DÄ internationalArchive44/2019Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes

Review article

Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes

Dtsch Arztebl Int 2019; 116: 747-54. DOI: 10.3238/arztebl.2019.0747

Buchert, R; Buhmann, C; Apostolova, I; Meyer, P T; Gallinat, J

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.

LNSLNS

The term “clinically uncertain parkinsonian syndrome” refers to symptom constellations with akinesia and at least one of the cardinal symptoms rigor, resting tremor, and postural instability (1). In addition to Parkinson’s disease (idiopathic parkinsonian syndrome, IPS) (2), the causes of parkinsonian syndromes include the atypical neurogenerative parkinsonian syndromes (APS) such as multiple system atrophy (MSA) (3), progressive supranuclear palsy (PSP) (e1), and corticobasal syndrome (CBS)—the latter of which neuropathologically often results from corticobasal degeneration (CBD) (e2). These have to be distinguished from symptomatic parkinsonian syndromes and other differential diagnoses. Symptomatic parkinsonian syndromes can develop as a result of structural brain lesions (ischemic, traumatic, tumor-related), medication effects, intoxication, as well as inflammatory and metabolic disorders. Of great importance in clinical practice is vascular parkinsonian syndrome in subcortical arteriosclerotic encephalopathy. The differential diagnoses include normal pressure hydrocephalus, essential tremor, and (rarely) dopa-responsive dystonia. The different symptomatic parkinsonian syndromes as well as the differential diagnoses require completely different therapeutic approaches, and early diagnosis is crucial. The early differential diagnosis of the neurodegenerative parkinsonian syndromes is also crucial for adequately patient-centered therapy. In IPS this means early medication treatment (e3) and, over the course of the illness, different pharmacological strategies in order to improve patients’ quality of life (e4, e5). Patients with APS have a much poorer prognosis and derive little benefit (MSA, PSP-P) or no benefit at all (CBS and PSP-RS) from dopamine substitution treatment (e6). The correct etiological classification is therefore important in order to advise patients from a sociomedical perspective and spare them from undergoing unhelpful treatment that potentially causes adverse effects while initiating adequate symptomatic treatment measures (e6).

The etiological classification of parkinsonian syndromes is done primarily on a clinical basis—that is, on the basis of symptoms and by using conventional additional investigations, such as cranial magnetic resonance imaging (MRI) in order to rule out structural lesions (1). In the setting of non-specialist care, the clinical IPS diagnosis is accurate in about 75%, when made by a movement disorder specialist the diagnosis is accurate in 80% at the initial examination and in about 85% during follow-up examinations (4). The clinical APS diagnosis is less accurate (e7, e8). These numbers demonstrate the need for additional investigations for the purpose of etiological classification in cases that are clinically uncertain.

The guideline “Idiopathic Parkinsonian Syndrome“ of the German Society of Neurology (DGN) and the Association of the Scientific Medical Societies in Germany (AWMF), which was updated in 2016, lists the following additional investigations:

  • Cerebral single-photon emission computed tomography (SPECT) with tracers for the dopamine transporter (DAT) (“DAT-SPECT should be undertaken early on in the disease course to confirm nigrostriatal deficit in clinically uncertain parkinsonian or tremor syndromes”) and
  • Cerebral positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose (FDG) to detect neuronal dysfunction/degeneration (“FDG-PET can be used in selected cases for the best possible differential diagnostic classification of neurodegenerative parkinsonian syndromes, especially for the differentiation of atypical neurodegenerative parkinsonian syndromes from idiopathic parkinsonian syndrome”) (1).

This review article summarizes studies of DAT-SPECT and FDG-PET for the indications mentioned in the guideline. We included recent publications (“recent” is taken to mean the time period since 2015—that is, after the literature selection for evaluating nuclear imaging in the DGN/AWMF guideline). DAT-SPECT will be discussed in greater detail here than FDG-PET because of the stronger guideline recommendation. For [123I]metaiodobenzylguanidine scintigraphy of the noradrenergic innervation of the heart for the purpose of distinguishing MSA from IPS, the reader is referred to the pertinent review articles (5, e9).

DAT-SPECT in the diagnostic evaluation of parkinsonian syndromes

We conducted a literature search in PubMed, using the search term “ioflupane OR FP-CIT OR datscan OR DAT-scan OR β-CIT OR ([(dopamine transporter) OR DAT] AND [(single photon emission tomography) OR SPECT OR SPET])”, which yielded 2476 hits on 17 June 2019. Furthermore, we undertook a backward search on the basis of selected publications and a forward search on Web of Science.

IPS and APS are accompanied by the loss of dopaminergic neurons in the substantia nigra and its nerve endings in the striatum (nigrostriatal degeneration) (e10e13). Symptomatic parkinsonian syndromes and the differential diagnoses mentioned above are as a rule not accompanied by nigrostriatal degeneration.

Reduced DAT availability in the striatum is an appropriate marker for nigrostriatal degeneration in IPS since the degeneration of dopaminergic nerve endings in the striatum is very pronounced even at the early disease stages (e14e16). Compensatory downregulation of the DAT expression in the remaining nerve endings results in more pronounced striatal DAT loss (e17e19). To differentiate parkinsonian syndromes with relevant nigrostriatal degeneration (IPS and APS) from parkinsonian syndromes without relevant nigrostriatal degeneration (symptomatic parkinsonian syndromes, differential diagnoses) on the basis of the availability of striatal DAT, the DAT ligand N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[123I] iodophenyl) nortropane ([123I]ioflupane, [123I]FP-CIT) has been licensed as a tracer for SPECT (6). No further DAT tracers for SPECT (e20e24) have been licensed to date.

As an in-vivo marker of nigrostriatal degeneration, DAT-SPECT is well validated by comparisons with postmortem examinations in rodents (e25e28), macaques (e29e31), and patients (79).

In order to assess the results of DAT-SPECT, visual interpretation of the image (without quantitative evaluation) is usually sufficient (10). Agreement between different readers is usually good or very good (11, e32, e33). The proportion of borderline findings is below 10% (12, e34). The direct comparison of DAT-SPECT and DAT-PET to detect nigrostriatal degeneration at the symptomatic stage of neurodegenerative parkinsonian syndromes does not show any practice-relevant inferiority for DAT-SPECT compared with DAT-PET, although PET provides superior image quality with respect to spatial resolution and statistical noise (13, e35, e36). The explanation is that motor symptoms in IPS become obvious only from a DAT loss of at least 50% in the posterior putamen (14), and this large effect can be detected reliably by using DAT-SPECT too (Figure 1).

Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng
Figure 1
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng

Prospective studies of the diagnostic accuracy of DAT-SPECT in clinically uncertain parkinsonian or tremor syndromes with postmortem verification are lacking. Studies that used the clinical diagnosis made by movement disorder specialists during the course of the illness as a reference showed a sensitivity of 78–100% (median 93%, 18 studies, of which five were recent, including 1963 patients, eTable) and a specificity of 70–100% (median 89%). Some of these studies possibly underestimated the diagnostic accuracy of DAT-SPECT because of the limitations of the clinical diagnosis as standard of truth. This is supported by the fact that the accuracy of DAT-SPECT improves with increasing time to follow-up to obtain the clinical reference diagnosis (11), probably because the clinical diagnostic accuracy improves over time (4). This assumption is also supported by a longitudinal study in which DAT-SPECT after 36 months showed in only two out of 99 patients a discordant finding compared with DAT-SPECT at the start of the study (15). In an annual loss of striatal DAT of 5% (IPS) to 10% (APS) (16), DAT-SPECT after three years would have been able to detect nigrostriatal degeneration that at the time of the initial examination was below the detectability threshold (17). Uncertainty in determining the sensitivity of DAT-SPECT originates not least from the fact that some patients with a clinical diagnosis of a neurodegenerative parkinsonian syndrome present with normal DAT availability according to DAT-SPECT; these patients are referred to as “subjects without evidence of dopaminergic deficit (SWEDD)” (18). Longitudinal studies in which most of the SWEDD had a normal finding on DAT-SPECT even after two to five years hint at clinical overdiagnosis of neurodegenerative parkinsonian syndrome as the most likely explanation for SWEDD (15, 19, e37).

Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1
Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1
eTable
Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1

The Movement Disorder Society lists a normal result on DAT-SPECT as an absolute exclusion criterion for the diagnosis of clinically certain or possible IPS (2). A pathological DAT-SPECT result was not included as a supporting criterion for a diagnosis of IPS because DAT-SPECT is not suitable for differentiating IPS from APS (2). For the diagnosis of probable MSA of the cerebellar type a pathological DAT-SPECT result is one of six additional characteristics of which at least one has to be present (3).

After DAT-SPECT, the diagnosis changes in 27–56% of patients with clinically uncertain parkinsonian or tremor syndrome (median 43%, 12 original studies, of these 8 recent ones, including a total of 2719 patients) (Table). In 33–72% of patients, DAT-SPECT results in changing treatment (median 43%). In a clinically certain diagnosis of IPS, DAT-SPECT probably affects management much less than in clinically uncertain cases (20).

Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1
Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1
Table
Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1

In sum, high diagnostic accuracy and a relevant effect on the diagnosis and therapy in clinically uncertain parkinsonian or tremor syndromes have been well confirmed as the basis of the guideline recommendations for DAT-SPECT; recent studies have added to the evidence (eTable, Table). The European IPS guideline recommends DAT-SPECT in the setting of significant diagnostic uncertainty, especially in atypical tremor manifestations (21). According to the British guideline, DAT-SPECT should be considered in case of uncertainty regarding the differentiation of parkinsonian syndrome with nigrostriatal degeneration and essential tremor (22).

Guideline recommendations for DAT-SPECT relate exclusively to clinically uncertain cases. A clinical uncertain parkinsonian or tremor syndrome is present if at least one of the following criteria is met (23, 24):

  • Only one of the three cardinal symptoms rigor, resting tremor, postural instability in addition to akinesia/bradykinesia
  • Two cardinal symptoms without akinesia/bradykinesia
  • Atypical symptoms
  • Only mild symptoms
  • Poor response to dopamine substitution treatment
  • Very slow/absent or very rapid progression of symptoms
  • Atypical age.

The primary suspected diagnoses are immaterial: DAT-SPECT serves the purpose of differentiating parkinsonian syndromes with nigrostriatal degeneration (independently of the cause of the degeneration) from parkinsonian syndromes without nigrostriatal degeneration (also independently of the etiology) in clinically uncertain cases. Application of these criteria for a clinically uncertain parkinsonian or tremor syndrome (explicitly or mutatis mutandis) results in a pretest probability for pathological DAT-SPECT findings of 27–79% (median 60%, eTable). Clinical uncertainty regarding the differentiation between IPS and APS is not an indication for DAT-SPECT (23).

In 2015, about 10 000 DAT-SPECT investigations were carried out in Germany (25). Assuming that of these, 1000–2000 were conducted in the setting of suspected Lewy body dementia (eBox), this corresponds to 30% of all patients with new-onset parkinsonism (incidence 33/100 000 per year [e38]). This speaks in favor of adequate use of DAT-SPECT. However, the rate of patients referred for DAT-SPECT when newly presenting with parkinsonism varies strongly between different movement disorder specialists (e39, e40). Model-based analyses of the cost effectiveness of DAT-SPECT assume 20–30% of clinically uncertain cases among all patients with early stage parkinsonian syndrome (26, e41).

DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease
DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease
eBox
DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease

The relevant effect of DAT-SPECT in clinically uncertain parkinsonian or tremor syndromes lies in enabling earlier correct diagnosis. As a result, patients benefit from receiving adequate treatment about 1–2 years earlier compared to clinical diagnosis alone (26, e42, e43). In individual cases, however, the time to correct diagnosis of a neurodegenerative parkinsonian syndrome on clinical grounds can be more than 10 years (e44).

Confirmation of the benefit of DAT-SPECT in the diagnostic evaluation of clinically uncertain parkinsonian or tremor syndromes in terms of patient-relevant endpoints—such as mortality, morbidity, and health related quality of life—is pending (27) and will probably only become possible once neuroprotective therapies become available.

For predicting α-synuclein pathology syndrome in patients with idiopathic REM sleep behavior disorder, DAT-SPECT probably yields independent information beyond clinical parameters and other investigations (e45e48). The prognostic value of DAT-SPECT at very early clinical stages—that is, before the occurrence of motor symptoms—has, however, not been definitively explored. Thus, routine clinical use of DAT-SPECT for this indication cannot be recommended at this time.

In Germany, DAT-SPECT using [123I]ioflupane is also licensed for distinguishing dementia with Lewy bodies from Alzheimer’s disease (eBox).

Safety

Ioflupane is a cocaine analogue with a high affinity for DAT (e49). For DAT-SPECT, the maximum administered dose is 0.325µg ioflupane, which occupies, at most, 1% of striatal DAT. Typical cocaine effects require at least 60% DAT occupancy to occur (e50).

Temporary adverse effects of a mild or moderate intensity—especially headache and nausea—affect a maximum of 4% of patients (28). In one of 1180 patients, limbic encephalopathy was diagnosed, with a possible causal association with a DAT-SPECT investigation conducted 81 days previously (28). No further indications of severe adverse effects have been documented (28).

Intravenous administration of the recommended amount of radioactivity of 180 MBq [123I]ioflupane (e51) leads to an effective radiation dose of 4.4 millisievert (mSv) (29). The mean effective dose from natural sources of radiation in Germany is 2.1 mSv per year (range 1–10 mSv). The primary risk associated with exposure to low doses of radiation is that of developing a radiation-induced tumor. In an effective radiation dose of 4.4 mSv at age 50 years or older, the lifetime risk of dying from tumor disease thus induced is below 1 : 5000. By comparison, the overall lifetime risk to die from cancer is about 1 : 5 (www.cancer.org/cancer/cancer-basics/lifetime-probability-of-developing-or-dying-from-cancer.html). The mean latency period between radiation exposure and the occurrence of an induced tumor is eight years for leukemia and thyroid cancer; for all other tumor diseases it is more than 10 years (www.bfs.de/DE/themen/ion/wirkung/krebs/einfuehrung/einfuehrung. html). By comparison, the median survival after a diagnosis of APS is 3–5 years (e52, e53).

Limitations

Relevant medication interactions are rare for DAT-SPECT. Before the investigation, only substances with direct DAT inhibition have to be discontinued: cocaine, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, modafinil, diethylpropion, mazindol, phentermine, bupropion, venlafaxine, radafaxine, fentanyl, ketamine, isoflurane, and phenyl-cyclidine-piperidine (30). The antidepressants venlafaxine and bupropion are of particular practical relevance. Antipsychotics do not have any relevant effect on DAT-SPECT and therefore do not have to be discontinued (30, e54). Smoking does not affect DAT-SPECT either (e55).

Because of partly lacking nigrostriatal degeneration in CBD, the sensitivity of DAT-SPECT for detecting CBD is limited (e56e58).

Lesions in the striatum or brainstem result in a defect in striatal tracer uptake on DAT-SPECT, which depending on its location cannot be distinguished from the typical pattern of nigrostriatal degeneration (e59, e60) (Figure 2). In order to avoid a misinterpretation of vascular lesions as an indication of nigrostriatal degeneration, DAT-SPECT should be interpreted in tandem with up-to-date structural imaging, preferably cranial MRI (31).

Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions
Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions
Figure 2
Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions

DAT-SPECT is not suitable for differentiating the various neurodegenerative parkinsonian syndromes (IPS, MSA, PSP, CBD) from each other (9, e61). The guideline names cerebral PET scanning using the glucose analogue [18F]fluorodeoxyglucose (FDG) as the best modality for this purpose (1).

FDG-PET in the differential diagnostic evaluation of neurodegenerative parkinsonian syndromes

FDG-PET of the brain depicts the regional cerebral glucose metabolism, which is closely connected to neuronal activity (e62e64). Thus, cerebral FDG-PET is a marker for regional neuronal dysfunction/degeneration. The strength of FDG-PET in the differential diagnostic evaluation of neurodegenerative parkinsonian syndromes lies in the identification of disease-specific patterns of findings on PET (Figure 3). To support the visual assessment of the PET images, voxel-based evaluations are used which compare the FDG-PET image of the patient with those of healthy persons voxel by voxel, in the simplest scenario by using z scores or t tests (e65, e66). The result of the voxel-based test can be superimposed on tomography sections (Figure 3). Voxel-based testing improves the accuracy of FDG-PET in detecting neurodegenerative disorders for inexperienced persons interpreting the findings as well as for experts (e67).

Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes
Figure 3
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes

A recent meta-analysis of FDG-PET to distinguish APS (MSA, PSP, CBD) from IPS showed a sensitivity of 91% (95% confidence interval [72; 98]) and a specificity of 91% [70; 98] in relation to the clinical diagnosis made by movement disorder specialists after a period of 1–2 years after the PET investigation (32). At the time of the PET, the clinical diagnosis was usually uncertain (32). FDG-PET offered good accuracy for differentiating MSA from PSP and CBD (33). Differentiating PSP from CBD was less successful, in particular PSP was miscategorized as CBD (34), which is consistent with the wide overlap between the tauopathies PSP and CBD (e68e71). New approaches to evaluating FDG-PET on the basis of voxel-based analysis of covariance allow for automatic and thus user-independent differentiation between the different neurodegenerative parkinsonian syndromes (35).

Longitudinal studies demonstrate the benefit of FDG-PET for predicting dementia in IPS (36, e72) and survival in suspected APS (37).

In view of the inherent uncertainties of the clinical differentiation of APS from IPS and APS among themselves, prospective studies with clinically relevant patient populations and postmortem verification of the diagnosis are needed for the further validation of FDG-PET for the differential diagnostic evaluation of neurodegenerative parkinsonian syndromes (38). Existing reports of case series with postmortem verification (35, e73e77) are not sufficient, even though they confirm the disease-specific patterns of findings from patient populations with a clinical diagnosis.

For further discussion of the role of FDG-PET in the diagnostic evaluation of neurodegenerative parkinsonian syndromes we refer readers to the recent literature (32, 38, 39).

Conflict of interest statement

Dr Buchert received financial support for conducting advanced training courses from GE Healthcare. He received study support from Pinax Pharma and Siemens. He received a honorarium from ABX-CRO for composing a manuscript.

Prof. Buhman received lecture fees from GE Healthcare.

Prof Meyer received travel expenses and lecture fees from GE Healthcare.

Prof. Gallinat received support for events or lectures from Lundbeck, Janssen-Cilag, Lilly, and Otsuka.

Dr. Apostolova declares that no conflict of interest exists.

Manuscript received on 1 March 2019, revised version accepted on
8 August 2019.

Translated from the original German by Birte Twisselmann, PhD.

Corresponding author
Dr. rer. nat. Ralph Buchert
Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie und
Nuklearmedizin, Universitätsklinikum Hamburg-Eppendorf
Martinistr. 52, 20246 Hamburg, Germany
r.buchert@uke.de

Cite this as:
Buchert R, Buhmann C, Apostolova I, Meyer PT, Gallinat J: Nuclear imaging in the diagnosis of clinically uncertain parkinsonian syndromes. Dtsch Arztebl Int 2019; 116: 747–54. DOI: 10.3238/arztebl.2019.0747

Supplementary material

For eReferences please refer to:
www.aerzteblatt-international.de/ref4419

eTable, eBox:
www.aerzteblatt-international.de/19m0747

1.
DGN, AWMF: S3-Leitlinie „Idiopathisches Parkinson-Syndrom“. AWMF-Register-Nummer: 030–010. 2016. www.awmf.org/uploads/tx_szleitlinien/030–010l_S3_Parkinson_Syndrome_Idiopathisch_2016–06.pdf (last accessed on 3 September 2019).
2.
Postuma RB, Berg D, Stern M, et al.: MDS clinical diagnostic criteria for Parkinson‘s disease. Mov Disord 2015; 30: 1591–601 CrossRef MEDLINE
3.
Gilman S, Wenning GK, Low PA, et al.: Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71: 670–6 CrossRef MEDLINE PubMed Central
4.
Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G: Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology 2016; 86: 566–76 CrossRef MEDLINE
5.
Meyer PT, Frings L, Hellwig S: Nuklearmedizinische Differenzialdiagnostik der Parkinson-Syndrome: Update 2016. Der Nuklearmediziner 2016; 39: 245–58 CrossRef
6.
Neumeyer JL, Wang SY, Gao YG, et al.: N-Omega-Fluoroalkyl Analogs of
(1r)-2-Beta-Carbomethoxy-3-Beta-(4-Iodophenyl)-Tropane (Beta-Cit) – radiotracers for positron emission tomography and single-photon emission computed-tomography imaging of dopamine transporters. J Med Chem 1994; 37: 1558–61 CrossRef MEDLINE
7.
Kraemmer J, Kovacs GG, Perju-Dumbrava L, Pirker S, Traub-Weidinger T, Pirker W: Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts. Mov Disord 2014; 29: 1767–73 CrossRef MEDLINE
8.
Colloby SJ, McParland S, O‘Brien JT, Attems J: Neuropathological correlates of dopaminergic imaging in Alzheimer‘s disease and Lewy body dementias. Brain 2012; 135: 2798–808 CrossRef MEDLINE
9.
Perju-Dumbrava LD, Kovacs GG, Pirker S, et al.: Dopamine transporter imaging in autopsy-confirmed parkinson‘s disease and multiple system atrophy. Movement Disord 2012; 27: 65–71 CrossRef MEDLINE
10.
Booij J, Dubroff J, Pryma D, et al.: Diagnostic performance of the visual reading of (123)I-Ioflupane SPECT images with or without quantification in patients with movement disorders or dementia. J Nucl Med 2017; 58: 1821–6 CrossRef MEDLINE
11.
Seibyl JP, Kupsch A, Booij J, et al.: Individual-reader diagnostic performance and between-reader agreement in assessment of subjects with Parkinsonian syndrome or dementia using 123I-ioflupane injection (DaTscan) imaging. J Nucl Med 2014; 55: 1288–96 CrossRef MEDLINE
12.
Albert NL, Unterrainer M, Diemling M, et al.: Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging 2016; 43: 1315–22 CrossRef MEDLINE
13.
Lee I, Kim JS, Park JY, et al.: Head-to-head comparison of (18)F-FP-CIT and (123) I-FP-CIT for dopamine transporter imaging in patients with Parkinson‘s disease: a preliminary study. Synapse 2018; 72: e22032 CrossRef MEDLINE
14.
Kordower JH, Olanow CW, Dodiya HB, et al.: Disease duration and the integrity of the nigrostriatal system in Parkinson‘s disease. Brain 2013; 136: 2419–31 CrossRef MEDLINE PubMed Central
15.
Marshall VL, Reininger CB, Marquardt M, et al.: Parkinson‘s disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT. Mov Disord 2009; 24: 500–8 CrossRef MEDLINE
16.
Pirker W, Djamshidian S, Asenbaum S, et al.: Progression of dopaminergic degeneration in Parkinson‘s disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study. Mov Disord 2002; 17: 45–53 CrossRef MEDLINE
17.
Suwijn SR, van Boheemen CJ, de Haan RJ, Tissingh G, Booij J, de Bie RM: The diagnostic accuracy of dopamine transporter SPECT imaging to detect nigrostriatal cell loss in patients with Parkinson‘s disease or clinically uncertain parkinsonism: a systematic review. Ejnmmi Res 2015; 5: 12 CrossRef MEDLINE PubMed Central
18.
Marek KL, Jennings DL, Seibyl JP, Grp PS: Long-term follow-up of patients with scans without evidence of dopaminergic deficit (SWEDD) in the ELLDOPA study. Neurology 2005;64(suppl 1): Abstract 274.
19.
Batla A, Erro R, Stamelou M, et al.: Patients with scans without evidence of dopaminergic deficit: a long-term follow-up study. Mov Disord 2014; 29: 1820–5 CrossRef MEDLINE
20.
Hickey PT, Kuchibhatla M, Scott B, Gauger L, Stacy MA: Dopamine transporter imaging has no impact on functional outcomes in de novo probable Parkinson‘s disease. J Parkinson Dis 2017; 7: 279–87 CrossRef MEDLINE
21.
Berardelli A, Wenning GK, Antonini A, et al.: EFNS/MDS-ES recommendations for the diagnosis of Parkinson‘s disease. Eur J Neurol 2013; 20: 16–34 CrossRef MEDLINE
22.
NICE: Parkinson’s disease in adults. National Institute for Health and Care Excellence (NICE) guideline [NG71], 2017. www.nice.org.uk/guidance/ng71 (last accessed on 3 September 2019).
23.
Catafau AM, Tolosa E, Da TCUPSSG: Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes. Mov Disord 2004; 19: 1175–82 CrossRef MEDLINE
24.
Booij J, Speelman JD, Horstink MW, Wolters EC: The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med 2001; 28: 266–72 CrossRef MEDLINE
25.
Hellwig D, Marienhagen J, Menhart K, Grosse J: [Nuclear medicine in Germany. Updated key data and trends from official statistics]. Nuklearmedizin 2017; 56: 55–68 CrossRef MEDLINE
26.
Van Laere K, Everaert L, Annemans L, Gonce M, Vandenberghe W, Vander Borght T: The cost effectiveness of 123I-FP-CIT SPECT imaging in patients with an uncertain clinical diagnosis of parkinsonism. Eur J Nucl Med Mol Imaging 2008; 35: 1367–76 CrossRef MEDLINE
27.
Kupsch AR, Bajaj N, Weiland F, et al.: Impact of DaTscan SPECT imaging on clinical management, diagnosis, confidence of diagnosis, quality of life, health resource use and safety in patients with clinically uncertain parkinsonian syndromes: a prospective 1-year follow-up of an open-label controlled study. J Neurol Neurosur Ps 2012; 83: 620–8 CrossRef MEDLINE
28.
Grosset DG, Tatsch K, Oertel WH, et al.: Safety analysis of 10 clinical trials and for 13 years after first approval of ioflupane 123I injection (DaTscan). J Nucl Med 2014; 55: 1281–7 CrossRef MEDLINE
29.
Booij J, Sokole EB, Stabin MG, Janssen AGM, de Bruin K, van Royen EA: Human biodistribution and dosimetry of [I-123]FP-CIT: a potent radioligand for imaging of dopamine transporters. Eur J Nucl Med 1998; 25: 24–30 CrossRef
30.
Booij J, Kemp P: Dopamine transporter imaging with [I-123]FP-CIT SPECT: potential effects of drugs. Eur J Nucl Med Mol I 2008; 35: 424–38 CrossRef MEDLINE
31.
Tatsch K, Buchert R, Bartenstein P, et al.: Dopamine Transporter SPECT with I-123 labelled FP-CIT (DaTSCANTM). Nuklearmedizin 2019; 58: 5–16 CrossRef MEDLINE
32.
Meyer PT, Frings L, Rucker G, Hellwig S: (18)F-FDG PET in Parkinsonism: differential diagnosis and evaluation of cognitive impairment. J Nucl Med 2017; 58: 1888–98 CrossRef MEDLINE
33.
Eckert T, Barnes A, Dhawan V, et al.: FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005; 26: 912–21 CrossRef MEDLINE
34.
Hellwig S, Amtage F, Kreft A, et al.: [18F]FDG-PET is superior to [¹²³I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology 2012; 79: 1314–22 CrossRef MEDLINE
35.
Niethammer M, Tang CC, Feigin A, et al.: A disease-specific metabolic brain network associated with corticobasal degeneration. Brain 2014; 137: 3036–46 CrossRef MEDLINE PubMed Central
36.
Pilotto A, Premi E, Caminiti SP, et al.: Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease. Neurology 2018; 90: E1029–E37 CrossRef MEDLINE
37.
Hellwig S, Frings L, Amtage F, et al.: 18F-FDG PET Is an early predictor of overall survival in suspected atypical parkinsonism. J Nucl Med 2015; 56: 1541–6 CrossRef MEDLINE
38.
Walker Z, Gandolfo F, Orini S, et al.: Clinical utility of FDG PET in Parkinson‘s disease and atypical parkinsonism associated with dementia. Eur J Nucl Med Mol Imaging 2018; 45: 1534–45 CrossRef MEDLINE PubMed Central
39.
Whitwell JL, Hoglinger GU, Antonini A, et al.: Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be? Mov Disord 2017; 32: 955–71 CrossRef MEDLINE PubMed Central
40.
Buchert R, Lange C, Apostolova I, Meyer PT: Dopamintransporter-SPECT mit [123I]FP-CIT: Empfehlungen für die visuelle Beurteilung. Der Nuklearmediziner 2015; 38: 40–7 CrossRef
e1.
Hoglinger GU, Respondek G, Stamelou M, et al.: Clinical diagnosis of progressive supranuclear palsy: The Movement Disorder Society Criteria. Movement Disord 2017; 32: 853–64 CrossRef MEDLINE PubMed Central
e2.
Armstrong MJ, Litvan I, Lang AE, et al.: Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: 496–503 CrossRef MEDLINE PubMed Central
e3.
Grosset D, Taurah L, Burn DJ, et al.: A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson‘s disease left untreated at diagnosis. J Neurol Neurosurg Psychiatry 2007; 78: 465–9 CrossRef MEDLINE PubMed Central
e4.
Diaz NL, Waters CH: Current strategies in the treatment of Parkinson‘s disease and a personalized approach to management. Expert Rev Neurother 2009; 9: 1781–9 CrossRef MEDLINE
e5.
Global Parkinson‘s Disease Survey Steering Committee: Factors impacting on quality of life in Parkinson‘s disease: results from an international survey. Mov Disord 2002; 17: 60–7 CrossRef MEDLINE
e6.
Levin J, Kurz A, Arzberger T, Giese A, Höglinger GU: The differential diagnosis and treatment of atypical Parkinsonism. Dtsch Arztebl Int 2016; 113: 61–9 CrossRef MEDLINE PubMed Central
e7.
Koga S, Aoki N, Uitti RJ, et al.: When DLB, PD, and PSP masquerade as MSA. An autopsy study of 134 patients. Neurology 2015; 85: 404–12 CrossRef MEDLINE PubMed Central
e8.
Koga S, Kouri N, Walton RL, et al.: Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype. Acta Neuropathologica 2018; 136: 389–404 CrossRef MEDLINE PubMed Central
e9.
Knudsen K, Borghammer P: Imaging the Autonomic Nervous System in Parkinson‘s Disease. Curr Neurol Neurosci Rep 2018; 18: 79 CrossRef MEDLINE
e10.
Dickson DW: Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 1999; 246 Suppl 2: II6–15 CrossRef MEDLINE
e11.
Dickson DW, Bergeron C, Chin SS, et al.: Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002; 61: 935–46 CrossRef MEDLINE
e12.
Piggott MA, Marshall EF, Thomas N, et al.: Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer‘s and Parkinson‘s diseases: rostrocaudal distribution. Brain 1999; 122 (Pt 8): 1449–68 CrossRef MEDLINE
e13.
Wenning GK, Ben-Shlomo Y, Magalhaes M, Daniel SE, Quinn NP: Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 1995; 58: 160–6 CrossRef MEDLINE PubMed Central
e14.
Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F: Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973; 20: 415–55 CrossRef
e15.
Niznik HB, Fogel EF, Fassos FF, Seeman P: The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. J Neurochem 1991; 56: 192–8 CrossRef MEDLINE
e16.
Fazio P, Svenningsson P, Cselenyi Z, Halldin C, Farde L, Varrone A: Nigrostriatal dopamine transporter availability in early Parkinson‘s disease. Mov Disord 2018; 33: 592–9 CrossRef MEDLINE
e17.
Lee CS, Samii A, Sossi V, et al.: In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson‘s disease. Ann Neurol 2000; 47: 493–503 CrossRef
e18.
Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V: Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. Neurology 2017; 88: 1461–7 CrossRef MEDLINE
e19.
Honkanen EA, Saari L, Orte K, et al.: No link between striatal dopaminergic axons and dopamine transporter imaging in Parkinson‘s disease. Mov Disord 2019; doi: 10.1002/mds.27777. [Epub ahead of print] CrossRef MEDLINE
e20.
Seibyl JP, Marek K, Sheff K, et al.: Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson‘s patients. J Nucl Med 1998; 39: 1500–8.
e21.
Van Laere K, De Ceuninck L, Dom R, et al.: Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-beta-CIT versus 99mTc-TRODAT-1. Eur J Nucl Med Mol Imaging 2004; 31: 1119–27 CrossRef MEDLINE
e22.
Kim HJ, Im JH, Yang SO, et al.: Imaging and quantitation of dopamine transporters with iodine-123-IPT in normal and Parkinson‘s disease subjects. J Nucl Med 1997; 38: 1703–11.
e23.
Fischman AJ, Bonab AA, Babich JW, et al.: Rapid detection of Parkinson‘s disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse 1998; 29: 128–41 CrossRef
e24.
Ziebell M: Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT. Dan Med Bull 2011; 58: B4279.
e25.
Andringa G, Drukarch B, Bol JG, et al.: Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson‘s disease. Neuroimage 2005; 26: 1150–8 CrossRef MEDLINE
e26.
Alvarez-Fischer D, Blessmann G, Trosowski C, et al.: Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson‘s disease. Neuroimage 2007; 38: 5–12 CrossRef MEDLINE
e27.
Back S, Raki M, Tuominen RK, Raasmaja A, Bergstrom K, Mannisto PT: High correlation between in vivo [123I]beta-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats. Ejnmmi Res 2013; 3: 46 CrossRef MEDLINE PubMed Central
e28.
Gleave JA, Farncombe TH, Saab C, Doering LC: Correlative single photon emission computed tomography imaging of [123I]altropane binding in the rat model of Parkinson‘s. Nucl Med Biol 2011; 38: 741–9 CrossRef MEDLINE
e29.
Ashkan K, Wallace BA, Mitrofanis J, et al.: SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson‘s disease. Parkinsonism Relat Disord 2007; 13: 266–75 CrossRef MEDLINE
e30.
Tian L, Karimi M, Brown CA, Loftin SK, Perlmutter JS: In vivo measures of nigrostriatal neuronal response to unilateral MPTP treatment. Brain Res 2014; 1571: 49–60 CrossRef MEDLINE PubMed Central
e31.
Karimi M, Tian L, Brown CA, et al.: Validation of nigrostriatal positron emission tomography measures: critical limits. Ann Neurol 2013; 73: 390–6 CrossRef MEDLINE PubMed Central
e32.
Papathanasiou N, Rondogianni P, Chroni P, et al.: Interobserver variability, and visual and quantitative parameters of (123)I-FP-CIT SPECT (DaTSCAN) studies. Ann Nucl Med 2012; 26: 234–40 CrossRef MEDLINE
e33.
Ahmed A, Huang JB, Chen K, Zubeldia JM, Booij J, Vijayakumar V: [I-123]Ioflupane imaging in Caucasians and non-Caucasians: are there any differences? J Neurol Sci 2018; 395: 159–63 CrossRef MEDLINE
e34.
Makinen E, Joutsa J, Johansson J, Maki M, Seppanen M, Kaasinen V: Visual versus automated analysis of [I-123]FP-CIT SPECT scans in parkinsonism. J Neural Transm (Vienna) 2016; 123: 1309–18 CrossRef MEDLINE
e35.
Eshuis SA, Jager PL, Maguire RP, Jonkman S, Dierckx RA, Leenders KL: Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson‘s disease and healthy controls. Eur J Nucl Med Mol Imaging 2009; 36: 454–62 CrossRef MEDLINE
e36.
Jakobson Mo S, Axelsson J, Jonasson L, et al.: Dopamine transporter imaging with [(18)F]FE-PE2I PET and [(123)I]FP-CIT SPECT-a clinical comparison. Ejnmmi Res 2018; 8: 100 CrossRef MEDLINE PubMed Central
e37.
Marek K, Seibyl J, Eberly S, et al.: Longitudinal follow-up of SWEDD subjects in the PRECEPT Study. Neurology 2014; 82: 1791–7 CrossRef MEDLINE PubMed Central
e38.
Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA: Time trends in the incidence of Parkinson disease. JAMA Neurol 2016; 73: 981–9 CrossRef MEDLINE PubMed Central
e39.
Oravivattanakul S, Benchaya L, Wu G, et al.: Dopamine Transporter (DaT) Scan utilization in a movement disorder center. Mov Disord Clin Pract 2016; 3: 31–5 CrossRef MEDLINE PubMed Central
e40.
Vlaar AM, de Nijs T, Kessels AG, et al.: Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. Eur Neurol 2008; 59: 258–66 CrossRef MEDLINE
e41.
Dodel RC, Hoffken H, Moller JC, et al.: Dopamine transporter imaging and SPECT in diagnostic workup of Parkinson‘s disease: a decision-analytic approach. Movement Disord 2003; 18: S52–S62 CrossRef MEDLINE
e42.
Bruggenjurgen B, Smala A, Chambers M: Cost-effectiveness of non-invasive imaging in the diagnosis of Parkinsonism. Value Health 2005; 8: Aabstract 15 CrossRef
e43.
Busca R, Antonini A, Lopatriello S, Berto P: Economic evaluation of SPECT-DaTSCAN in the diagnosis of patients with clinically uncertain Parkinsonism in Italy. Value Health 2005; 8: Abstract 14 CrossRef
e44.
Rajput AH, Rozdilsky B, Rajput A: Accuracy of clinical diagnosis in parkinsonism—a prospective study. Can J Neurol Sci 1991; 18: 275–8 CrossRef MEDLINE
e45.
Iranzo A, Santamaria J, Valldeoriola F, et al.: Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. Ann Neurol 2017; 82: 419–28 CrossRef MEDLINE
e46.
Postuma RB, Iranzo A, Hu M, et al.: Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 2019; 142: 744–59 CrossRef MEDLINE PubMed Central
e47.
Chahine LM, Iranzo A, Fernandez-Arcos A, et al.: Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder. NPJ Parkinsons Dis 2019; 5: 2 CrossRef MEDLINE PubMed Central
e48.
Meles SK, Vadasz D, Renken RJ, et al.: FDG PET, dopamine transporter SPECT, and olfaction: combining biomarkers in REM sleep behavior disorder. Mov Disord 2017; 32: 1482–6 CrossRef MEDLINE PubMed Central
e49.
Geisler S, Beindorff N, Cremer M, et al.: Characterization of [I-123]FP-CIT binding to the dopamine transporter in the striatum of tree shrews by quantitative in vitro autoradiography. Synapse 2015; 69: 497–504 CrossRef MEDLINE
e50.
Fowler JS, Volkow ND, Wang GJ, Gatley SJ, Logan J: [(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy. Nucl Med Biol 2001; 28: 561–72 CrossRef
e51.
Bundesamt für Strahlenschutz: Bekanntmachung der aktualisierten diagnostischen Referenzwerte für nuklearmedizinische Verfahren. Salzgitter: Bundesamt für Strahlenschutz 2012. www.bfs.de/DE/themen/ion/anwendung-medizin/diagnostik/referenzwerte/referenzwerte_node.html (last accessed on 3 September 2019.)
e52.
Coon EA, Sletten DM, Suarez MD, et al.: Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 2015; 138: 3623–31 CrossRef MEDLINE PubMed Central
e53.
Wenning GK, Litvan I, Jankovic J, et al.: Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry 1998; 64: 184–9 CrossRef MEDLINE PubMed Central
e54.
Brigo F, Matinella A, Erro R, Tinazzi M: [123I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson‘s disease and vascular or drug-induced parkinsonisms: a meta-analysis. Eur J Neurol 2014; 21: 1369–e90 CrossRef MEDLINE
e55.
Thomsen G, Knudsen GM, Jensen PS, et al.: No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT. EJNMMI Res 2013; 3: 39 CrossRef MEDLINE PubMed Central
e56.
Kaasinen V, Gardberg M, Roytta M, Seppanen M, Paivarinta M: Normal dopamine transporter SPECT in neuropathologically confirmed corticobasal degeneration. J Neurol 2013; 260: 1410–1 CrossRef MEDLINE
e57.
O‘Sullivan SS, Burn DJ, Holton JL, Lees AJ: Normal dopamine transporter single photon-emission CT scan in corticobasal degeneration. Mov Disord 2008; 23: 2424–6 CrossRef MEDLINE
e58.
Ceravolo R, Rossi C, Cilia R, et al.: Evidence of delayed nigrostriatal dysfunction in corticobasal syndrome: a SPECT follow-up study. Parkinsonism Relat Disord 2013; 19: 557–9 CrossRef MEDLINE
e59.
Tissot H, Frismand S, Marie PY, Gospodaru N, Verger A: 123I-FP-CIT-SPECT in encephalitis involving substantia nigra. Clin Nucl Med 2016; 41: e445–6 CrossRef MEDLINE
e60.
Peña E, Fernandez C: Abnormal DAT SCAN in a patient with parkinsonism after a midbrain ischemic lesion. Mov Disord 2012; 27: 205 CrossRef MEDLINE
e61.
Kaasinen V, Kankare T, Joutsa J, Vahlberg T: Presynaptic striatal dopaminergic function in atypical parkinsonisms: a meta-analysis of imaging studies. J Nucl Med 2019; pii: jnumed.119.227140. doi: 10.2967/jnumed.119.227140. [Epub ahead of print] CrossRef MEDLINE
e62.
Kadekaro M, Crane AM, Sokoloff L: Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proc Natl Acad Sci USA 1985; 82: 6010–3 CrossRef MEDLINE PubMed Central
e63.
Sokoloff L: Energetics of functional activation in neural tissues. Neurochem Res 1999; 24: 321–9 CrossRef MEDLINE
e64.
Harris JJ, Jolivet R, Attwell D: Synaptic energy use and supply. Neuron 2012; 75: 762–77 CrossRef MEDLINE
e65.
Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE: A diagnostic approach in Alzheimer‘s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238–48.
e66.
Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith C, Frackowiak RSJ: Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 1995; 2: 189–210 CrossRef
e67.
Burdette JH, Minoshima S, Vander Borght T, Tran DD, Kuhl DE: Alzheimer disease: improved visual interpretation of PET images by using three-dimensional stereotaxic surface projections. Radiology 1996; 198: 837–43 CrossRef MEDLINE
e68.
Hoglinger GU: Is it useful to classify progressive supranuclear palsy and corticobasal degeneration as different disorders? No. Mov Disord Clin Prac 2018; 5: 141–4 CrossRef MEDLINE PubMed Central
e69.
Hoglinger GU, Respondek G, Kovacs GG: New classification of tauopathies. Rev Neurol (Paris) 2018; 174: 664–8 CrossRef MEDLINE
e70.
Ling H, Macerollo A: Is it useful to classify PSP and CBD as different disorders? Yes. Mov Disord Clin Prac 2018; 5: 145–8 CrossRef MEDLINE PubMed Central
e71.
Hoglinger GU, Kassubek J, Csoti I, et al.: Differentiation of atypical Parkinson syndromes. J Neural Transm 2017; 124: 997–1004 CrossRef MEDLINE
