CAT 5: Uptake Pattern

This Critically Appraised Topic (CAT) supports the Clinical Summary: Diagnosis of Parkinson’s disease: use of presynaptic dopaminergic imaging. 

Appraised by Kevin Galbraith, 4 February 2016
Update due 2019

Clinical question
What is the pattern of uptake on DaTSCAN in parkinsonism and essential tremor?

Parkinson’s can be difficult to differentiate from other parkinsonian syndromes or essential tremor. DaTSCAN, which measures the density of nigrostriatial dopamine transporter sites, may in some cases help the clinician make the correct diagnosis.

The diagnostic accuracy of DaTSCAN in Parkinson’s and clinically uncertain parkinsonism has been addressed separately in a Parkinson’s UK CAT.

This CAT looks at the evidence contributing to our understanding of the uptake pattern in parkinsonism and essential tremor.

The Society for Nuclear Medicine (SNM) presents typical uptake patterns for normal aging, various parkinsonian syndromes, Alzheimer’s disease and essential tremor within a guideline developed in 2012 (presented below). The guideline is of moderate quality.

Nervous System Diseases / [Radionuclide imaging] AND (Tomography, Emission-Computed, Single-Photon / OR DaTSCAN OR dopaminergic imaging OR FP-CIT OR ioflupane OR Tropanes / [Diagnostic Use] OR tropanes)

Ovid Medline, adapted for Embase and Cochrane Library. All searches were up to December 2015. Studies in languages other than English were excluded. This yielded 640 studies. As there were many relevant primary studies on a wide variety of conditions, only guidelines and systematic reviews that covered parkinsonian conditions in general were selected. Two guidelines and one systematic review were found.

One guideline provided a well-referenced summary of DaTSCAN uptake patterns in a variety of conditions.(1) It is summarised, and critically appraised below.

Djang DSW, Janssen MJR, Bohnen N, Booij J, Henderson TA, Herholz K, et al. SNM practice guideline for dopamine transporter imaging with 123I-ioflupane SPECT 1.0. Journal of Nuclear Medicine. 2012;53(1):154-63.

A Society of Nuclear Medicine guideline addressing the indications, technical aspects, interpretation and reporting of DaT SPECT scans with 123-ioflupane (‘DaTSCAN’).

The information presented on uptake patterns is reproduced in a table below:

Condition / comparison Uptake pattern on DaTSCAN
Normal aging Some decrease in striatal binding, in both the caudate and putamen, at a rate of around 5% to 7% per decade. Small in comparison to decreases caused by disease, this should not normally interfere with interpretation.(2)
Parkinson’s / atypical parkinsonian
syndromes		 In Parkinson’s, a common pattern is decreased binding in the dorsal putamen contralateral to symptoms, progressing anteriorly and ipsilaterally over time. In atypical parkinsonian syndromes, loss of uptake tends to be more symmetrical, and to involve relatively more of the caudate. However, there is too much overlap to allow discrimination between Parkinson’s and atypical parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, and corticobasilar degeneration.(3-7)
Essential tremor Normal binding.(8)
Drug-induced parkinsonism Normal binding.(9)
Vascular parkinsonism Binding is normal or slightly diminished, except when an infarct directly involves a striatal structure. Even then, a deficit from an infarct often gives a ‘punched-out’ appearance, differing in morphology and quality from a typical presynaptic parkinsonian syndrome deficit.(10-12)
Psychogenic parkinsonism Normal binding.(5, 13)
Alzheimer’s disease / dementia with Lewy
bodies		 Striatal binding normal or only mildly diminished in Alzheimer’s disease and is significantly decreased in dementia with Lewy
bodies.(14, 15)

The guideline was critically appraised using the AGREE II instrument.(16) Points were noted and scores calculated (between zero and 100%) for each domain as follows:

  • Scope and purpose: Well described. Score 94%.
  • Stakeholder involvement: Details provided in separate document.(17) No stipulation that the writing committee should include a clinician directly involved in patient care. Nor was there mention of any methodological expertise in guideline development. It was unclear whether the wider public involved in the process comprise only the users of the SNM/ European Association of Nuclear Medicine (EANM) websites and members of the society, or general public or patients. Score 56%.
  • Rigour of development: A separate document on guideline development policy(17) stipulates documentation of search terms and criteria for inclusion of research articles in the guideline development, but the guideline itself did not include these items. Nor were strengths and limitations of the body of evidence stated. An iterative process of review was described(17) but there was no clear link between recommendations and supporting evidence. Precautions and contraindications were described in detail. The composition of the bodies providing external review was not clearly described. A clear procedure for updating the guideline was provided. Score 46%.
  • Clarity of presentation: The recommendations were specific, unambiguous and easily identifiable.Score 94%.
  • Applicability: The guideline did not describe facilitators and barriers to its application. There was no advice on how the recommendations can be put into practice. Potential resource implications were not covered. There were no monitoring or auditing criteria. Score 0%.
  • Editorial independence: There was no indication of external funding, and no indication that any funding body influenced content. The SNM and EANM stipulate conflict-of-interest screening criteria. Relevant documents are made available on their website. Score 83%.
  • Overall, the guideline was rated as of moderate quality. The greatest limitation was thought to be a lack of clarity regarding the search strategy. However, criteria for development were set in advance and were largely upheld.
  1. Djang DSW, Janssen MJR, Bohnen N, Booij J, Henderson
    TA, Herholz K, et al. SNM practice guideline for dopamine
    transporter imaging with 123I-ioflupane SPECT 1.0. Journal of Nuclear Medicine. 2012;53(1):154-63.
  2. Lavalaye J, Booij J, Reneman L, Habraken JB, van Royen EA. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers. Eur J Nucl Med. 2000;27(7):867-9.
  3. Benamer HTS, Patterson J, Grosset DG, Booij J, De Bruin K, Van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: The [123I]-FP-CIT study group. Movement Disorders. 2000;15(3):503-10.
  4. Booij J, Habraken JB, Bergmans P, Tissingh G, Winogrodzka A, Wolters EC, et al. Imaging of dopamine transporters with iodine-123-FP-CIT SPECT in healthy controls and patients with Parkinson’s disease. J Nucl Med. 1998;39(11):1879-84.
  5. Scherfler C, Schwarz J, Antonini A, Grosset D, Valldeoriola F, Marek K, et al. Role of DAT-SPECT in the diagnostic work up of Parkinsonism. Movement Disorders. 2007;22(9):1229-38.
  6. Vlaar AM, de Nijs T, Kessels AG, Vreeling FW, Winogrodzka A, Mess WH, et al. Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes. European Neurology. 2008;59(5):258-66.
  7. Vlaar AM, van Kroonenburgh MJ, Kessels AG, Weber WE.
    Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes. BMC neurology. 2007;7(1):27.
  8. Marshall VL, Reininger CB, Marquardt M, Patterson J, Hadley DM, Oertel WH, et al. Parkinson’s Disease is Overdiagnosed Clinically at Baseline in Diagnostically Uncertain Cases: A 3-Year European Multicenter Study with Repeat [I-123]FP-CIT SPECT. Movement Disorders. 2009;24(4):500-8.
  9. Lorberboym M, Treves TA, Melamed E, Lampl Y, Hellmann M, Djaldetti R. [123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson’s disease. Mov Disord. 2006;21(4):510-4.
  10. Marshall V, Grosset DG. Role of dopamine transporter imaging in the diagnosis of atypical tremor disorders. Movement Disorders. 2003;18 Suppl 7:S22-7.
  11. Lorberboym M, Djaldetti R, Melamed E, Sadeh M, Lampl Y. 123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism. Journal of Nuclear Medicine. 2004;45(10):1688-93.
  12. Gerschlager W, Bencsits G, Pirker W, Bloem BR, Asenbaum S, Prayer D, et al. [123I]beta-CIT SPECT distinguishes vascular parkinsonism from Parkinson’s disease. Movement Disorders. 2002;17(3):518-23.
  13. Felicio AC, Godeiro-Junior C, Moriyama TS, Shih MC, Hoexter MQ, Borges V, et al. Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study. Clin Neurol Neurosurg. 2010;112(4):282-5.
  14. McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt
    J, 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 Neurology.
    2007;6(4):305-13.
  15. Walker Z, Jaros E, Walker RW, Lee L, Costa DC, Livingston G, et al. Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. Journal of Neurology, Neurosurgery & Psychiatry. 2007;78(11):1176-81.
  16. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. Canadian Medical Association Journal. 2010;182(18):E839-E42.
  17. Delbeke D, Chiti A, Christian P, Darcourt J, Donohoe K,
    Flotats A, et al. SNMMI/EANM guideline for guideline development 6.0. Journal of nuclear medicine technology.
    2012;40(4):283-9.
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