REM Sleep Abnormalities Research Articles

Scoring sleep in neurodegenerative diseases: A pilot study in the synucleinopathies

BackgroundNeurodegenerative diseases often alter sleep architecture, complicating the application of the standard sleep scoring rules. There are no recommendations to overcome this problem. Our aim was to develop a scoring method that incorporates the stages previously applied in dementia with Lewy Bodies (DLB), anti-IgLON5 disease, and fatal insomnia, and to test it in patients with alpha-synucleinopathies. MethodsVideo-polysomnographies (VPSG) of nine patients (DLB:3, Parkinson's disease (PD):3, and multiple system atrophy (MSA):3) selected for their difficulty in applying standard rules were scored independently by two authors, using additional Sleep/Wake stages. These included Abnormal Wake, Subwake, Undifferentiated NREM sleep (UNREM), Poorly structured N2 (P–S N2) and abnormal REM sleep including REM without atonia (RWA), REM without low-amplitude, mixed-frequency EEG activity (RWL) and REM without rapid eye movements (RWR). ResultsPatients (4 females) had a median age of 74 (range 63–85). Six patients (all with PD or DLB) had abnormal EEG awake and Subwake stage. UNREM sleep was present in all patients, typically at sleep onset, and was the most common sleep stage in five. P–S N2 was recorded only in the three patients with MSA. Periods of normal and abnormal NREM coexisted in three patients. RWA was the predominant REM subtype, RWR occurred mainly in patients with MSA and RWL in those with DLB. Six patients had brief REM episodes into NREM sleep which we termed “Encapsulated RBD”. ConclusionOur scoring system allows an accurate description of the complex sleep-wake changes in patients with alpha-synucleinopathies.

0583 Prevalence and Incidence of Narcolepsy in the US General Population

Abstract Introduction Narcolepsy is a sleep disorder characterized by cataplexy, hypersomnolence, sleep fragmentation and manifestations of various REM sleep abnormalities. It is a rare orphan disorder and therefore, its prevalence is almost exclusively estimated by derivate from clinical samples. Consequently, the objective of this study was to assess the prevalence of narcolepsy in an US general population representative sample. Methods The epidemiological study was carried with 15,927 individuals from 15 US States using the Sleep-Eval system. The longitudinal study was in eight of these 15 states: 12,218 subjects were interviewed by phone during the first wave and 10,931 at the second wave three years apart. Prevalence rates were calculated with the large sample while the Incidence was calculated on the subjects who participated in both interviews (N=10,931). The same interview was completed in both waves. For the purpose of this study, an algorithm was created using the answers provided for each symptom to reach a diagnosis conclusion of Narcolepsy type 1 (NT1) or Narcolepsy type 2 (NT2) according to ICSD3. Results NT1 was identified in 0.0126% (95% CI: 0.000%-0.03%) of the whole sample. Prevalence was similar between men and women. NT1 did not differ significantly by age groups although it was slightly higher in individuals younger than 35 y.o. (0.0201% (95% CI: 0.000%-0.06%)) compared to 0.016% (95% CI: 0.000% to 0.047%) in the 35 to 54 y.o. group and none in the oldest group. NT2 was observed in 0.0251% (95% CI: 0.0005%-0.0497%) of the sample. NT2 prevalence was comparable between men and women and among age groups. Overall, 66.7% of narcolepsy individuals in the sample identified by Sleep-Eval were already diagnosed as such by a physician. The incidence rate was also very low at 0.0026% per year. Conclusion Our results support the fact that narcolepsy is indeed a rare disorder affecting 37.7 individuals per 100,000 inhabitants with a relatively low incidence at 2.6 individuals per 100,000 inhabitants per year. Recognition of the disorder by a physician was relatively high in the United States with 2/3 of the cases being already diagnosed. Support (if any) Data analysis study were funded by Tris Pharma and Takeda Pharmaceutical Company.

