Idiopathic Hypersomnia and Other Hypersomnia Syndromes.
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ABSTRACT:
SUBMITTER: Trotti LM
PROVIDER: S-EPMC8116415 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy.Methodology/principal findingsWe measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance.Conclusions/significanceOur study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.
| S-EPMC2832686 | biostudies-literature
Project description:Study objectivesWe 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.MethodsOne 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).ResultsOnline 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.ConclusionsSymptoms 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.
| S-EPMC7849804 | biostudies-literature
Project description:Objective/backgroundKnowledge of idiopathic hypersomnia symptomatology derives from clinical case series. Web-based registries provide complementary information by allowing larger sample sizes, with greater geographic and social diversity.Patients/methodsData were obtained from the Hypersomnia Foundation's online registry. Common clinical features of idiopathic hypersomnia and other central disorders of hypersomnolence were queried, for the last thirty days and when symptoms were most severe. Symptoms were compared between idiopathic hypersomnia participants with and without long sleep durations and between participants with idiopathic hypersomnia and those with either form of narcolepsy. Frequency of medication use and residual symptoms on medication were evaluated.ResultsFive-hundred sixty-three registry respondents were included, with idiopathic hypersomnia (n = 468), narcolepsy type 2 (n = 44), and narcolepsy type 1 (n = 51). "Brain fog," poor memory, and sleep drunkenness were all present in most idiopathic hypersomnia respondents, with brain fog and sleep drunkenness more commonly endorsed by those with long sleep durations. Eighty-two percent of participants with idiopathic hypersomnia were currently treated with medication, most commonly traditional psychostimulants such as amphetamine salts. Among treated patients, symptoms improved while on medication, but substantial residual hypersomnia symptoms remained. Participants with narcolepsy type 1 were more likely than those with idiopathic hypersomnia to endorse intentional and unintentional daytime naps and automatic behaviors.ConclusionsSymptoms of idiopathic hypersomnia extend well beyond excessive daytime sleepiness, and these symptoms frequently persist despite treatment. These findings highlight the importance of online registries in identifying gaps in the use and effectiveness of current treatments.
| S-EPMC7669698 | biostudies-literature
Project description:Narcolepsy and other syndromes associated with excessive daytime sleepiness can be challenging to treat. New classifications now distinguish narcolepsy/hypocretin deficiency (also called type 1 narcolepsy), a lifelong disorder with well-established diagnostic procedures and etiology, from other syndromes with hypersomnolence of unknown causes. Klein-Levin Syndrome, a periodic hypersomnia associated with cognitive and behavioral abnormalities, is also considered a separate entity with separate therapeutic protocols. Non hypocretin-related hypersomnia syndromes are diagnoses of exclusion. These diagnoses are only made after eliminating sleep deprivation, sleep apnea, disturbed nocturnal sleep, and psychiatric comorbidities as the primary cause of daytime sleepiness. The treatment of narcolepsy/hypocretin deficiency is well-codified, and involves pharmacotherapies using sodium oxybate, stimulants, and/or antidepressants, plus behavioral modifications. These therapies are almost always needed, and the risk-to-benefit ratio is clear, notably in children. Detailed knowledge of the pharmacological profile of each compound is needed to optimize use. Treatment for other syndromes with hypersomnolence is more challenging and less codified. Preferably, therapy should be conservative (such as modafinil, atomoxetine, behavioral modifications), but it may have to be more aggressive (high-dose stimulants, sodium oxybate, etc.) on a case-by-case, empirical trial basis. As cause and evolution are unknown in these conditions, it is important to challenge diagnosis and therapy over time, keeping in mind the possibility of tolerance and the development of stimulant addiction. Kleine-Levin Syndrome is usually best left untreated, although lithium can be considered in severe cases with frequent episodes. Guidelines are provided based on the literature and personal experience of the author.
| S-EPMC3480574 | biostudies-literature
Project description:Idiopathic hypersomnia (IH) is a rare neurological sleep disorder, characterized by excessive daytime sleepiness despite normal sleep duration, that can significantly impact patient's lives. The burden of IH goes beyond excessive daytime sleepiness, pervading all aspects of everyday life. Characteristic and burdensome symptoms of IH include sleep inertia/drunkenness, long sleep duration, and daytime cognitive dysfunction. This systematic review assessed current knowledge regarding IH diagnostic challenges and burden of illness. Literature searches for original epidemiological, clinical, humanistic, or economic research relevant to IH published between 2012 and 2022 in MEDLINE, Embase, Cochrane, gray literature (diagnostic criteria and treatment guidelines), conferences (2019-2022), and clinical trial databases yielded 97 articles. Findings indicate that IH remains a poorly defined diagnosis of exclusion that is difficult to distinguish from narcolepsy type 2 because of symptom overlap and inadequacies of objective testing. Consequently, individuals with IH endure diagnostic delays of up to 9 years. The economic burden of IH has not been characterized to any appreciable extent. Pharmacological treatment options can improve symptoms and functional status, but rarely restores normal levels of functioning. These findings highlight the need to reclassify central disorders of hypersomnolence. Further collaboration is now required between research groups to identify and validate objective markers to help redefine diagnostic criteria for IH. This would move IH into a position that could benefit from future targeted therapeutic interventions. The study was funded by Takeda Development Center Americas, Inc.
