Download PDF
Fortschr Neurol Psychiatr 2018; 86(S 01): S5-S9
DOI: 10.1055/a-0646-4164
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Intrajejunale Levodopa- und Apomorphin-Infusion zur Therapie motorischer Komplikationen bei fortgeschrittener Parkinson-Krankheit

Duodenale levodopa and apomorphine infusion for motor complications in advanced Parkinson’s disease
Angelo Antonini
1   Department of Neuroscience, University of Padua, Padua, Italy
,
Wolfgang H. Jost
2   Parkinson-Klinik Ortenau, Wolfach
› Author Affiliations
Further Information

Publication History

eingereicht 27 May 2018

akzeptiert 20 June 2018

Publication Date:
14 August 2018 (online)

    Permissions and Reprints

Zusammenfassung

Die Entwicklung motorischer Fluktuationen und Dyskinesien charakterisiert den Übergang vom frühen zum fortgeschrittenen Parkinson-Stadium. Aktuelle Strategien der oralen Therapie umfassen die stärkere Verteilung von Levodopa, ihre verlängerte Wirkdauer durch Gabe von Enzymblockern (MAO- und COMT-Hemmern) und Dopaminagonisten. Mit fortschreitender Krankheit wird die Motorik jedoch zunehmend abhängig von der Levodopa-Resorption und dessen Bioverfügbarkeit im Plasma, was schließlich zu motorischen Fluktuationen führt. Wenn Patienten nach der optimierten oralen Medikationsanpassung weiterhin funktionelle Einschränkungen bei den Aktivitäten des täglichen Lebens haben, sollten Infusionstherapien mit Apomorphin oder Levodopa und operative Verfahren (Tiefe Hirnstimulation) in Betracht gezogen werden. Im Vergleich zur pulsatilen oralen Therapie kann durch die Infusion von Apomorphin oder Levodopa eine kontinuierlichere striatale Stimulation der Dopaminrezeptoren erzielt werden, was zu einer signifikanten Reduktion der off-Zeiten und Dyskinesien, insbesondere der peak-dose-Dyskinesien, führt. Langjährige Erfahrungen mit diesen Behandlungen zeigen bedauerlicherweise, dass die motorischen Komplikationen durch eine kontinuierliche Stimulation des Rezeptors nicht komplett reversibel sind, was darauf hindeutet, dass Veränderungen der synaptischen Plastizität und Konnektivität nicht einfach rückgängig gemacht werden können, nachdem sie erst einmal etabliert sind. Wünschenswert wäre ein Einsatz zu einem früheren Zeitpunkt, zu dem sich motorische Komplikationen erst entwickeln und nicht in einem späten Stadium, wenn diese schon ausgeprägt sind. Vorläufige Ergebnisse beim frühen Einsatz der Tiefen Hirnstimulation oder einer frühen Pumpenbehandlung legen nahe, dass dies erfolgsversprechend erscheint, aber bevor es in der klinischen Praxis implementiert wird, bedarf es auch einer detaillierten Kosten-Nutzen-Analyse.

Abstract

Development of motor fluctuations and dyskinesia characterizes the transition from the early to the advanced Parkinson stage. Current oral therapeutic strategies aim at increasing the number of levodopa administrations and extending its benefit by the association of enzyme blockers (MAO- and COMT-inhibitors) and dopamine agonists. However, as disease progresses, mobility becomes progressively dependent on levodopa absorption and plasma bioavailability, resulting in disabling motor complications. If patients continue to experience off time with functional impact on activities of daily living after best oral medication adjustments, implementation of infusion therapies with apomorphine or levodopa, and surgical techniques should be considered. Compared with pulsatile oral therapy implementation of apomorphine and levodopa infusion determines more continuous striatal dopamine receptors stimulation resulting in significant reduction of off-time and dyskinesia, particularly peak-dose. However, long-term experience with these treatments shows that motor complications are not abolished by continuous receptor stimulation suggesting that synaptic plasticity and connectivity changes are not easily reversed once they are established. Early intervention ideally would target patients as soon as motor complications begin rather than at late stage. Preliminary evidence from early deep brain stimulation or early pump treatment suggests that this is feasible but before it is implemented in clinical practice it would require a detailed cost-benefit analysis.

