Periodic limb movement disorder in children: A systematic review.

This systematic review evaluates the scientific literature on pediatric periodic limb movement disorder (PLMD), adhering to PRISMA guidelines and utilizing PICOS criteria. The search across PubMed, EMBASE, and Scopus yielded 331 articles, with 17 meeting inclusion criteria. Diagnostic criteria evolved, with polysomnography and PLMS index ≥5 required since 2003. Also, PLMD diagnosis mandates clinical consequences like insomnia, hypersomnia, and fatigue, excluding comorbidities causing sleep disruption. Prevalence in children is low (0.3%), emphasizing the need for meticulous investigation. Comorbidities, particularly the bidirectional relationship with ADHD, were explored. Challenges in diagnosis and understanding arise from overlapping conditions such as sleep disordered breathing, psychotropic medication, and criteria non-adherence. Despite generally good study quality, weaknesses include sample size justification and biases. The periodic leg movement index shows high sensitivity but low specificity, underscoring strict diagnostic criteria adherence. Diverse metrics for symptoms necessitate standardized approaches. Family history of RLS in children with PLMD suggests unexplored aspects. Treatment, mainly iron supplementation, lacks standardized assessment metrics. The review emphasizes diagnostic and treatment challenges, recommending unbiased studies with precise techniques. Comprehensive research, quantifying PLMS and objectively assessing sleep parameters, is crucial for advancing understanding in pediatric PLMD. PROSPERO REGISTRATION NUMBER: CRD42021251406.

Pediatric sleep: current knowledge, gaps, and opportunities for the future.

This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline Development Committee assembled a panel of experts tasked to provide information to those interested in learning more about the field of pediatric sleep, including trainees. We cover the scope of pediatric sleep, including epidemiological studies and the development of sleep and circadian rhythms in early childhood and adolescence. Additionally, we discuss current knowledge of insufficient sleep and circadian disruption, addressing the neuropsychological impact (affective functioning) and cardiometabolic consequences. A significant portion of this White Paper explores pediatric sleep disorders (including circadian rhythm disorders, insomnia, restless leg and periodic limb movement disorder, narcolepsy, and sleep apnea), as well as sleep and neurodevelopment disorders (e.g. autism and attention deficit hyperactivity disorder). Finally, we end with a discussion on sleep and public health policy. Although we have made strides in our knowledge of pediatric sleep, it is imperative that we address the gaps to the best of our knowledge and the pitfalls of our methodologies. For example, more work needs to be done to assess pediatric sleep using objective methodologies (i.e. actigraphy and polysomnography), to explore sleep disparities, to improve accessibility to evidence-based treatments, and to identify potential risks and protective markers of disorders in children. Expanding trainee exposure to pediatric sleep and elucidating future directions for study will significantly improve the future of the field.

Periodic leg movements during sleep associated with antidepressants: A meta-analysis.

Studies explicitly reporting data concerning the evaluation of the effect of antidepressants on the periodic leg movements during sleep (PLMS) index obtained by polysomnography were reviewed and selected. A random-effects model meta-analysis was carried out. The level of evidence was also assessed for each paper. Twelve studies were included in the final meta-analysis, seven interventional and five observational. Most studies were characterized by Level III evidence (non-randomized controlled trials), with the exception of four studies, which were classified as Level IV (case series, case-control, or historically controlled studies). Selective serotonin reuptake inhibitors (SSRIs) were used in seven studies. The analysis of the assessments involving SSRIs or venlafaxine showed an overall large effect size, clearly much larger than that obtained with studies using other antidepressants. Heterogeneity was substantial. This meta-analysis confirms the previous reports on the increase in PLMS often associated with the use of SSRIs (and venlafaxine); however, the absent or smaller effect of the other categories of antidepressants needs to be confirmed by more numerous and better controlled studies.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment for restless legs symptoms and low serum ferritin in children with autism spectrum disorder.

