Atypical Parkinsonian Syndromes: Structural, Functional, and Molecular Imaging Features
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* Graham Keir
* Michelle Roytman
* Faizullah Mashriqi
* Shaya Shahsavarani
* Ana M. Franceschi

## Abstract

**SUMMARY:** Atypical parkinsonian syndromes, also known as Parkinson-plus syndromes, are a heterogeneous group of movement disorders, including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD). This review highlights the characteristic structural, functional, and molecular imaging features of these complex disorders. DLB typically demonstrates parieto-occipital hypometabolism with involvement of the cuneus on FDG-PET, whereas dopaminergic imaging, such as [123I]-FP-CIT SPECT (DaTscan) or fluorodopa (FDOPA)-PET, can be utilized as an adjunct for diagnosis. PSP typically shows midbrain atrophy on structural imaging, whereas FDG-PET may be useful to depict frontal lobe hypometabolism and tau-PET confirms underlying tauopathy. MSA typically demonstrates putaminal or cerebellar atrophy, whereas FDG-PET highlights characteristic nigrostriatal or olivopontocerebellar hypometabolism, respectively. Finally, CBD typically shows asymmetric atrophy in the superior parietal lobules and corpus callosum, whereas FDG and tau-PET demonstrate asymmetric hemispheric and subcortical involvement contralateral to the side of clinical deficits. Additional advanced neuroimaging modalities and techniques described may assist in the diagnostic work-up or are promising areas of emerging research.

## ABBREVIATIONS:

3D-SSP
:   3D stereotactic surface projection
AD
:   Alzheimer disease
ASL
:   arterial spin-labeling
APS
:   atypical parkinsonian syndrome
CBD
:   corticobasal degeneration
CBS
:   corticobasal syndrome
CIS
:   cingulate island sign
DaT
:   dopamine transporter
DaTscan
:   [123I]-FP-CIT SPECT
DIP
:   drug-induced parkinsonism
DLB
:   dementia with Lewy bodies
FA
:   fractional anisotropy
FDOPA
:   fluorodopa
MCP
:   middle cerebellar peduncle
MSA
:   multisystem atrophy
MSA-C
:   multisystem atrophy–cerebellar
MSA-P
:   multisystem atrophy–parkinsonian
PA
:   posterior atrophy
PD
:   Parkinson disease
PSP
:   progressive supranuclear palsy
rCBF
:   regional cerebral blood flow
rs-fMRI
:   resting-state functional MR imaging
RSN
:   resting-state network
SCP
:   superior cerebellar peduncle
SMA
:   supplementary motor area
VaP
:   vascular parkinsonism

Atypical parkinsonian syndromes (APSs), also known as Parkinson-plus syndromes, are a heterogeneous group of movement disorders presenting with early dementia, ataxia, dysautonomia, frequent falls, and ocular dysmotility in addition to parkinsonism. Patients with these syndromes, which include dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD), are often unresponsive to traditional Parkinson disease (PD) treatments and may even experience harm from such treatments. For example, dopaminergic treatment in DLB has been associated with worsening hallucinations or psychosis in up to one-third of patients.1 Therefore, accurate diagnosis is critical for the appropriate management of these patients. Though these syndromes are discussed individually, it is important to recognize that neuropathology has demonstrated that multiple neurodegenerative disease processes may occur in the same patient.2 In addition, protein abnormalities may be present before the onset of defining clinical features.3 This may at least partially explain the heterogeneity that is seen in the presentation of APS. Key structural and molecular imaging features of Parkinson disease and APS are highlighted in the Table.

View this table:
[Table1](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/T1)

Key structural and molecular imaging features in PD and APS

## DEMENTIA WITH LEWY BODIES

DLB is thought to be due to mutations in the alpha-synuclein gene that codes for the SYN protein. This protein is misfolded, forming Lewy bodies and Lewy neurites within the central nervous system, the same pathologic hallmark seen in PD. As such, both PD and DLB are often referred to as the spectrum of Lewy body disorders, along with Parkinson disease mild cognitive impairment and Parkinson disease dementia.4

The diagnosis of possible or probable DLB requires several central features, including progressive cognitive decline interfering with normal function, progressive memory impairment, as well as deficits in attention, executive function, or visuospatial ability (Online Supplemental Data).5 Core features of DLB include fluctuating cognition, recurrent well-formed visual hallucinations, rapid eye movement sleep behavior disorder, and extrapyramidal symptoms (ie, bradykinesia, resting tremor, and rigidity). Confirmation of possible or probable DLB requires pathologic confirmation at autopsy. Of note, if cognitive symptoms occur more than 1 year following the onset of motor symptoms, the diagnosis of Parkinson disease dementia should be recommended rather than DLB.5

### Structural Imaging

Structural imaging findings of DLB are generally nonspecific with varying patterns of atrophy. Therefore, the primary role for CT/MR imaging is to rule out alternate pathologies.6 Visual scales have been used with varying degrees of success. One such scale is the posterior atrophy (PA) scale by Koedam and colleagues.7 They described parieto-occipital sulcus widening as a cardinal feature of DLB. However, Oppedal et al8 studied 333 patients with DLB and 352 patients with Alzheimer disease (AD) and found no statistically significant difference between AD and DLB on the PA scale. They found that mesial temporal atrophy was significantly higher for patients with AD in comparison to DLB and that patients with DLB exhibited atrophy that spared the hippocampi. Per their conclusions, a normal mesial temporal atrophy score in conjunction with abnormal PA and abnormal global cortical atrophy scale-frontal is quite specific for DLB, allowing for possible differentiation from AD. Note, the global cortical atrophy scale-frontal scale scores the degree of frontal atrophy from 0 to 3 (none, mild, moderate, and severe) as determined by enlargement of the posterior cingulate and parieto-occipital sulci and loss of volume involving the precuneus and parietal cortex. Quantification studies utilizing voxel-based morphometry have demonstrated decreased gray matter attenuation in DLB involving the greater mesial temporal and dorsal brainstem regions.9

### Functional Imaging

There have been several interesting applications of functional imaging in the evaluation of DLB. Schumacher and colleagues10 used resting-state functional MR imaging (rs-fMRI) to demonstrate decreased within-network connectivity in patients with DLB compared with controls in 9 resting-state networks (lateral sensorimotor, medial sensorimotor, temporal, basal ganglia, right motor, thalamic, insular 1, anterior cingulate, and temporal pole). Of note, there was no significant difference in within-network connectivity of patients with DLB on dopaminergic medications and those who were not medicated. Patients with DLB tended to have lower connectivity between the left frontoparietal and occipital pole networks compared with AD.

Watson and colleagues11 demonstrated the potential utility of DTI to distinguish DLB from AD. They found reduced fractional anisotropy (FA) in patients with DLB compared with healthy controls, primarily involving the parieto-occipital white matter tracts as well as the pons and left thalamus. Meanwhile, patients with AD exhibited more diffuse changes.

Arterial spin-labeling (ASL) has also been evaluated in patients with DLB. Roquet et al12 demonstrated greater deficits in CBF in the frontal, insular, and temporal cortices in DLB compared with AD and healthy controls. Meanwhile, AD demonstrated greater CBF reductions in the parietal and parietotemporal cortices. They also found that prodromal DLB could be successfully distinguished by using this technique, though not as accurately classified as mild DLB.

