Longitudinal follow-up of SWEDD subjects in the PRECEPT Study

Neurology (Impact Factor: 8.29). 04/2014; 82(20). DOI: 10.1212/WNL.0000000000000424
Source: PubMed


To compare the clinical and imaging characteristics of those PRECEPT (Parkinson Research Examination of CEP-1347 Trial) subjects with a scan without evidence of dopaminergic deficit (SWEDD) to those with dopamine transporter (DAT) deficit scans at study baseline and during a 22-month follow-up.
Baseline (n = 799) and 22-month follow-up (n = 701) [(123)I] β-CIT SPECT scans were acquired. The percent change in [(123)I] β-CIT striatal binding ratio, the percentage of subjects requiring dopaminergic therapy, the change in Unified Parkinson's Disease Rating Scale (UPDRS) score, and the PRECEPT Study investigators' diagnosis at study termination were compared between SWEDD and DAT deficit subjects.
SWEDD subjects (n = 91) compared with DAT deficit subjects (n = 708) showed reduced UPDRS score at baseline (18.7 [SD 8.5] vs 25.5 [SD 10.5], p < 0.05) and minimal change in both [(123)I] β-CIT striatal binding ratio (-0.2% [SD 12.2] vs -8.5% [SD 11.9], p < 0.0001) and UPDRS score (0.5 [SD 6.9] vs 10.5 [SD 8.9], p < 0.0001) at follow-up assessments. At PRECEPT termination, the diagnosis by study investigators was changed from Parkinson disease (PD) to other disorders not associated with DAT deficit in 44% (95% confidence interval 34.2, 54.7) of SWEDD subjects compared with 3.6% (95% confidence interval 2.3, 5.1) of DAT deficit subjects.
These results indicate that subjects identified as having a SWEDD, with DAT imaging within the normal range, have minimal evidence of clinical or imaging PD progression. These data strongly suggest that SWEDD subjects are unlikely to have idiopathic PD.

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    • "The PRECEPT study, which was a longitudinal study of 91 SWEDDs suggests that these patients are unlikely to have idiopathic Parkinson's disease. After 22 months of follow-up there was little change in their clinical status and 44% of SWEDDs were diagnosed with an alternative disorder (Marek et al., 2014). Here, we have shown that SWEDD subjects, along with no evidence of a dopaminergic deficit, have no significant disruption in the raphe serotonergic system that could account for their clinical symptoms. "
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    ABSTRACT: Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
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    ABSTRACT: Dopaminergic brain imaging might aid early diagnosis of Parkinson disease (PD), but some patients with mild symptoms show no evidence of dopaminergic dysfunction at baseline, and apparently do not progress. Although some of these patients may have been misdiagnosed, others continue to fulfil PD diagnostic criteria despite normal follow-up brain scans.
    Nature Reviews Neurology 07/2014; 10(8). DOI:10.1038/nrneurol.2014.123 · 15.36 Impact Factor
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    ABSTRACT: Background: Little is known about the impact of providing individual research results to clinical trial participants or the impact of sharing such data. Objective: The objective of this follow-up study was to evaluate the desire of participants for learning their imaging results and the impact of this information on their perception of their PD diagnosis and care. Methods: The Parkinson Research Examination of CEP-1347 Trial evaluated the experimental treatment CEP-1347 obtaining dopamine transporter imaging at baseline and 22 months as a secondary outcome. Dopamine transporter imaging and results were categorized as 'dopamine transporter deficit', 'no dopamine transporter deficit' or 'indeterminate.' Self-administered surveys were provided on three occasions to subjects who chose to learn their dopamine transporter imaging results: prior to receiving imaging data, immediately following receipt of imaging information, and three months following image disclosure. Results: 656/777 subjects (84.4%) consented to receive their individual imaging data, comprising overall result categories of 86.3% 'dopamine transporter deficit', 10.4% 'no dopamine transporter deficit', and 3.4% 'indeterminate.' 99.6% of subjects believed their decision to receive data was correct. Following disclosure of imaging results, 97% of the 'dopamine transporter deficit' and 'indeterminate' subjects believed they had Parkinson disease compared with 34% of 'no dopamine transporter deficit' subjects. About 45% of participants reported that learning individual imaging data resulted in improved understanding of their diagnosis. Conclusion: The majority of research participants chose to learn their individual dopamine transporter imaging results and were satisfied with their decision. Disclosure of imaging information resulted in improved understanding of parkinsonian symptoms in nearly half of subjects, and less belief among 'no dopamine transporter deficit' subjects that they had a diagnosis of Parkinson disease.
    Journal of Parkinson's Disease 07/2014; 4(4). DOI:10.3233/JPD-140383 · 1.91 Impact Factor
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