Motor and Nonmotor Complications of Levodopa: Phenomenology, Risk Factors, and Imaging Features

Despite enormous advances in our current understanding of PD since James Parkinson described the shaking palsy 200 years ago, L-dopa, in clinical use since the 1960s, remains the gold standard of treatment. Virtually every patient with PD requires varying doses of L-dopa to manage motor and some nonmotor symptoms and retain an acceptable quality of life. However, after a period of treatment with L-dopa, a number of problems emerge; the key ones are motor and nonmotor fluctuations, a range of dyskinesias, and a combination of both. Nonmotor complications can range from behavioral problems to sensory, autonomic, and cognitive issues. Even with a wealth of data, both in animal models and in vivo imaging that address the pathophysiology of L-dopa-related motor and nonmotor complications, the treatment remains challenging and is an unmet need. Although refinement in types of dopamine replacement therapy and delivery systems have improved the management of L-dopa-related complications, the search for the ideal treatment continues. (C) 2018 International Parkinson and Movement Disorder Society