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Objectives: Poor sleep is frequently reported in children with neuromuscular diseases (NMD) and cerebral palsy (CP) however breathing disorders during sleep are often the clinical focus. Periodic limb movements (PLMs) have an increased prevalence in adults with NMD and may contribute to sleep disturbance in this population. We assessed the prevalence of PLMs in children with NMD or CP., Methods: Retrospective review of polysomnography (PSG) with leg electromyography in children age 1-18 years with NMD (including Duchenne muscular dystrophy, myotonic dystrophy, spinal muscular atrophy) or CP performed at a paediatric sleep centre 2004-2022., Results: Leg electromyography was available in at least 1 PSG in 239 children (125 NMD, 114 CP), and in 2 PSGs in 105 children (73 NMD, 32 CP). At initial PSG, 72 (30 %) were female with a median age 9y and respiratory disturbance index 3.5/h (interquartile range 1.3-9.9/h). Elevated PLM index (PLMI; >5/h) occurred in 9.6 % of each of the CP and NMD groups, quantified by initial PSG. Overall, PLMI increased from baseline (median 0, maximum 33/h) to follow-up (median 0, maximum 55.8/h; p < 0.05). In those with an elevated PLMI, arousal percentage attributable to PLMs was up to 25 % (median 7.5 %)., Conclusions: Elevated PLMI occurred at a higher prevalence in children with NMD and CP than reported in other clinic-referred paediatric populations. It is important that PLMs are not overlooked as identification and treatment may help improve sleep outcomes. Further research is required to understand the pathophysiology and consequences of PLMs specifically in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Patients with early onset scoliosis are at high risk of sleep disordered breathing, sleep disruption, and adverse consequences of poor sleep. In this study, we aim to assess the prevalence of periodic limb movements of sleep in a cohort of children with early onset scoliosis and identify factors that correlate with the presence of periodic limb movements., Methods: This is a retrospective chart review of 40 patients with EOS (ages 1-17 years) who underwent a PSG from 2003 through 2019. Data collected included age, sex, and polysomnography parameters. Descriptive statistics were used: independent T test and Pearson correlation., Results: The average age was 9.6 years (SD 5.2); 22 were female. Eleven patients (27.5%) had elevated periodic limb movement index (PLMI) (≥ 5). Those with PLMI ≥ 5 had arousal index of 15.4 (SD 7.2) and those with normal PLMI having an arousal index of 9.4 (SD 4.9); this reached statistical significance (p < 0.05). Those with elevated PLMI spent 4.9 (SD 8.3) minutes with saturations below 88%, while those with normal PLMI spent 1.0 (SD 1.8); this was statistically significant. There was a moderate positive correlation between arousal index, hypoxemia, and PLMI., Conclusion: The study suggests that children with early onset scoliosis have higher frequency of periodic limb movements during sleep, and these may be correlated with increased arousal and with hypoxemia., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Excessive fragmentary myoclonus (EFM) is a frequent finding during routine video-polysomnography (VPSG). We aimed to automatically measure the prevalence of EFM according to current American Academy of Sleep Medicine (AASM) criteria, and the fragmentary myoclonus index (FMI) in sleep stage N1, N2, N3, rapid eye movement (REM) sleep and wake in a large patient population. A total of 500 VPSG recordings of patients admitted to the Sleep Laboratory, Department of Neurology, Medical University of Innsbruck, Austria, between May 1, 2022 and February 28, 2023, were included. EFM according to AASM criteria and FMI were computed by applying a previously validated algorithm. EFM was automatically detected in 121 of the 500 Sleep Laboratory patients (24.2%, 95% confidence interval 20.1%-28.9%). FMI increased with age, male gender, apnea-hypopnea-index (AHI), oxygen desaturation index (ODI), and periodic leg movements of sleep (PLMS) index. FMI was highest in REM sleep behaviour disorder (RBD), followed by neurodegenerative and internal medicine diseases, but the increase in the FMI was not explained by the disease itself but rather by the age and sex of the patients. Almost a quarter of our patient population had EFM. However, the prevalence of EFM does not allow the drawing of any conclusions about the pathophysiology of EFM or even the determination of a pathological FMI cut-off value. Associations of the FMI with age, sex, AHI, ODI and PLMS are in line with previous studies, but the FMI needs to be evaluated in different disease entities to learn more about its pathophysiology., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Caucasian patients with restless legs syndrome (RLS) frequently exhibit periodic limb movements during sleep (PLMS), which may increase the risk of hypertension. We evaluated the positivity rate of PLMS and factors associated with positivity in Japanese patients with RLS, and tested whether the complications of PLMS are associated with the presence of hypertension., Methods: We retrospectively investigated polysomnographic data and the presence or absence of hypertension in patients with RLS. Patients with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or those taking antihypertensive medication were categorized as the group with hypertension., Results: Among 468 patients, 200 (42.7%) had periodic limb movement index (PLMI) values ≥ 15/h and 108 (23.1%) met the criteria of positivity for hypertension. Multiple logistic regression analysis revealed that only higher age was significantly associated with PLMI values ≥ 15/h. Multiple linear regression analyses of factors associated with an increased PLMI also showed that increased PLMI was significantly correlated with higher age and male sex, but not with the international restless legs scale scores. Multiple logistic regression analysis also revealed that higher age and body mass index, not PLMI values ≥ 15/h, were significantly associated with the presence of hypertension., Conclusion: The PLMS-positivity rate may be lower in Japanese patients with RLS than in Caucasian patients, and it increases with age and male sex, but not with the severity of the disorder. Furthermore, PLMS complications were not associated with the risk of hypertension in Japanese patients with RLS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuichi Inoue reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Yuichi Inoue reports a relationship with Astellas Pharma Inc that includes: speaking and lecture fees. Yuichi Inoue reports a relationship with MSD KK that includes: speaking and lecture fees. Yuichi Inoue reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Moeko Sato reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Meiji Seika Pharma Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with MSD KK that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Mochida Pharmaceutical Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Sumitomo Pharma Co Ltd that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Kentaro Matsui reports a relationship with Yoshitomi Pharmaceutical that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Eisai Co Ltd that includes: funding grants and speaking and lecture fees. Katsuji Nishimura reports a relationship with Yoshitomi Pharmaceutical that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Astellas Pharma Inc that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Mochida Pharmaceutical Co Ltd that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with MSD KK that includes: funding grants and speaking and lecture fees. Katsuji Nishimura reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: funding grants and speaking and lecture fees. Katsuji Nishimura reports a relationship with Sumitomo Pharma Co Ltd that includes: funding grants and speaking and lecture fees. Katsuji Nishimura reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Kyowa Kirin Co Ltd that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Torii Pharmaceutical Co Ltd that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Viatris Inc that includes: speaking and lecture fees. Katsuji Nishimura reports a relationship with Novartis that includes: funding grants. Katsuji Nishimura reports a relationship with Boehringer Ingelheim Ltd that includes: funding grants. Katsuji Nishimura reports a relationship with Tsumura & Co that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Obstructive sleep apnea is a well-established risk factor for cardiovascular disease (CVD). Recent studies have also linked periodic limb movements during sleep to CVD. We aimed to determine whether periodic limb movements during sleep and obstructive sleep apnea are independent or synergistic factors for CVD events or death., Methods and Results: We examined data from 1049 US veterans with an apnea-hypopnea index (AHI) <30 events/hour. The primary outcome was incident CVD or death. Cox proportional hazards regression assessed the relationships between the AHI, periodic limb movement index (PLMI), and the AHI×PLMI interaction with the primary outcome. We then examined whether AHI and PLMI were associated with primary outcome after adjustment for age, sex, race and ethnicity, obesity, baseline risk of mortality, and Charlson Comorbidity Index. During a median follow-up of 5.1 years, 237 of 1049 participants developed incident CVD or died. Unadjusted analyses showed an increased risk of the primary outcome with every 10-event/hour increase in PLMI (hazard ratio [HR], 1.08 [95% CI, 1.05-1.13]) and AHI (HR, 1.17 [95% CI, 1.01- 1.37]). Assessment associations of AHI and PLMI and their interaction with the primary outcome revealed no significant interaction between PLMI and AHI. In fully adjusted analyses, PLMI, but not AHI, was associated with an increased risk of primary outcome: HR of 1.05 (95% CI, 1.00-1.09) per every 10 events/hour. Results were similar after adjusting with Framingham risk score., Conclusions: Our study revealed periodic limb movements during sleep as a risk factor for incident CVD or death among those who had AHI <30 events/hour, without synergistic association between periodic limb movements during sleep and obstructive sleep apnea.