### Molecular Imaging

FDG-PET is a mainstay in the clinical assessment of patients with suspected DLB. FDG-PET demonstrates generalized hypometabolism, more profoundly affecting the parieto-occipital regions, including the medial occipital lobes (Fig 1). Compared with patients with posterior cortical atrophy, patients with DLB exhibit greater hypometabolism in the frontal lobes, anterior temporal lobes, and basal ganglia and tend to maintain greater hemispheric symmetry.13 The cingulate island sign (CIS) has been highlighted as a specific imaging biomarker in DLB, representing sparing of the posterior cingulate gyrus compared with the precuneus and cuneus on FDG-PET or SPECT. Interestingly, CIS may be most prominent when the Mini-Mental State Examination is near the score of 22. Less clear evidence of CIS at lower Mini-Mental State Examination scores is likely due to the progression of neurodegenerative disease.14 Statistical Parametric Mapping by using FDG-PET may be a helpful adjunct in the diagnosis of DLB. In a study by Caminiti et al,15 early SMP-t-maps of regions of interest had nearly 89% agreement with the clinical diagnosis of DLB at final follow-up compared with the initial clinical classification, which was only 46% accurate. They found that medial and lateral occipital cortex hypometabolism with involvement of temporoparietal and frontal cortices denoted DLB-like metabolic patterns, whereas bilateral temporoparietal and/or precuneus/posterior cingulate cortex hypometabolism denoted AD-like metabolic patterns.15

![FIG 1.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F1.medium.gif)

[FIG 1.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F1)

FIG 1. 
18F-FDG brain PET/MR imaging in DLB. *A*, 3D T1-MPRAGE sagittal image demonstrates posterior dominant (parieto-occipital) atrophy with widening of the parieto-occipital sulcus and to a lesser degree the calcarine fissure. *B*, Fused axial and (*C*) sagittal 3D T1-MPRAGE MR imaging-PET demonstrate preserved normal uptake in the posterior cingulate gyrus with hypometabolism in the precuneus consistent with cingulate island sign, typically seen in patients with dementia with Lewy bodies. *D*, 3D stereotactic surface projection (3D-SSP) PET cortical surface metabolic maps demonstrate abnormal FDG distribution pattern with moderate-to-severe hypometabolism in the parietotemporal regions, including in the mesial occipital lobe involving the primary visual cortex and cuneus. There is accompanying decreased tracer uptake in the bilateral precuneus with preserved normal binding in the posterior cingulate gyri consistent with cingulate island sign, which has been described in the setting of dementia with Lewy bodies. *E*, *Z* score statistical maps superimposed on FLAIR axials and 3D-SSP PET demonstrate significantly decreased values in bilateral occipital lobes, including in the cuneus, superior, and middle occipital gyri, and also in temporal and parietal regions, including in the precuneus and superior parietal lobules bilaterally.

Amyloid PET can be particularly helpful for identifying DLB in some patients. There is cortical uptake of amyloid tracers in 50%–70% of patients with DLB, which is not seen in PD and other forms of APS.16 In addition, amyloid imaging may also help to distinguish DLB from AD. In a postmortem assessment of 39 patients who were scanned antemortem, the amyloid tracer Parkinson disease dementia was able to distinguish solitary DLB from AD with or without DLB copathology with an accuracy of 93%. Patients with AD demonstrated higher Pittsburgh compound B standardized uptake value ratios than solitary patients with DLB.17

Dopaminergic imaging can be helpful in distinguishing DLB from AD. Presynaptic ligands targeting the dopamine transporter (DaT) have been particularly effective, warranting their place in the diagnostic criteria. In a study of 10 patients with autopsy-confirmed DLB, [123I]-FP-CIT SPECT (DaTscan; GE Healthcare) was able to predict 100% of DLB subjects by demonstrating reduced binding in the striatum. Furthermore, DaTscan was normal in all patients with clinically suspected DLB but negative autopsy, except 1 who had autopsy-confirmed AD.18 Similarly,18F-FP-CIT PET is highly sensitive for discriminating AD from DLB. By using a DaT availability cutoff of 2.48 for the whole striatum and a cutoff of 3.05 in the posterior putamen, Chung and colleagues19 were able to obtain a sensitivity of 100% and a specificity of 78.1%. The presynaptic tracer [18F]-FDOPA has demonstrated similar results in a case series by Khamis et al.20 This is particularly exciting given the advantages of FDOPA-PET over DaTscan, including superior spatial resolution, lower radiation burden, and shorter examination times (Fig 2). Postsynaptic D2 receptors, which are up-regulated in DLB, have been less frequently utilized. However, Walker and colleagues21 demonstrated the potential for [123I]-iodobenzamide SPECT to discriminate DLB from AD. They found a significantly lower caudate to putamen ratio of [123I]-iodobenzamide uptake in the left hemisphere compared with AD.21 Though the presynaptic and postsynaptic dopaminergic tracers are particularly effective at distinguishing DLB from AD, they cannot distinguish DLB from PD or other forms of APS.

![FIG 2.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F2.medium.gif)

[FIG 2.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F2)

FIG 2. 
Abnormal 18F-FDOPA-PET in dementia with Lewy bodies demonstrates decreased dopaminergic tracer uptake in the bilateral putamina and to a lesser degree in the caudate nuclei, also known as “loss of comma-tail” sign; findings are more pronounced on the left side.

Though not entirely intuitive, [123I] metaiodobenzylguanidine cardiac scintigraphy is remarkably effective for supporting the diagnosis of possible or probable DLB, given that patients with DLB typically demonstrate postganglionic cardiac sympathetic denervation. In a study of 85 patients with possible DLB, with 19 patients with DLB confirmed at autopsy, Slaets et al22 found that all patients with autopsy-confirmed DLB had a heart-to-mediastinum-uptake ratio less than 1.68. The specificity was not as high, however, with 1 of 3 patients with AD having heart-to-mediastinum-uptake ratio below this threshold.

## PROGRESSIVE SUPRANUCLEAR PALSY

PSP is a tauopathy characterized by parkinsonism with postural instability, bradykinesia, pseudobulbar syndrome with dysarthria and dysphagia, supranuclear palsy, and dementia. Given the varied clinical presentations of the different PSP phenotypes, the International Parkinson and Movement Disorder Society published criteria in 2017 that may be used to delineate among the varying PSP phenotypes (Online Supplemental Data).23 The National Institute of Neurological Disorders and Stroke and the Society for PSP also established criteria that are frequently used in clinical practice.24 Though the criterion standard remains diagnosis via pathology, imaging may accurately pinpoint afflicted areas of the brain and properly characterize the disease process, thereby improving patient management.

### Structural Imaging

There are several well-described structural imaging findings that are classic for PSP. The “hummingbird” or “penguin” sign refers to flattening of the upwardly convex superior margin of the midbrain seen on the midsagittal view (Fig 3). The “Mickey Mouse” sign describes rounding of the cerebral peduncles on the axial view at the level of the superior colliculi. The “morning glory” sign represents loss of the lateral convex margin of tegmentum. Additional findings include enlargement of the third ventricle and atrophy of the superior cerebellar peduncles (SCPs) with associated increased T2 signal.25 The visual assessment of SCP atrophy had sensitivity of 74% and specificity of 94% for identifying PSP in a study by Paviour et al.26 Kataoka et al25 found that patients with PSP with increased T2-weighted-FLAIR signal in the SCPs had significantly longer duration of symptoms compared with T2/FLAIR-negative patients with PSP. A widely utilized measurement is the midbrain anteroposterior diameter, because measurement of less than 12 mm has been associated with PSP. Though Righini et al27 demonstrated this threshold had a low sensitivity for detecting PSP, they also noted that the discrepancy may have been due to differences in technical factors, such as section thickness compared with prior research. Other measurements include by using a midbrain to pons ratio of less than 0.52 and midbrain measurement of <9.35 mm on midsagittal T1-weighted MR imaging. These thresholds yielded 100% specificity for discriminating PSP from MSA and healthy controls in a study by Massey et al.28

