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Disease stage dependency of motor and non-motor fluctuations in Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Recent data suggested a decrease in non-motor fluctuations in late-stage Parkinson’s disease (PD), but systematic data on non-motor fluctuations over the whole disease course are mainly lacking. We performed a meta-analysis of two studies with very similar cross-sectional cohort designs, namely the German multicenter Non Motor Fluctuation in PD study and the Swedish part of the European multicenter study Care for Late Stage Parkinsonism. We included only patients with documented motor fluctuations in the analyses. Disease stage was estimated using the Hoehn and Yahr score, motor symptoms using the Unified PD Rating Scale part III motor score and non-motor symptom (NMS) fluctuations using the modified version of the NMS scale assessing a broad range of NMS in motor On and Off state. We included 101 patients (55% men; median age: 71 (interquartile range, IQR 65–78) years with Hoehn and Yahr stages ranging from 1 to 5 [median (IQR) 3.0 (2.0–4.0); distribution of patients in Hoehn and Yahr stages was n = 42 (42%) in stages 2/3 and n = 48 (48%) in stages 4/5]. We found a clear dependency of non-motor burden on Hoehn and Yahr stage with increasing symptom severity, but decreasing fluctuation amplitudes for motor and NMS (difference of symptom severity between On and Off state) with disease stage progression. Indeed, in Hoehn and Yahr stage 5, we did not detect significant NMS fluctuations. Multivariate regression with major demographic and clinical covariates confirmed these results. In conclusion, NMS fluctuations showed a similar disease stage dependency as observed for motor fluctuations with decreasing fluctuation amplitude with disease progression.

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Acknowledgements

We acknowledge all collaborators of the NoMoFlu-PD study group and the international Parkinson’s disease non-motor group who have contributed to the concept of this work. The NoMoFlu-PD Study Group consists of the following structure: NoMoFlu-PD steering committee: K. Ray Chaudhuri, National Parkinson Foundation Centre of Excellence, Kings College Hospital and Kings College London and Biomedical Research Centre, Kings College London, UK; Georg Ebersbach, Movement Disorders Clinic, Beelitz-Heilstätten, Germany; Gerd Fuchs, Parkinson Clinic Wolfach, Wolfach, Germany; Wolfgang H. Jost, Dept. of Neurology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany; Per Odin, Dept. of Neurology, Klinikum Bremerhaven, Bermerhaven, Germany; Alexander Storch, Division of Neurodegenerative Diseases, Dept. of Neurology, Dresden University of Technology, and German Centre for Neurodegenerative Diseases (DZNE), Research Site Dresden, Dresden, Germany. Participating centers and investigators: Division of Neurodegenerative Diseases, Dept. of Neurology, Dresden University of Technology, and DZNE, German Centre for Neurodegenerative Diseases, Research Site Dresden, Dresden, Germany (Drs. Storch, Schneider, Wolz, Klingelhöfer, Fauser, Reichmann, Melzer, Stürwald, Schmidt [study nurse], A. Wolz [study nurse], C. Bosredon [study nurse]); Movement Disorders Clinic, Beelitz-Heilstätten, Germany (Drs. Nebe, Ebersbach); Dept. of Neurology, Klinikum Bremerhaven, Bremerhaven, Germany (Gies, Drs. Odin, Mahler); Parkinson Clinic Wolfach, Wolfach, Germany (Dr. Fuchs); Dept. of Neurology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany (Dr. Jost).

Funding

The NoMoFlu-PD study was supported in part by an unrestricted research grant from Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany, and the CLaSP consortium was mainly funded by a JPND grant provided by the Swedish Research Council (VR), CLaSP/JPND HC-559-002; MultiPark, the strategic research area for neuroscience at Lund University (the Swedish Parkinson Foundation; the Swedish Parkinson Academy, the Faculty of Medicine at Lund University). The financial sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had the final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Department of Neurology, University of Rostock, Gehlsheimer Straße 20, 18147, Rostock, Germany

    Alexander Storch

  2. German Center for Neurodegenerative Diseases (DZNE) Rostock, 18147, Rostock, Germany

    Alexander Storch

  3. Division of Neurology, Department of Clinical Sciences, Lund University, 22185, Lund, Sweden

    Kristina Rosqvist & Per Odin

  4. Movement Disorders Clinic, 14547, Beelitz-Heilstätten, Germany

    Georg Ebersbach

  5. Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, 22185, Lund, Sweden

    Per Odin

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  1. Alexander Storch
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  2. Kristina Rosqvist
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  4. Per Odin
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NoMoFlu-PD Study Group

Contributions

AS: Study concept and design, acquisition of data, analyzing of data, interpretation of data, drafting and finalizing the manuscript. KR: Acquisition of data, important critical revision of the manuscript. GE: Study concept and design, acquisition of data, interpretation of data, and critical revision of the manuscript. PO: Study concept and design, acquisition of data, interpretation of data, and critical revision of the manuscript.

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Correspondence to Alexander Storch.

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Conflict of interest

Dr. Storch has received funding from the Deutsche Forschungsgemeinschaft (DFG) and the Helmholtz-Association. He received unrestricted research grants from GKC Melbourne, Pfizer, and TEVA Pharma, honoraria for presentations/lectures/consultancies or advisory boards from AbbVie, Bayer Healthcare, Bial, GKC, Grünenthal, UCB, Zambon, Ca, AbbVie, TEVA, Lundbeck, and UCB Pharma, outside the submitted work. He has served on the editorial boards of Stem Cells, Stem Cells International, Open Biotechnology Journal, and the Journal of Biological Chemistry. Dr. Rosqvist has nothing to disclose. Dr. Ebersbach reports grants from Boheringer Ingelheim Pharma, Ingelheim, Germany, during the conduct of the study; personal fees from UCB Pharma, Germany, Zambon Pharma, Germany, AbbVie Pharma, Germany, Desitin Arzneimittel, Germany, Bial Pharma, Germany, Grünenthal, Germany, Kohlhammer Verlag, Germany, Thieme Verlag, Germany, Stada Pharma, Germany, Licher GmbH, Germany, AOK Nordost, Britannia Pharma, UK, Neurocrine Inc., USA, Neuroderm Inc, Israel, outside the submitted work. Dr. Odin has received unrestricted research grants from GKC Melbourne, as well as, honoraria for presentations/lectures/consultancies or advisory boards from AbbVie, Bial, Britannia, Decitin, GKC, Grünenthal, Nordic Infucare, Stada, UCB, Zambon, outside the submitted work. He has served on the editorial board of NPJ.

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Storch, A., Rosqvist, K., Ebersbach, G. et al. Disease stage dependency of motor and non-motor fluctuations in Parkinson’s disease. J Neural Transm 126, 841–851 (2019). https://doi.org/10.1007/s00702-019-02033-9

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