Contemporary Concise Review 2020: Sleep.

Obstructive sleep apnoea (OSA) now affects one-seventh of the world's population. Treatment of even mild OSA can improve daytime sleepiness and quality of life. Recent modifications to uvulopalatopharyngoplasty may make it a more widely applicable treatment option in selected patients with OSA. Diet and exercise have effects on sleep apnoea severity independent of weight loss. Insomnia has become increasingly common during the coronavirus disease 2019 (COVID-19) pandemic.

Sleep state instabilities in patients with periodic limb movements in sleep - Detection and quantification with heart rate variability.

BACKGROUND: Restless legs syndrome (RLS) has been thought to increase the risk of hypertension, cardiovascular events, and all-cause mortality. Periodic limb movements in sleep (PLMS) can be observed in most patients with RLS. Using non-invasive physiologic measurement and analysis, including heart rate variability (HRV) analysis, we aimed to investigate sleep quality and sleep state stability. METHOD: A total of 53 healthy controls and 15 patients with RLS and PLMS were recruited. Patients with other sleep-related disorders such as obstructive sleep apnea (OSA) and major depressive disorder (MDD) were excluded. Each subject was evaluated using sleep and mood questionnaires and had to undergo polysomnography (PSG). HRV analysis was applied to assess autonomic function and analyze correlations with the severity of periodic leg movements (PLM). The power of different brainwaves was analyzed using electroencephalogram (EEG). Electromyogram (EMG) was also used to explore the temporal correlation between changes in HRV and leg movement events. RESULTS: Compared with healthy controls, PLMS group had not only poorer perceived sleep and mood questionnaires scales but also reductions in parasympathetic-related HRV indices and increases in sympathetic-related HRV parameters. The changes were in proportion to the severity of PLM. Brainwaves and sleep stage which indicate "deep sleep" decreased in the PLMS group. There were no significant temporal correlations between changes in HRV and leg movement events. CONCLUSIONS: Our findings suggest that patients with RLS and PLMS have poorer subjective sleep and mood scales. Besides, objective sleep quality including HRV analysis and brainwaves analysis revealed reduced parasympathetic tone, increased sympathetic tone, and sleep disturbance, which reveal the possibility of a higher risk for secondary disease.

Actimetry-Documented Persistent Periodic Limb Movements During EEG-Confirmed Deep General Anesthesia: A Case Report.

Motor activity during general anesthesia (GA) without neuromuscular blockade is often interpreted as reflecting insufficient anesthesia. Here we present the case of an octogenarian undergoing deep sclerectomy with opioid-sparing electroencephalography (EEG)-guided anesthesia. Periodic leg movements (PLM) appeared during ongoing surgery while the patient's raw EEG displayed a pattern of deep anesthesia, evidenced by burst suppression. Recognizing PLM in the context of opioid-sparing GA is of importance for anesthesiologists, as deep anesthesia is not necessarily associated with a decrease in motor activity.

A 3-year observation of excessive daytime sleepiness after subthalamic deep brain stimulation in patients with Parkinson's disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN DBS) has a positive effect on sleep quality, but its effect on wake functions is controversial. This study evaluated the longitudinal changes of the quality of sleep and excessive daytime sleepiness (EDS) in Parkinson's disease (PD) patients undergoing STN DBS and identify which factors are associated with the presence of EDS before and after STN DBS. PATIENT AND METHODS: A total of 33 PD patients who underwent bilateral STN DBS between July 2011 and October 2015 were recruited. We evaluated subjective sleep quality assessed by Parkinson's Disease Sleep Scale (PDSS) and EDS using Epworth Sleepiness Scale (ESS) preoperatively and 6 months, 1 year, and 3 years postoperatively. RESULTS: There is a significant improvement in PDSS, and a noticeable change occurs immediately after the surgery. After DBS, the number of patients with persistent EDS gradually decreased, but patients with newly developed EDS were added. Baseline ESS score was highly correlated with EDS at 6 months and 1 year postoperatively, and older age of PD onset was highly associated with EDS at 1 year after DBS. At 3 years after DBS, the total PDSS score is a main contributing factor for EDS. There was no significant difference in dopamine agonist dose (agonist LED) and levodopa equivalent daily dose (LEDD) between groups with and without EDS at any time points. CONCLUSION: Bilateral STN DBS improves the subjective sleep quality, but EDS may improve or worsen. The risk factors for EDS change over time after STN DBS. Interestingly, dopaminergic medication did not affect EDS in DBS-treated PD patients.

Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. The Atahualpa Project.

BACKGROUND: Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. METHODS: Atahualpa residents aged more than or equal to 60 years enrolled in the Atahualpa Project undergoing polysomnography and MRI with time intervals less than or equal to 6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and more than 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. RESULTS: A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index more than or equal to 15 per hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and more than 10 BG-PVS in 44 (30%). In univariate analyses, silent LI (P = .035) and the presence of more than 10 enlarged BG-PVS (P = .034) were significantly higher among participants with a PLMS index more than or equal to 15 per hour. However, fully-adjusted multivariate models showed no significant association between PLMS index more than or equal to 15 per hour and any of the neuroimaging signatures of cSVD. CONCLUSIONS: This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

Risk of resistant hypertension associated with restless legs syndrome and periodic limb movements during sleep: a study on 673 treated hypertensive individuals.

OBJECTIVE: Given the limited data available in the literature, the aim of this study was to examine the risk of resistant hypertension (RHT) associated with restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) in a large sample of treated hypertensive individuals. METHODS: Demographic and polysomnographic (PSG) data from 673 treated hypertensive individuals recruited from the research database of the sleep laboratory of Erasme Hospital were analysed. After exclusion of the main causes of pseudo-resistance and secondary hypertension, RHT status was defined by the presence of an uncontrolled hypertension despite treatment with at least three antihypertensive agents (including a diuretic) from different classes in correct combination and at the highest tolerated doses or by the presence of controlled hypertension requiring the use of at least four antihypertensive agents. Logistic regression analyses were conducted to examine the risk of RHT associated with RLS and PLMS in treated hypertensive individuals. RESULTS: After adjustment for major confounding factors associated with RHT, multivariate logistic regression analysis revealed that frequent RLS (≥2 episodes/week) combined with PLMS index ≥26/h [odds ratio (OR) 2.20; 95% confidence interval (CI) 1.35-3.61, p = 0.021] was a significant risk factor of RHT in treated hypertensive individuals. CONCLUSION: In treated hypertensive individuals, frequent RLS combined with PLMS index ≥26/h is associated with higher risk of RHT which suggests that this pathology may be a secondary cause of RHT (eg, obstructive sleep apnoea syndrome and insomnia with short sleep duration) justifying the establishment of effective treatments in this particular subpopulation.

Images: Periodic Limb Movements During Sleep Noted on Ventral Thigh Surface Electromyography in an Above-the-Knee Amputated Stump.

None: Ventral thigh surface electromyography may be used to assess for periodic limb movements during sleep (PLMS) in a limb with an above-the-knee amputation. Presence of PLMS in the proximal portion of an amputated lower extremity supports theories of spinal and supraspinal mechanisms in PLMS generation, and demonstrates that intact distal motor efferent pathways and distal sensory afferent pathways are not absolutely necessary for the generation of periodic limb movements. CITATION: Chada A, Hoque R. Periodic limb movements during sleep noted on ventral thigh surface electromyography in an above-the-knee amputated stump. J Clin Sleep Med. 2019;15(8):1183-1184.

Association Between Periodic Limb Movements in Sleep and Cerebrovascular Changes in Children With Sickle Cell Disease.

STUDY OBJECTIVES: Periodic limb movements (PLMs) have been associated with increased risk of stroke, but there is currently scarce research exploring this relationship in the setting of sickle cell disease (SCD). The aim of this study was to explore whether increased PLMs in children with SCD are associated with increased risk of cerebrovascular disease and to determine if there are any clinical or laboratory differences between children with SCD with elevated periodic limb movement index (PLMI) versus those with normal PLMI. METHODS: This study is a comprehensive review of medical records of 129 children with SCD (aged ≤ 18 years) who had undergone polysomnography for evaluation of sleep-disordered breathing. RESULTS: Elevated PLMI (PLMI > 5 events/h) was present in 42% (54/129) of children with SCD. Children with elevated PLMI were found to have higher percentage of hemoglobin S, lower total iron, higher arousal index and tendency toward elevated transcranial Doppler velocity (P = .063, odds ratio = 3.9, 95% CI 0.93-16.22). While association between elevated PLMI and isolated cerebrovascular stenosis (P = .050, odds ratio 5.6, 95% CI 1.0-31.10) trended toward significance, there was significantly greater proportion of children with elevated PLMI who had cerebrovascular stenosis with Moyamoya disease (P = .046) as demonstrated by magnetic resonance imaging (MRI). CONCLUSIONS: The prevalence of elevated PLMI in children with SCD was higher than in previously published data. Elevated PLMI was significantly associated with greater rates of cerebrovascular disease as detected by MRI.

