@article{8c8fee46f4e64e7c980c16222a9f008f,
title = "The spectrum of “off” in Parkinson's disease: What have we learned over 40 years?",
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",
author = "Chou, {Kelvin L.} and Mark Stacy and Tanya Simuni and Janis Miyasaki and Oertel, {Wolfgang H.} and Sethi, {Kapil Dev} and Fernandez, {Hubert H.} and Fabrizio Stocchi",
note = "Funding Information: Dr. Fernandez has received research support from Abbvie , Biotie/Acorda Therapeutics , Michael J. Fox Foundation (grant 6163 ), Movement Disorders Society , NIH/NINDS (grant R01CA175100 ), Parkinson Study Group , Rhythm , Sunovion , but has no owner interest in any pharmaceutical company. He has received honoraria from Prime Education Inc. International Parkinson and Movement Disorders Society, Carling Communications, Medscape, and Vindico as a speaker in CME events and has received honoraria from AbbVie, Biogen, Blackthorn, Inventiv, Kyowa Hakko Kirin, Medscape, Voyager, Sunovion, and Pfizer Pharmaceuticals, as a consultant. He has received royalty payments from Demos Publishing for serving as a book author/editor and serves as a member of the publication committee for Acorda and Biotie Pharmaceuticals but does not receive any personal compensation for these. Funding Information: Dr. Miyasaki receives research support from the NIH PCORI (grant IHS 1408-20134 ), Allergan , and University Hospital Foundation , has served as a grant reviewer for the NINDS, has served on the Scientific Advisory Board of the Parkinson Society Canada, receives royalties from UpToDate and serves as a consultant for GE and Sunovion. Funding Information: Dr. Sethi receives research support from the National Parkinson Foundation , Accorda , Kyowa and US World Meds . He serves as a consultant for Sunovion, Adamas and Merz. Funding Information: Prof. Oertel is theHertie Senior Research Professor supported by the Chemical Heritage Foundation , Frankfurt/Main . He has received research support from the German Ministry of Education and Health , IPF and MJFF (grants 12546 , 11930 , 8140 ). He has served or serves as a consultant for Bristol Myer Squibb, Novartis, Roche, Sunovion and Neuroscience/UCB; has served on the advisory boards for Mundipharma, Novartis, UCB and Teva; owns stocks of Biogen Idec, Roche, Morphosys and Medigene; and has received speaker and travel honoraria from AbbVie, Desitin, Novartis, Neuropore/UCB. Funding Information: Dr. Chou receives research support from NIH (grant NS091856 ) and the Canadian Institutes of Health Research ( FRN126052 ) through University Health Network, participates as a site-PI in clinical trials sponsored by the Parkinson Study Group ( STEADY-PDIII , SURE-PD3 , NILO-PD ), receives royalties from UpToDate, Springer Publishing and Demos Health and serves as a consultant for Accordant and Sunovion. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2018",
month = jun,
doi = "10.1016/j.parkreldis.2018.02.001",
language = "English (US)",
volume = "51",
pages = "9--16",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
}