Associated factors of REM sleep without atonia in younger (? 50 years) hospitalized psychiatric patients
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ABSTRACT:
SUBMITTER: Buskova J
PROVIDER: S-EPMC7528593 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to ?-synuclein-dependent degeneration in RBD patients.
| S-EPMC5799338 | biostudies-literature
Project description:BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse.ObjectiveTo characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET.MethodsWe analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age-sex-matched controls (27). None had dream-enactment behavior history or received antidepressants. Phasic, tonic, "any," and phasic-burst duration RSWA measures were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index (RAI) was also determined. Statistical analysis was performed by Kruskal-Wallis rank-sum and Mann-Whitney tests.ResultsSM phasic RSWA was significantly greater for PD than ET patients and controls (12.5% ± 12.8% vs. 4.9% ± 6.7%, 3.9% ± 2.6%), as was SM "any" (13.54% ± 14.30% vs. 5.2% ± 7.6%, 4.2% ± 2.6%). RAI was significantly lower in PD than in ET and controls (0.78 ± 0.23 vs. 0.92 ± 0.09 vs. 0.90 ± 0.17, P ≤ 0.005), but no different between ET and controls. AT phasic and "any" RSWA was similar between the 3 groups. ET and control RSWA was similar in all measures. Two ET patients (8.7%) had SM RSWA similar to PD patients.ConclusionsElevated SM RSWA distinguished PD from ET in patients without dream-enactment symptoms and occurs frequently in PD patients, and in isolated tremor suggests underlying synucleinopathy. Prospective studies will further validate these findings.
| S-EPMC7780943 | biostudies-literature
Project description:Values for normative REM sleep without atonia (RSWA) remain unclear. Older age and male sex are associated with greater RSWA, and isolated elevated RSWA has been reported. We aimed to describe normative RSWA and characterize isolated RSWA frequency in adults without REM sleep behavior disorder (RBD). We visually quantified phasic, "any," and tonic RSWA in the submentalis (SM) and anterior tibialis (AT) muscles, and the automated Ferri REM Atonia Index during polysomnography in adults without RBD aged 21-88. We calculated RSWA percentiles across age and sex deciles and compared RSWA in older (≥ 65) versus younger (<65) men and women. Isolated RSWA (exceeding diagnostic RBD cutoffs, or >95th percentile) frequency was also determined. Overall, 95th percentile RSWA percentages were SM phasic, any, tonic = 8.6%, 9.1%, 0.99%; AT phasic and "any" = 17.0%; combined SM/AT phasic, "any" = 22.3%, 25.5%; and RAI = 0.85. Most phasic RSWA burst durations were ≤1.0 s (85th percentiles: SM = 1.07, AT = 0.86 seconds). Older men had significantly higher AT RSWA than older women and younger patients (all p < 0.04). Twenty-nine (25%, 18 men) had RSWA exceeding the cohort 95th percentile, while 17 (14%, 12 men) fulfilled diagnostic cutoffs for phasic or automated RBD RSWA thresholds. RSWA levels are highest in older men, mirroring the demographic characteristics of RBD, suggesting that older men frequently have altered REM sleep atonia control. These data establish normative adult RSWA values and thresholds for determination of isolated RSWA elevation, potentially aiding RBD diagnosis and discussions concerning incidental RSWA in clinical sleep medicine practice.
| S-EPMC6783903 | biostudies-literature
Project description:123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was performed to assess cardiac autonomic dysfunction and demonstrate its correlation with clinical and polysomnographic characteristics in patients with isolated rapid eye movement (REM) sleep behavior disorder. All subjects including 39 patients with isolated REM sleep behavior disorder and 17 healthy controls underwent MIBG cardiac scintigraphy for cardiac autonomic dysfunction assessment. The isolated REM sleep behavior disorder was confirmed by in-lab overnight polysomnography. A receiver operating curve was constructed to determine the cut-off value of the early and delayed heart-to-mediastinum ratio in patients with isolated REM sleep behavior disorder. Based on each cut-off value, a comparison analysis of REM sleep without atonia was performed by dividing isolated REM sleep behavior disorder patients into two groups. MIBG uptake below the cut-off value was associated with higher REM sleep without atonia. The lower heart-to-mediastinum ratio had significantly higher REM sleep without atonia (%), both with cut-off values of early (11.0 ± 5.6 vs. 29.3 ± 23.2%, p = 0.018) and delayed heart-to-mediastinum ratio (9.1 ± 4.3 vs. 30.0 ± 22.9%, p = 0.011). These findings indicate that reduced MIBG uptake is associated with higher REM sleep without atonia in isolated REM sleep behavior disorder.
