Periodic Limb Movements During Sleep Research Articles

The paradoxical impact of periodic limb movements on isolated REM sleep behavior disorder patients.

Recently, the α-synuclein origin and connectome model described two types of Parkinson's disease: "brain-first" and "body-first" subtypes. We aimed to investigate the role of periodic limb movements during sleep (PLMS) in identifying these subtypes starting from a prodromal stage of α-synucleinopathies. 191 patients with isolated REM sleep behavior disorder (iRBD) underwent video-polysomnography (vPSG), questionnaires, clinical interview, and neuropsychological battery. Patients who presented PLMS index (PLMSi) > 15 were compared with patients presenting PLMSi ≤ 15 on clinical questionnaires, vPSG, and neuropsychological domains with age as a covariate. Correlations were performed between PLMSi and vPSG and neuropsychological domains in both groups of iRBD. 48.2% of patients presented PLMSi > 15. iRBD subgroup with PLMSi > 15 performed better than the iRBD subgroup with PLMSi ≤ 15 in the executive function domain. In patients with PLMSi > 15 negative correlations were observed between PLMSi and some neuropsychological domains (memory, language, and executive function). Moreover, this subgroup was older and their PLMSi was positively correlated with wake-after-sleep onset and inversely correlated with total sleep time and sleep efficiency, suggesting a detrimental effect of PLM on sleep also in this cohort. Patients with PLMSi > 15 are characterized by a more preserved cognitive status, despite a more disrupted sleep. PLMSi could be explored in longitudinal studies concerning the "brain-first" and "body-first" model.

Exploring sex differences in periodic leg movements during sleep across the lifespan of patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) are prevalent sleep disorders with significant implications for health and well-being. While previous research has highlighted sex-related disparities in RLS and PLMS prevalence, comprehensive understanding of these differences across the lifespan remains limited. This study aims to explore sex differences in RLS and PLMS across diverse age groups, spanning ages 2 to over 80 years, and to investigate the underlying mechanisms influenced by sex hormones. MethodsA retrospective analysis was conducted on drug-free patients diagnosed with RLS, including 95 females (age range: 2–83.2 years) and 89 males (age range: 2–79.5 years). Polysomnographic recordings were analyzed to assess leg movement activity, including PLMS index and Periodicity index. ResultsA more rapid increase in PLMS index was observed in women starting before age 10, plateauing lower than men until around age 55. An increase in women occurred after 55, lasting over a decade, while in men, PLMS index continued to rise after 75. Conversely, Periodicity index displayed a simpler pattern, increasing progressively from prepuberty to around 35 in males and 45–50 in females. Females maintained a slightly higher Periodicity index than males for over a decade after this age. ConclusionThese findings underscore the complex interplay between sex hormones, age, and sleep disorders, highlighting the need for tailored approaches to diagnosis and management across diverse demographic cohorts. Further research is warranted to elucidate the underlying mechanisms and develop targeted interventions to optimize sleep health outcomes.

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome.

This study aimed to investigate sex-related differences in the response to ropinirole and pramipexole in patients with restless legs syndrome (RLS). By analysing clinical parameters and polysomnographic (PSG) findings, we sought to elucidate the potential factors related to sex disparities modulating treatment responses and sleep quality in RLS. A total of 41 drug-free patients with RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before the second night, 26 patients received an oral dose of 0.25 mg pramipexole whereas 15 received 0.5 mg ropinirole. After each PSG recording, patients self-evaluated the severity of their previous night symptoms by means of an ad hoc visual analogue scale (VAS). At baseline, sleep efficiency and percentage of Stage N2 tended to be higher in females while wakefulness after sleep onset was significantly higher in males. After treatment, total leg movements during sleep (LMS), periodic LMS (PLMS), and periodicity indexes were significantly lower in females than in males. The VAS score was lower after treatment in all patients, without differences between the two sexes. This study demonstrates a higher acute responsiveness of PLMS to dopamine agonists (pramipexole and ropinirole) in females than in males with RLS. These findings might be explained by differential sex-related expression of dopamine receptors, especially D3, within the central nervous system. In addition, our findings provide translational hints toward a better tailored and sex-specific approach to the treatment of RLS associated with PLMS, with dopamine agonist possibly associated with a better outcome in females than in males.

Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. A retrospective chart review of sleep studies was conducted in children aged 1-18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27-34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8-4.5) groups. There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

Positional obstructive sleep apnea and periodic limb movement during sleep: A large multi-center study.

The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms. We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity. The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups. The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.

Periodic limb movements in patients with suspected obstructive sleep apnea without comorbid conditions.

Periodic limb movement disorder (PLMD) and obstructive sleep apnea (OSA) are overlapping clinical syndromes with common risk factors. However, current literature has failed to establish a clear pathophysiological link between them. Thus, little is known about periodic limb movements (PLM) in otherwise healthy patients with suspected OSA. We performed a retrospective analysis of 112 patients (age: 44.5 ± 12.0 years, 14.3% female) with suspected OSA who underwent full night polysomnography for the first time. Patients with chronic diseases of any kind, recent infections, malignancies, or daily or regular use of any type of medication were excluded. Group comparisons were made based on the severity of OSA (using the apnea hypopnea index, AHI) or the periodic limb movement index (PLMI). Both, PLMI and the total number of periodic limb movements during sleep (PLMS), showed a significant increase in patients with severe OSA. In addition, AHI and apnea index (AI) were significantly higher in patients with PLMI >15/h, with a similar trend for hypopnea index (HI) (p < 0.001, p < 0.001, and p > 0.05, respectively). PLMI was significantly positive correlated with AHI, AI, and HI (r = 0.392, p < 0.001; r = 0.361, p < 0.001; and r = 0.212, p < 0.05, respectively). Patients with PLMI >15/h were significantly older (p < 0.001). There was no significant association between body mass index (BMI) and PLMI >15/h. We found a significant association between the severity of OSA and PLM in our study population with suspected OSA but without other comorbidities. PLMI and PLMS were significantly increased in patients with severe OSA. Future prospective studies with larger collectives should verify the presented results and should include mechanistic aspects in their evaluation.

Restless legs syndrome variants: A systematic review

IntroductionRestless Legs Syndrome (RLS) is a clinical syndrome that may manifest itself in non-leg parts of the body as well, called RLS variant, which is considered a distinct entity by some researchers. In this systematic review, we tried to evaluate various clinical features and effective treatments of RLS variants and compare them with that of typical RLS. MethodsThis study was conducted following the PRISMA guideline. The primary search was performed in the data resources of Medline (PubMed), Web of Science, and Scopus, as well as the Google Scholar search engine. The required data were extracted from the studies. ResultsIn this review, 1565 studies were initially identified and finally 39 studies were selected. The most common RLS variants were observed to involve hands, head, abdomen, and genitalia. These patients mostly complained of sleep disturbance and feelings of itching, tingling and twitching. Supportive diagnostic criteria of RLS including familial history of RLS, periodic limb movements during sleep (PLMS) and response to treatment with dopaminergic agents were assessed. ConclusionIt seems that patients with RLS variant can undergo the same diagnostic and therapeutic work-up as patients with conventional RLS. It is suggested that these two disorders fall into the same syndromic spectrum.

An expedited model for identifying potential patients with periodic leg movements.

Periodic leg movements during sleep (PLMS) may have crucial consequences in adults. This study aimed to identify baseline characteristics, symptoms, or questionnaires that could help to identify sleep-disordered breathing patients with significant PLMS. Patients aged 20-80 years who underwent polysomnography for assessing sleep disturbance were included. Various factors such as sex, age, body measurements, symptoms, apnea-hypopnea index (AHI), and sleep quality scales were analysed to determine the presence of PLMS. The study included 1480 patients with a mean age of 46.4 ± 13.4 years, among whom 110 (7.4%) had significant PLMS with a PLM index of 15 or higher. There were no significant differences observed in terms of sex or BMI between patients with and without significant PLMS. However, the odds ratios (OR) for PLMS were 4.33, 4.41, and 4.23 in patients who were aged over 50 years, had insomnia, or had an ESS score of less than 10, respectively. Notably, the OR increased up to 67.89 times in patients who presented with all three risk factors. Our analysis identified significant risk factors for PLMS: age over 50, self-reported insomnia, and lower daytime sleepiness levels. These findings aid in identifying potential PLMS patients, facilitating confirmatory examinations and managing associated comorbidities.

