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Advanced stages of PD: interventional therapies and related patient-centered care

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

During the last decades, symptomatic treatment of motor symptoms of Parkinson’s disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson’s disease held on November 22, 2014 in Frankfurt, Germany.

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References

  • Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP (2005) Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol 62(4):554–560. doi:10.1001/archneur.62.4.554

    Article  PubMed  Google Scholar 

  • Antonini A, Tolosa E (2009) Apomorphine and levodopa infusion therapies for advanced Parkinson’s disease: selection criteria and patient management. Expert Rev Neurotherapeutics 9:859–867. doi:10.1586/ern.09.48

    Article  CAS  Google Scholar 

  • Antonini A, Chaudhuri KR, Martinez-Martin P, Odin P (2010) Oral and infusion levodopa-based strategies for managing motor complications in patients with Parkinson’s disease. CNS Drugs 24:119–129. doi:10.2165/11310940-000000000-00000

    Article  PubMed  CAS  Google Scholar 

  • Antonini A, Yegin A, Preda C, Bergmann L, Poewe W, investigators Gs, coordinators (2015) Global long-term study on motor and non-motor symptoms and safety of levodopa-carbidopa intestinal gel in routine care of advanced Parkinson’s disease patients; 12-month interim outcomes. Parkinsonism Relat Disord 21(3):231–235. doi:10.1016/j.parkreldis.2014.12.012

    Article  PubMed  Google Scholar 

  • Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, Goetz CG, Halliday GM, Hardy J, Lang AE, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G (2014) Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson’s disease. Mov Disord 29(4):454–462. doi:10.1002/mds.25844

    Article  PubMed  PubMed Central  Google Scholar 

  • Borgemeester RWK, Drent M, Laar TV (2014) Long-term data on subcutaneous apomorphine in Parkinson’s disease patients; a retrospective analysis of a Dutch cohort of 139 patients [abstract]. Mov Disord 29(Suppl 1):351

    Google Scholar 

  • Boyle A, Ondo W (2015) Role of Apomorphine in the Treatment of Parkinson’s Disease. CNS Drugs 1–7 doi:10.1007/s40263-014-0221-z

  • Bredberg E, Nilsson D, Johansson K et al (1993) Intraduodenal infusion of a water-based levodopa dispersion for optimization of the therapeutic effect in severe parkinsons-disease. Eur J Clin Pharmacol 45:117–122

    Article  PubMed  CAS  Google Scholar 

  • Breit S, Schulz JB, Benabid AL (2004) Deep brain stimulation. Cell Tissue Res 318(1):275–288. doi:10.1007/s00441-004-0936-0

    Article  PubMed  Google Scholar 

  • Breit S, LeBas JF, Koudsie A, Schulz J, Benazzouz A, Pollak P, Benabid AL (2008) Pretargeting for the implantation of stimulation electrodes into the subthalamic nucleus: a comparative study of magnetic resonance imaging and ventriculography. Neurosurgery 62(Suppl 2):840–852. doi:10.1227/01.neu.0000316286.29995.4c

    PubMed  Google Scholar 

  • Bronte-Stewart H, Barberini C, Koop MM, Hill BC, Henderson JM, Wingeier B (2009) The STN β-band profile in Parkinson’sdisease is stationary and shows prolonged attenuation after deep brain stimulation. Exp Neurol 215(1):20–28

    Article  PubMed  CAS  Google Scholar 

  • Ceballos-Baumann A, Hack HJ (2011) Rotigotine transdermal patch in combination therapy for Parkinson’s disease–observations in routine clinical practice. Curr Med Res Opin 27(10):1899–1905. doi:10.1185/03007995.2011.611630

    Article  PubMed  CAS  Google Scholar 

  • Colzi A, Turner K, Lees AJ (1998) Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson’s disease. J Neurol Neurosurg Psychiatry 64(5):573–576

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Contarino MF, Bour LJ, Verhagen R, Lourens MA, de Bie RM, van den Munckhof P, Schuurman PR (2014) Directional steering: a novel approach to deep brain stimulation. Neurology 83(13):1163–1169. doi:10.1212/wnl.0000000000000823

    Article  PubMed  Google Scholar 

  • Deuschl G, Agid Y (2013) Subthalamic neurostimulation for Parkinson’s disease with early fluctuations: balancing the risks and benefits. Lancet Neurol 12(10):1025–1034. doi:10.1016/s1474-4422(13)70151-0

    Article  PubMed  Google Scholar 

  • Devos D, for the French DUODOPA Study Group (2009) Patient profile, indications, efficacy and safety of duodenal levodopa infusion in advanced Parkinson’s disease. Mov Disord 24:993–1000. doi:10.1002/mds.22450

    Article  Google Scholar 

  • Dewey RB Jr (2004) Management of motor complications in Parkinson’s disease. Neurology 62(6 Suppl 4):S3–S7

    Article  PubMed  Google Scholar 

  • Drapier S, Gillioz AS, Leray E, Peron J, Rouaud T, Marchand A, Verin M (2012) Apomorphine infusion in advanced Parkinson’s patients with subthalamic stimulation contraindications. Parkinsonism Relat Disord 18(1):40–44. doi:10.1016/j.parkreldis.2011.08.010

    Article  PubMed  Google Scholar 

  • Duker AP, Espay AJ (2013) Surgical treatment of Parkinson disease: past, present, and future. Neurol Clin 31(3):799–808. doi:10.1016/j.ncl.2013.03.007

    Article  PubMed  PubMed Central  Google Scholar 

  • Farris S, Giroux M (2013) Retrospective review of factors leading to dissatisfaction with subthalamic nucleus deep brain stimulation during long-term management. Surg Neurol Int 4:69. doi:10.4103/2152-7806.112612

    Article  PubMed  PubMed Central  Google Scholar 

  • Fasano A, Herzog J, Seifert E et al (2011) Modulation of gait coordination by subthalamic stimulation improves freezing of gait. MovDisord 26:844–851

    Google Scholar 

  • Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ (2014) Levodopa-carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord. doi:10.1002/mds.26123

    PubMed  PubMed Central  Google Scholar 

  • Follett KA, Weaver FM, Stern M et al (2010) Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 362(22):2077–2091

    Article  PubMed  CAS  Google Scholar 

  • Gancher ST, Nutt JG, Woodward WR (1991) Absorption of apomorphine by various routes in parkinsonism. Mov Disord 6(3):212–216

    Article  PubMed  CAS  Google Scholar 

  • Goetz CG, Poewe W, Rascol O, Sampaio C (2005) Evidence-based medical review update: pharmacological and surgical treatments of Parkinson’s disease: 2001 to 2004. Mov Disord 20(5):523–539. doi:10.1002/mds.20464

    Article  PubMed  Google Scholar 

  • Herzog J, Weiss PH, Assmus A, Wefer B, Seif C, Braun PM, Pinsker MO, Herzog H, Volkmann J, Deuschl G, Fink GR (2008) Improved sensory gating of urinary bladder afferents in Parkinson’s disease following subthalamic stimulation. Brain J Neurol 131(Pt 1):132–145. doi:10.1093/brain/awm254

    Google Scholar 

  • Hilker R, Antonini A, Odin P (2011) What is the best treatment for fluctuating Parkinson’s disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus? J Neural Transm 118:907–914

    Article  PubMed  CAS  Google Scholar 

  • Honig H, Antonini A, Martinez-Martin P et al (2009) Intrajejunal levodopa infusion in Parkinson’s disease: a pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov Disord 24:1468–1474. doi:10.1002/mds.22596

    Article  PubMed  Google Scholar 

  • Hughes AJ, Bishop S, Kleedorfer B, Turjanski N, Fernandez W, Lees AJ et al (1993) Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years. Mov Disord 8:165–170. doi:10.1002/mds.870080208

    Article  PubMed  CAS  Google Scholar 

  • Katzenschlager R, Hughes A, Evans A, Manson AJ, Hoffman M, Swinn L, Watt H, Bhatia K, Quinn N, Lees AJ (2005) Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: a prospective study using single-dose challenges. Mov Disord 20(2):151–157. doi:10.1002/mds.20276

    Article  PubMed  Google Scholar 

  • Kim HJ, Jeon BS, Lee JY, Paek SH, Kim DG (2012) The benefit of subthalamic deep brain stimulation for pain in Parkinson disease: a 2-year follow-up study. Neurosurgery 70(1):18–23. doi:10.1227/NEU.0b013e3182266664 (discussion 23–14)

    Article  PubMed  Google Scholar 

  • Manson AJ, Turner K, Lees AJ (2002) Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson’s disease: long-term follow-up study of 64 patients. Mov Disord 17(6):1235–1241. doi:10.1002/mds.10281

    Article  PubMed  Google Scholar 

  • Meier U, Diener HC (2007) Integrierte versorgung in der neurologie: integrierte versorgungskonzepte und kooperative versorgungsstrukturen. Georg Thieme Verlag, Stuttgart

    Book  Google Scholar 

  • Moro E, Volkmann J, Konig IR, Winkler S, Hiller A, Hassin-Baer S, Herzog J, Schnitzler A, Lohmann K, Pinsker MO, Voges J, Djarmatic A, Seibler P, Lozano AM, Rogaeva E, Lang AE, Deuschl G, Klein C (2008) Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology 70(14):1186–1191. doi:10.1212/01.wnl.0000307748.11216.03

    Article  PubMed  CAS  Google Scholar 

  • Morrell M (2006) Brain stimulation for epilepsy: can scheduled or responsive neurostimulation stop seizures? CurrOpinNeurol 19(2):164–168

    Google Scholar 

  • Naidu Y, Tluk S, Martin A, Jacobs S, Davidson C, Richards C, Martinez-Martin P, Chaudhuri KR (2009) Initiation of apomorphine infusion in advanced Parkinson’s disease and effect on non-motor symptoms compared to non-invasive strategies. Mov Disord 24(Suppl 1):S360

    Google Scholar 

  • Nyholm D, Remahl A, Dizdar N et al (2005) Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 64:216–223. doi:10.1212/01.WNL.0000149637.70961.4C

    Article  PubMed  CAS  Google Scholar 

  • Nyholm D, Johansson A, Lennernäs H, Askmark H (2012) Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial. Eur J Neurol 19:820–826. doi:10.1111/j.1468-1331.2011.03614.x

    Article  PubMed  CAS  Google Scholar 

  • Odekerken VJ, van Laar T, Staal MJ et al (2013) Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol 12(1):37–44

    Article  PubMed  Google Scholar 

  • Okun MS, Tagliati M, Pourfar M et al (2005) Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers. Arch Neurol 62:1250–1255

    Article  PubMed  Google Scholar 

  • Okun MS, Gallo BV, Mandybur G et al (2012) Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial. Lancet Neurol 11:140–149

    Article  PubMed  Google Scholar 

  • Olanow CW, Kieburtz K, Odin P, Espay AJ (2014) 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. doi:10.1016/S1474-4422(13)70293-X

    PubMed Central  Google Scholar 

  • Pfeiffer RF, Gutmann L, Hull KL Jr, Bottini PB, Sherry JH (2007) Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson’s disease. Parkinsonism Relat Dis 13(2):93–100. doi:10.1016/j.parkreldis.2006.06.012

    Article  Google Scholar 

  • Poewe W, Kleedorfer B, Wagner M, Bosch S, Schelosky L (1993) Continuous subcutaneous apomorphine infusions for fluctuating Parkinson’s disease. Long-term follow-up in 18 patients. Adv Neurol 60:656–659

    PubMed  CAS  Google Scholar 

  • Pollak P, Champay AS, Hommel M, Perret JE, Benabid AL (1989) Subcutaneous apomorphine in Parkinson’s disease. J Neurol Neurosurg Psychiatry 52(4):544

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Russmann H, Ghika J, Villemure JG, Robert B, Bogousslavsky J, Burkhard PR et al (2004) Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Neurology 63:1952–1954

    Article  PubMed  CAS  Google Scholar 

  • Schuepbach WMM, Rau J, Knudsen K et al (2013) Neurostimulation for Parkinson’s Disease with Early Motor Complications. N Engl J Med 368:610–622. doi:10.1056/NEJMoa1205158

    Article  PubMed  CAS  Google Scholar 

  • Schupbach M, Lohmann E, Anheim M, Lesage S, Czernecki V, Yaici S, Worbe Y, Charles P, Welter ML, Pollak P, Durr A, Agid Y, Brice A (2007) Subthalamic nucleus stimulation is efficacious in patients with Parkinsonism and LRRK2 mutations. Mov Disord 22(1):119–122. doi:10.1002/mds.21178

    Article  PubMed  Google Scholar 

  • Shoulson I, Glaubiger GA, Chase TN (1975) On-off response. Clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients. Neurology 25:1144–1148

    Article  PubMed  CAS  Google Scholar 

  • Stibe CM, Lees AJ, Kempster PA, Stern GM (1988) Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1(8582):403–406

    Article  PubMed  CAS  Google Scholar 

  • Stocchi F, Vacca L, De Pandis MF, Barbato L, Valente M, Ruggieri S (2001) Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson’s disease: long-term results. Neurol Sci Off J Italian Neurol Soc Italian Soc Clin Neurophysiol 22(1):93–94

