Hyperhidrosis in sleep disorders - A narrative review of mechanisms and clinical significance.

Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.

Stroke-related restless legs syndrome: Clinical and anatomo-functional characterization of an emerging entity.

BACKGROUND AND PURPOSE: Stroke-related restless legs syndrome (sRLS) secondary to ischemic lesions is an emerging entity and an interesting condition, but there are limited available data to help us further understand its underlying pathways. In this study, we characterized sRLS clinically, neuroanatomically and functionally. METHODS: Consecutive patients hospitalized in the Stroke Unit of the University Hospital of Strasbourg were assessed clinically and electrophysiologically for sRLS characteristics. They underwent brain magnetic resonance imaging for the neuroanatomical study of involved structures, and received functional evaluations with 18 F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography (PET) for glucose consumption, 123 I-FP-CIT ([123]I-2beta-carbometoxy-3beta-[4-iodophenyl]-N-[3-fluoropropyl]nortropane) single-photon emission computed tomography for dopamine reuptake and PET with 18 F-FDOPA ((3,4-dihydroxy-6-[18]F-fluoro-l-phenylalanine) for presynaptic dopaminergic synthesis. RESULTS: Sixteen patients with sRLS, eight women and eight men, aged 41-81 years, were included. The clinical characteristics of sRLS and idiopathic RLS were similar. Most patients presented with bilateral and symmetric de novo RLS. Eight patients had infarction in the lenticulostriate area (middle cerebral artery and internal carotid arteria). The body of the caudate nucleus was most commonly affected. Seven patients had sRLS secondary to ventral brainstem infarction (perforating branches of the basilar arteria) affecting the pons in six patients and the medulla oblongata in one patient. Both the corticospinal tract and the cortico-pontocerebellar fibres were lesioned in all patients with brainstem stroke. One patient had infarction in the left posterior cerebellar vermis and occipital area (posterior cerebral artery and superior cerebellar artery). Isotopic explorations showed a significantly increased dopaminergic tone in the striatum ipsilateral to lenticulostriate infarction. Dopamine fixation was normal in patients with stroke outside of the lenticulostriate area. CONCLUSIONS: Clinicians should be aware of the characteristics of sRLS for the appropriate diagnosis and treatment of this condition.

Migraine and sleep disorders: a systematic review.

Migraine and sleep disorders are common and often burdensome chronic conditions with a high prevalence in the general population, and with considerable socio-economic impact and costs.The existence of a relationship between migraine and sleep disorders has been recognized from centuries by clinicians and epidemiological studies. Nevertheless, the exact nature of this association, the underlying mechanisms and interactions are complex and not completely understood. Recent biochemical and functional imaging studies identified central nervous system structures and neurotransmitters involved in the pathophysiology of migraine and also important for the regulation of normal sleep architecture, suggesting a possible causative role, in the pathogenesis of both disorders, of a dysregulation in these common nervous system pathways.This systematic review summarizes the existing data on migraine and sleep disorders with the aim to evaluate the existence of a causal relationship and to assess the presence of influencing factors. The identification of specific sleep disorders associated with migraine should induce clinicians to systematically assess their presence in migraine patients and to adopt combined treatment strategies.

Drug-Induced Restless Legs Syndrome.

OBJECTIVE: To review the literature on drug-induced restless legs syndrome (DI-RLS). DATA SOURCES: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. RESULTS: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. CONCLUSIONS: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

Validation of a non-contact screening device for the combination of sleep-disordered breathing and periodic limb movements in sleep.

PURPOSE: Recent studies found that the non-contact screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of this disorder. However, it was reported that in patients with periodic limb movement in sleep (PLMS), this non-contact device overestimates the apnea-hypopnea index (AHI). We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is sum of the AHI and the period limb movement index (PLMI). METHODS: Between January 2011 and December 2013, we studied a mixed cohort of 57 patients (31 OSA, 19 PLMS). The easy-to-use non-contact device emits a very weak electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of the gold-standard polysomnography (PSG). RESULTS: We found that the SDI of the non-contact device correlated well with the sum of AHI and PLMI derived from PSG (r = 0.79, p = 0.01). For PSG-derived SDI cutoff ≥ 15/h, we obtained a sensitivity of 92.2% and a specificity of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio 0.03. CONCLUSIONS: The studied non-contact screening device detects accurately the combination of the sleep disorders SDB and/or PLM. However, further testing is required in order to specify the nature of the underlying sleep disorder. At the current stage of algorithm development, the clinical strength is that the studied non-contact device can be used as a rule-out screening device for SDB and PLM.

French Consensus: How to diagnose restless legs syndrome.

