Periodic Limb Movements During Sleep Research Articles

Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome

Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron-deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radioligand binding saturation experiments in rat brain tissue) of adenosine A1 receptors (A1R) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A2A receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for A1R downregulation in the PLMS and hyperarousal in RLS.

Longitudinal relationships of periodic limb movements during sleep and incident atrial fibrillation

ObjectivesThis study aimed to examine relationship between periodic limb movements during sleep (PLMS) and incident atrial fibrillation/flutter (AF). MethodsProspective 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. ResultsIn 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. ConclusionsAlthough PLMS do not predict AF incidence in the overall cohort, the findings suggest PLMS increases incident AF risk in the older subgroup.

The Comparisons of Cerebral Hemodynamics Induced by Obstructive Sleep Apnea with Arousal and Periodic Limb Movement with Arousal: A Pilot NIRS Study.

Obstructive sleep apnea syndrome (OSA) and restless legs syndrome (RLS) with periodic limb movement during sleep (PLMS) are two sleep disorders characterized by repetitive respiratory or movement events associated with cortical arousals. We compared the cerebral hemodynamic changes linked to periodic apneas/hypopneas with arousals (AHA) in four OSA-patients with periodic limb movements (PLMA) with arousals in four patients with RLS-PLMS using near-infrared spectroscopy (NIRS). AHA induced homogenous pattern of periodic fluctuations in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin, i.e., the decrease of HbO2 was accompanied by an increase of HHb during the respiratory event and resolved to reverse pattern when cortical arousal started. Blood volume (BV) showed the same pattern as HHb but with relative smaller amplitude in most of the AHA events.These changing patterns were significant as Wilcoxon signed-rank tests gave p < 0.001 when comparing the area under the curve of these hemodynamic parameters to zero. By contrast, in PLMA limb movements induced periodic increments in HbO2 and BV (Wilcoxon signed-rank tests, p < 0.001), but HHb changed more heterogeneously even during the events coming from the same patient. Heart rate (HR) also showed different patterns between AHA and PLMA. It significantly decreased during the respiratory event (Wilcoxon signed-rank test, p < 0.001) and then increased after the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001); while in PLMA HR first increased preceding the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001) and then decreased. The results of this preliminary study show that both AHA and PLMA induce changes in cerebral hemodynamics. The occurrence of cortical arousal is accompanied by increased HR in both events, but by different BV changes (i.e., decreased/increased BV in AHA/PLMA, respectively). HR changes may partially account for the increased cerebral hemodynamics during PLMA; whereas in AHA probable vasodilatation mediated by hypoxia/hypercapnia is more crucial for the post-arousal hemodynamics. The differences between changes of cerebral hemodynamics and HR may indicate different pathological mechanisms behind these two sleep disorder events.

Prevalence and Characteristics of Periodic Limb Movements during Sleep in Korean Adult Patients with Restless Legs Syndrome.

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). 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. 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. 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.

Mood Symptoms and Restless Legs Syndrome Without Periodic Limb Movements During Sleep: Is it a Clinical Subtype?

Frequently co-occurring restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are postulated to share common pathophysiology. The authors compared clinical characteristics and polysomnography (PSG) parameters among 155 idiopathic, untreated RLS patients who were stratified into three groups based on periodic limb movement index (PLMI). The authors found that RLS patients without PLMS (PLMI <5) had higher depression and anxiety scores, a lower total arousal index, longer latency to REM, and a higher spontaneous arousal frequency on PSG than RLS patients with PLMS. RLS severity was associated with PLMI in RLS patients with PLMS but not without PLMS. RLS without PLMS seems to be a phenotypically distinct clinical subtype of RLS. Future study should examine whether RLS without PLMS has a different clinical course, treatment response, and pathophysiology than RLS with PLMS.

Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).

Polysomnographic investigation of sleep architecture in children presenting with pediatric acute-onset neuropsychiatric syndrome (PANS). Fifteen consecutive subjects meeting criteria for PANS (mean age = 7.2 y; range 3-10 y) underwent single-night full polysomnography (PSG) read by a pediatric neurologist. Thirteen of 15 subjects (87%) had abnormalities detected with PSG. Twelve of 15 had evidence of rapid eye movement (REM) sleep motor disinhibition, as characterized by excessive movement, laughing, hand stereotypies, moaning, or the continuation of periodic limb movements during sleep (PLMS) into REM sleep. This study shows various forms of REM sleep motor disinhibition present in a population of children with PANS.

Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla

ObjectivesAltered brain iron homeostasis with regional iron deficiency has been previously reported in several studies of restless legs syndrome (RLS) patients. Inconsistencies still exist, however, in the reported iron changes in different brain regions and different RLS phenotypes. The purpose of this study was to assess differences in brain iron concentrations between RLS patients and healthy controls and their relation to severity of disease and periodic limb movement during sleep (PLMS). MethodsAssessment of brain iron was done using quantitative magnetic susceptibility measurement, which has been shown to correlate well with the tissue iron content in brain's gray matter. Thirty-nine RLS patients and 29 age-matched healthy controls were scanned at 7 T. Magnetic susceptibilities in substantia nigra (SN), thalamus, striatum, and several iron-rich gray matter regions were quantified and compared with related clinical measures. ResultsCompared with healthy controls, RLS patients showed significantly decreased magnetic susceptibility in the thalamus and dentate nucleus. No significant difference was found in the SN between RLS patients and healthy controls, but a significant correlation was observed between magnetic susceptibility in SN and the PLMS measure. ConclusionsUsing quantitative magnetic susceptibility as an in vivo indicator of brain iron content, the present study supports the general hypothesis of brain iron deficiency in RLS and indicates its possible link to PLMS.

Restless Legs Syndrome and Depression: Effect Mediation by Disturbed Sleep and Periodic Limb Movements

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. 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. 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. Depression is more common as RLS severity worsens. The RLS-depression relationship is modestly explained by sleep disturbance and PLMS.

Desmopressin (melt) therapy in children with monosymptomatic nocturnal enuresis and nocturnal polyuria results in improved neuropsychological functioning and sleep.

There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. The aim of this study was to investigate whether a decrease in nocturnal diuresis volume not only improves enuresis but also ameliorates disrupted sleep and (neuro)psychological dysfunction, the major comorbidities of this disorder. In this open-label, prospective phase IV study, 30 children with monosymptomatic nocturnal enuresis (MNE) underwent standardized video-polysomnographic testing and multi-informant (neuro)psychological testing at baseline and 6 months after the start of desmopressin treatment in the University Hospital Ghent, Belgium. Primary endpoints were the effect on sleep and (neuro)psychological functioning. The secondary endpoint was the change in the first undisturbed sleep period or the time to the first void. Thirty children aged between 6 and 16 (mean 10.43, standard deviation 3.08) years completed the study. The results demonstrated a significant decrease in periodic limb movements during sleep (PLMS) and a prolonged first undisturbed sleep period. Additionally, (neuro)psychological functioning was improved on several domains. The study demonstrates that the degree of comorbidity symptoms is at least aggravated by enuresis (and/or high nocturnal diuresis rate) since sleep and (neuro)psychological functioning were significantly ameliorated by treatment of enuresis. These results indicate that enuresis is not such a benign condition as has previously been assumed.

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

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

Derived Arterial Stiffness is Increased in Patients with Obstructive Sleep Apnea and Periodic Limb Movements during Sleep.

Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) have been associated with increased risk of cardiovascular disease (CVD). OSA has also been linked to increased large arterial stiffness, which is considered an independent risk factor for CVD. We utilized a previously validated index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) to seek comparison in patients with PLMS and OSA. Forty-nine adult male subjects, without known comorbidities that could affect arterial stiffness or on vasoactive medication, were retrospectively identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17), and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index (PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h. SIDVP was derived from the raw data of photoplethysmography of the nocturnal polysomnography, averaged for 2 min prior to sleep study initiation (baseline), after completion in the morning, and every half hour after sleep onset. The groups were age/body mass index-matched. Controls showed lower baseline, morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with PLMS (PLMI: 50.69 ± 9.7 events/h) and the OSA group (AHI: 29.7 ± 2 events/h) demonstrated similar overall SIDVP (6.78 ± 0.08 versus 6.94 ± 0.04, respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 ± 8, PLMI: 50.63 ± 7.2) group demonstrated the highest (7.40 ± 0.06, p < 0.001). Based on an easily reproducible and applicable marker of large arterial stiffness, patients with significant PLMS had higher SIDVP when compared to controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had the highest SIDVP, implying a possible additive effect of OSA and PLMS on arterial stiffness.

