Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: A longitudinal β‐CIT SPECT study

Abstract

Atypical parkinsonian syndromes (APS) such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration are characterized by poor response to antiparkinsonian medication and rapid clinical deterioration. We used SPECT and [123I]beta-CIT as a label of dopamine transporters to study the progression of presynaptic dopaminergic degeneration in Parkinson's disease (PD) and APS. Twenty-four PD patients with short disease duration (2.4 +/- 1.5 years), 12 PD patients with long disease duration (9.2 +/- 2.6 years), 10 patients with APS (disease duration 2.1 +/- 1.5 years), and nine patients with essential tremor (ET) underwent sequential [123I]beta-CIT SPECT imaging with an interval of 25.5 +/- 10.3 (13-63) months. The age-related decline of striatal beta-CIT binding was studied cross-sectionally in 30 healthy subjects. The ratio of striatum/cerebellum -1 at 20 hours after tracer injection, reflecting specific-to-nondisplaceable binding, was used as the primary SPECT outcome measure. At scan 1, striatal beta-CIT binding was reduced in PD patients with short disease duration (-42% compared with age-corrected normal values) and long disease duration (-51%), and APS (-36%), but normal in ET. During the observation period striatal beta-CIT binding significantly declined in patients with APS (14.9% per year) and short duration PD (7.1% per year), whereas PD patients with long disease duration and patients with ET showed no significant change of striatal beta-CIT binding between scans 1 and 2. The relative annual reduction from age-corrected normal values at the time of scan 1 was significantly higher in patients with APS than in PD patients with short disease duration (9.6 vs. 4.3%, P = 0.004). These results demonstrate a rapid decline of striatal beta-CIT binding in patients with atypical parkinsonian syndromes, exceeding the reduction in PD. The dopaminergic degeneration in PD appears to slow down during the course of the disease. SPECT with [123I]beta-CIT is a sensitive marker of disease progression in parkinsonian disorders.

Validation of an automated morphological MRI-based 123I-FP-CIT SPECT evaluation method

“…In patients with PS, the automated method showed decreased striatal DAT binding with increased disease duration in accordance with the other two evaluation techniques and earlier studies [26,27]. The "lower" putaminal uptake ratio derived from the automated method was inversely correlated with clinical measures such as Hoehn-Yahr score, MDS-UPDRS Total and MDS-UPDRS Parts II, III and IV scores, suggesting that the automated evaluation may be effective not only in the diagnosis of PS, but also in the assessment of disease severity.…”

Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images

“…However, quantitative analysis is useful to differentiate subjects with subtle localized or diffuse loss of DATs that can be difficult to sort out by visual inspection alone. Moreover, quantification is mandatory to measure disease progression (7)(8)(9)(10)(11) and to assess the efficacy of neuroprotective drugs (12,13).…”

123-I ioflupane (Datscan®) presynaptic nigrostriatal imaging in patients with movement disorders

“…Assessment of disease progression in PD Brain SPECT of DAT provides a quantitative biomarker for progression of dopaminergic degeneration in PD. (Nurmi et al, 2000;Staffen et al, 2000;Pirker et al, 2002). This fact is because DAT loss in PD agrees with loss of nigrostriatal dopaminergic neurons (Kaufman et al, 1991) (Fig.…”

“…The progression rate of dopaminergic degeneration is faster in PD than in normal subjects (Winogrodzka et al, 2003), and a correlation appears to exist between the range of decrease in DAT binding in SPECT imaging and disease duration (Marek et al, 1997). Dopaminergic degeneration in PD appears to decrease during the course of disease (Pirker et al, 2002). The mean progression rate of dopaminergic degeneration in the caudate is slower that in the putamen, suggesting that caudate nucleus function is relatively preserved in early stage PD (Winogrodzka et al, 2003).…”

“…A relative annual decrease of approximately 5%-10% has been found in global uptake rates with 123-β-CIT (Winogrodzka et al, 2003;Fearnley et al, 1991). In addition, DAT imaging may be of value for assessing neuroprotective therapies (Pirker et al, 2002). Various authors have shown that treatment with Ldopa or dopaminergic agonists in PD does not cause significant occupation or modulation in the number of striatal DAT labed with β-CIT (Innis et al, 1999;Ahlskog et al, 1999).…”