Nonmotor Fluctuations in Parkinson's Disease

The advanced stage of Parkinson's disease (PD) is characterized by motor complications such as motor fluctuations and dyskinesias induced by long-term levodopa treatment. Recent clinical research provides growing evidence that various nonmotor symptoms such as neuropsychiatric, autonomic, and sensory symptoms (particularly pain) also show fluctuations in patients with motor fluctuations (called nonmotor fluctuations or NMF). However, NMF have not yet been adequately considered in routine care of advanced PD patients and only few therapeutic studies are available. Since the pathophysiology of NMF remains largely unknown, innovative therapeutic concepts are largely missing. The close connection of NMF and motor fluctuations, however, strongly suggests that the strategies used to treat motor complications-namely continuous dopaminergic stimulation-also apply for the therapy of NMF. Future controlled clinical trials specifically addressing NMF are urgently warranted.