Periodic limb movement disorder of sleep in children

To characterize periodic limb movement disorder (PLMD) in a cohort of prepubertal children we examined sleep-related identifiable differences between children with PLMD and attention-deficit/hyperactivity disorder (ADHD), PLMD alone, and age-matched controls. Children were selected from a chart review of all children referred to a pediatric sleep medicine center and from a community survey of 5-7-year-old-children. Polysomnography (PSG) and parental report data from all children identified as having periodic limb movement index (PLMI) >5 were reviewed and compared with a cohort of age-matched controls. A total of 8.4% of children in the clinic-referred sample, and 11.9% of the children recruited from the community had PLMI >5. Of those, 44.4% were identified as having ADHD. Children with PLMD had significantly lower percentage of rapid eye movement (REM) than control children (P < 0.001). Children in the PLMD/ADHD group had a significantly greater number of arousals associated with PLM (PLMa) than children with PLMD only (P < 0.05). While a relationship between ADHD and PLMD was observed, it was weaker than previous reports (Chervin, R. D. et al. Sleep, 2002; 25: 213; Chervin, R. D. and Archbold, K. H. Sleep, 2001; 24: 313; Picchietti et al. J. Child Neurol., 1999; 13: 588; Picchietti et al. Mov. Disord., 1999; 14: 1000; Picchietti and Walters Sleep, 1999; 22: 297). Children in the PLMD/ADHD group were more likely to have PLMas than were children with PLMD only. We postulate that rather than a direct relationship between ADHD and PLMD, this link may be mediated by the presence of reduced REM sleep and more importantly by the sleep fragmentation associated with PLM-induced arousals.     

Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist

STUDY OBJECTIVES: To define which leg movements (LM) associated with restless legs syndrome (RLS) respond to dopamine-agonist treatment and verify if they fall within current diagnostic criteria for periodic LM during sleep (PLMS). DESIGN: Single-blind placebo-controlled study. SETTINGS: Sleep laboratory. PATIENTS: 43 consecutive untreated patients with idiopathic restless legs syndrome. INTERVENTIONS: Patients underwent clinical and neurophysiological evaluation, hematological screening, and 2 consecutive full-night polysomnographic studies. Before the second polysomnographic study, all patients were randomized to receive 0.25 mg of pramipexole or placebo. MEASUREMENTS AND RESULTS: LM parameters such as duration, amplitude, interval, and periodicity were analyzed. Compared to placebo, pramipexole significantly (P < 0.01) reduced PLMS while increasing sleep efficiency. Specifically we observed a significant (P < 0.01) reduction in LM ranging 2-4 s in duration and with intermovement interval of 6-46 s and a significant decrease in the periodicity of motor events. No effect of pramipexole was observed on isolated LM. CONCLUSIONS: These results support a heterogeneous basis for LM in RLS patients; while isolated LM do not respond to pramipexole treatment, most, but not all, PLMS classified by means of the current criteria do. Further studies with different pramipexole doses or dopamine agonists with different receptor-binding preference are warranted to better define the borders of dopamine response of PLMS.     

Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome

We compared periodic and non‐periodic leg movements during sleep and polysomnography in patients with narcolepsy with cataplexy (NC) with or without restless legs syndrome (RLS) with matched idiopathic RLS (iRLS) and control subjects. We enrolled 100 patients with NC: 17 having RLS were compared with 34 sex‐ and age‐matched patients without RLS and with 17 normal controls and 17 iRLS subjects. Periodic leg movements were highest in iRLS and lowest in controls, with those in NC with RLS very close to iRLS, but higher than those in NC without RLS. The periodicity indexes showed the highest value in iRLS followed by NC with or without RLS and, finally, by controls. The inter‐leg movement intervals peaked between 10 and 50 s in NC with RLS and in iRLS, the former did not display the nocturnal gradual decrease of periodic leg movements typical of iRLS. Periodic leg movements during sleep and polysomnography displayed specific features in RLS and NC, respectively, with NC with RLS showing an intermediate pattern. Even if RLS is only detected by targeted interview in NC, its frequency and impact on night‐time sleep architecture and continuity suggest that this condition should be routinely searched for in NC.     

