TY - JOUR
T1 - Peripheral neuropathy in Parkinson's disease
T2 - Levodopa exposure and implications for duodenal delivery
AU - Müller, Thomas
AU - Laar, Teus van
AU - Cornblath, David R.
AU - Odin, Per
AU - Klostermann, Fabian
AU - Grandas, Francisco J.
AU - Ebersbach, Georg
AU - Urban, Peter P.
AU - Valldeoriola, Francesc
AU - Antonini, Angelo
N1 - Funding Information:
Dr Klostermann has been an investigator in Abbott-sponsored (now AbbVie, Inc) studies. He received honoraria for advisory activities from Archimedes, UCB, and Abbott (now AbbVie, Inc), and holds grants from the German Research Foundation (Kl 1276/4 and Kl 1276/5).
Funding Information:
Dr Ebersbach has served as a consultant for Boehringer Ingelheim and Orion Corporation. Dr Ebersbach has received honoraria for presentations from Abbott Laboratories (now AbbVie, Inc); Boehringer Ingelheim; Desitin Pharma AB; GlaxoSmithKline; Lundbeck; Novartis; Orion Corporation; Teva Pharmaceutical Industries Ltd; Valeant Pharmaceuticals International, Inc; and Schwarz Pharma, Inc (UCB). Dr Ebersbach has also received grants for research from Deutsche Parkinson Gesellschaft (DPV) and Deutsche Forschungs-Gesellschaft (DFG).
Funding Information:
The authors would like to thank Michael Feirtag of The Curry Rockefeller Group, LLC, Tarrytown, NY, USA, for providing editorial and medical writing support. Funding for this support was provided by Abbott Laboratories (now AbbVie, Inc). Abbott Laboratories (now AbbVie, Inc) provided a medical accuracy review of the final manuscript but had no input on the development of the manuscript or presentation of the content. The authors are solely responsible for the content of the manuscript and also had final responsibility for the decision to submit for publication.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - Homocysteine
KW - Levodopa/carbidopa intestinal gel
KW - Parkinson's disease
KW - Peripheral neuropathy
KW - Vitamin B
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UR - http://www.scopus.com/inward/citedby.url?scp=84875554066&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2013.02.006
DO - 10.1016/j.parkreldis.2013.02.006
M3 - Review article
C2 - 23453891
AN - SCOPUS:84875554066
SN - 1353-8020
VL - 19
SP - 501
EP - 507
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 5
ER -