![FIG 3.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F3.medium.gif)

[FIG 3.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F3)

FIG 3. 
*A*, Sagittal 3D-FLAIR in patient with PSP demonstrates selective midbrain atrophy with prominent atrophy of the tegmentum without pontine atrophy and associated widening of the interpeduncular cistern, resembling the head and body of a hummingbird (“hummingbird sign”). *B*, Axial T2 demonstrates widening of the interpeduncular cistern (*arrow*) with rounded cerebral peduncles (“Mickey Mouse” sign) and increased lateral concavity of the midbrain tegmentum (“morning glory” sign). Note reduced midbrain AP diameter, with <12 mm from the interpeduncular fossa to the intercollicular groove considered abnormal. *C*, 3D stereotactic surface projection (3D-SSP) PET cortical surface metabolic maps demonstrate abnormal FDG distribution pattern with moderate-to-severe hypometabolism in the paramedian and dorsolateral frontal lobes, including in the premotor cortex, supplementary motor area, and anterior cingulate gyri bilaterally. *D*, *Z* score statistical maps superimposed on FLAIR axials and 3D-SSP PET demonstrate corresponding significantly decreased values in the bilateral frontal lobes, including in the middle and inferior frontal gyri, supplementary motor area, anterior cingulate gyri, and caudate nuclei.

### Functional Imaging

DTI has demonstrated some efficacy in differentiating PSP from other forms of APS. Whitwell et al29 found that, in contrast to corticobasal syndrome (CBS) and healthy controls, patients with PSP demonstrated reduced FA and increased mean diffusivity in infratentorial regions, primarily the SCPs and midbrain. Bharti et al30 demonstrated the potential of blood oxygen level–dependent rs-fMRI in the evaluation of PSP. Patients with PSP exhibited significantly higher within-network resting-state functional connectivity than controls in the default mode and cerebellum resting-state networks (RSNs). Patients with PSP also had significantly lower between-network resting-state functional connectivity between lateral visual and auditory RSNs as well as between the cerebellum and insula RSNs.

### Molecular Imaging

FDG-PET remains the clinical mainstay in the assessment of patients with PSP. Patients typically exhibit dorsal and paramedian frontal hypometabolism, including in the premotor cortex, supplementary motor area (SMA), and anterior cingulate, and may have decreased uptake in the midbrain and basal ganglia (Fig 3).31 Regional hypometabolism in the insular cortices has also been described.32 Regional differences in FDG-PET hypoperfusion have been observed in different clinical phenotypes of PSP. For example, hypometabolism in the anterior cingulate cortex correlates with vertical gaze palsy, thalamic hypometabolism with repeated unprovoked falls, decreased uptake in the midbrain with gait freezing, and left medial and dorsolateral frontal hypometabolism with nonfluent aphasia.33,34

On FDOPA-PET, PSP typically exhibits decreased FDOPA uptake in the caudate and anterior putamen to the same degree as in the posterior putamen. Furthermore, patients with PSP demonstrate more prominent and earlier loss of dopaminergic function when compared with PD.33 Yoo et al35 demonstrated the potential for DaTscan to differentiate PSP from frontotemporal dementia early in the disease course. By using a nonspecific binding ratio of 1.25 of the striatum to the remaining whole brain, they found 100% sensitivity and 84.6% specificity in discriminating between PSP and frontotemporal dementia.

The first-generation tau-PET tracer [18F]-flortaucipir has demonstrated efficacy in differentiating among PSP variants. Whitwell et al36 found that patients with the most common phenotype, Richardson syndrome, showed elevated uptake in the pallidum, putamen, thalamus, subthalamic nucleus, and red nucleus. Predominant speech/language disorder PSP cases demonstrated increased uptake in the pallidum, putamen, thalamus, and frontal lobe (left greater than right). The second-generation selective tau tracer [18F]-PI-2620 has demonstrated promise in the evaluation of PSP. By using postmortem autoradiography, Brendel et al37 found increased [18F]-PI-2620 binding in the basal ganglia and frontal cortex in patients with PSP, which co-localized with AT8-positive aggregated tau on immunohistochemistry. In vivo, [18F]-PI-2620 PET demonstrated increased uptake in the putamen and substantia nigra in PSP-Richardson syndrome, key regions involved in the pathophysiology of PSP, successfully differentiating PSP from AD, healthy controls, and disease controls (MSA). Another tau tracer, MK-6240, has not been as successful in the evaluation of PSP due to poor binding capability. This is possibly due to its high specificity for the 3R + 4R isoform of tau tangles unique to AD.38

## MULTIPLE SYSTEM ATROPHY

MSA encompasses a variety of neurodegenerative disorders with varying degrees of parkinsonism, cerebellar ataxia, and autonomic dysfunction. Patients are generally classified as having parkinsonian (MSA-P) or cerebellar (MSA-C) subtypes based on the predominating symptoms. Diagnostic criteria were developed by a consensus conference on MSA in 1998 and most recently revised in 2022 (Online Supplemental Data).39

### Structural Imaging

There are a few characteristic imaging features that are unique to MSA-P and MSA-C. MSA-P generally affects the putamen. The “putaminal rim” or “putaminal slit” sign describes T2/FLAIR hyperintensity along the lateral margin of the putamen (Fig 4). However, this appearance has also been noted in healthy patients, particularly at 3T MR imaging.40 MSA-P also typically demonstrates prominent T2*/SWI hypointensity in the putamen from iron deposition. Though this finding can be present in healthy controls, iron deposition is predominately dorsolateral in MSA-P, whereas in healthy patients, iron deposition initiates laterally and progresses medially.41,42 Putaminal T2 hypointensity has been described,41,43 though this may also be seen in other neurodegenerative diseases or acquired conditions.44 Associated putaminal volume loss may help to differentiate MSA from PD and related pathologies.45

![FIG 4.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F4.medium.gif)

[FIG 4.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F4)

FIG 4. 
Axial T2 at the level of the basal ganglia (*A* and *B*) in patient with MSA-P demonstrates putaminal atrophy and hyperintense linear rim surrounding the putamen, “putaminal rim” sign, typically described at 1.5T (*arrows*). Axial T2 (*C*) and FLAIR (*D*) images in patient with MSA-C demonstrate marked atrophy of the cerebellum and brainstem with accompanying cruciform hyperintensity in the pons (“hot cross bun” sign) (*arrows*). In another patient with MSA-C, axial (*E*) and coronal FLAIR (*F*) at the level of the middle cerebellar peduncles demonstrate volume loss with prominent hyperintense signal abnormality (“MCP” sign) (*arrows*).

In contrast to MSA-P, MSA-C tends to affect the infratentorial structures. The “hot cross bun” sign is a classic finding of MSA-C, representing cruciform hyperintensity in the pons on T2/FLAIR due to degeneration of pontocerebellar fibers (Fig 4). Though this sign is noted in up to 80% of patients, it is not specific for MSA-C, as it may also be seen in spinocerebellar ataxia.46 The middle cerebellar peduncle (MCP) sign is characterized by atrophy and T2/FLAIR signal hyperintensity of the middle cerebellar peduncles (Fig 4).47,48 Additional areas of atrophy in MSA-C include the cerebellar hemispheres, medulla, and basis pontis, with compensatory dilation of the 4th ventricle.