Periodic leg movements during sleep and wakefulness in narcolepsy

The objectives of the study were to measure the prevalence of periodic leg movements during NREM and REM sleep (PLMS) and while awake (PLMW) and to assess the impact of PLMS on nocturnal sleep and daytime functioning in patients with narcolepsy. One hundred and sixty-nine patients with narcolepsy and 116 normal controls matched for age and gender were included. Narcoleptics with high and low PLMS indices were compared to assess the impact of PLMS on sleep and Multiple Sleep Latency Test (MSLT) variables. More narcoleptics than controls had a PLMS index greater than 5 per hour of sleep (67% versus 37%) and an index greater than 10 (53% versus 21%). PLMS indices were higher both in NREM and REM sleep in narcoleptic patients, but the between-group difference was greater for REM sleep. A significant increase of PLMS index was also found with aging in both narcoleptic patients and controls. PLMW indices were also significantly higher in narcoleptic patients. Patients with an elevated index of PLMS had a higher percentage of stage 1 sleep, a lower percentage of REM sleep, a lower REM efficiency and a shorter MSLT latency. The present study demonstrates a high frequency of PLMS and PLMW in narcolepsy, an association between the presence of PLMS and measures of REM sleep and daytime functioning disruption. These results suggest that PLMS represent an intrinsic feature of narcolepsy.     

The prevalence of restless sleep disorder among a clinical sample of children and adolescents referred to a sleep centre

Restless sleep disorder (RSD) is a newly described sleep disorder in children characterized by large body movements and repositioning that lasts all night with at least five body movements per hour and a significant impact on daytime behaviours. The authors have previously identified and described the syndrome and compared the sleep parameters and sleep‐related movements to those in children with restless legs syndrome, normal controls and snorers. The current study is a retrospective review of the sleep diagnosis in 300 consecutive children seen and evaluated in a single sleep disorders centre; 252 children underwent polysomnography, as clinically indicated, to identify the proper diagnosis. The current research estimates the prevalence of RSD in a sleep clinical setting to be 7.7% and compares it to the prevalence of other common sleep disorders in the same setting. Another important addition to the literature is the fact that RSD can coexist with other sleep disorders, such as habitual snoring and parasomnia, without confounding the diagnosis.     

Time structure analysis of leg movements during sleep in REM sleep behavior disorder

STUDY OBJECTIVES: To compare the time structure of leg movements (LM) during sleep of patients with rapid eye movement (REM) sleep behavior disorder (RBD) with that of patients with restless legs syndrome (RLS) or control subjects. DESIGN: The polysomnographically recorded tibialis anterior activity during sleep was analyzed by means of a new approach able to consider duration, intermovement interval, sleep stage and time of night distribution, and periodicity. PATIENTS AND PARTICIPANTS: Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. MEASUREMENTS AND RESULTS: Most patients with RBD (85%) presented periodic leg movements during sleep (PLMS). PLMS occurred more frequently during non-REM sleep in patients with RLS and during REM sleep in patients with RBD. PLMS were shorter in duration, less often bilateral, and with a higher intermovement interval in patients with RBD compared to those with RLS. The number of PLMS decreased across the night in patients with RBD and in those with RLS, but not in control subjects. In all subjects, LM periodicity clearly depended on sleep state, with higher values during non-REM than during REM sleep. Patients with RBD showed a lower LM periodicity, compared with patients with RLS, in each of the sleep states. CONCLUSIONS: Significant differences, together with some similarities in LM time structure, were observed between patients with RBD and those with RLS; for this reason, our approach seems to indicate that their phenotype might be dependent on 2 factors: disease and sleep stage.     

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.     

Sleep/wake abnormalities in patients with periodic leg movements during sleep: Factor analysis on data from 24-h ambulatory polygraphy

Periodic Leg Movements (PLM) in sleep occur in a wide variety of sleep/wake disorders but their relationship with sleep disturbance, and notably with the concomitant existence of a 'restless legs' syndrome (RLS) remains unclear. We performed 24-h ambulatory polygraphy in a population of 54 consecutive, unselected patients with PLMs (Coleman's index greater than 5/h) who complained of different sleep disorders. A Principal Component Analysis (PCA) was conducted on seven variables from the sample, namely PLM index, patient's age, sleep stage changes per hour, sleep depth index (SWS+PS/TST), diurnal sleep time, number of awakenings exceeding 2 min and presence of a RLS. PCA yielded four independent factors. The PLM index and the changes of sleep stage clustered in a single factor, linking therefore sleep fragmentation to the frequency of PLMs. The second factor appeared to reflect a circadian sleep/wake disorder, combining diurnal sleep time with the number of long night awakenings. The third factor was mainly loaded by the patients' age and the sleep depth index, thus reflecting a well known relationship. Finally, the variable reflecting the existence of a RLS appeared isolated in a single factor, independent from the three previously described. These results confirm and extend the link between PLMs and sleep fragmentation, as well as the recently described dissociation between PLMs and diurnal somnolence. On the other hand, our analysis suggests that in PLM patients the concomitant existence of a RLS is not related to the frequency of occurrence of PLMs, at least when these latter are quantified independently of their arousal index.     

