This observational study investigates the neural correlates of complex walking tasks in patients with atypical Parkinsonian syndromes including Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Syndrome (CBS) using advanced neuroimaging and motion analysis techniques.
Gait dysfunction is a hallmark feature of atypical Parkinsonian syndromes that significantly impacts quality of life, increases fall risk, and contributes to disability. Understanding the neural basis of these gait abnormalities is critical for developing targeted therapies, optimizing deep brain stimulation, and identifying prognostic biomarkers.
| Field |
Value |
| NCT ID |
NCT06906276 |
| Status |
Recruiting |
| Study Type |
Observational |
| Conditions |
Atypical Parkinsonian Syndromes, PSP, MSA, CBS |
| Enrollment |
To be determined |
| Age Range |
Typically 40-85 years |
Atypical Parkinsonian syndromes (APS) share common gait features with Parkinson's disease but exhibit distinct patterns that reflect their underlying pathology:
Progressive Supranuclear Palsy (PSP):
- Early postural instability with backward falls
- Gait freezing more prominent than PD
- Reduced stride length and step height
- Axial rigidity affecting trunk movement
- "Rocket sign" - rapid retropulsion when pulled backward
Multiple System Atrophy (MSA):
- Wide-based, unsteady gait
- Cerebellar ataxia component (especially MSA-C)
- Orthostatic hypotension affecting walking
- Reduced balance reactions
Corticobasal Syndrome (CBS):
- Asymmetric gait disturbance
- Apraxia of gait
- Limb dystonia affecting walking
- Cortical sensory loss affecting balance
Gait abnormalities in APS contribute significantly to:
- Fall risk: 50-70% of patients experience falls
- Functional disability: Loss of independence in daily activities
- Caregiver burden: Requires assistance with mobility
- Institutionalization: Often leads to nursing home placement
- Psychological impact: Fear of falling, depression
Understanding the neural basis of gait dysfunction in APS offers several benefits:
Diagnostic Value:
- Differentiate APS subtypes from each other
- Identify distinct neural circuits involved
- Support early diagnosis
Therapeutic Targeting:
- Inform deep brain stimulation target selection
- Guide rehabilitation strategies
- Identify novel therapeutic targets
Prognostic Information:
- Predict disease progression
- Identify biomarkers for clinical trials
- Monitor treatment response
This study specifically examines complex walking tasks, which are more sensitive to subtle neurological dysfunction than simple walking:
Task Categories:
- Dual-task walking: Walking while performing cognitive or motor tasks
- Obstacle negotiation: Walking over obstacles
- Turning: 360-degree turns, pivot turns
- Variable surfaces: Walking on compliant surfaces
- Stair climbing: Ascending and descending stairs
Why Complex Tasks Matter:
- More demanding neural control
- Earlier detection of dysfunction
- Better correlates with real-world mobility
- Greater impact on daily function
The study employs multiple assessment modalities:
Functional MRI (fMRI):
- Brain activation patterns during imagined walking
- Regional activation in frontal, parietal, and cerebellar regions
- Connectivity analysis between motor planning areas
Gait Kinematics:
- Spatiotemporal parameters (stride length, cadence, velocity)
- Joint angles and movement symmetry
- Center of mass trajectory
Clinical Correlation:
- MDS-UPDRS motor assessment
- PSP Rating Scale (PSPRS)
- UMSARS for MSA
- Functional independence measures
Neuroimaging Endpoints:
- Regional brain connectivity during movement
- Structural MRI correlates
- Diffusion tensor imaging of white matter tracts
Clinical Endpoints:
- Relationship to disease duration and severity
- Comparison across APS subtypes (PSP vs MSA vs CBS)
- Falls frequency and risk assessment
- Quality of life measures
PSP presents with distinctive gait abnormalities that reflect midbrain and basal ganglia pathology:
Clinical Features:
- Early postural instability and falls (within first year)
- Gait freezing, especially when turning
- Reduced stride length
- Axial rigidity affecting trunk movement
- Vertical supranuclear gaze palsy
Neural Correlates:
- Midbrain atrophy
- Globus pallidus degeneration
- Frontal lobe involvement
- Cerebellar output disruption
This Study's Relevance:
Understanding the neural basis of these deficits could inform:
- Deep brain stimulation target selection (PPN vs STN)
- Rehabilitation strategies focusing on balance training
- Prognostic biomarkers for fall risk
MSA gait reflects both parkinsonian and cerebellar involvement:
Clinical Features:
- Wide-based, ataxic gait
- Cerebellar incoordination (especially MSA-C)
- Orthostatic hypotension causing dizziness
- Early autonomic failure
Neural Correlates:
- Brainstem degeneration
- Cerebellar white matter loss
- Putaminal atrophy
- Autonomic center involvement
CBS typically presents with asymmetric gait disturbance:
Clinical Features:
- Unilateral limb rigidity and dystonia
- Apraxia of gait
- Cortical sensory loss
- Myoclonus affecting balance
Neural Correlates:
- Asymmetric cortical atrophy
- Basal ganglia lesions
- White matter disconnection
Functional MRI (fMRI):
- Measures blood oxygen level dependent (BOLD) signal
- Identifies brain regions active during movement
- Can use imagined walking paradigms
Structural MRI:
- Voxel-based morphometry (VBM)
- Cortical thickness measurements
- Region-of-interest volumetric analysis
Diffusion Tensor Imaging (DTI):
- White matter tract integrity
- Structural connectivity analysis
- Identification of disconnection patterns
Motor Assessment Scales:
- MDS-UPDRS Part III (motor examination)
- PSP Rating Scale (PSPRS)
- UMSARS (Unified MSA Rating Scale)
- Tinetti Balance and Gait Assessment
Gait Analysis:
- Timed Up and Go (TUG) test
- 10-Meter Walk Test
- 6-Minute Walk Test
- Gait variability parameters
Functional Measures:
- Functional Independence Measure (FIM)
- Berg Balance Scale
- Fall frequency diary
Dual-task paradigms involve performing two tasks simultaneously. In gait studies, this typically means walking while performing a cognitive task (e.g., counting backward, naming animals):
Clinical Significance:
- Dual-task cost predicts fall risk
- Sensitive to executive dysfunction
- Reflects limited attentional resources
Expected Findings in APS:
- Greater dual-task interference than PD
- Different patterns across subtypes
- Correlation with frontal lobe involvement
The neural basis of dual-task interference involves:
- Attentional networks: Frontal parietal networks
- Executive function: Prefrontal cortex
- Task switching: Anterior cingulate cortex
- Motor planning: Supplementary motor area
Understanding gait-related neural activity informs surgical targeting:
Potential Targets:
- Subthalamic nucleus (STN)
- Globus pallidus interna (GPi)
- Pedunculopontine nucleus (PPN)
- Fornix (for memory-related aspects)
Target Selection:
- Gait freezing may respond to PPN stimulation
- Bradykinesia responds to STN
- Axial symptoms remain challenging
Neural correlates guide rehabilitation approaches:
Balance Training:
- Address specific deficits identified in imaging
- Customize to APS subtype
- Progressive difficulty
Assistive Devices:
- Selection based on gait pattern analysis
- Canes, walkers, wheelchairs
- Physical therapy protocols
The study may identify imaging biomarkers for:
- Disease progression
- Treatment response
- Clinical trial endpoints
- Prognostication
Walking in MRI:
- Real walking is difficult to assess in MRI scanners
- Use of imagined walking paradigms
- Treadmill walking with compatible MRI equipment
Disease Heterogeneity:
- APS subtypes have different pathology
- Disease stage affects findings
- Variable symptom presentation
Control Subjects:
- Need for age-matched controls
- Inclusion of PD patients for comparison
- Normal aging controls
This research could inform:
- Patient selection: Identify neural phenotypes for trials
- Endpoint development: Imaging biomarkers as endpoints
- Mechanistic studies: Understand drug effects on neural circuits
Understanding individual neural patterns could guide:
- Individualized rehabilitation
- Targeted neuromodulation
- Precision medicine approaches