Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, ß-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is ß-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.

Elevated periodic limb movement index is associated with hypoxemia in children with early onset scoliosis.

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.

Polysomnographic findings in children with 22q deletion & duplication syndrome: relationship to genetic diagnosis, parent-reported symptoms, and calcium levels.

PURPOSE: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome. In the current study, we assessed the relationship between parent-reported symptoms of obstructive sleep apnea (OSA) and polysomnographic (PSG) results in patients with 22q11.2DS. Additionally, we explored the relationships between genetic diagnosis, serum calcium and ferritin levels, and PSG results. METHODS: Retrospective chart review was completed for patients enrolled in our 22q Center's registry from 2015-2021. Data extracted included: patient characteristics, parent-reported sleep symptoms from the Childhood Sleep Habits Questionnaire (CSHQ), serum calcium and ferritin levels, and results from formal PSG. RESULTS: Overall, n = 89 encounters (60 unique patients) with PSG data demonstrated that there were no differences in OSA between those with deletion vs duplication, but PLMD was more common in those with deletion (35% vs 7%, p = 0.032). In a subset of n = 24 encounters with PSG and survey data in proximity, there were no significant associations between the CSHQ sleep-disordered breathing subscale and OSA presence or severity (p = 0.842). Likewise, we found no significant associations between the individual symptoms of OSA and PSG results (all p > 0.5). In those patients with available calcium (n = 44) and ferritin (n = 17) levels, we found a significant negative correlation between serum calcium and PLMS (r = -0.446, p = 0.002), but not ferritin (r = -0.067, p = 0.797) levels. CONCLUSIONS: Parent-reported symptoms do not predict the presence or severity of OSA in children with 22q11.2DS. There was a negative correlation between serum calcium, but not ferritin, and PLMS on PSG.

Effect of series of periodic limb movements in sleep on blood pressure, heart rate and high frequency heart rate variability.

INTRODUCTION: The phenomenon known as periodic limb movements in sleep (PLMS) has been linked to a change in autonomic nervous system (ANS) activity and its effect on circulatory regulation. Autonomic dysfunction or dysregulation in patients with PLMS has been described in some domains; however, any relationship between heart rate variability (HRV) and PLMS has not been clearly established. HRV analysis is a recognised, non-invasive research method that describes the influence of the ANS on heart rate (HR). The aim of our study was to further investigate the dysregulation of autonomic HR control in patients with PLMS. MATERIAL AND METHODS: We undertook a retrospective analysis of the polysomnographic (PSG), demographic and medical data of five patients with a total number of 1,348 PLMS. We analysed HR, HRV HF, systolic blood pressure (SBP), and diastolic blood pressure (DBP) for 10 heartbeats before the series of PLMS and 10 consecutive heartbeats as beat-to-beat measurements. The presented method of using successive, short, 10 RR interval segments refers to the time-frequency measurement, which is very clear and useful for presenting changes in the calculated parameters over time and thereby illustrating their dynamics. This method allowed us to assess dynamic changes in HRV HF during successive PLMS series. Statistical analysis was performed using IBM SPSS Statistics (v. 28.0.0.0). The Kruskal-Wallis test was performed to find statistically significant changes from baseline. RESULTS: No statistically significant changes in HR, SBP, or DBP were found in our group, although an increase in the value of the HRV HF was noted, suggesting an increase in intracardiac parasympathetic activity during the subsequent series of PLMS. CONCLUSIONS: Our study indicates an increase in parasympathetic activity during the appearance of successive PLMS, which, with the simultaneous lack of changes in HR, may suggest an increase in sympathetic activity, and therefore the appearance of so-called 'autonomic co-activation' resulting in the possibility of life-threatening cardiac events. CLINICAL IMPLICATIONS: Our findings add to the literature information regarding HRV in PLMS, and highlight the need for further studies to elucidate the effects of these conditions on the ANS, and on cardiovascular health.

Association between periodic limb movements during sleep and neuroimaging features of cerebral small vessel disease: A preliminary cross-sectional study.

