Abstract
Introduction
Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep phenomena. Narcolepsy can be distinguished into type 1 (NT1; with ...cataplexy) and type 2 (NT2; without cataplexy). It has been reported that sleep stage sequences at sleep-onset as well as sleep-wake dynamics across the night may be useful in the differential diagnosis of hypersomnia. Here we studied dynamic features of sleep stage transitions during whole night sleep in patients with NT1, NT2, and other types of hypersomnia (o-HS).
Methods
Twenty patients with NT1, 14 patients with NT2, and 35 patients with o-HS underwent overnight PSG. Transition probabilities between sleep stages (wake, N1, N2, N3, and REM) and survival curves of continuous runs of each sleep stage were compared between groups. Transition-specific survival curves of continuous runs of each sleep stage, dependent on the subsequent stage of the transition, were also compared.
Results
The probability of transitions from N1-to-wake was significantly greater in NT1 than in NT2 and o-HS while that from N1-to-N2 was significantly smaller in NT1 than in NT2 and o-HS. The probability of transitions from N2-to-REM was significantly smaller in NT1 than in o-HS. Wake and N1 were significantly more continuous in NT1 than in NT2; specifically, N1 followed by N2 was significantly more continuous in NT1 than in NT2 and o-HS. N2 was significantly less continuous in NT1 and NT2 than in o-HS; this was specifically confirmed for N2 followed by N1/wake. REM sleep was significantly less continuous in NT1 than in NT2 and o-HS; specifically, REM sleep followed by wake was significantly less continuous in NT1 than in o-HS. Continuity of N3 did not differ significantly between groups.
Conclusion
Dynamics of sleep stage transitions differed between NT1, NT2, and o-HS. Dynamic features of sleep such as sleep instability, persistency of wake/N1, and REM fragmentation may differentiate NT1 from NT2, while N2 continuity may differentiate narcolepsy from o-HS. The results suggest that sleep transition analysis may be of clinical utility and provide insights into the underlying pathophysiology of hypersomnia and narcolepsy.
Support
JSPS KAKENHI (18K17891 to AK).
Summary Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. ...Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1–2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.
The first COVID-19 contagion wave caused unprecedented restraining measures worldwide. In Italy, a period of generalized lockdown involving home confinement of the entire population was imposed for ...almost two months (9 March-3 May 2020). The present is the most extensive investigation aimed to unravel the demographic, psychological, chronobiological, and work-related predictors of sleep disturbances throughout the pandemic emergency. A total of 13,989 Italians completed a web-based survey during the confinement period (25 March-3 May). We collected demographic and lockdown-related work changes information, and we evaluated sleep quality, insomnia and depression symptoms, chronotype, perceived stress, and anxiety using validated questionnaires. The majority of the respondents reported a negative impact of confinement on their sleep and a delayed sleep phase. We highlighted an alarming prevalence of sleep disturbances during the lockdown. Main predictors of sleep disturbances identified by regression models were: female gender, advanced age, being a healthcare worker, living in southern Italy, confinement duration, and a higher level of depression, stress, and anxiety. The evening chronotype emerged as a vulnerability factor, while morning-type individuals showed a lower predisposition to sleep and psychological problems. Finally, working from home was associated with less severe sleep disturbances. Besides confirming the role of specific demographic and psychological factors in developing sleep disorders during the COVID-19 pandemic, we propose that circadian typologies could react differently to a particular period of reduced social jetlag. Moreover, our results suggest that working from home could play a protective role against the development of sleep disturbances during the current pandemic emergency.
Sleep in the United States Military Good, Cameron H; Brager, Allison J; Capaldi, Vincent F ...
Neuropsychopharmacology (New York, N.Y.),
01/2020, Letnik:
45, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The military lifestyle often includes continuous operations whether in training or deployed environments. These stressful environments present unique challenges for service members attempting to ...achieve consolidated, restorative sleep. The significant mental and physical derangements caused by degraded metabolic, cardiovascular, skeletomuscular, and cognitive health often result from insufficient sleep and/or circadian misalignment. Insufficient sleep and resulting fatigue compromises personal safety, mission success, and even national security. In the long-term, chronic insufficient sleep and circadian rhythm disorders have been associated with other sleep disorders (e.g., insomnia, obstructive sleep apnea, and parasomnias). Other physiologic and psychologic diagnoses such as post-traumatic stress disorder, cardiovascular disease, and dementia have also been associated with chronic, insufficient sleep. Increased co-morbidity and mortality are compounded by traumatic brain injury resulting from blunt trauma, blast exposure, and highly physically demanding tasks under load. We present the current state of science in human and animal models specific to service members during- and post-military career. We focus on mission requirements of night shift work, sustained operations, and rapid re-entrainment to time zones. We then propose targeted pharmacological and non-pharmacological countermeasures to optimize performance that are mission- and symptom-specific. We recognize a critical gap in research involving service members, but provide tailored interventions for military health care providers based on the large body of research in health care and public service workers.
