Parkinson's disease (PD) is the second-most common neurodegenerative disease with incidence of approximately 17 per 100,000.Diagnosis is based on clinical criteria, which can lead to inaccurate diagnosis. In a recent community-based study of 502 individuals with presumed PD, 26% were found not to have parkinsonism.
Neurodegenerative parkinsonian syndromes, such as idiopathic multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), can sometimes be difficult to differentiate from non-neurodegenerative parkinsonism etiologies, such as vascular parkinsonism, drug-induced parkinsonism, and essential tremors (ETs). Dopamine transporter (DaT) scan has been approved to aid in the differentiation between parkinsonian syndromes and ET in European countries since 2000, but has been approved by U.S. Food and Drug Administration for use in the Unites States just recently, in 2011.
DaT scan is performed by single-photon emission computed tomography (SPECT) using radioactive pharmaceutical [123I] FP-CIT (ioflupane I123) that binds to DaT proteins located in the presynaptic membrane on the terminals of dopaminergic projections from the SN to the striatum, providing a marker for dopamine terminal innervation.[2, 3] In two large studies comparing degenerative parkinsonism and nondegenerative tremor disorders, the positive percent agreement (i.e., having an abnormal scan when the clinical diagnosis is a neurodegenerative parkinsonian syndrome) was up to 97% and negative percent agreement (i.e., having a normal scan when the clinical diagnosis is a non-neurodegenerative parkinsonism or ET) was 74% to 97%.[4, 5]
In this study, we looked at the utilization pattern of DaT scan and its effect on clinical practice among movement disorders specialists in a single center.
Our study aimed to assess the movement disorder specialists' behavior in utilizing DaT scan as a tool to assist in the diagnosis of parkinsonian syndromes, and its effect on patient management.
We found highly variable physician utilization of DaT scans to facilitate their diagnosis from 5 to 33 per 100 new patients seen. The variable in the rate of DaT scan utilization appears to relate to physician preference rather than the number of years of experience.
Prescan clinical diagnosis was consistent with DaT scan result in only 57% when predicting neurodegenerative parkinsonism (i.e., pre-DaT diagnosis of neurodegenerative parkinsonism with an abnormal DaT scan result) and 65% when non-neurodegenerative parkinsonism was the prescan diagnosis. It would not be proper to calculate sensitivity/specificity/positive and negative predictive values of the scan in this study given that the cases included in this “real-world” experience were clinically ambiguous/challenging (hence the request for the DaT scan) despite the thorough evaluation of the referring fellowship-trained movement disorders neurologists. The accuracy of our diagnoses was lower than some studies that were previously reported on (70–90%).[3, 7] However, Catafau et al., as an example, also reported that their scans did not correlate well with the initial suspected diagnosis. In their study, the imaging results were not consistent with the prescan diagnoses in 36% of patients with presynaptic parkinsonian syndrome (PS) and 54% with nonpresynaptic PS. After imaging, diagnosis was changed in 52% of patients.
Interestingly, movement disorders clinicians were most accurate in suspecting ET (with a normal scan in 79% of cases) and least accurate in suspecting psychogenic parkinsonism, given that only 47% of the scans were normal. Our study underscores the difficulty of providing the correct diagnosis, and the significant percentage of disagreement between the prescan diagnosis and the scan results, even among fellowship-trained movement disorders neurologists, especially when atypical features are present and psychogenic disorder is suspected.
Although not absolute, based on our study, DaT scan appears to have a significant impact on the physician's decision on initiating or continuing on antiparkinsonian medications. Ninety-six percent of patients who have abnormal scan were maintained on antiparkinsonian medications compared to only 60% of those with prescan diagnosis of neurodegenerative parkinsonism. The result is similar to a previous study by Kupsch et al. that DaT scan has a significant impact on clinical management and diagnosis of patients with clinically uncertain parkinsonian syndromes.
Of interest, 24% of patients were started or continued on antiparkinsonian medications despite a normal DaT scan. We found that the most common reasons were parkinsonism that improved with dopamine replacement or worsened with dopamine withdrawal. There were also a few cases where the clinician did not believe the scan results.
Our study has several strengths, including the high volume of DaT scans from a single, tertiary referral center and surveying a large number of movement disorder specialists; our electronic medical record system allowed us to accurately include all scans obtained and assess in detail the pre- and postscan diagnoses, and the medication exposure of each patient. There are also several limitations. As mentioned, the study was retrospective in nature, with a great degree of selection bias. The pre- and postscan diagnosis was obtained from retrospective chart review. The scans were interpreted based on visual appearance only. Quantitative DaT-binding technique may improve the accuracy of the results. Some of the medications, which the subjects were taking, could have altered radioligand uptake, although the majority of those exposed to these medications still managed to have a normal scan. Most of the scans obtained were presumably from atypical cases where even the movement disorders specialists were unsure of their diagnosis. Nonetheless, the study underscores the utility of DaT scans in assisting the diagnosis of neurodegenerative parkinsonism, even among movement disorders neurologists. In this limited, retrospective, center-specific data, DaT scan utilization varied from specialist to specialist. It appeared to have had a significant impact on the medical management of the patients. DaT scan was most useful when the suspecting prescan diagnosis was psychogenic parkinsonism (given that the majority had an abnormal scan, refuting the diagnosis), but was also useful in other scenarios. In addition, there remained several cases where the clinicians prioritized the clinical presentation over the scan result. Specifically, clinicians were less willing to discontinue anti-PD medications if their patients showed continued improvement (or worsening of symptoms when medications were tapered) despite a normal DaT scan.
In summary, DaT scans can be helpful in proving (or disproving) the diagnosis of neurodegenerative parkinsonism when patients present with atypical or subtle features; however, it is still not viewed by clinicians as a test with 100% certainty and the results remain to be interpreted within the clinical context. Large, randomized, control trials studying the correlation between DaT scan and neuropathology, which is a gold standard of diagnosis of neurodegenerative parkinsonism, are needed.