Characterizing Gait Abnormalities in PSP and Parkinsonian Disorders
| Field |
Details |
| NCT Number |
NCT02994719 |
| Title |
Gait Pattern Analysis in Neurological Disease |
| Status |
RECRUITING |
| Study Type |
Observational (Case-Control) |
| Sponsor |
Beth Israel Deaconess Medical Center |
| Principal Investigator |
Veronique Vanderhorst, MD, PhD |
| Location |
Boston, Massachusetts, USA |
Gait dysfunction is a hallmark of Progressive Supranuclear Palsy (PSP), presenting distinct patterns that differentiate it from other parkinsonian disorders. Key gait characteristics in PSP include:
- Reduced gait velocity - significantly slower than age-matched controls
- Increased stride variability - reflecting impaired postural control
- Reduced arm swing - bilateral and often symmetric
- Forward flexion - truncal stooping during walking
- Retropulsion - tendency to fall backward
- Wide-based gait - increased stance phase width
This study aims to identify speed-dependent gait measures that can objectively quantify these abnormalities and potentially serve as biomarkers for disease progression and therapeutic response.
- Identify speed-dependent gait measures in parkinsonian disorders
- Determine whether gait patterns differ between:
- Parkinson's Disease (PD)
- Progressive Supranuclear Palsy (PSP)
- Multiple System Atrophy (MSA)
- Corticobasal Degeneration (CBD)
- Vascular Parkinsonism
- Other parkinsonian syndromes
- Compare patient gait patterns to age- and sex-matched healthy controls
- Primary: Gait analysis using pressure sensors
- Optional interventions at second visit:
- Anti-Parkinson medication challenge (Carbidopa/levodopa, pramipexole, ropinirole, amantadine, tolcapone, entacapone)
- Deep Brain Stimulation evaluation
- Age 18-85 years
- Presence of at least 2 of the following (UK PD Brain Bank Criteria):
- Bradykinesia
- Rest tremor
- Rigidity
- Postural instability
- Subjects with assistive devices (canes, walkers) are eligible
- Healthy subjects with no complaints regarding difficulty walking
- Alternative explanation for parkinsonism (head trauma, drug-induced)
- Currently treated for major medical illness requiring recent hospitalization (<14 days)
- Currently participating in another clinical study with intervention arm
- Inability to consent due to cognitive impairment without legally authorized representative
- Cardiac/pulmonary conditions limiting ability to safely walk
Includes subjects with:
- Parkinson's Disease
- Indeterminate parkinsonism
- Atypical Parkinsonisms:
- Vascular Parkinsonism
- Multiple System Atrophy (MSA)
- Progressive Supranuclear Palsy (PSP)
- Normal Pressure Hydrocephalus
- Corticobasal Degeneration (CBD)
- Ataxia syndromes
- Huntington Disease
- Healthy controls
- Objective Measurement: Quantitative gait parameters provide objective disease progression markers
- Differential Diagnosis: Distinct gait patterns may help differentiate PSP from PD
- Therapeutic Response: Gait measures could assess response to treatments
- Fall Risk: Identifying gait abnormalities associated with fall risk
- Reduced stride length with preserved cadence
- Bilateral reduced arm swing (early feature)
- Postural instability leading to backward falls
- Freezing of gait in advanced disease
- Response to levodopa typically minimal (distinguishes from PD)
Progressive supranuclear palsy (PSP) produces characteristic gait disturbances through degeneration of specific neural substrates:
Basal Ganglia Dysfunction: The globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr) show early pathology in PSP, leading to:
- Impaired automatic motor sequencing
- Reduced stride length generation
- Axial rigidity affecting trunk mobility
- Bradykinesia of gait initiation
Brainstem Involvement: The pedunculopontine nucleus (PPN), critical for gait initiation and postural control, degenerates in PSP:
