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Add comprehensive articles on Vascular Dementia and Wallerian Degeneration

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- Created a detailed article for Vascular Dementia covering key facts, terminology, imaging findings, differential diagnoses, pathology, clinical issues, and diagnostic checklist.
- Developed an extensive article on Wallerian Degeneration including key facts, terminology, imaging features, differential diagnoses, pathology, clinical issues, and diagnostic checklist.
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---
title: "Parkinsonian Syndromes"
docid: "2b99b31a-ec1a-4dce-bb63-2a101fe9f044"
breadcrumbs:
- "Nuclear Medicine"
- "Central Nervous System"
- "Neurodegeneration"
- "Parkinsonian Syndromes"
---
# KEY FACTS
- ## Terminology
- Chronic, progressive brain disorder characterized by loss of dopaminergic neurons that leads to tremors at rest, rigidity, slowed movements, and shuffling gait
- ## Imaging
- Dopamine transporters typically decreased for all Parkinson syndromes [Parkinson disease (PD) and atypical parkinsonism syndromes (APS)]
- Loss of dopaminergic neurons visualized on I-123 ioflupane (DaT) SPECT and F-18 fluorodopa (FDOPA) PET
- **I-123 ioflupane (DaT, FP-CIT) SPECT**
- Molecular imaging agent that binds to dopamine transporters located on presynaptic nigrostriatal axons
- **F-18 FDOPA PET**
- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
- Sensitivity > 90% for differentiating PD and essential tremor
- Normal DaT and FDOPA scans demonstrate comma-shaped uptake on axial images
- Abnormal scans demonstrate
- Asymmetric putamen activity
- Symmetrically decreased or absent putamen activity with preservation of caudate
- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
- Patient should be off all interfering dopaminergic medications
- ## Top Differential Diagnoses
- PD
- Multiple system atrophy
- Progressive supranuclear palsy
- Dementia with Lewy bodies
- Corticobasal degeneration
# TERMINOLOGY
- ## Definitions
- **Parkinsonian syndrome (PS)**
- Clinical syndrome presenting with any combination of bradykinesia, resting tremor, rigidity, and autonomic instability
- **Parkinson disease** **(****PD**) **(α-synucleinopathy)**
- Chronic progressive disorder caused by degenerative loss of dopaminergic neurons
- Classically present with bradykinesia and at least 1 of (i) tremor &/or (ii) rigidity
- Normal DaT scan considered essentially exclusionary for diagnosis
- **Atypical PS (APS)**
- Characterized by more rapid progression and poorer prognosis than PD
- Includes progressive supranuclear palsy (PSP; 4R-tauopathy), multiple system atrophy (MSA; α-synucleinopathy), and corticobasal degeneration (CBD; 4R-tauopathy)
- **Dementia with Lewy bodies (DLB) (****α****-synucleinopathy)**
- Dementia + visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity
- **Drug-induced parkinsonism (DIP**)
- Secondary parkinsonism, usually reversible
- **Vascular parkinsonism (VP)**
- Small vessel disease, multiple lacunar infarcts in basal ganglia
- **Essential tremor (ET)**
- Most common cause of action tremor in adults
- Slow, gradual progression
# IMAGING
- ## General Features
- Loss of dopaminergic neurons on I-123 ioflupane (DaT) SPECT or F-18 fluorodopa (FDOPA) PET
- Relatively normal F-18 FDG PET/CT
- Distinct abnormal patterns in APS
- ## Imaging Recommendations
- ### Best imaging tool
- **I-123 ioflupane (DaT, FP-CIT) SPECT**
- Molecular imaging agent that binds to dopamine (DA) transporters located on presynaptic nigrostriatal axons
- DA transporters typically decreased for all Parkinson syndromes (PD and APSs)
- DA transporters are located in putamen and caudate nuclei
- Demonstrates loss of dopaminergic neurons
- Sensitivity > 90% for differentiating PD and ET
- May be symmetric or asymmetric
- Differentiates PD and APS from ET and DIP
- PD and APS demonstrate decreased activity in putamen and caudate
- Does **not** differentiate PD from APS or between APSs
- Image interpretation
- Normal scans demonstrate comma-shaped uptake on axial images
- Abnormal scans demonstrate period-shaped uptake on axial images indicating more pronounced loss of uptake in putamen
- Abnormal uptake may be initially detected in contralateral putamen relative to clinical symptoms
- Abnormal patterns
- Asymmetric putamen activity
- Symmetrically decreased or absent putamen activity with preservation of caudate
- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
- **F-18 FDOPA PET**
- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
- Accumulation of F-18 fluorodopamine in striatum is visually detected on PET
- Similar uptake pattern as I-123 ioflupane in normal and disease states but benefits from better quality of PET
- Normal scan: Comma-shaped uptake on axial images visualizing caudate and putamen
- Abnormal scan: Asymmetric or decreased putamen activity with normal or decreased caudate activity
- **F-18 FDG PET/CT**
- Typically normal in PD
- Preserved F-18 FDG PET/CT in basal ganglia differentiates PD from PS
- **MIBG cardiac SPECT**
- Absent myocardial tracer binding in PD and LBD
- Typically preserved in APDs, DIP, VP, ET
- ### Protocol advice
- **I-123 ioflupane**
- Patient should be off all interfering dopaminergic medications
- Cocaine, amphetamines, and methylphenidate severely decrease binding
- Ephedrine and phentermine may decrease binding
- Bupropion, fentanyl, and some anesthetics may decrease binding
- Patient preparation
- Pretreat with thyroid blocker (400 mg of oral potassium solution or single dose of Lugol solution) 1 hour before tracer injection
- Pregnancy category C: Unknown whether I-123 can cause fetal damage or early termination of pregnancy
- Radiopharmaceutical: I-123 ioflupane
- Dose: 3-5 mCi (111-185 MBq) intravenously
- Dosimetry: Striata receives highest radiation exposure, followed by bladder, bowel, and lungs (assuming thyroid is blocked)
- Image acquisition: 3-6 hours after injection
- SPECT or SPECT/CT acceptable but attenuation correction is recommended
- Photopeak should be set to 159 keV ± 10%
- Low-energy, high-resolution collimator
- 128 x 128 matrix is recommended
- 30-second projection time (120 projections)
- **F-18 FDOPA**
- Patient preparation
- 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
- Carbidopa blocks systemic/peripheral decarboxylation of F-18 FDOPA to increase uptake in brain
- Patient should be off all interfering dopaminergic medications for at least 12 hours prior to F-18 FDOPA injection
- Aromatic L-amino acid decarboxylase (AADC) inhibitors (e.g., carbidopa, benserazide, etc.)