Introduction The recommended dosage range for sodium oxybate (SXB) among adults with narcolepsy is 6-9g per night orally, divided into 2 equal doses. The objective of this study was to describe ...real-world dosing of SXB among adults with narcolepsy. Methods The Nexus Narcolepsy Registry is an ongoing, self-reported online registry of adults diagnosed with narcolepsy. The study identified SXB users who had reported dosage data and compared those currently taking SXB vs those who previously discontinued. Of current users, those taking SXB <3 months (hereafter “new users”) vs ≥3 months (hereafter “established users”) also were compared. The survey assessed once-nightly or twice-nightly SXB dosing across the dose range (<4.5g, 4.5-<6g, 6-<9g, 9g, >9g), and equally-divided (1st dose=2nd dose) vs asymmetric dosing (1st dose≠2nd dose). Descriptive analyses and t tests assessed sample characteristics and dosing patterns. All P values are uncontrolled for multiplicity, hence, are nominal. Results Among all participants reporting SXB use (n=365), 65% were current users and 95% took SXB twice nightly. Average total nightly dose (standard deviation) was 7g (±1.9) and 3.6g (±0.9) for twice-nightly and once-nightly dosing, respectively. Among those who took SXB twice nightly, the total nightly dose was lower in those who discontinued vs current users (5.9g ±2.1 vs 7.6g ±1.6; P<0.001) and lower in new users vs established users (6.5g ±1.8 vs 7.7g ±1.5; P<0.001). Among all SXB users, 66% reported doses within the recommended dosage range of 6-9g per night; 80% of current users and 40% of discontinued users took 6-9g per night. Nearly 30% of all SXB users, 16% of current users, and 55% of discontinued users took <6g per night. Among all SXB users, 84% reported equally-divided dosing. For current new users and current established users, 96% and 83%, respectively, reported equally-divided dosing. Conclusion Among SXB users in the Nexus Narcolepsy Registry, the majority reported taking SXB twice nightly, with the total nightly dose equally divided. 17% of current established users reported asymmetric dosing, and 5% of all SXB users reported once-nightly dosing. Support (If Any) Jazz Pharmaceuticals
Introduction Type 1 narcolepsy (T1N) is a disorder characterized by hypersomnolence, cataplexy, sleep paralysis or sleep-related hallucination. Cataplexy is a sudden loss of muscle tone triggered by ...emotional changes such as laughing and is caused by the inappropriate activation of descending neural pathways that promote atonia. Type II narcolepsy (T2N) is a disorder like T1N but without cataplexy. It has been established that HLA-DQB1*0602 is a marker for narcolepsy on chromosome 6 across all ethnic groups. For patients with narcolepsy, the pattern of hypoperfusion on brain SPECT had been controversial on previous studies. Methods In this report, we demonstrated the imaging findings of narcolepsy cases with free of all drugs on Tc-99m ECD brain perfusion SPECT, which were firstly analyzed by the easy Z-score imaging system (eZIS) among the published literature. eZIS is a computer-assisted statistical analysis based on the comparison with age-classified ECD normal database. eZIS provides objective and reproducible interpretation of SPECT images and has been widely utilized in Japan. Results All cases consistently showed hypoperfusion in bilateral anterior to posterior cingulate gyrus. SPECT in early Alzheimer disease was hypoperfusion over medial temporal and posterior cingulate gyrus, compatible with the hypoperfusion area at our subjects. This result suggests that SPECT examinations by eZIS analysis clearly showed obvious hypoperfusion of the limbic system in narcolepsy. Conclusion This result suggests that SPECT examinations by eZIS analysis clearly showed obvious hypoperfusion of the limbic system in narcolepsy patient. Support (If Any) N/A
Introduction REM sleep behavior disorder (RBD), REM without atonia (RWA) and periodic limb movements in sleep (PLMS) are known as symptoms of Narcolepsy as it is listed in the International ...Classification of Sleep Disorders, third edition (ICSD3). The purpose of this study is to summarize polysomnographic findings and abnormal behavior related to REM sleep of patients with Narcolepsy diagnosed in our sleep clinic. Methods We conducted polysomnography (PSG) and multiple sleep latency test (MSLT) with 588 patients from the period of 2011 to 2016, 139 patients (80 male, 59 female patients, an average of 24.4yrs.) are diagnosed with Narcolepsy. Although cerebrospinal fluid orexin concentration measurement is not performed, narcolepsy with cataplexy attack is classified as type 1 (22 male and 26 female patients), narcolepsy without cataplexy attack is classified as type 2 (58 male, 33 female patients). We compared it about a difference of PSG and MSLT parameters and incidence of disordered behavior between Narcolepsy Type1 group and Type2 group. MannWhitney U test was used for the comparison between two groups. Results A significant difference was found between Narcolepsy Type1 and Type2 of REM sleep latency, %stageR, %RWA, and PLMSI in the PSG findings. In the MSLT findings, sleep latency was short and the number of SOREMP was increased in Type1 group. Rude behavior was observed at a higher rate in Type 1 patients than in Type 2 patients. Conclusion Our study showed that it was evident Narcolepsy Type1 patients having more REM related polysomnographic findings and rude behavior than Type2 patients. Support (If Any) none
