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Review
. 2019 Nov 1;116(44):747-754.
doi: 10.3238/arztebl.2019.0747.

Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes

Ralph Buchert  1 , Carsten Buhmann, Ivayla Apostolova, Philipp T Meyer, Jürgen Gallinat
Affiliations
Review

Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes

Ralph Buchert et al. Dtsch Arztebl Int. .

Abstract

Background: Parkinsonian syndromes are classified by etiology mainly on clinical grounds, that is, on the basis of the clinical manifestations and with the aid of conventional ancillary studies. In most cases, the clinical diagnosis is clear. In up to 30% of cases, however, the etiological classification remains uncertain after completion of the basic clinical diagnostic evaluation, and additional investigation with nuclear imaging may be indicated. In particular, cerebral single-photon emission computed tomography (SPECT) with dopamine transporter (DAT) ligands may be helpful. DAT-SPECT can be used to demonstrate or rule out nigrostriatal degeneration and thereby differentiate neurodegenerative parkinsonian syndromes from symptomatic parkinsonian syndromes and other differential diagnoses. Positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose (FDG) can be used to identify disease-specific patterns of neuronal dysfunction/degeneration in order to differentiate the various neurodegenerative parkinsonian syndromes from one another.

Methods: In this review, we summarize the current state of the evidence on DAT-SPECT and FDG-PET for the indications mentioned above on the basis of a selective review of the literature.

Results: DAT-SPECT has been adequately validated as an in vivo marker for nigrostriatal degeneration. Studies using the clinical diagnosis of a movement disorders specialist over the course of the disease as a reference have shown that DAT- SPECT is 78-100% sensitive (median, 93%) and 70-100% specific (median, 89%) for the differentiation of neurodegenerative parkinsonian syndromes from symptomatic parkinsonism and other differential diagnoses in clinically unclear cases. DAT- SPECT scanning led to a change of diagnosis in 27-56% of patients (median, 43%) and to a change of treatment in 33-72% (median, 43%). FDG-PET enables the differentiation of atypical neurodegenerative parkinsonian syndromes from the idiopathic parkinsonian syndrome (i.e., Parkinson's disease proper) with high sensitivity and specificity (both approximately 90%), when the clinical diagnosis by a movement disorders specialist over the course of the disease is used as a reference.

Conclusion: DAT-SPECT has been well documented to be highly diagnostically accurate and to have a relevant influence on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome. It has not yet been shown to improve patient-relevant endpoints such as mortality, morbidity, and health-related quality of life; proof of this will probably have to await the introduction of neuroprotective treatments. The current evidence for the high differential diagnostic accuracy of FDG-PET in neurodegenerative parkinsonian syndromes needs to be reinforced by prospective studies with neuropathological verification of the diagnosis.

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Figures

Figure 1
Figure 1
Typical DAT-SPECT findings in patients with idiopathic parkinsonian syndrome (IPS) showing reduced striatal DAT availability compared with a normal findng. The reduction is often left/right asymmetrical, usually more pronounced in the hemisphere that is contralateral to the clinically dominant side of the body (e78). The (posterior) putamen is almost always most strongly affected (e79). Motor symptoms in IPS manifest only after a DAT loss of about 50% in the putamen (14). A strong reduction in tracer uptake in the (contralateral) putamen is therefore the minimum finding on DAT-SPECT in IPS. A reduction that is only slight should as a rule not be seen as an indication of nigrostriatal degeneration (40, e80). The atypical neurodegenerative parkinsonian syndromes, especially PSP and MSA of the Parkinson type, show similar patterns of findings on DAT-SPECT as IPS (9). DAT-SPECT, single photon emission computed tomography with dopamine transporter ligands; MSA, multiple system atrophy; PSP, progressive supranuclear palsy
Figure 2
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. Depending on their localization, vascular lesions can also cause patterns of findings that on DAT-SPECT alone cannot be differentiated from nigrostriatal degeneration. DAT-SPECT should therefore by interpreted in tandem with up-to-date structural images, preferably MRI. DAT-SPECT, single photon emission computed tomography (SPECT) using dopamine transporter (DAT) ligands; MRI, magnetic resonance imaging
Figure 3
Figure 3
Disease specific FDG-PET results in neurodegenerative parkinsonian syndromes. The respective top line shows selected tomography sections of the FDG image, the bottom line shows the associated statistical map from voxel-based testing of the same patient compared with healthy persons (a statistically significant reduction in FDG uptake is marked in blue). Patients with a disorder on the Lewy body spectrum often (in IPS) or regularly (in IPS with dementia and dementia of the Lewy body type [DLB]) present with hypometabolism in the posterior brain regions and relative hypermetabolism in the putamen, motor cortex, and cerebellum (33). MSA is characterized by a reduction in FDG uptake in the putamen and/or cerebellum (e81). In PSP, regional hypometabolism can be observed in the medial frontal region, including the anterior cingulate cortex, in the dorsolateral frontal region, as well as in the caudate nucleus, thalamus, and brain stem (32, e73). In pathologically confirmed CBD, FDG-PET shows hypometabolism in the frontoparietal cortex and the striatum and thalamus, contralateral to the clinically more affected side of the body, as in the example shown (35, e73, e74, e77).
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