| S-EPMC8621819 | biostudies-literature
Project description:ObjectiveThe objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PD+FOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls.MethodsWe conducted overnight polysomnography studies in 4 groups of subjects: RBD, PD-FOG, PD+FOG, and controls. Tonic and phasic muscle activity during REM sleep were quantified using EMG recordings from the chin, compared among study groups, and correlated with disease metrics.ResultsThere were no significant differences in measures of disease severity, duration, or dopaminergic medications between the PD+FOG and PD-FOG groups. Tonic muscle activity was increased significantly (p < 0.007) in the RBD and PD+FOG groups compared to the PD-FOG and control groups. There was no significant difference in tonic EMG between the PD+FOG and RBD group (p = 0.364), or in tonic or phasic EMG between the PD-FOG and control group (p = 0.107). Phasic muscle activity was significantly increased in the RBD group compared to all other groups (p = 0.029) and between the PD+FOG and control group (p = 0.001), but not between the PD+FOG and PD-FOG groups (p = 0.059).ConclusionsThese findings provide evidence that increased muscle activity during REM sleep is a comorbid feature of patients with PD who exhibit FOG as a motor manifestation of their disease.
| S-EPMC3795590 | biostudies-literature
Project description:Compare nocturnal REM sleep without atonia (nRWA) and REM sleep behavior disorder (RBD) between pediatric patients with and without narcolepsy and determine if the nRWA index is a valid diagnostic biomarker for narcolepsy.Retrospective cohort study of children ages 6 to 18 years who completed a nocturnal polysomnogram (PSG) and Multiple Sleep Latency Test (MSLT). Our study sample included 11 patients with narcolepsy type 1 (NT1), 6 with narcolepsy type 2 (NT2), 12 with idiopathic hypersomnia (IH), and 11 with subjective hypersomnia (sHS). We compared group nRWA indices (epochs of RWA/total stage R sleep epochs) from the nocturnal PSGs and analyzed nRWA index receiver operating curve (ROC) statistics for narcolepsy diagnosis.The median nRWA index of patients with NT1 was 15 to 30 times higher compared to sHS and IH (Ps < .005) but similar to that of the NT2 group (P = .46). RBD was present in 25% of patients with narcolepsy (NT1 and NT2). In comparing those with and without narcolepsy, the nRWA index area under the curve was 0.87 (0.6), 95% confidence interval (CI) = 0.75 to 0.99, P < .001. The threshold of having ? 1% of stage R sleep epochs with nRWA yielded a sensitivity of 88.2%, 95% CI = 63.6-98.5 and specificity of 60.9%, 95% CI = 38.5 to 80.3 for diagnosis of narcolepsy. In contrast, a threshold of ? 8% yielded a specificity of 95.7%, 95% CI = 78.1 to 99.9 and sensitivity of 52.9%, 95% CI = 27.8 to 77.The nRWA index is a very good diagnostic biomarker of pediatric narcolepsy. Depending on the clinical cutoffs utilized, this biomarker can identify more children/adolescents with narcolepsy using just the PSG or reduce false-positive diagnostic results.
| S-EPMC5786844 | biostudies-other
Project description:Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson's disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4?mg/kg for 48?h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.
| S-EPMC6884572 | biostudies-literature
Project description:ObjectiveSleep complaints are frequent after acute COVID-19. Aim of this study was to videopolysomnographically evaluate sleep and sleep disorders after SARS-Cov2 infection.MethodsPatients with suspected sleep disorders after acute COVID-19 underwent video-polysomnography (v-PSG) at the Sleep Disorders Clinic, Department of Neurology, Medical University Innsbruck. V-PSG was conducted 4.2 (SD = 1.3) months after diagnosis of SARS-CoV-2 infection.ResultsEleven patients [nine men, age 52.5 (SD = 11.7) years; BMI 29 (SD = 5.2) kg/m2] were included. At 60 days follow-up after diagnosis, persisting breathing complaints were present in 7/11 (64%) patients. After v-PSG four patients (36%) were diagnosed with obstructive sleep apnea (OSA). Respiratory frequency during sleep was normal and no tachypnea, thoracoabdominal asynchrony, or periodic deep sighing were detected. Four patients (36%) showed REM sleep without atonia (RWA), and two additional patients showed an RWA index within the highest range of normality.ConclusionWe report videopolysomnographic findings in a series of eleven patients after acute COVID-19. A major finding of this study was the presence of isolated RWA, a recognized prodromal stage of RBD, in more than one third of the patients. Future videopolysomnographic investigations including quantification of RWA in patients after COVID-19 will give more insights into a possible acute or post-infectious CNS pathology related to the SARS-CoV-2 infection.