Schlüsselwörter

Levodopa Infusion - Duodopa - Apomorphin - Dyskinesien - Motorkomplikationen - wearing-off

Key words

levodopa infusion gel - Duodopa - apomorphine - dyskinesia - motor complications - wearing-off
 

  • Literatur

  • 1 Antonini A, Moro E, Godeiro C, Reichmann H. Medical and surgical management of advanced Parkinson’s disease. Mov Disord. 2018 doi: 10.1002 / mds.27340.
    PubMedGoogle Scholar
  • 2 Antonini A, Chaudhuri KR, Martinez-Martin P, Odin P. Oral and infusion levodopa-based strategies for managing motor complications in patients with Parkinson’s disease. CNS Drugs. 2010; 24: 119-129
    CrossrefPubMedGoogle Scholar
  • 3 Fox SH, Katzenschlager R, Lim SY. et al. The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2011; 26 Suppl 3 : S2-41
    CrossrefPubMedGoogle Scholar
  • 4 Pahwa R, Factor SA, Lyons KE. et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006; 66: 983-995
    CrossrefPubMedGoogle Scholar
  • 5 Odin P, Ray Chaudhuri K, Slevin JT. et al. National Steering Committees. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: Consensus from an international survey and discussion program. Parkinsonism Relat Disord. 2015; 21: 1133-1144
    CrossrefPubMedGoogle Scholar
  • 6 Antonini A, Tolosa E. Apomorphine and levodopa infusion therapies for advanced Parkinson’s disease: selection criteria and patient management. Expert Rev Neurother. 2009; 9: 859-867
    CrossrefPubMedGoogle Scholar
  • 7 Südmeyer M, Ebersbach G, Holtmann M. et al. Praktische Anwendung der Levodopa-Pumpe. Fortschr Neurol Psychiatr 2016; 84: 404-410
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Tönges L, Ceballos-Baumann A, Honig H. et al. Praktische Anwendung der kontinuierlichen Apomorphin-Pumpentherapie. Fortschr Neurol Psychiatr 2017; 85: 516-535
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Fahn S, Oakes D, Shoulson I. et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004; 351: 2498-2508
    CrossrefPubMedGoogle Scholar
  • 10 Sharma JC, Ross IN, Rascol O, Brooks D. Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. Eur J Neurol 2008; 15: 493-496
    CrossrefPubMedGoogle Scholar
  • 11 Stocchi F, Rascol O, Kieburtz K. et al. Initiating levodopa / carbidopa therapy with and without entacapone in early Parkinson disease. The STRIDE-PD study. Ann Neurol 2010; 68: 18-27
    CrossrefPubMedGoogle Scholar
  • 12 Maratos EC, Jackson MJ, Pearce RK. et al. Both short- and long-acting D-1 / D-2 dopamine agonists induce less dyskinesia than L-DOPA in the MPTP-lesioned common marmoset (Callithrix jacchus). Exp Neurol. 2003; 179: 90-102
    CrossrefPubMedGoogle Scholar
  • 13 Hadj Tahar A, Gregoire L, Bangassoro E, Bedard PJ. Sustained cabergoline treatment reverses levodopa-induced dyskinesias in parkinsonian monkeys. Clin Neuropharmacol. 2000; 23: 195-202
    CrossrefPubMedGoogle Scholar
  • 14 Stocchi F, Ruggieri S, Vacca L, Olanow CW. Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson’s disease. Brain. 2002; 125 (Pt 9) : 2058-2066
    CrossrefPubMedGoogle Scholar
  • 15 Antonini A, Isaias IU, Rodolfi G. et al. A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation. J Neurol. 2011; 258: 579-585
    CrossrefPubMedGoogle Scholar
  • 16 Jenner P, Katzenschlager R. Apomorphine- pharmacological properties and clinical trials in Parkinson’s disease. Parkinsonism Relat Disord . 2016; 33 Suppl 1 : S13-S21
    CrossrefPubMedGoogle Scholar
  • 17 Katzenschlager R, Hughes A, Evans A. et al. Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: a prospective study using single-dose challenges. Mov Disord. 2005; 20: 151-157
    CrossrefPubMedGoogle Scholar