### Functional Imaging

MR spectroscopy has been employed in the evaluation of MSA with variable and at times conflicting results. Multiple studies have shown a decreased NAA:Cr ratio in the lentiform nucleus compared with controls.49,50 However, this finding is not specific, as similar reductions have been found in PSP. MR spectroscopy abnormalities have also been reported in the pons, cerebellum, medulla, and frontal cortex.50 DTI has demonstrated decreased FA in the MCP, inferior cerebellar peduncle, basis pontis, and internal capsule. Decreased FA values in the MCP have been shown to correlate with clinical symptoms51 and occur early in the disease course of MSA-C.52 rs-fMRI demonstrates differing patterns of functional connectivity modifications in MSA-C and MSA-P compared with healthy controls. MSA-P demonstrates a reduced connectivity of the default mode network whereas MSA‐C demonstrates higher connectivity in the pontocerebellar network, which may play a role in disturbances of eye movement control.53 ASL may be a useful adjunct for identifying patients with MSA-C. Compared with controls, patients with MSA-C have demonstrated distinct disruption of regional cerebral blood flow (rCBF) in the cerebellum. The rCBF of the vermis demonstrated sensitivity of 95.8% and specificity of 100% in differentiating patients with MSA-C from controls.54

### Molecular Imaging

FDG-PET generally demonstrates regional hypometabolism corresponding to areas of atrophy and signal abnormality observed on structural imaging. Hypometabolism in MSA-P is often in a nigrostriatal distribution, particularly in the putamen (Fig 5), whereas hypometabolism in MSA-C is in an olivopontocerebellar distribution, with profound deficits in the brainstem and cerebellum (Fig 6).41,55 The degree of hypometabolism in the striatum and cerebellum correlates with severity of parkinsonism and ataxia, respectively.

![FIG 5.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F5.medium.gif)

[FIG 5.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F5)

FIG 5. 
18F-FDG brain PET/MR imaging in MSA-P. Fused FLAIR MR imaging-PET transaxial views (3-mm slices) scaled to highlight FDG-PET findings demonstrate abnormal FDG distribution pattern with markedly decreased tracer uptake in the bilateral putamina (L > R).

![FIG 6.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F6.medium.gif)

[FIG 6.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F6)

FIG 6. 
18F-FDG brain PET/MR imaging in MSA-C. *A*, 3D stereotactic surface projection (3D-SSP) PET cortical surface metabolic maps demonstrate abnormal FDG distribution pattern with moderate-to-severe hypometabolism in the cerebellum and brainstem. *B*, *Z* score statistical maps superimposed on FLAIR axial images and 3D-SSP PET demonstrate corresponding significantly decreased values in the cerebellum, including in the cerebellar vermis, cerebellar hemispheres, and middle cerebellar peduncles, and also in the brainstem, pons, and pontine tegmentum.

FDOPA-PET, a biomarker of nigrostriatal dysfunction, demonstrates decreased uptake in the caudate and putamen in MSA, as seen in other types of APS.41,45,49 DaTscan demonstrates reduced dopamine transporter availability in the striatum, with a more rapid decline in the caudate and anterior putamen,45 whereas [18F]-FP-CIT PET highlights decreased uptake in the dorsal striatum with preserved caudate uptake.56 Oh et al57 found that dual-phase [18F]-FP-CIT PET in conjunction with FDG-PET had greater than 90% accuracy for the differentiation of PD, MSA, PSP, and nondegenerative parkinsonism (Fig 7). 11C-raclopride, a selective D2 receptor antagonist, has shown promise in distinguishing MSA-P from PD in a study by Van Laere et al.58

![FIG 7.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F7.medium.gif)

[FIG 7.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F7)

FIG 7. 
Examples of axial (*A*) and coronal section (*B*) of delayed-phase 18F-FP-CIT PET, early-phase 18F-FP-CIT PET (*C*), and 18F-FDG-PET (*D*) of patients with nondegenerative parkinsonism (*1st row*), idiopathic Parkinson disease (IPD) (*2nd row*), MSA-C (*3rd row*), MSA-P (*4th row*), and PSP (*5th row*). The patient with IPD (*2nd row*) has decreased DaT binding of the bilateral dorsal posterior putamen, with relative sparing of the ventral putamen (*white arrow*) on delayed-phase 18F-FP-CIT PET and normal striatal metabolism or hypermetabolism in the bilateral dorsolateral putamen on early-phase 18F-FP-CIT PET and 18F-FDG-PET (*blue arrow*). The patients with MSA-C and MSA-P (*3rd and 4th rows*), have DaT loss not only in the posterior putamen but also in the ventral putamen (*white arrowhead*) on delayed-phase 18F-FP-CIT PET. On early-phase 18F-FP-CIT PET and 18F-FDG-PET, MSA showed hypometabolism in the cerebellar cortex (*blue arrowhead with white outline*) and/or hypometabolism in the basal ganglia (*blue arrowhead with white outline*). The patient with PSP has extensive DaT loss in both the putamen and caudate nuclei on delayed-phase 18F-FP-CIT PET (*yellow arrow*), which was characterized by hypometabolism in the medial frontal cortices (*black arrowhead with yellow outline*) and midbrain (*red arrow*) on early-phase 18F-FP-CIT PET and 18F-FDG-PET. Non-DP = nondegenerative parkinsonism. *Reproduced with permission from Oh M, Lee N, Kim C, et al. Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism. Sci Rep 2021;11:14992*.

MSA is an alpha-synucleinopathy, and therefore, cortical binding is not seen on amyloid or tau-PET. There is, however, some evidence that tau accumulation may play a role in the pathogenesis of MSA. [18F]-flortaucipir demonstrates increased binding in the putamen of patients with MSA.59 On the other hand, [18F]-PI-2620 demonstrated no uptake in patients with MSA, who served as disease controls in a study assessing this tracer as a PSP biomarker.37

## CORTICOBASAL DEGENERATION

CBD is a 4R-tauopathy that results in asymmetric degeneration of the basal ganglia and cortical dysfunction. Typical basal ganglia manifestations include asymmetric rigidity, apraxia, limb dystonia, and alien limb phenomenon, which are unresponsive to levodopa therapy. Cognitive symptoms include nonfluent aphasia, sensory loss, behavior changes, and executive dysfunction.60⇓-62 Accurate diagnosis of CBD is difficult for the clinician given the highly variable spectrum of presentations (Online Supplemental Data).63

### Structural Imaging

Patients with CBD typically demonstrate asymmetric frontoparietal atrophy, particularly in the perirolandic region and superior parietal lobule (Fig 8), typically contralateral to the side of motor symptoms.60 However, asymmetric atrophy is not specific to CBD, with the differential including other subtypes of frontotemporal lobar degeneration and atypical Alzheimer disease. CBD may demonstrate accompanying T2/FLAIR hyperintensity in the ipsilateral frontoparietal white matter. Atrophy of the corpus collosum has also been described.64 A minority of patients have demonstrated ipsilateral basal ganglia atrophy.

![FIG 8.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F8.medium.gif)

[FIG 8.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F8)

FIG 8. 
Corticobasal degeneration. *A*, Axial 3D T1-MPRAGE demonstrates asymmetric atrophy in the left cerebral hemisphere that is particularly pronounced in the left sensorimotor cortex and superior parietal lobule (*ellipse*). *B*, Sagittal 3D T1-MPRAGE in the same patient demonstrates marked atrophy of the corpus callosum, which is more pronounced posteriorly (*arrow*). *C*, 18F-FDG brain PET/MR imaging axial view at the level of the basal ganglia demonstrates marked asymmetric hypometabolism involving the left cerebral hemisphere, basal ganglia, and thalamus. *D*, Fused FLAIR MR imaging-PET transaxial views (3-mm slices) scaled to highlight FDG-PET findings also demonstrate hypometabolism in the left sensorimotor cortex and accompanying right-sided crossed cerebellar diaschisis.

