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 Levodopa-Responsive Primary Slow Orthostatic Tremor: A Premotor Sign of Parkinson’s Disease?

2020 ◽  
Vol 12 (1) ◽  
pp. 1-6
Author(s):  
Fumihito Yoshii ◽  
Wakoh Takahashi ◽  
Koji Aono
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Surface Electromyography ◽  
Specific Binding ◽  
Low Frequency ◽  
Orthostatic Tremor ◽  
Specific Binding Ratio ◽  
Dopaminergic Medication ◽  
Neurological Signs ◽  
Dat Spect

We present a case of primary orthostatic tremor (OT) responsive to dopaminergic medication. The patient was a 62-year-old woman, who had leg tremor on standing for 2 years. No parkinsonian or other neurological signs were observed. Surface electromyography of the quadriceps muscles showed regular 5–6 Hz muscle discharges. [123I]-FP-CIT DAT-SPECT imaging revealed decreased specific binding ratio values in the striatum compared with age-matched controls. Her leg tremor almost completely disappeared following administration of levodopa 200 mg and pramipexole 0.75 mg. Since her OT with low-frequency discharge was responsive to dopaminergic medication, we speculate that it may be a premotor sign of Parkinson’s disease.

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.

Asymmetry at Disease Onset Is Not a Predictor of Parkinson’s Disease Progression

2021 ◽  
pp. 1-6
Author(s):  
Marco Cotogni ◽  
Lucia Sacchi ◽  
Aleksander Sadikov ◽  
Dejan Georgiev
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
De Novo ◽  
Disease Onset ◽  
Asymmetry Index ◽  
The Body ◽  
Motor Disability ◽  
The Asymmetry

Background: Even though a significant fraction of Parkinson’s disease (PD) patients presents with only minor or no motor asymmetry, the motor symptoms in PD typically start on one side of the body and worse symptoms on the side of the disease onset usually persist long after the disease has become clinically bilateral. The asymmetric presentation of PD has been studied over the years, with some studies showing slower progression in PD subjects with asymmetric disease presentation. In other studies, however, it was not possible to relate the asymmetry to disease progression. Objective: The main objective of the present study was to assess the effect of asymmetry at disease onset on disease progression. Methods: Using the data available in the Parkinson’s Progression Markers Initiative (PPMI) database, at baseline, 423 subjects with de-novo PD were included in the study. Instead of dichotomizing the subjects in asymmetric and symmetric, we kept the asymmetry index and the non-motor, disability, and motor progression at one-, three-, and five-year follow-up continuous. Linear regression was used to correlate asymmetry indices and disease progression. Results: There was no correlation between neither clinically, nor DatSCAN defined asymmetry and non-motor, motor, and disability progression in the de-novo PD subjects with a 5-year follow-up. Conclusion: Asymmetry does not predict progression of PD. Further studies are needed to investigate whether early detection of asymmetry on clinical grounds could successfully distinguish between PD and symmetric types of atypical parkinsonism in the early stages of the disease.

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.

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.

Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson’s disease development: the utility of neuromelanin, diffusion MRI, and DAT-SPECT

2021 ◽  
Author(s):  
Hiroto Takahashi ◽  
Nobuo Kashiwagi ◽  
Atsuko Arisawa ◽  
Chisato Matsuo ◽  
Hiroki Kato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diffusion Tensor ◽  
Specific Binding ◽  
Mean Diffusivity ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal System ◽  
Sleep Behavior ◽  
Specific Binding Ratio ◽  
Preclinical Phase

Objectives: To assess the utility of examining the nigrostriatal system with magnetic resonance imaging (MRI) and dopamine transporter (DAT) imaging for evaluating the preclinical phase of Parkinson’s disease (PD). Methods: The subjects were 32 patients with early PD and a history of probable rapid eye movement sleep behavior disorder (RBD; PD group), 15 patients with idiopathic RBD (RBD group), and 24 age-matched healthy controls (HC group) who underwent neuromelanin and diffusion tensor MRI for analysis of the substantia nigra pars compacta (SNpc). The RBD and PD groups underwent DAT imaging. In the RBD group, totals of 39 MRI and 27 DAT imaging examinations were obtained longitudinally. For each value, intergroup differences and receiver-operating characteristic (ROC) analysis for diagnostic performance were examined statistically. Results: The neuromelanin value was significantly lower and the diffusion tensor values except fractional anisotropy were significantly higher in the RBD and PD groups than in the HC group. The DAT specific binding ratio (SBR) was significantly lower in the PD group than in the RBD group. The areas under the ROC curves (AUCs) for neuromelanin/mean diffusivity value in the SNpc were 0.76/0.82 for diagnosing RBD and 0.83/0.80 for diagnosing PD. The AUC for the SBR for discriminating PD from RBD was 0.87. Conclusions: MRI and DAT imaging may be useful for evaluating sequential nigrostriatal changes during the preclinical phase of PD. Advances in knowledge: MRI detects nigrostriatal changes in both RBD and early PD, and DAT imaging detects nigrostriatal changes during the transition to PD in RBD.

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.

Dopaminergic Correlates of Orthostatic Hypotension in de novo Parkinson’s Disease

2020 ◽  
pp. 1-9
Author(s):  
Tadashi Umehara ◽  
Hisayoshi Oka ◽  
Atsuo Nakahara ◽  
Tomotaka Shiraishi ◽  
Takeo Sato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Orthostatic Hypotension ◽  
De Novo ◽  
Single Photon ◽  
Anterior Part ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Dopamine Depletion ◽  
Dat Spect

Background: Orthostatic hypotension (OH) at an early stage of Parkinson’s disease (PD) predicts poor prognosis, which may suggest degeneration of dopaminergic neurons affects sympathetic function, causing OH. Objective: We tested the hypothesis that striatal dopaminergic depletion is associated with OH in PD. Methods: Out of 99 patients with newly diagnosed untreated PD, 81 patients were enrolled according to our selection criteria. All patients underwent head-up tilt-table testing and striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. The association between hemodynamic changes and 123I-FP-CIT uptake was examined. Results: 123I-FP-CIT uptake in the putamen, especially the anterior part and left side, was related not only to motor severity but also to OH. Change in systolic blood pressure correlated negatively with 123I-FP-CIT uptake in bilateral anterior putamen (left: p <  0.01, right: p <  0.05) and left posterior putamen (p <  0.05). Patients with OH had more severe dopamine depletion in left anterior (p = 0.008) and posterior (p = 0.007) putamen at a similar motor severity than did patients without OH even though both groups have similar baseline characteristics. An analysis of asymmetry index showed patients with OH had symmetrically decreased dopamine levels in anterior putamen when compared to those without OH (p = 0.024). Conclusion: OH is closely related to striatal dopamine depletion in PD. This relation may help to account for the prognostic value of OH.

SPECT-Befunde bei Hemiparkinson-Syndrom mit 99mTc-HMPAO

1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Neuronal Activity ◽  
Tracer Uptake ◽  
The Body ◽  
99Mtc Hmpao ◽  
Do So

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.

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