Associations between sleep,daytime sleepiness and functional outcomes in adolescents with ADHD

Objective/backgroundAdolescents with attention-deficit/hyperactivity disorder (ADHD) experience greater difficulties in the domains of sleep, daytime sleepiness, and functioning compared to their peers. However, the relationship between these domains has not been fully elucidated. This study aimed to examine the relationship between sleep problems (including daytime sleepiness), ADHD severity, and functional outcomes (irritability, sluggish cognitive tempo, homework difficulties, and substance use) in a sample of adolescents with ADHD.Patients/methodsEighty-two adolescents (13–17 years) and their families participated in the study. Sleep was measured by both adolescent and parent-report. Adolescent irritability and sluggish cognitive tempo were reported by both adolescents and parents, while other variables were reported by a single reporter (homework difficulties – parent; ADHD severity – parent; substance use – adolescent). Analyses controlled for demographic factors and internalising and externalising comorbidities.ResultsA weak relationship was found between adolescent-reported sleep problems and daytime sleepiness, which became non-significant in adjusted analyses (β = −0.19, p = 0.115). In adjusted analyses, there was an association between adolescent-reported sleep problems and adolescent-reported irritability (β = −0.27, p = 0.023) as well as between adolescent-reported daytime sleepiness and parent-reported sluggish cognitive tempo (β = 0.28, p = 0.033). In adjusted analyses, parent-reported adolescent sleep problems were associated with ADHD severity (β = 0.54, p = <0.001), parent-reported sluggish cognitive tempo (β = 0.64, p = <0.001), both reporters of irritability (parent-report: β = 0.32, p = 0.004; adolescent-report: β = 0.29, p = 0.022), and homework problems (β = 0.37, p = 0.003). Parent-reported daytime sleepiness was associated with parent-reported sluggish cognitive tempo (β = 0.34, p = 0.024).ConclusionsThis study demonstrates the importance of a holistic assessment of adolescents with ADHD, not only focusing on symptomatology but also on sleep problems and functional outcomes. The importance of multi-informant assessment of sleep problems is also reinforced.     

Restless legs syndrome after high-risk TIA and minor stroke: association with reduced quality of life

BackgroundRestless legs syndrome (RLS) is a movement disorder that is associated with poor quality of life and depressive symptoms in the general population. Emerging evidence suggests that RLS is closely associated with cerebrovascular disease. We assessed the effect of RLS on quality of life after stroke and transient ischemic attack (TIA).MethodsIn this single-center prospective study, we recruited patients within 14 days of high-risk TIA or minor stroke. Patients were diagnosed with RLS using a questionnaire based on the 2003 International RLS Study Group criteria, and diagnoses were confirmed by a sleep neurologist. Follow-up assessments were conducted within 2–6 months of recruitment. The outcome of quality of life was measured using the Stroke-specific Quality of Life (SS-QoL).ResultsOf the 94 patients recruited into the study, 23 (24.4%) were diagnosed with RLS: 11 were newly diagnosed with RLS and 12 had RLS preceding the index stroke/TIA. There were no significant differences in baseline characteristics between those with or without RLS. Median SS-QoL in patients with RLS was lower at baseline (p = 0.008) and at follow-up (p = 0.002). RLS patients had more depressive symptoms at follow-up (p = 0.007). Ordinal logistic regression demonstrated that RLS was negatively associated with quality of life at baseline (OR = 0.28; p = 0.010) and at follow-up (OR = 0.14; p = 0.029), independent of functional outcome and depressive symptoms.ConclusionsRLS is common after stroke or TIA and negatively affects the quality of life. Screening for RLS after cerebrovascular events may be warranted, and future research should assess whether treatment of RLS can improve post-stroke quality of life.     