0671 Identifying Disruptive Nocturnal Behaviors in Trauma Associated Sleep Disorder with Video-Polysomnography on Consecutive Nights

Abstract Introduction Trauma associated sleep disorder (TSD) manifests with trauma-related nightmares, disruptive nocturnal behaviors (DNB), and autonomic hyperactivity. Although patients with TSD frequently report DNB, events are infrequently identified during in-lab polysomnography (PSG), possibly due to a sense of safety imparted by a monitored environment. It is unknown if patients with TSD acclimate to the lab environment if studied on consecutive nights. Given the infrequent and potentially subtle nature of DNB and REM sleep abnormalities, the objective of this study was to compare self-reported and PSG characteristics from two consecutive nights of PSG in patients with TSD. Methods Individuals were initially screened for TSD with the Pittsburgh Sleep Quality Index Addendum. Those reporting trauma-related nightmares and DNB underwent a structured clinical interview to confirm the diagnosis. Patients with TSD completed 2 consecutive nights of attended in-lab PSG with post-PSG dream/nightmare questionnaire. Video-PSG analysis was performed including detailed review of movements, excluding epochs with sleep disordered breathing. REM sleep analysis included quantifying “any” electromyographic (EMG) activity as an objective measurement for REM without atonia. ANOVA was used for statistical analysis. Results We diagnosed 15 individuals (11 males; 14 service members, 1 Veteran; average age 32.2 years) with TSD. Traumatic exposures were combat-related in 40% and physical or sexual assault related in 60%. There was a significant difference between proximal limb movements on night 1 vs night 2 (1.0 ± 1.73 vs 10.3 ± 4.04; p=0.02). There was a significant difference in the amount of increased EMG tone using 3 second REM mini epochs between the 2 nights (153 ± 147.8 mini epochs vs 417 ± 35.1; p=0.04). No difference was detected between nights for vocalizations or sleep parameters including total REM sleep time and percentage. Nightmares were reported by 33% during their first night PSG vs 66% during their second PSG. Conclusion In patients with TSD, there was an increase in the number of proximal limb movements, total mini epochs of “any” REM EMG activity, and nightmares during the second night of consecutive in-lab PSG testing. More than one night of in-lab PSG evaluation is likely required to best characterize the severe nocturnal disruptions of TSD. Support (if any)

0141 Short-Term Stability of Sleep Parameters in Comorbid Nightmares and Chronic Insomnia Disorder

Abstract Introduction Nightmares are highly comorbid with insomnia and have been associated, yet not consistently, with distinct polysomnographic (PSG) disturbances, such as reduced total sleep time (TST), sleep efficiency and slow wave sleep as well as increased nocturnal awakenings and wake after sleep onset (WASO) or abnormal REM sleep. However, most prior studies have relied on a single night of PSG and the degree of stability of sleep parameters or overall differences between individuals with nightmares comorbid with insomnia disorder (NCI), individuals with chronic insomnia disorder (CID) and otherwise good sleeping controls (GSC), remain unknown. Therefore, the aim of this study was to determine if there were significant differences amongst these aforementioned groups in the way their sleep changes across time while being studied in the lab. Methods A total of 142 GSC, 126 CID and 24 NCI participants underwent 8-hour PSG recordings for 4 consecutive nights. Outcomes included sleep continuity, architecture, and REM-related parameters across nights 1 through 4. Intraclass correlation coefficients (ICC) with mixed-effect variances and repeated-measure analysis of variance (ANOVA) were used to determine short-term stability as well as between-subjects and time-by-group interaction effects, respectively. Results ICC were similar across groups on all outcomes (ICCs>0.6) except that the NCI group did not display stability for WASO, stage 1 sleep, REM latency or REM interval. There were no significant time-by-group interaction effects on PSG parameters (ps>0.05). There were significant between-group effects for SOL, number of awakenings, WASO, TST, REM latency, and number of REM episodes (all ps< 0.05), where the NCI group showed significantly longer SOL (58.10±11.08), shorter TST (6.64 hours±1.02), and less REM episodes (3.81±0.76). Conclusion This study suggests greater night-to-night variability and overall disturbance in nighttime sleep continuity and REM sleep in individuals with NCI. These disturbances may be attributed to the occurrence of nightmares, causing wakefulness out of REM sleep, as well as a greater level of hyperarousal as evidenced by the greater SOL and reduced TST, relative to the other groups. These data also suggest the utility of objective sleep measures in nightmare research and clinical practice alike. Support (if any) National Institutes of Health (UL1TR000127)

The association of saccadic abnormalities with rem sleep in patients with Huntington's disease

BackgroundHuntington's disease (HD) is a progressive neurodegenerative disorder characterised by chorea, cognitive impairment, psychiatric and behavioral disturbances. Sleep disturbances including reduced REM sleep have been observed in HD. ObjectivesThe aim of the study was to study the polysomnography findings in HD and to assess whether oculomotor abnormalities are associated with poor REM sleep. MethodsTwenty-nine genetically confirmed HD patients underwent clinical evaluation including extraocular movement and OKN examination. Twenty-six patients and 15 controls underwent overnight video polysomnography (VPSG). ResultsVPSG of 23 HD patients and 13 controls were considered for analysis. Compared to controls, HD patients had higher median wake period and higher WASO percentage (p = 0.005). REM sleep percentage was reduced significantly in HD in comparison to controls (p < 0.001). Out of 23 patients, only two patients had REM sleep above 20% while 14 patients had REM sleep percentage less than 15%. Poor horizontal OKN (grades 2 and 3) was associated with the presence of low REM sleep percentage (REM sleep less than 15%) (p = 0.02). Low REM sleep was also associated with severe illness (UHDRS) (p = 0.038). ConclusionAn association between decreased REM sleep and OKN abnormalities indicate that EOM abnormalities seen in HD could lead to errors in scoring REM sleep. To understand the actual degree of decreased REM sleep percentage will require additional parameters in AASM guidelines to score REM sleep in patients with EOM abnormalities like that seen in HD.

633 Dysregulated REM Sleep in Children with Moebius syndrome

Abstract Introduction Moebius syndrome (MBS) is a rare disorder characterized by failure of development of the 6th and 7th cranial nerve nuclei located in the pons. Though the congenital lesion abuts the pontine tegmentum, sleep architecture has not been evaluated in MBS. Methods We report the clinical features of three children with MBS, and discuss implications for “developmental” RBD. Results Three clinically and MRI brain scan-confirmed MBS children, age 0.5 to 16 years, mean 8.5 ± 6.3 years, were evaluated for disrupted sleep, with repetitive crying (1/3), yelling (2/3), agitation in sleep (2/3), and injuring a co-sleeping sibling (1/3); 3/3 had REM sleep without atonia while 2/3 had RBD. REM sleep was reduced in all three: 21.7% in the infant (reference REM percentage value in infancy is about 40%), 11.4% in subject 2 and 3% in subject 3. Treatment with clonazepam (patients 2 and 3) or melatonin (patient 1) had variable results. Conclusion Children with Moebius syndrome have both quantitative (reduced percentage) and qualitative abnormalities of REM sleep (RSWA/RBD). The association of MBS with RSWA/RBD suggests more extensive involvement than published in literature, with extension into the sub-laterodorsal pontine tegmentum and “REM-off” neurons. Moebius syndrome might serve as a model for study of “developmental” REM sleep behavior disorder. Support (if any):

1079 Is PTSD In Young Women Associated With Rem Sleep Abnormalities?

Abstract Introduction The increase in violence against young women has a high impact on the prevalence of Posttraumatic stress disorder (PTSD). The lifetime prevalence of PTSD is twice as high in women. However, most studies assessing sleep disturbances in PTSD were conducted predominantly in male samples and combat veterans. Objective: To analyze the sleep of young women with and without PTSD. Hypothesis: Women with PTSD have worse sleep quality, higher arousability, and higher muscle activity during REM sleep. Methods Case-controlled study with young women. Seventy-four women who suffered sexual assault and developed PTSD (DSM-5); and 64 women from the community without PTSD. Women were recruited from the PTSD outpatient clinic (Universidade Federal de São Paulo, Brazil).Clinician-Administered Posttraumatic Stress Scale (CAPS 5), Beck Depression and Anxiety Inventories (BDI) (BAI), full in-lab Polysomnography (PSG), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Índex (PSQI), Fatigue Impact Scale (FIS), and Insomnia Severity Índex (ISI) were applied to all participants. Analysis of variance, regression models, and general linear modeling were used. Results Patients mean age was 28 vs 24 for the control group (p=0.004). CAPS mean score in PTSD-group was 42.5±9.1. BDI, BAI, FIS, PSQI, ISI scores were worse in PTSD-group (p&amp;lt;0.05, all). Pittsburgh Sleep Quality Index (PSQI) score was significantly associated with CAPS 5 independently of depression, fatigue, and sleep fragmentation. The PTSD women had lower total sleep time (p= 0.01) and lower REM sleep percentage (p=0.04). However, the control group had higher arousal index (p=.0.01) and had higher muscle activity during REM sleep (p=0.03) than PTSD. Conclusion Women with PTSD had significantly worse score in PSQI, FIS, and ISI. PSQI score was associated with PTSD severity. However, when PSG results are concerned, we found higher sleep fragmentation in the control group. We speculate that women with PTSD may have felt safer and taken care of in the lab, which might explain the difference between objective and subjective measures of sleep quality in PTSD. Support Acknowledgments: FAPESP: Fundação de Apoio à pesquisa de São Paulo, AFIP: Associação Incentivo a Pesquisa

1074 Fear Reactivity And Sleep In Trauma-Exposed Males And Females With And Without PTSD

Abstract Introduction Sleep disturbance is considered central to mechanisms of PTSD development and maintenance, and fear learning protocols have been used as laboratory models to understand PTSD disease mechanisms. Some research indicates that fear learning may influence subsequent sleep, especially REM sleep, and that sleep may influence subsequent extinction. In this study, we examined the relationship of startle reactivity during conditioning and later extinction with objectively-measured sleep in PTSD-positive and negative subjects. Methods These analyses were performed as part of a larger study of PTSD and sleep. Thirty-four (34) trauma-exposed male and female participants with and without PTSD completed a fear-potentiated startle conditioning procedure at 9:45am, followed by a PSG-monitored nap (13:30-15:30), followed by an extinction protocol at 4:30pm. All visits were preceded by an adaptation nap visit at least 7 days prior. Eye-blink EMG was used to measure startle reactivity. Mixed-model analyses were performed in SPSS. Results PTSD-positive subjects had higher REM sleep duration (p&amp;lt;.05) and a trend towards shorter REM sleep latency (p=.06). There were no other group or sex effects on standard PSG sleep parameters. During conditioning, PTSD-positive status was associated with higher startle reactivity across stimulus types (p&amp;lt;.01), driven by increased reactivity in PTSD-positive vs. PTSD-negative females. A PTSD x sex interaction effect on startle reactivity showed the opposite effect in males (p&amp;lt;.01). Higher startle reactivity during conditioning predicted longer sleep latency during the subsequent nap (p&amp;lt;.05), but reactivity during conditioning and extinction did not otherwise show a relationship to standard PSG sleep measures. Conclusion These findings are consistent with previous research indicating REM sleep abnormalities as well as heightened fear responses in PTSD. While the observed relationship between higher startle and longer sleep latency is consistent with studies indicating that stress affects subsequent sleep, further research in larger samples is needed to understand causal mechanisms and to advance our understanding of sleep-PTSD mechanisms. Support VA Career Development Award-5IK2CX000871-05

0746 Dynamics of Sleep Stage Transitions in Patients with Narcolepsy and Other Hypersomnias

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).

Abnormal REM Sleep Atonia Control in Patients With Chronic Post-Traumatic Stress Disorder (1607)

Abnormal REM Sleep Atonia Control in Patients With Chronic Post-Traumatic Stress Disorder (1607)

Sleep architecture in adolescents hospitalized during a suicidal crisis

Objective/backgroundRates of suicide attempts in Canadian youths are concerning. Adolescence is a sensitive period for the emergence of both sleep and mood problems, two major risk factors for suicidality. This naturalistic study aimed to define the sleep profile of adolescents under the combined influence of suicidality, depression and pharmacotherapy during hospitalization for a suicidal crisis. Patients/methodsSeventeen suicidal adolescents (15.0 + 1.2years, 82% females) with major depression were recruited from a Canadian pedopsychiatric inpatient unit. Seventeen non-depressed adolescents were retrospectively collated from another database (15.0 + 1.1years, 83% females). None of the participants had a history of sleep disorders or significant medical conditions. ResultsCompared to controls, suicidal adolescents had a longer sleep onset latency (Z = −4.5, p < 0.001), longer REM latency (Z = −3.2, p = 0.001), higher percentage of NREM1 sleep t(33) = -2.6, p = 0.020), and higher REM density (Z = −2.8, p = 0.004) than controls. Higher REM density correlated with higher CDI-II scores (r = 0.55, p = 0.27) A significant interaction indicated that the two groups had similar NREM3 percentages in the first two-thirds of the night, but that the suicidal group had significantly lower NREM3 percentage than the controls in the last third of the night (F(2,66) = 3.4, p = 0.041). ConclusionsSignificant sleep abnormalities were observed during hospitalization for a suicidal crisis in a sample of depressed and mostly medicated adolescents. This included sleep initiation and REM sleep latency abnormalities, shallower sleep and high REM density. Future studies should decipher the relative effects of depression, suicidality and medication on sleep. These findings stress the need to address sleep disturbances in the management of suicidality in adolescents.

