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title: "Parkinsonian Syndromes"
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docid: "2b99b31a-ec1a-4dce-bb63-2a101fe9f044"
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authors:
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- key: "9d40c5b1-57d2-442c-9daf-8d8d9d53e24b"
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value: "Akiva Mintz, MD, PhD, MHA, CFA"
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- key: "cfdbf358-617e-410b-994f-8b48b03fdb8c"
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value: "Jongho Kim, MD, PhD, FACNM"
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- key: "1f262abe-db83-4f18-99af-00bd3045cd4d"
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value: "Marc Benayoun, MD, PhD"
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breadcrumbs:
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-
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name: "Nuclear Medicine"
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slug: "nuclear-medicine"
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treeNodeId: "2406533f-6523-4211-841e-b92d6f8cf34e"
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-
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name: "Central Nervous System"
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slug: "central-nervous-system"
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treeNodeId: "bd6b5c36-69df-4f18-af9c-96cc24b52d8f"
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name: "Neurodegeneration"
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slug: "neurodegeneration"
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treeNodeId: "f2b87cc7-926d-4915-8ec5-ca61a82e8bc9"
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-
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name: "Parkinsonian Syndromes"
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slug: "parkinsonian-syndromes"
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treeNodeId: null
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category: "Nuclear Medicine"
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cmeTopicId: "ecf24fff-01ac-47ef-ba50-e1e58401f6f2"
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documentVersionId: "371cf6e0-aa4a-42ef-9166-db16550d8593"
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imageCount: 12
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lastUpdated: "06/06/25"
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pageDescription: "Parkinsonian Syndromes"
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pageKeywords: "Nuclear Medicine, Central Nervous System, Neurodegeneration, Parkinsonian Syndromes"
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pageTitle: "Parkinsonian Syndromes | STATdx"
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enhancedTitle: "Parkinsonian Syndromes"
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type: "DX"
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references: true
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breadcrumbs:
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- "Nuclear Medicine"
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- "Central Nervous System"
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- "Neurodegeneration"
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- "Parkinsonian Syndromes"
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---
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# KEY FACTS
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- ## Terminology
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- Chronic, progressive brain disorder characterized by loss of dopaminergic neurons that leads to tremors at rest, rigidity, slowed movements, and shuffling gait
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- ## Imaging
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- Dopamine transporters typically decreased for all Parkinson syndromes [Parkinson disease (PD) and atypical parkinsonism syndromes (APS)]
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- Loss of dopaminergic neurons visualized on I-123 ioflupane (DaT) SPECT and F-18 fluorodopa (FDOPA) PET
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- **I-123 ioflupane (DaT, FP-CIT) SPECT**
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- Molecular imaging agent that binds to dopamine transporters located on presynaptic nigrostriatal axons
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- **F-18 FDOPA PET**
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- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
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- Sensitivity > 90% for differentiating PD and essential tremor
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- Normal DaT and FDOPA scans demonstrate comma-shaped uptake on axial images
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- Abnormal scans demonstrate
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- Asymmetric putamen activity
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- Symmetrically decreased or absent putamen activity with preservation of caudate
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- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
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- Patient should be off all interfering dopaminergic medications
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- ## Top Differential Diagnoses
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- PD
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- Multiple system atrophy
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- Progressive supranuclear palsy
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- Dementia with Lewy bodies
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- Corticobasal degeneration
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# TERMINOLOGY
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- ## Definitions
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- **Parkinsonian syndrome (PS)**
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- Clinical syndrome presenting with any combination of bradykinesia, resting tremor, rigidity, and autonomic instability
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- **Parkinson disease** **(****PD**) **(α-synucleinopathy)**
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- Chronic progressive disorder caused by degenerative loss of dopaminergic neurons
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- Classically present with bradykinesia and at least 1 of (i) tremor &/or (ii) rigidity
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- Normal DaT scan considered essentially exclusionary for diagnosis
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- **Atypical PS (APS)**
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- Characterized by more rapid progression and poorer prognosis than PD
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- Includes progressive supranuclear palsy (PSP; 4R-tauopathy), multiple system atrophy (MSA; α-synucleinopathy), and corticobasal degeneration (CBD; 4R-tauopathy)
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- **Dementia with Lewy bodies (DLB) (****α****-synucleinopathy)**
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- Dementia + visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity
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- **Drug-induced parkinsonism (DIP**)
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- Secondary parkinsonism, usually reversible
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- **Vascular parkinsonism (VP)**
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- Small vessel disease, multiple lacunar infarcts in basal ganglia
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- **Essential tremor (ET)**
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- Most common cause of action tremor in adults
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- Slow, gradual progression
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# IMAGING
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- ## General Features
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- Loss of dopaminergic neurons on I-123 ioflupane (DaT) SPECT or F-18 fluorodopa (FDOPA) PET
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- Relatively normal F-18 FDG PET/CT
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- Distinct abnormal patterns in APS
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- ## Imaging Recommendations
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- ### Best imaging tool
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- **I-123 ioflupane (DaT, FP-CIT) SPECT**
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- Molecular imaging agent that binds to dopamine (DA) transporters located on presynaptic nigrostriatal axons
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- DA transporters typically decreased for all Parkinson syndromes (PD and APSs)
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- DA transporters are located in putamen and caudate nuclei
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- Demonstrates loss of dopaminergic neurons
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- Sensitivity > 90% for differentiating PD and ET
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- May be symmetric or asymmetric
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- Differentiates PD and APS from ET and DIP
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- PD and APS demonstrate decreased activity in putamen and caudate
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- Does **not** differentiate PD from APS or between APSs
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- Image interpretation
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- Normal scans demonstrate comma-shaped uptake on axial images
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- Abnormal scans demonstrate period-shaped uptake on axial images indicating more pronounced loss of uptake in putamen
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- Abnormal uptake may be initially detected in contralateral putamen relative to clinical symptoms
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- Abnormal patterns
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- Asymmetric putamen activity
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- Symmetrically decreased or absent putamen activity with preservation of caudate
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- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
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- **F-18 FDOPA PET**
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- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
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- Accumulation of F-18 fluorodopamine in striatum is visually detected on PET
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- Similar uptake pattern as I-123 ioflupane in normal and disease states but benefits from better quality of PET
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- Normal scan: Comma-shaped uptake on axial images visualizing caudate and putamen
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- Abnormal scan: Asymmetric or decreased putamen activity with normal or decreased caudate activity
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- **F-18 FDG PET/CT**
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- Typically normal in PD
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- Preserved F-18 FDG PET/CT in basal ganglia differentiates PD from PS
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- **MIBG cardiac SPECT**
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- Absent myocardial tracer binding in PD and LBD
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- Typically preserved in APDs, DIP, VP, ET
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- ### Protocol advice
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- **I-123 ioflupane**
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- Patient should be off all interfering dopaminergic medications
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- Cocaine, amphetamines, and methylphenidate severely decrease binding
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- Ephedrine and phentermine may decrease binding
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- Bupropion, fentanyl, and some anesthetics may decrease binding
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- Patient preparation
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- Pretreat with thyroid blocker (400 mg of oral potassium solution or single dose of Lugol solution) 1 hour before tracer injection
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- Pregnancy category C: Unknown whether I-123 can cause fetal damage or early termination of pregnancy
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- Radiopharmaceutical: I-123 ioflupane
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- Dose: 3-5 mCi (111-185 MBq) intravenously
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- Dosimetry: Striata receives highest radiation exposure, followed by bladder, bowel, and lungs (assuming thyroid is blocked)
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- Image acquisition: 3-6 hours after injection
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- SPECT or SPECT/CT acceptable but attenuation correction is recommended
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- Photopeak should be set to 159 keV ± 10%
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- Low-energy, high-resolution collimator
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- 128 x 128 matrix is recommended
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- 30-second projection time (120 projections)
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- **F-18 FDOPA**
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- Patient preparation
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- Premedicate with 150 mg of carbidopa orally at least 60 minutes (and no longer than 120 minutes) prior to administration of F-18 FDOPA injection
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- Carbidopa blocks systemic/peripheral decarboxylation of F-18 FDOPA to increase uptake in brain
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- Patient should be off all interfering dopaminergic medications for at least 12 hours prior to F-18 FDOPA injection
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- Aromatic L-amino acid decarboxylase (AADC) inhibitors (e.g., carbidopa, benserazide, etc.)