e72.
Bohnen NI, Koeppe RA, Minoshima S, et al.: Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study. J Nucl Med 2011; 52: 848–55 CrossRef MEDLINE
e73.
Zalewski N, Botha H, Whitwell JL, Lowe V, Dickson DW, Josephs KA: FDG-PET in pathologically confirmed spontaneous 4R-tauopathy variants. J Neurol 2014; 261: 710–6 CrossRef MEDLINE
e74.
Cordato NJ, Halliday GM, McCann H, et al.: Corticobasal syndrome with tau pathology. Mov Disord 2001; 16: 656–67 CrossRef MEDLINE
e75.
Josephs KA, Duffy JR, Strand EA, et al.: Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129: 1385–98 CrossRef MEDLINE PubMed Central
e76.
Klein RC, de Jong BM, de Vries JJ, Leenders KL: Direct comparison between regional cerebral metabolism in progressive supranuclear palsy and Parkinson‘s disease. Mov Disord 2005; 20: 1021–30 CrossRef MEDLINE
e77.
Tetzloff KA, Duffy JR, Strand EA, et al.: Clinical and imaging progression over 10 years in a patient with primary progressive apraxia of speech and autopsy-confirmed corticobasal degeneration. Neurocase 2018; 24: 111–20 CrossRef MEDLINE PubMed Central
e78.
Kaasinen V: Ipsilateral deficits of dopaminergic neurotransmission in Parkinson‘s disease. Ann Clin Transl Neurol 2016; 3: 21–6 CrossRef MEDLINE PubMed Central
e79.
Kaasinen V, Vahlberg T: Striatal dopamine in Parkinson disease: a meta-analysis of imaging studies. Ann Neurol 2017; 82: 873–82 CrossRef MEDLINE
e80.
Apostolova I, Taleb DS, Lipp A, et al.: Utility of follow-up dopamine transporter SPECT with 123I-FP-CIT in the diagnostic workup of patients with clinically uncertain parkinsonian syndrome. Clin Nucl Med 2017; 42: 589–94 CrossRef MEDLINE
e81.
Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD: Differentiating multiple system atrophy from Parkinson‘s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosur Ps 2002; 73: 517–23 CrossRef MEDLINE PubMed Central
e82.
Armstrong MJ, Weintraub D: The case for antipsychotics in dementia with Lewy bodies. Mov Disord Clin Pract 2017; 4: 32–5 CrossRef MEDLINE PubMed Central
e83.
Fujimi K, Sasaki K, Noda K, et al.: Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: The hisayama study. Brain Pathol 2008; 18: 317–25 CrossRef PubMed Central
e84.
Hogan DB, Fiest KM, Roberts JI, et al.: The prevalence and incidence of dementia with Lewy bodies: a systematic review. Can J Neurol Sci 2016; 43: S83–S95 CrossRef MEDLINE
e85.
McKeith I, O‘Brien J, Walker Z, et al.: Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007; 6: 305–13 CrossRef
e86.
Walker Z, Jaros E, Walker RW, et al.: Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry 2007; 78: 1176–81 CrossRef MEDLINE PubMed Central
e87.
McCleery J, Morgan S, Bradley KM, Noel-Storr AH, Ansorge O, Hyde C: Dopamine transporter imaging for the diagnosis of dementia with Lewy bodies. Cochrane Database Syst Rev 2015; 1: CD010633 CrossRef
e88.
Walker RW, Walker Z: Dopamine transporter single photon emission computerized tomography in the diagnosis of dementia with Lewy bodies. Mov Disord 2009; 24 (Suppl 2): S754–9 CrossRef MEDLINE
e89.
Thomas AJ, Attems J, Colloby SJ, et al.: Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB. Neurology 2017; 88: 276–83 CrossRef MEDLINE PubMed Central
e90.
Beach TG, Adler CH, Lue L, et al.: Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 2009; 117: 613–34 CrossRef MEDLINE PubMed Central
e91.
van der Zande JJ, Booij J, Scheltens P, Raijmakers PG, Lemstra AW: [(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2016; 43: 1060–6 CrossRef MEDLINE PubMed Central
e92.
Jung Y, Jordan LG, 3rd, Lowe VJ, et al.: Clinicopathological and (123)I-FP-CIT SPECT correlations in patients with dementia. Ann Clin Transl Neurol 2018; 5: 376–81 CrossRef MEDLINE PubMed Central
e93.
Lloyd JJ, Petrides G, Donaghy PC, et al.: A new visual rating scale for Ioflupane imaging in Lewy body disease. Neuroimage Clin 2018; 20: 823–9 CrossRef MEDLINE PubMed Central
e94.
Sonni I, Ratib O, Boccardi M, et al.: Clinical validity of presynaptic dopaminergic imaging with (123)I-ioflupane and noradrenergic imaging with (123)I-MIBG in the differential diagnosis between Alzheimer‘s disease and dementia with Lewy bodies in the context of a structured 5-phase development framework. Neurobiol Aging 2017; 52: 228–42 CrossRef MEDLINE
e95.
Morgan S, Kemp P, Booij J, et al.: Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT. J Neurol Neurosurg Psychiatry 2012; 83: 1063–70 CrossRef MEDLINE
e96.
McKeith IG, Boeve BF, Dickson DW, et al.: Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 2017; 89: 88–100 CrossRef MEDLINE PubMed Central
e97.
Ba F, Martin WR: Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical practice. Parkinsonism Relat Disord 2015; 21: 87–94 CrossRef MEDLINE
e98.
Vlaar AM, van Kroonenburgh MJ, Kessels AG, Weber WE: Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes. BMC Neurol 2007; 7: 27 CrossRef MEDLINE PubMed Central
e99.
O‘Brien JT, Oertel WH, McKeith IG, et al.: Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials. BMJ Open 2014; 4: e005122 CrossRef MEDLINE PubMed Central
e100.
Parkinson Study Group: A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in parkinsonism. Neurology 2000; 55: 1540–7 CrossRef MEDLINE
e101.
Benamer TS, Patterson J, Grosset DG, et al.: Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000; 15: 503–10 CrossRef
e102.
Weng YH, Yen TC, Chen MC, et al.: Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson‘s disease from healthy subjects. J Nucl Med 2004; 45: 393–401.
e103.
Jakobson Mo S, Linder J, Forsgren L, Riklund K: Accuracy of visual assessment of dopamine transporter imaging in early Parkinsonism. Mov Disord Clin Pract 2015; 2: 17–23 CrossRef MEDLINE PubMed Central
e104.
Gayed I, Joseph U, Fanous M, et al.: The impact of DaTscan in the diagnosis of Parkinson disease. Clin Nucl Med 2015; 40: 390–3 CrossRef MEDLINE
e105.
Werner RA, Marcus C, Sheikhbahaei S, et al.: Visual and semiquantitative accuracy in clinical baseline 123I-Ioflupane SPECT/CT imaging. Clinical Nuclear Medicine 2019; 44: 1–3 CrossRef MEDLINE
e106.
Buchert R, Lange C, Spehl TS, et al.: Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting. EJNMMI Res 2019; 9: 37 CrossRef MEDLINE PubMed Central
e107.
Skanjeti A, Castellano G, Elia BO, et al.: Multicenter semiquantitative evaluation of (123)I-FP-CIT brain SPECT. J Neuroimaging 2015; 25: 1023–9 CrossRef MEDLINE
e108.
Bouwmans AE, Vlaar AM, Mess WH, Kessels A, Weber WE: Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson‘s disease: prospective cohort study in 196 patients. BMJ Open 2013; 3: pii: e002613 CrossRef MEDLINE PubMed Central
e109.
Ziebell M, Andersen BB, Thomsen G, et al.: Predictive value of dopamine transporter SPECT imaging with [¹²³I]PE2I in patients with subtle parkinsonian symptoms. Eur J Nucl Med Mol Imaging 2012; 39: 242–50 CrossRef MEDLINE
e110.
Felicio AC, Godeiro-Junior C, Shih MC, et al.: Evaluation of patients with clinically unclear parkinsonian syndromes submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1. J Neurol Sci 2010; 291: 64–8 CrossRef MEDLINE
e111.
Vlaar AM, de Nijs T, van Kroonenburgh MJ, et al.: The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans. BMC Neurol 2008; 8: 42 CrossRef MEDLINE PubMed Central
e112.
Tolosa E, Borght TV, Moreno E, Uncertain DC: Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study. Mov Disord 2007; 22: 2346–51 CrossRef MEDLINE
e113.
Plotkin M, Amthauer H, Klaffke S, et al.: Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm (Vienna) 2005; 112: 677–92 CrossRef MEDLINE
e114.
Eerola J, Tienari PJ, Kaakkola S, Nikkinen P, Launes J: How useful is [123I] beta-CIT SPECT in clinical practice? J Neurol Neurosurg Psychiatry 2005; 76: 1211–6 CrossRef MEDLINE PubMed Central
e115.
Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K: (123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 2004; 61: 1224–9 CrossRef MEDLINE
e116.
Lokkegaard A, Werdelin LM, Friberg L: Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand. Eur J Nucl Med Mol Imaging 2002; 29: 1623–9 CrossRef MEDLINE
e117.
Crotty GF, O‘Corragain OA, Bogue C, Crotty J, O‘Sullivan SS: The utility of dopamine transporter scans for diagnosing Parkinsonian disorders. Ir Med J 2018; 111: 751.
e118.
Mirpour S, Turkbey EB, Marashdeh W, El Khouli R, Subramaniam RM: Impact of DAT-SPECT on management of patients suspected of Parkinsonism. Clin Nucl Med 2018; 43: 710–4 CrossRef MEDLINE
e119.
Yomtoob J, Koloms K, Bega D: DAT-SPECT imaging in cases of drug-induced parkinsonism in a specialty movement disorders practice. Parkinsonism Relat Disord 2018; 53: 37–41 CrossRef MEDLINE
e120.
Graebner AK, Tarsy D, Shih LC, et al.: Clinical impact of 123I-ioflupane SPECT (DaTscan) in a movement disorder center. Neurodegener Dis 2017; 17: 38–43 CrossRef MEDLINE
e121.
Bega D, Gonzalez-Latapi P, Zadikoff C, Spies W, Simuni T: Is there a role for DAT-SPECT imaging in a specialty movement disorders practice? Neurodegener Dis 2015; 15: 81–6 CrossRef MEDLINE
e122.
Covington MF, Sherman S, Lewis D, Lei H, Krupinski E, Kuo PH: Patient survey on satisfaction and impact of 123I-ioflupane dopamine transporter imaging. PLoS One 2015; 10: e0134457 CrossRef MEDLINE PubMed Central
e123.
Sadasivan S, Friedman JH: Experience with DaTscan at a tertiary referral center. Parkinsonism Relat Disord 2015; 21: 42–5 CrossRef MEDLINE
e124.
Thiriez C, Itti E, Fenelon G, et al.: Clinical routine use of dopamine transporter imaging in 516 consecutive patients. J Neurol 2015; 262: 909–15 CrossRef MEDLINE
Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf: Dr. rer. nat. Ralph Buchert, PD Dr. med. Ivayla Apostolova
Department of Neurology, University Medical Center Hamburg-Eppendorf: Prof. Dr. med. Carsten Buhmann
Department of Nuclear Medicine, Medical Center—University of Freiburg: Prof. Dr. med. Dr. nat. med. Philipp T. Meyer
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf: Prof. Dr. med. Jürgen Gallinat
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng
Figure 1
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng
Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions
Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions
Figure 2
