Neuroimaging for Parkinsonian Syndromes (NCT03872102)

Overview

Overview

This observational neuroimaging study employs advanced imaging techniques to characterize brain changes in Progressive Supranuclear Palsy (PSP) and related Parkinsonian syndromes. The study addresses a critical gap in our understanding of how tau pathology manifests on different imaging modalities and how these findings correlate with clinical phenotypes["@neuroimaging"].

Neuroimaging plays a pivotal role in the diagnosis and monitoring of atypical parkinsonism. Unlike Parkinson's Disease (PD), where dopaminergic degeneration is the primary finding, PSP and related disorders show distinct patterns of atrophy, metabolic changes, and network disruption that can be visualized with modern imaging techniques.

Study Details

| Field | Value |
|-------|-------|
| NCT Number | NCT03872102 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | PSP, PD, MSA |
| Sponsor | French Research Consortium |
| Sites | Multiple centers in France |
| Enrollment Target | 200+ participants |
| Duration | 3-year study with longitudinal imaging |

Scientific Rationale

The Role of Neuroimaging in Atypical Parkinsonism

Neuroimaging has evolved from a primarily exclusionary tool to a positive diagnostic modality in atypical parkinsonism. While conventional MRI remains useful for ruling out secondary causes, advanced techniques can now visualize the specific pathological changes that define each disorder.

MRI Patterns in PSP

The diagnosis of PSP has evolved with the recognition that multiple clinical phenotypes exist beyond the classic Richardson's syndrome. MRI findings vary substantially by subtype[@whittwell2017]:

PET and Molecular Imaging

Multiple PET tracers provide insights into the underlying pathology[@nicastro2020]:

| Tracer | Target | Findings in PSP |
|--------|--------|-----------------|
| [^18F]FDG | Glucose metabolism | Hypometabolism in frontal cortex, brainstem, striatum |
| [^11C]PiB | Amyloid | Typically negative (distinguishes from AD) |
| [^18F]AV-1451 | Tau | Variable binding in basal ganglia, brainstem, cortical regions |

Diffusion Tensor Imaging

DTI reveals microstructural damage that often precedes visible atrophy[@bailey2013]:

• Reduced fractional anisotropy (FA) in the superior cerebellar peduncle — specific for PSP
• Increased mean diffusivity (MD) in the basal ganglia and brainstem

Emerging Imaging Techniques

The field is moving toward integrated multimodal approaches:

Objectives

Primary Objectives

Secondary Objectives

Neuroimaging Modalities

Magnetic Resonance Imaging

The study employs comprehensive MRI protocols:

Positron Emission Tomography

PET imaging provides molecular insights:

Clinical Correlation

The study includes comprehensive clinical assessments:

• PSP Rating Scale (PSPRS)
• MDS-UPDRS Parts I-IV
• Timed Up and Go Test
• Quantitative oculomotor assessment
• MoCA (Montreal Cognitive Assessment)

Eligibility Criteria

Inclusion Criteria

• Clinically diagnosed PSP (any subtype) or related disorder[@hoglinger2017]
• Age 40-85 years
• MRI compatibility (no pacemakers, cochlear implants)
• Ability to cooperate with imaging procedures

Exclusion Criteria

• Secondary parkinsonism (vascular, drug-induced)
• Significant white matter disease (Fazekas score > 2)
• Contraindications to PET imaging

Significance

Accurate neuroimaging provides critical benefits:

Improved Diagnostic Accuracy

Imaging supports clinical diagnosis and can differentiate PSP from:

• PD: Midbrain atrophy, SCP involvement
• MSA: Hot cross bun sign, pontine atrophy
• CBS: Asymmetric cortical atrophy

Earlier Diagnosis

Advanced techniques may identify prodromal changes:

• Subtle midbrain changes before overt atrophy
• Microstructural changes on DTI before clinical conversion

Objective Outcome Measures

Imaging endpoints complement clinical measures in trials:

• Atrophy rates are objective and reproducible
• DTI metrics show sensitivity to change

Comparison with Other Imaging Studies

This study complements other neuroimaging initiatives:

• [MARKERS-NDD](/clinical-trials/markers-ndd-progression-markers-nct06596746): Focuses on comprehensive biomarker development
• [Tau PET studies](/clinical-trials/18f-pmbb3-pet-tauopathy-nct03625128): Tau-specific imaging
• [Synaptic loss in MSA](/clinical-trials/synaptic-loss-msa-nct05121012): Synaptic density imaging

PSP Subtypes and Their Imaging Signatures

Richardson's Syndrome (PSP-RS)

Classic PSP shows characteristic imaging:

• Midbrain atrophy with "hummingbird sign"
• Ventral pons atrophy
• SCP degeneration
• FDG-PET: Hypometabolism in frontal cortex, brainstem

PSP-Parkinsonism (PSP-P)

The parkinsonian variant shows:

• Less pronounced midbrain atrophy
• More prominent putaminal changes
• Variable SCP involvement

PSP-Cortical (PSP-CBS)

Features of corticobasal syndrome with PSP:

• Asymmetric cortical atrophy (frontoparietal)
• FDG-PET: Asymmetric hypometabolism

Future Directions

Clinical Translation

The study aims to develop clinically applicable tools:

Clinical Trial Applications

Validated imaging biomarkers will enable:

• Smaller sample sizes (30-50% reduction)
• Shorter trial duration
• Surrogate endpoints for accelerated approval

See Also

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy)
• [Tau Protein](/proteins/tau)
• [MRI in Neurodegeneration](/mechanisms/neuroimaging-biomarkers)

External Links

• [Neuroimaging for Parkinsonian Syndromes - ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT03872102)
• [Movement Disorder Society - PSP Diagnostic Criteria](https://www.movementdisorders.org/)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Neuroimaging for Parkinsonian Syndromes (NCT03872102) discovered through SciDEX knowledge graph analysis: