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

2020 ◽  
Vol 10 (4) ◽  
pp. 1561-1569 ◽  
Author(s):  
Sven R. Suwijn ◽  
Hamdia Samim ◽  
Carsten Eggers ◽  
Alberto J. Espay ◽  
Susan Fox ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Clinical Features ◽  
Spect Imaging ◽  
Emission Computed Tomography ◽  
Test Accuracy ◽  
Dat Spect ◽  
Nigrostriatal Degeneration ◽  
Early Parkinson’S Disease

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.

The Association of Visually Guided Saccades and DAT-SPECT Findings in Parkinson’s Disease

2021 ◽  
Vol 84 (2) ◽  
pp. 110-118
Author(s):  
Makoto Kobayashi ◽  
Satoshi Kuwabara
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Target Location ◽  
Photon Emission ◽  
Motor Dysfunction ◽  
Emission Computed Tomography ◽  
Visually Guided ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Nigrostriatal Degeneration

<b><i>Background:</i></b> In individuals with Parkinson’s disease (PD), visually guided saccades (VGSs) reportedly reflect general motor dysfunction and cognitive impairments. However, it has not been fully elucidated whether the VGS abnormalities result from nigrostriatal degeneration or other PD-related neural changes. <b><i>Methods:</i></b> We measured VGS latency and gain in 50 PD participants and 56 age-matched normal controls (NCs), and PD participants underwent dopamine transporter (DAT) single-photon emission computed tomography (SPECT) within 2 months of the measurement. VGSs were evoked by a white dot on a monitor, which was presented at the center and pseudo-randomly jumped off horizontally (10° or 20° eccentricity) or vertically (10° or 15°). First, we compared the parameters between PD participants and NCs for each target location. Second, in the participants who exhibited striatal DAT asymmetry on SPECT, VGSs contralaterally directed to the more severely affected striatum were compared with those ipsilaterally directed. Third, effects of the DAT-SPECT specific binding ratio (SBR) on VGSs were analyzed. <b><i>Results:</i></b> PD participants demonstrated prolonged latencies when the target was presented at the upward 15° eccentricity and decreased gains at all target locations. Contralateral VGSs relative to the side of the more severely affected striatum were more delayed and hypometric than ipsilateral. The SBR had a significant positive effect on VGS gain. <b><i>Conclusions:</i></b> In participants with PD, saccadic abnormalities were emphasized when VGSs were directed contralaterally to the more severely affected striatum. Moreover, the dopaminergic nigrostriatal degeneration on DAT-SPECT was mainly associated with VGS gain.

scholarly journals High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marco J. Russo ◽  
Christina D. Orru ◽  
Luis Concha-Marambio ◽  
Simone Giaisi ◽  
Bradley R. Groveman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Diagnostic Performance ◽  
De Novo ◽  
Alpha Synuclein ◽  
Diagnostic Tools ◽  
Dat Spect ◽  
Progression Markers ◽  
Early Parkinson’S Disease

AbstractAlpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

scholarly journals Impact of DaTscan Imaging on Clinical Decision Making in Clinically Uncertain Parkinson’s Disease

2021 ◽  
pp. 1-5
Author(s):  
Jonathan R. Isaacson ◽  
Salima Brillman ◽  
Nisha Chhabria ◽  
Stuart H. Isaacson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Clinical Decision Making ◽  
Photon Emission ◽  
Case Series ◽  
Emission Computed Tomography ◽  
Medication Therapy ◽  
Clinical Scenarios ◽  
The Impact

Background: The diagnosis of Parkinson’s disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful. Objective/Methods: In the current paper, we describe clinical scenarios for which DaTscan imaging was used in a prospective case series of 201 consecutive patients in whom a movement disorder specialist ordered DaTscan imaging to clarify NSDD. We describe the impact of DaTscan results on changing or confirming pre-DaTscan clinical diagnosis and on post-DaTscan treatment changes. Results/Conclusion: DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present. These include in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations. We also found DaTscan imaging to be useful to determine underlying NSDD in patients with PD diagnosis for 3-5 years but without apparent clinical progression or development of motor fluctuations. Overall, in 201 consecutive patients with clinically questionable NSDD, DaTscan was abnormal in 58.7% of patients, normal in 37.8%, and inconclusive in 3.5%. DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients.

Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's disease

2004 ◽  
Vol 10 (6) ◽  
pp. 375-379 ◽  
Author(s):  
K.L Chou ◽  
H.I Hurtig ◽  
M.B Stern ◽  
A Colcher ◽  
B Ravina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diagnostic Accuracy ◽  
Spect Imaging ◽  
Early Parkinson’S Disease

scholarly journals Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
R. Matthew Hutchison ◽  
Karleyton C. Evans ◽  
Tara Fox ◽  
Minhua Yang ◽  
Jerome Barakos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Alpha Synuclein ◽  
Emission Computed Tomography ◽  
Phase 2 ◽  
Dat Spect

Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523. Date submitted: October 19, 2017. First Posted: October 24, 2017.

Analysis of the clinical features of early Parkinson’s disease with comparatively integrated intestinal function

2018 ◽  
Vol 39 (11) ◽  
pp. 1847-1856
Author(s):  
Xiaoxue Guan ◽  
Yuchan Wang ◽  
Qun Li ◽  
Ming Wei ◽  
Lili Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Features ◽  
Intestinal Function ◽  
Early Parkinson’S Disease

The utility of the combined use of 123I-FP-CIT SPECT and neuromelanin MRI in differentiating Parkinson's disease from other parkinsonian syndromes

2018 ◽  
Vol 60 (2) ◽  
pp. 230-238 ◽  
Author(s):  
Eiji Matsusue ◽  
Yoshio Fujihara ◽  
Kenichiro Tanaka ◽  
Yuki Aozasa ◽  
Manabu Shimoda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Photon ◽  
Photon Emission ◽  
Contrast Ratio ◽  
Emission Computed Tomography ◽  
Specific Information ◽  
Specific Binding Ratio ◽  
Significant Difference ◽  
Dat Spect

Background Neuromelanin magnetic resonance imaging (NmMRI) and 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) provide specific information that distinguishes Parkinson's disease (PD) from non-degenerative parkinsonian syndrome (NDPS). Purpose To determine whether a multiparametric scoring system (MSS) could improve accuracy compared to each parameter of DAT-SPECT and NmMRI in differentiating PD from NDPS. Material and Methods A total of 49 patients, including 14 with NDPS, 30 with PD, and five with atypical parkinsonian disorder (APD) underwent both NmMRI and DAT-SPECT and were evaluated. The average (Ave) and the asymmetry index (AI) were calculated in the substantia nigra compacta area (SNc-area), SNc midbrain-tegmentum contrast ratio (SNc-CR), and specific binding ratio (SBR). Cut-off values were determined, using receiver operating characteristic (ROC) analysis, for the differentiation of PD from NDPS on the statistically significant parameters. All cases were scored as either 1 (PD) or 0 (NDPS) for each parameter according to its threshold. These individual scores were totaled for each case, yielding a combined score for each case to obtain a cut-off value for the MSS. Results The Ave-SNc-area, Ave-SNc-CR, and Ave-SBR in PD were significantly lower than those in NDPS. The AI-SNc-area and AI-SBR in PD were significantly higher than those in NDPS. Of the five parameters, the highest accuracy was 93% for the Ave-SNc-area. For the MSS, a cut-off value of 3 was the accuracy of 96%. Besides, no significant difference was observed between PD and APD on all parameters. Conclusion An MSS has comparable or better accuracy compared to each parameter of DAT-SPECT and NmMRI in distinguishing PD from NDPS.

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