SOMAS - an open-source software for the analysis of muscle activity during sleep.

Respiratory-related leg movements (RRLMs) may contribute to the cardiovascular risk associated with obstructive sleep apnea (OSA). Selective serotonin reuptake inhibitors (SSRIs), but not bupropion, increase periodic leg movements in sleep. This study examines whether patients with OSA using SSRIs have more RRLMs than those taking bupropion or no antidepressant. Patients with an apnea-hypopnea index (AHI) of at least 10 events/h during a full-night diagnostic study or split-night study, who were taking bupropion (n = 32), an SSRI (n = 31), or no antidepressant (n = 31), were selected from a database of prestudy questionnaires. RRLMs were scored according to World Association of Sleep Medicine 2016 standards. Patients using SSRIs had significantly greater overall RRLM% (defined as the percentage of respiratory events associated with a leg movement, including apneas, hypopneas, and respiratory effort-related arousals), RRLM index, and periodic limb movement index relative to patients using bupropion and control patients. The difference between the RRLM% in the SSRI and bupropion groups was limited to patients undergoing split-night studies, and that of the SSRI and control groups was limited to patients undergoing full-night diagnostic studies. The greater number of RRLMs and PLMs in the SSRI group may contribute to treatment-emergent insomnia often seen with SSRI use. Fragmented sleep and elevated autonomic nervous system activation associated with increased RRLMs in patients with OSA taking SSRIs might also limit the tolerability of antidepressant treatment, as well as increase the risk for cardiovascular disease.

To assess the performance of a new method for automatic detection of periodic leg movements during sleep. Leg movements during sleep were visually detected in the tibialis anterior muscles recordings of 15 patients with restless legs syndrome and 15 normal controls. Leg movements were detected automatically by means of a new computer method with which electromyogram signals are first digitally band-pass filtered and then rectified; subsequently, the detection of leg movements is performed by using 2 thresholds: one for the starting point and another to detect the end point of each leg movement. Sensitivity and false-positive rate were obtained; the American Sleep Disorders Association parameters were also computed, and the results analyzed by means of the Kendall W coefficient, the linear correlation coefficient and the Bland-Altman plots. N/A. Fifteen patients with restless legs syndrome and periodic leg movements and 15 controls. High values of the Kendall W coefficient of concordance between automatic and visual analysis were found with values close to 1 and the linear correlation coefficient for leg movements index and total leg movements index was > 0.950 (p < .000001). The Bland-Altman plots provided the limits of agreement between visual and computer detection, which were -9.01 and +9.89 for the periodic leg movement index. None of the normal controls was found to have periodic leg movement indexes >5 after automatic analysis. Our method can be applied to the clinical evaluation of periodic leg movements during sleep, with some caution in patients with a low periodic leg movement indexes. Large-scale research application is possible and can be considered as reliable.

Introduction Restless Legs Syndrome (RLS) and its associated motor manifestations, such as periodic leg movements during sleep (PLMS), exhibit significant sex-related differences in prevalence, progression, and treatment response. Epidemiological studies suggest a higher prevalence of RLS in women, but the underlying mechanisms remain unclear. This presentation combines two studies to explore: (1) sex differences in PLMS patterns across various age groups and hormonal stages, and (2) sex-specific responses to dopamine agonists (DA), pramipexole and ropinirole, in adult RLS patients. Methods In the first study, a retrospective analysis of 184 drug-free RLS patients (95 females, 89 males, ages 2–83 years) evaluated PLMS index and periodicity index via polysomnographic (PSG) recordings, stratified by age. The second study analyzed 41 drug-free adult RLS patients (26 treated with pramipexole, 15 with ropinirole) using baseline and post-treatment PSG. Treatment efficacy was assessed through changes in sleep parameters, movement indices, and a Visual Analogue Scale (VAS) for symptom severity. Results The first study revealed distinct age-related PLMS trends: women experienced a rapid PLMS increase before age 10, plateauing until menopause, followed by a sharp rise post-55 years. Men showed a more gradual PLMS increase, peaking after age 75. Periodicity index increased progressively in both sexes but remained slightly higher in women during midlife. These patterns aligned with hormonal shifts and autonomic nervous system modulation. In the second study, DA treatment reduced total leg movements, PLMS, and periodicity index in all patients, with greater reductions in women. Women exhibited higher sleep efficiency and lower wakefulness after sleep onset compared to men. The VAS scores improved across both sexes, though no sex differences were observed. Conclusion These findings underscore the complex interplay between sex, age, and neurophysiological factors in RLS. Hormonal changes and differential D3 receptor expression likely contribute to the observed disparities in PLMS progression and DA response. The results highlight the need for personalized, sex-specific approaches in RLS management, considering both lifespan dynamics and pharmacological nuances. Future guidelines should integrate these insights to optimize treatment efficacy and improve sleep outcomes for diverse demographic groups. Support (if any)