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

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

Contactless detection of periodic leg movements during sleep: A 3D video pilot study

In clinical practice, the quality of polysomnographic recordings in children and patients with neurodegenerative diseases may be affected by sensor displacement and diminished total sleep time due to stress during the recording. In the present study, we investigated if contactless three‐dimensional (3D) detection of periodic leg movements during sleep was comparable to polysomnography. We prospectively studied a sleep laboratory cohort from two Austrian sleep laboratories. Periodic leg movements during sleep were classified according to the standards of the World Association of Sleep Medicine and served as ground truth. Leg movements including respiratory‐related events (A1) and excluding respiratory‐related events (A2 and A3) were presented as A1, A2 and A3. Three‐dimensional movement analysis was carried out using an algorithm developed by the Austrian Institute of Technology. Fifty‐two patients (22 female, mean age 52.2 ± 15.1 years) were included. Periodic leg movement during sleep indexes were significantly higher with 3D detection compared to polysomnography (33.3 [8.1–97.2] vs. 30.7 [2.9–91.9]: +9.1%, p = .0055/27.8 [4.5–86.2] vs. 24.2 [0.00–88.7]: +8.2%, p = .0154/31.8 [8.1–89.5] vs. 29.6 [2.4–91.1]: +8.9%, p = .0129). Contactless automatic 3D analysis has the potential to detect restlessness mirrored by periodic leg movements during sleep reliably and may especially be suited for children and the elderly.     

Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment

Periodic limb movements during sleep (PLMS) and obstructive sleep apnea syndrome (OSAS) are two common sleep disorders. The similarity in periodicity of periodic limb movements (PLMs) and obstructive sleep apneas (OSAs) led us to hypothesize the existence of a common central generator responsible for the periodicity of both OSAs and PLMs. In order to test this hypothesis, we compared apnea periodicity before continuous positive airway pressure (CPAP) treatment with PLMs periodicity during CPAP treatment in 26 OSA patients, consecutively recorded and treated in our sleep laboratory. The investigation on CPAP was performed twice, once during the initial evaluation and once during a follow-up evaluation after 3 months of home treatment with CPAP. Our results showed that, in this sample, 16 patients out of 26 had an association of OSAS and PLMS, defined as the occurrence of at least 5 PLMs per hour of sleep. The mean apnea interval - measured as the time between the beginning of two successive apneas - was 43.1 s (+/-15.2, SD) and the mean PLM interval - calculated in the same way - was 29.6 s (+/-15.2) during the baseline night, 28.5 s (+/-15.7) during the first CPAP night, and 29.8 s (+/-14.8) during the second CPAP night. Thus, the periodicity of the two phenomena (apneas and PLMs) was different, both before and after CPAP treatment (P< 0.05). When considering the interval between the end of an event (apnea or PLM) and the beginning of the next one the mean apnea interval was 19.5 s (+/-11. 6), and the mean PLM interval was 28.1 s (+/-15.3) during the untreated night, 26.6 s (+/-16) during the first CPAP night and 27.9 s (+/-15) during the second CPAP night. The shortening of apnea intervals with this method of measuring intervals reflects the longer duration of apneas as compared to PLMs. Again the intervals between PLMs were not different between each other but the intervals between apneas were different from the intervals between PLMs (P< 0. 05) These results show that the periodicity of PLMs is different from that of OSAs, suggesting that sleep apneas and PLMs are not generated by a common central generator.     

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

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

Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting-list haemodialysed patients. One hundred transplanted and 50 waiting-list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h(-1), respectively. The 10-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting-list group (P = 0.094); the proportion of severe disease was twice as high in waiting-list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10-year estimated risk of stroke in the transplanted group [10 (7-17) versus 5 (4-10); P = 0.002] and a higher 10-year coronary heart disease risk in both the transplanted [18 (8-22) versus 7 (4-14); P = 0.002], and the waiting-list groups [11 (5-18) versus 4 (1-9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting-list dialysis patients.     

