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Weiss D, Volkmann J, Fasano A, et al. Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?. Ann Neurol. 2021;90(5):699-710doi: 10.1002/ana.26164.
Weiss, D., Volkmann, J., Fasano, A., Kühn, A., Krack, P., & Deuschl, G. (2021). Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?. Annals of neurology, 90(5), 699-710. https://doi.org/10.1002/ana.26164
Weiss, Daniel, et al. "Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?." Annals of neurology vol. 90,5 (2021): 699-710. doi: https://doi.org/10.1002/ana.26164
Weiss D, Volkmann J, Fasano A, Kühn A, Krack P, Deuschl G. Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?. Ann Neurol. 2021 Nov;90(5):699-710. doi: 10.1002/ana.26164. Epub 2021 Jul 20. PMID: 34235776.
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Ann Neurol. 2021 Nov;90(5):699-710. doi: 10.1002/ana.26164. Epub 2021 Jul 20.

Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease?.

Annals of neurology

Daniel Weiss, Jens Volkmann, Alfonso Fasano, Andrea Kühn, Paul Krack, Günther Deuschl

Affiliations

  1. Centre for Neurology, Department for Neurodegenerative Diseases, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  2. Department of Neurology, University Hospital and Julius-Maximilian-University, Würzburg, Germany.
  3. Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, ON, Canada.
  4. Division of Neurology, University of Toronto, Toronto, ON, Canada.
  5. Krembil Brain Institute, Toronto, ON, Canada.
  6. Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada.
  7. Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  8. Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
  9. Department of Neurology, University Hospital Schleswig Holstein (UKSH), Christian-Albrechts-University Kiel, Kiel, Germany.

PMID: 34235776 DOI: 10.1002/ana.26164

Abstract

In Parkinson's disease, both motor and neuropsychiatric complications unfold as a consequence of both incremental striatal dopaminergic denervation and intensifying long-term dopaminergic treatment. Together, this leads to 'dopaminergic sensitization' steadily increasing motor and behavioral responses to dopaminergic medication that result in the detrimental sequalae of long-term dopaminergic treatment. We review the clinical presentations of 'dopaminergic sensitization', including rebound off and dyskinesia in the motor domain, and neuropsychiatric fluctuations and behavioral addictions with impulse control disorders and dopamine dysregulation syndrome in the neuropsychiatric domain. We summarize state-of-the-art deep brain stimulation, and show that STN-DBS allows dopaminergic medication to be tapered, thus supporting dopaminergic desensitization. In this framework, we develop our integrated debatable viewpoint of "changing gears", that is we suggest rethinking earlier use of subthalamic nucleus deep brain stimulation, when the first clinical signs of dopaminergic motor or neuropsychiatric complications emerge over the steadily progressive disease course. In this sense, subthalamic deep brain stimulation may help reduce longitudinal motor and neuropsychiatric symptom expression - importantly, not by neuroprotection but by supporting dopaminergic desensitization through postoperative medication reduction. Therefore, we suggest considering STN-DBS early enough before patients encounter potentially irreversible psychosocial consequences of dopaminergic complications, but importantly not before a patient shows first clinical signs of dopaminergic complications. We propose to consider neuropsychiatric dopaminergic complications as a new inclusion criterion in addition to established motor criteria, but this concept will require validation in future clinical trials. ANN NEUROL 2021;90:699-710.

© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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