BACKGROUND: Restless legs syndrome (RLS) may be underdiagnosed in children with autism spectrum disorder (ASD) due to difficulty expressing the symptoms in their own words. In addition, administration of oral iron may be particularly difficult in children with ASD. METHODS: This was a retrospective, open-label case series of children with ASD, restless legs (RL) symptoms, and serum ferritin <30 µg/L, who either had failed or did not tolerate oral iron, and were subsequently treated with intravenous (IV) ferric carboxymaltose (FCM). Patients received a single dose of IV FCM, 15 mg/kg up to a maximum dose of 750 mg. Data collected pre- and eight weeks post-infusion included presenting symptoms, serum ferritin, iron profile, and Clinical Global Impression Scale (CGI-Severity pre- and CGI-Improvement post-infusion). Adverse effects were assessed. RESULTS: Nineteen children, 4-11 years old (12 male, median age 6, interquartile range (IQR 4-11) were included. A definite RLS diagnosis was identified in 6 verbal children (31.6%). RL symptoms (designated probable RLS) in the 13 other children met all RLS diagnostic criteria except "improvement of symptoms with movement," which was not definitively determined. Baseline median values were: ferritin 10 µg/L (IQR 10-16), iron 66.5 µg/dL (IQR 57-96), TIBC 382 µg/dL (IQR 360-411) and transferrin saturation 19% (IQR 14-28). Median CGI-S was 4 (moderate symptoms) (IQR 3-4). At eight weeks after IV FCM, all measures were improved. Median ferritin was 68 µg/L (IQR 62.5-109, p < 0.00045). Median CGI-I was 1 (very much improved) (IQR 1-2). All children meeting definite RLS criteria improved. Three children in the probable RLS group did not improve. Children meeting the full RLS criteria had lower baseline ferritin levels than those with a probable diagnosis (9 µg/L, IQR 9-10 vs. 13 µg/L, IQR 10-16, Mann-Whitney test p < 0.045). Adverse effects included lightheadedness, gastrointestinal discomfort, fever, and headache among others. CONCLUSIONS: The majority of children (84.2%) with ASD, restless legs symptoms, and serum ferritin <30 µg/L had clinical improvement and significantly better serum iron parameters after a single IV FCM infusion. Although larger, randomized trials are needed, IV FCM appears to be a promising treatment for this subset of children with ASD.

Leg movements during sleep in children treated with serotonergic antidepressants.

STUDY OBJECTIVES: To evaluate leg movements during sleep (LMS) in children taking serotonergic antidepressants, compared to those of children with restless legs syndrome (RLS) and controls, and to assess the time structure of intermovement intervals (IMI). METHODS: Twenty-three children (12 girls, mean age 14.1 years) on antidepressants and with a total LMS index ≥ 15/h, 21 drug-naïve RLS children (11 girls, mean age 13.6 years) also with total LMS index ≥ 15/h, and 35 control children (17 girls, mean age 14.3 years) were recruited. LMS were scored and a series of parameters was calculated, along with the analysis of their time structure. RESULTS: Children taking antidepressants showed higher total and periodic LMS (PLMS) indexes than both controls and RLS children, as well as higher short-interval and isolated LMS indexes than controls. LMS periodicity was highest in children on antidepressants. In children taking antidepressants, a well-defined PLMS IMI peak corresponding to approximately 10-60 s, with a maximum at approximately 20 s was present, which was much less evident in RLS patients and absent in controls. A progressive decrease of PLMS during the night and more frequent arousals were found in children on antidepressants and with RLS. CONCLUSIONS: Children taking serotonergic antidepressants show higher periodicity LMS than children with RLS or controls and have a higher number of PLMS through the night. Antidepressant-associated PLMS in children seem to have features similar to PLMS of adults with RLS. Whether this is a marker of an increased risk to develop RLS later in life needs to be determined.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment of pediatric restless legs syndrome and periodic limb movement disorder.