Correct diagnosis of restless legs syndrome (RLS) is essential to patient care and treatment. Diagnosis is most often clinical and based on diagnostic criteria: the need to move the legs accompanied to varying degrees by unpleasant sensations, predominantly during the evening and improved by movement. In rare cases, clinical examination is insufficient and a polysomnography is necessary. Once a positive diagnosis has been made, a neurological examination and an assessment of iron status are required. The severity of the RLS must be evaluated to determine whether a specific treatment is necessary. Before treatment, it is essential to ensure that a definite diagnosis of RLS has been made and the phenotype characterised. This enables a personal treatment plan and limits the risk of augmentation syndrome.

Periodic limb movement in sleep and sickle cell disease: a neglected association?

High frequency of periodic limb movements in sleep (PLMS) has been described among children with sickle cell disease (SCD), but there is little information about PLMS among adults with SCD. We aim to determine the frequency of PLMS among adults with SCD and to identify possible associations with iron status and haemolytic parameters. We analysed polysomnography on 99 adults: 74 with sickle cell anaemia (HbSS), 19 with HbSC (double heterozygosis HbS and HbC) and 6 with HbS-beta thalassaemia. Laboratory data were collected close to the time of the polysomnography examination. The prevalence of PLMS > 5/h was 70% and of PLMS > 15/h 36%, in the total group of patients. No differences were observed regarding gender, use of hydroxyurea and iron parameters. Logistic regression showed an association between PLMS > 15/h and hemolytic parameters: absolute reticulocyte count (p = 0.03) and unconjugated bilirubin (p = 0.01). Our data suggest that PLMS may be associated with manifestations of greater severity in SCD.

Clinical management of restless legs syndrome in end-stage renal disease patients.

Restless legs syndrome (RLS) is a common neurological movement disorder, characterized by restless and unpleasant sensations in the deep inside of legs. The symptoms of RLS are less noticeable during daytime, but more prevalent at night. Therefore, the disorder can induce low quality of life, insomnia, and impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is especially problematic due to premature discontinuation of dialysis and increased mortality. The prevalence of RLS among dialysis patients is much higher compared to the prevalence of the same disorder in patients with normal renal functions. Even though there are recommended treatment guidelines for the general population established by Medical Advisory Board of the RLS foundation, which include the use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids, limited information is available on the effects of these therapies in ESRD patients. Since the existing clinical data were extrapolated from small sample sizes in short-term clinical trials, further clinical studies are still needed to better assess the efficacy, safety, and tolerability of these medications in patients with ESRD.

Restless Legs Syndrome: clinical features, diagnosis and a practical approach to management.

Restless legs syndrome (RLS) is a chronic neurological disorder that interferes with rest and sleep. It has a wide spectrum of symptom severity, and treatment is started when symptoms become bothersome. Dopamine agonists and calcium channel apha-2-delta antagonists (gabapentin, gabapentin enacarbil and pregabalin) are first-line treatments; calcium channel alpha-2-deltas are preferred over dopamine agonists because they give less augmentation, a condition with symptom onset earlier in the day and intensification of RLS symptoms. Dopamine agonists can still be used as first-line therapy, but the dose should be kept as low as possible. Iron supplements are started when the serum ferritin concentration is ≤75 µg/L, or if the transferrin saturation is less than 20%. For severe or resistant RLS, a combined treatment approach can be effective. Augmentation can be very challenging to treat and lacks evidenced-based guidelines.

Rotigotine in Hemodialysis-Associated Restless Legs Syndrome: A Randomized Controlled Trial.

BACKGROUND: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. STUDY DESIGN: Double-blind placebo-controlled study. SETTING & PARTICIPANTS: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] ≥ 15) and Periodic Limb Movement Index (PLMI) ≥ 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. INTERVENTION: Following randomization and titration (≤21 + 3 days) to optimal-dose rotigotine (1-3mg/24 h) or placebo, patients entered a 2-week maintenance period. Polysomnography was performed at baseline and the end of maintenance. OUTCOMES & MEASUREMENTS: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. RESULTS: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7±0.4 for rotigotine and 1.3±0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P=0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P=0.05] and -0.81 [95% CI, -1.94 to 0.33; P=0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (≥50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (≥2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). LIMITATIONS: Small sample size and short duration. CONCLUSIONS: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients.

Restless Legs Syndrome and Depression: Effect Mediation by Disturbed Sleep and Periodic Limb Movements.

