Reliability of visual assessment by non-expert nuclear medicine physicians and appropriateness of indications of [123I]FP-CIT SPECT imaging by neurologists in patients with early drug-naive Parkinson’s disease

Purpose: To determine the reliability of visual assessment of [123I]FP-CIT SPECT imaging by non-experts in dopamine transporter (DAT) SPECT imaging in patients with early drug-naive Parkinson’s disease (PD). Also, we explored the indications of DAT SPECT imaging in clinical practice by neurologists. Methods: We collected [123I]FP-CIT SPECT scans of the Levodopa in EArly Parkinson’s disease (LEAP) trial participants that were made prior to recruitment, as part of routine clinical work-up. All scans were reassessed by an expert in DAT imaging. A survey on the use of DAT SPECT imaging was sent to all referring neurologists. Results: The concordance of the initial local assessment and the expert reassessment was 98.7%. The survey showed that neurologists requested DAT SPECT imaging in only 73.6% of patients to differentiate between a neurodegenerative disease and non-neurodegenerative parkinsonism. Conclusions: Visual assessment of [123I]FP-CIT SPECT imaging by community nuclear medicine physicians in patients with early PD is reliable. Neurologists who request DAT SPECT scans are not always aware that the high accuracy is limited only to the differentiation between neurodegenerative and non-neurodegenerative parkinsonism. A significant portion of neurologists who request DAT SPECT scans is not always aware that the high accuracy is limited to the differentiation between neurodegenerative and non-neurodegenerative parkinsonism as DAT SPECT cannot reliably distinguish the various Parkinsonian syndromes

Value of Clinical Signs in Identifying Patients with Scans without Evidence of Dopaminergic Deficit (SWEDD)

Background: In clinical trials that recruited patients with early Parkinson's disease (PD), 4-15% of the participants with a clinical diagnosis of PD had normal dopamine transporter single photon emission computed tomography (DAT SPECT) scans, also called 'scans without evidence of dopaminergic deficit' (SWEDD). Objective: To investigate in patients with a clinical diagnosis of PD, if specific clinical features are useful to distinguish patients with nigrostriatal degeneration from those that have no nigrostriatal degeneration. Methods: We performed a diagnostic test accuracy study. Patients that participated in the Levodopa in Early Parkinson's disease trial, a clinical trial in patients with early PD, were asked to participate if they had not undergone DAT SPECT imaging earlier. The index tests were specific clinical features that were videotaped. A panel of six neurologists in training (NT), six general neurologists (GN), and six movement disorders experts (MDE) received a batch of ten videos consisting of all SWEDD subjects and a random sample of patients with abnormal DAT SPECT scans. The raters analyzed the videos for presence of specific signs and if they suspected the patient to have SWEDD. The reference test was visually assessed DAT SPECT imaging. Results: Of a total of 87 participants, three subjects were SWEDDs (3.4%). The overall intraclass correlation coefficient (ICC) of the Parkinsonian signs was poor to moderate with ICCs ranging from 0.14 to 0.67. NT correctly identified 50.0% of the SWEDD subjects, GN 33.3%, and MDE 66.7%. Conclusion: Our study suggests that the selected videotaped clinical features cannot reliably distinguish patients with a clinical diagnosis of PD and an abnormal DAT SPECT from patients with clinical PD and a SWEDD

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson’s disease: the LEAP-study

Abstract Background The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson’s disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. Methods To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson’s Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson’s Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. Discussion The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. Trial registration ISRCTN30518857 , EudraCT number 2011-000678-7