### Functional Imaging

DTI in CBD demonstrates decreased FA in the corticospinal tract, frontal/prefrontal white matter, and the corpus callosum of the affected hemisphere.29 Blood oxygen level–dependent fMRI features decreased activation of the sensorimotor, parietal cortices, and SMA contralateral to the affected hand on thumb opposition tasks.64 Multiple studies by using MR spectroscopy have demonstrated decreased NAA:Cr in the basal ganglia and frontal cortex.65,66 The marked asymmetry of the changes is most useful in differentiating CBD from other APS entities.64 Furthermore, ASL has demonstrated rCBF asymmetry in similar regions as structural atrophy, such as the perirolandic and parietal cortex, though possibly with higher sensitivity.67

### Molecular Imaging

FDG-PET findings typically parallel patterns of atrophy on structural imaging, featuring asymmetric hypometabolism in the frontoparietal cortices, sensorimotor cortex, basal ganglia, and thalamus contralateral to the clinically affected side (Fig 8). Crossed cerebellar diaschisis has also been observed.34,60,68 Patterns of hypometabolism in CBD typically parallel clinical presentation; for example, the superior and middle frontal gyri as well as the SMA are implicated in patients with apraxia, whereas the left anterior insula and frontal operculum are hypometabolic in patients with language deficits.69 FDOPA-PET demonstrates decreased binding in the striatum predominately contralateral to the clinically affected side. However, some patients may show a more symmetric decreased radiotracer uptake pattern, though not as extensive as in PD.64 Presynaptic dopaminergic SPECT ligands including [123I]-β-CIT and [123I]-FP-CIT70 may demonstrate higher baseline striatal binding in APS relative to Parkinson disease; however, the rate of striatal binding decreases faster in APS. In fact, CBD may have normal DaTscan at presentation, likely related to delayed neuronal loss compared with MSA and PSP.60,71

Tau imaging by using [18F]-flortaucipir and [18F]-THK-5351 demonstrates increased uptake in the frontoparietal cortices, basal ganglia, and thalamus contralateral to the clinically affected side.70,72 By using the second-generation ligand [18F]-PI-2620, Palleis et al73 demonstrated increased radiotracer uptake in the basal ganglia and dorsolateral prefrontal cortex in both patients with beta-amyloid positive and negative CBS. However, [18F]-PI-2620 uptake was higher in beta-amyloid-positive CBS.73,74

## NONDEGENERATIVE PARKINSONIAN SYNDROMES

Nondegenerative or “secondary parkinsonism” can result from vascular events, medications, or other insults, such as infection or trauma. Vascular parkinsonism (VaP) is difficult to diagnose due to its clinical heterogeneity and overlapping features with other forms of parkinsonism. Notably, parkinsonism with prominent white matter hyperintensities on MR imaging does not necessarily imply the diagnosis of VaP.75 The only definite causes of VaP are ischemic or hemorrhagic lesions involving the substantia nigra or nigrostriatal pathway.76 Presynaptic dopaminergic imaging, such as 123FP-CIT SPECT (DaTscan), is essential in these patients, typically demonstrating preserved or mildly decreased striatal uptake. In acute cases, a reduction in uptake has been observed ipsilateral to the side of infarct.77 Presynaptic imaging may help predict response to levodopa therapy, which can have a negative effect on these patients.78

There are many medications known to cause drug-induced parkinsonism (DIP), with neuroleptics being the most common. If DIP is suspected, discontinuation of the offending medication will typically improve symptoms. A systematic review reported complete recovery at 6 months in 94.85% of patients with DIP following the discontinuation of cinnarizine and flunarizine.79 When medications cannot be discontinued, dopamine transporter imaging (DaTscan or FDOPA) can be useful. These studies typically demonstrate normal uptake in DIP,80⇓-82 in contrast to the decreased striatal uptake in neurodegenerative parkinsonism.

## DIAGNOSTIC ALGORITHM

A proposed algorithm for APS imaging assessment is shown in Fig 9, demonstrating an approach that may be helpful in the evaluation of APS, depending on the clinical features and suspected etiologies. For example, following a neurologic examination and cognitive assessment, the patient may have fluctuating cognition and visual hallucinations with extrapyramidal symptoms, suspicious for DLB. In this case, an FDG-PET can be obtained to exclude AD and DaTscan or FDOPA-PET may be obtained to evaluate for dopaminergic degeneration. Alternatively, if the patient demonstrates a primary movement disorder, the imaging should be tailored to the specific symptoms. For patients with specific clinical features, such as cerebellar signs (suggesting MSA-C) or vertical gaze palsy (suggesting PSP), the imaging evaluation should be optimized to detect these disorders. For example, in PSP, MR imaging can be utilized to assess for midbrain volume loss, and if detected, then further imaging may not be required. Otherwise, FDG-PET may be considered, which typically demonstrates frontal lobe hypometabolism in PSP. This may then be confirmed with tau-PET. DaTscan or FDOPA-PET would not be useful in this case, as it would demonstrate decreased striatal binding and not help to differentiate among the APS subtypes. Though many of the discussed advanced neuroimaging techniques are not represented in this algorithm, these remain active areas of investigation that may someday find their way into mainstream clinical practice or perhaps aid in very specific diagnostic dilemmas.

![FIG 9.](http://www.ajnr.org/http://ajnr-stage2.highwire.org/content/ajnr/early/2024/08/29/ajnr.A8313/F9.medium.gif)

[FIG 9.](http://www.ajnr.org/content/early/2024/08/29/ajnr.A8313/F9)

FIG 9. 
Imaging algorithm for the diagnosis of atypical parkinsonian syndromes.

## Conclusions

APS encompasses a heterogeneous group of movement disorders, for which neuroimaging plays a critical role in diagnosis. With an abundance of emerging techniques and radiotracers available to evaluate these conditions, it is essential for neuroradiologists to be aware of the strengths and limitations of each technique so that they can appropriately advise the referring physician, thereby contributing to timely diagnosis and treatment.

## Footnotes

*   [Disclosure forms](https://www.ajnr.org/sites/default/files/additional-assets/Disclosures/December%202024/0047.pdf) provided by the authors are available with the full text and PDF of this article at [www.ajnr.org](http://www.ajnr.org).

## References

1.  1.Goldman JG, Goetz CG, Brandabur M, et al. Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies. Mov Disord 2008;23:2248–50 doi:10.1002/mds.22322 pmid:18823039
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.22322&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=18823039&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000261442600016&link_type=ISI) 

2.  2.Dugger BN, Adler CH, Shill HA, et al; Arizona Parkinson’s Disease Consortium. Concomitant pathologies among a spectrum of parkinsonian disorders. Parkinsonism Relat Disord 2014;20:525–29 doi:10.1016/j.parkreldis.2014.02.012 pmid:24637124
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.parkreldis.2014.02.012&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=24637124&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

3.  3.Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 2017;9:a028035 doi:10.1101/cshperspect.a028035 pmid:28062563
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6ImNzaHBlcnNwZWN0IjtzOjU6InJlc2lkIjtzOjExOiI5LzcvYTAyODAzNSI7czo0OiJhdG9tIjtzOjM4OiIvYWpuci9lYXJseS8yMDI0LzA4LzI5L2FqbnIuQTgzMTMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

4.  4.Irwin DJ, Hurtig HI. The contribution of tau, amyloid-beta and alpha-synuclein pathology to dementia in Lewy body disorders. J Alzheimer’s Dis Park 2018;8:444
    
    

5.  5.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 doi:10.1212/WNL.0000000000004058 pmid:28592453
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1212/WNL.0000000000004058&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

6.  6.Broski SM, Hunt CH, Johnson GB, et al. Structural and functional imaging in parkinsonian syndromes. Radiographics 2014;34:1273–92 doi:10.1148/rg.345140009 pmid:25208280
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1148/rg.345140009&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=25208280&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