BACKGROUND: Iron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD. METHODS: This was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed. RESULTS: Thirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between "very much improved" and "much improved". Ferritin increased from 14.6 µg/L±7.01 to 112.4 µg/L±65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild. CONCLUSIONS: Children with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Heart rate changes associated with the different types of leg movements during sleep in children, adolescents and adults with restless legs syndrome.

The objective of this study was to describe in detail the heart rate changes accompanying short-interval leg movements during sleep, periodic leg movements during sleep, and isolated leg movements during sleep in children and adolescents with restless legs syndrome, and to compare them with the same findings in adults with restless legs syndrome. We analysed time series of R-R intervals synchronized to the onset of short-interval leg movements during sleep, periodic leg movements during sleep or isolated leg movements during sleep that entailed an arousal during non-rapid-eye-movement sleep. We assessed cardiac activation based on the heart rate changes with respect to baseline during non-rapid-eye-movement sleep without leg movements. All types of leg movements recorded during sleep were accompanied by important heart rate changes also in children, with an overall impact similar to that observed in adults. In all age groups, heart rate changes accompanying short-interval leg movements during sleep were constituted by a tachycardia, without a subsequent relative bradycardia, that was instead evident for periodic leg movements during sleep and isolated leg movements during sleep. Moreover, an age-related decline of the relative bradycardia following the heart rate increase, in association with periodic leg movements during sleep and isolated leg movements during sleep, was observed. Our findings show that important heart rate changes accompany all leg movements during sleep at all ages in restless legs syndrome, with significant age-related differences. This information represents an important contribution to the ongoing scientific debate on the possibility and opportunity to treat periodic leg movements during sleep.

Scoring of large muscle group movements during sleep: an International Restless Legs Syndrome Study Group position statement.

There is a gap in the manuals for scoring sleep-related movements because of the absence of rules for scoring large movements. A taskforce of the International Restless Legs Syndrome Study Group (IRLSSG) elaborated rules that define the detection and quantification of movements involving large muscle groups. Consensus on each of the criteria in this article was reached by testing the presence of consensus on a first proposal; if no consensus was achieved, the concerns were considered and used to modify the proposal. This process was iterated until consensus was reached. A preliminary analysis of the duration of movements involving large muscle groups was also carried out on data from two previous studies, which, however, used a visual analysis of video-polysomnographic (PSG) recordings obtained from children or adults. Technical specifications and scoring rules were designed for the detection and quantification of large muscle group movements during sleep with a duration between 3 and 45 seconds in adults or 3 and 30 seconds in children, characterized by an increase in electromyographic activity and/or the occurrence of movement artifact in any combination of at least two recommended channels and not meeting the criteria for any other type of movement. Large muscle group movements are often accompanied by sleep stage changes, arousals, awakenings, and heart rate rises. The absence of clear and detailed rules defining them has likely impeded the development of studies that might disclose their clinical relevance; these new rules fill this gap.

Restless sleep in children: A systematic review.

This systematic review assessed the prevalence of restless sleep in children, documented the association of restless sleep with other conditions, and summarized the existing evidence regarding whether restless sleep should be considered a distinct sleep disorder. A comprehensive search of electronic databases was performed using the broad search term "restless sleep" in all fields. Of the 266 articles retrieved, 107 were retained for inclusion in this review. The majority (n = 93) were observational studies. The studies were grouped under several pathologic/condition categories: sleep-disordered breathing (n = 19); adenotonsillectomy (n = 7); respiratory disorders, otitis media, and smoke exposure (n = 12); sleep-related movement disorders and restless sleep disorder (n = 11); neurologic or psychiatric disorders (n = 7); Down syndrome/other neurodevelopmental disorders (n = 10); sleep-related bruxism and other sleep disorders (n = 7); and restless sleep in the general population/mixed clinical samples (n = 18). A high prevalence of restless sleep was found in children with many of these underlying conditions, likely related to associated inherent sleep disruption and frequent awakenings (e.g., apnea and periodic limb movements), pain, sleep instability, and caregiver perception. The majority of studies identified restless sleep as reported by the caregiver, only 34 studies attempted to define restless sleep further. Four studies provided supportive evidence for designating restless sleep as an independent sleep disorder, restless sleep disorder (RSD). This review highlights the fact that the prevalence, etiology and sequelae (including daytime impairments) of restless sleep in children are important topics deserving of further research and that clinical definitions based on empirical evidence need to be developed. The designation of "primary" versus "secondary" restless sleep may be a useful construct, especially with regard to developing clinical trials and treatment algorithms.