Restless legs syndrome, periodic limb movements during sleep and cardiovascular risk.

Multiple mechanisms may modulate an association between restless legs syndrome/Willis-Ekbom disease (RLS/WED) and cardiovascular disease (CVD), including chronic sleep deprivation, intermittent, periodic limb movements in sleep (PLMS)-related autonomic fluctuations and possible autonomic dysfunction intrinsically associated with RLS per se. The purpose of this paper is to review the existing RLS/WED literature focusing on the pathophysiologic evidence for possible associations between RLS/WED and PLMS with CVD and events (CVE). Specific intrinsic dysautonomic aspects of the disease, which may contribute to generating CVD, are separately discussed. The association between RLS/WED and both CV risk factors and CVD still remains elusive. Although several shared pathophysiological causes could explain these possible relationships, the emerging body of literature focusing on these disorders remains controversial. Not only longitudinal population-based studies and meta-analyses, but also more animal models and therapeutic interventions are needed in order to build a sufficiently robust body of evidence on this topic.

It twitches without kicking - An association between fragmentary myoclonus and arousal?

OBJECTIVE: Fragmentary myoclonus (FM) is a polysomnographic motor phenomenon of unknown clinical relevance. This study investigates FM prevalence, gender differences, sleep stage distribution and association with clinical factors using recently introduced advanced FM scoring criteria. METHODS: We analyzed polysomnographic recordings of 178 patients of a mixed sleep-disorder patient cohort. FM indices (FMI) of newly introduced 25 µV (FMI25) and standard 50 µV (FMI50) amplitude cut-offs were calculated. RESULTS: FMI25 and FMI50 were higher in men compared to women. FMI were higher during wakefulness and lower during S3 compared to all other sleep stages, with stronger effects in men compared to women. FMI25 was correlated with higher age, lower mean oxygen saturation, lower sleep efficiency, higher periodic limb movement (PLM) index, shorter sleep period time and higher arousal index. Linear regression showed that age predicted higher FMI25 in both males and females. Additionally, higher arousal index predicted higher FMI25 in women only. FMI were not associated with the presence of sleep-related breathing disorders. CONCLUSIONS: We suggest FM represents a ubiquitous motor phenomenon occurring spontaneously during relaxed wakefulness and sleep, primarily in men and with advanced age. SIGNIFICANCE: In women, particularly FMI25 may be a surrogate marker for more frequent arousals and sleep fragmentation.

Improvement of Parasomnias After Treatment of Restless Leg Syndrome/ Periodic Limb Movement Disorder in Children.

STUDY OBJECTIVES: Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias commonly coexist with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children, leading to speculation that RLS/PLMD may precipitate or worsen parasomnias. However, there are limited data about the effect of the treatment of RLS/PLMD on parasomnias in children. Hence, we performed this study to determine whether the treatment of RLS/PLMD with oral iron therapy is associated with improvement of parasomnias in children. METHODS: A retrospective database was created for children with RLS/PLMD who were treated with iron therapy. These participants were followed for at least 1 year at Cincinnati Children's Hospital Medical Center. All participants had ferritin level testing and were treated with iron therapy. In addition, all participants underwent polysomnography before starting iron therapy for RLS/PLMD except for one participant who was already on iron but required a higher dose. Most participants underwent polysomnography after iron therapy. RESULTS: A total of 226 participants were identified with the diagnosis of RLS/PLMD. Of these, 50 had parasomnias and 30 of them were treated with iron therapy. Of the 30 participants, RLS symptoms improved in 15 participants (50%) and resolution of parasomnias was noted in 12 participants (40%) participants after iron therapy. Repeat polysomnography after iron therapy was performed in 21 participants (70%). After iron therapy, there was a significant decrease in periodic limb movement index (17.2 ± 8.8 [before] versus 6.7 ± 7.3 [after] events/h, P < .001). In addition, there were significant decreases in PLMS (24.52 ± 9.42 [before] versus 7.50 ± 7.18 [after] events/h, P < .0001), PLMS-related arousals (4.71 ± 1.81 [before] versus 1.35 ± 1.43 [after] events/h, P < .0001), and total arousals (11.65 ± 5.49 [before] versus 8.94 ± 3.65 [after] events/h, P < .01) after iron therapy. CONCLUSIONS: Parasomnias are common in our cohort of children with RLS/PLMD. Iron therapy was associated with a significant improvement in periodic limb movement index, RLS symptoms, and resolution of a significant proportion of NREM sleep parasomnias, suggesting that RLS/PLMD may precipitate NREM sleep parasomnia.

Periodic Limb Movements in a Comatose Patient: Case Report.

Periodic limb movements (PLMs) may occur as a primary condition or be associated with other pathologies, such as sleep disorders. However, PLMs have not been described in comatose patients. We report the case of a 66-year-old man, with no history of sleep disorders, who presented PLMs during coma caused by an extensive right hemispheric abscess inducing midline shift. These movements were further characterized by video and electromyographic recordings, which displayed bilateral periodic bursts of the tibialis anterior muscles, occurring every 7 to 15 seconds, with no concomitant electroencephalographic correlate. After a long period of hospitalization, the patient eventually regained consciousness and PLMs seem to persist, only in sleep. To the best of our knowledge, this is the first report showing that PLMs may be observed in a setting where the networks supporting consciousness are lost, namely in a coma of structural etiology.

Validation of a new data-driven automated algorithm for muscular activity detection in REM sleep behavior disorder.

BACKGROUND: Documentation of REM sleep without atonia is fundamental for REM sleep behavior disorder (RBD) diagnosis. The automated REM atonia index (RAI), Frandsen index (FRI) and Kempfner index (KEI) were proposed for this, but achieved moderate performances. NEW METHOD: Using sleep data from 27 healthy controls (C), 29 RBD patients and 36 patients with periodic limb movement disorder (PLMD), we developed and validated a new automated data-driven method for identifying movements in chin and tibialis electromyographic (EMG) signals. A probabilistic model of atonia from REM sleep of controls was defined and movements identified as EMG areas having low likelihood of being atonia. The percentages of movements and the median inter-movement distance during REM and non-REM (NREM) sleep were used for distinguishing C, RBD and PLMD by combining three optimized classifiers in a 5-fold cross-validation scheme. RESULTS: The proposed method achieved average overall validation accuracies of 70.8% and 61.9% when REM and NREM, and only REM features were used, respectively. After removing apnea and arousal-related movements, they were 64.2% and 59.8%, respectively. COMPARISON WITH EXISTING METHOD(S): The proposed method outperformed RAI, FRI and KEI in identifying RBD patients and in particular achieved higher accuracy and specificity for classifying RBD. CONCLUSIONS: The results show that i) the proposed method has higher performances than the previous ones in distinguishing C, RBD and PLMD patients, ii) removal of apnea and arousal-related movements is not required, and iii) RBD patients can be better identified when both REM and NREM muscular activities are considered.

Periodic Limb Movements During Sleep Are Not Associated With Hypertension in a Clinical Cohort of Korean Adults.

BACKGROUND: There is growing evidence of increased cardiovascular risk including hypertension in patients with periodic limb movements during sleep (PLMS). In a multiethnic cohort study, the association between prevalent hypertension and PLMS varied according to ethnicity. We evaluated whether PLMS are associated with hypertension in Koreans. METHODS: We enrolled 1,163 subjects who had polysomnography (PSG) from 2 tertiary hospitals. All subjects completed a sleep questionnaire before the PSG study. Coincidental hypertension was recorded according to past medical history. We analyzed the association between periodic limb movement index (PLMI), periodic limb movement associated with arousal index (PLMAI), and coincidental hypertension. Covariates were age, sex, body mass index (BMI), restless legs syndrome, apnea-hypopnea index (AHI), arousal index, and average oxygen saturation. RESULTS: A total of 304 subjects (26.1%) had hypertension. The proportion of subjects with hypertension in the PLMI ≥ 15 category was higher than that in the PLMI < 15 category (32.4% vs. 25.0%; P = 0.04). The proportion of subjects with hypertension in the PLMAI ≥ 1 category was 32.6%, which was higher than that in the PLMAI < 1 category (24.6%; P = 0.02). In a multivariate regression model, neither PLMI (odds ratio [OR], 1.12; 95% confidence interval [CI] 0.75-1.68) nor PLMAI (OR, 1.21; 95% CI 0.83-1.76) were associated with hypertension. Statistical significance was found between coincidental hypertension and the following variables: age, smoking history, BMI, and AHI. CONCLUSIONS: In a retrospective hospital-based study, there was no association between coincidental hypertension and PLMI/PLMAI in Koreans.