Evidence on the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease is lacking. This study aimed to assess the association between the PLMS index and the neuroimaging features of cerebral small vessel disease on magnetic resonance imaging. Consecutive patients diagnosed with cerebral small vessel disease were enrolled. Data on the clinical characteristics, polysomnography, and brain magnetic resonance imaging were collected. The Accubrain software was used to calculate automatically the volume of white matter hyperintensities, the number of lacunar infarctions, and cerebral microbleeds. The severity of white matter hyperintensities, enlarged basal ganglia perivascular spaces, and the total cerebral small vessel disease scores were also rated visually using semiquantitative scales. The severity of PLMS was measured using the PLMS index, and the patients were divided into two groups using an established cut-off value of ≥15 per hour. Logistic regression was used to examine the association between PLMS and the neuroimaging features of cerebral small vessel disease. In total, 37 patients were included in the final analyses. The mean age was 66.49 ± 11.31 years, and 73.0% were males. The mean PLMS index was 19.30 ± 10.18. In univariate analyses, it was found that patients with cerebral small vessel disease with a PLMS index ≥15 had increased enlarged basal ganglia perivascular spaces (OR 6.136, 95%CI 1.101-34.214) and increased total cerebral small vessel disease scores (OR 6.0, 95%CI 1.253-28.742). Only the association between the PLMS index and the total cerebral small vessel disease burden score remained statistically significant after adjusting for age, sex, and the presence of moderate to severe obstructive sleep apnea syndrome. In conclusion, an elevated PLMS index is likely to be associated with a greater cerebral small vessel disease burden. PLMS might be a novel potential marker of cerebral small vessel disease.

Clinical characteristics of periodic limb movements during sleep categorized by continuous positive airway pressure titration polysomnography in patients with obstructive sleep apnea.

PURPOSE: The presence of periodic limb movements during sleep (PLMS) varies among patients with obstructive sleep apnea (OSA) undergoing treatment with continuous positive airway pressure (CPAP). The factors associated with this variation are unknown. METHODS: PLMS were defined as a periodic leg movements index of > 15/h. Patients with OSA and PLMS were categorized into four groups depending on diagnostic and CPAP titration polysomnography (PSG). A multinomial logistic regression analysis was performed using a non-PLMS group as the reference category. RESULTS: This study included 861 patients with OSA who underwent a full-night CPAP titration PSG. The proportions of the subjects with PLMS on both PSGs (persistent PLMS), those with CPAP-emergent PLMS, and those with CPAP-resolved PLMS were 12.9%, 9.2%, and 3.9%, respectively. Compared with the non-PLMS group, the persistent group was more likely to be of older age and male sex and has a higher body mass index and restless legs syndrome (RLS). Patients in the CPAP-emergent group were also older and more likely to have RLS as well as more severe apnea. Patients in the CPAP-resolved group were more likely to be women, of older age, have a higher body mass index, but less severe apnea. CONCLUSIONS: PLMS elicited by CPAP are more likely to occur in older patients with more severe sleep apnea and comorbid RLS, whereas OSA patients in which PLMS resolve after CPAP are more likely to be women and have milder sleep apnea. Persistent PLMS share clinical characteristics with PLMS in general population.

Periodic limb movements during sleep are associated with poor health-related quality of life in patients with obstructive sleep apnea.

PURPOSE: The clinical significance of the comorbidity of periodic limb movements during sleep (PLMS) in sleep-disordered breathing remains unclear. This study aimed to determine whether or not the presence of PLMS is related to depressed mood and poor quality of life in subjects with obstructive sleep apnea (OSA). METHODS: We defined PLMS as a periodic leg movement index of > 15/h. Scores for the Medical Outcomes Study Short Form Health Survey and Beck Depression Inventory were assessed with multiple logistic or linear regression analyses. RESULTS: Of 1370 subjects with OSA, a prevalence of PLMS was 14.1%. Older age, men, and obesity were positively associated with PLMS. PLMS occurred in 17%, 15%, and 12% of mild, moderate, and severe subjects with OSA, respectively. Severe OSA was less likely to be associated with PLMS than mild OSA. PLMS negatively correlated with physical and mental component summary scores of the health survey but not with Beck Depression Inventory scores after controlling for confounding variables. PLMS were significantly associated with poor sleep architecture on polysomnography. However, the relationship between PLMS and disturbed sleep was no longer significant after adjusting for age. CONCLUSIONS: Health-related quality of life, including physical and mental health but not depressive symptoms, was worse in subjects with OSA and PLMS than in those without PLMS.

Prevalence of periodic limb movement in sleep in people with epilepsy: A semi-structured literature review.

