A new visual rating scale for Ioflupane imaging in Lewy body disease.
TL;DR: A new robust and reliable rating scale for 123I-Ioflupane brain images in Lewy body disease that encompasses appearances seen in dementia with Lewy bodies, demonstrated high accuracy in autopsy confirmed cases and offers advantages over the existing visual rating scale.
About: This article is published in NeuroImage: Clinical.The article was published on 2018-01-01 and is currently open access. It has received 11 citations till now. The article focuses on the topics: Dementia with Lewy bodies & Dementia.
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TL;DR: Basic concepts and definitions of dementia with Lewy bodies are presented, based on the current understanding, that should guide the community to address open questions that will lead to improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies.
Abstract: Dementia with Lewy bodies (DLB) is an age-associated neurodegenerative disorder producing progressive cognitive decline that interferes with normal life and daily activities. Neuropathologically, DLB is characterised by the accumulation of aggregated α-synuclein protein in Lewy bodies and Lewy neurites, similar to Parkinson’s disease (PD). Extrapyramidal motor features characteristic of PD, are common in DLB patients, but are not essential for the clinical diagnosis of DLB. Since many PD patients develop dementia as disease progresses, there has been controversy about the separation of DLB from PD dementia (PDD) and consensus reports have put forward guidelines to assist clinicians in the identification and management of both syndromes. Here, we present basic concepts and definitions, based on our current understanding, that should guide the community to address open questions that will, hopefully, lead us towards improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies.
181 citations
TL;DR: DAT-SPECT has been well documented to be highly diagnostically accurate and to have a relevant influence on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome, but it has not yet been shown to improve patient-relevant endpoints such as mortality, morbidity, and health-related quality of life.
Abstract: Background Parkinsonian syndromes are classified by etiology mainly on clinical grounds, that is, on the basis of the clinical manifestations and with the aid of conventional ancillary studies. In most cases, the clinical diagnosis is clear. In up to 30% of cases, however, the etiological classification remains uncertain after completion of the basic clinical diagnostic evaluation, and additional investigation with nuclear imaging may be indicated. In particular, cerebral single-photon emission computed tomography (SPECT) with dopamine transporter (DAT) ligands may be helpful. DAT-SPECT can be used to demonstrate or rule out nigrostriatal degeneration and thereby differentiate neurodegenerative parkinsonian syndromes from symptomatic parkinsonian syndromes and other differential diagnoses. Positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose (FDG) can be used to identify disease-specific patterns of neuronal dysfunction/degeneration in order to differentiate the various neurodegenerative parkinsonian syndromes from one another. Methods In this review, we summarize the current state of the evidence on DAT-SPECT and FDG-PET for the indications mentioned above on the basis of a selective review of the literature. Results DAT-SPECT has been adequately validated as an in vivo marker for nigrostriatal degeneration. Studies using the clinical diagnosis of a movement disorders specialist over the course of the disease as a reference have shown that DAT- SPECT is 78-100% sensitive (median, 93%) and 70-100% specific (median, 89%) for the differentiation of neurodegenerative parkinsonian syndromes from symptomatic parkinsonism and other differential diagnoses in clinically unclear cases. DAT- SPECT scanning led to a change of diagnosis in 27-56% of patients (median, 43%) and to a change of treatment in 33-72% (median, 43%). FDG-PET enables the differentiation of atypical neurodegenerative parkinsonian syndromes from the idiopathic parkinsonian syndrome (i.e., Parkinson's disease proper) with high sensitivity and specificity (both approximately 90%), when the clinical diagnosis by a movement disorders specialist over the course of the disease is used as a reference. Conclusion DAT-SPECT has been well documented to be highly diagnostically accurate and to have a relevant influence on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome. It has not yet been shown to improve patient-relevant endpoints such as mortality, morbidity, and health-related quality of life; proof of this will probably have to await the introduction of neuroprotective treatments. The current evidence for the high differential diagnostic accuracy of FDG-PET in neurodegenerative parkinsonian syndromes needs to be reinforced by prospective studies with neuropathological verification of the diagnosis.
27 citations
TL;DR: It is found that the circularity obtained from DAT-SPECT images could help in distinguishing NC and PD and the classification performance of ML was significantly improved using circularity in SBRs together.
Abstract: Objective To assess the classification performance between Parkinson’s disease (PD) and normal control (NC) when semi-quantitative indicators and shape features obtained on dopamine transporter (DAT) single photon emission computed tomography (SPECT) are combined as a feature of machine learning (ML). Methods A total of 100 cases of both PD and normal control (NC) from the Parkinson’s Progression Markers Initiative database were evaluated. A summed image was generated and regions of interests were set to the left and right striata. Area, equivalent diameter, major axis length, minor axis length, perimeter and circularity were calculated as shape features. Striatum binding ratios (SBRputamen and SBRcaudate) were used as comparison features. The classification performance of the PD and NC groups according to receiver operating characteristic analysis of the shape features was compared in terms of SBRs. Furthermore, we compared the classification performance of ML when shape features or SBRs were used alone and in combination. Results The shape features (except minor axis length) and SBRs indicated significant differences between the NC and PD groups (p < 0.05). The top five areas under the curves (AUC) were as follows: circularity (0.972), SBRputamen (0.972), major axis length (0.945), SBRcaudate (0.928) and perimeter (0.896). When classification was done using ML, AUC was as follows: circularity and SBRs (0.995), circularity alone (0.990), and SBRs (0.973). The classification performance was significantly improved by combining SBRs and circularity than by SBRs alone (p = 0.018). Conclusion We found that the circularity obtained from DAT-SPECT images could help in distinguishing NC and PD. Furthermore, the classification performance of ML was significantly improved using circularity in SBRs together.
26 citations
TL;DR: Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically, and over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease.
Abstract: Background Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. Aims
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. Method
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. Results
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3. Conclusions
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
15 citations
TL;DR: In this paper, the authors re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and Parkinson’s disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans.
Abstract: Purpose The aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and Parkinson’s disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans Methods Thirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR) Results Patients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously No statistically significant differences were observed between the AD and HC Conclusions This study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD
10 citations
References
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TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Abstract: Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
26,847 citations
TL;DR: A practical guideline for clinical researchers to choose the correct form of ICC is provided and the best practice of reporting ICC parameters in scientific publications is suggested.
12,717 citations
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Abstract: Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
9,411 citations
"A new visual rating scale for Ioflu..." refers result in this paper
...All of the subjects in that study had clinical diagnoses of PD or APD and given the relatively low accuracy clinical compared to pathological diagnosis (Hughes et al., 1992), one might expect that some of the 165 subjects did not in fact have any cortical Lewy body disease....
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Newcastle upon Tyne Hospitals NHS Foundation Trust1, Newcastle University2, Mayo Clinic3, University of Nottingham4, Istanbul University5, University of British Columbia6, University of California, Los Angeles7, Veterans Health Administration8, Drexel University9, Stavanger University Hospital10, Tohoku University11, King's College London12, Pierre-and-Marie-Curie University13, University of California, San Diego14, McGill University15, Rush University Medical Center16, Autonomous University of Madrid17, Neuroscience Research Australia18, National Institutes of Health19, University of Tokyo20, University of North Carolina at Chapel Hill21, Tel Aviv University22, University of Pennsylvania23, University College London24, University of Louisville25, Lund University26, University of Pittsburgh27, University of Washington28, Juntendo University29, Complutense University of Madrid30, University of Göttingen31, Kanazawa University32
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.
4,258 citations