Association between restless legs syndrome and peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND The coexistence of peripheral neuropathy (PN) and restless legs syndrome/Ekbom disease (RLS/WED) is relatively frequent, but its prevalence has shown a high variability across studies. In addition, several reports have shown data suggesting the presence of PN in patients with idiopathic RLS. METHODS We undertook a search using the PubMed, EMBASE, and Web of Science Databases, from 1966 until December 6,2020, crossing the search term "Restless legs syndrome" with "neuropathy", "polyneuropathy" (PNP), and "peripheral neuropathy", and identified the references of interest for this topic, and performed a meta-analysis, according to PRISMA guidelines, and a calculation of pooled prevalences, where appropriate, using standard methods. RESULTS RLS has been reported in 5.2%-53.7% of patients with PN (average 21.5%;95%CI =18.6-24.5%), and PN in 0-87.5% of patients with RLS (average 41.8%;95% CI 39.9-43.6%), being both significantly more frequent than in controls. The heterogeneity across studies could be due to differences in the diagnostic criteria both for RLS and PN used. RLS is a frequent clinical complaint in patients with PN of different etiologies, mainly diabetic PN, uremic PNP, familial amyloid PNP, Charcot-Marie-Tooth disease, and chronic dysimmune inflammatory PNP. Recent neurophysiological findings suggest the presence of small sensory fiber loss (SSFL) in patients diagnosed with idiopathic RLS, but it remains to be determined whether RLS associated with SSFL and idiopathic RLS are different clinical entities. CONCLUSIONS Future studies including clinical and neurophysiological assessment and skin biopsy involving a large series of patients with PN and RLS are needed for a better understanding of the association between these two entities.