Continuous subcutaneous apomorphine in advanced Parkinson’s disease patients treated with deep brain stimulation
- 33 Downloads
Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson’s disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS.
We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12 years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments.
Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03).
In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.
KeywordsAdvanced Parkinson’s disease Deep brain stimulation Apomorphine Treatment
ÁS: conception, design, analysis and interpretation of data, drafting, review, and final approval. GF-P: design, acquisition of data, analysis, and interpretation of data, critical review, and final approval. BA: design, acquisition of data, critical review, and final approval. JLR: critical review and final approval. EA: critical review and final approval. MTR: critical review and final approval. MG: critical review and final approval. AC: acquisition of data, critical review, and final approval.
The study did not receive funding.
Compliance with ethical standards
Conflicts of interest
ÁS has received honoraria from Britannia/Italfarmaco, and Abbvie; GFP from Italfarmaco and UCB; BA from Italfarmaco and Abbvie; AC from Abbvie and Zambon; MTR, JLR, EA, and MG have no conflicts of interest.
This study was performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Since this is a retrospective clinical study, no informed consent was required.
- 1.Martinez-Martin P, Kulisevsky J, Mir P, Tolosa E, García-Delgado P, Luquin MR (2018) Validation of a simple screening tool for early diagnosis of advanced Parkinson’s disease in daily practice: the CDEPA questionnaire. NPJ Parkinsons Dis 4:20. https://doi.org/10.1038/s41531-018-0056-2 CrossRefGoogle Scholar
- 3.Pollak P (2013) Deep brain stimulation for Parkinson’s disease—patient selection. Handb Clin Neurol 116:97–105. https://doi.org/10.1016/B978-0-444-53497-2.00009-7 CrossRefGoogle Scholar
- 4.Katzenschlager R, Poewe W, Rascol O, Trenkwalder C, Deuschl G, Chaudhuri KR, Henriksen T, van Laar T, Spivey K, Vel S, Staines H, Lees A (2018) Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 17:749–759. https://doi.org/10.1016/S1474-4422(18)30239-4 CrossRefGoogle Scholar
- 5.Auffret M, Drapier S, Vérin M. Pharmacological insights into the use of apomorphine in Parkinson’s disease: clinical relevance (2018). Clin Drug Investig 38: 287–312. https://doi.org/10.1007/s40261-018-0619-3
- 6.Nyholm D. Duodopa® treatment for advanced Parkinson’s disease: a review of efficacy and safety (2012). Parkinsonism Relat Dis 18: 916–929 https://doi.org/10.1016/j.parkreldis.2012.06.022
- 7.Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A; LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study (2014). Lancet Neurol 13: 141–149. https://doi.org/10.1016/S1474-4422(13)70293-X
- 10.Volkmann J, Albanese A, Antonini A, Chaudhuri KR, Clarke CE, de Bie RM, Deuschl G, Eggert K, Houeto JL, Kulisevsky J, Nyholm D, Odin P, Østergaard K, Poewe W, Pollak P, Rabey JM, Rascol O, Ruzicka E, Samuel M, Speelman H, Sydow O, Valldeoriola F, van der Linden C, Oertel W (2013) Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 260:2701–2714. https://doi.org/10.1007/s00415-012-6798-6 CrossRefGoogle Scholar
- 12.R Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/
- 15.Martins de Campos A, Braz L, Linhares P, Rosas MJ (2017) Deep brain stimulation for Parkinson’s disease: subcutaneous apomorphine as an alternative for patients unable to tolerate surgery under local anesthesia. J Neurol Sci 378:137–139. https://doi.org/10.1016/j.jns.2017.04.048 CrossRefGoogle Scholar
- 16.Carron R, Fraix V, Maineri C, Seigneuret E, Piallat B, Krack P, Pollak P, Benabid AL, Chabardès S (2011) High frequency deep brain stimulation of the subthalamic nucleus versus continuous subcutaneous apomorphine infusion therapy: a review. J Neural Transm (Vienna) 118915:924. https://doi.org/10.1007/s00702-010-0556-7 Google Scholar
- 17.Varma TR, Fox SH, Eldridge PR, Littlechild P, Byrne P, Forster A, Marshall A, Cameron H, McIver K, Fletcher N, Steiger M (2003) Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson’s disease patients previously reliant on apomorphine. J Neurol Neurosurg Psychiatry 74:170–174CrossRefGoogle Scholar
- 18.De Gaspari D, Siri C, Landi A, Cilia R, Bonetti A, Natuzzi F, Morgante L, Mariani CB, Sganzerla E, Pezzoli G, Antonini A (2006) Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson’s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus. J Neurol Neurosurg Psychiatry 77:450–453. https://doi.org/10.1136/jnnp.2005.078659 CrossRefGoogle Scholar
- 19.Alegret M, Valldeoriola F, Martí M, Pilleri M, Junqué C, Rumià J, Tolosa E (2004) Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson’s disease. Mov Disord 19:1463–1469. https://doi.org/10.1002/mds.20237 CrossRefGoogle Scholar
- 20.Antonini A, Isaias IU, Rodolfi G, Landi A, Natuzzi F, Siri C, Pezzoli G (2011) A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation. J Neurol 258:579–585. https://doi.org/10.1007/s00415-010-5793-z CrossRefGoogle Scholar
- 21.Borgemeester RW, Drent M, van Laar T Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson’s disease patients (2016). Parkinsonism Relat Disord 23: 17–22. https://doi.org/10.1016/j.parkreldis.2015.11.013
- 23.Juhász A, Deli G, Aschermann Z, Janszky J, Harmat M, Makkos A, Kovács M, Komoly S, Balás I, Dóczi T, Büki A, Kovács N (2017) How efficient is subthalamic deep brain stimulation in reducing dyskinesia in Parkinson’s disease? Eur Neurol 77:281–287. https://doi.org/10.1159/000455208 CrossRefGoogle Scholar