scholarly journals Circuit imaging biomarkers in preclinical and prodromal Parkinson's disease

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Sanne K. Meles ◽  
Wolfgang H. Oertel ◽  
Klaus L. Leenders
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fdg Pet ◽  
Structural Damage ◽  
Photon Emission ◽  
Disease Process ◽  
Nigrostriatal System ◽  
Imaging Biomarkers ◽  
Emission Computed Tomography ◽  
Increased Risk

AbstractParkinson’s disease (PD) commences several years before the onset of motor features. Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Two categories of patients are ideal to study the early disease stages. Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents a well-known prodromal stage of PD in which pathology is presumed to have reached the lower brainstem. The majority of patients with iRBD will develop manifest PD within years to decades. Another category encompasses non-manifest mutation carriers, i.e. subjects without symptoms, but with a known mutation or genetic variant which gives an increased risk of developing PD. The speed of progression from preclinical or prodromal to full clinical stages varies among patients and cannot be reliably predicted on the individual level. Clinical trials will require inclusion of patients with a predictable conversion within a limited time window. Biomarkers are necessary that can confirm pre-motor PD status and can provide information regarding lead time and speed of progression. Neuroimaging changes occur early in the disease process and may provide such a biomarker. Studies have focused on radiotracer imaging of the dopaminergic nigrostriatal system, which can be assessed with dopamine transporter (DAT) single photon emission computed tomography (SPECT). Loss of DAT binding represents an effect of irreversible structural damage to the nigrostriatal system. This marker can be used to monitor disease progression and identify individuals at specific risk for phenoconversion. However, it is known that changes in neuronal activity precede structural changes. Functional neuro-imaging techniques, such as 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (18F-FDG PET) and functional magnetic resonance imaging (fMRI), can be used to model the effects of disease on brain networks when combined with advanced analytical methods. Because these changes occur early in the disease process, functional imaging studies are of particular interest in prodromal PD diagnosis. In addition, fMRI and 18F-FDG PET may be able to predict a specific future phenotype in prodromal cohorts, which is not possible with DAT SPECT. The goal of the current review is to discuss the network-level brain changes in pre-motor 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.

scholarly journals Diagnosis of Parkinson’s Disease. Part 1. The Potential of Functional Neuroimaging

Doctor Ru ◽  
2020 ◽  
Vol 19 (9) ◽  
pp. 6-12
Author(s):  
M.R. Sapronova ◽  
◽  
D.V. Dmitrenko ◽  
N.A. Schnaider ◽  
A.A. Molgachev ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Neuroimaging ◽  
Single Photon ◽  
Photon Emission ◽  
Transcranial Sonography ◽  
Emission Computed Tomography ◽  
Resonance Spectroscopy ◽  
Positron Emission ◽  
Neuroimaging Techniques

Objective of the Review: To describe available functional neuroimaging techniques for use in patients with Parkinson’s disease (PD). Key Points: Parkinson’s disease is a neurodegenerative disorder which affects 2-3% of people older than 65 years. The main neuropathological hallmarks of PD are an accumulation of alpha-synuclein aggregates in the cellular cytoplasm and a loss of neurons in the pars compacta of the substantia nigra, leading to dopamine deficiency. Clinical symptoms of the disease appear when the underlying neural impairment is already advanced, which significantly reduces treatment options. Over the two last decades, functional neuroimaging techniques such as positron emission tomography, single-photon emission computed tomography, proton magnetic resonance spectroscopy, and transcranial sonography have increasingly been used for diagnosing PD during patients’ lifetime and understanding the neuropathological mechanisms and compensatory reactions underlying its symptoms, as well as for monitoring the progression of PD. Conclusion: Modern functional neuroimaging techniques not only facilitate differential diagnosis of PD, but also make it possible to detect the disease at its early/preclinical stage. Keywords: Parkinson’s disease, neuroimaging, positron emission tomography, single-photon emission computed tomography, proton magnetic resonance spectroscopy, transcranial sonography.