Prevalence and determinants of periodic limb movements in the general population.

Periodic limb movements during sleep (PLMS) are sleep phenomena characterized by periodic episodes of repetitive stereotyped limb movements. The aim of this study was to describe the prevalence and determinants of PLMS in a middle to older aged general population. Data from 2,162 subjects (51.2% women, mean age = 58.4 ± 11.1 years) participating in a population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Assessments included laboratory tests, sociodemographic data, personal and treatment history, and full polysomnography at home. PLMS index (PLMSI) was determined, and PLMSI > 15/h was considered as significant. Prevalence of PLMSI > 15/h was 28.6% (31.3% in men, 26% in women). Compared to subjects with PLMSI ≤ 15/h, subjects with PLMSI > 15/h were older (p < 0.001), were predominantly males (p = 0.007), had a higher proportion of restless legs syndrome (RLS; p < 0.001), had a higher body mass index (p = 0.001), and had a lower mean glomerular filtration rate (p < 0.001). Subjects with PLMSI > 15/h also had a higher prevalence of diabetes, hypertension, and beta-blocker or hypnotic treatments. The prevalence of antidepressant use was higher, but not statistically significant (p = 0.07). Single nucleotide polymorphisms (SNPs) within BTBD9 (rs3923809), TOX3 (rs3104788), and MEIS1 (rs2300478) genes were significantly associated with PLSMI > 15/h. Conversely, mean hemoglobin and ferritin levels were similar in both groups. In the multivariate analysis, age, male gender, antidepressant intake, RLS, and rs3923809, rs3104788, and rs2300478 SNPs were independently associated with PLMSI > 15/h. PLMS are highly prevalent in our middle-aged European population. Age, male gender, RLS, antidepressant treatment, and specific BTBD9, TOX3, and MEIS1 SNP distribution are independent predictors of PLMSI > 15/h.

Possible effect of periodic limb movements during sleep on the sleepiness of patients with sleep disordered breathing

We aimed to conduct a cross-sectional study in order to investigate the effect of periodic limb movements during sleep (PLMS) on daytime sleepiness in patients with sleep disordered breathing especially those with obstructive sleep apnea syndrome (OSAS), diagnosed by polysomnography (PSG). Our subjects included 233 male patients who visited our institute during the 25-month period between June 2012 and June 2013. We scored the number of Periodic Limb Movements per hour as the Periodic Limb Movements Index (PLMI) on standard PSG, and considered that periodic limb movements during sleep was present in the patients with PLMI >15/h. Non-PLMS group included those patients with PLMI ≤15/h. To assess the sleepiness of participants, we used Japanese version of the Epworth Sleepiness Scale (JESS) and Japanese version of the Pittsburgh Sleep Quality Index. We compared the sleep parameters and sleepiness indicators between patients with PLMS and age, apnea–hypopnea index (AHI), and body mass index-matched non-PLMS control groups. JESS scores were higher in patients with PLMS than in non-PLMS in both low AHI (<15/h) and high AHI (≥15/h) strata. However, the difference was statistically significant only in high AHI stratum (P = 0.399 and 0.001, respectively). In conclusion, PLMS was associated with increased JESS especially in patients with moderate-to-severe OSAS. Although the magnitude of the difference in those with AHI <15/h was smaller and statistically insignificant in the present study, this issue warrants further investigation by enrolling more patients with AHI <15/h.

Impact of sleep disturbances on kidney function decline in the elderly.