Consensus Guidelines on Rodent Models of Restless Legs Syndrome.

Restless legs syndrome (RLS) is a chronic sensorimotor disorder diagnosed by clinical symptoms. It is challenging to translate the diagnostic self-reported features of RLS to animals. To help researchers design their experiments, a task force was convened to develop consensus guidelines for experimental readouts in RLS animal models. The RLS clinical diagnostic criteria were used as a starting point. After soliciting additional important clinical features of RLS, a consensus set of methods and outcome measures intent on capturing these features-in the absence of a face-to-face interview-was generated and subsequently prioritized by the task force. These were, in turn, translated into corresponding methods and outcome measures for research on laboratory rats and mice and used to generate the final recommendations. The task force recommended activity monitoring and polysomnography as principal tools in assessing RLS-like behavior in rodents. Data derived from these methods were determined to be the preferred surrogate measures for the urge to move, the principal defining feature of RLS. The same tools may be used to objectively demonstrate sleep-state features highly associated with RLS, such as sleep disturbance and number and periodicity of limb movements. Pharmacological challenges and dietary or other manipulations that affect iron availability are desirable to aggravate or improve RLS-like behavior and lend greater confidence that the animal model being proffered replicates key clinical features of RLS. These guidelines provide the first consensus experimental framework for researchers to use when developing new rodent models of RLS. © 2020 International Parkinson and Movement Disorder Society.

Comparison between oral ferrous sulfate and intravenous ferric carboxymaltose in children with restless sleep disorder.

STUDY OBJECTIVES: Recent work has identified clinical and polysomnographic features of a newly defined pediatric sleep disorder, restless sleep disorder (RSD). One of these features is low serum ferritin. In this retrospective, pilot study, we assess the response to iron supplementation. Children were given oral ferrous sulfate (FS) or intravenous ferric carboxymaltose (IV FCM). METHODS: Children 5-18 years old with a diagnosis of RSD were evaluated clinically. Serum ferritin, iron profile, and video-polysomnography were obtained at baseline. Oral or IV iron supplementation was offered as part of routine care. Oral FS was one 325 mg tablet daily or 3 mg/kg/day liquid for 3 months. IV FCM was 15 mg/kg, up to 750 mg as a single infusion. Adverse effects were assessed. Ferritin and iron profile were checked after 2-3 months. Eight weeks after FCM, the phosphorus level was checked. Clinical Global Impression (CGI) scale was obtained pre- and posttreatment. RESULTS: A total of 15 children received oral FS and 15 IV FCM. Baseline RSD severity, age, gender, or pretreatment lab values did not differ significantly between groups. CGI-improvement median score was "minimally improved" after oral FS and "much improved" after IV FCM (effect size 1.008, p < 0.023). All iron parameters were found to be significantly higher after intravenous iron treatment than oral iron, especially ferritin (effect size 3.743, p < 0.00003). Adverse effects: constipation, three with FS; noncompliance, one with FS; syncope, one with FCM infusion; and hypophosphatemia, zero post-FCM. CONCLUSIONS: In this retrospective, clinical case series, RSD responded to iron supplementation with improvement in both clinical and laboratory parameters. The response was greater with IV FCM than oral FS.