Gender differences in clinical,laboratory and polysomnographic features of restless legs syndrome

Restless legs syndrome is a common neurological disorder with a clear female predominance. This study aims to evaluate gender differences in clinical, laboratory and polysomnographic features in patients with restless legs syndrome. For this retrospective analysis, 42 women and 42 men from the Innsbruck RLS database matched by age and therapy were included. Demographic data as well as different severity scales (IRLS, RLS‐6 and CGI) were evaluated. Laboratory parameters included several indicators of serum iron status. In all patients, polysomnography was performed according to the AASM guidelines, and periodic leg movements during sleep were scored according to the AASM criteria. IRLS, RLS‐6 and CGI revealed more severe symptoms in women (IRLS median [range]: 17.5 [0–35] versus 13.5 [0–32], p = 0.028; RLS‐6 median [range]: 18 [0–39] versus 12 [1–42], p = 0.014). Women had lower serum ferritin levels than men (median [range] in μg L^?1: 74 [9–346] versus 167 [15–389], p < 0.001). Twenty‐two women and eight men (53.7% versus 22.2%, p = 0.003) had ferritin values below 75 μg L^?1. Periodic leg movements during sleep indices were significantly lower in women than in men (median [range] in number per hr: 11.4 [0–62.5] versus 40 [0–154], p = 0.004, and 12.6 [0–58.5] versus 40 [0.5–208], p = 0.002, for night I and night II, respectively). Restless legs syndrome severity as measured by validated scales was worse in women, while periodic leg movements during sleep indices were higher in men. These results suggest a possible gender difference in phenotypical presentation of restless legs syndrome, manifesting with predominantly sensory symptoms in women and predominantly motor symptoms in men.     

Central respiratory pauses, sighs, and gross body movements during sleep in children

Sighs (SIs) and gross body movements (GMs) during sleep are common spontaneous, arousal behaviors during sleep. These physiological behaviors either precede or follow central respiratory pauses (CPs) during sleep in normal subjects. However, little attention has been paid to the temporal relationships between CPs and spontaneous behaviors except in early infancy. In the present study, the age- and state-related changes in the frequency and duration of apnea-behavior relationships were studied cross-sectionally in 19 healthy children aged between 3 months and 7 years of age. CPs, SIs, and GMs were assessed in a single all-night polysomnography and respiratory inductive plethysmography. We divided the data into two age groups: less and more than 15 months of age. The results showed that frequency of CPs > or = 10 s increased with age, while the frequency of GMs and SIs decreased. Isolated CPs appeared more frequently during rapid-eye-movement sleep (REMS) than during nonrapid-eye-movement sleep (NREMS). The frequency of both SIs and GMs that appeared after CPs was higher during REMS than during NREMS. The sum of CPs preceded by SI, and CPs preceded by GM accounted for about 75% of all central apnea events. These two events appeared more frequently during NREMS than during REMS and the duration of both events in NREMS increased significantly with age. During NREMS, few and delayed behaviors thought to restart respiration after CPs have been described. Future work should examine developmental differences in the occurrence of physiological behaviors in relation to CP in NREMS and REMS.     

Premenstrual dysphoric disorder amongst Nigerian university students: prevalence, comorbid conditions, and correlates

Summary Aims: The rate of premenstrual dysphoric disorder (PMDD) amongst sub-Saharan Africans is unknown. This study aimed to estimate the rate of PMDD amongst Nigerian undergraduates and to evaluate psychosocial correlates and comorbid psychiatric conditions. Method: Female university students (n = 410) completed questionnaires detailing sociodemographic, menstruation, and gynaecological history. They also completed the Big Five Personality Inventory (BFI), and the presence of PMDD and any other DSM-IV axis 1 psychiatric diagnosis was assessed with the Mini International Neuropsychiatric Interview (MINI). Results: The prevalence of PMDD was 6.1% and the correlates included older age (p = 0.001), painful menstruation (p = 0.006), and high score on neuroticism scale (p = 0.019). Compared with participants without PMDD, participants with PMDD have significantly higher rates for the following psychiatric diagnoses: dysthymia (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.68–8.69), major depressive disorder (OR, 17.00; 95% CI, 6.72–43.00), panic disorder (OR, 4.39; 95% CI, 1.35–14.30), and generalised anxiety disorder (OR, 1.21; 95% CI, 1.21–17.83). Conclusion: The rate of PMDD in sub-Saharan African women was comparable to that in the western cultures. Planning and implementing an effective strategy to manage perimenstrual problems in this region should be an issue of priority. Correspondence: A. O. Adewuya, Department of Psychiatry, Lagos State University College of Medicine, PMB 21266, Ikeja, Lagos State, Nigeria