While sleep disturbances are frequent in renal disease patients, no studies have examined prospectively the associations between sleep disturbances and kidney function decline in community-dwelling elderly subjects.Glomerular filtration rates (eGFRs) were estimated at baseline and at 11-year follow-up. A glomerular filtration decline over the follow-up period was defined as a percentage decline greater than or equal to the cut-off value of the highest tertile of kidney function decline (22%) in 1105 subjects. Excessive daytime sleepiness (EDS) and insomnia complaints were self-rated at baseline. Restless legs syndrome (RLS) and its age at onset were assessed at study end-point. An ambulatory polysomnography recording was performed during the follow-up in 277 subjects. Apnoea-hypopnoea index (AHI), periodic limb movements during sleep (PLMS) and total sleep time were analysed.An increased risk of eGFR decline was associated with EDS (OR 1.67, 95% CI 1.18-2.34) and RLS (OR 1.98, 95% CI 1.18-3.30) independently of potential confounders including cardiovascular risk factors. Among insomnia complaints, a borderline association with eGFR decline was found for early morning awakening only. High AHI (≥30 events·h(-1)) and short total sleep time (<6 h), but not PLMS were linked to eGFR decline in crude associations, but only AHI remained significantly associated after multi-adjustments.EDS, RLS and AHI constitute independent risk factors for kidney glomerular function decline.

Age and severity matched comparison of gender differences in the prevalence of periodic limb movements during sleep in patients with obstructive sleep apnea.

The aim of this study was to investigate gender differences of periodic limb movements during sleep (PLMS) in patients with obstructive sleep apnea (OSA). This was a case-control study recruiting 364 patients with OSA (182 men, 182 women) matched for age and apnea-hypopnea index (AHI). All participants underwent overnight polysomnography (PSG), followed by the multiple sleep latency test (MSLT) and the Epworth Sleepiness Scale (ESS). Women with OSA had a significantly higher prevalence of PLMS than men (24.2 vs. 15.9%, p < 0.05). Women with OSA showed an increased prevalence of PLMS compared to men in the younger group aged ≤55years (23.0 vs. 10.6%, p < 0.05), but not in the older groups >55years (25.3 vs. 21.6%, p > 0.05). Binary linear regression analysis in OSA patients confirmed that women were more likely to have PLMS than men (OR 1.71, 95% CI 1.00-2.92), particularly in patients with age ≤55years old (OR 2.48, 95% CI 1.06-5.79), after adjusting for age, BMI, AHI, and habits of smoking and drinking. The results demonstrate that, for patients with OSA, young women had significantly increased prevalence of PLMS compared to young men, but there was no difference in prevalence of PLMS between the men and women in the older age group.

Restless Legs Syndrome: Would You Like That with Movements or Without?

The restless legs syndrome (RLS) is a common sensorimotor condition that often results in discomfort and sleep disturbance. Diagnosis of RLS is entirely clinical and based upon a patient’s description of subjective symptoms, and thus when considering RLS diagnosis non-specificity is a real problem. RLS is associated with periodic limb movements during sleep (PLMS) in up to 90% of RLS sufferers; however, their presence is neither sufficient nor necessary for the diagnosis of RLS. The disease RLS and the motor phenomenon of PLMS share similarities in various areas, which include pathophysiology, pharmacology, genetics, and epidemiology. The purpose of this opinion piece is to outline the many similarities between RLS and PLMS in order to make an argument for the inclusion of PLMS as a supplementary diagnostic criterion of RLS, termed electro-clinical RLS, which would consist of the current clinical RLS diagnosis plus PLMS. This additional criterion could be used in cases where diagnosis is unclear to increase specificity or in research projects where proper diagnosis is desired at the investigational level.

Putting the periodicity back into the periodic leg movement index: an alternative data-driven algorithm for the computation of this index during sleep and wakefulness

ObjectiveTo evaluate an alternative index for periodic leg movements during sleep (PLMS) and wakefulness (PLMW) expected to be similar to the standard index when leg movement activity is genuinely periodic, but significantly lower when periodicity is low. Subjects and methodsOne-hundred-and-seven subjects with restless legs syndrome (RLS) were retrospectively identified and included (47 males, 60 females, mean age 56.9 years), along with 63 controls (33 males, 30 females, 42.2 years). Night-to-night variability was analysed in a subgroup of 17 subjects with RLS. PLMW were evaluated in a subgroup of 66 RLS subjects. Two ‘alternative’ PLMS/PLMW indices were calculated: one increased the lower limit of the inter-movement intervals from 5 to 10 s (‘Alt1’) and another additionally considered only series not interrupted by LMs with a short inter-movement interval (‘Alt2’). ResultsDespite a high correlation between methods, only the Alt2 algorithm provided significantly different results, with PLMS/PLMW indices being consistently lower than those provided by the other two methods. The difference was more evident in the controls and during wakefulness, when periodicity was lower. The difference between the Alt2 and the standard PLMS index showed a significantly negative correlation with the Periodicity Index. Night-to-night variability was similar for all PLMS indices and significantly higher than the variability seen in the Periodicity Index. ConclusionThis methodological study introduces an alternative to the standard PLMS/PLMW indices, initiating the validation process for a new way of computing the PLMS/PLMW index, more adherent to the parameters that allows a reliable evaluation of their periodicity.