Coexistence of periodic limb movements during sleep with restless legs syndrome and its association with hypertension in Japanese patients

BackgroundCaucasian 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. MethodsWe 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. ResultsAmong 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. ConclusionThe 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.

Detecting periodic leg movements during sleep (PLMS) in restless legs syndrome (RLS) using the NTX100 tonic motor activation (TOMAC) system

Detecting periodic leg movements during sleep (PLMS) in restless legs syndrome (RLS) using the NTX100 tonic motor activation (TOMAC) system

Periodic Limb Movements during Sleep in Acute Stroke: Prevalence, Severity and Impact on Post-Stroke Recovery.

Periodic Limb Movements during Sleep (PLMS) have been described to be frequently present in stroke patients. We aimed to evaluate the prevalence and severity of PLMS in acute stroke patients and clarify the association between PLMS and coexisting Sleep Disordered Breathing (SDB). Additionally, we focused on identifying variables that could independently predict the presence of PLMS in patients with acute stroke. The potential impact of PLMS on stroke outcome at three months was investigated as well. In this study, we performed overnight polysomnography on consecutive stroke patients within 72 h from symptom onset. Data regarding clinical and imaging characteristics were prospectively collected. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Epworth-Sleepiness Scale (ESS) were used to evaluate stroke severity on admission, stroke outcome at three months and history of daytime sleepiness, respectively. We documented PLMS and SDB using standard polysomnography criteria. We prospectively assessed 126 patients with acute stroke [109 with ischemic and 17 with hemorrhagic stroke, mean age 60 ± 11 years, 68% men, median NIHSS score on admission: 3 (IQR: 2-7)]. The overall rate of PLMS in our cohort was 76%, and the rate of SDB among patients with PLMS was 83%. PLMS detection rates differed significantly (p-value: <0.001) according to SDB, with PLMS prevalence increasing with greater SDB severity. SDB could independently (OR:4.869, 95% CI: 1.884-12.784, p-value: 0.001) predict the presence of PLMS in the acute stroke phase in multivariable analyses adjusting for potential confounders. Moreover, baseline stroke severity (NIHSS-score increase in per-1 point: OR: 0.819, 95% CI: 0.737-0.895, p-value < 0.001) and PLMS (OR:0.099, 95% CI: 0.009-0.482, p-value = 0.015) were significantly associated with the likelihood of excellent functional outcome (mRS-scores: 0-1) at 3 months. The common presence of mostly severe PLMS in patients with acute stroke and their negative effect on stroke outcomes point out the necessity for early PLMS detection and treatment.

Periodic leg movements during sleep and cognitive functioning in the older general population

ObjectiveThe 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. MethodsWe 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. ResultsA 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. ConclusionsThis 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.

Periodic Limb Movements during Sleep in Children, Adolescents, and Adults with Narcolepsy: A Cross-Sectional Study in China

Objectives. This study is aimed at determining the prevalence and effects of periodic limb movements during sleep (PLMS) on nighttime sleep and daytime sleepiness in children/adolescents and adults with narcolepsy. Methods. A total of 94 patients with narcolepsy were recruited in this study. They were classified into two groups including children/adolescents (&lt;18 years, n = 41 ) and adults (≥18 years, n = 53 ). All participants completed face-to-face interviews and underwent polysomnography assessment followed by multiple sleep latency test. Demographic, clinical, and sleep parameters were compared between narcoleptic patients with and without PLMS. Linear regression analysis was performed to determine the association between PLMS and sleep parameters. Results. Thirty-eight (40.4%) patients with narcolepsy were defined as having PLMS, and there was a higher prevalence of PLMS in the children/adolescents than in the adults with narcolepsy (56.1% vs. 28.3%, respectively, P = 0.006 ). Narcoleptic patients with PLMS had a significantly shorter total sleep time, lower sleep efficiency (SE), and more wakefulness after sleep onset (WASO) than those without PLMS in adults (all P &lt; 0.05 ). After adjusting for the potential confounders, PLMS was significantly associated with lower SE ( adjusted β = − 0.327 ; 95% CI: -0.608, 0.044; P = 0.025 ) and more WASO ( adjusted β = 0.330 ; 95% CI: 0.038, 0.520; P = 0.028 ) in adults with narcolepsy. Conclusions. There is a high prevalence of PLMS in narcolepsy, especially in children and adolescent patients. PLMS is associated with nighttime sleep disturbance in adults with narcolepsy but is not a risk factor for daytime sleepiness both in children/adolescents and adults with narcolepsy.