Objective: The current evidence of a relationship between periodic leg movements during sleep (PLMS) and cognitive functioning is limited and inconsistent. This cross-sectional study assessed associations between PLMS and cognitive functioning among community-dwelling older adults., Methods: We included community-dwelling older adults who underwent a polysomnography and a cognitive assessment. The PLMS index (PLMI) and PLMS arousal index (PLMAI) were categorized into tertiles: PLMI <5/h (reference), 5-29.9/h, ≥30/h; and PLMAI <1/h (reference), 1-4.9/h, ≥5/h. The cognitive assessment consisted of ten scores covering the main cognitive domains: global cognition, processing speed, executive function, language, episodic verbal memory, and visuospatial function. Associations between PLMI, PLMAI, and cognitive scores were assessed using regression unadjusted and adjusted models., Results: A total of 579 individuals without dementia were included (mean age: 71.5 ± 4.4 years; men 45.4%). The number of participants in the high-PLMI categories, 5-29.9/h and ≥30/h, was 185 (32.0%) and 171 (29.5%), respectively. Participants in the high-PLMI categories showed no significant difference compared to the reference group regarding their cognitive performance according to the unadjusted and adjusted models. Similarly, we found no association between PLMAI severity and cognitive functioning., Conclusions: This study shows no cross-sectional association between PLMS severity and cognitive functioning among community-dwelling older adults. However, given the paucity of data in this field, further studies are needed to clarify the relationship between PLMS and cognitive functioning., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Restless sleep disorder (RSD) is a condition recently described by a group of sleep experts who developed diagnostic and polysomnographic criteria after conducting a comprehensive review of the available literature where poor sleep or restless sleep is a symptom alone or that accompanies other disorders. This group defined RSD as a condition characterized by parental complaints of frequent jerking movements during sleep, position changes, and sleep disruption that cause significant impairment during the day. Diagnostic criteria include the presence of symptoms for at least 3 months, 3 times a week, and at least 5 movements per hour on polysomnography. Changes in behavior during the day, such as drowsiness, irritability, and hyperactivity that are not explained by a medical, pharmacological, or behavioral condition, should be considered. Its estimated prevalence is 7.7% of children referred for sleep problems. Children often have ferritin levels below 50 µg/l, a point in common with restless legs syndrome. Treatment consists of iron supplements, which have shown benefits in these children. To establish the diagnosis, secondary symptoms of medical origin or other sleep disorders such as restless legs syndrome or periodic limb movement disorder must be ruled out. The objective of this report is to review the current recommendations on this entity, describe the clinical, pathophysiological, and polysomnographic keys, in order to highlight the need to publicize this condition and expand studies in age groups other than those already defined and to generate treatment guidelines.

Although periodic limb movement during sleep (PLMS) and restless legs syndrome (RLS) are common in children and adolescents, they are relatively overlooked as a target of treatment. PLMS has been evaluated as having a lower clinical significance than RLS. This study examined the relationship of socio-behavioral factors of PLMS in Korean adolescents and checked whether PLMS is associated with excessive daytime sleepiness (EDS), depending on whether restless legs symptoms accompany it. In a cross-sectional study, 25,789 adolescents between 12 and 18 years of age (15.76 ± 1.73 years; female 51.49%) were evaluated using an online survey. Various self-report questionnaires were used to assess PLMS and RLS symptoms, EDS, sleep habits, and various socio-behavioral factors. The prevalence of self-perceived PLMS and restless legs symptoms were 903 (3.50%) and 1311 (5.08%), respectively. Of the 1311 participants, 399 had self-perceived PLMS. The odds ratios (ORs) for self-perceived PLMS in participants with restless legs symptoms were: males (OR = 1.528; 95% CI: 1.145-2.040), usually/always experienced apnea apnea (OR, 3.006; 95% CI, 1.954-4.624), increased proneness to Internet addiction (OR = 1.013; 95% CI: 1.001-1.025), sometimes/often consuming coffee (OR = 1.312; 95% CI: 1.015-1.695), EDS (OR = 0.826; 95% CI: 0.488-1.398), and perceived insufficient sleep (OR = 1.143; 95% CI: 0.835-1.565). The male gender, witness apnea, consuming coffee, and being prone to Internet addiction were identified as factors significantly associated with self-perceived PLMS in participants with restless legs symptoms. However, EDS and insufficient sleep were associated with self-perceived PLMS in the absence of restless legs symptoms.

Background and Objectives: To investigate the association between various medication classes and the periodic limb movement index (PLMI) in a clinical cohort of adults who completed in-laboratory polysomnography., Methods: A single, diagnostic, overnight, in-laboratory polysomnogram was completed for 3,488 patients consecutively referred from 2010 to 2015 to determine PLMI. Medication use and medical comorbidities were collected through patient questionnaires. Associations between medication classes and PLMI were ascertained using multivariable ordinal logistic regression models., Results: The median age of the cohort was 56.0 years (48.2% male). After adjusting for age, sex, body mass index, relevant comorbidities, and sleep measures, the use of selective serotonin reuptake inhibitors (SSRIs) (odds ratio [OR] 1.52) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (OR 1.99) was associated with increased PLMI. Conversely, gabapentinoids (OR 0.71), stimulants (OR 0.52), benzodiazepines (OR 0.79), and dopamine agonists (OR 0.38) were associated with decreased PLMI. A non-statistically significant trend for decreased PLMI with neuroleptic use was observed. No significant associations were found between PLMI and the use of antihypertensives, statins, tricyclic antidepressants, bupropion, anticoagulants, antiplatelets, modafinil, and antihistamines., Discussion: The use of SSRIs and SNRIs was associated with elevated PLMI while the use of gabapentinoids, stimulants, benzodiazepines, and dopamine agonists was associated with decreased PLMI. These results can assist physicians in managing periodic limb movements in sleep (PLMS) and invite further research into the relationship between PLMS and medications with the modulating effects of dose, formulation type, and time of administration., Classification of Evidence: This study provides Class II evidence that SSRIs and SNRIs are associated with elevated PLMI while gabapentinoids, stimulants, benzodiazepines, and dopamine agonists are associated with decreased PLMI., (© 2022 American Academy of Neurology.)

