title: 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-naïve 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy. Electronic address: comi@med.unipmn.it.
authors.forename: C
authors.initials: C
authors.lastname: Comi
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Magistrelli
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy.
authors.forename: G D
authors.initials: GD
authors.lastname: Oggioni
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Carecchio
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Fleetwood
authors.affiliation: Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Eastern Piedmont, "Amedeo Avogadro", Novara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cantello
authors.affiliation: Parkinson's Disease and Movement Disorders Centre, Neurology Unit, San Pio X Clinic, Fondazione Opera San Camillo, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mancini
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, IRCCS Ospedale San Camillo, Venice, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antonini
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Alpha-synuclein; Levodopa; Peripheral neuropathy; Vitamin B deficiency