A peripheral pathway to restless legs syndrome? Clues from familial amyloid polyneuropathy

Background: The relationship between restless legs syndrome (RLS) and peripheral neuropathy remains unclear. In order to clarify this relationship, we investigated if RLS is increased in familial amyloid polyneuropathy related to transthyretin (TTR-FAP) and investigated factors associated with RLS in this population. Methods: RLS frequency was compared between TTR-FAP patients and controls. Secondly, TTR-FAP patients with and without RLS were compared regarding demographic and clinical characteristics. Results: RLS frequency was significantly increased in TTR-FAP, with 18/98 (18.4%) cases contrasting with 5/104 (4.8%) controls (p-value 0.002). This difference remained significant after adjusting for confounders. In TTR-FAP patients, female sex (p-value 0.037), obesity (p-value 0.036) and weight excess (pvalue 0.048) were associated with RLS, contrary to other classical RLS risk factors. Conclusions: RLS frequency is increased in TTR-FAP, thus supporting an association between RLS and neuropathy. This may represent a peripheral pathway in RLS pathogenesis. Furthermore, our results suggest that female sex and obesity/weight excess may be risk factors for RLS development among TTRFAP patients.