Background: The association between restless legs syndrome (RLS) and Parkinson's disease (PD) remains controversial, with epidemiologic and descriptive evidence suggesting some potential overlap while mechanistic/genetic studies suggesting relative independence of the conditions., Objective: To examine a known, objectively measured endophenotype for RLS, periodic leg movements (PLMS) in sleep, in patients with PD and relate that objective finding to restless legs symptoms., Methods: We performed polysomnography for one (n = 8) or two (n = 67) consecutive nights in 75 PD patients and examined the association of PLMS with restless legs symptoms., Results: We found no association between restless legs symptoms and PLMS in PD. Prevalence of both was similar to data reported previously in other PD samples., Conclusion: We interpret these results as suggesting that restless legs symptoms in PD patients may represent a different phenomenon and pathophysiology than RLS in the non-PD population.

Study Objectives: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls., Methods: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.2 years) with a diagnosis of MS underwent a telephone interview assessing the 5 standard diagnostic criteria for RLS and polysomnography. Sleep architecture and leg movement activity during sleep were subsequently compared: 1) 40 patients with MS without RLS (MS-RLS) vs 28 healthy controls; 2) 17 patients with MS with RLS (MS+RLS) vs 35 patients with iRLS; 3) MS+RLS vs MS-RLS., Results: MS-RLS and MS+RLS presented increased sleep latency, percentage of sleep stage N1, and reduced total sleep time compared to healthy controls and iRLS, respectively. The periodic limb movements during sleep (PLMS) index was higher in MS-RLS than in healthy controls ( P = .035) and lower in MS+RLS compared to iRLS ( P = .024). PLMS in MS+RLS were less periodic, less often bilateral, and with shorter single movements compared to the typical PLMS in iRLS., Conclusions: MS is a risk factor for RLS, PLMS, and for a lower sleep quality in comparison to healthy patients. PLMS in MS+RLS are fewer and shorter if compared to iRLS. Our results suggest a dissociation between motor (PLMS) and sensory symptoms (RLS sensory component) in RLS secondary to MS, with possible treatment implications., Citation: Ferri R, Sparasci D, Castelnovo A, et al. Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome. J Clin Sleep Med . 2022;18(1):11-20., (© 2022 American Academy of Sleep Medicine.)

Study Objectives: To assess the frequency of restless legs syndrome (RLS), periodic limb movements during sleep (PLMS), and their overlap in a large sample of patients with multiple sclerosis (MS). To compare clinical and paraclinical findings among four subgroups of patients: RLS-/PLMS- (patients without RLS and PLMS), RLS+/PLMS- (patients with RLS and without PLMS), RLS-/PLMS (patients without RLS and with PLMS), and RLS+/PLMS+ (patients with both RLS and PLMS)., Methods: In this cross-sectional, observational, instrumental study, 86 patients (M/F: 27/59; mean age 48.0 ± 10.8 years) with a diagnosis of MS underwent a telephone interview assessing the five standard diagnostic criteria for RLS. Seventy-six participants underwent polysomnography (PSG) and maintenance of wakefulness test (MWT). Instrumental and clinical findings were subsequently statistically compared to investigate their association with RLS and PLMS index (PLMSI)., Results: RLS and PLMS (PLMSI ≥15/h) frequency in patients with MS were of 31.4% and 31.6%, respectively. Among patients with RLS, 37.5% had a PLMSI of at least 15/h. RLS-/PLMS+ group showed higher wake after sleep onset (p = 0.01), stage shifts per hour (p = 0.03), increased stage N1 (p = 0.03), and reduction in stage N3 (p = 0.01) compared to RLS-/PLMS-. RLS had no influence on clinical and PSG parameters (p = 0.45)., Conclusions: RLS is highly frequent in patients with MS. The frequency of PLMS is comparable to the general population. The low percentage of patients with RLS having a high PLMSI, together with the absence of correlation between RLS and female gender and older age, supports the existence of a distinct symptomatic form of RLS in MS., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2021 Asian Pacific Society of Respirology.)

Periodic leg movements during sleep (PLMS) are a frequent finding in nocturnal sleep registrations that include tibialis anterior electromyographic signals. Different PLMS scoring rules exist and can have a major impact on PLMS frequency, which tends to be underappreciated. There is no consistent evidence that frequent PLMS are a causal risk factor for clinically significant outcomes. Several critical open questions are identified that need to be addressed, including but not limited to the consideration of the full range of all sleep-related leg movement activity., Competing Interests: Disclosure Dr S. Fulda is supported by Swiss National Science Foundation (SNSF) grants No. 320030-160009 and 320030-179194., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Restless legs syndrome (RLS) is a sensory-motor neurological disorder that is associated with high levels of distress and sleep disturbance. Cross-sectional and longitudinal evidence suggests that individuals suffering from RLS may be at an increased risk of certain psychiatric illnesses and cardiovascular diseases. There also is evidence for increased mortality rates in RLS patients, although contrasting results do exist. Periodic limb movements of sleep (PLMS), repetitive leg movement observed in most RLS patients, and sleep disturbance may mediate the relationship between RLS and long-term morbidity. This article summarizes the literature investigating the potential consequences of both RLS and PLMS., Competing Interests: Disclosure Dr J.W. Winkelman reports acting as a consultant to Avadel, UpToDate, OrbiMed, and CVS and reports receiving research support from Luitpold, Merck and the RLS Foundation. Mr B. Wipper reports no disclosures. The authors did not receive any funding for the purposes of writing this review article., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Epilepsy is a prevalent health problem worldwide in all ages, and it is essential to identify disease markers for diagnosis and treatment. Periodic limb movements in sleep (PLMS) are a common finding in polysomnography (PSG). Still, its clinical relevance in people with epilepsy (PWE) is unknown. The aim of this review was to compare PLMS frequency in PWE and controls., Methods: A semi-structured literature review was conducted using PubMed in search of relevant studies in English on August 23, 2019, with the search terms "sleep," "epilepsy," or "seizure," and "polysomnography" in the title and/or abstract. The research was complemented with citation analysis and manual search using Google Scholar. Studies involved PWE and comparative controls using PSG with reported PLMS index (PLMI)., Results: Seven studies were identified. Only two showed a statistically significant difference in PLMI between cases and controls, and in another study, cases had uncontrolled seizures. In general, studies did not adjust for potential confounders including demographics, apnea-hypopnea index, or medication use., Conclusions: We found few studies exploring the prevalence of PLMS in PWE. In the majority, PLMI did not differ from controls. Further studies are warranted given the prevalence of sleep disturbances in epilepsy., Competing Interests: Declarations of interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We sought to assess the prevalence, correlates, and consequences of periodic limb movements of sleep (PLMS) in persons with obstructive sleep apnea (OSA) and the effect (worsening or improvement) of continuous positive airway pressure (CPAP) therapy on PLMS in a large prospective multicenter randomized controlled trial., Methods: We performed retrospective analyses of data from the Apnea Positive Pressure Long-term Efficacy Study, a prospective multicenter randomized controlled trial. A total of 1,105 persons with OSA enrolled in this study underwent a polysomnographic investigation at baseline, another one for CPAP titration, and another study 6 months after randomization to either active CPAP or sham CPAP., Results: Of all participants, 19.7% had PLM index (PLMI) ≥10/hour, 14.8% had PLMI ≥15/hour, 12.1% had PLMI ≥20/hour, 9.3% had PLMI ≥25/hour, and 7.5% had PLMI ≥30/hour. The odds of having a PLMI ≥10 were higher in older participants (odds ratio [OR] 1.03, p < 0.001), men (OR 1.63. p = 0.007), those using antidepressants (OR 1.48. p = 0.048), and those with higher caffeine use (OR 1.01, p = 0.04). After controlling for OSA and depression, PLMS were associated with increased sleep latency, reduced sleep efficiency, and reduced total sleep time. No significant relationships were noted between PLMS frequency and subjective sleepiness (Epworth Sleepiness Scale score) or objective sleepiness (Maintenance of Wakefulness Test). There was no differential effect of CPAP in comparison to sham CPAP on PLMS after 6 months of therapy., Conclusions: PLMS are common in patients with OSA and are associated with a significant reduction in sleep quality over and above that conferred by OSA. Treatment with CPAP does not affect the severity of PLMS., (© 2019 American Academy of Neurology.)