Prevalence and quality of life and sleep in children and adolescents with restless legs syndrome/Willis-Ekbom disease

ObjectiveTo estimate the prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) and its impact on sleep and quality of life in children and adolescents.MethodsThis was a cross-sectional study conducted in the Municipality of Cássia dos Coqueiros, Brazil. Participants included 383 children and adolescents 5–17 years of age. A comparison group was randomly matched by gender and age with the RLS/WED-affected individuals, pairing one by one.ResultsInterviews were conducted for 383 individuals by a neurologist experienced in sleep medicine. RLS/WED was diagnosed using the essential clinical criteria for definitive RLS/WED in children recommended by the International Restless Legs Syndrome Study Group. Sleep and quality of life were evaluated using the Sleep Behavior Questionnaire (SBQ) and the Health-related Quality of Life Questionnaire─Pediatric Quality of Life Inventory (PedsQL). Comparisons were established with a group of randomly selected individuals without RLS/WED, matched by age and gender (control group). The prevalence of RLS/WED symptoms that manifested at least twice a week was 1.9%. The average age of children with RLS/WED was higher compared to the general population (11.5 ± 2.3 vs 9.9 ± 2.5, p < 0.005). A family history of RLS/WED was detected in 90.9% of the patients. The scores obtained by SBQ were higher (53.9 ± 9.4 vs 47.6 ± 10.9, p < 0.047), whereas the scores achieved by PedsQL were lower (69.8 ± 14.8 vs 81.9 ± 10.4, p < 0.003) in children with RLS/WED compared to controls.ConclusionThe prevalence of RLS/WED symptoms manifested at least twice in the preceding week was 1.9% in children and adolescents. Worsened sleep and quality of life were observed in the study.     

Daily life impairments associated with self-reported childhood/adolescent attention-deficit/hyperactivity disorder and experiences of diagnosis and treatment: Results from the European Lifetime Impairment Survey

The Lifetime Impairment Survey assessed impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children/adolescents from six European countries. Parents/caregivers of children/adolescents aged < 20 years with ADHD (ADHD group; n = 535) and without ADHD (control group; n = 424) participated in an online survey. History of ADHD diagnosis was self-reported. ADHD and control groups were compared using impairment and symptom scales; higher scores indicate greater impairment. Mean (SD) age at ADHD diagnosis was 7.0 (2.8) years, following consultation of 2.7 (2.6) doctors over 20.4 (23.9) months. Parents/caregivers (64%; 344/535) reported frustration with some aspect of the diagnostic procedure; 74% (222/298) were satisfied with their child's current medication. ADHD had a negative impact on children/adolescents in all aspects of life investigated. The ADHD group had a higher mean (SD) school impairment score (2.7 [0.7]) compared with the control group (2.1 [0.7]; P < 0.001) and were more likely to be in the bottom of their class (P < 0.001). These data provide insights into impairments associated with ADHD in childhood/adolescence, and identify areas for improvement in its management and treatment.     

Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: A case-control study

BackgroundRestless Legs Syndrome (RLS) is associated with impaired central dopaminergic neurotransmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in parkinsonian disorders is poorly documented.ObjectiveTo determine the prevalence of RLS in patients with Parkinson's Disease (PD), Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).MethodsWe evaluated 187 consecutive patients with parkinsonian disorders (PD = 134, PSP = 27, MSA = 21, DLB = 5) and 172 healthy controls. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria and the severity of RLS was assessed in patients with definite RLS. Quality of sleep was evaluated with established scales.ResultsThe prevalence of RLS was higher in patients compared to controls (9.6% vs. 2.9%; p = 0.009) and was highest in PD (11.9%). RLS was present in only one patient each with MSA and PSP and none with DLB. The mean IRLSSG severity score of patients was 16.2 ± 6.5. The global Pittsburgh Sleep Quality Index score and Epworth Sleepiness Scale score were significantly higher in patients compared to controls (p < 0.001). PD patients with RLS had lower Parkinson's Disease Sleep Scale (PDSS) score compared to patients without RLS (p = 0.023). There was no significant difference in gender, age, duration and severity of PD between the two groups.ConclusionsOur study found a higher prevalence of RLS in PD compared to healthy controls or other parkinsonian disorders. Apart from PDSS score, there was no significant difference in the clinical characteristics of PD patients with and without RLS.     

An epidemological study of obsessive compulsive disorder in adolescents from India

ObjectivesThere is scarce data on the prevalence of OCD among adolescents in India. This study reports point prevalence of OCD among school students (age 12–18 years) in the Kerala state of India and examines its association with ADHD, psychological distress, tobacco/alcohol abuse, suicide risk and history of sexual abuse.Method7560 students of 73 schools were self-administered the OCD subsection of Clinical Interview Schedule–Revised, the Composite International Diagnostic Interview (CIDI) for obsessive compulsive symptoms and other relevant instruments to identify OCD and related clinical measures. A diagnosis of ICD-10 OCD was derived through the CIS-R algorithm which required duration of at least 2 weeks and at least a thought/behavior to be resisted along with a cut-off score for severity and impairment.ResultsIn the sample, 50.3% were males with a mean age of 15.2 years (range of 12–18 years). The response rate was 97.3% (7380 valid responses). 0.8% (n = 61) fulfilled criteria for OCD with a male predominance (1.1 vs. 0.5%, p = 0.005). Prevalence was higher among Muslims and increased with age. Taboo thoughts (62.3%) and mental rituals (45.9%) were the commonest symptoms. Those with OCD had significantly higher suicidal thoughts (59 vs. 16.3%, p < 0.01) suicide attempts (24.6 vs. 3.8%, p < 0.01), ADHD (28 vs. 4%, p < 0.001), sexual abuse (24.6 vs. 4.2%, p < 0.01), and tobacco use (23 vs. 6.8%, p = 0.01). They also reported greater psychological distress and poorer academic performance.ConclusionsOCD is common among adolescents in India. Its associations with ADHD, sexual abuse, psychological distress, poorer academic performance and suicidal behavior are additional reasons for it to be recognized and treated early.     

Assessing health-related quality of life in patients with restless legs syndrome in Korea: Comparison with other chronic medical diseases

BackgroundThere have been few quality of life (QoL) studies of patients with restless legs syndrome (RLS) in Asian countries. We studied the QoL of patients with RLS and compared it to normal controls and patients with hypertension, type 2 diabetes, or osteoarthritis in Korea.MethodsA total of 215 RLS patients (141 female; mean age 51.7 ± 13.5) were enrolled. All patients completed the questionnaires, including all the Korean versions of SF-36, RLS QoL, the International RLS Severity scale (IRLS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory-2 (BDI-2). These results were compared with the scores from normal controls (N = 214) and from patients with hypertension (196), uncomplicated type 2 diabetes (185), or osteoarthritis of the knee (177).ResultsThe SF-36 QoL in patients with RLS was lower than that of the normal controls, and even lower than patients with hypertension or diabetes, but higher than those with osteoarthritis. The SF-36 Qol of RLS patients showed a significantly negative correlation with the severity of RLS symptoms (r = ?0.430, p < 0.001) and the severity of depression (r = ?0.565, p < 0.001), but was not significantly related to gender, age, or age-of-symptom onset (early or late-onset). Step-wise multiple regression identified three factors related to SF-36 QoL: depression (46.5% of RLS had responses on BDI-2 indicating depression) (β = ?.899, p < 0.001), RLS symptom severity (K-IRLS) (β = ?.718, p < 0.001), and gender (female) (β = ?6.128, p = 0.007).ConclusionsThese findings show that RLS has a considerable impact on the QoL of Koreans, which is comparable with studies of western countries. The QoL impairment relates to the degree of depression with RLS for Koreans.     

