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ABSTRACT
Much of our pathophysiologic understanding of the etiology of restless leg syndrome (RLS) incriminates abnormalities within the central nervous system (CNS). However, peripheral neuropathy is classically listed as a risk factor for RLS. This discrepancy is difficult to reconcile. If there truly is a connection between neuropathy and RLS, it has important implications for the screening and treatment of RLS, and it challenges our current concepts of RLS as a predominantly CNS disease.
The proposed association between RLS and peripheral neuropathy is based upon case reports, conflicting case-control studies, and findings from pathological studies. Prevalence estimates of RLS among peripheral neuropathy patients range from 5.2% to 37%. Initial reports found increased prevalence of RLS in patients with acquired neuropathy, but recently a large blinded case-control study did not confirm these results. Furthermore, in this recent study, neuropathy subjects often endorsed RLS-like symptoms, which could not be confirmed on diagnostic evaluation, suggesting that symptom overlap between RLS and neuropathic pain may be a common confound. This study also showed an increased prevalence of RLS selectively among hereditary neuropathy patients, which raises questions about the genetic relationship between RLS and neuropathy. Small pathologic studies have detected features of subclinical sensory neuropathy in some RLS patients. If confirmed, these findings may suggest the existence of a separate subclinical neuropathy/RLS syndrome, the nature of which must be further delineated.
Keywords: restless legs syndrome, peripheral neuropathy, prevalence, review, genetics
INTRODUCTION
Wherefore to some, when being abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions of the tendons, and so great a restlessness and tossing of their members ensue, that the diseased are no more able to sleep, than if they were in the place of the greatest torture.
Penned in 1672, this description by Sir Thomas Willis, a royal physician to King Charles I of England, may be the earliest formal documentation of RLS [1]. Despite this poetic entry into the medical literature, RLS then proceeded to pass largely out of recognition until the late 1800s when it resurfaced as "anxietas tibiarum", a sign of hysteria and/or neurosis [2]. It was not until 1944 that RLS regained medical creditability, when Ekbom published an observational review of 34 cases. In this publication,...