OBJECTIVE: To investigate an association between restless legs syndrome (RLS) and depression and to what extent sleep disturbance, periodic limb movements during sleep (PLMS), and antidepressant medication mediate this relationship. METHODS: A cross-sectional analysis was conducted of the Osteoporotic Fractures in Older Men Study data in 982 men assessed for RLS (International RLS Study Group scale [IRLSS]) and depression (Geriatric Depression Scale [GDS]), who underwent actigraphy (for sleep latency/efficiency) and polysomnography (for PLMS). Men were split into three groups: no RLS (N = 815), mild RLS (IRLSS ≤ 12, N = 85), moderate-to-severe RLS (IRLSS > 12, N = 82). Depression was defined as GDS score ≥ 6. Logistic and linear regression assessed associations of RLS and depression or number depressive symptoms, respectively. Models were adjusted for age, site, race, education, body mass index, personal habits, benzodiazepine/dopaminergic medication, physical activity, cardiovascular risk factors, and apnea-hypopnea index. RESULTS: Of 982 men, 167 (17.0%) had RLS. Depression was significantly associated with moderate-to-severe RLS after adjustment (versus no RLS: OR [95% CI] 2.85 [1.23, 6.64]). Further adjustment for potential mediators attenuated effect size modestly, most for sleep efficiency (OR: 2.85-2.55). Compared with no RLS, moderate-to-severe RLS was associated with the number of depressive symptoms after adjustment (adjusted means [95% CI]; no RLS: 1.14 [1.05, 1.24] versus IRLSS > 12: 1.69 [1.32, 2.11]). Further adjustment for potential mediators did not alter effect size. For men with PLMS index at least median, number of depressive symptoms significantly increased as RLS category became more severe. CONCLUSION: Depression is more common as RLS severity worsens. The RLS-depression relationship is modestly explained by sleep disturbance and PLMS.

Scaling exponent values as an ordinary function of the ratio of very low frequency to high frequency powers in heart rate variability over various sleep stages.

PURPOSE: To assess the physiological meanings of the detrended fluctuation analysis (DFA) slope α and its relationship to spectral measures in heart rate variability, this study investigated changes of α and its corresponding spectral measures over various night-sleep stages. METHODS: The overall DFA α and natural-logarithm-transformed power values of the spectral parameters ln[high-frequency (HF)], ln[low-frequency (LF)], and ln[very-low-frequency (VLF)], and their relationship from one 5-min proper electrocardiography segment in each of pre-sleep-wakefulness (AWK), non-rapid eye movement stage 2 (N2), slow-wave (N3), the first and the latest rapid-eye movement sleep (REM1, and REM2), were computed in 93 otherwise healthy males (44.1 ± 7.7 years.) with wide-ranged apnea-hypopnea, periodic-limb movement and arousal indices (19.0 ± 20.9, 4.7 ± 9.9, and 10.7 ± 18.2 h, respectively). RESULTS: While ln(HF) dipped from AWK, N2, and N3 to REM1 then rebounded to the origin level at REM2, ln(VLF) dipped from AWK to N2, N3 trough, and then surged to levels surpassing AWKs and N2s at REM1 and REM2. ln(LF/HF), ln(VLF/HF), and α dipped from AWK and N2 to N3 trough, surged to levels surpassing AWKs, and N2s at REM1 then became attenuated at REM2. By general linear modeling, the relationship between α and the corresponding spectral values can be seen over various stages as α = b 0 + 0.147 × ln(VLF/HF) (R (2) = 0.766), regardless of age and sleep-sympathoexcitatory episodes. CONCLUSION: The REM sleep attenuations appeared in ln(HF) and its derivatives, such as ln(LF/HF), ln(VLF/HF), and the overall DFA slope α values. The quantitative function of ln(VLF/HF) describes the α values constantly for overnight sleep stages, and it is not affected by age, LF, PLM, and AHI. Our findings therefore suggest that in sleep studies with spectral HRV measures, ln(VLF/HF) as a surrogate of the overall DFA slope α should be calculated at the same time.

The effect of memantine on sleep architecture and psychiatric symptoms in patients with Alzheimer's disease.