- 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
- Radiopharmaceutical: F-18 FDOPA
- Dose: 5 mCi (185 MBq) intravenously
- Image acquisition: 80-100 minutes after injection
- PET attenuation correction CT
- Dosimetry: Critical organ is bladder wall
- F-18 FDG PET/CT
- Patient preparation
- Patient should fast, stop IV fluids containing dextrose, stop parenteral feeding for 4-6 hours
- Blood sugar should be 150-200 mg/dL
- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 minutes
- Radiopharmaceutical: F-18 FDG
- Dose: 5-20 mCi (185-740 MBq)
- Dosimetry: Urinary bladder receives largest dose
- Image acquisition: 30-60 minutes after injection
- ## Artifacts and Quality Control
- Certain medications can significantly alter scan appearance and should be discontinued/documented
- Ensure patient is off competing medications if activity is diffusely low
# DIFFERENTIAL DIAGNOSIS
- [Parkinson Disease](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
- I-123 ioflupane/F-18 FDOPA positive
- Amyloid PET negative
- 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
- MR T2* can show loss of swallowtail sign in substantia nigra
- ## Atypical Parkinsonian Syndromes
- [MSA](/document/multiple-system-atrophy/4fb9af00-e0bd-4164-8f61-4011ddc8bf9e)
- Family of neurodegenerative disorders
- Symptoms include parkinsonism, ataxia, and autonomic dysfunction
- Cerebellar dominant (MSA-C) and parkinsonian dominant (MSA-P)
- F-18 FDG PET
- MSA-C shows decreased activity in cerebellum
- MSA-P shows decreased putamen activity
- Amyloid PET negative
- I-123 ioflupane/F-18 FDOPA positive
- MR shows volume loss/T2 hyperintensity in cerebellum, middle cerebellar peduncles, and putamen
- [PSP](/document/progressive-supranuclear-palsy/840ed321-c0ab-4069-a07e-ad416232f916)
- Symptoms include parkinsonism, bradykinesia, rigidity, **vertical gaze palsy**, dysphagia, dysarthria
- Amyloid PET negative
- Ioflupane SPECT positive
- Decreased F-18 FDG activity in basal ganglia, frontal lobes, anterior cingulate, midbrain
- Volume loss in midbrain with relatively preserved pons, MR hummingbird sign or Mickey Mouse sign
- [DLB](/document/lewy-body-dementia/f6a4382b-f0f7-4582-a703-7f695c65656f)
- Symptoms include dementia, visual hallucinations, parkinsonism
- I-123 ioflupane/F-18 FDOPA positive
- Amyloid PET is positive in > 50% of patients
- F-18 FDG PET/CT shows generalized reduced cortical uptake most pronounced in occipital region and sparing posterior cingulate gyrus cingulate island sign
- [CBD](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
- Cognitive/behavioral symptoms precede movement dysfunction
- Symptoms include akinesia, rigidity, dystonia, apraxia, executive dysfunction, aphasia, "alien limb" phenomenon
- Patients do not respond to levodopa
- I-123 ioflupane/F-18 FDOPA positive, typically asymmetric and decreased contralateral to symptoms
- Amyloid PET negative
- F-18 FDG PET/CT relative decreased activity in contralateral cortex and basal ganglia
- May be caused by increased ipsilateral uptake
- ## Benign Essential Tremor
- Negative I-123 ioflupane/F-18 FDOPA
- ## Vascular Parkinsonism
- Negative I-123 ioflupane/F-18 FDOPA
- ## Drug-Induced Parkinsonism
- Negative I-123 ioflupane/F-18 FDOPA
# PATHOLOGY
- ## General Features
- PD accounts for > 70% of parkinsonian patients
- α-synuclein skin biopsy shows high sensitivity for PD, MSA, and DLB
- Loss of dopaminergic neurons
- Affected neurons project from substantia nigra (midbrain) to putamen and caudate
- Putamen typically affected earlier and more severely
- Symptoms begin to show after ~ 50% of neurons are affected
# CLINICAL ISSUES
- ## Presentation
- ### Most common signs/symptoms
- Rigidity, tremor, bradykinesia, autonomic instability
- ## Demographics
- Prevalence of ~ 1% in adults > 65 years
# DIAGNOSTIC CHECKLIST
- ## Image Interpretation Pearls
- 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)
- Cardiac MIBG may be helpful in diagnosing PD and DLB, though is typically normal in other PSs
- ## Reporting Tips
- Reporting scheme in literature
- Normal: 2 comma-shaped areas of uptake
- Abnormal grade 1: Asymmetric uptake [normal (comma shape) on one side and abnormal (period shape) on other side]
- Abnormal grade 2: Abnormal (period shape) reduced putamen activity bilaterally
- Abnormal grade 3: Markedly reduced uptake bilaterally
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