title: Levodopa and neuropathy risk in patients with Parkinson disease: Effect of COMT inhibition.
abstract: Our purpose was to determine whether the use of catechol-O-methyltransferase-inhibitors (ICOMT) can reduce the risk of developing levodopa (LD)-induced neuropathy in Parkinson's disease (PD) patients.
  
  
  
  A multicentre study of 197 PD patients was performed. 144 were exposed to LD for more than three years (LELD group); 53 simultaneously assumed Entacapone for at least eighteen months (LELD_ICOMT group).
  
  
  
  The prevalence of neuropathy in LELD patients was 19.4% whereas it was 5.7% in LELD_ICOMT group with a significant difference (p = 0.025). In LELD_ICOMT cohort the daily LD dose and serum VB12 levels were significantly higher (p < 0.0001), the serum Hcy levels were significantly lower (p = 0.001) compared to LELD group.
  
  
  
  Our results suggest that ICOMT could have a protective effect on the development of LD-induced neuropathy. Their action probably occurs through the metabolic rebalancing of the one-carbon-pathway cycle and is independent of the PD duration and severity and the duration of LD intake.
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy. Electronic address: giovannicossu1@gmail.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cossu
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, Ospedale S. Chiara Via Roma 67, 56126, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceravolo
authors.affiliation: Neurology Unit, University of Torino, Ospedale Molinette, C.so Bramante, 88, 10126, Torino, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zibetti
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Arca
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ricchi
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Paribello
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Murgia
authors.affiliation: Neurology Unit, University of Torino, Ospedale Molinette, C.so Bramante, 88, 10126, Torino, Italy.
authors.forename: Aristide
authors.initials: A
authors.lastname: Merola
authors.affiliation: Neurology Unit, University of Torino, Ospedale Molinette, C.so Bramante, 88, 10126, Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Romagnolo
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, Ospedale S. Chiara Via Roma 67, 56126, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nicoletti
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, Ospedale S. Chiara Via Roma 67, 56126, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palermo
authors.affiliation: Department of Public Health University, Clinical and Molecular Medicine, University of Cagliari, 09042, Monserrato, Cagliari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mereu
authors.affiliation: Neurology Unit, University of Torino, Ospedale Molinette, C.so Bramante, 88, 10126, Torino, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lopiano
authors.affiliation: Neurology Unit, Azienda Ospedaliera Brotzu Cagliari, P.le Ricchi 1, 009134, Cagliari Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Melis
authors.affiliation: Department of Neurosciences, Ophthalmology & Genetics University of Genova, Via De Toni, 5, 16132, Genova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abbruzzese
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, Ospedale S. Chiara Via Roma 67, 56126, Pisa, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D065098:Catechol O-Methyltransferase Inhibitors / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D007980:Levodopa
keywords: COMT inhibition; Levodopa; Parkinson's disease; Peripheral neuropathy