Synergien statt Rivalitäten – die missverstandenen Rollen von kontinuierlicher intrajejunaler Levodopatherapie und Tiefer Hirnstimulation in der Behandlung des Morbus Parkinson – eine Expertenmeinung

Zusammenfassung

In der Therapie des Morbus Parkinson kommen sowohl die intrajejunale Applikation von Levodopa/Carbidopa Intenstinalgel (LCIG) und seit kurzem Levodpoa/Carbidopa/Entacapon Intestinalgel (LECIG) als auch die Tiefe Hirnstimulation (THS) zum Einsatz. Obwohl diese Verfahren sich in Ihren Wirkungs- und Nebenwirkungsprofilen sowie dem Zeitpunkt des Einsatzes deutlich unterscheiden, wird die Therapieeinleitung beider Verfahren häufig simultan erst bei Erreichen eines fortgeschrittenen Erkrankungsstadiums geprüft. Aus Sicht der Autoren erreichen Patienten aber mitunter zu unterschiedlichen Zeitpunkten ihrer Erkrankung die Meilensteine für die Indikationsstellung eines der jeweiligen Verfahren. Hierbei spielt die individuelle Krankheitsentwicklung eine tragende Rolle. Die Idee, dass alle Patienten zu einem bestimmten und definierten Zeitpunkt nahezu gleichzeitig Kandidat für ein bestimmtes Verfahren werden, erscheint den Autoren als falsch. Im Rahmen dieser Übersichtsarbeit werden darum die Therapieformen hinsichtlich ihrer Wirksamkeit für verschiedene Ziel-Symptome vorgestellt, die simultane Abwägung über den Zeitpunkt des Einsatzes hinterfragt und eine individualisierte Therapieevaluation – mit Augenmerk auf Lebensqualität und gesellschaftliche Teilhabe – abgeleitet mit dem Ziel das Konzept des „Entweder – Oder“ aufzuweichen und in ein patientenzentriertes „Welches – Wann“ zu überführen.

Abstract

In the therapy of Parkinson̓s disease, both the intrajejunal administration of Levodopa/Carbidopa Intestinal Gel (LCIG) and, more recently, Levodopa/Carbidopa/Entacapone Intestinal Gel (LECIG), as well as deep brain stimulation (DBS), are employed. These approaches differ significantly in their efficacy and side effect profiles, as well as the timing of their use. Yet, the initiation of therapy for both methods is often simultaneously considered when patients have reached an advanced stage of the disease. From the authors' perspective, however, patients may reach the milestones for the indication of one of these respective treatments at different points in the course of the disease. Individual disease progression plays a pivotal role in this regard. The concept that all patients become candidates for a specific treatment at a predefined time appears erroneous to the authors. In the context of this review, therefore, the therapeutic modalities are presented in terms of their efficacy for different symptoms, the notion of simultaneous timing of their initiation is questioned, and an individualized therapy evaluation is derived, with a focus on quality of life and participation.

Schlüsselwörter

Morbus Parkinson - LCIG - LECIG - DBS - Intensivierte Therapieverfahren

Key words

Parkinson̓s Disease - Deep brain stimulation - Levodopa/Carbidopa/Entacapone Intestinal Gel - Levodopa/Carbidopa Intestinal Gel, - Intensified therapeutic procedures