Atypical patterns of findings on DAT-SPECT—for example, reduction of tracer uptake more pronounced in the caudate nucleus than in the putamen—are often caused by vascular lesions
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes
Figure 3
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes
Key messages
Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1
Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1
Table
Original studies of the effect of DAT-SPECT on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome*1
DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease
DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease
eBox
DAT-SPECT in the differentiation of dementia with Lewy bodies from Alzheimer’s disease
Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1
Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1
eTable
Original studies of the diagnostic accuracy of DAT-SPECT for detecting nigrostriatal degeneration in patients with clinically uncertain parkinsonian or tremor syndrome and a clinical diagnosis based on clinical follow-up as standard of truth*1
1.DGN, AWMF: S3-Leitlinie „Idiopathisches Parkinson-Syndrom“. AWMF-Register-Nummer: 030–010. 2016. www.awmf.org/uploads/tx_szleitlinien/030–010l_S3_Parkinson_Syndrome_Idiopathisch_2016–06.pdf (last accessed on 3 September 2019).
2.Postuma RB, Berg D, Stern M, et al.: MDS clinical diagnostic criteria for Parkinson‘s disease. Mov Disord 2015; 30: 1591–601 CrossRef MEDLINE
3.Gilman S, Wenning GK, Low PA, et al.: Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71: 670–6 CrossRef MEDLINE PubMed Central
4.Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G: Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology 2016; 86: 566–76 CrossRef MEDLINE
5.Meyer PT, Frings L, Hellwig S: Nuklearmedizinische Differenzialdiagnostik der Parkinson-Syndrome: Update 2016. Der Nuklearmediziner 2016; 39: 245–58 CrossRef
6.Neumeyer JL, Wang SY, Gao YG, et al.: N-Omega-Fluoroalkyl Analogs of
(1r)-2-Beta-Carbomethoxy-3-Beta-(4-Iodophenyl)-Tropane (Beta-Cit) – radiotracers for positron emission tomography and single-photon emission computed-tomography imaging of dopamine transporters. J Med Chem 1994; 37: 1558–61 CrossRef MEDLINE
7.Kraemmer J, Kovacs GG, Perju-Dumbrava L, Pirker S, Traub-Weidinger T, Pirker W: Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts. Mov Disord 2014; 29: 1767–73 CrossRef MEDLINE
8.Colloby SJ, McParland S, O‘Brien JT, Attems J: Neuropathological correlates of dopaminergic imaging in Alzheimer‘s disease and Lewy body dementias. Brain 2012; 135: 2798–808 CrossRef MEDLINE
9.Perju-Dumbrava LD, Kovacs GG, Pirker S, et al.: Dopamine transporter imaging in autopsy-confirmed parkinson‘s disease and multiple system atrophy. Movement Disord 2012; 27: 65–71 CrossRef MEDLINE
10.Booij J, Dubroff J, Pryma D, et al.: Diagnostic performance of the visual reading of (123)I-Ioflupane SPECT images with or without quantification in patients with movement disorders or dementia. J Nucl Med 2017; 58: 1821–6 CrossRef MEDLINE
11.Seibyl JP, Kupsch A, Booij J, et al.: Individual-reader diagnostic performance and between-reader agreement in assessment of subjects with Parkinsonian syndrome or dementia using 123I-ioflupane injection (DaTscan) imaging. J Nucl Med 2014; 55: 1288–96 CrossRef MEDLINE
12.Albert NL, Unterrainer M, Diemling M, et al.: Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging 2016; 43: 1315–22 CrossRef MEDLINE
13.Lee I, Kim JS, Park JY, et al.: Head-to-head comparison of (18)F-FP-CIT and (123) I-FP-CIT for dopamine transporter imaging in patients with Parkinson‘s disease: a preliminary study. Synapse 2018; 72: e22032 CrossRef MEDLINE
14.Kordower JH, Olanow CW, Dodiya HB, et al.: Disease duration and the integrity of the nigrostriatal system in Parkinson‘s disease. Brain 2013; 136: 2419–31 CrossRef MEDLINE PubMed Central
15.Marshall VL, Reininger CB, Marquardt M, et al.: Parkinson‘s disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT. Mov Disord 2009; 24: 500–8 CrossRef MEDLINE
16.Pirker W, Djamshidian S, Asenbaum S, et al.: Progression of dopaminergic degeneration in Parkinson‘s disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study. Mov Disord 2002; 17: 45–53 CrossRef MEDLINE
17.Suwijn SR, van Boheemen CJ, de Haan RJ, Tissingh G, Booij J, de Bie RM: The diagnostic accuracy of dopamine transporter SPECT imaging to detect nigrostriatal cell loss in patients with Parkinson‘s disease or clinically uncertain parkinsonism: a systematic review. Ejnmmi Res 2015; 5: 12 CrossRef MEDLINE PubMed Central
18.Marek KL, Jennings DL, Seibyl JP, Grp PS: Long-term follow-up of patients with scans without evidence of dopaminergic deficit (SWEDD) in the ELLDOPA study. Neurology 2005;64(suppl 1): Abstract 274.
19.Batla A, Erro R, Stamelou M, et al.: Patients with scans without evidence of dopaminergic deficit: a long-term follow-up study. Mov Disord 2014; 29: 1820–5 CrossRef MEDLINE
20.Hickey PT, Kuchibhatla M, Scott B, Gauger L, Stacy MA: Dopamine transporter imaging has no impact on functional outcomes in de novo probable Parkinson‘s disease. J Parkinson Dis 2017; 7: 279–87 CrossRef MEDLINE
21.Berardelli A, Wenning GK, Antonini A, et al.: EFNS/MDS-ES recommendations for the diagnosis of Parkinson‘s disease. Eur J Neurol 2013; 20: 16–34 CrossRef MEDLINE
22.NICE: Parkinson’s disease in adults. National Institute for Health and Care Excellence (NICE) guideline [NG71], 2017. www.nice.org.uk/guidance/ng71 (last accessed on 3 September 2019).
23.Catafau AM, Tolosa E, Da TCUPSSG: Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes. Mov Disord 2004; 19: 1175–82 CrossRef MEDLINE
24.Booij J, Speelman JD, Horstink MW, Wolters EC: The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med 2001; 28: 266–72 CrossRef MEDLINE
25.Hellwig D, Marienhagen J, Menhart K, Grosse J: [Nuclear medicine in Germany. Updated key data and trends from official statistics]. Nuklearmedizin 2017; 56: 55–68 CrossRef MEDLINE
26.Van Laere K, Everaert L, Annemans L, Gonce M, Vandenberghe W, Vander Borght T: The cost effectiveness of 123I-FP-CIT SPECT imaging in patients with an uncertain clinical diagnosis of parkinsonism. Eur J Nucl Med Mol Imaging 2008; 35: 1367–76 CrossRef MEDLINE
27.Kupsch AR, Bajaj N, Weiland F, et al.: Impact of DaTscan SPECT imaging on clinical management, diagnosis, confidence of diagnosis, quality of life, health resource use and safety in patients with clinically uncertain parkinsonian syndromes: a prospective 1-year follow-up of an open-label controlled study. J Neurol Neurosur Ps 2012; 83: 620–8 CrossRef MEDLINE
28.Grosset DG, Tatsch K, Oertel WH, et al.: Safety analysis of 10 clinical trials and for 13 years after first approval of ioflupane 123I injection (DaTscan). J Nucl Med 2014; 55: 1281–7 CrossRef MEDLINE
29.Booij J, Sokole EB, Stabin MG, Janssen AGM, de Bruin K, van Royen EA: Human biodistribution and dosimetry of [I-123]FP-CIT: a potent radioligand for imaging of dopamine transporters. Eur J Nucl Med 1998; 25: 24–30 CrossRef
30.Booij J, Kemp P: Dopamine transporter imaging with [I-123]FP-CIT SPECT: potential effects of drugs. Eur J Nucl Med Mol I 2008; 35: 424–38 CrossRef MEDLINE
31.Tatsch K, Buchert R, Bartenstein P, et al.: Dopamine Transporter SPECT with I-123 labelled FP-CIT (DaTSCANTM). Nuklearmedizin 2019; 58: 5–16 CrossRef MEDLINE
32.Meyer PT, Frings L, Rucker G, Hellwig S: (18)F-FDG PET in Parkinsonism: differential diagnosis and evaluation of cognitive impairment. J Nucl Med 2017; 58: 1888–98 CrossRef MEDLINE
33.Eckert T, Barnes A, Dhawan V, et al.: FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005; 26: 912–21 CrossRef MEDLINE
34.Hellwig S, Amtage F, Kreft A, et al.: [18F]FDG-PET is superior to [¹²³I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology 2012; 79: 1314–22 CrossRef MEDLINE
35.Niethammer M, Tang CC, Feigin A, et al.: A disease-specific metabolic brain network associated with corticobasal degeneration. Brain 2014; 137: 3036–46 CrossRef MEDLINE PubMed Central
36.Pilotto A, Premi E, Caminiti SP, et al.: Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease. Neurology 2018; 90: E1029–E37 CrossRef MEDLINE
37.Hellwig S, Frings L, Amtage F, et al.: 18F-FDG PET Is an early predictor of overall survival in suspected atypical parkinsonism. J Nucl Med 2015; 56: 1541–6 CrossRef MEDLINE
38.Walker Z, Gandolfo F, Orini S, et al.: Clinical utility of FDG PET in Parkinson‘s disease and atypical parkinsonism associated with dementia. Eur J Nucl Med Mol Imaging 2018; 45: 1534–45 CrossRef MEDLINE PubMed Central
39.Whitwell JL, Hoglinger GU, Antonini A, et al.: Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be? Mov Disord 2017; 32: 955–71 CrossRef MEDLINE PubMed Central
40.Buchert R, Lange C, Apostolova I, Meyer PT: Dopamintransporter-SPECT mit [123I]FP-CIT: Empfehlungen für die visuelle Beurteilung. Der Nuklearmediziner 2015; 38: 40–7 CrossRef
e1.Hoglinger GU, Respondek G, Stamelou M, et al.: Clinical diagnosis of progressive supranuclear palsy: The Movement Disorder Society Criteria. Movement Disord 2017; 32: 853–64 CrossRef MEDLINE PubMed Central
e2.Armstrong MJ, Litvan I, Lang AE, et al.: Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: 496–503 CrossRef MEDLINE PubMed Central
e3.Grosset D, Taurah L, Burn DJ, et al.: A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson‘s disease left untreated at diagnosis. J Neurol Neurosurg Psychiatry 2007; 78: 465–9 CrossRef MEDLINE PubMed Central
e4.Diaz NL, Waters CH: Current strategies in the treatment of Parkinson‘s disease and a personalized approach to management. Expert Rev Neurother 2009; 9: 1781–9 CrossRef MEDLINE
e5.Global Parkinson‘s Disease Survey Steering Committee: Factors impacting on quality of life in Parkinson‘s disease: results from an international survey. Mov Disord 2002; 17: 60–7 CrossRef MEDLINE
e6.Levin J, Kurz A, Arzberger T, Giese A, Höglinger GU: The differential diagnosis and treatment of atypical Parkinsonism. Dtsch Arztebl Int 2016; 113: 61–9 CrossRef MEDLINE PubMed Central
e7.Koga S, Aoki N, Uitti RJ, et al.: When DLB, PD, and PSP masquerade as MSA. An autopsy study of 134 patients. Neurology 2015; 85: 404–12 CrossRef MEDLINE PubMed Central
e8.Koga S, Kouri N, Walton RL, et al.: Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype. Acta Neuropathologica 2018; 136: 389–404 CrossRef MEDLINE PubMed Central