Comparison of computerized methods for rapid eye movement sleep without atonia detection.

Rapid eye movement (REM) sleep without atonia detection is a prerequisite for diagnosis of REM sleep behavior disorder (RBD). As the visual gold standard method is time-consuming and subjective, several automated methods have been proposed. This study aims to compare their performances: The REM atonia index (RAI), the supra-threshold-REM-activity metric, the Frandsen index, the short/long muscle activity indices, and the Kempfner index algorithms were applied to 27 healthy control participants (C), 25 patients with Parkinson's disease (PD) without RBD (PD-RBD), 29 patients with PD and RBD (PD + RBD), 29 idiopathic patients with RBD, and 36 patients with periodic limb movement disorder (PLMD). The indices were calculated in various configurations: (1) considering all muscle activities; (2) excluding the ones related to arousals; (3) excluding the ones during apnea events; (4) excluding the ones before and after apnea events; (5) combining configurations 2 and 3; and (6) combining configurations 2 and 4. For each of these configurations, the discrimination capability of the indices was tested for the following comparisons: (1) (C, PD-RBD, PLMD) vs (PD + RBD, RBD); (2) C vs RBD; (3) PLMD vs RBD; (4) C vs PD-RBD; (5) C vs PLMD; (6) PD-RBD vs PD + RBD; and (7) C vs PLMD vs RBD. Results showed varying methods' performances across the different configurations and comparisons, making it impossible to identify the optimal method and suggesting the need of further improvements. Nevertheless, RAI seems the most sensible one for RBD detection. Moreover, apnea and arousal-related movements seem not to influence the algorithms' performances in patients' classification.

Clinical significance of periodic limb movements during sleep: the HypnoLaus study.

OBJECTIVE: Periodic limb movements during sleep (PLMS) are prevalent in the general population, but their impact on sleep and association with cardiometabolic disorders are a matter of debate. METHODS: Data from 2162 participants (51.2% women, mean age 58.4 ± 11.1 years) of the population-based HypnoLaus study (Lausanne, Switzerland) were collected. Subjective sleep complaints and habits were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale (ESS). Participants underwent a full polysomnography (PSG) at home and were evaluated for the presence of hypertension, diabetes, and metabolic syndrome. RESULTS: Participants with a PLMS index (PLMSI) > 15/h (28.6% of the sample) had longer subjective sleep latency (18.6 ± 17.2 vs. 16.1 ± 14.3 min, p = 0.014) and duration (7.1 ± 1.2 vs. 6.9 ± 1.1 h, p < 0.001) than participants with PLMSI ≤ 15/h. At the PSG, they spent more time in stage N2 sleep (49.0 ± 11.2 vs. 45.5 ± 9.8%, p < 0.001), less in stage N3 (17.6 ± 8.2 vs. 20.6 ± 8.4%, p < 0.001) and in REM sleep (20.3 ± 6.4 vs. 22.4 ± 6.0%, p < 0.001), and exhibited longer REM latency (104.2 ± 70.2 vs. 91.7 ± 58.6 min, p < 0.001) and higher arousal index (26.5 ± 12.3 vs. 19.2 ± 9.7 n/h, p < 0.001). Participants with a PLMSI > 15/h had a lower ESS scores and higher prevalence of hypertension, diabetes, and metabolic syndrome. Multivariate analysis adjusting for confounding factors confirmed the independent association of PLMSI > 15/h with subjective sleep latency and duration, and with objective sleep structure disturbances. However, the associations with sleepiness and cardiovascular risk factors disappeared. CONCLUSIONS: In our large middle-age European population-based sample, PLMSI > 15/h was associated with subjective and objective sleep disturbances but not with sleepiness, hypertension, diabetes, or metabolic syndrome.

Parasomnias and Sleep-Related Movement Disorders in Older Adults.

Parasomnias and sleep-related movement disorders are important problems in older adults. Sleep paralysis is rare, but may occur in families. In a minority of patients with disorders of arousal, the episodes persist until the age of 70. Zolpidem and other medications may induce sleepwalking and sleep-related eating. Most patients with idiopathic rapid eye movement (REM) sleep behavior disorder eventually develop Parkinson's disease or dementia with Lewy bodies. Anti-IgLON5 disease includes abnormal behaviors in NREM and REM sleep. Restless legs syndrome prevalence increases with age. A severe form of periodic limb movements in sleep may mimic REM sleep behavior disorder.