scholarly journals Clinical Differentiation of Essential Tremor and Parkinson's Disease

2013 ◽  
Vol 6 ◽  
pp. CCRep.S11903 ◽  
Author(s):  
Robert Fekete ◽  
Jin Li
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Essential Tremor ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Postural Tremor ◽  
Arm Swing ◽  
Rest Tremor ◽  
Dopaminergic Terminal

We present clinical features and tremor characterization in a patient with Parkinson's disease (PD) as well as in two cases of essential tremor (ET) with some parkinsonian features but no evidence of dopaminergic terminal loss on 123I-FP-CIT Single Photon Emission Computed Tomography (SPECT). Relatively slow frequency rest tremor and bilateral upper extremity bradykinesia without decrementing amplitude were observed in the ET cases, with unilaterally decreased arm swing in case 3. Alternating rest tremor and re-emergent tremor with 13 second latency was confirmed in the PD case. Re-emergent tremor had alternating characteristics, which to our knowledge has not been previously reported. The ET cases had synchronous postural tremor. Alternating re-emergent tremor in PD provides further evidence for re-emergent tremor as an analogue of rest tremor in PD. Two cases of ET with synchronous postural tremor and one to two year history of parkinsonian features had no evidence of dopaminergic terminal loss up to 40 years after the initial onset of ET. Tremor synchronicity characterization can assist in differential diagnosis between the two disorders.

scholarly journals Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson’s disease: a cross-sectional study

2020 ◽  
pp. jnnp-2020-324266
Author(s):  
Hiba Kazmi ◽  
Zuzana Walker ◽  
Jan Booij ◽  
Faraan Khan ◽  
Sachit Shah ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Emission Computed Tomography ◽  
Imaging Features ◽  
Cross Sectional ◽  
Screening Questionnaire ◽  
Imaging Results ◽  
Increased Risk

BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.MethodsIn a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.ResultsPatients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD screening questionnaire (mean (SD) 1.8 (1.9) vs 0.8 (1.2); p=0.01), Movement Disorder Society Unified Parkinson’s Disease Rating Scale total (mean (SD) 19.2 (12.7) vs 6.1 (5.7); p<0.001), REM-sleep behaviour disorder screening questionnaire (mean (SD) 4.3 (3.2) vs 2.1 (2.1); p=0.001), Lille Apathy Rating Scale (mean (SD) −23.3 (9.6) vs −27.0 (4.7); p=0.04) and the Scales for Outcomes in PD-Autonomic (mean (SD) 14.9 (8.7) vs 7.7 (4.9); p<0.001). Twenty-four per cent of patients with LOD versus 4% HC had an abnormal 123I-ioflupane SPECT scan (p=0.04).ConclusionsLOD is associated with increased rates of motor and non-motor features of PD/DLB and of abnormal 123I-ioflupane SPECTs. These results suggest that patients with LOD should be considered at increased risk of PD/DLB.

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.

scholarly journals Clinical implications of early caudate dysfunction in Parkinson’s disease

2019 ◽  
Vol 90 (10) ◽  
pp. 1098-1104 ◽  
Author(s):  
Jacopo Pasquini ◽  
Rory Durcan ◽  
Louise Wiblin ◽  
Morten Gersel Stokholm ◽  
Lynn Rochester ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Single Photon ◽  
Photon Emission ◽  
Subsequent Development ◽  
Single Photon Emission Ct ◽  
Dopaminergic Dysfunction ◽  
Increased Risk ◽  
Clinically Significant

ObjectiveAlthough not typical of Parkinson’s disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.MethodsPatients with PD and healthy controls were identified from the Parkinson’s Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <–2 SDs compared with the controls’ mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding.ResultsAt baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).ConclusionsEarly significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.