| S-EPMC11359170 | biostudies-literature
Project description:IntroductionPatients with either Idiopathic Hypersomnia or Narcolepsy demonstrate excessive daytime somnolence (EDS) with resultant inattention mimicking Attention Deficit Hyperactivity Disorder (ADHD). Patients with ADHD also often express sleep problems including EDS. Thus, patients with ADHD and patients with idiopathic hypersomnia or narcolepsy may share inattention and daytime drowsiness as common features. However, it is not known whether EDS patients with idiopathic hypersomnia or narcolepsy also have increased movement (hyperactivity) like ADHD patients, the determination of which is the purpose of this study.MethodsWe studied 12 patients (7 Narcolepsy type 2 and 5 Idiopathic Hypersomnia) with EDS as shown by Multiple Sleep Latency Test which served as the gold standard for entry into the study. Twelve subjects without symptoms of EDS served as the control group. None of the participants had a previous history of ADHD. Each participant underwent a one-hour session laying at 45 degrees with surveys about the need to move and actigraphy as an objective measure of movement.ResultsSleep-disordered patients with EDS reported more symptoms of inattention and hyperactivity on the ADHD Self-Report Scale. At each of the time points patients with EDS had a clear trend to express the need to move more than controls on the Suggested Immobilization Test (SIT). For the total 60 minutes, a large effect size for the need to move during the SIT test was found between patients and controls (Cohen's d = 0.61, p=0.01). Patients with EDS did not express a need to move more to combat drowsiness than controls, nor did actigraphy show any difference in objective movement between patients and controls during the SIT.ConclusionPatients with EDS express inattention and a need to move more than controls. However, hyperactivity was not verified by objective measurement, nor did the EDS patients express a need to move to combat drowsiness more than controls. Thus, a hypothesis to be further tested, is whether narcolepsy and idiopathic hypersomnia may be more a model of the inattentive form of ADHD rather than the combined or inattentive/hyperactive form of ADHD. Further studies are needed to explore the relationship between EDS and hyperactivity.
| S-EPMC10494784 | biostudies-literature
Project description: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.
| S-EPMC5916770 | biostudies-literature
Project description:Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient's life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia.
| S-EPMC10445641 | biostudies-literature
Project description:RationaleAlthough patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for its diagnosis due to the lack of symptom recognition. Here, we present a case of idiopathic hypersomnia (IH), a CDH, wherein early diagnosis was aided by a video footage of a spontaneous sleep attack.Patient concernsA 21-year-old man lost consciousness while driving and experienced an accident. He had complained of excessive daytime sleepiness (EDS) over half a year. During his hospitalization for close monitoring of the loss of consciousness, an in-room surveillance camera captured a 14-minutes long spontaneous sleep attack, during which he experienced general muscle weakness and loss of consciousness without warnings or convulsions leading to a fall from the bed. There were no abnormalities in vital signs.DiagnosesThere was no significant cataplexy and less than 2 sleep-onset rapid eye movements (SOREM) in 2 sleep latency tests, with a mean sleep latency of 2.1 and 4.6 minutes. Other sleep deprivation syndromes were excluded from differential diagnosis and finally, a diagnosis of IH was confirmed according to the criteria of the Third Edition of the International Classification of Sleep Disorders. During the course of the disease, attention-deficit/hyperactive disorder (ADHD) and a gaming disorder also diagnosed.InterventionsPharmacological treatment with modafinil was administered for IH and methylphenidate for ADHD. Cognitive behavioral therapy was performed for the gaming disorder.OutcomesThe EDS improved, and sleep attacks were no longer observed. The disruption of daily life caused by the gaming disorder was also reduced.LessonsVideo recordings of sleep attacks are beneficial for identifying the cause of loss of consciousness. Home video recordings may be helpful in the early diagnosis of IH.
| S-EPMC10869082 | biostudies-literature
Project description:Study objectivesIdiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH.MethodsAdults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period.ResultsOf 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants.ConclusionsA single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.
| S-EPMC10485568 | biostudies-literature