Study Objectives: Increased periodic limb movements of sleep (PLMS), > 5 events/h, are present in 1.2% to 7.7% of healthy children and associated with hypertension, attention deficit, and hyperactivity. This study sought to determine the prevalence of elevated PLMS in a large cohort of children with Down syndrome (DS) and their correlation with OSA and ferritin levels., Methods: Retrospective chart review of all children with DS ages 2 to 18 years in whom single baseline polysomnography (PSG) was performed at a pediatric hospital over 5 years., Results: A total of 418 children met inclusion criteria. Three hundred fifty-six children (85%) were referred because of concerns about sleep-disordered breathing; 49 (12%) were referred for screening per American Academy of Pediatrics (AAP) guidelines; and 13 (3%) because of concerns about restless legs or periodic limb movement disorder. One hundred thirty-nine children (33.3%) had elevated PLMS; they were younger (6.3 years) than those without elevated PLMS (7.7 years). OSA was present in 176/418 (42.1%) children, including 13/49 (26.2%) asymptomatic children referred for screening PSG. Ferritin levels were only recorded in the charts of 65 of the children with elevated PLMS (46.7%); in 36 (55.4%) levels were < 50 ng/mL., Conclusions: PLMS were increased in a substantial number of this large cohort of children with DS. Additional studies are necessary to assess utility of laboratory testing to predicting PLMS in similar, at-risk, populations. Screening PSG has value in identifying OSA in young, ostensibly asymptomatic children with DS. The prevalence of OSA increased with age in this cohort, unlike in typical children, requiring health care providers to remain vigilant for its emergence across the lifespan., (© 2020 American Academy of Sleep Medicine.)

Introduction: Although the pathophysiology of periodic limb movements in sleep (PLMS) is not well understood, there is increasing belief that management of PLMS can modulate humans' general health. The aim of this study is to investigate the associations between risk factors including the use of antidepressants, hypnotics, and antihistamines as well as of caffeine, alcohol, and nicotine and the occurrence of PLMS and periodic limb movement disorder (PLMD)., Methods: Patients with either chronic fatigue or insomnia who underwent polysomnography as standardized clinical assessment were included in a retrospective study. Associations were calculated between substance use and sleep variables., Results: Tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitor (SNRI) are significantly associated with higher rates of PLMS. Additionally, SNRI is significantly positive associated with PLMD, as also seen for selective serotonin reuptake inhibitors (SSRI). The most frequently used SSRI escitalopram was significantly positively associated with PLMS and PLMD. A significantly negative association was found between paroxetine and PLMS. Benzodiazepines are negatively associated with PLMS and PLMD. Sedative antidepressants, antihistamines, and substance use are not associated with PLMS nor PLMD in this study., Discussion: This retrospective study adds supportive evidence to the association of drug classes with PLMS and PLMD. These findings may impact on clinical management of patients with a combined anxiety or mood disorder in need for these drug classes on the one hand and a significant sleep architecture disturbance through PLMS, potentially contributing to daytime symptoms, on the other hand., Competing Interests: Authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Study Objectives: Little is known about comorbidities in children who have elevated periodic limb movement index (PLMI) during overnight polysomnogram (PSG). The aim of this study is to identify comorbidities in children with elevated PLMI (PLMI > 5) versus children with PLMI < 5 presenting to a pediatric sleep center., Methods: This study was a retrospective review of all clinically indicated PSGs obtained consecutively from 3/2017-3/2019 at Seattle Children's Sleep Disorders Center. Data collected included demographics, clinical presentation, medications, medical history, family history specifically for restless legs syndrome (RLS), ferritin levels, and PSG metrics. Characteristics between those with (cases) elevated PLMI (AASM criteria) and without (controls) were summarized., Results: We identified 148 subjects with elevated PLMI (67% male, mean age 7.95 years, range 1-20), yielding a PLMI > 5 prevalence of 5%. There were 188 controls included (58% male, mean age 8.0 years, range 1-19). Neither sex (chi-square = 2.8, NS) nor age (Mann-Whitney U = 1339.5, NS) differed between groups. Case subjects had a higher prevalence of RLS, snoring, insomnia, mood disorders, behavioral problems, morning headaches, chronic kidney disease, epilepsy, and chronic heart disease. Similarly, the use of antidepressants, antipsychotics, antiseizure medication, and other medications was statistically more frequent in children with elevated PLMS. The prevalence of PLMI > 5 was 5% and the prevalence of periodic limb movement disorder (PLMD) was 0.3% in children referred to polysomnography. Ferritin levels did not differ., Conclusions: We identified the prevalence of PLMD in a sleep medicine-referred population. We have also identified comorbidities and medications associated with elevated PLMI in children.No clinical trial., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: To measure the level of sleep disorders among patients with chronic obstructive pulmonary disease, and to see if there was any difference in terms of demographic variables and socioeconomic status., Methods: The cross-sectional descriptive observational study was conducted from March to June 2017, and data was collected through purposive sampling from different tertiary health care centres of Faisalabad, Pakistan. Sleep-50-Urdu scale was used to measure sleep disorders among patients with chronic obstructive pulmonary disease. SPSS 21 was used for data analysis., Results: Of the 140 respondents 70(50%) each were males and females with an overall mean age of 48.64±17.39 years. The patients had significantly high level of narcolepsy (p<0.05), but those from high socioeconomic status had relatively lower level of narcolepsy (p<0.05). Male patients and people from lower socioeconomic status also suffered from sleep apnoea and insomnia along with chronic obstructive pulmonary disease (p<0.05)., Conclusions: Narcolepsy along with sleep apnoea and insomnia were significantly more prevalent among chronic obstructive pulmonary disease patients from lower socioeconomic status.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Study Objectives: Limb movements during sleep (LMS) and periodic limb movements during sleep (PLMS) have been shown to vary by age in children. In the current study, we examined this relationship in more detail in a large clinically referred sample adjusting for iron status and sex., Methods: Retrospective data analysis was done on a large pediatric population who underwent an overnight sleep study and had ferritin levels measured within 30 days of sleep study between May 2013 and October 2017 at pediatric sleep center. Patients with obstructive or central sleep apneas were excluded., Results: A total of 1,070 patients were included in the study, with 60% males. Younger age and male sex were associated with increased PLMS and LMS. In addition, there was an increase in PLMS and LMS during adolescence that subsided at a later age, independent of sex. These associations remained significant in models controlling for ferritin level. Ferritin level, in contrast, was not a significant predictor of PLMS or LMS when controlling for sex and age., Conclusions: Age and sex may need to be considered when interpreting limb movement indices in pediatric sleep patients regardless of ferritin level., (© 2020 American Academy of Sleep Medicine.)

