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PurposeThis study investigated the basal autonomic regulation in patients with obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS) emerging after therapy with continuous positive airway pressure (CPAP).MethodsData of patients with OSA undergoing a first polysomnography for diagnosis and a second polysomnography for therapy with CPAP were reviewed. Patients with OSA showing PLMS on the first polysomnography were excluded. By using heart rate variability analysis, epochs without any sleep events and continuous effects from the second polysomnography were retrospectively analyzed.ResultsOf 125 eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not showing PLMS on both polysomnography (non-PLMS group) were randomly selected for the analysis. No significant differences in the demographic characteristics and variables of polysomnographies were identified between the groups. Although one trend of low root mean square of successive differences (RMSSD) between intervals of adjacent normal heart beats (NN intervals) in the PLMS group was observed, patients in the PLMS group had significantly low normalized high-frequency (n-HF) and high-frequency (HF) values, but high normalized low frequency (n-LF) and high ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS on the second polysomnography was significantly associated with RMSSD (β = − 6.7587, p = 0.0338), n-LF (β = 0.0907, p = 0.0148), n-HF (β = − 0.0895, p = 0.0163), log LF/HF ratio (β = 0.4923, p = 0.0090), and log HF (β = − 0.6134, p = 0.0199).ConclusionsPatients with OSA showing PLMS emerging after therapy with CPAP may have a basal sympathetic predominance with potential negative cardiovascular effects.

Introduction: This guideline establishes clinical practice recommendations for treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in adults and pediatric patients. Methods: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the grading of recommendations assessment, development, and evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. Good Practice Statement: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS: 1. In all patients with clinically significant RLS, clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity). Testing should ideally be administered in the morning avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw. Analysis of iron studies greatly influences the decision to use oral or intravenous (IV) iron treatment. Consensus guidelines, which have not been empirically tested, suggest that supplementation of iron in adults with RLS should be instituted with oral or IV iron if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20%, and only with IV iron if serum ferritin is between 75 and 100 ng/mL. In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations. These iron supplementation guidelines are different than for the general population. 2. The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, antidopaminergic medications, and untreated obstructive sleep apnea. 3. RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered. Recommendations: The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength (“strong” or “conditional”). A “strong” recommendation (ie, “We recommend…”) is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO (Patient, Intervention, Comparator, Outcome) question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation. Adults with RLS: 1. In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil (strong recommendation, moderate certainty of evidence) 2. In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin (strong recommendation, moderate certainty of evidence). 3. In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin (strong recommendation, moderate certainty of evidence). 4. In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status (see good practice statement for iron parameters) (strong recommendation, moderate certainty of evidence). 5. In adults with RLS, the AASM suggests the use of IV low molecular weight iron dextran over no IV low molecular weight iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence). 6. In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence). 7. In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, moderate certainty of evidence) 8. In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole (conditional recommendation, low certainty of evidence). 9. In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids (conditional recommendation, moderate certainty of evidence). 10. In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation (conditional recommendation, moderate certainty of evidence). 11. In adults with RLS, the AASM suggests against the standard use of levodopa (conditional recommendation, very low certainty of evidence). Remarks: levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 12. In adults with RLS, the AASM suggests against the standard use of pramipexole (conditional recommendation, moderate certainty of evidence). Remarks: pramipexole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 13. In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine (conditional recommendation, low certainty of evidence). Remarks: transdermal rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 14. In adults with RLS, the AASM suggests against the standard use of ropinirole (conditional recommendation, moderate certainty of evidence). Remarks: ropinirole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 15. In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS (conditional recommendation, moderate certainty of evidence). 16. In adults with RLS, the AASM suggests against the use of carbamazepine (conditional recommendation, low certainty of evidence). 17. In adults with RLS, the AASM suggests against the use of clonazepam (conditional recommendation, very low certainty of evidence). 18. In adults with RLS, the AASM suggests against the use of valerian (conditional recommendation, very low certainty of evidence). 19. In adults with RLS, the AASM suggests against the use of valproic acid (conditional recommendation, low certainty of evidence). 20. In adults with RLS, the AASM recommends against the use of cabergoline (strong recommendation, moderate certainty of evidence). Special adult populations with RLS: 21. In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin (conditional recommendation, very low certainty of evidence). 22. In adults with RLS and ESRD, the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% (conditional recommendation, moderate certainty of evidence). 23. In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C (conditional recommendation, low certainty of evidence). 24. In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa (conditional recommendation, low certainty of evidence). Remarks: levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 25. In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine (conditional recommendation, very low certainty of evidence). Remarks: rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). Adults with PLMD: 26. In adults with PLMD, the AASM suggests against the use of triazolam (conditional recommendation, very low certainty of evidence). 27. In adults with PLMD, the AASM suggests against the use of valproic acid (conditional recommendation, very low certainty of evidence). Children with RLS: 28. In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (conditional recommendation, very low certainty of evidence). Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025;21(1):137–152.