Consensus diagnostic criteria for a newly defined pediatric sleep disorder: restless sleep disorder (RSD).

BACKGROUND: Restless sleep is a frequent complaint in clinical practice and has been reported in the medical literature since the 1970s. Most often, it has been described in association with specific sleep or medical conditions. However, more recently, publications have emerged that describe a disorder characterized by restless sleep as the core feature. To assess this further, the International Restless Legs Syndrome Study Group (IRLSSG) appointed a task force composed of international sleep experts. METHODS: A committee of 10 sleep clinicians developed a set of 16 consensus questions to review, conducted a comprehensive literature search, and extensively discussed potential diagnostic criteria. The committee recommendations were reviewed and endorsed by the IRLSSG Executive Committee. RESULTS: Based on the medical literature and expert clinical experience, the task force found sufficient evidence to formulate diagnostic criteria for a clinical entity designated "restless sleep disorder" (RSD). Eight essential criteria were agreed upon, which include a complaint of restless sleep, observed large body movements during sleep, video-polysomnographic documentation of 5 or more large body movements/hour, occurrence at least three times a week for at least three months, clinically significant impairment, and differentiation from other conditions that might secondarily cause restless sleep. However, the current evidence limits application to ages 6-18 years. Diagnostic coding, addition to existing diagnostic nosologies, and name selection are discussed. CONCLUSIONS: Consensus diagnostic criteria for RSD have been developed, which are intended to improve clinical practice and promote further research.

Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome.

The objective of this observational cohort study was to analyse the age-related changes of periodic leg movements during sleep using the newest international scoring rules, to expand past analyses, including patients in the paediatric age range, and also to analyse the changes of short-interval and isolated leg movements during sleep throughout the lifespan. One hundred and sixty-five patients (84 women) with restless legs syndrome were recruited in the following age groups: 16 preschoolers (≤5 years of age), 29 school-age children (6-12 years), 19 adolescents (13-17 years), 17 young adults (19-40 years), 47 adults (41-60 years) and 37 seniors (>60 years). Total, periodic, short-interval and isolated leg movements during sleep and periodicity indexes were obtained by polysomnography. The total index showed (quartic polynomial interpolation) a decrease before 10 years, followed by a steady increase up to 30 years, a relatively stable period until 60 years, and a final increase up to 80 years. This course was almost entirely due to changes in periodic movements. Isolated movements did not change significantly and short-interval movements showed only an increase in seniors. Our study indicates that, in restless legs syndrome, the total index shows a peculiar and unique course throughout the lifespan, mainly due to periodic movements. These age-related changes may mirror developmental changes in network complexity known to occur in dopaminergic circuits. These data further confirm the need to better assess the periodicity of leg movements in sleep during the human development period, in order to obtain clinically useful information.

Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report.

BACKGROUND: Brain iron deficiency has been implicated in the pathophysiology of RLS, and current RLS treatment guidelines recommend iron treatment when peripheral iron levels are low. In order to assess the evidence on the oral and intravenous (IV) iron treatment of RLS and periodic limb movement disorder (PLMD) in adults and children, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force to review these studies and provide evidence-based and consensus guidelines for the iron treatment of RLS in adults, and RLS and PLMD in children. METHODS: A literature search was performed to identify papers appearing in MEDLINE from its inception to July 2016. The following inclusion criteria were used: human research on the treatment of RLS or periodic limb movements (PLM) with iron, sample size of at least five, and published in English. Two task force members independently evaluated each paper and classified the quality of evidence provided. RESULTS: A total of 299 papers were identified, of these 31 papers met the inclusion criteria. Four studies in adults were given a Class I rating (one for IV iron sucrose, and three for IV ferric carboxymaltose); only Class IV studies have evaluated iron treatment in children. Ferric carboxymaltose (1000 mg) is effective for treating moderate to severe RLS in those with serum ferritin <300 µg/l and could be used as first-line treatment for RLS in adults. Oral iron (65 mg elemental iron) is possibly effective for treating RLS in those with serum ferritin ≤75 µg/l. There is insufficient evidence to make conclusions on the efficacy of oral iron or IV iron in children. CONCLUSIONS: Consensus recommendations based on clinical practice are presented, including when to use oral iron or IV iron, and recommendations on repeated iron treatments. New iron treatment algorithms, based on evidence and consensus opinion have been developed.

