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The Timing of Continuous Dopaminergic Stimulation for Optimal Clinical Outcomes

Published Online: July 15th 2012 European Neurological Review, 2012;7(Suppl. 1):20–6 DOI: http://doi.org/10.17925/ENR.2012.07.S1.20
Authors: Christian Winkler
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Abstract
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Abstract:
Overview

The timing of continuous dopaminergic stimulation (CDS) treatment is an important consideration for achieving optimal motor functioning in Parkinson’s disease patients. Delaying treatment with levodopa/carbidopa intestinal gel (LCIG) infusion in patients with severe ‘on-off’ fluctuations may result in a poorer and slower response, while early initiation of CDS therapy increases the chance of achieving continuous ‘on’ without dyskinesia. Furthermore, overnight LCIG infusion is indicated when there is severe akinesia overnight, but daytime-only LCIG infusion treatment can lead to a reduction in overnight motor fluctuations after several months.

Keywords

Parkinson’s disease, levodopa, continuous dopaminergic stimulation, levodopa/carbidopa intestinal gel infusion, motor fluctuations

Article:

The timing of continuous dopaminergic stimulation (CDS) therapy is an important consideration in achieving the most favourable motor outcomes. According to the official product information in Germany, levodopa/carbidopa intestinal gel (LCIG) infusion should be used for the ‘treatment of advanced, levodopa-responsive Parkinson’s disease with severe motor fluctuations AND hyper-/dyskinesia when available antiparkinsonian treatment is not satisfying anymore’.1 In Germany, younger patients without cognitive impairments are more likely to receive deep brain stimulation (DBS), while older patients with cognitive impairments are more likely to receive LCIG infusion therapy. In addition, there is a tendency in Germany for DBS to be performed when there is only ‘wearing off’ in patients, while LCIG infusion treatment is not initiated before there are more severe motor fluctuations including hyperkinesia. An interesting question is whether this approach to use LCIG treatment later in the course of the disease compared with DBS is optimal. Two patient cases are presented here to illustrate the effects of starting LCIG infusion at different stages of Parkinson’s disease (PD), and the effects of daytime-only LCIG infusion on overnight motor fluctuations.

Case Reports
Baseline Motor Performance
Two patient cases are presented and these are referred to as ‘Patient 1’ and ‘Patient 2’. Patient 1 is a man in his early 60s who experienced severe motor fluctuations. Sometimes he only had good motor ‘on’ for about 20 % of the day and was either ‘off’ or ‘on with severe dyskinesia’ for the remainder of the day. He sometimes shifted from ‘on’ with severe dyskinesia directly to the ‘off’ phase, and had very difficult nights with severe ‘off’ phases (see Table 1A). Patient 1 had depression, cognitive impairment and slight hallucinations, and was taking the following medications when he first presented at ourdepartment: levodopa 200 mg every three hours (six times daily), entacapone 200 mg every three hours (six times daily), amantadine 200 mg twice daily, cabergoline 4 mg once daily and levodopa at request (up to 600 mg a day). Most of the levodopa at request was taken at night to treat severe night-time ‘off’ phases. He also took mirtazapine 15 mg in the evening and escitalopram 10 mg in the morning for his depression, and quetiapine 25 mg in the evening for his hallucinations.

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Disclosure

Christian Winkler attended a Solvay/Abbott advisory board meeting in 2010 and has received payment from the company for clinical talks. Since 2011, he has been lecturing twice a year at Abbott’s Duodopa® Specialist Training in Basel, Switzerland, and receives payment for this. He has also attended advisory board meetings for Orion Pharma and UCB Pharma GmbH.

Correspondence

Christian Winkler, Department of Neurology, University Hospital Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany. E: christian.winkler@uniklinik-freiburg.de

Support

The V International Forum on Parkinson’s Disease (Helsinki, Finland, 6–7 May 2011) was funded by an unrestricted educational grant from Abbott. Abbott funded the development of this supplement by ESP Bioscience (Crowthorne, UK). Emily Chu and Nicole Meinel of ESP Bioscience provided medical writing and editorial support to the author in the development of this publication. Abbott had the opportunity to review and comment on the publication’s content; however, all decisions regarding content were made by the author.

Received

2013-06-22T00:00:00

References

  1. Duodopa® product information, Abbott Products GmbH, Hannover, Germany, January 2011.
  2. García J, Carlsson T, Döbrössy M, et al., Impact of dopamine to serotonin cell ratio in transplants on behavioral recovery and L-DOPA-induced dyskinesia, Neurobiol Dis, 2011;43:576–87.
  3. Lee CS, Cenci MA, Schulzer M, Björklund A, Embryonic ventral mesencephalic grafts improve levodopa-induced dyskinesia in a rat model of Parkinson’s disease, Brain, 2000;123:1365–79.
  4. Carlsson T, Winkler C, Burger C, et al., Reversal of dyskinesias in an animal model of Parkinson’s disease by continuous L-DOPA delivery using rAAV vectors, Brain, 2005;128:559–69.
  5. Björklund T, Carlsson T, Cederfjäll EA, et al., Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson’s disease, Brain, 2010;133:496–511.

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