Publication History

Received: 27 September 2023

Accepted after revision: 30 December 2023

Article published online:
12 February 2024

• Literatur

• 1 Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA 2020; 323: 548-560 DOI: 10.1001/jama.2019.22360.
• 2 Armstrong MJ, Okun MS. Choosing a Parkinson Disease Treatment. JAMA 2020; 323: 1420 DOI: 10.1001/jama.2020.1224.
• 3 Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM. et al. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 2011; 26: 399-406 DOI: 10.1002/mds.23462.
• 4 Hechtner MC, Vogt T, Zöllner Y. et al. Quality of life in Parkinson’s disease patients with motor fluctuations and dyskinesias in five European countries. Parkinsonism Relat Disord 2014; 20: 969-974 DOI: 10.1016/j.parkreldis.2014.06.001.
• 5 Storch A, Schneider CB, Wolz M. et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 2013; 80: 800-809 DOI: 10.1212/WNL.0b013e318285c0ed.
• 6 Coelho M, Ferreira JJ. Late-stage Parkinson disease. Nat Rev Neurol 2012; 8: 435-442 DOI: 10.1038/nrneurol.2012.126.
• 7 Luquin M-R, Kulisevsky J, Martinez-Martin P. et al. Consensus on the Definition of Advanced Parkinson’s Disease: A Neurologists-Based Delphi Study (CEPA Study). Parkinsons Dis 2017; 2017: 4047392 DOI: 10.1155/2017/4047392.
• 8 Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet 2021; 397: 2284-2303 DOI: 10.1016/S0140-6736(21)00218-X.
• 9 Antonini A, D’Onofrio V, Guerra A. Current and novel infusion therapies for patients with Parkinson’s disease. J Neural Transm 2023; 101: 1349–1358 DOI: 10.1007/s00702-023-02693-8.
• 10 Timpka J, Nitu B, Datieva V. et al. Device-Aided Treatment Strategies in Advanced Parkinson’s Disease. Int Rev Neurobiol 2017; 132: 453-474 DOI: 10.1016/bs.irn.2017.03.001.
• 11 Nyholm D, Jost WH. Levodopa–entacapone–carbidopa intestinal gel infusion in advanced Parkinson’s disease: real-world experience and practical guidance. Ther Adv Neurol Disord 2022; 15 17562864221108018 DOI: 10.1177/17562864221108018.
• 12 Marsili L, Bologna M, Miyasaki JM. et al. Device-aided therapies for advanced Parkinson disease: insights from an international survey. Neurol Sci 2021; 42: 2961-2964 DOI: 10.1007/s10072-021-05106-4.
• 13 Deuschl G, Antonini A, Costa J. et al. European Academy of Neurology/Movement Disorder Society-European Section Guideline on the Treatment of Parkinson’s Disease: I. Invasive Therapies. Movement Disorders 2022; 37: 1360-1374 DOI: 10.1002/mds.29066.
• 14 Pürner D, Hormozi M, Weiß D et al. Nationwide Retrospektive Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease. Neurology 2023; 101.DOI: 10.121/WNL.0000000000207858
• 15 Mathur S, Stamford J. Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Patient’s Perspective. Journal of Parkinson’s Disease 2021; 11: S141 DOI: 10.3233/JPD-212650.
• 16 Fasano A, Fung VSC, Lopiano L. et al. Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients. BMC Neurol 2019; 19: 50 DOI: 10.1186/s12883-019-1276-8.
• 17 Deuschl G, Schade-Brittinger C, Krack P. et al. A Randomized Trial of Deep-Brain Stimulation for Parkinson’s Disease. New England Journal of Medicine 2006; 355: 896-908 DOI: 10.1056/NEJMoa060281.
• 18 Schuepbach WMM, Rau J, Knudsen K. et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 2013; 368: 610-622 DOI: 10.1056/NEJMoa1205158.
• 19 Pflug C, Bihler M, Emich K. et al. Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study. Dysphagia 2018; 33: 41-50 DOI: 10.1007/s00455-017-9831-1.
• 20 Hardoff R, Sula M, Tamir A. et al. Gastric emptying time and gastric motility in patients with Parkinson’s disease. Mov Disord 2001; 16: 1041-1047 DOI: 10.1002/mds.1203.
• 21 Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol 2006; 5: 677-687 DOI: 10.1016/S1474-4422(06)70521-X.
• 22 Davis KL, Edin HM, Allen JK. Prevalence and cost of medication nonadherence in Parkinson’s disease: evidence from administrative claims data. Mov Disord 2010; 25: 474-480 DOI: 10.1002/mds.22999.
• 23 Bestetti A, Capozza A, Lacerenza M. et al. Delayed Gastric Emptying in Advanced Parkinson Disease: Correlation With Therapeutic Doses. Clin Nucl Med 2017; 42: 83-87 DOI: 10.1097/RLU.0000000000001470.