OBJECTIVE: Behavioural and psychological symptoms of dementia (BPSD) are commonly present in patients with Alzheimer's disease (AD). Disturbed sleep quality is also observed in AD patients. However, the effects of memantine on sleep architecture have not been investigated. The purpose of this study was to investigate the effects of memantine on polysomnography (PSG) variables and BPSD. METHODS: In total, 12 patients with AD (mean age: 79.0±4.1 years old) were enrolled in this study. The following tests were performed: the Neuropsychiatric Inventory for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, and PSG for evaluation of sleep architecture. After baseline examinations, patients were treated with memantine according to a standard prescription protocol. After being treated with 20 mg/day of memantine for 4 weeks, examinations were carried out again. RESULTS: All subjects completed the trial. The mean MMSE and NPI scores were 22.6±3.4 and 13.8±12.9, respectively. Treatment with memantine significantly decreased the NPI score (5.8±4.3, p<0.01). There were significant decreases in the scores of subscales for anxiety (p=0.04) and irritability/lability (p=0.04). PSG demonstrated a longer total sleep time (TST) (p<0.01), increases in sleep efficiency (p<0.01) and time spent in stage II (% TST, p=0.02), and decreases in nocturnal awakening (p<0.01), the periodic limb movement index (p<0.01), and time spent in stage I (% TST, p=0.02). CONCLUSION: Memantine was effective for reducing fragmented sleep and improving BPSD, and was well tolerated.

Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

INTRODUCTION: Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. METHODS: A retrospective chart review of sleep studies was conducted in children aged 1-18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. RESULTS: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27-34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8-4.5) groups. CONCLUSIONS: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

Periodic limb movements in patients with suspected obstructive sleep apnea without comorbid conditions.

Background: Periodic limb movement disorder (PLMD) and obstructive sleep apnea (OSA) are overlapping clinical syndromes with common risk factors. However, current literature has failed to establish a clear pathophysiological link between them. Thus, little is known about periodic limb movements (PLM) in otherwise healthy patients with suspected OSA. Methods: We performed a retrospective analysis of 112 patients (age: 44.5 ± 12.0 years, 14.3% female) with suspected OSA who underwent full night polysomnography for the first time. Patients with chronic diseases of any kind, recent infections, malignancies, or daily or regular use of any type of medication were excluded. Group comparisons were made based on the severity of OSA (using the apnea hypopnea index, AHI) or the periodic limb movement index (PLMI). Results: Both, PLMI and the total number of periodic limb movements during sleep (PLMS), showed a significant increase in patients with severe OSA. In addition, AHI and apnea index (AI) were significantly higher in patients with PLMI >15/h, with a similar trend for hypopnea index (HI) (p < 0.001, p < 0.001, and p > 0.05, respectively). PLMI was significantly positive correlated with AHI, AI, and HI (r = 0.392, p < 0.001; r = 0.361, p < 0.001; and r = 0.212, p < 0.05, respectively). Patients with PLMI >15/h were significantly older (p < 0.001). There was no significant association between body mass index (BMI) and PLMI >15/h. Conclusion: We found a significant association between the severity of OSA and PLM in our study population with suspected OSA but without other comorbidities. PLMI and PLMS were significantly increased in patients with severe OSA. Future prospective studies with larger collectives should verify the presented results and should include mechanistic aspects in their evaluation.

Coexistence of periodic limb movements during sleep with restless legs syndrome and its association with hypertension in Japanese patients.

BACKGROUND: Caucasian patients with restless legs syndrome (RLS) frequently exhibit periodic limb movements during sleep (PLMS), which may increase the risk of hypertension. We evaluated the positivity rate of PLMS and factors associated with positivity in Japanese patients with RLS, and tested whether the complications of PLMS are associated with the presence of hypertension. METHODS: We retrospectively investigated polysomnographic data and the presence or absence of hypertension in patients with RLS. Patients with systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or those taking antihypertensive medication were categorized as the group with hypertension. RESULTS: Among 468 patients, 200 (42.7%) had periodic limb movement index (PLMI) values ≥ 15/h and 108 (23.1%) met the criteria of positivity for hypertension. Multiple logistic regression analysis revealed that only higher age was significantly associated with PLMI values ≥ 15/h. Multiple linear regression analyses of factors associated with an increased PLMI also showed that increased PLMI was significantly correlated with higher age and male sex, but not with the international restless legs scale scores. Multiple logistic regression analysis also revealed that higher age and body mass index, not PLMI values ≥ 15/h, were significantly associated with the presence of hypertension. CONCLUSION: The PLMS-positivity rate may be lower in Japanese patients with RLS than in Caucasian patients, and it increases with age and male sex, but not with the severity of the disorder. Furthermore, PLMS complications were not associated with the risk of hypertension in Japanese patients with RLS.

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). 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 RLS and PLMD in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 3631 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.

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline.

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 (GRADE) 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, TIBC). The test 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 ng/mL 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, anti-dopaminergic medications, and untreated obstructive sleep apnea (OSA).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 (i.e., "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 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 (LMW) iron dextran over no IV LMW iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence).6. Recommendation 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, low 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, 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).

Too little or too much nocturnal movements in Parkinson's disease: A practical guide to managing the unseen.

Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.

Periodic limb movement disorder in children: A systematic review.

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