Restless Legs Syndrome and Peripheral Neuropathy—A Critical Review

Review Article

Submission date: 21st June 2009, Revision date: 27th July 2009, Acceptance date: 7th August 2009


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

Correspondence: Dr Ronald B. Postuma, Division of Neurology, L7-305 Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. Tel: +1-514-934-8058; fax: +1-514-934-8265; e-mail: ron.postuma@mcgill.ca