The accuracy and difference of scoring rules and methods to score respiratory event-related leg movements in obstructive sleep apnea patients

ObjectiveTo compare manual scoring: 1) to the American Academy of Sleep Medicine (AASM) auto-scoring rules. 2) to the AASM and World Association of Sleep Medicine (WASM) rules, and evaluate the accuracy of the AASM and WASM for respiratory event-related limb movements (RRLM) in diagnostic and continuous positive airway pressure (CPAP) titration polysomnography (PSG). MethodsWe retrospectively, re-scored diagnostic and CPAP titration PSGs of 16 patients with obstructive sleep apnea (OSA), using manual re-scoring by the AASM (mAASM) and WASM (mWASM) criteria for RRLM, periodic limb movements during sleep (PLMS), and limb movements (LM), which were compared to auto-scoring by the AASM (aAASM). ResultsIn diagnostic PSG, significant differences were found in LMs (p < 0.05), RRLM (p = 0.009) and the mean duration of PLMS sequences (p = 0.013). In CPAP titration PSG, there was a significant difference in RRLM (p = 0.008) and PLMS with arousal index (p = 0.036). aAASM underestimated LM and RRLM, especially in severe OSA. Changes in RRLM and PLMS with arousal index between diagnostic and titration PSG were significantly different between aAASM and mAASM, but there was no significant difference between scoring by mAASM and mWASM. The ratio of PLMS and RRLM changes between diagnostic and CPAP titration PSG was 0.257 in mAASM and 0.293 in mWASM. ConclusionsIn addition to the overestimation of RRLM by mAASM compared to aAASM, mAASM may also be more sensitive than aAASM in detecting RRLM changes in the titration PSG. Despite intuitive differences in the definition of RRLM between AASM and WASM rules, RRLM results between mAASM and mWASM were not significant and about 30% of RRLMs might be scored as PLMS by both scoring rules.

Effects of iron-deficient diet on sleep onset and spinal reflexes in a rodent model of Restless Legs Syndrome.

Restless Legs Syndrome (RLS) is a common sensorimotor and a sleep disorder that affects 2.5-10% of the European and North American populations. RLS is also often associated with periodic leg movements during sleep (PLMS). Despite ample evidence of genetic contributions, the underlying mechanisms that elicit the sensory and motor symptoms remain unidentified. Clinically, RLS has been correlated with an altered central iron metabolism, particularly in the brain. While several animal models have been developed to determine the outcome of an altered iron homeostasis on brain function, the potential role of an altered iron homeostasis on sleep and sensorimotor circuits has not yet been investigated. Here, we utilize a mouse model to assess the effects of an iron-deficient (ID) but non-anemic state on sleep time and episodes, and sensorimotor reflexes in male and female mice. We found that animals on the ID diet displayed an increased expression of the transferrin receptor in the spinal cord, confirming the results of previous studies that focused only on the impact of ID in the brain. We also demonstrate that the ID diet reduced hematocrit levels compared to controls but not into the anemic range, and that animals on the ID diet exhibited RLS-like symptoms with regard to sleep onset and spinal cord reflex excitability. Interestingly, the effects on the spinal cord were stronger in females than in males, and the ID diet-induced behaviors were rescued by the return of the animals to the control diet. Taken together, these results demonstrate that diet-induced ID changes to CNS function are both inducible and reversible, and that they mimic the sleep and sensorimotor RLS symptoms experienced in the clinic. We therefore propose replacing the commonly used phrase "brain iron deficiency" (BID) hypothesis in the RLS research field with the term "iron deficiency in the central nervous system" (ID-CNS), to include possible effects of altered iron levels on spinal cord function.

