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.

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.

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.

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.

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).

Positional Obstructive Sleep Apnea and Periodic Limb Movements During Sleep: A Large Multicenter Study.

OBJECTIVES: The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movements during sleep (PLMS) remain unclear. We investigated these relationships with respect to the severity of OSA and explored the underlying mechanisms. METHODS: We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography at four clinical centers over a 5-year period, utilizing event-synchronized analysis. We evaluated the periodic limb movement index (PLMI) and the periodic limb movement with arousal index (PLMAI). The impacts of POSA on the PLMI, PLMAI, and PLMS were analyzed in relation to the severity of OSA. RESULTS: The mean PLMI, the mean PLMAI, and the prevalence of PLMS were significantly lower in participants with severe OSA compared to the mild and moderate OSA groups. The mean PLMI among those with mild OSA exceeded that of control participants. Furthermore, the mean PLMI (4.8±12.7 vs. 2.6±9.8 events/hr, P<0.001), the mean PLMAI (0.9±3.7 vs. 0.5±3.3 events/hr, P<0.001), and the prevalence of PLMS (11% vs. 5.3%, P<0.001) were higher in patients with POSA than in those with non-positional OSA. This PLMS finding was particularly pronounced among those with severe OSA (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.065-2.267) and was less evident in the mild (OR, 0.559; 95% CI, 0.303-1.030) and moderate (OR, 1.822; 95% CI, 0.995-3.339) groups. CONCLUSION: Patients with POSA, especially those with severe OSA, exhibit a comparatively high prevalence of PLMS. In cases involving prominent PLMS, the diagnosis and treatment of POSA and OSA should be considered.

Gabapentinoid Prescribing Practices at a Large Academic Medical Center.

Objective: To evaluate indications for gabapentinoid prescription at an academic medical center. Patients and Methods: We retrospectively reviewed patients aged 18 years or older who were prescribed gabapentinoids (gabapentin or pregabalin) during the 2019 calendar year at an academic medical center in the US Midwest. Patient demographic characteristics, indications for gabapentinoid prescription, and prescribing clinician specialities were abstracted from a random sample, and the findings were extrapolated to the overall cohort. Results: A total of 6205 prescriptions for gabapentinoids were initially identified. In the random sample of prescriptions (n=721), 89.5% were for gabapentin and 10.5% were for pregabalin. More women than men were prescribed gabapentinoids, and the mean ± SD patient age was 58.6±16.9 years. The top 5 indications for gabapentinoid prescriptions were neuropathic pain, musculoskeletal pain, restless legs syndrome, anxiety, and headache. A majority (66.7%) of prescriptions had substantial-to-modest evidence, but 29.0% of prescriptions had conflicting or insufficient evidence. Conclusion: To our knowledge, this study is one of the first to manually review clinical notes from multiple clinical specialities to ascertain indications for gabapentinoid prescriptions. Although most prescriptions had modest evidence to support their use, a high percentage of gabapentinoid prescriptions were issued for indications not supported by robust evidence. This suggests that prescribers are gravitating toward gabapentinoid use for reasons that are currently not fully understood. Clinician intent for off-label gabapentinoid prescriptions at the point of care should be further studied to understand the factors that lead to these clinical decisions.

[Periodic limb movements in sleep and cerebral small vessel disease progression: a prospective cohort study]. / Periodicheskie dvizheniya konechnostei vo sne i progressirovanie tserebral'noi mikroangiopatii: prospektivnoe kogortnoe issledovanie.

OBJECTIVE: To determine the predictive role of periodic limb movements in sleep (PLMS) in cerebral small vessel disease (cSVD) progression rate. MATERIAL AND METHODS: Fifty patients with cSVD, aged 60-75 y.o., were enrolled. The study protocol included MRI assessment of white matter hyperintensities (WMH), nocturnal actigraphy and cognitive assessment. Depending on the PLMS, the main (PLM index ≥15) and the control (PLM index <15) groups were formed. The second visit was carried out in one year follow-up period, the examination consisted of brain MRI and cognitive assessment under the same protocol. ANCOVA was performed to determine if PLMS influence the degree of MRI- and neuropsychological changes. RESULTS: A significant effect of PLMS on the increase in the volume of WMH was revealed, both in the form of an increase in the index by more than 15 movements per hour (p=0.03), and quantitatively in the form of a connection with the index value (p=0.048). The influence of PLMS on the progression of cognitive dysfunction has not been found, however, it has been shown that the presence of PLMS is associated with lesions in the deep white matter (r=0.42, p<0.0001), and the results of neuropsychological tests are associated with lesions in the periventricular and juxtacortical WMH (p < 0.05 for each test). CONCLUSION: PLMS predict WMH progression in cSVD.

A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia.