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.

Prospective associations of sleep apnea, periodic limb movements, and plasma fibrinogen level.

PURPOSE: Our previous cross-sectional study showed that periodic limb movements during sleep (PLMS) were frequently found in patients with obstructive sleep apnea (OSA) and that both OSA and PLMS were associated with higher plasma fibrinogen levels. We explored the longitudinal relationships among these factors. METHODS: Plasma fibrinogen levels were measured in 333 consecutive patients who underwent polysomnography to diagnose OSA. Patients who initiated continuous positive airway pressure (CPAP) underwent follow-up polysomnography after 3 months of CPAP use. They were categorized into groups with good or poor adherence (% days with ≥ 4 h/night of CPAP use ≥ 70% or < 70%, respectively). Changes in sleep parameters and plasma fibrinogen levels during the treatment period were compared between these groups. RESULTS: The cross-sectional analysis of all reviewed 333 patients indicated that fibrinogen levels were associated with the severities of OSA and PLMS. The 60 patients (27 good and 33 poor adherence) who underwent follow-up polysomnography were included in the longitudinal analysis. The median (interquartile range) periodic limb movement index did not change significantly from CPAP titration to the 3-month follow-up (good adherence: 10.5 (0-23.8) to 10.8 (0-70.2) events/h, p = 0.21; poor adherence: 1.2 (0-14.3) to 0.8 (0-15.7) events/h, p = 0.67). However, the plasma fibrinogen level significantly decreased only in the good adherence group (good adherence: baseline 275 ± 46 to follow-up 255 ± 47 mg/dl, p < 0.01; poor adherence: 277 ± 52 to 284 ± 70 mg/dl, p = 0.48). CONCLUSIONS: These results did not support a longitudinal association between PLMS and OSA. However, good adherence to CPAP could reduce plasma fibrinogen levels, thus ameliorating elevations in plasma fibrinogen as a risk factor for future cardiovascular events.

Periodic limb movements during sleep may reduce excessive daytime sleepiness in men with obstructive sleep apnea.

PURPOSE: The impact of periodic limb movements during sleep (PLMS) on excessive daytime sleepiness (EDS) is controversial. We investigated the relationship between PLMS and EDS in men with obstructive sleep apnea (OSA). METHODS: This was a cross-sectional study of men with OSA. PLMS parameters were a PLM index (PLMI) > 15 per hour of sleep and a PLM-arousal index (PLMAI) > 5 per hour of sleep. The Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory were used. EDS was defined as an ESS score ≥ 11. Multivariate logistic regression analysis was performed with adjustments for several covariates. RESULTS: Of 1111 men with OSA, 14.0% (n = 156) had a PLMI > 15/h, and 3.7% (n = 41) had a PLMAI > 5/h. EDS was noted in 39.5% (n = 439) of men. Men with a PLMI > 15/h were less likely to have EDS (odd ratio [OR], 0.598; 95% confidence interval [CI], 0.414-0.864; p = 0.006). This association remained significant after controlling for age, body mass index, depressive symptoms, total sleep time, and severity of OSA (OR, 0.675; 95% CI, 0.456-0.999; p = 0.049). Men with a PLMAI > 5/h were less likely to have EDS, but this result did not reach statistical significance (OR, 0.550; 95% CI, 0.273-1.109; p = 0.095). CONCLUSIONS: PLMS defined as PLMI > 15/h are significantly and inversely associated with EDS in men with OSA, even after controlling for several confounding variables.

Sleep spindles, K-complexes, limb movements and sleep stage proportions may be biomarkers for amnestic mild cognitive impairment and Alzheimer's disease.

PURPOSE: Sleep disturbances are common in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients. Non-rapid eye movement stage 3 (N3), rapid eye movement stage (REM), spindle density, and K-complex (KC) density are decreased in MCI and AD patients. Periodic limb movements in sleep (PLMS) are increased in other neurodegenerative diseases. We aimed to distinguish amnestic mild cognitive impairment (aMCI) patients from the overall population of MCI patients by comparing the N3 and REM proportions, the morphological characteristics of spindles and KCs and the periodic limb movement index (PLMI) among control, aMCI and AD subjects. METHODS: In 92 subjects (30 controls, 32 aMCI and 30 AD), sleep stages, spindles, KCs and PLMS were recorded during the second of two nights of polysomnography (PSG). We compared the above parameters among the three groups. RESULTS: AD and aMCI subjects had lower proportions of N3 and REM, poorer spindle and KC activities and more frequent PLMS than controls. These alterations were associated with decreased Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. We determined cut-off values for distinguishing aMCI and AD using logistic regression and receiver operating characteristic (ROC) analyses. CONCLUSIONS: AD and aMCI patients have abnormal sleep stage proportions, spindles, KCs and PLMS. The combination of the above alterations may distinguish aMCI and AD patients from controls with high specificity and sensitivity.

