantified eye movements, and median frequency. Three algorithms were used for MSE classification: support vector machine (SVM), random forest (RF), and an artificial neural network (long short-term memory [LSTM] network). Data of 53 patients were used for the training of the classifiers, and 23 for testing. RESULTS: MSEs were identified with a high performance (sensitivity, specificity, precision, accuracy, and Cohen's kappa coefficient). Training revealed that delta power and the ratio theta/(alpha + beta) were most relevant features for the RF classifier and eye movements for the LSTM network. CONCLUSIONS: The automatic detection of MSEs was successful for our EEG-based definition of MSEs, with good performance of all algorithms applied.

Optimizing Actigraphic Estimation of Sleep Duration in Suspected Idiopathic Hypersomnia.

STUDY OBJECTIVES: To determine the optimal Actiwatch 2 setting configuration for the estimation of total sleep time (TST) in persons with suspected idiopathic hypersomnia. METHODS: Thirty-three patients with a diagnosis of idiopathic hypersomnia (28 female; mean age = 33.7 ± 10.5) underwent ad libitum polysomnography with concurrent use of the Actiwatch 2. Actiwatch 2 sleep-wake activity threshold (SWAT; Low, Medium, and High) and sleep immobility onset and offset (SIOO; 5, 10, 15, 20, 25, and 30 epoch) duration were modified during data processing. The resultant 18 unique setting combinations were subsequently evaluated using Bland-Altman and epoch comparison analyses to determine optimal settings relative to polysomnography. RESULTS: Low SWAT + 25 Epoch SIOO displayed the least divergence from polysomnography (mean difference 3.4 minutes). Higher SWAT and lower SIOO increased sensitivity and accuracy, but at the expense of reducing specificity and the ability to accurately estimate TST. CONCLUSIONS: These results demonstrate that actigraphic settings should be carefully considered when estimating sleep duration. The Low + 25 Epoch configuration is indicated as most optimal for estimating TST in persons with suspected idiopathic hypersomnia. COMMENTARY: A commentary on this article appears in this issue on page 539.

Disease-specific attention impairment in disorders of chronic excessive daytime sleepiness.

OBJECTIVE: Patients with chronic excessive daytime sleepiness (EDS) complain of substantial attention deficits. However, their underlying neuronal dysfunction is largely unknown. Previous studies showed similar attention performances in central disorders of hypersomnolence suggesting that EDS-related cognitive impairment is independent of its cause. The aim of the current study was to further explore attentional profiles in disorders of chronic EDS. METHODS: Ten patients with narcolepsy type 1 (NT1; age 26.7 ± 9.3 years), 14 patients with idiopathic hypersomnia (IH; age 26.7 ± 9.3 years), 14 patients with subjective EDS (sEDS; age 31.4 ± 14.3 years), ie, a mean sleep latency >8 min in the multiple sleep latency test (MSLT), and 20 healthy controls (HC; age 32.6 ± 11.3 years) performed the vigilance task and the selective attention task of the test battery SLEEP® (Vienna Test System Neuro®). We assessed mean response time (RT) and standard deviation of RT separately for the first and the second half of the vigilance task to evaluate performance changes over time (time on task effect; TOT). RESULTS: A significant interaction effect between group and TOT on the mean RT in the vigilance task suggests partly group-specific attention deficits. Combining paradigms of sustained and selective attention discriminated patients with NT1, IH, sEDS and HC. Behavioral results were unrelated to the mean sleep latency in the MSLT. CONCLUSIONS: Discriminative performance of the sustained and selective attention tasks indicate disease-specific components of attention in NT1, IH, and sEDS. Different temporal dynamics of attentional control efficiency might be one factor underlying group differences.

Precision Medicine for Idiopathic Hypersomnia.

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness despite normal or prolonged sleep. IH is distinguished from narcolepsy by the female predominance, severe morning inertia, continuous drowsiness (rather than sleep attacks), unrefreshing naps, absence of cataplexy, sleep onset in REM periods, and hypocretin deficiency. In IH, the multiple sleep latency test demonstrates low sensitivity, specificity, and reproducibility, compared with prolonged sleep monitoring. In some IH cases, an endogenous hypnotic peptide stimulating GABA receptors during wakefulness is suspected, which are improved by anti-GABA drugs. The benefits of modafinil, sodium oxybate, mazindol, and pitolisant were found in mostly retrospective studies.

