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We present a patient with chronic insomnia resistant to traditional pharmacologic (e.g., sedative-hypnotics) and nonpharmacologic (e.g. cognitive behavioral therapy for insomnia; CBT-I) therapy. A finding of elevated serum homocysteine triggered a whole genome sequencing analysis which revealed a homozygous methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T/C677T; dbSNP rs1801133). Interventions targeting her polymorphism-dependent loss of function successfully resolved her insomnia. This case demonstrates a genomic approach for insomnia whereby successful treatment was focused on optimizing the patient's metabolome which was altered as a result of a missense single nucleotide polymorphism.

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.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.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.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.

Study Objectives To evaluate leg movements during sleep (LMS) in children taking serotonergic antidepressants, compared to those of children with restless legs syndrome (RLS) and controls, and to assess the time structure of intermovement intervals (IMI). Methods Twenty-three children (12 girls, mean age 14.1 years) on antidepressants and with a total LMS index ≥ 15/h, 21 drug-naïve RLS children (11 girls, mean age 13.6 years) also with total LMS index ≥ 15/h, and 35 control children (17 girls, mean age 14.3 years) were recruited. LMS were scored and a series of parameters was calculated, along with the analysis of their time structure. Results Children taking antidepressants showed higher total and periodic LMS (PLMS) indexes than both controls and RLS children, as well as higher short-interval and isolated LMS indexes than controls. LMS periodicity was highest in children on antidepressants. In children taking antidepressants, a well-defined PLMS IMI peak corresponding to approximately 10–60 s, with a maximum at approximately 20 s was present, which was much less evident in RLS patients and absent in controls. A progressive decrease of PLMS during the night and more frequent arousals were found in children on antidepressants and with RLS. Conclusions Children taking serotonergic antidepressants show higher periodicity LMS than children with RLS or controls and have a higher number of PLMS through the night. Antidepressant-associated PLMS in children seem to have features similar to PLMS of adults with RLS. Whether this is a marker of an increased risk to develop RLS later in life needs to be determined.

STUDY OBJECTIVES: Restless sleep is a very common parental complaint in children with attention-deficit/hyperactivity disorder (ADHD), but restless sleep has been seen in association with other comorbidities such as restless legs syndrome and obstructive sleep apnea. Restless sleep disorder (RSD) needs to be identified from other disorders when evaluating children with ADHD. In this study we aim to identify the prevalence of RSD in children with ADHD referred to our sleep center. METHODS: This is a retrospective study of children with ADHD who underwent polysomnography. The following diagnostic and descriptive data were obtained for each patient: age, sex, presence/absence of RSD, other sleep disorders, psychiatric comorbidities, and medications. RSD was diagnosed per diagnostic criteria. RESULTS: There were 66 children with ADHD. All of them underwent polysomnography, 17 were females, and 49 were males. Mean age was 11.6 years (± 3.6 standard deviation). The complaint of restless sleep was reported by the parents of 54 (81.1%) of the children; however, only 6 of them (9.1%) were diagnosed with RSD. Seventy-one percent had obstructive sleep apnea and 19.7% had restless legs syndrome. A significant number of patients had psychiatric comorbidities and were on various medications. CONCLUSIONS: Although restless sleep is a common complaint reported in 81.1% of children with ADHD, only 9.1% had RSD. Most causes of restless sleep are secondary and associated with other sleep disorders, psychiatric comorbidities, or medication use. CITATION: Kapoor V, Ferri R, Stein MA, Ruth C, Reed J, DelRosso LM. Restless sleep disorder in children with attention-deficit/hyperactivity disorder. J Clin Sleep Med. 2021;17(4):639–643.

Introduction The etiology of restless sleep has recently been identified as secondary to various medical and sleep conditions. Parents of children with ADHD complain of restless sleep and sleep disturbances in their children. We aimed to assess restless sleep causes in our patient population with ADHD and establish the prevalence of restless sleep disorder (RSD), as recently defined. Methods A retrospective study of children with ADHD who underwent polysomnography was carried out. Diagnostic and descriptive information collected for each patient included age, sex, polysomnographic parameters, sleep disorders, psychiatric comorbidities, and medications. Results Sixty-six PSGs were reviewed. The mean age of children was 11.6 (±3.6 SD) years; 17 were female and 49 were male. Parents of 54 (81.1%) children had concerns of restlessness during sleep; 47 (71.2%) children had obstructive sleep apnea, 17 (25.8%) had PLMS ≥5/hour, 13 (19.7%) had RLS, 6 (9.1%) had RSD, 27 (41%) had depression or anxiety, 5 (7.6%) had insomnia. Conclusion In a pediatric sleep medicine referred group of patients with ADHD, who are known to have significant sleep and psychiatric comorbidities, obstructive sleep apnea, RLS, and RSD were found to be the most prevalent sleep disorders, whereas depression and anxiety were the most common psychiatric disorders. Complaint of secondary restless sleep seems to be common, while primary restless sleep disorder was seen in approximately 9% of children. The results of this study aid pediatricians and child psychiatrists in screening children with ADHD for associated sleep disorders. Support (if any)