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      Intrastriatal gradient analyses of 18F-FDOPA PET scans for differentiation of Parkinsonian disorders

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          Highlights

          • FDOPA PET allows quantification of presynaptic dopaminergic functioning in vivo .

          • Subregional analysis within the striatum provides additional diagnostic value for differentiation within Parkinsonian disorders.

          • Depletion of F-DOPA uptake in both patients with idiopathic Parkinson's disease and patients with atypical Parkinsonism preferentially affects the posterior part of the putamen.

          • A more linear decrease of FDOPA uptake from the head of the caudate nucleus to the posterior putamen is present in patients with IPD than in APD.

          Abstract

          Aim

          L -3,4-dihydroxy-6–18F-fluorophenylalanine (18F-DOPA PET may be used to distinguish subjects with Parkinsonism from those with symptoms not originating from impaired dopaminergic transmission. However, it is not routinely utilized to discriminate Idiopathic Parkinson's disease (IPD) from Atypical Parkinsonian Disorders (APD). We investigated the potential of FDOPA PET to discriminate between IPD and APD, with a focus on the anterior-to-posterior decline in het striatum, considered to be more specific for IPD.

          Materials and methods

          18F-DOPA PET data from a total of 58 subjects were retrospectively analyzed. 28 subjects had idiopathic Parkinson's disease (14 male, 14 female; age at scan 61 +- 11,5), 13 atypical Parkinsonian disease (7 male, 6 females; age at scan: 69,6 +- 6,4) and 17 were controls (6 male, 11 female; age at scan 65,3 +-8,6). Regional striatal-to-occipital ratio's (RSOR's) were calculated, as well as multiple in-line VOI's from the caudate nucleus to the posterior part of the putamen. The linearity of anteroposterior decline was determined by a linear regression fit and associated R squared values. ROC curves were calculated to assess the diagnostic performance of these measurements. Data contralateral to the clinically most affected side were used for analysis.

          Results

          ROC curve analysis for differentiation between controls and Parkinsonism patients showed the highest AUC for the caudate nucleus-to-posterior putamen ratio (AUC = 0.930; p < 0.00) and for the R squared value for the linear regression fit (AUC = 0.948; p = 0.006). For discrimating IPD from APD, the highest AUC was found for the caudate nucleus-to-anterior putamen ratio (0.824; p < 0.001)

          Conclusions

          Subregional analysis of the striatum in F-DOPA PET scans may provide additional diagnostic information in patients screened for a  presynaptic dopaminergic deficit. A more linear decrease from the head of the caudate nucleus to the posterior putamen was  present in patients with IPD, although this feature did not have additional diagnostic value over the RSOR analysis.

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          Most cited references17

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          A clinicopathologic study of 100 cases of Parkinson's disease.

          The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease.
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            Multiple system atrophy: a review of 203 pathologically proven cases.

            We report the clinicopathological features of 203 cases of pathologically proven multiple system atrophy (MSA) from 108 publications up to February 1995. The majority of patients showed symptoms in their early fifties, and men were more commonly affected than women (ratio of 1.3:1). Most patients suffered from some degree of autonomic failure (74%). Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). The response to levodopa was poor in most patients, but there was a subgroup with a good response, who also often developed axial levodopa-induced dyskinesias. Other characteristic features included severe dysarthria, stridor, and, in a few patients, contractures and dystonia (antecollis). Mild or moderate intellectual impairment occurred in some cases, but severe dementing illness was most unusual. The main pathological change comprised cell loss and gliosis in the putamen, caudate nucleus, external pallidum, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, and intermediolateral cell columns of the spinal cord. However, other neuronal populations were also involved to varying degrees, such as the thalamus, vestibular nucleus, dorsal vagal nucleus, corticospinal tracts, and anterior horn cells. Characteristic glial and/or neuronal cytoplasmic inclusions were identified in all cases in which they were sought, irrespective of clinical presentation. Akinesia correlated with the degree of nigral and putaminal cell loss, whereas rigidity was related only to the later. Tremor was unrelated to cell loss at any site. Ataxia correlated with the degree of olivopontocerebellar atrophy. Pyramidal signs were associated with pyramidal tract pallor. Our analysis also confirmed an association of postural hypotension with intermediolateral cell column degeneration.
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              Accuracy of clinical diagnosis in parkinsonism--a prospective study.

              Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 years experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M-50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                03 January 2020
                2020
                03 January 2020
                : 25
                : 102161
                Affiliations
                [a ]Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands
                [b ]Department of Neurology, University of Groningen, University Medical Center Groningen, the Netherlands
                Author notes
                [* ]Corresponding author. g.n.stormezand01@ 123456umcg.nl
                [1]

                Shared first authorship.

                Article
                S2213-1582(19)30507-8 102161
                10.1016/j.nicl.2019.102161
                6976972
                31981888
                9bacb23c-6265-4e33-a4bc-ff5d6b3c70c2
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 21 May 2019
                : 30 December 2019
                : 31 December 2019
                Categories
                Regular Article

                pet,parkinson's disease,atypical parkinsonism
                pet, parkinson's disease, atypical parkinsonism

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