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Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Parkinson’s disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients’ quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

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Acknowledgements

Funding was provided by AbbVie Deutschland.

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Authors and Affiliations

  1. Department of Neurology, University of Leipzig, 04103, Leipzig, Germany

    Joseph Classen

  2. Parkinson-Klinik Ortenau, 77709, Wolfach, Germany

    Jiri Koschel

  3. Lasurstr. 27, 07551, Gera, Germany

    Christian Oehlwein

  4. Department of Neurology, Medical University Innsbruck and Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria

    Klaus Seppi

  5. Department of Neurology, Asklepios Klinik Barmbek, 22291, Hamburg, Germany

    Peter Urban

  6. Department of Neurology, Lindenbrunn Hospital, 31863, Coppenbrügge, Germany

    Christian Winkler

  7. Department of Neurology, University of Bonn, 53127, Bonn, Germany

    Ullrich Wüllner

  8. Department of Neurology, University of Rostock, 18147, Rostock, Germany

    Alexander Storch

  9. German Centre for Neurodegenerative Diseases (DZNE) Rostock, 18147, Rostock, Germany

    Ullrich Wüllner & Alexander Storch

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  1. Joseph Classen
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All authors participated in drafting the manuscript and its critical revision. All authors approved the manuscript prior to its submission.

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Correspondence to Joseph Classen.

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Conflict of interest

Joseph Classen has received unrestricted research grants from St. Jude Medical and Medtronic, and honoraria for presentations/advisory boards/consultations from Bayer Pharma, UCB, AbbVie, Desitin, Zambon, and royalties from Thieme Verlag and Kohlhammer Verlag outside the submitted work. Klaus Seppi reports grants from Medical University Innsbruck, Oesterreichische Nationalbank Nationalbank (Austrian Central Bank, Anniversary Fund; project no.: 14174), Austrian Science Fund (FWF: Der Wissenschaftsfonds; project no.: KLI82-B00), Michael J. Fox Foundation (project: PPMI study), personal fees from International Parkinson and the Movement Disorder Society, Teva, UCB, Lundbeck, AOP Orphan, Roche and Abbvie outside the submitted work. Alexander Storch has received unrestricted research grants from Boehringer Ingelheim, TEVA Pharma and Global Kinetics Cooperation (GKC, Melbourne, Australia), and honoraria for presentations/advisory boards/consultations from GKC, Pfizer Ltd. UK, Mundipharma, UCB, Grünenthal, AbbVie, TVA, MEDA, Desitin, Medtronic, Zambon, and royalties from Kohlhammer Verlag and Elsevier Press outside the submitted work. Jiri Koschel, Christian Oehlwein, Peter Urban, Christian Winkler, Ullrich Wüllner had nothing to disclose.

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Classen, J., Koschel, J., Oehlwein, C. et al. Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues. J Neural Transm 124, 1029–1036 (2017). https://doi.org/10.1007/s00702-017-1757-0

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