The spectrum of "off" in Parkinson's disease: What have we learned over 40 years?

Kelvin L Chou; Mark Stacy; Tanya Simuni; Janis Miyasaki; Wolfgang H Oertel; Kapil Sethi; Hubert H Fernandez; Fabrizio Stocchi

doi:10.1016/j.parkreldis.2018.02.001

The spectrum of "off" in Parkinson's disease: What have we learned over 40 years?

Parkinsonism Relat Disord. 2018 Jun:51:9-16. doi: 10.1016/j.parkreldis.2018.02.001. Epub 2018 Feb 2.

Authors

Kelvin L Chou¹, Mark Stacy², Tanya Simuni³, Janis Miyasaki⁴, Wolfgang H Oertel⁵, Kapil Sethi⁶, Hubert H Fernandez⁷, Fabrizio Stocchi⁸

Affiliations

¹ Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: klchou@med.umich.edu.
² Department of Neurology, Duke University Medical Center, Durham, NC, USA.
³ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴ Division of Neurology, Department of Medicine, University of Alberta, Kaye Edmonton Clinic, Canada.
⁵ Department of Neurology, University Clinic, Philipps Universität Marburg, Marburg, Germany; Institute for Neurogenomics, Helmholtz Center for Health and Environment, Munich, Germany.
⁶ Department of Neurology, Medical College of Georgia at Augusta University, Augusta, GA, USA.
⁷ Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA.
⁸ Department of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele Roma, Roma, Italy.

PMID: 29456046
DOI: 10.1016/j.parkreldis.2018.02.001

Abstract

The terms "on" and "off" were used by Marsden and his contemporaries over 40 years ago to describe times when Parkinson's disease patients experienced good motor function ("on") and immobility ("off"). Yet there remains no published consensus definition of "off", leading clinicians and patients to develop individualized impressions of "off" determinations. In this paper, we first discuss the evolution of the terminology and understanding of "off" states since Marsden's time, which now include non-motor as well as motor symptoms. We then review pathophysiology and risk factors for the development of "off" states as well as tools to detect the "off" state, before proposing a practical definition of "off" for consideration. A common, practical definition of the "off" state could improve clinical recognition of "off" symptoms and lead to significant benefit for patients.

Keywords: Motor complications; Motor fluctuations; Non-motor fluctuations; Off; Parkinson's disease; Wearing off.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antiparkinson Agents / adverse effects*
Humans
Levodopa / adverse effects*
Parkinson Disease* / complications
Parkinson Disease* / drug therapy
Parkinson Disease* / physiopathology

Substances

Antiparkinson Agents
Levodopa