title: Peripheral neuropathy in Parkinson's disease: levodopa exposure and implications for duodenal delivery.
abstract: In advanced Parkinson's disease (PD) patients, continuous intra-duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established approach in the management of motor complications that cannot be further improved by conventional oral therapy. In general, tolerability of LCIG has resembled that of oral dopaminergic therapy; however, cases of symptomatic peripheral neuropathy (PN), sometimes severe, have been reported in patients receiving LCIG. Cases are generally a sensorimotor polyneuropathy with both subacute and chronic onsets, often associated with vitamin B12 and/or B6 deficiency. Rare cases clinically resemble Guillain-Barré syndrome. In the absence of prospectively collected data on possible associations between LCIG and PN, it is prudent to explore potential mechanisms that may explain a possible relationship. The PN may be linked to use of high-dose levodopa, promoting high levels of homocysteine and methylmalonic acid or reduced absorption of vitamins essential for homocysteine metabolism. Cases of LCIG-associated PN often have responded to vitamin supplementation without need for LCIG cessation, although LCIG cessation is sometimes necessary. It may be advisable to monitor vitamin B12/B6 status before and after patients start LCIG and be vigilant for signs of PN. Prospective, large-scale, long-term studies are needed to clarify whether vitamin supplementation and routine use of a catechol-O-methyltransferase inhibitor may help prevent PN in LCIG recipients and whether these measures should be routine practice in patients with PD on high-dose oral levodopa.
authors: Department of Neurology, St. Joseph Krankenhaus Berlin-Weißensee, Gartenstr. 1, 13088 Berlin, Germany. th.mueller@alexius.de
authors: Thomas
authors: T
authors: Müller
authors: Teus
authors: T
authors: van Laar
authors: David R
authors: DR
authors: Cornblath
authors: Per
authors: P
authors: Odin
authors: Fabian
authors: F
authors: Klostermann
authors: Francisco J
authors: FJ
authors: Grandas
authors: Georg
authors: G
authors: Ebersbach
authors: Peter P
authors: PP
authors: Urban
authors: Francesc
authors: F
authors: Valldeoriola
authors: Angelo
authors: A
authors: Antonini
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa