Gait Analysis Parameter and Upper Limb Evaluation in Neurological Disease

Overview

Overview

The ActiLiège-Adult study is a prospective, longitudinal, observational study designed to collect natural history data on adult patients with neurological or metabolic diseases affecting movement. This study focuses on characterizing gait parameters and upper limb function in conditions including PSP, Parkinson's disease, and other movement disorders.

Trial Details

| Field | Value |
|-------|-------|
| NCT Number | NCT07136844 |
| Status | Recruiting |
| Phase | Observational |
| Sponsor | Centre Hospitalier Universitaire de Liège |
| Location | Liège, Belgium |
| Start Date | 2024 |
| Estimated Completion | 2027 |

Study Objectives

The primary objectives of this study include:

Relevance to PSP

Progressive supranuclear palsy is characterized by early gait disturbances, postural instability, and progressive bradykinesia. Quantitative assessment of gait parameters using wearable sensors provides objective measures that can:

• Track disease progression more precisely than clinical scales
• Identify early markers of gait dysfunction
• Monitor treatment response in clinical trials
• Distinguish PSP from other parkinsonian syndromes

Methodology

The study employs:

• Wearable sensors for continuous gait monitoring
• Quantitative movement analysis systems
• Standardized clinical assessments including UPDRS and PSP-specific scales
• Longitudinal follow-up to characterize disease progression

References

Clinical Background: Gait Disorders in PSP

Pathophysiology of Gait Disturbance in PSP

Progressive supranuclear palsy (PSP) is a 4R-tauopathy characterized by prominent midbrain atrophy and accumulation of neurofibrillary tangles in subcortical structures. The gait disturbance in PSP is distinct from other parkinsonian syndromes and reflects the specific pattern of neurodegeneration.

Key brain regions affected in PSP that contribute to gait dysfunction include:

• Substantia nigra pars compacta: Dopaminergic cell loss affects motor initiation and coordination
• Globus pallidus internus: Excessive inhibitory output disrupts voluntary movement
• Red nucleus and pedunculopontine nucleus: Damage to these structures impairs postural control and locomotion
• Superior cerebellar peduncle: Cerebellar output disruption affects movement coordination
• Frontal cortex: Executive dysfunction contributes to gait apraxia and impaired motor planning

• Broad-based gait: Widened stance for increased stability
• Reduced stride length: Markedly decreased step length compared to PD
• Impaired turning: Characteristic "en bloc" turning where the entire body rotates together
• Early falls: Forward falling due to axial rigidity and postural instability
• Absence of arm swing: Reduced or absent arm swing even in early stages

Quantitative Gait Assessment Technologies

Wearable Inertial Sensors

Modern gait analysis utilizes body-worn inertial measurement units (IMUs) containing:

• Accelerometers: Measure linear acceleration in three axes (x, y, z)
• Gyroscopes: Quantify angular velocity during movement
• Magnetometers: Provide absolute orientation in Earth's magnetic field

• Spatiotemporal parameters (stride length, cadence, velocity)
• Gait variability metrics (step time variability, swing time variability)
• Symmetry indices (left-right asymmetries in timing and coordination)
• Phase coordination (timing relationships between left and right steps)

Instrumented Walkway Systems

Pressure-sensitive walkways (e.g., GAITRite, Zeno walkway) provide:

• Precise footfall timing and positioning
• Foot pressure distribution analysis
• Center of pressure trajectory
• Step length and width measurements
• Real-time visualization of gait patterns

3D Motion Capture Systems

For detailed biomechanical analysis:

• Marker-based optical tracking (Vicon, OptiTrack)
• Depth camera systems (Kinect, Azure Kinect)
• Provides joint angle trajectories
• Enables kinematic and kinetic analysis

Upper Limb Assessment in Neurodegeneration

Upper limb function assessment is critical in PSP and related disorders:

Motor Function Tests

Bradykinesia Assessment

Bradykinesia in the upper limb manifests as:

• Reduced movement amplitude
• Decreased movement speed
• Increased movement latency
• Fatigue during repeated movements
• Lack of movement automaticity

• Finger tapping tasks (frequency, amplitude, rhythm)
• Pronation-supination movements
• Alternating hand movements
• Complex sequential motor tasks

Rigidity Assessment

Axial and appendicular rigidity can be quantified using:

• Myotonometry (muscle tone measurement)
• Biomechanical torque measurement
• Electromyographic analysis of resting muscle activity

Clinical Relevance of Quantitative Measures

Advantages Over Clinical Scales

| Feature | Standard Clinical Scales | Quantitative Movement Analysis |
|---------|--------------------------|--------------------------------|
| Objectivity | Moderate | High |
| Sensitivity to change | Limited | Excellent |
| Detectable differences | Gross | Subtle |
| Longitudinal tracking | Periodic | Continuous |
| Standardization | Variable | High |
| Reproducibility | Moderate | Excellent |

Applications in Clinical Trials

Quantitative gait and upper limb assessment provides:

• Primary endpoints for disease-modifying trials
• Biomarkers for treatment response
• Subgroup identification based on motor phenotypes
• Natural history characterization

Disease Progression Monitoring

Quantitative measures enable:

• Detection of progression before clinical worsening
• Objective quantification of rate of decline
• Identification of prognostic biomarkers
• Personalized outcome prediction

Scientific Rationale for the ActiLiège-Adult Study

Natural History Importance

Understanding the natural history of PSP is essential for:

Cross-Disease Comparisons

The ActiLiège-Adult study's multi-disease approach allows:

• Phenotypic comparison: How does PSP gait differ from PD, CBS, and MSA?
• Diagnostic differentiation: Can quantitative measures distinguish tauopathies from synucleinopathies?
• Shared mechanisms: What common pathways underlie movement dysfunction across disorders?
• Biomarker generalization: Do promising biomarkers generalize across conditions?

Biomarker Discovery

Quantitative movement data can reveal:

• Gait signatures specific to each disease
• Progression markers that predict clinical decline
• Early markers detectable before overt symptoms
• Treatment-responsive outcomes for clinical trials

Methodology Details

Sensor Placement and Configuration

Standard sensor placement for comprehensive movement analysis:

Data Processing Pipeline

Raw IMU Data → Signal Filtering → Event Detection → Feature Extraction → Statistical Analysis

Key Processing Steps

Clinical Assessment Integration

The study combines quantitative measures with standard clinical evaluations:

• MDS-UPDRS: Comprehensive parkinsonism assessment
• PSPRS: PSP-specific severity rating
• MoCA: Cognitive screening
• BBS: Balance assessment
• TUG: Functional mobility test
• ADL scales: Functional independence measures

Eligibility Criteria Details

Inclusion Criteria Rationale

Exclusion Criteria Rationale

Future Directions

Clinical Implementation

Quantitative movement analysis will enable:

Technology Development

Emerging technologies include:

• Soft robotics: Wearable assistance devices
• AI-powered analysis: Automated interpretation pipelines
• Edge computing: On-device processing for real-time feedback
• Multi-modal integration: Combining wearable and ambient sensing

References