Objective: An association between migraine and sleep disturbances in children was reported, yet limited clinical data exist. The current study addresses the clinical presentation, polysomnographic (PSG) characteristics, and comorbid sleep diagnoses of children with migraine referred to the sleep clinic., Patients: A retrospective review was performed of headache center patients evaluated by the sleep center between 2007 and 2017. Children ≤18 years old, diagnosed with migraine headache, and who had PSG within one year of evaluation in the headache clinic, were included. PSG findings, as well as demographics, were compared to a group of controls aged 5-14 years-old., Results: In sum, 185 children with a diagnosis of migraine were included: 39% males, 75% Caucasian, mean age 13.5 ± 3.4, and 57% obese. Additionally, 180 children were included in the control group. The common presenting sleep symptoms were snoring (66%), sleep onset and sleep maintenance problems (25%), and excessive daytime sleepiness (20%). For the sleep diagnosis, 40% had obstructive sleep apnea (OSA), 27% had insomnia, 15% had periodic limb movement disorder (PLMD), and 6% had a central disorder of hypersomnolence. In terms of sleep architecture, children with migraine had significantly higher NREM 2 (p < 0.001) and a lower percentage of NREM3 (p < 0.001) compared to controls after adjustment for demographics and the presence of sleep-disordered breathing., Conclusions: Children referred to the sleep clinic who also had migraine, experience various types of sleep complaints. OSA, insomnia, and PLMD were relatively common in this population. Changes in sleep architecture, specifically increased NREM2 and decreased slow wave sleep compared to the control group, were also observed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Depression causes sleep disturbance and is associated with various sleep-related disorders. However, how depression affects the symptomatic presentation of different sleep-related disorders is unclear. In this study, we investigated the sleep parameters of different sleep-related disorders between depressive and non-depressive patients. A total of 785 patients underwent polysomnography in a mental hospital from Jan 2012 to Jun 2013. We first analyzed variables between the depressive and non-depressive groups. The patients were then divided into four groups: obstructive sleep apnea (OSA, n = 339), restless leg syndrome (RLS, n = 51), periodic limb movement disorder (PLMD, n = 58) and comorbid group (OSA and RLS, n = 46). We next compared sleep measures between the depressive and non-depressive subjects within each groups. The patients with OSA and depression were significantly associated with a higher periodic limb movement index. Significantly more patients with RLS patients and depression had initial insomnia complaints. However, significantly more patients with PLMD and depression middle insomnia. Compared with non-depressive population, depressive patients had higher comorbidity with RLS and PLMD. Depression may have different association with the sleep parameters in different sleep-related disorders. Further investigations are needed to investigate how these findings may affect patients' awareness and clinicians' diagnosis and management of sleep-related disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Study Objectives: Periodic limb movements in sleep (PLMS) are frequent motor phenomena; however, population-based data are scarce. We assessed the prevalence of PLMS and factors associated with PLMS within two German population-based cohorts, the SHIP-TREND and BiDirect., Methods: Single-night polysomnography was performed on 1107 subjects recruited from the general population (mean age: 52.9 years, 54.1% men) in the SHIP-TREND and on 247 participants (mean age: 57.6 years, 50.6% men) in the BiDirect. PLMS were evaluated using the standard criteria of the American Academy of Sleep Medicine. Sociodemographic data, behavioral variables, medical history, current medication, and other sleep disorders were assessed., Results: The prevalence of PLMS index (PLMSI) >15/hour was 32.4% (SHIP-TREND) and 36.4% (BiDirect). In multivariable models, age (odds ratio [OR] = 1.05 per +1 year), male gender (OR = 2.20), restless legs syndrome (OR = 2.32), physical inactivity (OR = 1.52), current smoking (OR = 1.49), diabetes (OR = 2.13), antidepressant use (OR = 2.27), lower serum magnesium (OR per -0.1 mmol/L = 1.27) showed a positive, and the intake of beta-blockers an inverse association with PLMSI >15/hour in SHIP-TREND. In BiDirect, age (OR = 1.13 per +1 year), body mass index (OR = 1.11 per +1 kg/m2), and restless legs syndrome (OR = 8.77) were significantly associated with PLMSI >15/hour., Conclusions: A high PLMSI is frequent in the German population. Age, male gender, restless legs syndrome, physical inactivity, current smoking, obesity, diabetes, antidepressant use, and lower magnesium were independently associated with PLMSI >15/hour in at least one of the cohorts., (© Sleep Research Society 2018. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Periodic limb movements in sleep (PLMS) are associated with adverse outcomes in patients with heart failure (HF). The aim of this study was to investigate whether PLMS change in response to adaptive servo-ventilation (ASV) for central sleep apnea (CSA) in patients with HF. We examined polysomnographic studies conducted between 2010 and 2014 at Mayo Clinic, Rochester, Minnesota (n = 14,444). In those, 314 of 579 patients with CSA completed the sleep study with a protocol that began with diagnostic polysomnography, followed by continuous positive airway pressure, and, for persistent CSA, by ASV titration. Patients with HF (n = 118) had a significantly higher median PLM index compared with those without HF (n = 196): 33.7 versus 6.1 events/h (p <0.001). HF was associated with a significant PLM arousal index (PLMAI) increase from diagnostic trial to ASV (odds ratio [OR]  = 1.79, p = 0.032) after adjusting for demographics, co-morbidities and medications. In patients aged >68 years, HF was associated with PLMI and PLMAI increases during ASV (OR  = 2.16, p = 0.016 and OR  = 2.05, p = 0.024), which persisted in multivariable models (OR  = 2.36, p = 0.025 and OR  = 2.33, p = 0.026). In multivariable analysis, patients with ejection fraction ≤45% had higher odds of increased PLMAI during ASV than those with ejection fraction >45% (OR  = 1.98, p = 0.022). In conclusion, PLMS may increase in HF patients after suppression of CSA by ASV. Whereas the clinical significance of increased post-ASV PLMS in HF prognosis needs to be determined, these increases may contribute to worsening outcomes in HF patients with CSA treated with ASV., (Copyright © 2018. Published by Elsevier Inc.)

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.

Study Objectives: The purpose of this study is to examine the association of abnormal periodic limb movements during sleep (PLMS) with neurocognitive and behavioral outcomes in adolescents with attention-deficit/hyperactivity disorder (ADHD) from the general population., Methods: Four hundred twenty-one adolescents (17.0 ± 2.3 years, 53.9% male) from the Penn State Child Cohort, a random general population sample, underwent 9 hr polysomnography, clinical history, physical examination, neurocognitive evaluation, and completed the Child or Adult Behavioral Checklist (C/ABCL). The presence of ADHD was ascertained by parent- or self-report of receiving a diagnosis of ADHD. PLMS were defined as a PLM index (PLMI) of ≥5 events per hour of sleep., Results: Adolescents with ADHD (n = 98) had a significantly higher PLMI (5.4 ± 7.3) and prevalence of PLMS (35%) when compared with controls (3.4 ± 5.6, p = 0.006 and 21%, p = 0.004). Significant interactions between ADHD and PLMS showed that adolescents with both disorders (n = 35) were characterized by deficits in control interference, as measured by Stroop test, and elevated internalizing behaviors, as measured by C/ABCL. ADHD severity and externalizing behaviors were elevated in a dose-response manner across ADHD-alone (n = 63) and ADHD + PLMS groups. The association of ADHD with other neurocognitive functions did not vary as a function of PLMS., Conclusions: PLMS are significantly more frequent in adolescents with ADHD. Importantly, adolescents with both disorders not only have worse neurobehavioral functioning than adolescents with ADHD-alone but specifically presented with executive deficits and anxiety symptoms. These data suggest that PLMS may be a marker of more severe underlying neurobiological deficits in adolescents with ADHD and comorbid internalizing problems.