  • 18 Martinez-Martin P, Reddy P, Katzenschlager R. et al. EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov Disord. 2015; 30: 510-516
    CrossrefPubMedGoogle Scholar
  • 19 Borgemeester RW, Drent M, van Laar T. Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson’s disease patients. Parkinsonism Relat Disord. 2016; 23: 17-22
    CrossrefPubMedGoogle Scholar
  • 20 Todorova A, Samuel M, Brown RG, Chaudhuri KR. Infusion therapies and development of impulse control disorders in advanced Parkinson disease: Clinical experience after 3 years’ follow-up. Clin Neuropharmacol. 2015; 38: 132-134
    CrossrefPubMedGoogle Scholar
  • 21 Drapier S, Eusebio A, Degos B. et al. Quality of life in Parkinson’s disease improved by apomorphine pump: the OPTIPUMP cohort study. J Neurol. 2016; 263: 1111-1119
    CrossrefPubMedGoogle Scholar
  • 22 Katzenschlager R, Poewe W, Rascol O. et al. Double-blind, randomised, placebo-controlled, phase iii study (Toledo) to evaluate the efficacy of apomorphine subcutaneous infusion in reducing ‘off’ time in Parkinson’s disease patients with motor fluctuations not well controlled on optimised medical treatment Mov Disord 2017 32. (Suppl. 2) : S518-519
    PubMed
  • 23 Sesar Á, Fernández-Pajarín G, Ares B. et al. Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients. J Neurol. 2017; 264: 946-954
    CrossrefPubMedGoogle Scholar
  • 24 Nyholm D, Nilsson Remahl AI, Dizdar N. et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology. 2005; 64: 216-223
    CrossrefPubMedGoogle Scholar
  • 25 Wirdefeldt K, Odin P, Nyholm D. Levodopa-carbidopa intestinal gel in patients with Parkinson’s disease: a systematic review. CNS Drugs. 2016; 30: 381-404
    CrossrefPubMedGoogle Scholar
  • 26 Olanow CW, Kieburtz K, Odin P. et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014; 13: 141-149
    CrossrefPubMedGoogle Scholar
  • 27 Timpka J, Nitu B, Datieva V. et al. Device-aided treatment strategies in advanced Parkinson’s disease. Int Rev Neurobiol. 2017; 132: 453-474
    PubMedGoogle Scholar
  • 28 Antonini A, Odin P, Lopiano L. et al. Effect and safety of duodenal levodopa infusion in advanced Parkinson’s disease: a retrospective multicenter outcome assessment in patient routine care. J Neural Transm. 2013; 120: 1553-1558
    CrossrefPubMedGoogle Scholar
  • 29 Timpka J, Fox T, Fox K. et al. Improvement of dyskinesias with L-dopa infusion in advanced Parkinson’s disease. Acta Neurol Scand 2016; 133: 451-458
    CrossrefPubMedGoogle Scholar
  • 30 Antonini A, Fung VS, Boyd JT. et al. Effect of levodopa-carbidopa intestinal gel on dyskinesia in advanced Parkinson’s disease patients. Mov Disord. 2016; 31: 530-537
    CrossrefPubMedGoogle Scholar
  • 31 Antonini A, Poewe W, Chaudhuri KR. et al.; GLORIA study co-investigators Levodopa-carbidopa intestinal gel in advanced Parkinson’s: Final results of the GLORIA registry. Parkinsonism Relat Disord. 2017; 5: 13-20
    PubMedGoogle Scholar
  • 32 Lang AE, Rodriguez RL, Boyd JT. et al., Integrated safety of levodopa‐ carbidopa intestinal gel from prospective clinical trials. Mov Disord 2016; 31: 538-546
    CrossrefPubMedGoogle Scholar
  • 33 Odin P, Ray Chaudhuri K, Slevin JT. et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: Consensus from an international survey and discussion program. Parkinsonism Relat Disord. 2015; 21: 1133-1144
    CrossrefPubMedGoogle Scholar
  • 34 Schuepbach WM, Rau J, Knudsen K. et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med. 2013; 368: 610-622
    CrossrefPubMedGoogle Scholar
  • 35 Trenkwalder C, Chaudhuri KR, García Ruiz PJ. et al. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease – Clinical practice recommendations. Parkinsonism Relat Disord 2015; 21: 1023-1030
    CrossrefPubMedGoogle Scholar