Cortisol,inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan

BackgroundHypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, inflammation and imbalance of neurotrophins have been suggested in attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. The aim of this study is to investigate the levels of salivary cortisol across 4-time points during the day, and of morning plasma inflammatory biomarkers and neurotrophins, in youth with ADHD and in typically developing youth (TD), with stratification by age, ADHD subtypes and oppositional defiant disorder (ODD) comorbidity in Taiwan.MethodsWe conducted a case-control study measuring saliva cortisol levels at 4 different time points during the day (at awakening, noon, 1800 h and bedtime) and morning plasma levels of inflammatory and neurotrophins biomarkers in youth with ADHD (n = 98, age 6–18 years old with mean age 9.32 ± 3.05 years) and TD (n = 21, age 6–18 years old with mean age 9.19 ± 2.96 years) in Taiwan.ResultsOur study showed that youth with ADHD had lower levels of bedtime salivary cortisol (effects size (ES) = −0.04, p = .023), with children with the combined form of the disorder (with inattention, hyperactivity and impulsivity all present) having the lowest awakening salivary cortisol levels. ADHD youth also had higher levels of plasma high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 (ES = 0.85–1.20, p < .0001), and lower plasma tumor necrosis factor-alpha (ES = −0.69, p = .009) and brain-derived neurotrophic factors (BDNF) (ES = −1.13, p < .0001). Both ADHD groups regardless of ODD comorbidity had higher levels of IL-6 (p < .0001) and lower levels BDNF (p < .0001).ConclusionThe lower bedtime salivary cortisol levels and higher levels of inflammatory biomarkers in youth with ADHD further support the role of abnormal HPA axis and inflammation in ADHD. Moreover, the lower levels of BDNF in ADHD also indicate that BDNF may be a potential biomarker in this disorder that is part of a broader biological dysfunction.     

Ankle-brachial index and peripheral artery disease are not related to restless legs syndrome

ObjectiveOur aim was to investigate the relationship between impaired peripheral arterial circulation as measured by ankle-brachial index (ABI) and restless legs syndrome (RLS) in the general population.MethodsData are derived from three independent, German population-based, prospective studies: the control sample of BiDirect (N = 966), the second follow-up of SHIP (N = 2333), and a subsample of SHIP-Trend (N = 1269). RLS was assessed with questions based on the RLS minimal criteria. ABI was measured with an automated method in BiDirect and with Doppler ultrasound in both SHIP studies. An ABI score below 0.9 was indicative of peripheral arterial disease (PAD). Co-morbidities, medications and behavioural factors were self-reported. Additional measurements included body mass index and haemoglobin from blood serum. For BiDirect, a follow-up with identical methodology was performed after a median of 2.5 years.ResultsIn cross-sectional analyses, decreased ABI was not significantly associated with RLS as outcome in multivariable logistic regression models adjusted for several potential confounders (BiDirect: odds ratio (OR) = 1.07 for a −0.1 change in ABI, 95% confidence interval (CI): 0.81–1.42, p = 0.62; SHIP-2: OR = 0.99, CI: 0.85–1.16, p = 0.94; SHIP-Trend: OR = 0.99, CI: 0.87–1.13, p = 0.88). Similar non-significant results were achieved using PAD (instead of ABI) as an independent variable. In BiDirect, baseline ABI was not a significant predictor of incident RLS in longitudinal analysis (OR = 0.77, CI: 0.53–1.12, p = 0.17).ConclusionResults from three independent studies suggest that reduced ABI is not a risk factor for RLS in the general population.     

Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

Restless legs syndrome is highly prevalent in patients with post-polio syndrome

ObjectiveFew studies have quantified the prevalence of restless legs syndrome (RLS) in patients with post-polio syndrome (PPS). Our objective was to assess the prevalence and severity of RLS in patients with PPS and to examine the demographic characteristics of this population.MethodThis was a cross-sectional study conducted from April 2010 to May 2012 at the outpatient Neuromuscular Disorders clinic of Universidade Federal de São Paulo, São Paulo, Brazil. We evaluated 119 patients with PPS, consecutively recruited, and investigated for RLS based on the diagnostic criteria established by the International Restless Legs Syndrome Study Group (IRLSSG). Patients were evaluated with the Brazilian version of the IRLSSG severity scale.ResultsThe prevalence of RLS was 36% (n = 43; 32 women and 11 men). The ages at onset of RLS (median = 41 years) and PPS (median = 41 years) were concurrent, and the correlation between onset of symptoms of RLS and onset of symptoms of PPS was positive and very strong (Spearman r = 0.93, p = 0.01). The median RLS severity was 23 (range, 20–28). Low educational achievement and depression were predictive of RLS development.ConclusionIn the largest population of patients with PPS studied to date, our results indicate a high prevalence of RLS, marked disease severity, and concomitant onset of both conditions in many patients with PPS. Further studies are needed to elucidate a possible pathophysiologic mechanism linking these two conditions. We suggest that all post-polio patients with sensory and motor complaints in the legs be investigated for RLS.     