Specific T-cell activation in peripheral blood and cerebrospinal fluid in central disorders of hypersomnolence.

An autoimmune-mediated process in the pathophysiology of narcolepsy type 1 (NT1) is highly suspicious, if this pathomechanism is transferable to other types of central disorders of hypersomnolence (CDH), is still controversial. The association of NT1 with HLA class II system implicates a T-cell-mediated autoimmunity, in which helper CD4+ T-cells and cytotoxic CD8+ T-cells may be pathogenic. This study aimed to identify specific immune profiles in peripheral blood (PB) and cerebrospinal fluid (CSF) in different types of CDH. Forty-three people with polysomnographically confirmed CDH (24 idiopathic hypersomnia [IH], 12 NT1, and 7 NT2) were compared with 24 healthy controls (HC). PB and CSF were analyzed with multiparameter flow cytometry to distinguish between subclasses of peripheral and intrathecal immune cells and specific surface markers of T-cells. The overall proportion of helper CD4+ T-cells and cytotoxic CD8+ T-cells in PB and CSF did not differ between the patients and HC. Activated HLA-DR+ CD4+ T-cells and HLA-DR+ CD8+ T-cells in PB and CSF both in NT1, NT2 and IH were significantly increased compared with HC. A significant correlation of HLA-DR+ CD4+- and HLA-DR+ CD8+ T-cells with higher amounts of excessive daytime sleepiness was found in the NT1 and IH groups, indicating an association of activated T-cells in the central nervous system with an increase in sleepiness. These findings provide further evidence of a T-cell-mediated autoimmunity not only in NT1, but also in NT2 and IH. Moreover, the identification of activated cytotoxic CD8+ T-cells further supports the evidence of T-cell-mediated neuronal damage, which has previously been suggested in NT1.

Nocturnal sleep architecture in idiopathic hypersomnia: a systematic review and meta-analysis.

BACKGROUND: Current sleep medicine nosology places increased importance on nocturnal polysomnographic sleep recordings in the diagnosis of central nervous system disorders of hypersomnolence, particularly idiopathic hypersomnia (IH). OBJECTIVE: Determine what differences in sleep staging and architecture exist between IH and healthy controls using meta-analysis. METHODS: Systematic review identified relevant studies that included nocturnal polysomnography data for IH and healthy control groups. Meta-analysis compared standardized mean differences (Hedge's g) for total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), rapid eye movement (REM) sleep percentage, slow wave sleep (SWS) percentage, and REM latency (REML). Moderator analyses were also conducted for variables with significant heterogeneity among studies. RESULTS: The meta-analysis included 10 studies. Relative to controls, IH demonstrated increased TST (pooled g = 0.92; 95% CI: 0.46 to 1.38, p < 0.0001) and REM percentage (pooled g = 0.36, 95% CI: 0.09 to 0.64, p = 0.01), decreased SOL (pooled g = -0.46; 95% CI: -0.81 to -0.12, p = 0.009) and SWS percentage (pooled g = -0.28, 95% CI: -0.50 to -0.07, p = 0.01), without significant differences in SE (pooled g = 0.03; 95% CI: -0.32 to 0.38, p = 0.86) or REML (pooled g = 0.14, 95% CI: -0.21 to 0.49, p = 0.42). Moderator analysis demonstrated a significant effect of sex on SE, with a higher proportion of women to men significantly predicting lower SE between in IH and controls (p < 0.0001). CONCLUSIONS: IH is associated with several changes in sleep staging and architecture relative to healthy persons, including alterations in REM and SWS not currently delineated in nosological constructs. Further research is indicated to clarify how these findings are related the pathophysiology of IH and related disorders.

Update on treatment for idiopathic hypersomnia.