Sirs: The Restless Legs Syndrome (RLS) is characterized by a disagreeable sensation in the limbs and motor restlessness occurring at rest, especially in the evening and at night, which improves temporarily with activity [1]. More than 80 % of RLS patients have periodic legs movements (PLM) during sleep (PLMS) and wakefulness (PLMW) [2, 3]. D3-receptors nonergoline dopaminergic agents, such as pramipexole and ropirinole, are commonly used in RLS therapy, although detailed data on their effect on PLM are lacking. The aim of our study was to determine pramipexole efficacy on RLS symptoms and motor component by means of the Suggested Immobilization Test (SIT). Twenty-four never treated patients (mean age 62.4 ± 7.1 years; 13 females, 11 males) were selected according to the standard diagnostic criteria defined by the International RLS Study Group (IRLSSG) [2]. On the basis of the medical history, neurological examination, laboratory tests, electroneurography and F-wave, 20 patients were classified as having primary RLS, and 4 as secondary RLS (2 renal failure, 1 peripheral neuropathy, 1 paraneoplastic peripheral neuropathy). The initial dose of pramipexole was of 0.125 mg/d at 7 p. m., and it was increased every 3 days by 0.125 mg/d until a satisfactory control of symptoms was achieved or until side effects began to appear. At evaluation time therapy ranged from 0.25 to 0.50 mg/d. The subjective assessment of the global RLS severity was performed between 30 and 60 days (mean 39) after reaching the final dosage of pramipexole by using the IRLSSG Rating Scale [4]. This is a recently validated scale consisting in a clinician-administered questionnaire ranging from 0 to 40 points (1 to 10 points = mild, 11 to 20 points = moderate, 21 to 30 points = severe and 31 to 40 points = very severe). SIT was validated in 1998 as a polygraphic test able to identify and score PLMW [5]. During the test the patients were asked to sit at a 45-degree angle in bed with their legs outstretched, and were instructed not to move. Sleep was scored by a standard method; if any patient fell asleep he was awakened after 20 seconds of any stage of sleep [6]. Coleman’s criteria were used to score PLMW, whereas duration criterion was considered for any single movement that ranged from 0.5 to 10 seconds, because during wakefulness movements may often exceed 5 seconds [5, 7]. The following measures were made: Movement Index (MI = number of leg movements per hour of SIT), number of leg movements during the first 30 minutes of recording (MIF30), number of leg movements during the last 30 minutes of recording (MIL30), Lateralization Index (LI = left + right movements/MI), Mean Interval between Movements in seconds (MIM), Mean Duration of single movements in seconds (MD), the minute of appearance of first movement (Mst). According to Montplaisir et al. MI > 40 was considered abnormal [5]. Ten patients (mean age 61.2 ± 8.6 years; 5 females, 5 males) affected by primary RLS underwent SIT at baseline (without medication) and between 30 and 60 days (mean 46 days) after reaching the final dosage of pramipexole. Comparison between IRLSSG Rating Scale and SIT data, recorded before and after treatment, was made by using the paired-sample t-test. All 24 patients completed the study. The mean IRLSSG Rating Scale score was 22.6 (SD±6.3) at baseline, and significantly decreased to 11.3 (SD±6.5) between 30–60 days after therapy (Fig. 1). Moreover the mean MI also significantly decreased from 118.8 (SD±74.5) to 54.9 (SD±53.2). PLMW were most prevalent in the second half hour of SIT. Reduction in PLMW occurred mainly in the first 30 minutes (–55 %) as compared with the last 30 minutes (–47 %). Pramipexole significantly increased both the mean Mst and MIM, while MD and LI did not change with therapy (Tab. 1). Low doses of pramipexole have significantly improved the subjective symptoms of RLS. Patients reported that the improvement was achieved a few days after treatment, with a good compliance. Pramipexole also produced a significant reduction in PLMW, but LETTER TO THE EDITORS

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.

Diagnosis of restless leg syndrome (RLS) in Parkinson's disease (PD) is difficult because of clinical confounds. The suggested immobilization test (SIT) is validated for diagnosis of primary RLS. This study evaluated the usefulness of the SIT for diagnosis of RLS in PD. We compared SIT scores, as well as polysomnography measures in 50 patients with PD (25 with RLS, 25 without), 25 patients with primary RLS, and 25 age/sex matched controls. Mean leg discomfort score was increased in patients with PD and RLS compared to PD without RLS, and also in patients with primary RLS compared to controls. Leg discomfort was significantly higher at the end of the test in patients with RLS compared to patients without RLS. Intensity of leg discomfort was similar between patients with RLS, with or without PD. Using a mean leg discomfort cutoff of 11, we showed sensitivity of 91% and specificity of 72% for RLS diagnosis in PD during symptomatic time intervals. Periodic leg movements index during the SIT did not differ between groups. Periodic leg movements index during sleep and wakefulness was increased in patients with primary RLS compared to controls, but did not differ between patients with PD, with and without RLS. The sensory SIT is a simple test that may help diagnose RLS in patients with PD.