• 24 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. The Lancet Neurology 2014; 13: 141-149 DOI: 10.1016/S1474-4422(13)70293-X.
• 25 Nyholm D, Nilsson Remahl AIM, Dizdar N. et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005; 64: 216-223 DOI: 10.1212/01.WNL.0000149637.70961.4C.
• 26 Freire-Alvarez E, Kurča E, Lopez Manzanares L. et al. Levodopa-Carbidopa Intestinal Gel Reduces Dyskinesia in Parkinson’s Disease in a Randomized Trial. Mov Disord 2021; 36: 2615-2623 DOI: 10.1002/mds.28703.
• 27 Antonini A, Poewe W, Chaudhuri KR. et al. Levodopa-carbidopa intestinal gel in advanced Parkinson’s: Final results of the GLORIA registry. Parkinsonism & Related Disorders 2017; 45: 13-20 DOI: 10.1016/j.parkreldis.2017.09.018.
• 28 Fasano A, Gurevich T, Jech R. et al. Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study. Mov Disord 2021; 36: 1853-1862 DOI: 10.1002/mds.28596.
• 29 Busk K, Nyholm D. Long-term 24-h levodopa/carbidopa gel infusion in Parkinson’s disease. Parkinsonism Relat Disord 2012; 18: 1000-1001 DOI: 10.1016/j.parkreldis.2012.04.010.
• 30 Cruse B, Morales-Briceño H, Chang FCF. et al. 24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease. NPJ Parkinsons Dis 2018; 4: 34 DOI: 10.1038/s41531-018-0070-4.
• 31 Senek M, Nielsen EI, Nyholm D. Levodopa-entacapone-carbidopa intestinal gel in Parkinson’s disease: A randomized crossover study. Mov Disord 2017; 32: 283-286 DOI: 10.1002/mds.26855.
• 32 Öthman M, Widman E, Nygren I. et al. Initial Experience of the Levodopa-Entacapone-Carbidopa Intestinal Gel in Clinical Practice. J Pers Med 2021; 11: 254 DOI: 10.3390/jpm11040254.
• 33 Grund KE, Zipfel A, Duckworth-Mothes B. et al. Optimised endoscopic access for intrajejunal levodopa application in idiopathic Parkinson’s syndrome. J Neural Transm (Vienna) 2023; 130: 1383–1394 DOI: 10.1007/s00702-023-02601-0.
• 34 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 DOI: 10.1002/mds.26067.
• 35 Fernandez HH, Standaert DG, Hauser RA. et al. Levodopa-carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord 2015; 30: 500-509 DOI: 10.1002/mds.26123.
• 36 Rus T, Premzl M, Križnar NZ. et al. Adverse effects of levodopa/carbidopa intrajejunal gel treatment: A single-center long-term follow-up study. Acta Neurol Scand 2022; 146: 537-544 DOI: 10.1111/ane.13675.
• 37 Limousin P, Krack P, Pollak P. et al. Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 1998; 339: 1105-1111 DOI: 10.1056/NEJM199810153391603.
• 38 Krack P, Pollak P, Limousin P. et al. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 1998; 121: 451-457 DOI: 10.1093/brain/121.3.451.
• 39 Kleiner-Fisman G, Herzog J, Fisman DN. et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 2006; 21: S290-S304 DOI: 10.1002/mds.20962.
• 40 deSouza R-M, Moro E, Lang AE. et al. Timing of deep brain stimulation in Parkinson disease: a need for reappraisal?. Ann Neurol 2013; 73: 565-575 DOI: 10.1002/ana.23890.
• 41 Suarez-Cedeno G, Suescun J, Schiess MC. Earlier Intervention with Deep Brain Stimulation for. Parkinson’s Disease. Parkinsons Dis 2017; 2017: 9358153 DOI: 10.1155/2017/9358153.
• 42 Hacker ML, Turchan M, Heusinkveld LE. et al. Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes. Neurology 2020; 95: e393-e401 DOI: 10.1212/WNL.0000000000009946.
• 43 Fox SH, Katzenschlager R, Lim S-Y. et al. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord 2018; 33: 1248-1266 DOI: 10.1002/mds.27372.
• 44 Limousin P, Foltynie T. Long-term outcomes of deep brain stimulation in Parkinson disease. Nat Rev Neurol 2019; 15: 234-242 DOI: 10.1038/s41582-019-0145-9.
• 45 Mahlknecht P, Foltynie T, Limousin P. et al. How Does Deep Brain Stimulation Change the Course of Parkinson’s Disease?. Movement Disorders 2022; 37: 1581-1592 DOI: 10.1002/mds.29052.
• 46 Bove F, Mulas D, Cavallieri F. et al Long-term Outcomes (15 Years) After Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease. Neurology 2021; 97: e254–e262. DOI: 10.1212/WNL.0000000000012246.
• 47 Hacker ML, Meystedt JC, Turchan M. et al. Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease. Neuromodulation 2023; 26: 451-458 DOI: 10.1016/j.neurom.2022.10.051.
