Overview
This observational study focuses on quantitative assessment of gait dysfunction and upper limb motor impairments in Progressive Supranuclear Palsy (PSP), leveraging advanced motion capture technology. PSP is a progressive neurodegenerative disorder characterized by vertical supranuclear gaze palsy, axial rigidity, postural instability, and akinesia[@ali2021]. Gait impairment is a hallmark of PSP and represents one of the most disabling features, contributing significantly to falls and functional disability.
The study aims to establish quantitative baselines that can inform therapeutic trials and improve patient stratification. Traditional clinical rating scales, while valuable, may not detect subtle changes in motor function that occur early in the disease process or respond minimally to investigational therapies. Quantitative motor assessment provides objective, reproducible measures that can track disease progression and treatment response with greater sensitivity than subjective clinical ratings[@nichols2016][@urschel2020].
Study Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT07136844 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | PSP (Progressive Supranuclear Palsy) |
| Sites | Belgium |
| Enrollment | Ongoing |
| Classification | Natural History Study |
Scientific Background
Gait Dysfunction in PSP
...Overview
This observational study focuses on quantitative assessment of gait dysfunction and upper limb motor impairments in Progressive Supranuclear Palsy (PSP), leveraging advanced motion capture technology. PSP is a progressive neurodegenerative disorder characterized by vertical supranuclear gaze palsy, axial rigidity, postural instability, and akinesia[@ali2021]. Gait impairment is a hallmark of PSP and represents one of the most disabling features, contributing significantly to falls and functional disability.
The study aims to establish quantitative baselines that can inform therapeutic trials and improve patient stratification. Traditional clinical rating scales, while valuable, may not detect subtle changes in motor function that occur early in the disease process or respond minimally to investigational therapies. Quantitative motor assessment provides objective, reproducible measures that can track disease progression and treatment response with greater sensitivity than subjective clinical ratings[@nichols2016][@urschel2020].
Study Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT07136844 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | PSP (Progressive Supranuclear Palsy) |
| Sites | Belgium |
| Enrollment | Ongoing |
| Classification | Natural History Study |
Scientific Background
Gait Dysfunction in PSP
Gait impairment in PSP differs substantially from other parkinsonian syndromes. Patients characteristically exhibit a distinctive gait pattern that reflects the underlying neuropathology involving the brainstem, basal ganglia, and cortical regions[@schneider2017]. The progressive supranuclear palsy rating scale (PSPRS) includes gait and balance items that capture the progressive nature of these motor impairments.
Key gait characteristics include[@ali2021][@nichols2016]:
- Reduced gait velocity: Significantly slower walking speed compared to healthy controls (often 30-50% reduction)
- Reduced cadence: Fewer steps per minute indicating bradykinesia
- Increased double support time: Greater proportion of gait cycle spent with both feet on the ground, reflecting postural instability
- Abnormal antero-posterior sway: Excessive forward-backward trunk movement during walking
- Reduced arm swing: Bilateral reduction in arm swing due to axial rigidity
- Freezing of gait: Episodic inability to initiate movement, particularly in tight spaces
- Retropulsion: Tendency to fall backward, especially when suddenly stopped
Research using instrumented walkway analysis and 3D motion capture has demonstrated that spatiotemporal, kinematic, and kinetic gait measures effectively differentiate PSP patients from controls[@ali2021]. These objective measures correlate with clinical disease severity scores, suggesting they may serve as sensitive biomarkers for disease progression and treatment response.
Upper Limb Involvement
While PSP is primarily characterized by axial motor symptoms, upper limb bradykinesia and dystonia are common and contribute to functional impairment[@urschel2020]. Quantitative assessment of upper limb function provides valuable data on:
- Finger tapping speed and amplitude: Reduced frequency and amplitude compared to controls
- Pronation-supination movements: Slowing and reduced range of motion
- Grip strength: Often reduced, correlating with disease severity
- Precision handling: Impaired fine motor control affecting daily activities
- Dystonic posturing: Involuntary muscle contractions causing abnormal postures
- Reaction time: Prolonged response latencies indicating cognitive-motor integration deficits
These measures complement gait analysis by providing a comprehensive picture of motor involvement across body regions.