Evaluation of sleep organization in patients with attention deficit hyperactivity disorder (ADHD) and ADHD as a comorbidity of epilepsy

Objective/backgroundEpilepsy or attention deficit hyperactivity disorder (ADHD) can influence sleep organization in different ways. The aim of this study was to evaluate sleep organization in children and adolescents with ADHD and epilepsy, and to analyze the influence of methylphenidate.MethodsThis was an observational, cross-sectional study of children and adolescents with epilepsy, who were seizure free for at least three months, and were also diagnosed with ADHD. They were selected from the epilepsy and child neurology outpatient clinic of a university hospital in Brazil. After sample size calculation, patients were consecutively included into four different groups, with 21 patients each: epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate, only ADHD, and a healthy control group. All participants were evaluated with the Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for five nights/days.ResultsActigraphic analysis showed a higher number of night awakenings in the epilepsy + ADHD groups; they were most prominent in the group without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk for sleep disturbances in the epilepsy + ADHD without methylphenidate and the ADHD groups (p < 0.001).ConclusionPrimary ADHD as a comorbidity of epilepsy impairs sleep organization in children, and the use of short-acting methylphenidate seems to improve it. Both objective (actigraphic) and subjective (SDSC) measures showed significant sleep alterations between primary ADHD and ADHD as a comorbidity of epilepsy; this was most prominent in the group without methylphenidate.     

Acute post-stroke restless legs syndrome: the body of caudate nucleus considerations

ObjectivesTo investigate the relationship between the lesion location and post-stroke restless legs syndrome (RLS).MethodsA total of 376 patients with acute cerebral infarction were recruited from Tangshan Gongren Hospital, Department of Neurology between May 2016 and May 2017, all of whom were evaluated for RLS. Established RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in 2012. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS). The lesion location was evaluated with magnetic resonance imaging (MRI). The associations between the lesion location and post-stroke RLS were then analyzed by logistic regression.ResultsA total of 49 patients (13.03%) had RLS. The multivariate logistic regression model adjusting for post-stroke RLS risk factors including gender, age, history of hypertension, history of diabetes, history of stroke, smoking, drinking, body mass index (BMI), NIHSS, hemoglobin, platelet and homocysteine determined that body of caudate nucleus and pontine were significantly associated with post-stroke RLS with odds ratio (OR) of 26.26 (95% confidence interval (CI): 9.41–73.28,p < 0.001) and OR of 4.37 (95% CI: 1.24–15.34, p = 0.021). The stepwise logistic regression model with temporal lobe, parietal lobe, occipital lobe, frontal lobe, callosum, body of caudate nucleus, thalamus, lenticulo capsule, corona radiata, centrum semi-ovale and pontine as potential predictors yielded a predictor mode. The stepwise logistic regression predictor mode indicated that body of caudate nucleus and pontine predicted post-stroke RLS with similar OR to multivariate models of 23.61 (95% CI: 9.53–58.51, p < 0.001) and 4.46 (95% CI: 1.38–14.4, p = 0.012).ConclusionsThe ischemic infarcts located in body of caudate nucleus, pontine are significantly associated with post-stroke RLS. Body of caudate nucleus acute infarcts may play a role in the development of post-stroke RLS.     

Higher nocturnal systolic blood pressure in patients with restless legs syndrome compared with patients with insomnia

BackgroundThere is evidence linking restless legs syndrome (RLS) with increased blood pressure (BP), but the mechanism of this relation remains unclear. Is the BP increased due to some features of RLS or to deterioration of sleep caused by RLS? This study compared values of nocturnal BP in patients with RLS and patients with insomnia. If increased BP in RLS is a consequence of disordered sleep, then it should be similar to increased BP in insomnia.MethodsPolysomnographic recordings of patients admitted to a sleep center with RLS or insomnia were analyzed. Demographic and clinical data, objective sleep parameters, and nocturnal BP were compared.ResultsRecordings of 35 patients with RLS and 33 patients with insomnia were analyzed. The groups did not significantly differ in terms of demographic traits or prevalence of other comorbidities. Patients with RLS had significantly higher systolic BP during the night (122.4 ± 13.8 vs 116.3 ± 13.4; p = 0.03) and during sleep (121.4 ± 13.3 vs 115.7 ± 13.3; p = 0.04). The only significant difference in sleep architecture was an increased number of periodic limb movements in sleep (PLMS) and PLMS with arousal in the RLS group (25.5 ± 24.6 vs 13.9 ± 22.7; p = 0.02 and 4.7 ± 5.4 vs 2.1 ± 3.4; p = 0.01).ConclusionOur results suggest that patients with RLS have higher nocturnal BP than patients with insomnia, and that increased PLMS is related to the increase in BP.     