0002 FINE MAPPING GENOME-WIDE ASSOCIATION IN NARCOLEPSY DEFINES NOVEL DISEASE MECHANISMS

Type 1 narcolepsy is characterized by sleepiness, REM sleep abnormalities and loss of muscle tone triggered by positive emotions (cataplexy). The cause of type 1 narcolepsy is a loss of neurons producing the hypocretin/orexin peptide likely of autoimmune origin. Our aim was to discover novel genetic variants in narcolepsy and fine map the potentially causative variants using our transethnic sample and cellular models. A worldwide narcolepsy collaboration was built over the last two decades. Within this consortium, we examined genetic variants using a transethnic GWAS in Asian, African American and Caucasian samples (N=5,500 cases and 30,000 controls). The function of leading variants was examined using eQTL analysis in dendritic and T cell models, data from the ENCODE and GTEx consortiums and by examining the effect of individual variants on flu vaccination response. In addition the effect of genetic variants on immune cell development was examined using mass cytometry. We confirmed existing risk associations (TRA, TRB, IFNAR1, CTSH and P2RY11) and discovered novel loci that predisposed individuals to narcolepsy in CD207, SIRPG, PPP2R2C, ZFAND2A, FLT3, LPP and PRF1. Fine mapping of association suggests a functional polymorphism in position A91V in PRF1, a variant that is directly affecting T and NK cell mediated cell killing. Furthermore, leading variant in IFNAR1 affected IFNAR1 expression after flu infection in dendritic cells suggesting causality for the development of narcolepsy through changes in dendritic cell phenotype. The results further stress the effect of T cell-dendritic cell interactions in the development of narcolepsy and find causal disease pathways. The novel loci may explain how hypocretin cells are destroyed and support a T cell mediated autoimmune attack in narcolepsy susceptibility. World Wide Narcolepsy Consortium, European Narcolepsy Network, Sigrid Juselius Foundation, Finnish Cultural Foundation.

Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs.

REM sleep behavior disorder and periodic leg movements during sleep in ALS

To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS). A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography. A total of 22 patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total sleep time, increased wakefulness after sleep onset, shortened REM and slow-wave sleep, and decreased sleep efficiency, compared to controls. Polysomnographic abnormalities were not different in patients reporting good or poor sleep and were not correlated to clinical and demographic variables. The PLMS index was significantly higher in patients with ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index > 15/h, vs 4 (15.4%) controls (P < 0.001). Finally, two patients with ALS (4.9%) had RBD, and two more patients presented RSWA (4.9%), whereas no controls showed abnormalities of REM sleep. Patients with ALS frequently present abnormalities of sleep that can be documented both at the clinical interview and at the polysomnographic evaluation, including insomnia, fragmented sleep, and increased PLMS. Moreover, abnormalities of REM sleep can be found in some of these patients.

Genetics of rapid eye movement sleep in humans.

The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases.

Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder

BackgroundPatients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown. ObjectiveTo evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length. MethodsThe clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype–phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video. ResultsThe patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control. ConclusionThe nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems.

Circulating CD4+ T cells in narcolepsy patients react to hypocretin and cross-react with hemagglutinin from an influenza strain linked to increased narcolepsy incidence (HUM2P.336)

Abstract Narcolepsy, a disorder characterized by daytime sleepiness, cataplexy, and REM sleep abnormalities, is caused by the loss of ~70,000 hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (HCRT). The strong association of narcolepsy with HLA DQA1*01:02/DQB1*06:02 (DQ0602) has led to the hypothesis that narcolepsy is an autoimmune disease, but direct evidence has been lacking. We recently reported discovery of circulating CD4+ T cells reactive to two homologous DQ0602-binding HCRT epitopes (HCRT56-68, HCRT87-99) in narcolepsy patients, but not in DQ0602+ healthy control subjects. Based on epidemiologic evidence linking narcolepsy with the 2009 H1N1 influenza A strain (pH1N1) we measured levels of circulating HCRT56-68, HCRT87-99 reactive T cells in narcolepsy patients who had received the seasonal influenza vaccine (containing pH1N1) and found them to be increased. We identified a pH1N1-specific hemagglutinin epitope with homology to the narcolepsy-associated HCRT epitopes; in vitro stimulation of narcolepsy CD4+T cells with this epitope increased the frequency of HCR-reactive T cells. To directly test for molecular mimicry between the HCRT and pH1N1 epitopes, we have used tetramer staining and single cell TCR sequencing. We conclude that narcolepsy is associated with an autoimmune response to HCRT, which can be triggered by cross-reactive T cell responses to pathogen-derived peptides.