Assessment Methods
3D Motion Capture Analysis
The study employs a multi-camera motion capture system with reflective markers placed according to standardized protocols (e.g., Plug-in Gait model). This allows precise tracking of[@colombo2019]:
- Joint angles: Hip, knee, ankle, shoulder, elbow, and wrist angles throughout movement
- Center of mass trajectory: Body center of mass tracking for balance assessment
- Limb segment coordination: Inter-limb and intra-limb coordination patterns
- Temporal-spatial parameters: Step length, stride length, stance/swing phases
- Kinematic profiles: Velocity and acceleration of body segments
- Dynamic stability margins: Assessment of balance during perturbed walking
Instrumented Walkway
Force-sensitive walkway plates (e.g., GAITRite system) capture ground reaction forces during walking, enabling calculation of:
- Vertical ground reaction forces: Peak forces and loading rates
- Propulsive impulses: Forward propulsion generation
- Braking impulses: Deceleration during heel strike
- Mediolateral stability: Side-to-side sway during stance
- Weight distribution: Symmetry between limbs
- Center of pressure trajectory: Foot pressure mapping
Wearable Sensor Arrays
In addition to laboratory-based assessment, wearable inertial measurement units (IMUs) may be used to enable[@bhatt2019]:
- Continuous monitoring: Extended data collection in home environments
- Real-world gait patterns: Detection of natural walking in daily life
- Correlation with laboratory measures: Validation against gold-standard systems
- Free-living analysis: Assessment of gait during unstructured activity
- Fall detection: Automatic identification of fall events
- Activity classification: Differentiation between walking, standing, sitting
Standardized Clinical Ratings
Quantitative measures are correlated with established clinical scales:
- PSP Rating Scale (PSPRS): Disease-specific rating of functional impairment
- Unified Parkinson's Disease Rating Scale (UPDRS) Part III: Motor examination
- Berg Balance Scale: Functional balance assessment
- Timed Up and Go (TUG) test: Mobility and fall risk assessment
- Functional Independence Measure (FIM): Activities of daily living
- Montreal Cognitive Assessment (MoCA): Cognitive screening
Objectives
The study pursues several interconnected goals:
Characterize gait patterns in PSP subtypes: Differentiate between Richardsonson's syndrome, PSP-Parkinsonism, and Corticobasal Syndrome based on quantitative motor measures[@litvan2018]
Quantify upper limb bradykinesia and dystonia: Develop objective measures of upper limb motor involvement
Correlate motor findings with imaging biomarkers: Link quantitative motor data with MRI and PET findings to understand neuroanatomical correlates
Establish quantitative baselines for therapeutic trials: Create reference data for clinical trial design
Validate portable motion capture devices against laboratory systems: Assess accuracy of wearable devices for remote monitoringClinical Significance
Quantitative measurement of gait and motor function enables major advances in clinical care and research[@gnanapavan2019]:
Disease Monitoring
- Objective tracking: Quantify disease progression beyond clinical rating scales
- Sensitive detection: Identify subtle treatment effects in early-phase clinical trials
- Differential diagnosis: Distinguish PSP from other parkinsonian syndromes
- Subtype classification: Identify distinct motor phenotypes within PSP
Patient Stratification
- Subgroup identification: Patients with distinct motor phenotypes
- Enrichment strategies: Select patients most likely to show treatment response
- Fall risk prediction: Identify patients at highest risk for falls
- Prognostic markers: Predict functional decline trajectory
Therapeutic Development
- Sensitive outcome measures: Provide endpoints for interventional studies
- Biomarker validation: Correlate digital measures with clinical endpoints
- Regulatory acceptance: Support approval of digital outcome measures
- Personalized medicine: Enable tailored therapeutic approaches
Eligibility Criteria
Inclusion Criteria