Introduction The MSLT is the gold-standard for the assessment of CNS hypersomnia. Current AASM practice parameters suggest outcomes from an MSLT to be ‘suspect’ when ≤6 hours of TST is obtained the ...night prior. However, this threshold is often challenging to obtain for patients with narcolepsy, a condition associated with high state lability and low sleep efficiency. The goal of this study is to evaluate the relationship between short PSG sleep on MSLT outcomes. Methods PSGs and 5-nap MSLTs for those 13 years and older were extracted from SleepMed’s deidentified clinical repository. Only diagnostic PSGs occurring the night prior to MSLT were included. Those with moderate/severe OSA (RDI>10/hr) were excluded. Sleep was categorized as very short TST≤5 hr., short 5.1-5.9 hr., and recommended ≥6 hr.. Analyses included Chi Square and logistic regression. Results The final sample was 2752 patients with mean age 36 years (range 13-90; 73% Caucasian; 68% female) and a mean ESS of 12.5 +/- 6.3. The prevalence of very short, short, and recommended sleep durations was 12.1%, 25.1%, and 62.7%, respectively. Short sleep (dichotomized as <6 hr vs. >6 hr) was most common in those ≥60 yr (55% vs. 36% in <60 yr). The likelihood of a MSL ≤8 min decreased with decreasing PSG TST (≤5 hr=40%, 5.1-5.9 hr=54%, ≥6hr=61%; X2=50; p<.001). Similarly, the likelihood of ≥2 REMs decreased with decreasing TST (≤5 hr=13%, 5.1-5.9 hr=21%, ≥6hr=23%; X2=17.5; p<.001). Thus, short TST (<6hr) was associated with reduced odds of an MSLT consistent with narcolepsy (MSL≤8 & ≥2 REMs; OR: 0.75; p=.01). This relationship attenuated but persisted when controlling for age≥60 (OR: 0.79, p=.04). Conclusion Short PSG sleep, based on AASM practice parameters, occurs in over 1/3rd of patients undergoing an MSLT and influences outcomes in the opposite manner of what one may expect. Sleep adequacy before the MSLT should be kept in mind when interpreting MSLT results, especially for older individuals where nocturnal sleep continuity is decreased and diurnal REM is reduced. Support (If Any)
Introduction Recognized by the National Organization for Rare Disorders, narcolepsy is characterized by debilitating sleepiness (type 1 and type 2) and cataplexy (type 1). Medications for narcolepsy ...have dangerous side effects and potential for abuse. Patients often have residual symptoms despite treatment. Pitolisant, a selective histamine H3-receptor modulator, recently became available for the treatment of sleepiness and cataplexy. We hypothesized that many patients with narcolepsy have residual symptoms and may benefit from treatment with pitolisant. Methods We conducted a retrospective, electronic chart review using ICD-9-CM and ICD-10-CM narcolepsy-related diagnostic codes (347.01; G47.411; 347.00; G47.419; 347.10; 347.11) of outpatients evaluated at Rush University Medical Center between June 2011 and December 2018. Records were queried for demographics, medical comorbidities, polysomnography (PSG) and multiple sleep latency tests (MSLT), symptoms (sleepiness, cataplexy, hypnopompic/hypnogogic hallucinations, sleep paralysis, sleep fragmentation), and medication use. Results Of the 97 patients analyzed, patients were predominantly white (56.2%), middle aged (39 years, SD=15.64), overweight (BMI: 28.22, SD= 8.03 kg/m2) and female (58%). A minority of patients had narcolepsy type 1 (35%). On MSLT, the average mean sleep latency and number of SOREMPs was 4.8 minutes (SD=3.9 min) and 2.24 (SD=1.5), respectively. The most common medical comorbidity was obstructive sleep apnea (38.1%), followed by depression (24.7%) and hypertension (19.6%). Only 16.5% of patients reported insufficient sleep (Total sleep time <7 hours). Residual sleepiness and sleep fragmentation were reported in 64.9% and 29.9% of patients, respectively. Among patients with narcolepsy type 1, 59% reported residual cataplexy. Overall, 75.3% of patients reported at least one residual symptom. Modafinil was most commonly prescribed (41.2%), followed by amphetamines (32%), antidepressants (25.8%), and sodium oxybate (21.6%). Many patients were taking at least two medications (26.8%) and some were taking three medications (10.3%). Conclusion At a large tertiary care center, over three quarters of patients with narcolepsy reported residual symptoms. Recognizing patients at risk leads to increased access to new treatments, including pitolisant. More research is needed to assess impact of pitolisant access on patient outcomes. Support (If Any) N/A
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