e9.Knudsen K, Borghammer P: Imaging the Autonomic Nervous System in Parkinson‘s Disease. Curr Neurol Neurosci Rep 2018; 18: 79 CrossRef MEDLINE
e10.Dickson DW: Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 1999; 246 Suppl 2: II6–15 CrossRef MEDLINE
e11.Dickson DW, Bergeron C, Chin SS, et al.: Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002; 61: 935–46 CrossRef MEDLINE
e12.Piggott MA, Marshall EF, Thomas N, et al.: Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer‘s and Parkinson‘s diseases: rostrocaudal distribution. Brain 1999; 122 (Pt 8): 1449–68 CrossRef MEDLINE
e13.Wenning GK, Ben-Shlomo Y, Magalhaes M, Daniel SE, Quinn NP: Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry 1995; 58: 160–6 CrossRef MEDLINE PubMed Central
e14.Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F: Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973; 20: 415–55 CrossRef
e15.Niznik HB, Fogel EF, Fassos FF, Seeman P: The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. J Neurochem 1991; 56: 192–8 CrossRef MEDLINE
e16.Fazio P, Svenningsson P, Cselenyi Z, Halldin C, Farde L, Varrone A: Nigrostriatal dopamine transporter availability in early Parkinson‘s disease. Mov Disord 2018; 33: 592–9 CrossRef MEDLINE
e17.Lee CS, Samii A, Sossi V, et al.: In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson‘s disease. Ann Neurol 2000; 47: 493–503 CrossRef
e18.Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V: Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. Neurology 2017; 88: 1461–7 CrossRef MEDLINE
e19.Honkanen EA, Saari L, Orte K, et al.: No link between striatal dopaminergic axons and dopamine transporter imaging in Parkinson‘s disease. Mov Disord 2019; doi: 10.1002/mds.27777. [Epub ahead of print] CrossRef MEDLINE
e20.Seibyl JP, Marek K, Sheff K, et al.: Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson‘s patients. J Nucl Med 1998; 39: 1500–8.
e21.Van Laere K, De Ceuninck L, Dom R, et al.: Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-beta-CIT versus 99mTc-TRODAT-1. Eur J Nucl Med Mol Imaging 2004; 31: 1119–27 CrossRef MEDLINE
e22.Kim HJ, Im JH, Yang SO, et al.: Imaging and quantitation of dopamine transporters with iodine-123-IPT in normal and Parkinson‘s disease subjects. J Nucl Med 1997; 38: 1703–11.
e23.Fischman AJ, Bonab AA, Babich JW, et al.: Rapid detection of Parkinson‘s disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse 1998; 29: 128–41 CrossRef
e24.Ziebell M: Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT. Dan Med Bull 2011; 58: B4279.
e25.Andringa G, Drukarch B, Bol JG, et al.: Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson‘s disease. Neuroimage 2005; 26: 1150–8 CrossRef MEDLINE
e26.Alvarez-Fischer D, Blessmann G, Trosowski C, et al.: Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson‘s disease. Neuroimage 2007; 38: 5–12 CrossRef MEDLINE
e27.Back S, Raki M, Tuominen RK, Raasmaja A, Bergstrom K, Mannisto PT: High correlation between in vivo [123I]beta-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats. Ejnmmi Res 2013; 3: 46 CrossRef MEDLINE PubMed Central
e28.Gleave JA, Farncombe TH, Saab C, Doering LC: Correlative single photon emission computed tomography imaging of [123I]altropane binding in the rat model of Parkinson‘s. Nucl Med Biol 2011; 38: 741–9 CrossRef MEDLINE
e29.Ashkan K, Wallace BA, Mitrofanis J, et al.: SPECT imaging, immunohistochemical and behavioural correlations in the primate models of Parkinson‘s disease. Parkinsonism Relat Disord 2007; 13: 266–75 CrossRef MEDLINE
e30.Tian L, Karimi M, Brown CA, Loftin SK, Perlmutter JS: In vivo measures of nigrostriatal neuronal response to unilateral MPTP treatment. Brain Res 2014; 1571: 49–60 CrossRef MEDLINE PubMed Central
e31.Karimi M, Tian L, Brown CA, et al.: Validation of nigrostriatal positron emission tomography measures: critical limits. Ann Neurol 2013; 73: 390–6 CrossRef MEDLINE PubMed Central
e32.Papathanasiou N, Rondogianni P, Chroni P, et al.: Interobserver variability, and visual and quantitative parameters of (123)I-FP-CIT SPECT (DaTSCAN) studies. Ann Nucl Med 2012; 26: 234–40 CrossRef MEDLINE
e33.Ahmed A, Huang JB, Chen K, Zubeldia JM, Booij J, Vijayakumar V: [I-123]Ioflupane imaging in Caucasians and non-Caucasians: are there any differences? J Neurol Sci 2018; 395: 159–63 CrossRef MEDLINE
e34.Makinen E, Joutsa J, Johansson J, Maki M, Seppanen M, Kaasinen V: Visual versus automated analysis of [I-123]FP-CIT SPECT scans in parkinsonism. J Neural Transm (Vienna) 2016; 123: 1309–18 CrossRef MEDLINE
e35.Eshuis SA, Jager PL, Maguire RP, Jonkman S, Dierckx RA, Leenders KL: Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson‘s disease and healthy controls. Eur J Nucl Med Mol Imaging 2009; 36: 454–62 CrossRef MEDLINE
e36.Jakobson Mo S, Axelsson J, Jonasson L, et al.: Dopamine transporter imaging with [(18)F]FE-PE2I PET and [(123)I]FP-CIT SPECT-a clinical comparison. Ejnmmi Res 2018; 8: 100 CrossRef MEDLINE PubMed Central
e37.Marek K, Seibyl J, Eberly S, et al.: Longitudinal follow-up of SWEDD subjects in the PRECEPT Study. Neurology 2014; 82: 1791–7 CrossRef MEDLINE PubMed Central
e38.Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA: Time trends in the incidence of Parkinson disease. JAMA Neurol 2016; 73: 981–9 CrossRef MEDLINE PubMed Central
e39.Oravivattanakul S, Benchaya L, Wu G, et al.: Dopamine Transporter (DaT) Scan utilization in a movement disorder center. Mov Disord Clin Pract 2016; 3: 31–5 CrossRef MEDLINE PubMed Central
e40.Vlaar AM, de Nijs T, Kessels AG, et al.: Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. Eur Neurol 2008; 59: 258–66 CrossRef MEDLINE
e41.Dodel RC, Hoffken H, Moller JC, et al.: Dopamine transporter imaging and SPECT in diagnostic workup of Parkinson‘s disease: a decision-analytic approach. Movement Disord 2003; 18: S52–S62 CrossRef MEDLINE
e42.Bruggenjurgen B, Smala A, Chambers M: Cost-effectiveness of non-invasive imaging in the diagnosis of Parkinsonism. Value Health 2005; 8: Aabstract 15 CrossRef
e43.Busca R, Antonini A, Lopatriello S, Berto P: Economic evaluation of SPECT-DaTSCAN in the diagnosis of patients with clinically uncertain Parkinsonism in Italy. Value Health 2005; 8: Abstract 14 CrossRef
e44.Rajput AH, Rozdilsky B, Rajput A: Accuracy of clinical diagnosis in parkinsonism—a prospective study. Can J Neurol Sci 1991; 18: 275–8 CrossRef MEDLINE
e45.Iranzo A, Santamaria J, Valldeoriola F, et al.: Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. Ann Neurol 2017; 82: 419–28 CrossRef MEDLINE
e46.Postuma RB, Iranzo A, Hu M, et al.: Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 2019; 142: 744–59 CrossRef MEDLINE PubMed Central
e47.Chahine LM, Iranzo A, Fernandez-Arcos A, et al.: Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder. NPJ Parkinsons Dis 2019; 5: 2 CrossRef MEDLINE PubMed Central
e48.Meles SK, Vadasz D, Renken RJ, et al.: FDG PET, dopamine transporter SPECT, and olfaction: combining biomarkers in REM sleep behavior disorder. Mov Disord 2017; 32: 1482–6 CrossRef MEDLINE PubMed Central
e49.Geisler S, Beindorff N, Cremer M, et al.: Characterization of [I-123]FP-CIT binding to the dopamine transporter in the striatum of tree shrews by quantitative in vitro autoradiography. Synapse 2015; 69: 497–504 CrossRef MEDLINE
e50.Fowler JS, Volkow ND, Wang GJ, Gatley SJ, Logan J: [(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy. Nucl Med Biol 2001; 28: 561–72 CrossRef
e51.Bundesamt für Strahlenschutz: Bekanntmachung der aktualisierten diagnostischen Referenzwerte für nuklearmedizinische Verfahren. Salzgitter: Bundesamt für Strahlenschutz 2012. www.bfs.de/DE/themen/ion/anwendung-medizin/diagnostik/referenzwerte/referenzwerte_node.html (last accessed on 3 September 2019.)
e52.Coon EA, Sletten DM, Suarez MD, et al.: Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 2015; 138: 3623–31 CrossRef MEDLINE PubMed Central
e53.Wenning GK, Litvan I, Jankovic J, et al.: Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry 1998; 64: 184–9 CrossRef MEDLINE PubMed Central
e54.Brigo F, Matinella A, Erro R, Tinazzi M: [123I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson‘s disease and vascular or drug-induced parkinsonisms: a meta-analysis. Eur J Neurol 2014; 21: 1369–e90 CrossRef MEDLINE
e55.Thomsen G, Knudsen GM, Jensen PS, et al.: No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT. EJNMMI Res 2013; 3: 39 CrossRef MEDLINE PubMed Central
e56.Kaasinen V, Gardberg M, Roytta M, Seppanen M, Paivarinta M: Normal dopamine transporter SPECT in neuropathologically confirmed corticobasal degeneration. J Neurol 2013; 260: 1410–1 CrossRef MEDLINE
e57.O‘Sullivan SS, Burn DJ, Holton JL, Lees AJ: Normal dopamine transporter single photon-emission CT scan in corticobasal degeneration. Mov Disord 2008; 23: 2424–6 CrossRef MEDLINE
e58.Ceravolo R, Rossi C, Cilia R, et al.: Evidence of delayed nigrostriatal dysfunction in corticobasal syndrome: a SPECT follow-up study. Parkinsonism Relat Disord 2013; 19: 557–9 CrossRef MEDLINE
e59.Tissot H, Frismand S, Marie PY, Gospodaru N, Verger A: 123I-FP-CIT-SPECT in encephalitis involving substantia nigra. Clin Nucl Med 2016; 41: e445–6 CrossRef MEDLINE
e60.Peña E, Fernandez C: Abnormal DAT SCAN in a patient with parkinsonism after a midbrain ischemic lesion. Mov Disord 2012; 27: 205 CrossRef MEDLINE
e61.Kaasinen V, Kankare T, Joutsa J, Vahlberg T: Presynaptic striatal dopaminergic function in atypical parkinsonisms: a meta-analysis of imaging studies. J Nucl Med 2019; pii: jnumed.119.227140. doi: 10.2967/jnumed.119.227140. [Epub ahead of print] CrossRef MEDLINE
e62.Kadekaro M, Crane AM, Sokoloff L: Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proc Natl Acad Sci USA 1985; 82: 6010–3 CrossRef MEDLINE PubMed Central
e63.Sokoloff L: Energetics of functional activation in neural tissues. Neurochem Res 1999; 24: 321–9 CrossRef MEDLINE
e64.Harris JJ, Jolivet R, Attwell D: Synaptic energy use and supply. Neuron 2012; 75: 762–77 CrossRef MEDLINE
e65.Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE: A diagnostic approach in Alzheimer‘s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238–48.
e66.Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith C, Frackowiak RSJ: Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 1995; 2: 189–210 CrossRef