7.  7.Koedam EL, Lehmann M, van der Flier WM, et al. Visual assessment of posterior atrophy development of a MRI rating scale. Eur Radiology 2011;21:2618–25 doi:10.1007/s00330-011-2205-4 pmid:21805370
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00330-011-2205-4&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=21805370&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

8.  8.Oppedal K, Ferreira D, Cavallin L, et al; Alzheimer's Disease Neuroimaging Initiative. A signature pattern of cortical atrophy in dementia with Lewy bodies: a study on 333 patients from the European DLB consortium. Alzheimers Dement 2019;15:400–09 doi:10.1016/j.jalz.2018.09.011 pmid:30439333
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.jalz.2018.09.011&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30439333&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

9.  9.Nakatsuka T, Imabayashi E, Matsuda H, et al. Discrimination of dementia with Lewy bodies from Alzheimer’s disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated lie algebra. Neuroradiology 2013;55:559–66 doi:10.1007/s00234-013-1138-9 pmid:23322456
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00234-013-1138-9&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=23322456&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000319166300005&link_type=ISI) 

10. 10.Schumacher J, Peraza LR, Firbank M, et al. Functional connectivity in dementia with Lewy bodies: a within- and between-network analysis. Hum Brain Mapp 2018;39:1118–29 doi:10.1002/hbm.23901 pmid:29193464
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/hbm.23901&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=29193464&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

11. 11.Watson R, Blamire AM, Colloby SJ, et al. Characterizing dementia with Lewy bodies by means of diffusion tensor imaging. Neurology 2012;79:906–14 doi:10.1212/WNL.0b013e318266fc51 pmid:22895591
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjg6Ijc5LzkvOTA2IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

12. 12.Roquet D, Sourty M, Botzung A, et al. Brain perfusion in dementia with Lewy bodies and Alzheimer’s disease: an arterial spin labeling MRI study on prodromal and mild dementia stages. Alzheimer’s Res Ther 2016;8:1–13
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1186/s13195-016-0175-0&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=27915998&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

13. 13.Whitwell JL, Graff-Radford J, Singh TD, et al. 18F-FDG PET in posterior cortical atrophy and dementia with Lewy bodies. J Nucl Med 2017;58:632–38 doi:10.2967/jnumed.116.179903 pmid:27688479
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam51bWVkIjtzOjU6InJlc2lkIjtzOjg6IjU4LzQvNjMyIjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

14. 14.Iizuka T, Iizuka R, Kameyama M. Cingulate island sign temporally changes in dementia with Lewy bodies. Sci Rep 2017;7:14745 doi:10.1038/s41598-017-15263-2 pmid:29116145
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1038/s41598-017-15263-2&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=29116145&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

15. 15.Caminiti SP, Sala A, Iaccarino L, et al. Brain glucose metabolism in Lewy body dementia: implications for diagnostic criteria. Alzheimer’s Res Ther 2019;11:1–14
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1186/s13195-019-0485-0&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

16. 16.Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med Technol 2013;41:11–18 doi:10.2967/jnumed.110.076315 pmid:23396994
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiam5tdCI7czo1OiJyZXNpZCI7czo3OiI0MS8xLzExIjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

17. 17.Kantarci K, Lowe VJ, Chen Q, et al. β-amyloid PET and neuropathology in dementia with Lewy bodies. Neurology 2020;94:e282–91 doi:10.1212/WNL.0000000000008818 pmid:31862783
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjk6Ijk0LzMvZTI4MiI7czo0OiJhdG9tIjtzOjM4OiIvYWpuci9lYXJseS8yMDI0LzA4LzI5L2FqbnIuQTgzMTMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

18. 18.Walker RWH, Walker Z. Dopamine transporter single photon emission computerized tomography in the diagnosis of dementia with Lewy bodies. Mov Disord 2009;24 Suppl 2:S754–59 doi:10.1002/mds.22591 pmid:19877236
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.22591&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

19. 19.Chung SJ, Lee YH, Yoo HS, et al. Distinct FP-CIT PET patterns of Alzheimer’s disease with parkinsonism and dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2019;46:1652–60 doi:10.1007/s00259-019-04315-6 pmid:30980099
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00259-019-04315-6&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30980099&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

20. 20.Khamis K, Giladi N, Levine C, et al. The added value of 18F-FDOPA PET/CT in the work-up of patients with movement disorders. Neurograph 2019;9:344–48 doi:10.3174/ng.1900004
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.3174/ng.1900004&link_type=DOI) 

21. 21.Walker Z, Costa DC, Janssen AG, et al. Dementia with Lewy bodies: a study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med 1997;24:609–14 doi:10.1007/BF00841397 pmid:9169566
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/BF00841397&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=9169566&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=A1997XG49400005&link_type=ISI) 

22. 22.Slaets S, Van Acker F, Versijpt J, et al. Diagnostic value of MIBG cardiac scintigraphy for differential dementia diagnosis. Int J Geriatr Psychiatry 2015;30:864–69 doi:10.1002/gps.4229 pmid:25363642
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/gps.4229&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=25363642&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

23. 23.Höglinger GU, Respondek G, Stamelou M, et al; Movement Disorder Society-Endorsed PSP Study Group. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov Disord 2017;32:853–64 doi:10.1002/mds.26987 pmid:28467028
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.26987&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

24. 24.Hauw JJ, Daniel SE, Dickson D, et al. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 1994;44:2015–19 doi:10.1212/wnl.44.11.2015 pmid:7969952
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjEwOiI0NC8xMS8yMDE1IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

25. 25.Kataoka H, Tonomura Y, Taoka T, et al. Signal changes of superior cerebellar peduncle on fluid-attenuated inversion recovery in progressive supranuclear palsy. Parkinsonism Relat Disord 2008;14:63–65 doi:10.1016/j.parkreldis.2007.03.001 pmid:17481936
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.parkreldis.2007.03.001&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=17481936&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000253747700013&link_type=ISI) 

26. 26.Paviour DC, Price SL, Stevens JM, et al. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology 2005;64:675–79 doi:10.1212/01.WNL.0000151854.85743.C7 pmid:15728291
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjg6IjY0LzQvNjc1IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

27. 27.Righini A, Antonini A, De Notaris R, et al. MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol 2004;25:927–32
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=15205125&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000222067600006&link_type=ISI) 

28. 28.Massey LA, Micallef C, Paviour DC, et al. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy. Mov Disord 2012;27:1754–62 doi:10.1002/mds.24968 pmid:22488922
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.24968&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=22488922&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

29. 29.Whitwell JL, Schwarz CG, Reid RI, et al. Diffusion tensor imaging comparison of progressive supranuclear palsy and corticobasal syndromes. Parkinsonism Relat Disord 2014;20:493–98 doi:10.1016/j.parkreldis.2014.01.023 pmid:24656943
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.parkreldis.2014.01.023&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=24656943&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

30. 30.Bharti K, Bologna M, Upadhyay N, et al. Abnormal resting-state functional connectivity in progressive supranuclear palsy and corticobasal syndrome. Front Neurol 2017;8:248 doi:10.3389/fneur.2017.00248 pmid:28634465
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.3389/fneur.2017.00248&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=28634465&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

31. 31.Zhao P, Zhang B, Gao S. 18F-FDG PET study on the idiopathic Parkinson’s disease from several parkinsonian-plus syndromes. Parkinsonism Relat Disord 2012;18 Suppl 1:S60–62 doi:10.1016/S1353-8020(11)70020-7 pmid:22166456
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/S1353-8020(11)70020-7&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=22166456&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