- Clinically definite or probable PSP (per NINDS-SPSP criteria)[@litvan2018]
- Ability to walk independently or with minimal assistance (assistive device acceptable)
- Capacity to provide informed consent
- Age 40-85 years
- Willingness to attend multiple assessment sessions
Exclusion Criteria
- Significant orthopedic conditions affecting gait (e.g., severe arthritis, joint replacement)
- Severe visual impairment preventing safe ambulation
- Active psychiatric disease interfering with participation
- Inability to follow assessment protocols
- Significant comorbidities affecting life expectancy
- Prior deep brain stimulation surgery
- Active participation in other interventional trials
Biomarker Connections
Imaging Correlations
Motor findings are correlated with neuroimaging biomarkers:
Structural MRI
- Midbrain atrophy measurement
- Superior cerebellar peduncle atrophy
- Subcortical volume measurements
- PSP-specific imaging markers
Functional Imaging
- FDG-PET hypometabolism patterns
- Tau PET ligand binding
- Dopaminergic integrity (DAT-SPECT)
Diffusion Imaging
- White matter tract integrity
- Microstructural changes in motor pathways
Biochemical Markers
- Neurofilament light chain (NfL) in plasma/CSF
- Tau species (total and phosphorylated)
- Inflammatory markers
- Genetic markers (MAPT mutations)
Clinical Correlations
| Motor Measure | Clinical Correlation |
|--------------|---------------------|
| Gait velocity | PSPRS total score |
| Double support time | Falls frequency |
| Arm swing amplitude | UPDRS-III upper limb items |
| Timed Up and Go | Functional independence |
| Postural sway | Balance test scores |
Mechanistic Pathways
Mermaid diagram (expand to render)
Competitive Landscape
Quantitative motor assessment in PSP is being evaluated in multiple contexts:
| Initiative | Focus | Approach |
|------------|-------|----------|
| BioFINDER 2 | Biomarker validation | Multi-modal assessment |
| MOTIVE-PSP | Tau PET validation | Imaging correlation |
| This study | Quantitative baselines | 3D motion capture |
| Various pharma trials | Endpoint development | Digital outcomes |
This study aligns with broader efforts to develop objective biomarkers in PSP:
- BioFINDER 2 Study: Swedish cohort characterizing PSP biomarkers using tau PET and CSF analysis
- MOTIVE-PSP: Initiative to validate tau PET ligands in PSP
- FEEMSA Study: Focused on FEEMSA scale validation in PSP
- PSP Genetics Program: Understanding genetic modifiers of phenotype
- Progressive Supranuclear Palsy Clinical Trials: Multiple interventional studies requiring sensitive endpoints
See Also
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Corticobasal Syndrome](/diseases/corticobasal-syndrome)
- [Tauopathies](/mechanisms/tauopathies)
- [Deep Brain Stimulation](/treatments/deep-brain-stimulation)
External Links
- [ClinicalTrials.gov: NCT07136844](https://clinicaltrials.gov/study/NCT07136844)
- [PubMed Search: PSP Gait Analysis](https://pubmed.ncbi.nlm.nih.gov/?term=PSP+gait+analysis+motion+capture)
- [PSPA International](https://www.psp.org/)
References
[Ali et al., Laboratory based assessment of gait and balance impairment in patients with progressive supranuclear palsy (2021)](https://pubmed.ncbi.nlm.nih.gov/34461552/)
[Nichols et al., Quantitative gait analysis in atypical parkinsonian syndromes (2016)](https://pubmed.ncbi.nlm.nih.gov/27179263/)
[Colombo et al., Wearable sensors for assessment of movement disorders (2019)](https://doi.org/10.3390/s19020444)
[Gnanapavan et al., Biomarkers in progressive supranuclear palsy (2019)](https://pubmed.ncbi.nlm.nih.gov/30770531/)
[Litvan et al., Clinical diagnostic criteria for PSP: consensus recommendations (2018)](https://pubmed.ncbi.nlm.nih.gov/30594947/)
[Postuma et al., MDS consensus criteria for Parkinson's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25475930/)
[Bhatt et al., Digital biomarkers for neurodegenerative diseases (2019)](https://doi.org/10.1038/s41746-019-0098-5)
[Schneider et al., Motor subtypes in parkinsonian disorders (2017)](https://doi.org/10.3233/JPD-179001)
[Urschel et al., Quantitative motor assessment in PSP (2020)](https://pubmed.ncbi.nlm.nih.gov/32162049/)