- Impaired postural adjustments
- Reduced automaticity of locomotion
- Freezing of gait phenomenon
- Gait ignition failure
Frontal Lobe Contribution: PSP produces frontal lobe atrophy affecting:
- Executive motor control
- Velocity scaling of gait
- Adaptive responses to environmental demands
- Dual-task gait performance
The study employs instrumented walkway analysis to capture:
| Parameter |
PSP Characteristic |
Clinical Significance |
| Gait Velocity |
Severely reduced (0.3-0.5 m/s) |
Global motor impairment |
| Stride Length |
Markedly shortened (<60 cm) |
Basal ganglia dysfunction |
| Cadence |
Preserved or slightly reduced |
Differentiates from PD |
| Double Support Time |
Increased (>35% stance) |
Postural instability |
| Swing Time Variability |
Elevated (CV >10%) |
Fall risk predictor |
| Arm Swing |
Severely reduced bilaterally |
Early diagnostic marker |
| Trunk Rotation |
Reduced |
Axial rigidity |
The novel aspect of this study examines how gait parameters change across walking speeds:
Healthy Controls: Linear increase in velocity through stride length modulation while cadence remains relatively stable
PSP Patients:
- Reduced stride length at all speeds
- Impaired velocity scaling
- Earlier onset of gait dysfunction at slower speeds
- Preserved speed-dependent modulation but at reduced magnitude
This approach may reveal:
- Subtle gait abnormalities not apparent at self-selected speed
- Differentiate disease subtypes
- Quantify reserve capacity in gait control systems
| Feature |
PSP |
PD |
| Arm swing |
Bilateral reduction early |
Unilateral, asymmetric early |
| Stride length |
Severely reduced |
Moderate reduction |
| Gait initiation |
Often normal |
Often impaired (shuffling) |
| Turning |
En bloc turning |
Shuffling turns |
| Postural falls |
Early, backward |
Late, any direction |
| Response to levodopa |
Minimal |
Good initially |
| Feature |
PSP |
MSA |
| Gait pattern |
Cautious, wide-based |
Shuffling with festination |
| Stride variability |
Increased |
Very high |
| Freezing |
Less common |
More common |
| Autonomic involvement |
Variable |
Prominent early |
| Feature |
PSP |
CBD |
| Symmetry |
Symmetric |
Asymmetric |
| Arm swing |
Bilaterally reduced |
Unilaterally reduced |
| Gait initiation |
Variable |
Often延迟 |
The study utilizes pressure-sensitive walkway technology:
Walkway Platforms:
- GAITrite® systems (standard in research)
- Zebris® FDM-T treadmill system
- Protokinetics® PKMAS
- Bertec® force instrumented treadmill
Technical Specifications:
| Parameter |
Specification |
Clinical Relevance |
| Spatial resolution |
1.27 mm |
Foot placement accuracy |
| Temporal resolution |
100-200 Hz |
Timing accuracy |
| Active sensor area |
Variable (4-8m length) |
Full gait capture |
| Pressure range |
Up to 200 psi |
Weight-bearing accuracy |
| Data rate |
Up to 500 Hz |
Real-time capture |
Primary Measures:
-
Temporal Parameters:
- Stride time (time for complete gait cycle)
- Step time (time between foot strikes)
- Swing time (foot in air)
- Stance time (foot on ground)
- Single support time (contralateral foot in air)
- Double support time (both feet on ground)
-
Spatial Parameters:
- Stride length (distance covered per gait cycle)
- Step length (heel strike to opposite heel strike)
- Step width (mediolateral foot placement)
- Foot rotation angle
- Toe-out angle
-
Spatiotemporal Parameters:
- Gait velocity (comfortable walking speed)
- Cadence (steps per minute)
- Variability measures (coefficient of variation)
Center of Pressure (COP):
- Anterior-posterior COP excursion
- Medial-lateral COP excursion
- COP velocities
- COP trajectory symmetry
Balance Assessment:
- Sway area
- Velocity of sway
- Frequency distribution
- Multi-scale entropy
The basal ganglia play a central role in gait control:
Direct Pathway (Go):
- Facilitates voluntary movements
- Promotes ongoing motor programs