Leg movement activity during sleep in school-age children and adolescents: a detailed study in normal controls and participants with restless legs syndrome and narcolepsy type 1.

Study Objectives: To evaluate leg movement activity during sleep (LMS) in normal school-age children and adolescents, to eventually establish age-specific periodic LMS (PLMS) index thresholds that support the diagnosis of restless legs syndrome (RLS), and to evaluate the utility of other LMS indices. Methods: Polysomnographic recordings from 61 controls, 46 children with RLS, and 44 children with narcolepsy type 1 (NT1) were analyzed for total leg movements (LMS), PLMS, and isolated leg movements (ISOLMS) duration and indices, separately for school-age children and adolescents. Moreover, intermovement interval (IMI) graphs and time-of-night distribution of LMS were analyzed, and cut-off thresholds for PLMS index and total LMS index were assessed for the separation of RLS from controls. Results: All indices tended to decrease from school-age children to adolescents in normal controls and in NT1, whereas in RLS, only PLMS index increased. All school-age children had a similar IMI distribution with a single peak at IMI 2-4 s followed by gradual decline. In adolescents with RLS, a second peak at IMI 10-50 s was seen. Time-of-night distribution of most indices decreased in RLS, whereas most tended to increase in NT1. A PLMS index cutoff of 2 per hour best differentiated RLS from controls in school-age children (accuracy 70.0%) and in adolescents (accuracy 70.8%); however, most participants with NT1 also showed PLMS indices higher than this threshold. Conclusions: PLMS index alone does not reliably predict the diagnosis of RLS in children and adolescents. However, analyses of IMI distribution and time-of-night distribution provide additional elements to support a diagnosis of RLS.

Pharmacokinetics of rotigotine transdermal system in adolescents with idiopathic restless legs syndrome (Willis-Ekbom disease).

OBJECTIVE: To investigate the pharmacokinetics (PK) of rotigotine transdermal system in adolescents with moderate-to-severe idiopathic restless legs syndrome (RLS). METHODS: This multicenter, open-label, dose-escalation study enrolled patients ≥13 to <18 years of age. Rotigotine transdermal patches were applied daily and up-titrated weekly: 0.5, 1, 2, 3 mg/24 h. Blood samples were collected on the final day of each dose step. Primary PK variables were the apparent total body clearance (CL/f; L/h) and volume of distribution at steady state (VSS/f; L) of unconjugated rotigotine for each dose step, calculated for the PK per-protocol set (PKPPS). Other PK, safety, and efficacy variables (International RLS Study Group Rating Scale [IRLS]; Clinical Global Impressions Item 1 [CGI-1]) were assessed. RESULTS: Of 24 patients who received rotigotine, 23 completed all dose steps and 17 formed the PKPPS. Least-squares mean (95% confidence interval) CL/f and VSS/f values were broadly similar across all dose steps (CL/f: 0.5 mg/24 h: 676.86 [408.50-1121.51]; 1 mg/24 h: 671.72 [459.11-982.80]; 2 mg/24 h: 937.56 [658.50-1334.89]; 3 mg/24 h: 1088.77 [723.47-1638.53]; VSS/f: 5403.16 [2850.67-10,241.17]; 6220.79 [3842.05-10,072.28]; 7114.01 [4547.88-11,128.07]; 6037.92 [3598.36-10,131.41]). Among 23 patients with efficacy data, mean IRLS and CGI-1 scores improved at each dosage level. Adverse events reported by ≥3 patients were nausea (seven) and application site reactions (four). CONCLUSIONS: Key PK properties of rotigotine in adolescent patients with moderate-to-severe idiopathic RLS were comparable to those previously observed in adults. Rotigotine improved RLS symptoms and was well tolerated. ClinicalTrials.gov: NCT01495793.

Periodic leg movements during sleep: phenotype, neurophysiology, and clinical significance.

Periodic leg movements during sleep (PLMS) are the most important objective finding in restless legs syndrome (RLS). During the last decade, PLMS have been very important for the assessment and comprehension of their pathophysiological correlates, which have been paralleled by the emergence of new computer-assisted and data-driven rules for their identification, scoring, and analysis. The present article focused on the most relevant PLMS-related findings of the last decade, and sought to provide a coherent and comprehensive overview on this enigmatic motor phenomenon. First, a clear description was made on the identification, quantification, and scoring of PLMS and their associated events. This was followed by a description of the current knowledge of their neurophysiologic aspects. Then, the typical phenotype of genuine PLMS in RLS and other clinical conditions was described, allowing for their careful separation from other sleep leg motor activities. In addition, the most recent findings on the genetics of PLMS were briefly summarized, followed by the current evidence on their clinical correlates, which is another rapidly advancing field of research. The description of the specific aspects of PLMS in children was also carefully reported, with important clues on their evaluation in this age group. Finally, further research was proposed, which may lead to consideration of PLMS as a clinically significant concern, independent of the association with RLS.

Achievements, challenges, and future perspectives of epidemiologic research in restless legs syndrome (RLS).

In the 20 years since the initial consensus on a common definition for restless legs syndrome (RLS), over 600 scientific reports on epidemiological aspects of RLS have been published. Most are descriptive and address important issues such as prevalence, familial patterns, comorbidities, and quality of life. While the establishment of prospective cohort studies and the use of secondary data sources are rather new to RLS research, both options significantly broaden the possibilities for analysis of disease risk factors. These two options, as well as the inclusion of a broader phenotyping of individual patients, have great potential to elucidate etiologic factors for RLS and expand knowledge about this common disorder. This article summarizes achievements in the area of RLS epidemiology, describes current challenges, and highlights future perspectives in the field.

Depth and Distribution of Symptoms in Restless Legs Syndrome/ Willis-Ekbom Disease.

STUDY OBJECTIVES: To determine the depth and distribution of sensory discomfort in idiopathic restless legs syndrome/Willis-Ekbom disease (RLS) and RLS concurrent with other leg conditions, specifically peripheral neuropathy, sciatica, leg cramps, and arthritis. METHODS: RLS subjects (n = 122) were divided into 71 idiopathic RLS and 51 RLS-C, or Comorbid, groups. All subjects were examined by an RLS expert, answered standardized RLS questionnaires, and received a body diagram to draw the location and depth of their symptoms. RESULTS: Age was 63.04 ± 12.84 years, with 77 females and 45 males. All patients had lower limb involvement and 43/122 (35.25%) also had upper limb involvement. Of the 122 subjects, 42.62% felt that the RLS discomfort was only deep, 9.84% felt that the discomfort was only superficial, and 47.54% felt both superficial and deep discomfort. There were no defining characteristics in depth or distribution of RLS sensations that differentiated those patients with idiopathic RLS from those patients with RLS associated with other comorbid leg conditions. The sensation of arthritis was felt almost exclusively in the joints and not in the four quadrants of the leg, whereas the exact opposite was true of RLS sensations. CONCLUSIONS: Depth and distribution cannot be used as a discriminative mechanism to separate out idiopathic RLS from RLS comorbid with other leg conditions. Although seen in clinical practice, the total absence of patients with non-painful RLS only in the joints in the current study attests to the rarity of this presentation and raises the possibility of misdiagnosis under these circumstances. We recommend that such patients not be admitted to genetic or epidemiological studies.