Combined Use of 123i-fp-cit Spect and 123i-mibg Scintigraphy for Differentiation of Progressive Supranuclear Palsy Subtypes and Parkinson's Disease

2020 ◽  
Author(s):  
Keita Sakurai ◽  
Shohei Inui ◽  
Yufuko Saito ◽  
Satoko Sakakibara ◽  
Rina Hashimoto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Progressive Supranuclear Palsy ◽  
Single Photon ◽  
Photon Emission ◽  
Washout Rate ◽  
Emission Computed Tomography ◽  
Mibg Scintigraphy ◽  
Adaptive Boosting ◽  
Specific Binding Ratio

Abstract Background:This study was undertaken to investigate the utility of 123I-ioflupane (123I-FP-CIT) single photon emission computed tomography (SPECT), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy and both of these to differentiate among progressive supranuclear palsy (PSP), including typical cases and other subtypes, and Parkinson’s disease (PD).Methods: Twenty-five patients with typical PSP (Richardson's syndrome; PSP-RS), 14 atypical ones (PSP-variants; PSP-V) and 42 PD who underwent both 23I-FP-CIT SPECT and 123I-MIBG scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of the striatum and midbrain and anteroposterior and asymmetry ratio of the striatal SBR on 123I-FP-CIT SPECT and heart-to-mediastinum (H/M) ratio and washout rate (WR) on 123I-MIBG scintigraphy were used as quantitative measures. The classifier performance based on adaptive boosting was evaluated using five-fold cross-validation for these measures.Results: Midbrain SBR and the striatal anteroposterior ratio were statistically lower in PSP-RS than PD. On the other hand, there were no significant differences in any other quantitative measures among PSP-RS, PSP-V and PD. Striatal and midbrain SBRs and anteroposterior ratio of PSP-V were approximately in-between those of PSP-RS and PD. PD showed the lowest early and delayed H/M ratios and highest WR of any group. The combination of 123I-FP-CIT and 123I-MIBG was useful in discriminating PSP-RS and PSP-V from PD, while 123I-FP-CIT was superior to 123I-MIBG in differentiating PSP-RS from PSP-V.Conclusion: The combination of 123I-FP-CIT SPECT and 123I-MIBG scintigraphy, rather than either alone, may be a useful differential diagnostic tool to differentiate patients with PSP-RS, PSP-V and PD.

scholarly journals [99mTc]-HM-PAO SPECT in Parkinson's Disease

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S101-S108 ◽  
Author(s):  
G. Pizzolato ◽  
M. Dam ◽  
N. Borsato ◽  
B. Saitta ◽  
C. Da Col ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Photon ◽  
Photon Emission ◽  
Tracer Uptake ◽  
Emission Computed Tomography ◽  
Anticholinergic Drugs ◽  
Scanning Procedure ◽  
Subcortical Regions ◽  
Severity Of The Disease

Thirty-six patients affected by Parkinson's disease were studied using single photon emission computed tomography (SPECT) and [99mTc]–HM-PAO as a tracer. The scanning procedure was performed 16–24 h after discontinuation of specific therapy. Tracer activity ratios were determined in 10 pairs of cerebellar, cortical, and subcortical regions. Data were compared with those of 10 age-matched controls. Most of the regions examined did not show any relevant change between parkinsonian and control subjects. Notably, mean activity in striatal regions were similar in the two groups. Increased activity in caudate–putamen was found in patients who were on chronic DOPA therapy. Side-to-side asymmetries in the basal ganglia increased with the severity of the disease. Significant reductions of tracer uptake, from control values, were observed bilaterally in the parietal cortex. These deficits were more pronounced in patients with mental deterioration and in subjects who had been chronically treated with anticholinergic drugs. Parietal perfusion deficits in parkinsonian patients resemble those described in Alzheimer's dementia. These findings suggest that the heterogeneous alterations of regional cerebral blood flow (rCBF) in parkinsonian patients reflect the multifactorial pathophysiology of the disease.

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