Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).

The clinical profile and therapy response during follow-up of patients with normal presynaptic dopamine imaging supports the diagnosis of a non-degenerative movement disorder in nearly all cases.

Dopamine transporter (DAT) imaging detects presynaptic dopamine neuronal dysfunction and thereby assists differentiation of conditions with and without dopamine deficit. In atypical tremor disorders, DAT imaging can differentiate between Parkinson's disease (PD), where dopamine deficit is demonstrated on DAT imaging, and essential tremor, where no dopamine deficit is found. DAT imaging may be particularly informative in monosymptomatic rest tremors, benign tremulous Parkinson's syndrome, and in the elderly in whom essential tremor may be accompanied by pseudoparkinsonism.

Between 4% and 14% of patients diagnosed with Parkinson's disease and entering clinical trials have normal presynaptic dopaminergic imaging. The effects of antiparkinsonian therapy have varied in these studies, and the consequences of stopping treatment are not reported. We present 11 patients who initially fulfilled diagnostic criteria and were treated for Parkinson's disease but in whom emerging diagnostic doubts led to antiparkinsonian therapy withdrawal, which was achieved without deterioration. Such cases represent a nondegenerative form of Parkinsonism, which does not benefit from dopaminergic therapy. Prospective vigilance regarding this category is of importance in clinical practice and clinical trials.