Motor and non-motor fluctuations in Parkinson's disease: the knowns and unknowns of current therapeutic approaches.

Neurodegeneration in Parkinson's disease is chronically progressive, and no disease-modifying therapies have been approved so far. Fluctuations emerge in eventually all people with Parkinson's disease, and may lead to a high burden of motor and non-motor disability and significantly impair participation if they are inadequately treated. In recent years, the range of therapeutic options has expanded considerably. While different types of oral dopaminergic substances are initially applied to control fluctuations, additional routes of administration now encompass sublingual, inhalative, subcutaneous and transdermal applications. Different choices exist for on-demand and continuous pump therapies, as well as for deep brain stimulation. In this narrative review, we summarize the state of the art in the identification and treatment of motor and non-motor fluctuations in Parkinson's disease. Moreover, we discuss practical aspects of managing fluctuations, address yet unresolved questions and we offer insights into upcoming clinical developments.