To describe the objective sleep of patients receiving chemotherapy for multiple myeloma (MM) prior to stem cell transplantation. A descriptive study with repeated measures. An international referral center in an urban area of the southern United States. A convenience sample of a subset of 12 patients with MM, recruited from a randomized, controlled trial. Objective sleep was assessed using two nights of polysomnography, one obtained before and one after a second cycle of high-dose chemotherapy prior to stem cell transplantation. Demographic and clinical data were obtained through a retrospective chart review. Objective sleep including sleep characteristics, sleep-related respiratory events, and periodic limb movements (PLMs) of sleep. Sleep was characterized by a relatively short sleep time, excessive time spent awake after the onset of sleep, and poor sleep efficiency (objective sleep quality). Patients spent more than the expected percent of time in non-rapid eye movement sleep and less in rapid eye movement sleep. Arterial oxyhemoglobin saturation nadirs reflected episodes of low arterial oxygen saturation. PLMs during sleep were in the mildly elevated range. Findings suggest that patients had poor sleep efficiency (objective sleep quality) and were slightly better sleepers after receiving a second cycle of high-dose chemotherapy. A number of patients also demonstrated obstructive sleep apnea and frequent PLMs. Findings support the need for additional investigation of sleep in patients with MM, particularly poor sleep efficiency and PLMs. Improving sleep may improve quality of life by decreasing associated symptoms such as pain, fatigue, and depression. Oncology nurses should consider assessing patients with MM for insomnia symptoms, excessive daytime sleepiness, obstructive sleep apnea, and a history of jerking or kicking their legs when asleep. Those symptoms may suggest the need for additional investigation of a possible sleep disorder, which may negatively influence mood and function.

Sleep-disordered breathing (SDB) is highly prevalent and accompanied by a considerable reduction in quality of life and an increase in cardiovascular morbidity and mortality. To diagnose SDB and to assess the localization of an airway obstruction, multichannel pressure measurements in the pharynx and esophagus have been used but are still under debate. Specifically, these devices are often labeled to be uncomfortable for patients and to influence the parameters of sleep recordings. The aims of the current study were to determine the tolerability of multilevel pressure measurement and to assess their impact on the parameters of polysomnography (PSG). Patients who were referred for two nights of standard PSG for diagnostic purposes were included. The device for multilevel pressure recordings was applied in addition to PSG on one of the two nights according to a randomization protocol. Tolerability of the device was assessed and the most relevant outcome measures of PSG were compared between the nights with and without the pressure sensor. All polysomnographic data were analyzed by the same trained observer who was blinded to the presence of the pressure catheter. Fifty-one patients were included in the trial. Ten of the patients tolerated insertion of the pressure catheter but complained about persisting discomfort during the night, requiring removal of the device. Forty-one patients tolerated the multilevel pressure transducer, which is equivalent to a tolerability of 80 %. The results of the sleep parameters are based on the data of 31 patients. The pressure device minimally influenced the outcome data of the PSG. None of the recorded differences however were clinically relevant or statistically significant. Pressure measurements with devices of small diameter (≈2 mm) are well accepted by patients and have a tolerability of at least 80 %. The impact of multilevel pressure recordings on objective sleep parameters is negligible. The study strongly supports the use of multilevel pressure recordings and disproves the most relevant objections against their use.

Study Objectives: The aim of this study was to describe the clinical and polysomnographic characteristics of patients with high frequency leg movements (HFLM) on polysomnographic recording. Methods: Among 486 patients (male 232, female 254) referred for overnight diagnostic PSG over a 9-month period, 37 patients demonstrated HFLM: 19 males (8.2% of PSGs) and 18 females (7.1% of PSGs). An equal number of age- and sex-matched consecutive patients who did not show HFLM were selected. HFLM was defined as ≥ 4 discrete leg movements occurring at a frequency of 0.3–4.0 Hz. Results: Two-thirds (64.3%) of all HFLMs occurred during waking; 35.7% occurred during sleep. Of those HFLM episodes occurring during sleep, 44.8% occurred during stage 1, 45.1% during stage 2, 0.6% during stages 3 and 4, and 9.5% during REM. The movements usually appeared unilaterally, but sometimes they showed a bilateral pattern. The mean frequency was 1.6 ± 0.6 Hz (range 0.4–3.7), the mean number of episodes of HFLM per subject per night was 26.5 ± 30.5 (range 2–111), and the mean duration per episode was 17.6 ± 35.4 sec (range 1.5 sec-6.1 minutes). The mean HFLM index, (total number of HFLM divided by the time in bed, in hours), was 107.7 ± 254.5 (range 2.0–1078.3). Patients with HFLM complained of RLS symptoms significantly more often than the group without HFLM (p < 0.05). Conclusion: Further studies are needed to establish criteria for scoring HFLM. Examination of other patient cohorts with HFLM will be needed to determine whether HFLM are in fact associated with RLS. Citation: Yang C; Winkelman JW. Clinical and polysomnographic characteristics of high frequency leg movements. J Clin Sleep Med 2010;6(5):431–438.

