Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease
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Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation
Published on: July 16, 2014
Dominik Pürner1, Mohammad Hormozi1, Daniel Weiß1
1From the Klinik und Poliklinik für Neurologie (D.P., P.K.G., B. Haslinger, A.M.J., A.W., P.L.), Klinikum rechts der Isar der TU München, Munich; Neurologische Universitätsklinik (M.H., D.W.), Universitätsklinikum Tübingen; Klinik und Poliklinik für Neurologie (M.T.B., H.J.), Uniklinik Köln, Cologne; Klinik für Neurologie (T.P.), Universitätsklinikum Jena; Universitätsklinik und Poliklinik für Altersmedizin (T.P.), Universitätsmedizin Halle (Saale); Klinik und Poliklinik für Neurologie (E.G., M.P.-N.), Universitätsklinikum Hamburg-Eppendorf, Hamburg; Klinik und Poliklinik für Neurologie (B.F., L.K.), Universitätsklinikum Carl Gustav Carus an der TU Dresden; Klinik für Neurologie und Neurophysiologie (N.S., M.R.), Universitätsklinikum Freiburg; Klinik für Neurologie (C.v.R., U.S.), Universitätsmedizin Göttingen; Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (C.v.R.), Standort Göttingen; Klinik für Neurologie (M.W.), Elblandklinikum Meißen, Meissen; Klinik für Neurologie (A.A., M.S.), Klinikum Ernst von Bergmann Potsdam; Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson (G.E., D.G.), Beelitz-Heilstätten, Beelitz; Klinik und Poliklinik für Neurologie der Universität Regensburg am medbo Bezirksklinikum Regensburg (Z.K., E.T.); Klinik für Neurologie (W.M., S.P.), Universitätsklinikum Schleswig-Holstein, Campus Kiel; Klinik für Neurologie (P.P.-G., S.W.), Christophorus-Klinik Dülmen; Parkinson Fachklinik Haag i. OB (V.R., J.S.); Klinik und Poliklinik für Neurologie (S.B., A.F.), Universitätsmedizin Greifswald; Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (A.F.), Standort Rostock/Greifswald; Neurologische Klinik und Poliklinik (C.W.I.), Universitätsklinikum Würzburg; Klinik für Neurologie (P.K.), Charité-Universitätsmedizin Berlin; Klinik für Neurologie (A.A.K.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin; Gertrudis-Klinik Biskirchen (I.C.), Parkinson-Zentrum, Leun-Biskirchen; Klinik für Neurologie und Gerontoneurologie (B. Herting, S.v.d.L.), DIAKONEO Diak Klinikum, Diakonie-Klinikum Schwäbisch Hall; Klinik für Neurologie (A.A.B., R.L.), Marienhaus Klinikum St. Wendel-Ottweiler; Parkinson-Klinik Ortenau (W.H.J., J.K.), Wolfach; Institut für KI und Informatik in der Medizin (B. Haller), Klinikum rechts der Isar der TU München, Munich; Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (P.L.), Standort München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (P.L.), Germany.
Background And Objectives:
Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications.
Methods:
Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT.
Results:
A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS.
Discussion:
Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection.
Classification Of Evidence:
This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.
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