Study Objectives: To investigate the prevalence of concurrent periodic limb movements during sleep (PLMS) and restless leg syndrome (RLS), as well as the prevalence of PLMS and RLS separately. Additionally, we document these prevalences by age, race/ethnicity, sex, and obesity status., Methods: Cross-sectional data from 2041 Multi-Ethnic Study of Atherosclerosis (MESA) Sleep ancillary study participants were used. PLMS (>15 periodic limb movements per hour of sleep) was measured by polysomnography. RLS symptoms were assessed using the 2009 International Restless Legs Syndrome Study Group clinical criteria., Results: The prevalence of RLS with PLMS was 6.7%, RLS alone 16.1%, and PLMS alone 21.2%. RLS with PLMS was prevalent in 7.0% of whites, 4.9% of blacks, 10.1% of Hispanics, and 3.3% of Chinese-Americans. In adjusted models, odds of RLS with PLMS was higher for those older than 67 years versus those younger (odds ratio [OR] [95% confidence interval [CI]] = 1.62 [1.09-2.40]). Relative to white participants, the prevalence of RLS with PLMS tended to be lower among blacks (0.56 [0.32-0.96]). The prevalence of concurrent RLS and PLMS did not statistically differ by sex or obesity status. RLS alone was more common in women., Conclusions: Approximately 7% of our sample had RLS with PLMS ("electro-clinical RLS"). This condition was more common among older individuals, did not vary by sex, and was less common among blacks. The findings provide some of the first information about the prevalence of concurrent RLS and PLMS in a community-based sample and show distinct sex and race associations for RLS versus electro-clinical RLS.

Objective: To define the prevalence, time course, and associated factors of periodic limb movements during sleep (PLMS) in patients with ischemic stroke or TIA., Methods: Patients enrolled in the prospective Sleep-Disordered Breathing in Transient Ischemia Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE) study underwent a double polysomnographic investigation in the acute and chronic phases after stroke/TIA, together with a MRI brain scan and a 24-hour blood pressure evaluation. The prevalence of PLMS in patients was compared with that in a matched sample of randomly selected healthy controls from the HypnoLaus cohort. One hundred sixty-nine recordings were performed in the acute phase and 191 after 3 months (210 recordings were obtained from the same 105 patients in both phases) and were compared to those of 162 controls., Results: The mean number of PLMS per hour and the percentage of participants with a PLMS index >10 and >15 per hour were similar between patients and controls. PLMS remained stable from the acute to the chronic phase after stroke. Factors positively associated with PLMS were age, body mass index, and history of hypertension. Blood pressure over 24 hours and the burden of cerebrovascular damage were similar between the groups with PLMS and without PLMS., Conclusions: PLMS are equally frequent in patients with stroke/TIA and the general population. The absence of higher blood pressure values and of a greater vascular brain damage found in patients with PLMS compared to those without PLMS might be due to a greater use of antihypertensive medication among patients with PLMS, which corresponds to a higher prevalence of previous diagnosis of hypertension in these patients., (© 2018 American Academy of Neurology.)

Introduction: Obstructive sleep apnea (OSA) and periodic limb movements (PLMs) have been associated with an increased risk of cardiovascular disease. There is limited data on the relationship between OSA and PLMs with atrial fibrillation and resistant hypertension in stroke and transient ischemic attack (TIA) patients., Methods: Consecutive stroke and TIA patients referred by a vascular neurologist for diagnostic polysomnography (PSG) from September 1, 2012 to August 31, 2015 were included in a retrospective analysis. Baseline clinical characteristics, PSG results and outcomes were collected to identify the frequency of and factors associated with PLMs (mild 5 to 10/h; severe ≥15/h), PLM arousals (≥5/h) and moderate-severe OSA (apna-hypopnea Index ≥15) including atrial fibrillation and resistant hypertension., Results: Among 103 patients (mean age, 60±15 y; 50% female; 61% nonwhites; 77% ischemic stroke; 23% resistant hypertension) who underwent PSG, 20% had mild PLMs, 28% had severe PLMs, 14% had PLM arousals, and 22% had moderate-severe OSA. Factors associated with moderate-severe OSA included older age (odds ratio, 1.06; 95% confidence interval, 1.02-1.11) and presence of atrial fibrillation (odds ratio, 4.26; 95% confidence interval, 1.17-15.44). Nonwhite race was associated with lower likelihood of mild and severe PLMs, whereas female sex was associated with lower likelihood of PLM arousals. OSA and PLMs were not associated with resistant hypertension., Conclusions: A significant number of stroke and TIA patients who underwent PSG have PLMs and moderate-severe OSA. Stroke and TIA patients with atrial fibrillation are more likely to have moderate-severe OSA and may benefit from PSG evaluation.

Background: Questionnaires indicate that patients with liver disease have disturbed sleep. However, polysomnographic studies to quantify sleep architecture and sleep disorders in this population are lacking. The current study compared polysomnographic findings of two groups of patients with clinically stable but severe end-stage pathology of the liver and heart., Methods: This was a prospective study of consecutive patients with end-stage liver disease or severe heart failure (HF)., Measurements and Results: Patients underwent full-night, attended polysomnography along with a number of laboratory tests. Polysomnograms were scored blindly. Compared to HF patients, patients with cirrhosis suffered from severe periodic limb movements during sleep (PLMS), with an index of 39/hour associated with excessive arousals. In patients with cirrhosis, serum iron and ferritin levels were either at the upper normal limit or elevated. There were significant correlations between severity of PLMS versus blood levels of bilirubin (r = 0.73, p = 0.004) and ammonia (r = 0.74, p = 0.017)., Conclusions: This was the first polysomnographic study of patients with stable cirrhosis demonstrating severely disturbed sleep infrastructure and presence of excessive PLMS with arousals. The pathobiochemical mechanisms of these findings remain to be established. Independent of the mechanisms, these polysomnographic findings confirmed the subjective reports of poor sleep by patients with cirrhosis. Further, a subset of patients with cirrhosis acquired a syndrome similar to idiopathic Parkinson's disease, which per se was frequently associated with PLMS; the current results were consistent with this notion. Future studies are needed to determine if PLMS of cirrhosis is an early indication of incident Parkinsonian syndrome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Periodic limb movements of sleep (PLMS) are usually comorbid with hypertension, tachycardia, and coronary arterial diseases, which are also risk factors for cerebrovascular accidents (CVA). However, evidence about the relationship between CVA and PLMS is still weak. The aim of this study was to investigate (1) the prevalence of CVA in patients with PLMS, and (2) the severity of PLMS in patients with or without CVA through a meta-analysis., Methods: The electronic databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov were searched. The inclusion criteria were (1) articles investigating comorbidity between PLMS and CVA, and (2) clinical trials in humans., Results: This meta-analysis included (1) 9,823 patients with PLMS and 9,416 controls from 5 studies to analyze the prevalence of CVA in PLMS, and (2) 158 patients with PLMS with CVA and 88 PLMS controls without CVA from 3 studies to analyze the severity of PLMS with and without CVA. The results showed (1) significantly higher comorbidity rates of CVA in the patients with PLMS than in the controls without PLMS (OR 1.267, p = 0.019), and (2) higher PLM index in the patients with CVA than in the controls (Hedges' g = 0.860, p = 0.001; means difference: 4.435, p = 0.016)., Conclusions: The results revealed (1) a worse severity of PLMS in the patients with CVA, and (2) increased prevalence of CVA in the patients with PLMS. Based on our results, the patients had a higher prevalence of CVA within 8 years of a diagnosis of PLMS compared to those without PLMS by about 1.3-fold. Whether (1) patients with PLMS receiving treatment have a similar incidence of stroke to those without PLMS, and (2) secondary stroke prevention can lower the severity of PLMS or whether those with severe PLMS have a higher risk of stroke is still inconclusive. Future studies investigating the prevalence of CVA in patients with PLMS should use a follow-up period of over 8 years., (© 2018 S. Karger AG, Basel.)