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.

Effects of controlled dehydration on sleep quality and quantity: A polysomnographic study in healthy young adults.

Dehydration is associated with several alternations in body homeostasis involving both physiological and mental aspects. In addition some studies have reported a negative effect of dehydration on subjectively assessed sleep-related parameters. The aim of the current study was to examine for the first time the effect of controlled dehydration on sleep quality and quantity using the gold-standard method of polysomnography. Twelve healthy male volunteers participated in this study (23.4 ± 0.8 years). Participants performed an in-house full polysomnographic assessment in two different occasions taking place in random order: (i) in a dehydrated state; and (ii) in a euhydrated state. In the dehydration scenario, the participants were allowed to consume only 1.25 L of non-caffeinated fluids, while during the euhydrated state participants had to drink at least 3 L of non-caffeinated fluids during the last 24 hr before the polysomnographic study. Urine specific gravity was assessed by refractrometry on collection day in order to assess hydration status. Participants who did not fulfil the hydration criteria were rescheduled. All participants successfully completed the two polysomnographic studies without any complaints or adverse effects reported. No significant differences were found in any of the examined indices of sleep quality and quantity between the dehydration and euhydration scenarios (p > .05). This is the first study to show that controlled mild dehydration does not seem to affect sleep quality and quantity in young healthy adults. More research is necessary to further verify these conclusions and assess whether other parameters are involved in the manifestation of sleep disturbances.

Periodic limb movements during sleep are associated with cardiovascular diseases: A systematic review and meta-analysis.

Periodic limb movements during sleep present with repetitive movements, typically in the lower limbs, during sleep. Periodic limb movements during sleep have been proposed to be associated with increased risk of heart diseases. The aim of this study was to examine the co-morbidity rates of heart disease, including acute myocardial infarction, coronary artery disease and cardiovascular disease, in subjects with or without periodic limb movements during sleep through a meta-analysis. An electronic review of PubMed, Embase, ScienceDirect, Cochrane Library, ProQuest, Web of Science, ClinicalKey and ClinicalTrials.gov was performed. Clinical studies, case-controlled trials and cohort studies were all included in the search. Case reports or series, and non-clinical studies were excluded. A meta-analysis of the results of six studies comparing the prevalence of coronary artery disease/acute myocardial infarction/cardiovascular disease in subjects with/without periodic limb movements during sleep was performed. There were significantly higher co-morbidity rates of coronary artery disease (odds ratio = 1.568, 95% confidence interval: 1.187-2.073, p = 0.002) and cardiovascular disease (odds ratio = 1.279, 95% confidence interval: 1.095-1.494, p = 0.002), but not acute myocardial infarction (odds ratio = 1.272, 95% confidence interval = 0.942-1.718, p = 0.117), in the periodic limb movements during sleep group than in the non-periodic limb movements during sleep group. This meta-analysis highlights the importance of a significantly high prevalence of coronary artery disease and cardiovascular disease in subjects with periodic limb movements during sleep. Further studies should be focused on the potential pathophysiology, and whether treatment for periodic limb movements during sleep can improve the outcome of heart disease.

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability.

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea-hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/- periodic limb movements during sleep (5 ≤ apnea-hypopnea index < 30 events per hr), - obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, - obstructive sleep apnea/- periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time- and frequency-domain heart rate variability measures were calculated over 5-min periods of stable stage 2 non-rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea-hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea-hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea-hypopnea index and low periodic limb movement index, and compared with those with low apnea-hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea-hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.

Abnormal sleep in patients with epileptic or dissociative (non-epileptic) seizures: a polysomnography study.