Correlates of PLMs variability over multiple nights and impact upon RLS diagnosis

To document the association between restless legs syndrome (RLS) and high ferritin levels in five patients. The five patients were male, mean age: 59 years (range: 36-73 years). The patients were referred for RLS (two of them blood donors), in two cases associated with obstructive sleep apnea. Patients underwent a video-PSG recording. Serum iron and serum ferritin were determined. All patients fulfilled the clinical criteria for RLS: leg paresthesias associated with an urge to move, motor restless-ness, worsening of symptoms during the evening and night, and partial relief with activity, difficulty falling asleep, and presence of nocturnal awakenings due to RLS. Neurological examination, EEGs, EMGs and MRIs were normal. Video-PSGs recordings showed a disturbed and fragmented sleep with a reduction in total sleep time, low sleep efficiency, respiratory abnormalities with an apnea-hipopnea index > 10/h in two cases, and in all of them a periodic leg movements index > 5/h. The serum iron levels were within the normal range in all cases, whereas those in serum ferritin levels were high. To our knowledge the association of normal serum iron with high serum ferritin levels in patients diagnosed clinically and polygraphically as having RLS with periodic leg movements has not been described before. The notion of an involvement of a dopaminergic mechanism in the pathophysiology of RLS is supported by the decrease in the values of serum ferritin concentration observed in one patient during follow-up while being treated with dopaminergic agents.

The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2–4 Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at −4~−3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.

To analyze periodic leg movements (PLM) during sleep in patients with narcolepsy and compare the results with those obtained in normal controls and subjects with restless legs syndrome (RLS). We recruited 40 HLA DQB1*0602-positive patients with narcolepsy/cataplexy, 22 with RLS, and 22 controls. The time structure of their polysomnographically recorded LMs was analyzed by means of an approach particularly able to consider their periodicity. Nineteen patients with narcolepsy had a PLM index greater than 15. The distribution of inter-LM intervals was clearly bimodal in RLS and narcoleptics, with 1 peak at 2 to 4 seconds and another at around 22 to 26 seconds; in the range 22 to 40 seconds, patients with RLS had values significantly higher than patients with narcolepsy. All periodicity parameters were significantly lower in the narcolepsy group. Finally, the distribution of the number of PLM per hour of sleep was bell shaped in normal controls and patients with narcolepsy, whereas patients with RLS showed a progressive decrease throughout the night. Most narcoleptic patients show a high number of LMs that are significantly less periodic than those of patients with RLS. PLM are in functional interrelationship with the cyclic alternating pattern, which is reduced in patients with narcolepsy; decreased arousal fluctuations during sleep may be one of the factors influencing the reduction in periodicity of LMs during sleep in narcolepsy.

To analyze cyclic alternating pattern (CAP) in restless legs syndrome (RLS) and the eventual changes induced by the acute administration of pramipexole. Sleep clinic in a scientific research institute. Placebo or pramipexole 0.25 mg. Thirty-four patients were included: 19 patients received 0.25 mg of pramipexole and 15 were given placebo. The control group included 13 normal subjects. Nocturnal polysomnography was carried out in all subjects, and a second night was recorded after pramipexole or placebo was administered to patients with RLS. Sleep stages, CAP, and leg movement activity were scored following standard criteria. At baseline, rapid eye movement sleep latency was significantly longer in patients with RLS than in normal control subjects, and the periodic leg movement during sleep index (PLMS) was also significantly higher. On the contrary, many CAP parameters appeared to be significantly different, with a general increase in CAP rate in patients with RLS. Acute administration of pramipexole induced moderate changes in sleep architecture (increased number of stage shifts/h, sleep efficiency, and percentage of stage 2 sleep; decreased wakefulness after sleep onset; and a lower PLMS index. No effects of treatment on CAP were observed. Patients with RLS show significant abnormalities in sleep microstructure, represented by an excessive sleep instability/discontinuity. Acute pramipexole administration seems to exert no action on these abnormalities; the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of presleep RLS symptoms and PLMS.