32. 32.Tripathi M, Dhawan V, Peng S, et al. Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography. Neuroradiology 2013;55:483–92 doi:10.1007/s00234-012-1132-7 pmid:23314836
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00234-012-1132-7&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=23314836&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

33. 33.Niccolini F, Politis M. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism. Eur J Nucl Med Mol Imaging 2016;43:2244–54 doi:10.1007/s00259-016-3464-8 pmid:27470326
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00259-016-3464-8&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=27470326&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

34. 34.Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005;26:912–21 doi:10.1016/j.neuroimage.2005.03.012 pmid:15955501
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.neuroimage.2005.03.012&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=15955501&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000230211100027&link_type=ISI) 

35. 35.Yoo HS, Chung SJ, Kim SJ, et al. The role of 18F-FP-CIT PET in differentiation of progressive supranuclear palsy and frontotemporal dementia in the early stage. Eur J Nucl Med Mol Imaging 2018;45:1585–95 doi:10.1007/s00259-018-4019-y pmid:29728749
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00259-018-4019-y&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=29728749&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

36. 36.Whitwell JL, Tosakulwong N, Botha H, et al. Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants. NeuroImage Clin 2020;25:102152
    
    

37. 37.Brendel M, Barthel H, van Eimeren T, et al. Assessment of 18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol 2020;77:1408–19 doi:10.1001/jamaneurol.2020.2526 pmid:33165511
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1001/jamaneurol.2020.2526&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=33165511&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

38. 38.Aguero C, Dhaynaut M, Normandin MD, et al. Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta Neuropathol Commun 2019;7:37 doi:10.1186/s40478-019-0686-6 pmid:30857558
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1186/s40478-019-0686-6&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30857558&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

39. 39.Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society criteria for the diagnosis of multiple system atrophy. Mov Disord 2022;37:1131–48 doi:10.1002/mds.29005 pmid:35445419
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.29005&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=35445419&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

40. 40.Lee WH, Lee CC, Shyu WC, et al. Hyperintense putaminal rim sign is not a hallmark of multiple system atrophy at 3T. AJNR Am J Neuroradiol 2005;26:2238–42 pmid:16219828
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=16219828&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

41. 41.1.  Franceschi AM, 
    2.  Franceschi D
    
    Zamora C, Muhleman M, Castillo M. Multiple system atrophy. In: Franceschi AM, Franceschi D, eds. Hybrid PET/MR Neuroimaging: A Comprehensive Approach. Springer-Verlag; 2022:361–82
    
    

42. 42.Aquino D, Bizzi A, Grisoli M, et al. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology 2009;252:165–72 doi:10.1148/radiol.2522081399 pmid:19561255
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1148/radiol.2522081399&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=19561255&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000268362900020&link_type=ISI) 

43. 43.Tha KK, Terae S, Tsukahara A, et al. Hyperintense putaminal rim at 1. 5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy. BMC Neurol 2012;12:39 doi:10.1186/1471-2377-12-39 pmid:22708511
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1186/1471-2377-12-39&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=22708511&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

44. 44.Mascalchi M, Vella A, Ceravolo R. Movement disorders: role of imaging in diagnosis. J Magn Reson Imaging 2012;35:239–56 doi:10.1002/jmri.22825 pmid:22271273
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/jmri.22825&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=22271273&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

45. 45.Brooks DJ, Seppi K; Neuroimaging Working Group on MSA. Proposed neuroimaging criteria for the diagnosis of multiple system atrophy. Mov Disord 2009;24:949–64 doi:10.1002/mds.22413 pmid:19306362
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.22413&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=19306362&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

46. 46.Lee YC, Liu CS, Wu HM, et al. The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia. Eur J Neurol 2009;16:513–16 doi:10.1111/j.1468-1331.2008.02524.x pmid:19187260
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1111/j.1468-1331.2008.02524.x&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=19187260&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

47. 47.Bhattacharya K, Saadia D, Eisenkraft B, et al. Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm. Arch Neurol 2002;59:835–42 doi:10.1001/archneur.59.5.835 pmid:12020268
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1001/archneur.59.5.835&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=12020268&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000175594900023&link_type=ISI) 

48. 48.Cicilet S, Furruqh F, Biswas A, et al. Hot cross bun and bright middle cerebellar peduncle signs in cerebellar type multiple system atrophy. BMJ Case Rep 2017:bcr-2017-220576 doi:10.1136/bcr-2017-220576
    
    [FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6ImNhc2VyZXBvcnRzIjtzOjU6InJlc2lkIjtzOjI4OiIyMDE3L29jdDMxXzEvYmNyLTIwMTctMjIwNTc2IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

49. 49.Chandran V, Stoessl AJ. Imaging in multiple system atrophy. Neurology & Clinical Neurosc 2014;2:178–87 doi:10.1111/ncn3.125
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1111/ncn3.125&link_type=DOI) 

50. 50.Kim H-J, Jeon B, Fung VSC. Role of magnetic resonance imaging in the diagnosis of multiple system atrophy. Mov Disord Clin Pract 2016;4:12–20 doi:10.1002/mdc3.12404 pmid:30363358
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mdc3.12404&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30363358&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

51. 51.Shiga K, Yamada K, Yoshikawa K, et al. Local tissue anisotropy decreases in cerebellopetal fibers and pyramidal tract in multiple system atrophy. J Neurol 2005;252:589–96 doi:10.1007/s00415-005-0708-0 pmid:15834652
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00415-005-0708-0&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=15834652&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000229439900012&link_type=ISI) 

52. 52.Oishi K, Konishi J, Mori S, et al. Reduced fractional anisotropy in early-stage cerebellar variant of multiple system atrophy. J Neuroimaging 2009;19:127–31 doi:10.1111/j.1552-6569.2008.00262.x pmid:18498329
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1111/j.1552-6569.2008.00262.x&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=18498329&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

53. 53.Filippi M, Sarasso E, Agosta F. Resting-state functional MRI in parkinsonian syndromes. Mov Disord Clin Pract 2019;6:104–17 doi:10.1002/mdc3.12730 pmid:30838308
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mdc3.12730&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30838308&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

54. 54.Zheng W, Ren S, Zhang H, et al. Spatial patterns of decreased cerebral blood flow and functional connectivity in multiple system atrophy (cerebellar-type): a combined arterial spin labeling perfusion and resting state functional magnetic resonance imaging study. Front Neurosci 2019;13:777 doi:10.3389/fnins.2019.00777 pmid:31417345
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.3389/fnins.2019.00777&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=31417345&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

55. 55.Meyer PT, Frings L, Rücker G, et al. 18F-FDG PET in parkinsonism: differential diagnosis and evaluation of cognitive impairment. J Nucl Med 2017;58:1888–98 doi:10.2967/jnumed.116.186403 pmid:28912150
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam51bWVkIjtzOjU6InJlc2lkIjtzOjEwOiI1OC8xMi8xODg4IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

56. 56.Hong C-M, Ryu H-S, Ahn B-C. Early perfusion and dopamine transporter imaging using 18F-FP-CIT PET/CT in patients with parkinsonism. Am J Nucl Med Mol Imaging 2018;8:360–72 pmid:30697456
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=30697456&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

57. 57.Oh M, Lee N, Kim C, et al. Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism. Sci Rep 2021;11:14992 doi:10.1038/s41598-021-94040-8 pmid:34294739
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1038/s41598-021-94040-8&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=34294739&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

58. 58.Van Laere K, Clerinx K, D’Hondt E, et al. Combined striatal binding and cerebral influx analysis of dynamic 11C-raclopride PET improves early differentiation between multiple-system atrophy and Parkinson disease. J Nucl Med 2010;51:588–95 doi:10.2967/jnumed.109.070144 pmid:20237023
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam51bWVkIjtzOjU6InJlc2lkIjtzOjg6IjUxLzQvNTg4IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