e67.Burdette JH, Minoshima S, Vander Borght T, Tran DD, Kuhl DE: Alzheimer disease: improved visual interpretation of PET images by using three-dimensional stereotaxic surface projections. Radiology 1996; 198: 837–43 CrossRef MEDLINE
e68.Hoglinger GU: Is it useful to classify progressive supranuclear palsy and corticobasal degeneration as different disorders? No. Mov Disord Clin Prac 2018; 5: 141–4 CrossRef MEDLINE PubMed Central
e69.Hoglinger GU, Respondek G, Kovacs GG: New classification of tauopathies. Rev Neurol (Paris) 2018; 174: 664–8 CrossRef MEDLINE
e70.Ling H, Macerollo A: Is it useful to classify PSP and CBD as different disorders? Yes. Mov Disord Clin Prac 2018; 5: 145–8 CrossRef MEDLINE PubMed Central
e71.Hoglinger GU, Kassubek J, Csoti I, et al.: Differentiation of atypical Parkinson syndromes. J Neural Transm 2017; 124: 997–1004 CrossRef MEDLINE
e72.Bohnen NI, Koeppe RA, Minoshima S, et al.: Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study. J Nucl Med 2011; 52: 848–55 CrossRef MEDLINE
e73.Zalewski N, Botha H, Whitwell JL, Lowe V, Dickson DW, Josephs KA: FDG-PET in pathologically confirmed spontaneous 4R-tauopathy variants. J Neurol 2014; 261: 710–6 CrossRef MEDLINE
e74.Cordato NJ, Halliday GM, McCann H, et al.: Corticobasal syndrome with tau pathology. Mov Disord 2001; 16: 656–67 CrossRef MEDLINE
e75.Josephs KA, Duffy JR, Strand EA, et al.: Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129: 1385–98 CrossRef MEDLINE PubMed Central
e76.Klein RC, de Jong BM, de Vries JJ, Leenders KL: Direct comparison between regional cerebral metabolism in progressive supranuclear palsy and Parkinson‘s disease. Mov Disord 2005; 20: 1021–30 CrossRef MEDLINE
e77.Tetzloff KA, Duffy JR, Strand EA, et al.: Clinical and imaging progression over 10 years in a patient with primary progressive apraxia of speech and autopsy-confirmed corticobasal degeneration. Neurocase 2018; 24: 111–20 CrossRef MEDLINE PubMed Central
e78.Kaasinen V: Ipsilateral deficits of dopaminergic neurotransmission in Parkinson‘s disease. Ann Clin Transl Neurol 2016; 3: 21–6 CrossRef MEDLINE PubMed Central
e79.Kaasinen V, Vahlberg T: Striatal dopamine in Parkinson disease: a meta-analysis of imaging studies. Ann Neurol 2017; 82: 873–82 CrossRef MEDLINE
e80.Apostolova I, Taleb DS, Lipp A, et al.: Utility of follow-up dopamine transporter SPECT with 123I-FP-CIT in the diagnostic workup of patients with clinically uncertain parkinsonian syndrome. Clin Nucl Med 2017; 42: 589–94 CrossRef MEDLINE
e81.Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD: Differentiating multiple system atrophy from Parkinson‘s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosur Ps 2002; 73: 517–23 CrossRef MEDLINE PubMed Central
e82.Armstrong MJ, Weintraub D: The case for antipsychotics in dementia with Lewy bodies. Mov Disord Clin Pract 2017; 4: 32–5 CrossRef MEDLINE PubMed Central
e83.Fujimi K, Sasaki K, Noda K, et al.: Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: The hisayama study. Brain Pathol 2008; 18: 317–25 CrossRef PubMed Central
e84.Hogan DB, Fiest KM, Roberts JI, et al.: The prevalence and incidence of dementia with Lewy bodies: a systematic review. Can J Neurol Sci 2016; 43: S83–S95 CrossRef MEDLINE
e85.McKeith I, O‘Brien J, Walker Z, et al.: Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007; 6: 305–13 CrossRef
e86.Walker Z, Jaros E, Walker RW, et al.: Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry 2007; 78: 1176–81 CrossRef MEDLINE PubMed Central
e87.McCleery J, Morgan S, Bradley KM, Noel-Storr AH, Ansorge O, Hyde C: Dopamine transporter imaging for the diagnosis of dementia with Lewy bodies. Cochrane Database Syst Rev 2015; 1: CD010633 CrossRef
e88.Walker RW, Walker Z: Dopamine transporter single photon emission computerized tomography in the diagnosis of dementia with Lewy bodies. Mov Disord 2009; 24 (Suppl 2): S754–9 CrossRef MEDLINE
e89.Thomas AJ, Attems J, Colloby SJ, et al.: Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB. Neurology 2017; 88: 276–83 CrossRef MEDLINE PubMed Central
e90.Beach TG, Adler CH, Lue L, et al.: Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 2009; 117: 613–34 CrossRef MEDLINE PubMed Central
e91.van der Zande JJ, Booij J, Scheltens P, Raijmakers PG, Lemstra AW: [(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2016; 43: 1060–6 CrossRef MEDLINE PubMed Central
e92.Jung Y, Jordan LG, 3rd, Lowe VJ, et al.: Clinicopathological and (123)I-FP-CIT SPECT correlations in patients with dementia. Ann Clin Transl Neurol 2018; 5: 376–81 CrossRef MEDLINE PubMed Central
e93.Lloyd JJ, Petrides G, Donaghy PC, et al.: A new visual rating scale for Ioflupane imaging in Lewy body disease. Neuroimage Clin 2018; 20: 823–9 CrossRef MEDLINE PubMed Central
e94.Sonni I, Ratib O, Boccardi M, et al.: Clinical validity of presynaptic dopaminergic imaging with (123)I-ioflupane and noradrenergic imaging with (123)I-MIBG in the differential diagnosis between Alzheimer‘s disease and dementia with Lewy bodies in the context of a structured 5-phase development framework. Neurobiol Aging 2017; 52: 228–42 CrossRef MEDLINE
e95.Morgan S, Kemp P, Booij J, et al.: Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT. J Neurol Neurosurg Psychiatry 2012; 83: 1063–70 CrossRef MEDLINE
e96.McKeith IG, Boeve BF, Dickson DW, et al.: Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 2017; 89: 88–100 CrossRef MEDLINE PubMed Central
e97.Ba F, Martin WR: Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical practice. Parkinsonism Relat Disord 2015; 21: 87–94 CrossRef MEDLINE
e98.Vlaar AM, van Kroonenburgh MJ, Kessels AG, Weber WE: Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes. BMC Neurol 2007; 7: 27 CrossRef MEDLINE PubMed Central
e99.O‘Brien JT, Oertel WH, McKeith IG, et al.: Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials. BMJ Open 2014; 4: e005122 CrossRef MEDLINE PubMed Central
e100.Parkinson Study Group: A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in parkinsonism. Neurology 2000; 55: 1540–7 CrossRef MEDLINE
e101.Benamer TS, Patterson J, Grosset DG, et al.: Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000; 15: 503–10 CrossRef
e102.Weng YH, Yen TC, Chen MC, et al.: Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson‘s disease from healthy subjects. J Nucl Med 2004; 45: 393–401.
e103.Jakobson Mo S, Linder J, Forsgren L, Riklund K: Accuracy of visual assessment of dopamine transporter imaging in early Parkinsonism. Mov Disord Clin Pract 2015; 2: 17–23 CrossRef MEDLINE PubMed Central
e104.Gayed I, Joseph U, Fanous M, et al.: The impact of DaTscan in the diagnosis of Parkinson disease. Clin Nucl Med 2015; 40: 390–3 CrossRef MEDLINE
e105.Werner RA, Marcus C, Sheikhbahaei S, et al.: Visual and semiquantitative accuracy in clinical baseline 123I-Ioflupane SPECT/CT imaging. Clinical Nuclear Medicine 2019; 44: 1–3 CrossRef MEDLINE
e106.Buchert R, Lange C, Spehl TS, et al.: Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting. EJNMMI Res 2019; 9: 37 CrossRef MEDLINE PubMed Central
e107.Skanjeti A, Castellano G, Elia BO, et al.: Multicenter semiquantitative evaluation of (123)I-FP-CIT brain SPECT. J Neuroimaging 2015; 25: 1023–9 CrossRef MEDLINE
e108.Bouwmans AE, Vlaar AM, Mess WH, Kessels A, Weber WE: Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson‘s disease: prospective cohort study in 196 patients. BMJ Open 2013; 3: pii: e002613 CrossRef MEDLINE PubMed Central
e109.Ziebell M, Andersen BB, Thomsen G, et al.: Predictive value of dopamine transporter SPECT imaging with [¹²³I]PE2I in patients with subtle parkinsonian symptoms. Eur J Nucl Med Mol Imaging 2012; 39: 242–50 CrossRef MEDLINE
e110.Felicio AC, Godeiro-Junior C, Shih MC, et al.: Evaluation of patients with clinically unclear parkinsonian syndromes submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1. J Neurol Sci 2010; 291: 64–8 CrossRef MEDLINE
e111.Vlaar AM, de Nijs T, van Kroonenburgh MJ, et al.: The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans. BMC Neurol 2008; 8: 42 CrossRef MEDLINE PubMed Central
e112.Tolosa E, Borght TV, Moreno E, Uncertain DC: Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study. Mov Disord 2007; 22: 2346–51 CrossRef MEDLINE
e113.Plotkin M, Amthauer H, Klaffke S, et al.: Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm (Vienna) 2005; 112: 677–92 CrossRef MEDLINE
e114.Eerola J, Tienari PJ, Kaakkola S, Nikkinen P, Launes J: How useful is [123I] beta-CIT SPECT in clinical practice? J Neurol Neurosurg Psychiatry 2005; 76: 1211–6 CrossRef MEDLINE PubMed Central
e115.Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K: (123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 2004; 61: 1224–9 CrossRef MEDLINE
e116.Lokkegaard A, Werdelin LM, Friberg L: Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand. Eur J Nucl Med Mol Imaging 2002; 29: 1623–9 CrossRef MEDLINE
e117.Crotty GF, O‘Corragain OA, Bogue C, Crotty J, O‘Sullivan SS: The utility of dopamine transporter scans for diagnosing Parkinsonian disorders. Ir Med J 2018; 111: 751.
e118.Mirpour S, Turkbey EB, Marashdeh W, El Khouli R, Subramaniam RM: Impact of DAT-SPECT on management of patients suspected of Parkinsonism. Clin Nucl Med 2018; 43: 710–4 CrossRef MEDLINE
e119.Yomtoob J, Koloms K, Bega D: DAT-SPECT imaging in cases of drug-induced parkinsonism in a specialty movement disorders practice. Parkinsonism Relat Disord 2018; 53: 37–41 CrossRef MEDLINE
e120.Graebner AK, Tarsy D, Shih LC, et al.: Clinical impact of 123I-ioflupane SPECT (DaTscan) in a movement disorder center. Neurodegener Dis 2017; 17: 38–43 CrossRef MEDLINE
e121.Bega D, Gonzalez-Latapi P, Zadikoff C, Spies W, Simuni T: Is there a role for DAT-SPECT imaging in a specialty movement disorders practice? Neurodegener Dis 2015; 15: 81–6 CrossRef MEDLINE
e122.Covington MF, Sherman S, Lewis D, Lei H, Krupinski E, Kuo PH: Patient survey on satisfaction and impact of 123I-ioflupane dopamine transporter imaging. PLoS One 2015; 10: e0134457 CrossRef MEDLINE PubMed Central
e123.Sadasivan S, Friedman JH: Experience with DaTscan at a tertiary referral center. Parkinsonism Relat Disord 2015; 21: 42–5 CrossRef MEDLINE
e124.Thiriez C, Itti E, Fenelon G, et al.: Clinical routine use of dopamine transporter imaging in 516 consecutive patients. J Neurol 2015; 262: 909–15 CrossRef MEDLINE