Quality of "on": a novel therapeutic objective in advanced Parkinson's disease

Parkinson's disease (PD) is typically managed by dopaminergic supplementation. As the disease progresses, most patients receiving levodopa treatment develop motor and non-motor symptoms that may be managed with therapy modifications. However, in time, they become refractory to conventional medical treatment and require device-aided therapies (DATs). The characterization of "on-off" periods and therapeutic efficacy variables in DATs have received ample attention in the literature, but only limited information is available on variables that affect the well-being of patients during "on" periods unrelated to their duration. In this Point of View article, therefore, we reflected on the concept of the quality of "on" periods - that is to say, the motor and non-motor fluctuating symptoms experienced during "on" time by patients with advanced PD (APD) treated with DATs that must be addressed and defined by acknowledging those issues raised by the patients as essential to their well-being. To explore this definition, a panel of experts in movement disorders met to discuss and subsequently conducted an exhaustive literature search. By this approach, we offer an analysis of symptoms that impact the quality of "on" periods in patients undergoing DATs which may be modifiable with therapy and propose a definition and initial approach to consider the quality of "on" as a therapeutic goal in treating persons with APD.