Disrupted Nighttime Sleep in Narcolepsy

Characterize disrupted nighttime sleep (DNS) in narcolepsy, an important symptom of narcolepsy. A panel of international narcolepsy experts was convened in 2011 to build a consensus characterization of DNS in patients with narcolepsy. A literature search of the Medline (1965 to date), Medline In-Process (latest weeks), Embase (1974 to date), Embase Alert (latest 8 weeks), and Biosis (1965 to date) databases was conducted using the following search terms: narcolepsy and disrupted nighttime sleep, disturbed nighttime sleep, fragmented sleep, consolidated sleep, sleep disruption, and narcolepsy questionnaire. The purpose of the literature search was to identify publications characterizing the nighttime sleep of patients with narcolepsy. The panel reviewed the literature. Nocturnal sleep can also be disturbed by REM sleep abnormalities such as vivid dreaming and REM sleep behavior disorder; however, these were not reviewed in the current paper, as we were evaluating for idiopathic sleep disturbances. The literature reviewed provide a consistent characterization of nighttime sleep in patients with narcolepsy as fragmented, with reports of frequent, brief nightly awakenings with difficulties returning to sleep and associated reports of poor sleep quality. Polysomnographic studies consistently report frequent awakenings/arousals after sleep onset, more stage 1 (S1) sleep, and more frequent shifts to S1 sleep or wake from deeper stages of sleep. The consensus of the International Experts' Panel on Narcolepsy was that DNS can be distressing for patients with narcolepsy and that treatment of DNS warrants consideration. Clinicians involved in the management of patients with narcolepsy should investigate patients' quality of nighttime sleep, give weight and consideration to patient reports of nighttime sleep experience, and consider DNS a target for treatment.

REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics.

To examine the prevalence and clinical characteristics of REM sleep behavior disorder (RBD) and subclinical RBD in the Korean elderly population. A community-based Korean Longitudinal Study on Cognitive Aging and Dementia and time-synchronized video-polysomnography (vPSG) in a laboratory. Sleep laboratory in a university hospital. 348 individuals aged 60 years or older. N/A. Among 696 subjects who were invited to participate in a vPSG study, 348 completed the vPSG. RBD was diagnosed when subjects showed REM sleep without atonia (RSWA) in the vPSG, and had history of complex and vigorous behaviors during sleep or abnormal REM sleep behaviors in the vPSG. Subjects with RSWA but no abnormal REM sleep behaviors were diagnosed with subclinical RBD. Seven subjects (5 male, 2 female) had RBD, three of whom (1 male, 2 female) had Parkinson disease. Two subjects reported history of sleep-related injury. The crude prevalence of RBD and idiopathic RBD was 2.01% (95% confidence interval [CI] = 0.54% to 3.49%) and 1.15% (95% CI = 0.03% to 2.27%). An age and sex-adjusted prevalence estimate of RBD and idiopathic RBD in the Korean elderly was 2.01% and 1.34%. Eighteen subjects were diagnosed with subclinical RBD, and the prevalence of subclinical RBD was estimated to be 4.95%. RBD and subclinical RBD are not rare in the elderly in the community with abnormal REM sleep behaviors of RBD being mild to injurious and violent. The clinical significance and long-term progression of subclinical RBD needs to be further explored, given the prevalence and its possible relation to RBD.

Defining muscle activities for assessment of rapid eye movement sleep behavior disorder: From a qualitative to a quantitative diagnostic level

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enacting behavior. Its polysomnographic hallmark is loss of physiological REM muscle atonia. Current diagnostic criteria require both a typical history of RBD or videographic documentation of abnormal REM-sleep related behaviors and the polysomnographic demonstration of REM sleep without atonia with "the electromyographic (EMG) finding of excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or limb EMG twitching". Until now, there has not been a generally accepted consensus on how muscle activity during REM sleep should be scored. Moreover, current diagnostic criteria do not specify which muscle or muscle combinations are the most suitable for differentiating between RBD and non-RBD. The term "excessive" refers to the scorer's subjective impression and not to objective quantitative cutoff values. This article reviews published manual and computer-assisted scoring methods of EMG activity that are applied in RBD research. It includes the existing studies on EMG activity assessment in different muscles, available data on night-to-night variability, as well as recently established quantitative EMG cutoff values. The research that has been undertaken in the last years has greatly improved RBD diagnosis, taking it from a qualitative to a quantitative level. This development is of upmost importance, since RBD is often the first non-motor symptom of a neurodegenerative disease.