Mirtazapine is a Food and Drug Administration-approved atypical antidepressant used off-label for insomnia. Mirtazapine has been associated with movement disorders in adults. A 9-year-old female was seen in the sleep clinic for symptoms of insomnia, nocturnal awakenings, restless sleep, and growing pains. Mirtazapine was started prior to presentation for severe insomnia. A sleep study showed frequent repetitive leg movements prior to sleep onset as well as significant periodic limb movement disorder with a periodic limb movement index of 25.1/hour. The child was found to have a ferritin level of 23 ng/mL and an iron saturation of 10%. There were concerns that the presence of iron deficiency along with the use of mirtazapine may have contributed to the elevated periodic limb movement index. After starting iron therapy to treat the child's iron deficiency, mirtazapine was weaned off, with further clinical improvements in sleep quality reported. A follow-up sleep study showed a resolution of her periodic limb movement disorder with a periodic limb movement index of 1.4/hour. This is the first pediatric case to describe a sleep-related movement disorder associated with the use of mirtazapine and polysomnographic data to support resolution after discontinuation of mirtazapine along with iron therapy. CITATION: Hawkins M. A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia. J Clin Sleep Med. 2023;19(7):1369-1373.

[Abnormal nocturnal behavior mimicking REM sleep behavior disorder episodes in a patient with periodic limb movement disorder].

Periodic limb movement disorder (PLMD) is a condition in which patients experience frequent periodic limb movements of sleep (PLMS). Synchronized arousal responses cause sleep fragmentation, resulting in insomnia, daytime sleepiness, and fatigue. A 59-year-old man was identified as having intense sleep-talking and body movements, suggesting rapid eye movement (REM) sleep behavior disorder (RBD). Attended video-polysomnography (PSG) revealed that sleep-talking and body movements occurred only during non-REM sleep and were associated with PLMS-induced arousals (periodic leg movement arousal index, 53.2/h). Pramipexole administration improved events during sleep and daytime sleepiness, and the PSG findings and clinical course led to a diagnosis of PLMD. This case demonstrates that PLMD mimics the symptoms of RBD and that a detailed analysis of monitored video PSG is crucial to confirm the diagnosis of RBD and to identify or exclude other causes of sleep talking and behavior.

Rotigotine is effective for depressive symptoms accompanying periodic limb movement disorder or restless legs syndrome.

We report two cases who had been diagnosed with major depression, but found to have periodic limb movement disorder (PLMD) or restless legs syndrome (RLS) as major disorder. Both patients had difficulties in occupational and/or daily lives. In neither case, antidepressants were effective in symptom remission. In contrast, rotigotine transdermal patch was effective not only for core symptoms of PLMD or RLS but also for accompanying depressive symptoms. Since PLMD and RLS are associated with dopaminergic dysfunction etiologically, a dopamine receptor agonist rotigotine might be a good choice for patients with PLMD or RLS accompanying depression.

Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study.

Background and purpose: Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods: The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results: Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26-3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90-5.30, p < 0.001), followed by patients aged 45-64 years (HR = 1.69, 95% CI = 1.26-2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12-2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97-5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53-4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04-1.65, p < 0.05). Conclusion: Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.

Parasomnias and Sleep-Related Movement Disorders in Older Adults.

Sleep paralysis is rare in the elderly but may occur particularly in families suffering from this phenomenon. In a minority of patients with disorders of arousal, the episodes persist until the age of 70. Zolpidem and other medications may induce sleepwalking and sleep eating-related syndrome. Most patients with idiopathic REM sleep behavior disorder (RBD) eventually develop Parkinson disease and dementia with Lewy bodies. Anti-IgLON5 disease includes abnormal behaviors in both nonrapid eye movement sleep and rapid eye movement sleep (REM) sleep. Restless legs syndrome prevalence increases with age until the sixth decade. A severe form of periodic limb movements in sleep may clinically mimic REM sleep behavior disorder (RBD).

Large body movements on video polysomnography are associated with daytime dysfunction in children with restless sleep disorder.

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.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment of pediatric restless legs syndrome and periodic limb movement disorder.

BACKGROUND: Iron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD. METHODS: This was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed. RESULTS: Thirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between "very much improved" and "much improved". Ferritin increased from 14.6 µg/L±7.01 to 112.4 µg/L±65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild. CONCLUSIONS: Children with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Restless Legs Syndrome: Contemporary Diagnosis and Treatment.

Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs while at rest, relief upon movement or getting up to walk, and worsened symptom severity at night. RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency. Genetic predisposition with a family history is common. The pathogenesis of RLS remains unclear but is likely to involve central nervous system dopaminergic dysfunction, as well as other, undefined contributing mechanisms. Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms, especially when augmentation develops. Augmentation is characterized by more intense symptom severity, earlier symptom occurrence, and often, symptom spread from the legs to the arms or other body regions. Some people with RLS have adequate symptom control with non-pharmacological measures such as massage or temperate baths. First-line management options include iron-replacement therapy in those with evidence for reduced body-iron stores or, alternatively, with prescribed gabapentin or pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine. Second-line therapies include intravenous iron infusion in those who are intolerant of oral iron and/or those having augmentation with intense, severe RLS symptoms, and opioids including tramadol, oxycodone, and methadone. RLS significantly impacts patients' quality of life and remains a therapeutic area sorely in need of innovation and a further pipeline of new, biologically informed therapies.

Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important.

BACKGROUND: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. OBJECTIVE: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. METHODS: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or >10. RESULTS: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. CONCLUSIONS: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.

Comorbidities in children with elevated periodic limb movement index during sleep.

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.