title: Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study.
abstract: The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥ 3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037-1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130-5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical-neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa.
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceravolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cossu
authors.forename: Monica
authors.initials: M
authors.lastname: Bandettini di Poggio
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zibetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Frosini
authors.forename: Valentina
authors.initials: V
authors.lastname: Nicoletti
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
authors.forename: Rosa
authors.initials: R
authors.lastname: Iodice
authors.forename: Marina
authors.initials: M
authors.lastname: Picillo
authors.forename: Aristide
authors.initials: A
authors.lastname: Merola
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lopiano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Paribello
authors.forename: Davide
authors.initials: D
authors.lastname: Manca
authors.forename: Maurizio
authors.initials: M
authors.lastname: Melis
authors.forename: Roberta
authors.initials: R
authors.lastname: Marchese
authors.forename: Paolo
authors.initials: P
authors.lastname: Borelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mereu
authors.forename: Paolo
authors.initials: P
authors.lastname: Contu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abbruzzese
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D015995:Prevalence; D012306:Risk; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D000978:Antiparkinson Agents; D006710:Homocysteine; D007980:Levodopa; D014805:Vitamin B 12
keywords: Parkinson's disease; peripheral neuropathy