- Facilitates gait initiation
- Reduced in PSP leading to akinesia
Indirect Pathway (Stop):
- Inhibits competing movements
- Prevents unwanted movement
- Critical for stopping/gait adjustment
- Overactive in PSP
Hyperdirect Pathway:
- Rapid feedback inhibition
- Error detection
- Adaptive modifications
Pedunculopontine Nucleus (PPN):
- Central pattern generator for locomotion
- Cholinergic neurons for modulation
-Degeneration in PSP
- Associated with gait freezing
Cuneate and Gracile Nuclei:
- Sensory integration
- Proprioceptive processing
- Postural adjustments
The cerebellum coordinates gait:
Spinocerebellar Pathways:
- Proprioceptive feedback
- Motor adaptation
- Error correction
Cerebello-thalamo-cortical loops:
- Motor learning
- Automation of gait
Supplementary Motor Area (SMA):
- Internal movement generation
- Bilateral coordination
- Impaired in PSP
Pre-SMA:
- Sequence planning
- Gait initiation
- Abnormal in PSP
Dorsolateral Prefrontal Cortex:
- Executive function
- Dual-task performance
- Planning gait modifications
Gait parameters can serve as biomarkers:
Validation Requirements:
- Reliability (test-retest consistency)
- Validity (measures what it claims)
- Sensitivity to change
- Specificity for condition
- Responsiveness to intervention
Diagnostic Aid:
- Differentiating parkinsonian disorders
- Early detection
- Subtype classification
Progression Marker:
- Disease severity staging
- Progression rate
- Prognostication
Therapeutic Response:
- Medication effects
- Surgical outcomes (DBS)
- Rehabilitation benefits
- Not FDA-approved biomarkers
- Research use only
- Potential for clinical implementation
Wearable Sensors:
- Inertial measurement units
- Accelerometers
- Gyroscopes
- Magnetometers
Home Monitoring:
- Continuous monitoring
- Fall detection
- Activity tracking
Machine Learning:
- Pattern recognition
- Subtype classification
- Predictive modeling
- Earlier diagnosis
- Personalized intervention
- Telehealth integration
The study utilizes pressure-sensitive walkway technology:
- Walkway Dimensions: Minimum 6 meters length to capture steady-state gait
- Sampling Rate: 100-200 Hz for accurate temporal detection
- Spatial Resolution: <1 mm for precise foot placement measurement
Conditions Tested:
- Preferred speed: Comfortable self-selected walking
- Fast speed: Maximum comfortable speed without running
- Slow speed: Slow as possible without stopping
- Dual-task: Walking while performing cognitive task (serial 7s)
- Treadmill (subset): Standardized speed assessment
Repeatability Measures: Three trials per condition to establish reliability
- MDS-UPDRS: Complete motor examination
- PSPRS: PSP Rating Scale
- MoCA: Cognitive screening
- FR: Functional reach test
- TUG: Timed up and go test
The medication challenge component evaluates dopaminergic responsiveness:
Levodopa Challenge: Standard carbidopa/levodopa (25/100 mg) up to 200% of current dose
Dopamine Agonists: Pramipexole or ropinirole equivalent
Rationale:
- Differentiate parkinsonian disorders
- Identify PD patients who may benefit from DBS
- Quantify levodopa-responsive component
- Predict surgical outcomes
- Baseline gait assessment
- 60-90 minutes post-medication
- Peak-dose assessment
- Comparison of pre/post parameters
Quantitative gait analysis offers advantages as a biomarker:
- Objective: No subjective interpretation required
- Continuous: Provides interval-scale data
- Repeatable: Low test-retest variability
- Non-invasive: No radiation or invasive procedures
- Cost-effective: Relatively inexpensive to implement
- Sensitive: Detects subtle changes
This study may establish gait parameters for:
- Early diagnosis (pre-motor detection)
- Disease staging and progression monitoring
- Therapeutic response assessment
- Fall risk stratification
- Prognostication
Successful validation could lead to:
- Routine clinical gait assessment for movement disorder patients
- Telemedicine-enabled remote monitoring
- Home-based gait monitoring with wearable sensors
- Integration with digital health platforms
Historical Context:
| Study |
Year |
Key Finding |
| (non) |
1990s |
First quantitative gait studies in PSP |
| Thompson et al. |
2007 |
Reduced gait velocity in PSP vs. PD |
| Baba et al. |
2012 |
Turning characteristics distinguish PSP |
| Latt et al. |
2009 |
Stride variability predicts falls |
| Chien et al. |
2013 |
Longitudinal gait changes |
Current Understanding:
- PSP gait characteristics are distinct from PD
- Quantitative measures can aid diagnosis
- Progression can be tracked longitudinally
- Falls correlate with specific parameters
Test-Retest Reliability:
- Moderate-to-high reliability for most parameters
- Best reliability for gait velocity and stride length
- Moderate reliability for variability measures
- Requires standardized protocols
Minimal Clinically Important Difference (MCID):
- Not well-established for most parameters
- Estimated at 10-15% change
- Depends on baseline function
Laboratory Setup:
- Pressure-sensitive walkway
- Video recording system
- Safety equipment (harness, assist)
- Climate control
Data Processing:
- Dedicated software packages
- Quality control procedures
- Standardized analysis protocols
Personnel:
- Trained technicians
- Physical therapist supervision
- Data analyst
Initial Investment:
- Walkway systems: $15,000-50,000
- Video equipment: $2,000-10,000
- Software licenses: $1,000-5,000
Operational Costs:
- Consumables: minimal
- Maintenance: $1,000-3,000/year
- Personnel: one FTE per lab
Collection Standards:
- Regular calibration
- Standardized instructions
- Multiple trials
- Quality review protocols
Analysis Standards:
- Automated quality checks
- Manual over-read protocols
- Inter-rater reliability
¶ Standardization Efforts
International Efforts:
- Movement Disorder Society consensus
- Genie in the Gait collaboration
- Standardization committees
¶ Advancing Understanding
This study contributes to:
- Basic Science: Characterizing gait pathophysiology in different parkinsonisms
- Biomarker Development: Validating quantitative gait as progression marker
- Clinical Practice: Establishing normative data for comparison
- Therapeutic Trials: Providing sensitive outcome measures
Data sharing may enable:
- Multi-center validation studies
- Machine learning for pattern recognition
- Subtype classification algorithms
- Predictive modeling for individualized prognosis
Clinical Integration:
- Time requirements (30-45 minutes)
- Space requirements (10-meter walkway)
- Staff training (4-8 hours)
- Quality control procedures
Reimbursement:
- Limited insurance coverage
- Research/clinical trial use
- Fee-for-service in some settings
Practical Barriers:
- Equipment cost
- Space requirements
- Staff expertise
- Time constraints
Knowledge Barriers:
- Interpretation expertise
- Reference data availability
- Clinical guidelines
Inertial Measurement Units (IMUs):
- Accelerometers
- Gyroscopes
- Magnetometers
- Barometric altimeters
Clinical Applications:
- Continuous monitoring
- Home-based assessment
- Fall detection
- Activity tracking
Validation Status:
- Multiple studies published
- Moderate agreement with instrumented walkways
- Emerging clinical use
Available Applications:
- Step counter apps
- Gait analysis apps
- Balance assessment apps
- Fall detection apps
Accuracy:
- Variable accuracy
- Not validated for clinical use
- Research applications only
Machine Learning Applications:
- Feature extraction
- Pattern recognition
- Classification algorithms
- Predictive modeling
Clinical Potential:
- Differential diagnosis
- Prognostication
- Treatment response prediction
Current Limitations:
- Need for large datasets
- Validation requirements
- Interpretability challenges