Background: Periodic leg movements during sleep (PLMS) have been associated with an increased risk for cardiovascular diseases and there is a high prevalence of PLMS found in patients with obstructive sleep apnea syndrome (OSAS). We evaluated patients with transient ischemic attack (TIA) for PLMS and respiratory related leg movements (RRLM), versus a control group without TIA., Methods: Twenty-five patients with TIA and 34 patients with no vascular diagnosis were referred for polysomnography. Diagnosis of PLMS was made if the periodic leg movement index (PLMI) was ≥5 and clinical significant as PLMI ≥15., Results: There was no significant difference in PLMI ≥5 and ≥15 between patients with and without TIA. In the absence of OSAS, 2 out of 5 TIA patients (40%) had a PLMI ≥15 compared to 1 of the 19 patients without TIA (5%; p = 0.037). There was no increase in RRLMs when OSAS was present., Conclusions: TIA patients did not have higher PLMI compared to controls, and in the presence of OSAS, there was no increase in RRLMs compared to patients without TIA. In selective patients, PLMS could be associated with cardiovascular diseases, since PLMS was clinically more often found in the TIA group without OSAS., (© 2018 S. Karger AG, Basel.)

Background: Growing evidence indicates that periodic limb movements of sleep (PLMS) may be related to increased risk of developing cardiovascular disease. However, the association of PLMS with atrial fibrillation (AF) is unclear, especially in patients with sleep-disordered breathing (SDB). This study sought to investigate whether PLMS were associated with increased AF prevalence, independent of established risk factors., Methods: We performed a cross-sectional study of patients who underwent attended polysomnography at Mayo Clinic from 2011 to 2014. The association of PLMS with AF prevalence was estimated by using logistic regression models., Results: 15,414 patients were studied, 76.3% of individuals with SDB defined by apnea-hypopnea index (AHI) ≥5/h, and 15.3% with a diagnosis of AF. In univariate logistic modelling, individuals with periodic limb movement index (PLMI) ≥30/h had higher odds of AF (odds ratio [OR] 1.96, 95% confidence interval [CI]1.79-2.16, p<0.001) when compared to patients with PLMI <15/h. After multivariate adjustment (for age, race, sex, history of smoking, hypertension, diabetes, coronary artery disease, heart failure, cerebrovascular disease, renal disease, iron deficiency anemia, chronic obstructive pulmonary disease, AHI, arousal index), in mild SDB patients, a PLMI ≥30/h or periodic limb movement arousal index (PLMAI) ≥5/h had significantly higher odds of AF than those with PLMI <15/h (OR 1.21, 95% CI 1.00-1.47, p=0.048) or PLMAI <1/h (OR 1.27, 95% CI 1.03-1.56, p=0.024)., Conclusions: Frequent PLMS are independently associated with AF prevalence in patients with mild SDB. Further studies are needed to better understand the relationship with incident AF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Study Objectives: To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS)., Aims and Methods: Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center., Results: Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals., Conclusions: Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and identified prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors., (© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To systematically review the current evidence examining restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) as prognostic factors for all-cause mortality and incident cardiovascular events (CVE) in longitudinal studies published in the adult population., Methods: All English language studies (from 1947 to 2016) found through Medline and Embase, as well as bibliographies of identified articles, were considered eligible. Quality was evaluated using published guidelines., Results: Among 18 cohorts (reported in 13 manuscripts), 15 evaluated the association between RLS and incident CVE and/or all-cause mortality and 3 between PLMS and CVE and mortality. The follow-up periods ranged from 2 to 20 years. A significant relationship between RLS and CVE was reported in four cohorts with a greater risk suggested for severe RLS with longer duration and secondary forms of RLS. Although a significant association between RLS and all-cause mortality was reported in three cohorts, a meta-analysis we conducted of the four studies of highest quality found no association (pooled hazard ratio = 1.09, 95% confidence interval: 0.80-1.78). A positive association between PLMS and CVE and/or mortality was demonstrated in all included studies with a greater risk attributed to PLMS with arousals., Conclusions: The available evidence on RLS as a prognostic factor for incident CVE and all-cause mortality was limited and inconclusive; RLS duration, severity, and secondary manifestations may be important in understanding a possible relationship. Although very limited, the current evidence suggests that PLMS may be a prognostic factor for incident CVE and mortality., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: 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)., Methods: A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography., Results: 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., Conclusion: 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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Primary restless leg syndrome (RLS) and periodic limb movements in sleep (PLMS) frequently co-exist, obscuring the boundaries between the two conditions. In such instances, a study of secondary cases with focal lesions such as post-stroke RLS and PLMS (psRLS and psPLMS, respectively) can be helpful in identifying characteristics of the individual conditions., Materials and Methods: Patients who had suffered strokes and who subsequently developed psRLS or psPLMS were recruited. To determine the overall features of psRLS/PLMS, historical cases were selected from the literature. All cases with either psRLS or psPLMS alone were further analyzed to elucidate the distinctive pathomechanisms of the two conditions., Results: Six patients with either psRLS or psPLMS were recruited from our hospital; two patients had both conditions contemporaneously. The literature contains details on 30 cases of psRLS or psPLMS. The causative lesion was most frequently located in the pons. We found that psRLS was more often bilateral, and usually detected later in time. Lesions in both the pontine base and tegmentum (together) were associated with unilateral psPLMS, whereas lesions in the corona radiata and adjacent basal ganglia were associated with bilateral RLS. Lesions confined to the corona radiata resulted in either unilateral or bilateral RLS., Conclusions: The observed differences in the clinical and radiological features of psRLS and psPLMS suggest that the pathophysiologies of the two conditions are distinct. Further research is needed to understand the pathophysiologies of primary RLS and PLMS., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Little is known about the pediatric population at an increased risk of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). Polysomnographic data from the Caffeine for Apnea of Prematurity-Sleep (CAPS) study showed a high prevalence of elevated periodic limb movement index (PLMI) in a cohort of ex-preterm children, but the clinical importance of this finding, such as association with RLS, is unknown. We hypothesized that ex-preterm children would have a high prevalence of RLS and PLMD., Methods: Ex-preterm children enrolled in CAPS, now aged 5-12 years, completed home polysomnography (PSG) and standardized questionnaires. A diagnosis of RLS or PLMD was established by participants meeting the International Classification of Sleep Disorders, 3rd edition, criteria based on questionnaires and polysomnograms. The clinically available serum ferritin levels were assessed., Results: In total, 167 participants underwent polysomnography and completed all questionnaires. The overall prevalence of RLS was 14/167 (8.4%). An additional 13 subjects (7.8%) were found to have PLMD. Of the 26 participants who had PLMI > 5/h, seven (26.9%) had RLS and 13 (50%) had PLMD. The serum ferritin levels were <50 mcg/L (range -38.4) for all eight participants referred for testing., Conclusions: Children with a history of prematurity have a high prevalence of RLS, particularly those with elevated periodic limb movements. Iron deficiency likely contributes to RLS and PLMD symptoms in this population. Clinicians evaluating ex-preterm children with sleep disturbances should evaluate for RLS and PLMD. Further studies including serum ferritin evaluation are required to confirm these findings., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Restless leg syndrome (RLS) and periodic limb movement (PLM) disorder (PLMD) can affect sleep quality and interfere with daytime functioning. Whether the co-morbidity of RLS further worsens daytime symptoms, sleep architecture and quality in patients with PLMs, is not yet fully clarified., Methods: Sleep (polysomnography) and daytime symptoms of 47 drug-free patients, assigned to isolated PLMD or co-morbid RLS subgroups, were compared to controls in a retrospective cohort-study (n = 501). Associations between perceived sleep quality, fatigue, sleepiness, mood and sleep variables were explored descriptively., Results: Although co-morbid patients showed worsened sleep quality, both patient groups showed similar sleepiness and affective symptoms. While significantly differing from controls, patients presented similarly increased light sleep, decreased slow-wave sleep and lowered sleep efficiency. Altered sleep quality, fatigue and sleepiness were significantly correlated to decreased slow-wave sleep and sleep fragmentation. Affective symptoms, fatigue and perceived sleep quality also correlated to PLM index., Conclusions: Sleep structure and efficiency were similarly impacted in isolated PLMD and in co-morbid RLS. RLS mainly worsened perceived sleep quality. Given that systematic treatment for isolated PLMD is currently not recommended, such results may question whether no or different-from-RLS treatment strategies are compatible with optimal care., (© 2017 S. Karger AG, Basel.)