INTRODUCTION: Idiopathic hypersomnia (IH) is a poorly characterized orphan central disorder of hypersomnolence responsible for excessive daytime sleepiness (EDS), prolonged nighttime sleep and sleep inertia that often require long-term symptomatic stimulant medication. To date, no drug has currently the authorization for the treatment of IH patients worldwide. Areas covered: The authors reviewed data on pharmacological treatment of IH obtained from published literature (Medline/PubMed/Web of Science) and Clinicaltrial.gov database from 1997 to 2017. Most of data on treatment of IH derived from observational studies and case series with only three well-designed clinical trials available. Expert opinion: In two recent randomized, double-blind, placebo-controlled trials, modafinil improves EDS in IH. Most of other wakefulness-promoting agents labeled for narcolepsy have similar efficacy in cases series of IH patients. Pitolisant and sodium oxybate show promising results in two retrospective studies. The efficacy of γ-aminobutyric acid-A receptor antagonists on objective EDS needs to be clarified. All these medications are used off-label for the management of EDS in IH. Specific clinical instruments and objective tests are required in IH to better evaluate the severity of EDS and responsiveness to medications, but also prolonged sleep and sleep inertia, to optimize the whole management of IH patients.

Ability of the Multisensory Jawbone UP3 to Quantify and Classify Sleep in Patients With Suspected Central Disorders of Hypersomnolence: A Comparison Against Polysomnography and Actigraphy.

STUDY OBJECTIVES: To evaluate the ability of a multisensory fitness tracker, the Jawbone UP3 (JB3), to quantify and classify sleep in patients with suspected central disorders of hypersomnolence. METHODS: This study included 43 patients who completed polysomnography (PSG) and a Multiple Sleep Latency Test (MSLT) with concurrent wrist-worn JB3 and Actiwatch 2 (AW2) recordings for comparison. Mean differences in nocturnal sleep architecture variables were compared using Bland-Altman analysis. Sensitivity, specificity, and accuracy were derived for both devices relative to PSG. Ability of the JB3 to detect sleep onset rapid eye movement periods (SOREMPs) during MSLT naps was also quantified. RESULTS: JB3 demonstrated a significant overestimation of total sleep time (39.6 min, P < .0001) relative to PSG, but performed comparably to AW2. Although the ability of the JB3 to detect epochs of sleep was relatively good (sensitivity = 0.97), its ability to distinguish light, deep, and REM sleep was poor. Similarly, the JB3 did not correctly identify a single SOREMP during any MSLT nap opportunity. CONCLUSIONS: The JB3 did not accurately quantify or classify sleep in patients with suspected central disorders of hypersomnolence, and was particularly poor at identifying REM sleep. Thus, this device cannot be used as a surrogate for PSG or MSLT in the assessment of patients with suspected central disorders of hypersomnolence.

Associations Between Neuropsychological, Neurobehavioral and Emotional Functioning and Either Narcolepsy or Idiopathic Hypersomnia in Children and Adolescents.

STUDY OBJECTIVES: Narcolepsy and idiopathic hypersomnia are chronic neurological sleep disorders characterized by hypersomnolence or excessive daytime sleepiness. This review aims to systematically examine the scientific literature on the associations between narcolepsy and idiopathic hypersomnia and their effect on intellectual functioning, academic achievement, behavior, and emotion. METHODS: Published studies that examined those associations in children and adolescents were included. Studies in which children or adolescents received a clinical diagnosis, and in which the associated function was measured with at least one objective instrument were included. Twenty studies published between 1968 and 2017 were eligible for inclusion in this review. RESULTS: There does not appear to be a clear association between intellectual functioning and narcolepsy or idiopathic hypersomnia; however, limited research is an obstacle to obtaining generalizability. The variability in results from studies investigating associations between academic achievement and these two hypersomnolence disorders suggests that further research using standardized and validated assessment instruments is required to determine if there is an association. Behavior and emotion appear to be significantly affected by narcolepsy. Only two studies included populations of children and adolescents with idiopathic hypersomnia. CONCLUSIONS: Further research using larger populations of children and adolescents with narcolepsy or idiopathic hypersomnia while utilizing standardized and validated instruments is required, because the effect of these conditions of hypersomnolence varies and is significant for each individual.