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).
This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.
There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [(123)I] FP-CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre-synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre-synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [(123)I] FP-CIT scans. Mean [(123)I] FP-CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP-CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre-synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP-CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP.
What is the role of androgen deprivation therapy (ADT) on prostate specific membrane antigen (PSMA) expression? Should patients stop or even start ADT treatment prior to PSMA-ligand Positron Emission Tomography Imaging (PET)? Current situation Prostate cancer (PCa) is the second most common solid tumour in men with more than 1.3 million cases diagnosed and more than 350,000 deaths estimated to have occurred in 2018 [1]. ADT is an integral part of treatment for high-risk, recurrent or metastatic prostate cancer. Therefore, imaging of patients prior to, during or after ADT is common. It is known that results from molecular imaging can be influenced by various treatments (e.g. chemotherapy in FDG PET, somatostatin-analogues in DOTA-peptide PET). This editorial aims to outline the current knowledge of interaction between PSMA-ligand uptake in PET and ADT.
There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.
The areas found to be hypoperfused in this study are consistent with known functions of fronto-striatal circuits. A wide range of perfusion patterns is seen, however, and no characteristic patterns for behavioural subgroups has been documented with this technique.
Positron emission tomography (PET) has been successfully used to image colorectal cancer (CRC). This study evaluated the accuracy of 2-[(18)F]-fluoro-2-deoxy- D-glucose (FDG) PET for the detection and staging of recurrent CRC and the consequent impact on clinical management. Forty-two patients previously treated for CRC were investigated for suspected recurrence and, if recurrence was confirmed, the extent of disease was evaluated. All patients underwent whole-body FDG-PET and computed tomography (CT) scan and results were compared to assess sensitivity, specificity and diagnostic accuracy for each modality. We then assessed the FDG-PET directed alteration in clinical management from that planned on the basis of spiral CT results. FDG-PET was more sensitive (93%) than CT (73%) for detection of recurrence (specificity 58% and 75%, respectively). FDG-PET yielded a correct diagnosis in 35 (83%) out of 42 patients, while CT did so in 31 patients (74%). FDG-PET was more accurate than CT for staging local recurrence (sensitivity 100%, specificity 86% with FDG-PET vs 75% and 100%, respectively, with CT) and CRC liver metastases (sensitivity 100% vs 45%; specificity 100% for both). Overall, PET upstaged 8 out of 30 patients (27%) and altered patient management in 16 (38%) cases. This study confirms that FDG-PET is more sensitive than CT for the detection and staging of recurrent CRC. The results also indicate that FDG-PET is an accurate means of selecting appropriate patients for operative treatment. When applied to routine clinical practice, patient management is altered.
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