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Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

Single-photon emission computed tomography (SPECT) markers allow measuring the integrity of the brain dopaminergic system in vivo. We used dopamine transporter (DAT) SPECT with [(123)I]FP-CIT and dopamine D(2)/D(3) receptor SPECT with [(123)I]IBZM to evaluate whether there is a reduction of DAT and/or D(2)/D(3) receptor SPECT in treated and untreated patients with Parkinsonian syndrome (PS). We found that almost a quarter of our patients treated with anti-Parkinsonian medication prior to SPECT imaging did not show evidence of a presynaptic dopaminergic deficit while 37% of untreated patients were diagnosed as having Parkinson's disease. 17% of treated patients had additional loss of D(2)/D(3) receptor binding capacity in concordance with the clinical follow-up diagnoses of multiple system atrophy, progressive nuclear palsy, and vascular Parkinsonism. Apart from 38% clinically uncertain cases, SPECT was in concordance with 75% of initial clinical diagnoses. 25% were reclassified as indicated by SPECT findings and confirmed by a 1.5-year clinical follow-up. We conclude that dopamine SPECT may support establishing or refuting the clinical diagnosis and, therefore, help to make the decision for or against dopaminomimetic treatment in cases with PS.