59. 59.Cho H, Choi JY, Lee SH, et al. 18F-AV-1451 binds to putamen in multiple system atrophy. Mov Disord 2017;32:171–73 doi:10.1002/mds.26857 pmid:27859717
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.26857&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=27859717&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

60. 60.1.  Franceschi AM, 
    2.  Franceschi D
    
    Niethammer M. Corticobasal degeneration. In: Franceschi AM, Franceschi D, eds. Hybrid PET/MR Neuroimaging: A Comprehensive Approach. Springer-Verlag; 2022:373–86
    
    

61. 61.Mahapatra RK, Edwards MJ, Schott JM, et al. Corticobasal degeneration. Lancet Neurol 2004;3:736–43 doi:10.1016/S1474-4422(04)00936-6 pmid:15556806
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/S1474-4422(04)00936-6&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=15556806&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000225283500020&link_type=ISI) 

62. 62.Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci 2011;45:350–53 doi:10.1007/s12031-011-9624-1 pmid:21853287
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s12031-011-9624-1&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=21853287&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

63. 63.Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013;80:496–503 doi:10.1212/WNL.0b013e31827f0fd1 pmid:23359374
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjg6IjgwLzUvNDk2IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

64. 64.Seritan AL, Mendez MF, Silverman DHS, et al. Functional imaging as a window to dementia: corticobasal degeneration. J Neuropsychiatry Clin Neurosci 2004;16:393–99 doi:10.1176/jnp.16.4.393 pmid:15616165
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1176/jnp.16.4.393&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=15616165&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

65. 65.Abe K, Terakawa H, Takanashi M, et al. Proton magnetic resonance spectroscopy of patients with parkinsonism. Brain Res Bull 2000;52:589–95 doi:10.1016/s0361-9230(00)00321-x pmid:10974501
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/S0361-9230(00)00321-X&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=10974501&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000089134300019&link_type=ISI) 

66. 66.Tedeschi G, Litvan I, Bonavita S, et al. Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson’s disease and corticobasal degeneration. Brain 1997;120 (Pt 9):1541–52 doi:10.1093/brain/120.9.1541 pmid:9313638
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1093/brain/120.9.1541&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=9313638&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

67. 67.Yamaguchi T, Ikawa M, Enomoto S, et al. Arterial spin labeling imaging for the detection of cerebral blood flow asymmetry in patients with corticobasal syndrome. Neuroradiology 2022;64:1829–37 doi:10.1007/s00234-022-02942-9 pmid:35399110
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s00234-022-02942-9&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=35399110&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

68. 68.Blin J, Vidailhet M, Pillon B, et al. Corticobasal degeneration: decreased and asymmetrical glucose consumption as studied with PET. Mov Disord 1992;7:348–54 doi:10.1002/mds.870070409 pmid:1484530
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.870070409&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=1484530&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=A1992JR78800008&link_type=ISI) 

69. 69.Pardini M, Huey ED, Spina S, et al. FDG-PET patterns associated with underlying pathology in corticobasal syndrome. Neurology 2019;92:e1121–35 doi:10.1212/WNL.0000000000007038 pmid:30700592
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjExOiI5Mi8xMC9lMTEyMSI7czo0OiJhdG9tIjtzOjM4OiIvYWpuci9lYXJseS8yMDI0LzA4LzI5L2FqbnIuQTgzMTMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

70. 70.Cho H, Baek MS, Choi JY, et al. 18F-AV-1451 binds to motor-related subcortical gray and white matter in corticobasal syndrome. Neurology 2017;89:1170–78 doi:10.1212/WNL.0000000000004364 pmid:28814462
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjEwOiI4OS8xMS8xMTcwIjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

71. 71.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 doi:10.1002/mds.1265 pmid:11835438
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.1265&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=11835438&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000173606500009&link_type=ISI) 

72. 72.Kikuchi A, Okamura N, Hasegawa T, et al. In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology 2016;87:2309–16 doi:10.1212/WNL.0000000000003375 pmid:27794115
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjEwOiI4Ny8yMi8yMzA5IjtzOjQ6ImF0b20iO3M6Mzg6Ii9ham5yL2Vhcmx5LzIwMjQvMDgvMjkvYWpuci5BODMxMy5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

73. 73.Palleis C, Brendel M, Finze A, et al; German Imaging Initiative for Tauopathies (GII4T). Cortical [18F]PI-2620 binding differentiates corticobasal syndrome subtypes. Mov Disord 2021;36:2104–15 doi:10.1002/mds.28624 pmid:33951244
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.28624&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=33951244&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

74. 74.Tezuka T, Takahata K, Seki M, et al. Evaluation of [18 F] PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies. Brain Commun 2021;3:1–13
    
    

75. 75.Wardlaw JM, Smith EE, Biessels GJ, et al; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822–38 doi:10.1016/S1474-4422(13)70124-8 pmid:23867200
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/S1474-4422(13)70124-8&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=23867200&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000322690600020&link_type=ISI) 

76. 76.Vizcarra JA, Lang AE, Sethi KD, et al. Vascular parkinsonism: deconstructing a syndrome. Mov Disord 2015;30:886–94 doi:10.1002/mds.26263 pmid:25997420
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1002/mds.26263&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=25997420&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

77. 77.Ma KKY, Lin S, Mok VCT. Neuroimaging in vascular parkinsonism. Curr Neurol Neurosci Rep 2019;19:102 doi:10.1007/s11910-019-1019-7 pmid:31773419
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1007/s11910-019-1019-7&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=31773419&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

78. 78.Antonini A, Vitale C, Barone P, et al. The relationship between cerebral vascular disease and parkinsonism: the VADO study. Parkinsonism Relat Disord 2012;18:775–80 doi:10.1016/j.parkreldis.2012.03.017 pmid:22531611
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1016/j.parkreldis.2012.03.017&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=22531611&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000306541200012&link_type=ISI) 

79. 79.Rissardo JP, Caprara ALF. Cinnarizine- and flunarizine-associated movement disorder: a literature review. Egyp J Neurol Psych Neurosurg 2020;56:61
    
    

80. 80.Pitton Rissardo J, Caprara ALF. Neuroimaging techniques in differentiating Parkinson’s disease from drug-induced parkinsonism: a comprehensive review. Clin Pract 2023;13:1427–48 doi:10.3390/clinpract13060128 pmid:37987429
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.3390/clinpract13060128&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=37987429&link_type=MED&atom=%2Fajnr%2Fearly%2F2024%2F08%2F29%2Fajnr.A8313.atom) 

81. 81.Laruelle M, Abi-Dargham A, van Dyck CH, et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A 1996;93:9235–40 doi:10.1073/pnas.93.17.9235 pmid:8799184
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMDoiOTMvMTcvOTIzNSI7czo0OiJhdG9tIjtzOjM4OiIvYWpuci9lYXJseS8yMDI0LzA4LzI5L2FqbnIuQTgzMTMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

82. 82.Burn DJ, Brooks DJ. Nigral dysfunction in drug-induced parkinsonism: an 18F-dopa PET study. Neurology 1993;43:552–56 doi:10.1212/wnl.43.3\_part\_1.552 pmid:8451000
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjE1OiI0My8zX1BhcnRfMS81NTIiO3M6NDoiYXRvbSI7czozODoiL2FqbnIvZWFybHkvMjAyNC8wOC8yOS9ham5yLkE4MzEzLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

*   Received January 15, 2024.
*   Accepted after revision April 16, 2024.


*   © 2024 by American Journal of Neuroradiology