0872 Periodic limb movements during sleep and hypertension: A systematic review and meta-analysis

Abstract Introduction Several studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking. Methods We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird. Results Out of 572 potentially relevant articles, six eligible cross-sectional studies were included in the data analysis which included 8,949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot showed no publication bias. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12–1.41). Conclusion Our analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association. Support (if any)

Time to rest a hypothesis? Accumulating evidence that periodic leg movements during sleep are not increased in children with attention deficit hyperactivity disorder (ADHD): results of a case-control study and a meta-analysis.

To address the hypothesis that periodic leg movements during sleep (PLMS) are more frequent in children with attention deficit hyperactivity disorder (ADHD) when compared to typically developing (TD) children. To that end we both analyzed PLMS in a recent case-control study and conducted a systematic review and meta-analysis of PLMS frequency in children with ADHD and TD children. In our case-control study we compared PLMS frequency of 24 children with ADHD (mean age 11 years, 17 male) to that of 22 age matched typically developing (TD) children (mean age 10 years, 12 male). A subsequent meta-analysis included 33 studies that described PLMS frequency in groups of children with ADHD and/or groups of TD children. The case-control study did not show any differences in the frequency of PLMS between children with ADHD and TD children, a result that was consistent across a range of different definitions of PLMS, which in turn had a significant and systematic effect on PLMS frequency. The meta-analysis compared the average PLMS indices and the proportion of children with elevated PLMS indices between children with ADHD and TD children and across a number of analyses did not find any meta-analytic results that supported the hypothesis that PLMS are more frequent in children with ADHD. Our results suggest that PLMS are not more frequent in children with ADHD compared to TD children. A finding of frequent PLMS in a child with ADHD should therefore be considered a separate disorder and prompt specific diagnostic and therapeutic strategies.

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible. The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis. Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation. Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed. Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(4):811-822.

Periodic limb movements during sleep and risk of hypertension: A systematic review

BackgroundSeveral studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking. MethodsWe conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird. ResultsOut of 572 potentially relevant articles, six eligible studies were included in the data analysis. Studies (6 cross-sectional) included 8949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot and Egger's regression asymmetry test showed no publication bias with P-value ≥0.05. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12–1.41). ConclusionsOur analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association.

Periodic limb movement in sleep before and after continuous positive airway pressure titration in obstructive sleep-apnea patients

Background Periodic limb movement during sleep (PLMS) could exist with patients diagnosed as obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the most competent therapy for OSA. However, its effect on PLM remains controversial. Aim To evaluate PLMS prevalence in OSA patients and the impact of CPAP titration on PLM outcome. Patients and methods Patients with history suggestive of OSA underwent full attended diagnostic and CPAP titration sleep study. On baseline polysomnography, OSA patients with PLM less than 5 were considered pure OSA and those with periodic limb-movement index more than or equal to 5 were considered combined group. Post-CPAP titration, patients were considered CPAP responders, CPAP persistent, CPAP emergent, or non-PLM group according to response of PLM. Results Out of 100 included OSA patients, the combined group was found in 53 patients. CPAP responder group was reported in 27 patients, while 25 and 24 patients were considered CPAP persistent and CPAP emergent, respectively. CPAP-emergent group showed significantly higher apnea–hypopnea index (AHI) than non-PLM group on baseline polysomnography. On the other hand, AHI was comparable in CPAP-persistent and responder group, despite normalization of AHI in both groups after titration. On multivariate regression analysis, old age was found to be an independent predictor for both persistence and emergence of PLM and higher AHI was an independent predictor in CPAP-emergent group. Conclusion PLMS can coexist with OSA in old-age patients, which may persist after CPAP titration. Elderly patients, especially those with baseline higher AHI, may also present with CPAP-emergent PLMS.