    CAS  Google Scholar 

  • Sudmeyer M, Volkmann J, Wojtecki L, Deuschl G, Schnitzler A, Moller B (2012) Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson’s disease and their family members. Der Nervenarzt 83(4):481–486. doi:10.1007/s00115-011-3400-x

    Article  PubMed  CAS  Google Scholar 

  • Tyne H, Parsons J, Sinnott A, Fox S, Fletcher N, Steiger M (2004) A 10 year retrospective audit of long-term apomorphine use in Parkinson’s disease. J Neurol 251(11):1370–1374. doi:10.1007/s00415-004-0547-4

    Article  PubMed  Google Scholar 

  • van Laar T, Postma AG, Drent M (2010) Continuous subcutaneous infusion of apomorphine can be used safely in patients with Parkinson’s disease and pre-existing visual hallucinations. Parkinsonism Relat Disord 16(1):71–72. doi:10.1016/j.parkreldis.2009.05.006

    Article  PubMed  Google Scholar 

  • Volkmann J, Albanese A, Antonini A et al (2013) Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 260:2701–2714. doi:10.1007/s00415-012-6798-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Weaver FM, Follett K, Stern M et al (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301:63–73

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Weiss D, Walach M, Meisner C, Fritz M, Scholten M, Breit S, Plewnia C, Bender B, Gharabaghi A, Wachter T, Kruger R (2013) Nigral stimulation for resistant axial motor impairment in Parkinson’s disease? A randomized controlled trial. Brain J Neurol 136(Pt 7):2098–2108. doi:10.1093/brain/awt122

    Article  Google Scholar 

  • Zibetti M, Merola A, Artusi CA et al (2013) Levodopa/carbidopa intestinal gel infusion in advanced Parkinson’s disease: a 7-year experience. Eur J Neurol 21:312–318. doi:10.1111/ene.12309

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank G. Hipp for careful revision and valuable comments on the manuscript. Work of R.K. is funded by the National Research Fund, Luxembourg within the PEARL program (FNR/P13/6682797/Krüger) and the National Center for Excellence in Research—Parkinson’s disease (NCER-PD).

Conflict of interest

M. Hahne received remuneration for lectures and/or counseling services from the following companies: Desitin Pharma, Glaxo Smith-Kline GmbH & Co. KG, Orion Pharma, UCB Pharma. W.H. Jost received remuneration for lectures and/or counseling services from the following companies: Abbvie, Desitin Pharma, Medtronic, UCB Pharma, Zambon. Christian Winkler participated in advisory boards for Abbott, AbbVie, Orion Pharma GmbH and UCB. He received honoraria for talks from Abbott, AbbVie, Licher MT and UCB. C. Redecker received remuneration for lectures and/or counseling services from the following companies: Desitin Pharma, AbbVie Pharma, TEVA Pharma, Bayer Pharma, Novartis Pharma, Orion Pharma, UCB Pharma. P. Lingor received research support of the German Research Council (DFG), the Michael J Fox Foundation, the Else Kröner-Fresenius Foundation, as well as speaker’s honoraria and counseling remuneration from Abbvie and BayerVital. R. Krüger received research grants of the German Research Council (DFG; KR2119/8-1), the Michael J Fox Foundation, the German Federal Ministry for Education and Research (BMBF, COURAGE-PD, Mito-PD) and the Fond National de Recherche (FNR; PEARL and NCER-PD), Luxembourg, as well as speaker’s honoraria from Abbvie, B. Braun GmbH, St Jude Medical, and Medtronic. M.Lorrain received renumeration for lectures and/or counseling services from the following companies: Abbvie, Desitin Pharma, UCB Pharma, Medtronic, TEVA Pharma. Rüdiger Hilker has received speaker honoraria from Medtronic, Orion, GlaxoSmithKline, TEVA, Cephalon, Solvay, Desitin, Ipsen, Merz, Archimedes Pharma and Boehringer Ingelheim as well as travel funding from Medtronic, Allergan and Cephalon. He has served on a scientific advisory board for Cephalon and has received research funding from the Deutsche Parkinson Vereinigung (dPV), Bundesministerium für Bildung und Forschung and Goethe University Frankfurt.

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Krüger, R., Hilker, R., Winkler, C. et al. Advanced stages of PD: interventional therapies and related patient-centered care. J Neural Transm 123, 31–43 (2016). https://doi.org/10.1007/s00702-015-1418-0

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