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

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. (C) 2018 Elsevier Ltd. All rights reserved.