BACKGROUND AND PURPOSE: The aim of this study was to identify the prevalence of sleep disorders and measure the objective sleep quality in patients with seizure disorders. METHODS: Patients admitted for video electroencephalography monitoring were prospectively recruited and polysomnography was performed on the third night of monitoring. RESULTS: A total of 4/44 (9%) patients with epilepsy and 2/22 (9%) patients with dissociative seizures were found to have mild sleep-disordered breathing. Three (7%) patients with epilepsy were found to have mild or moderate obstructive sleep apnea-hypopnea syndrome (OSAHS) and three (14%) patients with dissociative seizures had mild or moderate OSAHS. Most patients with sleep-disordered breathing or OSAHS were overweight or obese. Time awake after sleep onset was high in both groups. There were no significant differences in sleep architecture between the groups except for a difference in average N3 sleep stage proportion. Periodic limb movements (PLMs) were common in both groups and 27% of patients with dissociative seizures had both high PLM rates and high arousal indices, suggesting a high prevalence of probable PLM disorder in that group (compared with 9% in the epilepsy group). CONCLUSIONS: Our findings contradict the commonly reported high comorbidity of OSAHS and epilepsy, and question its purported clinical relevance. High rates of PLMs were found in patients with dissociative seizures. In both patient groups, high awake after sleep onset times were indicative of sleep disruption, which can have an epileptogenic effect and is known to increase dissociative tendencies.

[Effects of continuous positive airway pressure on periodic limb movements during sleep in patients with obstructive sleep apnea].

Objective: To investigate the effects of continuous positive airway pressure (CPAP) on periodic limb movements during sleep (PLMS) in patients with obstructive sleep apnea (OSA). Methods: The polysomnography (PSG) data of 828 consecutive OSA outpatients from January 2015 to January 2017 who had undergone overnight CPAP titration were analyzed retrospectively. On the basis of changes in periodic limb movements index (PLMI) values (cut off level≥15/h) from baseline PSG (BPSG) to CPAP titration PSG, patients were assigned to one of the following four groups: persistent, CPAP-emergent, CPAP-disappeared, and non-PLMS. Results: Among 828 patients, 756 (91.3%) were male and 72 (8.7%) were female. The mean age was (45.7±10.7) years old, the mean body mass index (BMI) was (27.6±3.5) kg/m(2). The rate of patients was 3.9% in the persistent group, 10.3% in the CPAP-emergent group, 7.5% in the CPAP-disappearance group, and 78.4% in the non-PLMS group. Multivariate Logistic regression analysis revealed that female appeared to be associated with the persistent group (P=0.004); older age and higher apnea-hypopnea index (AHI) on BPSG appeared to be associated with the CPAP-emergent group (P=0.012, 0.030). On the other hand, older age was negatively associated with the non-PLMS group (P=0.006). Conclusion: Elderly patients with higher AHI at BPSG may present with CPAP-emergent PLMS.

Post-stroke restless leg syndrome and periodic limb movements in sleep.

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.

While Isolated Periodic Limb Movement Disorder Significantly Impacts Sleep Depth and Efficiency, Co-Morbid Restless Leg Syndrome Mainly Exacerbates Perceived Sleep Quality.

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.

Periodic limb movements in sleep are followed by increases in EEG activity, blood pressure, and heart rate during sleep.

PURPOSE: Periodic limb movements in sleep (PLMS) are related to arousal, sympathetic activation, and increases in blood pressure (BP), but whether they are part of the arousal process or causative of it is unclear. Our objective was to assess the temporal distribution of arousal-related measures around PLMS. METHODS: Polysomnographic recordings of six patients with restless legs syndrome were analyzed. We analyzed 15 PLMS, plus three 5-s epochs before and after each movement, for every patient. Mean values per epoch of blood pressure (BP), heart rate (HR), and electroencephalographic (EEG) power were calculated. For each patient, six 5-s epochs of undisturbed sleep were analyzed as controls. RESULTS: Alpha + beta EEG power, systolic BP, and HR were significantly increased following PLMS. The EEG power and HR increases were noticed in the first epoch after PLMS, whereas that of systolic BP was observed in the second and third epochs following a PLMS. No significant changes occurred in the epochs of undisturbed sleep. CONCLUSIONS: The results suggest that PLMS are followed by arousal-related nervous system events. Given the high frequency of PLMS throughout the night, they could be a potential risk factor for nocturnal arrhythmias and hypertension, in addition to causing sleep deprivation.