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- DA agonists, DA reuptake inhibitors, DA-releasing agents (DRAs), such as psychostimulants of amphetamine class, peripheral catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors
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- Radiopharmaceutical: F-18 FDOPA
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- Dose: 5 mCi (185 MBq) intravenously
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- Image acquisition: 80-100 minutes after injection
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- PET attenuation correction CT
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- Dosimetry: Critical organ is bladder wall
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- F-18 FDG PET/CT
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- Patient preparation
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- Patient should fast, stop IV fluids containing dextrose, stop parenteral feeding for 4-6 hours
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- Blood sugar should be 150-200 mg/dL
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- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 minutes
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- Radiopharmaceutical: F-18 FDG
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- Dose: 5-20 mCi (185-740 MBq)
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- Dosimetry: Urinary bladder receives largest dose
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- Image acquisition: 30-60 minutes after injection
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- ## Artifacts and Quality Control
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- Certain medications can significantly alter scan appearance and should be discontinued/documented
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- Ensure patient is off competing medications if activity is diffusely low
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# DIFFERENTIAL DIAGNOSIS
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- [Parkinson Disease](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
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- I-123 ioflupane/F-18 FDOPA positive
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- Amyloid PET negative
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- F-18 FDG PET grossly normal, but PD-related metabolic pattern reported as increased pallidal, thalamic, and motor cortical metabolic activity associated with decreased lateral premotor and parietooccipital cortical activity
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- MR T2* can show loss of swallowtail sign in substantia nigra
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- ## Atypical Parkinsonian Syndromes
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- [MSA](/document/multiple-system-atrophy/4fb9af00-e0bd-4164-8f61-4011ddc8bf9e)
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- Family of neurodegenerative disorders
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- Symptoms include parkinsonism, ataxia, and autonomic dysfunction
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- Cerebellar dominant (MSA-C) and parkinsonian dominant (MSA-P)
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- F-18 FDG PET
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- MSA-C shows decreased activity in cerebellum
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- MSA-P shows decreased putamen activity
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- Amyloid PET negative
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- I-123 ioflupane/F-18 FDOPA positive
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- MR shows volume loss/T2 hyperintensity in cerebellum, middle cerebellar peduncles, and putamen
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- [PSP](/document/progressive-supranuclear-palsy/840ed321-c0ab-4069-a07e-ad416232f916)
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- Symptoms include parkinsonism, bradykinesia, rigidity, **vertical gaze palsy**, dysphagia, dysarthria
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- Amyloid PET negative
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- Ioflupane SPECT positive
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- Decreased F-18 FDG activity in basal ganglia, frontal lobes, anterior cingulate, midbrain
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- Volume loss in midbrain with relatively preserved pons, MR hummingbird sign or Mickey Mouse sign
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- [DLB](/document/lewy-body-dementia/f6a4382b-f0f7-4582-a703-7f695c65656f)
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- Symptoms include dementia, visual hallucinations, parkinsonism
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- I-123 ioflupane/F-18 FDOPA positive
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- Amyloid PET is positive in > 50% of patients
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- F-18 FDG PET/CT shows generalized reduced cortical uptake most pronounced in occipital region and sparing posterior cingulate gyrus cingulate island sign
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- [CBD](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
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- Cognitive/behavioral symptoms precede movement dysfunction
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- Symptoms include akinesia, rigidity, dystonia, apraxia, executive dysfunction, aphasia, "alien limb" phenomenon
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- Patients do not respond to levodopa
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- I-123 ioflupane/F-18 FDOPA positive, typically asymmetric and decreased contralateral to symptoms
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- Amyloid PET negative
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- F-18 FDG PET/CT relative decreased activity in contralateral cortex and basal ganglia
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- May be caused by increased ipsilateral uptake
