Elsevier

Sleep Medicine Reviews

Volume 13, Issue 2, April 2009, Pages 149-156
Sleep Medicine Reviews

Clinical review
Diagnosis and management of restless legs syndrome in children

https://doi.org/10.1016/j.smrv.2008.12.002Get rights and content

Summary

Recent published evidence suggests that restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are common condition in children and adolescents. It is likely that if left untreated, RLS and PLMD may lead to adverse cardiovascular and neurocognitive consequences. However, the diagnosis of RLS and PLMD in children is challenging, particularly because children are relatively unable to describe typical RLS symptoms. The International Restless Legs Study Group has recently published consensus criteria for the diagnosis of RLS and PLMD in children. In addition to clinical description of RLS symptoms, supportive evidence including the presence of clinical sleep disturbances, documented periodic limb movements in sleep from overnight sleep study and family history of restless legs syndrome may be required. Few if any controlled studies have addressed the management of RLS and PLMD, which may involve both non-pharmacologic and pharmacologic approaches. In this context, the importance of avoidance of aggravating factors and good sleep hygiene cannot be overemphasized. Children with evidence of low-iron storage, i.e., low-serum ferritin and/or iron levels may likely benefit from iron therapy. While there is overall limited experience regarding the use of dopaminergic agents in children with RLS and PLMD, published reports suggesting efficacy of compounds such as levodopa, ropinirole, pramipexole and pergolide have emerged. Other medications including benzodiazepine, anti-convulsants, alpha-adrenergic and opioid medications have not been adequately studied in children. Children with RLS and PLMD should have regular follow-up visits to evaluate clinical improvement and to monitor adverse effects from the selected therapy. Based on aforementioned findings, it is clear that a substantial research effort is needed to evaluate the pathophysiology, clinical presentation, treatment modalities, and overall long-term outcome of children with RLS and PLMD.

Introduction

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by the prototypic complaint of a strong, nearly irresistible urge to move the legs. Periodic limb movements in sleep (PLMS) are characterized by periodic episodes of repetitive and highly stereotypic limb movements during sleep.1 Periodic limb movement disorder (PLMD) is defined as the presence of periodic limb movement during sleep associated with symptoms of insomnia or excessive daytime sleepiness. RLS and PLMD are closely related. Most patients with PLMD do not manifest RLS symptoms; however, approximately 80% of adult RLS and 63–74% of pediatric RLS cases have PLMS.2, 3, *4

While most of the literature on RLS and PLMD has addressed the adult population, RLS and PLMD have been reported in children. In fact, careful history reveals that in 40% of adults suffering from RLS, the initial onset of symptoms will occur before 20 years of age.2, 5 Unfortunately, it was only until very recently that the initial epidemiological study of RLS was reported in children.6 Based on this particular large scale survey, it appears that RLS is common in children and adolescents with an estimated prevalence of 1.9% in school aged children and 2% in adolescents in whom there were no significant gender differences.6 Such figures, if confirmed by additional studies, would indicate that approximately 984,000 children are affected by RLS in the United States alone.

The etiology of pediatric RLS and PLMD is currently poorly understood. It remains unclear as to which specific role(s) are played by genetic factors, dopamine dysfunction, and low-iron stores in the pathophysiology of RLS and PLMD. A recent study indicated the presence of a significant association between RLS and PLMD and a common variant in an intron of BTBD9 on chromosome 6p21.1, emphasizing the potential for both genetic predisposition and genetic susceptibility to the occurrence of RLS and PLMD.7 In addition, ethnic differences may also be present.49 There is also a significant proportion of shared co-morbidity between Attention-deficit hyperactivity disorder (ADHD) and RLS and PLMD, implying the potential interactions between factors involved in the pathogenesis of ADHD and those underlying the onset and evolution of RLS and PLMD.50 However, despite substantial evidence pointing to a critical role for iron in adult with RLS and PLMD, we are unaware of specific studies that have addressed these issues in children.

The diagnosis of RLS in children can be quite challenging due to their inability to recognize or verbalize the presence of classic RLS symptoms. The International Restless Legs Study Group has published a set of proposed consensus criteria for reaching the diagnosis of RLS and PLMD in pediatric populations.8 Although RLS is a clinical diagnosis, supportive evidence such as presence of PLMS or family history of RLS, may be required in children. To further compound the already heightened level of uncertainty, the guidelines from the Standard of Practice Committee of the American Academy of Sleep Medicine state that no specific recommendations can be made regarding treatment of children with RLS and PLMD.1 However, since most children with RLS and PLMD may have low-iron stores, they may benefit from iron therapy, and any decision regarding use of other pharmacological agents will have to follow arbitrary and individualized algorithms, none of which has thus far sustained critical scientific validation. This paper will therefore proceed with a literature review on the diagnostic criteria and management of RLS and PLMD in children, with the understanding that few if any of the findings and potential recommendations emanating from such review are constrained by scientific scrutiny.

Section snippets

Diagnostic criteria in children and adolescents

The process of reaching the diagnosis of RLS in children is fraught with substantial challenging issues, particularly because young children may not be able to recognize and describe typical RLS symptoms or because these symptoms may not become manifest at very young ages. Indeed, the interval between the initial sleep consultation and the diagnosis of definite RLS revolves around 4.4 years.9 In addition, the period of time elapsing between onset of clinical sleep disturbances and the diagnosis

Consequences

As in sleep-disordered breathing, RLS and PLMD can lead to both cardiovascular and neurocognitive consequences. Several recent studies have shown that RLS and PLMD in the adult population is associated with a rise in nocturnal blood pressure and hypertension.15, 16 The mechanism underlying blood pressure changes may be related to autonomic activation in the context of repeated arousals.17 Currently, there are no data available on the cardiovascular consequences of RLS and PLMD in children.

Non-pharmacologic

It is important to identify medications or other factors that could aggravate RLS and PLMD and examine ways of discontinuing these medications. For instance, selective serotonin reuptake inhibitor (SSRI), metoclopramide, diphenhydramine, sleep deprivation, nicotine, caffeine, and alcohol have all been shown to either promote or aggravate RLS and PLMD.*10, 14 Parents should be advised to avoid caffeine in these children. Regular sleep routines and good sleep hygiene are essential for the

Acknowledgements

DG is supported by National Institutes of Health grant HL65270, the Commonwealth of Kentucky Research Challenge for Excellence Trust Fund, and the Children's Foundation Endowment for Sleep Research. LKG is supported by an investigator initiated grant from Merck Company.

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