The Role of Periodic Limb Movements During Sleep in Restless Legs Syndrome

Periodic leg movements during sleep (PLMS) are a highly active research topic and accumulating recent evidence has led to reevaluation of key aspects on the role of PLMS in restless legs syndrome (RLS). This article summarizes the recent developments in 3 areas: the relationship of PLMS to cortical arousals in patients with RLS, the differential effect of dopaminergic and non-dopaminergic treatment on PLMS, and the possible emergence of PLMS as a sleep-related cardiovascular risk factor.

Nocturnal periodic limb movements decrease antioxidant capacity in post-stroke women.

Considerable evidence suggests that periodic limb movements during sleep (PLMS) are associated with cardiovascular risk and poor stroke outcome. However, the pathogenesis for this association in stroke patients remains largely unknown. This cross-sectional study enrolled 112 consecutive patients who were admitted to rehabilitation ward due to ischemic stroke. Polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers including C-reactive protein, interleukin 6, total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine were conducted. Patients were stratified into three categories according to their PLMS index. Patients in the PLMS index ≥15 group were significantly older (P = 0.011), presented a significantly higher National Institute of Health Stroke Scale at stroke onset (P = 0.032), and lower Barthel index (P = 0.035) than patients in the PLMS index <5 group. The level of TAC differed significantly (P = 0.018) among the three groups. Multivariate linear regression analyses show that the PLMS index was negatively and independently correlated with TAC (P = 0.024) in women. Besides, multivariate logistic regression analyses also reveal that patients with a PLMS index ≥15 compared with the referent PLMS index <5 had a 7.58-fold increased relative hazard for stroke recurrence (odds ratio 7.58, [1.31-43.88], P = 0.024). This study suggests that PLMS was independently associated with decreased antioxidant capacity in women with ischemic stroke.

An Evidence-based Analysis of the Association between Periodic Leg Movements during Sleep and Arousals in Restless Legs Syndrome.

To analyze statistically the association between periodic leg movements during sleep (PLMS) and arousals, in order to eventually support or challenge the current scoring rules and to further understand their reciprocal influence. Sleep research center. Twenty untreated consecutive patients with restless legs syndrome (RLS) (13 women and 7 males, mean age 60.9 y). In each recording, we selected all PLMS/arousal pairs that met the following inclusion criteria: (a) PLMS events that were separated from another PLMS event (preceding or following) by at least 10 s of EMG inactivity; (b) arousal events separated from another arousal event (preceding or following) by at least 10 s of stable EEG baseline activity; (c) PLMS/arousal pairs were then selected among events identified according to the previous two criteria, when PLMS and arousals were separated (offset-to-onset) by no more than 10 s, regardless of which was first. We selected a mean of 46.1 (SD 25.55) PLMS/arousal pairs per subject; in these pairs, average PLMS duration was 3.2 s (0.65) and average arousal duration was 6.5 s (0.92). Within these event pairs, the great majority (on average 98.4%, SD 3.88) was separated by less than 0.5 s (i.e., between the end of one event and the onset of the other, regardless of which was first). Arousal onsets preceded PLMS onset in 41.2% of pairs, while the opposite was true for the remaining 58.8% of pairs. A significant correlation between PLMS duration and arousal duration was also found (r = 0.447, P < 0.000001). The results of this study support the current rule for the definition of the association between periodic leg movements during sleep (PLMS) and arousals. The tight time relationship between PLMS and arousals and their correlated durations seem to indicate that both events might be regulated by a complex mechanism, rather than being connected by a simple reciprocal cause/effect relationship.