Peripheral nervous system involvement in Parkinson's disease: Evidence and controversies

Abstract Background In recent years, non-motor features of Parkinson's disease (PD) have received increasing attention and PD is currently considered a systemic rather than a pure basal ganglia disorder. Among the systemic features, peripheral neuropathy (PN) is a recent acquisition since the first case–control study reporting increased frequency of PN in PD dates back to 2008. Methods We reviewed available literature on peripheral nervous system (PNS) involvement in PD. Results Evidence of α-synuclein deposition in the PNS and small nerve fiber deterioration in both drug-naive and treated PD patients is becoming stronger. In addition, several recent reports documented a significant role of levodopa exposure together with group B vitamin deficiency in facilitating the development of PN and case reports suggested that treatment with continuous levodopa intestinal infusion may increase the risk of acute PN compared to both oral levodopa and other dopaminergic treatments. Conclusion It is currently debated whether PN is an intrinsic disease-related feature, a consequence of levodopa treatment or both. In this review, we will discuss the different hypotheses, as well as our perspective on open issues and controversies.