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- ## Benign Essential Tremor
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- Negative I-123 ioflupane/F-18 FDOPA
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- ## Vascular Parkinsonism
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- Negative I-123 ioflupane/F-18 FDOPA
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- ## Drug-Induced Parkinsonism
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- Negative I-123 ioflupane/F-18 FDOPA
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# PATHOLOGY
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- ## General Features
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- PD accounts for > 70% of parkinsonian patients
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- α-synuclein skin biopsy shows high sensitivity for PD, MSA, and DLB
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- Loss of dopaminergic neurons
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- Affected neurons project from substantia nigra (midbrain) to putamen and caudate
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- Putamen typically affected earlier and more severely
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- Symptoms begin to show after ~ 50% of neurons are affected
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Rigidity, tremor, bradykinesia, autonomic instability
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- ## Demographics
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- Prevalence of ~ 1% in adults > 65 years
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# DIAGNOSTIC CHECKLIST
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- ## Image Interpretation Pearls
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- I-123 ioflupane SPECT/F-18 FDOPA each differentiate between diseases related to DA loss (PD and APS) and those that mimic them clinically (benign tremor and VP)
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- Cardiac MIBG may be helpful in diagnosing PD and DLB, though is typically normal in other PSs
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- ## Reporting Tips
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- Reporting scheme in literature
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- Normal: 2 comma-shaped areas of uptake
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- Abnormal grade 1: Asymmetric uptake [normal (comma shape) on one side and abnormal (period shape) on other side]
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- Abnormal grade 2: Abnormal (period shape) reduced putamen activity bilaterally
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- Abnormal grade 3: Markedly reduced uptake bilaterally
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cc5405dd-1797-4f98-b1a1-127b9159f5f1
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## References
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# Selected References
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1. [Jost WH et al: Neuroimaging in multiple system atrophy: clinical implications and novel developments. J Neural Transm (Vienna). ePub, 2025](http://www.ncbi.nlm.nih.gov/pubmed/?term=40214765%5Bpmid%5D)
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1. [Hastings A et al: Neuropathologic validation and diagnostic accuracy of presynaptic dopaminergic imaging in the diagnosis of parkinsonism. Neurology. 102(11):e209453, 2024](http://www.ncbi.nlm.nih.gov/pubmed/?term=38759132%5Bpmid%5D)
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1. [American College of Radiology: ACRE–ACNM–SNMMI practice parameter for the performance of dopamine transporter (DaT) single photon emission computed tomography (SPECT) imaging for movement disorders. Updated 2022. Accessed May 17, 2025. https://gravitas.acr.org/PPTS/DownloadPreviewDocument?DocId=134](https://gravitas.acr.org/PPTS/DownloadPreviewDocument?DocId=134)
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1. [Pirtošek Z et al: Update on the management of Parkinson's disease for general neurologists. Parkinsons Dis. 2020:9131474, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32300476%5Bpmid%5D)
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1. [Broski SM et al: Structural and functional imaging in parkinsonian syndromes. Radiographics. 34(5):1273-92, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25208280%5Bpmid%5D)
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1. [Bajaj N et al: Clinical utility of dopamine transporter single photon emission CT (DaT-SPECT) with (123I) ioflupane in diagnosis of parkinsonian syndromes. J Neurol Neurosurg Psychiatry. 84(11):1288-95, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23486993%5Bpmid%5D)
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1. [Djang DS et al: SNM practice guideline for dopamine transporter imaging with 123I-ioflupane SPECT 1.0. J Nucl Med. 53(1):154-63, 2012](http://www.ncbi.nlm.nih.gov/pubmed/?term=22159160%5Bpmid%5D)
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1. [Access Data: FDA prescribing information for DaTscan website. Updated 2011. Accessed April 11, 2025. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022454sOrig1s000Lbl.pdf](http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022454sOrig1s000Lbl.pdf)
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1. [Tang CC et al: Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol. 9(2):149-58, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20061183%5Bpmid%5D)
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1. [Booij J et al: Dopamine transporter imaging with [(123)I]FP-CIT SPECT: potential effects of drugs. Eur J Nucl Med Mol Imaging. 35(2):424-38, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=17968545%5Bpmid%5D)
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1. [Ibrahim N et al: The sensitivity and specificity of F-DOPA PET in a movement disorder clinic. Am J Nucl Med Mol Imaging. 6(1):102-9, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27069770%5Bpmid%5D)