Introduction: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome and periodic limb movement disorder. Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat restless legs syndrome and periodic limb movement disorder in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations. Results: The literature search resulted in 3,631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med . 2025;21(1):153–199.

Abstract Restless sleep disorder (RSD) is a newly defined sleep-related movement disorder characterized by large muscle movements (LMM) in sleep. We examined the sleep study, clinical characteristics, and daytime functioning in children with RSD and compared them to children with periodic limb movement disorder (PLMD) or restless legs syndrome (RLS). Video polysomnography from 47 children with restless sleep was retrospectively reviewed for LMM and age- and sex-matched to 34 children with PLMD and 12 children with RLS. Data examined included PSG characteristics, ferritin, Pediatric Quality of Life (PedsQL), and Epworth Sleepiness Scale (ESS). Fourteen children met the clinical criteria for RSD with an LMM index of 5 or more per hour of sleep. Mean ESS was elevated in patients with RSD compared to either the PLMD or RLS groups though the result did not reach statistical significance (RSD = 10.20 ± 6.81, PLMD = 6.19 ± 4.14, RLS = 6.25 ± 4.90). The PedsQL score was significantly decreased in the RLS group compared to RSD and was reduced overall in all three groups (PedsQL Total RSD = 70.76 ± 18.05, PLMD = 57.05 ± 20.33, RLS = 53.24 ± 16.97). Serum ferritin values were similar in all three groups (RSD = 26.89 ± 10.29, PLMD = 33.91 ± 20.31, RLS = 23.69 ± 12.94 ng/mL, p = ns). Children with RSD demonstrate increased daytime sleepiness compared to PLMD or RLS and all three disease groups showed decreased quality of life. Further studies are needed to examine long-term consequences of RSD.

Abstract Study Objectives: To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Aims and Methods: Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Results: Patients were 15 men and 2 women with a median age of 66 (range: 48–77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Conclusions: Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and identified prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors.

Abstract Study Objectives: To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men. Methods: We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition. Results: After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test – Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05–2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores. Conclusions: Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function.

Abstract Study Objectives Little is known about comorbidities in children who have elevated periodic limb movement index (PLMI) during overnight polysomnogram (PSG). The aim of this study is to identify comorbidities in children with elevated PLMI (PLMI > 5) versus children with PLMI < 5 presenting to a pediatric sleep center. Methods This study was a retrospective review of all clinically indicated PSGs obtained consecutively from 3/2017-3/2019 at Seattle Children’s Sleep Disorders Center. Data collected included demographics, clinical presentation, medications, medical history, family history specifically for restless legs syndrome (RLS), ferritin levels, and PSG metrics. Characteristics between those with (cases) elevated PLMI (AASM criteria) and without (controls) were summarized. Results We identified 148 subjects with elevated PLMI (67% male, mean age 7.95 years, range 1–20), yielding a PLMI > 5 prevalence of 5%. There were 188 controls included (58% male, mean age 8.0 years, range 1–19). Neither sex (chi-square = 2.8, NS) nor age (Mann–Whitney U = 1339.5, NS) differed between groups. Case subjects had a higher prevalence of RLS, snoring, insomnia, mood disorders, behavioral problems, morning headaches, chronic kidney disease, epilepsy, and chronic heart disease. Similarly, the use of antidepressants, antipsychotics, antiseizure medication, and other medications was statistically more frequent in children with elevated PLMS. The prevalence of PLMI > 5 was 5% and the prevalence of periodic limb movement disorder (PLMD) was 0.3% in children referred to polysomnography. Ferritin levels did not differ. Conclusions We identified the prevalence of PLMD in a sleep medicine–referred population. We have also identified comorbidities and medications associated with elevated PLMI in children. No clinical trial