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

ABSTRACT 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. © 2018 International Parkinson and Movement Disorder Society