Background: Periodic leg movements (PLMs) are a disorder characterized by regularly recurring movements of the legs during sleep. It is unclear that PLMs contributes to poor prognosis in patients with cardiovascular disease (CVD) and sleep-disordered breathing (SDB). The aim of this observational study is to determine whether the presence of PLMs affect the long-term outcomes in the patients with CVD and SDB, treating with positive airway pressure (PAP) devices. Methods and results: We studied 181 SDB (apnea-hypopnea index [AHI] ≥15) patients with a history of hospitalization due to CVD, who diagnosed by overnight polysomnography and then treated with PAP devices for secondary prevention. The frequency of PLMs per hour of sleep was quantified as the PLM index (PLMI). Eighty five patients who could continue with PAP therapy were enrolled. They were classified into 2 groups; PLMs group (PLMI ≥30/h) and non-PLMs group (PLMI <30/h). The main outcome measures were cardiovascular death and hospitalization due to CVD during 24 months follow-up. A figure illustrates Kaplan-Meier curves. The hazard ratio was calculated using the Cox proportional hazard model. The univariate predictors of the main outcome were hemoglobin, estimated glomerular filtration rate, brain natriuretic peptide (BNP), left ventricular ejection fraction and PLMI ≥30/h. The multivariate analysis revealed that PLMI ≥30/h (HR, 3.19; 95% CI, 1.07-9.48; p=0.037) and BNP (HR, 1.002; 95% CI, 1.00-1.04; p=0.01) were significantly independent variables for cardiovascular events. ![Figure][1] Kaplan-Meier event free survival curves Conclusion: The PLMs affects long-term cardiovascular outcomes in patients with CVD and SDB, treating with PAP devices. [1]: pending:yes

Etiologies of Sleep-Related Movement Disorders (SRMD)

Restless legs syndrome (RLS), also referred to as a Willis-Ekbom disease (WED), is a neurological illness that equally affects women and men1. RLS is a set of sensory and motor symptoms that are triggered by rest (e.g. lying down or sitting), either when one is trying to go to sleep or during periods of peaceful wakefulness. The symptoms worsen in the evening and early hours of the night during the day or night cycle. RLS is still diagnosed clinically using subjective complaints. Thus, the subsequent four symptoms were created and determined as minimum criteria for RLS diagnosis by the IRLSSG2,3. In the general community, RLS affects 5% to 15% of people, yet it is commonly misdiagnosed and untreated. It is more common in women and rises with age. RLS may be primary (idiopathic) or secondary, and it may be linked to illnesses including end-stage renal disease, pregnancy, or iron-deficiency anemia1,4. Sleep initiation and maintenance were found to be severely impacted by unpleasant sensations in individuals with RLS5. Sleep disturbance is caused by PLMS, which can be found in eighty to ninety percent of RLS patients. A series of flexion movement at the ankle, knee, and hip is distinguished of PLMS (PLMS, periodic leg movements of Sleep) which are repetitive leg jerks. They happen while sleeping, especially in the first and second NREM phases, as well as while relaxing awake (PLMW, periodic leg movements during awake). PLMS has been related with cortical arousal and awaking, insomnia, and excessive drowsiness during day6. The prolonged recurrence of these symptoms severely reduced the sleep quality of people with RLS, perhaps leading to the onset of anxiety and depression7. Improper sleep cycles among RLS sufferers could affect their health, productivity, and social activities5. However irregular sleep patterns and sensory issues during the day may have an impact on ADLs, QoL and even cause cognitive impairment. RLS has been responsible for daytime exhaustion, excessive sleepiness, increased physical and mental health issues, and symptoms of anxiety and sadness6. DOI: https://doi.org/10.52783/jchr.v15.i6.10944

Gabapentin enacarbil XR is a new extended-release formulation which attempts to overcome the reduced efficacy of shorter-acting gabapentin, with sustained delivery over a 24-hour period. It is a gabapentin prodrug which is efficiently and rapidly converted to gabapentin during active transport throughout the length of the intestine via high-capacity monocarboxylate type 1 nutrient transporters unlike its predecessor, which is absorbed via low-capacity transporters largely confined to the upper intestinal region. Its lack of saturable absorption allows for dose-proportional absorption and hence increased bioavailability. Several clinical trials addressing its efficacy in moderate to severe restless legs syndrome (RLS) demonstrate improvements in the International RLS Rating Scale after a 2-week to 3-month period. Open-label studies of 52 weeks’ duration showed maintenance of symptom reduction with once-daily administration of the extended-release formulation. The most commonly reported treatment-emergent adverse effects were somnolence and dizziness. Although the incidence of emergent adverse effects is high, it is comparable with that of gabapentin. No studies thus far have documented augmentation as an issue, unlike that observed with most dopaminergic agents. In addition, both dopamine precursors and agonists have not been shown to increase slow wave sleep or improve overall sleep architecture consistently despite improvement in the periodic leg movement index, in contrast with gabapentin enacarbil. Presently, gabapentin enacarbil has not been approved by the Therapeutic Goods Administration or Medsafe for use in RLS. The cost of this medication may also be a potential barrier for many patients. Future comparative efficacy studies with gabapentin, first-line dopaminergic agents, rotigotine, being the other once daily RLS medication, and pregabalin, the structural analog of gabapentin, will be necessary.