Objective: To investigate an association between restless legs syndrome (RLS) and depression and to what extent sleep disturbance, periodic limb movements during sleep (PLMS), and antidepressant medication mediate this relationship., Methods: A cross-sectional analysis was conducted of the Osteoporotic Fractures in Older Men Study data in 982 men assessed for RLS (International RLS Study Group scale [IRLSS]) and depression (Geriatric Depression Scale [GDS]), who underwent actigraphy (for sleep latency/efficiency) and polysomnography (for PLMS). Men were split into three groups: no RLS (N = 815), mild RLS (IRLSS ≤ 12, N = 85), moderate-to-severe RLS (IRLSS > 12, N = 82). Depression was defined as GDS score ≥ 6. Logistic and linear regression assessed associations of RLS and depression or number depressive symptoms, respectively. Models were adjusted for age, site, race, education, body mass index, personal habits, benzodiazepine/dopaminergic medication, physical activity, cardiovascular risk factors, and apnea-hypopnea index., Results: Of 982 men, 167 (17.0%) had RLS. Depression was significantly associated with moderate-to-severe RLS after adjustment (versus no RLS: OR [95% CI] 2.85 [1.23, 6.64]). Further adjustment for potential mediators attenuated effect size modestly, most for sleep efficiency (OR: 2.85-2.55). Compared with no RLS, moderate-to-severe RLS was associated with the number of depressive symptoms after adjustment (adjusted means [95% CI]; no RLS: 1.14 [1.05, 1.24] versus IRLSS > 12: 1.69 [1.32, 2.11]). Further adjustment for potential mediators did not alter effect size. For men with PLMS index at least median, number of depressive symptoms significantly increased as RLS category became more severe., Conclusion: Depression is more common as RLS severity worsens. The RLS-depression relationship is modestly explained by sleep disturbance and PLMS., Competing Interests: FINANCIAL DISCLOSURE Dr. Koo has no conflicts of interest to disclose. Dr. Blackwell reports no disclosures. Dr. Lee reports no disclosures. Dr. Stone is funded by NIH: RO1 2803205. Dr. Louis reports no disclosures. Dr. Redline has received a grant from the Resmed Foundation; her institution has received equipment for use in NIH funded studies and is supported by multiple NIH grants., (Published by Elsevier Inc.)

Study Objectives: To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men., Methods: We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition., Results: After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test - Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05-2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores., Conclusions: Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function., (© 2016 Associated Professional Sleep Societies, LLC.)

Objectives: This study aimed to examine relationship between periodic limb movements during sleep (PLMS) and incident atrial fibrillation/flutter (AF)., Methods: Prospective multicenter cohort (n = 2273: adjudicated AF group; n = 843: self-reported AF group) of community-dwelling men without prevalent AF were followed for an average of 8.3 years (adjudicated) and 6.5 years (self-reported). PLMS index (PLMI, <5 (ref), ≥5 to <30, ≥30) and PLM arousal index (PLMAI, <1 (ref), ≥1 to <5, ≥5) were measured by polysomnography. Incident adjudicated and self-reported AF were analyzed by Cox proportional hazards and logistic regression, respectively, and adjusted for age, clinic, race, body mass index (BMI), alcohol use, cholesterol level, cardiac medications, pacemaker, apnea-hypopnea index, renal function, and cardiac risk. The interaction of age and PLMS was examined., Results: In this primarily Caucasian (89.8%) cohort of older men (mean age 76.1 ± 5.5 years) with BMI of 27.2 ± 3.7, there were 261 cases (11.5%) of adjudicated and 85 cases (10.1%) of self-reported incident AF. In the overall cohort, PLMI and PLMAI were not associated with adjudicated or self-reported AF. There was some evidence of an interaction of age and PLMI (p = 0.08, adjudicated AF) and PLMAI (p ≤ 0.06, both outcomes). Among men aged ≥76 years, the highest PLMI tertile was at increased risk of adjudicated AF (≥30 vs. <5; hazard ratio (HR) = 1.63, 1.01-2.63) and the middle PLMAI tertile predicted increased risk of both outcomes (1 to <5 vs. <1; adjudicated, HR = 1.65, 1.05-2.58; self-reported HR = 5.76, 1.76-18.84). No such associations were found in men aged <76 years., Conclusions: Although PLMS do not predict AF incidence in the overall cohort, the findings suggest PLMS increases incident AF risk in the older subgroup., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Study Objectives: The aim of this study was to investigate the prevalence and characteristics of periodic limb movements during sleep (PLMS) in Korean patients with restless legs syndrome (RLS)., Methods: Unmedicated adult patients with idiopathic RLS (n = 354) who underwent polysomnography at three major sleep centers in tertiary hospitals were included. Characteristics of PLMS in RLS were analyzed using the time structure of polysomnographically recorded leg movements and periodicity indices (PIs). RLS severity and subjective sleep quality were assessed., Results: Out of 354 patients with idiopathic RLS (mean age: 52.9 ± 12.0 years), 150 patients (42.3%) had RLS with a PLMS index greater than 15 events/h, and 204 (57.9%) had a PLMS index greater than 5 events/h. The distribution of inter-LM intervals was bimodal, and high PIs (0.86 ± 0.10) were observed in patients with RLS and PLMS (PLMS index > 15 events/h). The PLMS index was positively correlated with age (r = 0.228; p < 0.001), the periodic limb movements in wakefulness index (r = 0.455, p < 0.001) and arousal index (r = 0.174, p = 0.014), but not with RLS severity and parameters of sleep quality. In multivariate analysis, age and male gender were independently associated with PLMS > 15 events/h., Conclusions: The prevalence of PLMS in Korean patients with RLS was lower than that observed in Western countries, but the characteristics of PLMS were not different. Ethnic differences and/or different genetic backgrounds may contribute to the varying prevalence of PLMS in RLS., (© 2016 American Academy of Sleep Medicine.)