• 48 Shalash A, Alexoudi A, Knudsen K. et al. The impact of age and disease duration on the long term outcome of neurostimulation of the subthalamic nucleus. Parkinsonism Relat Disord 2014; 20: 47-52 DOI: 10.1016/j.parkreldis.2013.09.014.
• 49 Dafsari HS, Martinez-Martin P, Rizos A. et al. EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Movement Disorders 2019; 3: 353-365 DOI: 10.1002/mds.27626.
• 50 Merola A, Romagnolo A, Bernardini A. et al. Earlier versus later subthalamic deep brain stimulation in Parkinson’s disease. Parkinsonism Relat Disord 2015; 21: 972-975 DOI: 10.1016/j.parkreldis.2015.06.001.
• 51 Du T, Yuan T, Zhu G. et al. The effect of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation in Parkinson’s disease patients. CNS Neuroscience & Therapeutics 2022; 28: 2163-2171 DOI: 10.1111/cns.13958.
• 52 Muellner, Pineau, Maltete, et al. STN-DBS in Parkinson’s disease with early motor complications – A 10 year follow-up [abstract]. Mov Disord. 2016
• 53 Schuepbach WMM, Tonder L, Schnitzler A. et al. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease. Neurology 2019; 92: e1109–e1120 DOI: 10.1212/WNL.0000000000007037.
• 54 Frizon LA, Hogue O, Achey R. et al. Quality of Life Improvement Following Deep Brain Stimulation for Parkinson Disease: Development of a Prognostic Model. Neurosurgery 2019; 85: 343 DOI: 10.1093/neuros/nyy287.
• 55 Liu Y, Li F, Luo H. et al. Improvement of Deep Brain Stimulation in Dyskinesia in Parkinson’s Disease: A Meta-Analysis. Frontiers in Neurology 2019; 10 DOI: 10.3389/fneur.2019.00151.
• 56 Sansur CA, Frysinger RC, Pouratian N. et al. Incidence of symptomatic hemorrhage after stereotactic electrode placement. J Neurosurg 2007; 107: 998-1003 DOI: 10.3171/JNS-07/11/0998.
• 57 Rughani AI, Hodaie M, Lozano AM. Acute complications of movement disorders surgery: effects of age and comorbidities. Mov Disord 2013; 28: 1661-1667 DOI: 10.1002/mds.25610.
• 58 Zrinzo L, Foltynie T, Limousin P. et al. Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg 2012; 116: 84-94 DOI: 10.3171/2011.8.JNS101407.
• 59 Bratsos S, Karponis D, Saleh SN. Efficacy and Safety of Deep Brain Stimulation in the Treatment of Parkinson’s Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Cureus 2018; 10: e3474 DOI: 10.7759/cureus.3474.
• 60 Honey CR, Hamani C, Kalia SK. et al. Deep Brain Stimulation Target Selection for Parkinson’s Disease. Can J Neurol Sci 2017; 44: 3-8 DOI: 10.1017/cjn.2016.22.
• 61 Nijhuis FAP, Esselink R, de Bie RMA. et al. Translating Evidence to Advanced Parkinson’s Disease Patients: A Systematic Review and Meta-Analysis. Mov Disord 2021; 36: 1293-1307 DOI: 10.1002/mds.28599.
• 62 Rajan R, Garg K, Srivastava AK. et al. Device-Assisted and Neuromodulatory Therapies for Parkinson’s Disease: A Network Meta-Analysis. Mov Disord 2022; 37: 1785-1797 DOI: 10.1002/mds.29160.
• 63 Regidor I, Benita V, Del Álamo de Pedro M. et al. Duodenal Levodopa Infusion for Long-Term Deep Brain Stimulation-Refractory Symptoms in Advanced Parkinson Disease. Clin Neuropharmacol 2017; 40: 103-107 DOI: 10.1097/WNF.0000000000000216.
• 64 Marras C, Lang A, Krahn M. et al. Quality of life in early Parkinson’s disease: Impact of dyskinesias and motor fluctuations. Movement Disorders 2004; 19: 22-28 DOI: 10.1002/mds.10642.
• 65 Antonini A, Stoessl AJ, Kleinman LS. et al. Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease: a multi-country Delphi-panel approach. Curr Med Res Opin 2018; 34: 2063-2073 DOI: 10.1080/03007995.2018.1502165.
• 66 Höglinger G, Trenkwalder C. Parkinson-Krankheit, S2k-Leitlinie. Deutsche Gesellschaft für Neurologie (Hrsg.)
• 67 Antonini A, Odin P, Schmidt P. et al. Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson’s disease patients inadequately controlled on oral medications. Parkinsonism & Related Disorders 2021; 92: 59-66 DOI: 10.1016/j.parkreldis.2021.10.009.
• 68 Südmeyer, Pedrosa, Siebecker, et al. Real-world utility of MANAGE PD tool by physicians and patients in Germany. Movement Disorders 2023; MovDis DOI: 10.1002/mds.29544.