Empathic accuracy in adolescents with autism spectrum disorders and adolescents with attention-deficit/hyperactivity disorder

In research on theory of mind (ToM) in individuals with an autism spectrum disorder (ASD) mainly static mind-reading tasks were used. In this study both a static (Eyes Test) and a more naturalistic (empathic accuracy task) ToM measure were used to investigate the perspective taking abilities of adolescents with ASD (n = 13), adolescents with attention-deficit/hyperactivity disorder (ADHD; n = 13) and typically developing adolescents (n = 18). An innovative aspect concerns the standard stimulus tapes of the empathic accuracy task, which showed interactions between dyads of one adolescent with ADHD and one adolescent without ADHD. In this way, we were able to compare the ‘readability’ of the thoughts and feelings of adolescents with and without ADHD. The results clearly demonstrate the impairment in perspective taking abilities of adolescents with ASD, both on the static and naturalistic mind-reading task. Moreover, the empathic accuracy task seems to be a useful and promising method to assess ToM abilities in adolescents, with or without clinical problems. Finally, thoughts and feelings of target persons with ADHD seemed to be less easy to read than the thoughts and feelings of typically developing target persons.     

Contrasting painless and painful phenotypes of pediatric restless legs syndrome: a twin family study

ObjectiveThis study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders.MethodsIn a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets.ResultsData were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04).ConclusionsPediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS.     

Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.Methods137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).ResultsMean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with log CRP (r(129) = 0.19, p = 0.03). Those patients with at least 45 PLMs/h had an odds ratio of 3.56 (95% CI 1.26–10.03, p = 0.02, df = 1) for having elevated CRP compared to those with fewer than 45 PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ?45 PLMs/h was 8.60 (95% CI 1.23 to 60.17, p = 0.03, df = 10).ConclusionsPLMs are associated with increased inflammation, such that those RLS patients with at least 45 PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.     

Bidirectional association between irritable bowel syndrome and restless legs syndrome: a systematic review and meta-analysis

BackgroundSeveral observational studies have shown that patients with irritable bowel syndrome (IBS) may have a high risk of restless legs syndrome (RLS). This systematic review and meta-analysis aimed to comprehensively investigate the bidirectional association between IBS and RLS.MethodsAll conservational studies on IBS and RLS were searched in MEDLINE (assessed by PubMed), Embase, Web of Science, CINAHL, the Cochrane Library database and Google Scholar from inception to June 14, 2020. The Newcastle–Ottawa Scale and Agency for Healthcare Research and Quality were used to assess the methodological quality of the cohort and cross-sectional studies, respectively. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using Reviewer Manager 5.3.ResultA total of five cross-sectional studies of moderate methodological quality and one cohort study of high methodological quality were included in our review. Four cross-sectional studies and one cohort study involving 86 438 individuals met the criteria of IBS predicating the onset of RLS. Patients with IBS had a nearly three-fold increased odds of RLS compared with controls (OR = 2.60, 95%CI: 2.17–3.12, P < 0.00001; I² = 48%, P = 0.11). Three sensitivity analyses confirmed the robustness of the pooled result. Two cross-sectional studies involving 3581 individuals met the criteria of RLS predicating the onset of IBS. RLS patients had a nearly four-fold increased odds of IBS compared with controls without RLS (OR = 3.87, 95%CI: 1.73–8.66, P = 0.0010; I² = 77%, P = 0.04).ConclusionIn this systematic review and meta-analysis, we found a substantial bidirectional association between IBS and RLS. More prospective, high-quality, population-based studies are warranted in the future.