Authors: Angelo Antonini MD, PhD
Article first published online: 28 NOV 2014 | DOI: 10.1002/mdc3.12113
Clinicians are often challenged with the early diagnosis of Parkinson's disease (PD), particularly when patients' manifestations do not completely fulfill diagnostic criteria. The setting has become even more complex following the discovery of genetic forms and the possibility to identify at-risk individuals earlier than in the past. The increased understanding on PD progression persuaded both researchers and pharmaceutical companies that any present and future neuroprotective therapeutic strategy would have to be tested well before clinical manifestations have occurred. This environment has increased the search toward a surrogate biomarker for early diagnosis.
Dopamine transporter (DAT) imaging has been available for more than a decade in Europe and recently also in the United States and could possibly represent a biomarker improving diagnostic accuracy in uncertain cases because it can detect dopamine nerve terminal loss in the striatum. Analysis of DAT imaging in the research arena has been increasingly executed with regions of interest and semiautomated software. However, in clinical nuclear medicine, visual assessment is still the standard. The uptake pattern is visualized in the transversal plane as a symmetrical comma or bean-shaped uptake in the striatum, whereas the typical, pathological feature in degenerative parkinsonism is a rather asymmetrical, dot-shaped uptake. Comparative studies between the two methods yielded conflicting results.
In the current issue of Movement Disorders Clinical Practice, Susanna Jakobson Mo and coauthors report on the results of DAT imaging with single-photon emission CT (DAT-SPECT) in 171 incidental, levodopa-naïve, parkinsonian patients and 37 healthy controls comparing visual and semiquantitative assessment. Patients were followed for an average time of 4.6 years after diagnosis. They found 10 patients who had clinical manifestations of parkinsonism, but normal DAT-SPECT uptake at baseline. Surprisingly, the mean UPDRS motor score in these subjects was 25.5 and no different from those who had abnormal scan. Moreover, both visual and semiquantitative analyses were performed and yielded similar results. Technically, these subjects would be defined as scans without evidence of dopaminergic deficit (SWEDDs). Most important, 9 of 10 SWEDD subjects had additional DAT-SPECT scans (three in 1 case), all confirming initial normal findings.
These results look remarkably similar to another recent publication by Marek et al., who analyzed SWEDD data collected in the context of PRECEPT (Parkinson Research Examination of CEP-1347 Trial), a multicenter, randomized, double-masked, placebo-controlled study examining the efficacy and long-term safety of CEP-1347 as a potential disease-modifying treatment for patients with early PD. Of a total of 90 SWEDDs, after 2 years of follow-up, 44% of SWEDDs continued to fulfill PD diagnostic criteria and 17% had required dopaminergic therapy.
These findings further confirm that, occasionally, discrepancy exists between imaging and clinical observation of parkinsonism. The most obvious explanation is that SWEDDs do not have PD. Dystonic tremor or vascular parkinsonism have been suggested as causes of misdiagnosis, but the presence of persistent, relatively elevated motor UPDRS score in the current study would speak against this hypothesis. However, many conditions may manifest with parkinsonism and present with normal imaging. To minimize misdiagnosis, accurate clinical examination remains critical while imaging should be used only as a supportive, but not as a diagnostic, instrument.