| S-EPMC7985859 | biostudies-literature
Project description:BackgroundPrevious work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep.Methodology/principal findingsTo determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control.Conclusions/significanceThese findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD).
| S-EPMC3197189 | biostudies-literature
Project description:ImportanceIncidence of colorectal cancer (CRC) is increasing among younger adults. However, data on precursor lesions in patients who are asymptomatic, especially those aged younger than 50 years, are lacking.ObjectiveTo analyze the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas, and serrated lesions, as well as the incidence of CRC in patients older than age 20 years.Design, setting, and participantsThis cohort study was conducted among 296 170 patients who received a screening colonoscopy within a national screening colonoscopy registry from 2012 to 2018 in Austria, including 11 103 patients aged younger than 50 years. CRC incidence was analyzed using data from Statistic Austria from 1988 to 2018. Data were analyzed in September 2021.Main outcome and measuresThe prevalence of adenomas and other lesions and the incidence of CRC in individuals aged 20 years or older were assessed.ResultsAmong 296 170 patients included in the study (median [IQR] age, 60 [54-68] years; 150 813 females [50.9%]), 11 103 patients (3.7%) were aged younger than 50 years and 285 067 patients (96.3%) were aged 50 years or older. Among patients younger than age 50 years, 1166 individuals (10.5%; NNS = 9) had adenomas and 389 individuals (3.9%; NNS = 26) had at least 1 advanced adenoma, while among those aged 50 years or older, 62 384 individuals (21.9%; NNS = 5) had adenomas and 19 680 individuals (6.9%; NNS = 15) had at least 1 advanced adenoma. Among 1128 males aged 40 to 44 years, 160 individuals (14.2%; NNS = 7) had at least 1 adenoma, and among 1398 females aged 40 to 44 years, 114 individuals (8.1%; NNS = 12) had at least 1 adenoma. The prevalence of adenomas for individuals aged 45 to 49 years vs 50 to 54 years was 490 of 2879 males (17.1%; NNS = 6) vs 8269 of 40 935 males (20.2%; NNS = 5) and 284 of 2792 females (10.2%; NNS = 10) vs 4997 of 40 303 females (12.4%; NNS = 8), respectively. Prevalence of adenomas changed from 61 of 498 individuals (12.4%) in 2008 to 150 of 1064 individuals (14.1%) in 2018 among those younger than 50 years and from 2646 of 12 166 individuals (21.8%) to 10 673 of 37 922 individuals (28.2%) among those aged 50 years and older. The prevalence of advanced adenomas changed from 20 individuals (4.0%) in 2008 to 55 individuals (5.2%) in 2018 in individuals younger than 50 years and from 888 individuals (7.3%) in 2008 to 2578 individuals (6.8%) in 2018 among those aged 50 years and older. Among individuals younger than age 50 years, CRC incidence per 100 000 individuals changed from 9.1 incidents in 1988 to 10.2 incidents in 2018 among males (average annual percentage change [AAPC], 0.5%; 95% CI, 0.1% to 1.0%) and from 9.7 incidents in 1988 to 7.7 incidents in 2018 among females, with a nonsignificant AAPC (-0.2%; 95% CI, -0.7% to 0.3%). Among individuals aged 50 years or older, CRC incidence per 100 000 individuals changed from 168 incidents in 1988 to 97 incidents in 2018 among females (AAPC, -1.8%; 95% CI, -1.9% to -1.6%), and 217 incidents in 1988 to 143 incidents in 2018 among males (AAPC, -1.2%; 95% CI, -1.3% to -1.1%).ConclusionIn this study, CRC incidence decreased after 1988 in Austria among individuals older than 50 years, while among patients younger than 50 years, incidence increased among males but decreased among females. Prevalence of adenomas increased in all age groups, while advanced adenoma prevalence increased among patients younger than 50 years but decreased in patients aged 50 years and older.
| S-EPMC10701609 | biostudies-literature