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1. [Eshuis SA et al: Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson's disease. Eur J Nucl Med Mol Imaging. 33(2):200-9, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16228235%5Bpmid%5D)
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1. [Dhawan V et al: Comparative analysis of striatal FDOPA uptake in Parkinson's disease: ratio method versus graphical approach. J Nucl Med. 43(10):1324-30, 2002](http://www.ncbi.nlm.nih.gov/pubmed/?term=12368370%5Bpmid%5D)
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1. [Brooks DJ: Imaging approaches to Parkinson disease. J Nucl Med. 51(4):596-609, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20351351%5Bpmid%5D)
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1. [Eckert T et al: FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage. 26(3):912-21, 2005](http://www.ncbi.nlm.nih.gov/pubmed/?term=15955501%5Bpmid%5D)
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1. [Marek K et al: [123I.] Neurology. 57(11):2089-94, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11739831%5Bpmid%5D)
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## Images
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### Selected Images
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*Axial graphic demonstrates brain anatomy and expected area of uptake (blue) in the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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*Axial graphic demonstrates brain anatomy and expected area of uptake (blue) in the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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||||
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*Axial graphic demonstrates brain anatomy and expected area of uptake (blue) in the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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||||
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||||
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||||
*Axial graphic demonstrates brain anatomy and expected area of uptake (blue) in the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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||||
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||||
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||||
*Axial graphic demonstrates brain anatomy and expected area of uptake (blue) in the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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*Axial graphic shows normal uptake (orange) of I-123 ioflupane or F-18 FDOPA overlaid on the head of the caudate <img src='img/arrows/BO.png'/> and putamen <img src='img/arrows/WS.png'/>.*
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*Axial I-123 ioflupane SPECT shows normal putamen activity <img src='img/arrows/WS.png'/> and caudate activity <img src='img/arrows/WO.png'/>. These finding are not consistent with Parkinson disease (PD) or atypical parkinsonism syndromes (APS).*
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||||
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*Axial I-123 ioflupane SPECT shows absent left putamen activity <img src='img/arrows/WS.png'/>, preserved but decreased right putamen activity <img src='img/arrows/WC.png'/>, and preserved caudate activity <img src='img/arrows/WO.png'/>. These findings are consistent with PD or APS.*
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||||
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||||
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*Axial I-123 ioflupane SPECT shows absent bilateral putamen activity <img src='img/arrows/WS.png'/> and preserved caudate activity <img src='img/arrows/WO.png'/>. These finding are consistent with PD or APS.*
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*Axial I-123 ioflupane SPECT shows absent bilateral putamen activity and almost absent caudate activity. These findings are consistent with PD or APS if patient was not on any interfering medications.*
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*Quantitative analysis of I-123 ioflupane SPECT shows the bilateral caudates have abnormally low uptake <img src='img/arrows/CS.png'/> of radiotracer compared with normal controls. Note that this would be difficult to discern on visual analysis alone <img src='img/arrows/CO.png'/>.*
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*Quantitative analysis of I-123 ioflupane SPECT in the same patient shows the bilateral posterior putamina have abnormally low uptake <img src='img/arrows/CS.png'/> of radiotracer compared with normal controls. Visual analysis of the putamina <img src='img/arrows/CO.png'/> supports the quantitative analysis.*
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*Axial I-123 ioflupane SPECT images in a patient with suspected PD show no significant uptake in the caudate or putamen <img src='img/arrows/CS.png'/>. After the scan, it was revealed that the patient was taking modafinil, which has been reported to bind to the dopamine transporter and inhibit dopamine reuptake.*
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||||
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||||
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||||
*Axial I-123 ioflupane SPECT images in the same patient after discontinuation of modafinil show significant uptake in the caudate <img src='img/arrows/CO.png'/> but decreased/absent uptake in the putamen <img src='img/arrows/CS.png'/>.*
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||||
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||||
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### Additional Images
|
||||
|
||||
|
||||
*Axial I-123 ioflupane SPECT shows bilateral a comma-shaped appearance, consistent with a normal study. Note the slight asymmetry between sides, which may be secondary to head positioning.*
|
||||
|
||||
|
||||
*Axial I-123 Ioflupane SPECT images of the same patient from superior <img src='img/arrows/CS.png'/> to inferior <img src='img/arrows/WS.png'/> demonstrate the full appearance of caudate heads and putamen.*
|
||||
|
||||
Reference in New Issue
Block a user