Overview
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This observational study investigates the neural correlates of complex walking tasks in patients with [atypical Parkinsonian syndromes](/diseases/atypical-parkinsonian-syndromes) including [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy) (PSP), [Multiple System Atrophy](/diseases/multiple-system-atrophy) (MSA), and [Corticobasal Syndrome](/diseases/corticobasal-syndrome) (CBS) using advanced neuroimaging and motion analysis techniques["@nct"].
...Overview
Mermaid diagram (expand to render)
This observational study investigates the neural correlates of complex walking tasks in patients with [atypical Parkinsonian syndromes](/diseases/atypical-parkinsonian-syndromes) including [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy) (PSP), [Multiple System Atrophy](/diseases/multiple-system-atrophy) (MSA), and [Corticobasal Syndrome](/diseases/corticobasal-syndrome) (CBS) using advanced neuroimaging and motion analysis techniques["@nct"].
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.
Study Details
| 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 |
Background: Gait in Atypical Parkinsonian Syndromes
Gait Dysfunction Across APS Subtypes
Atypical Parkinsonian syndromes (APS) share common gait features with [Parkinson's disease](/diseases/parkinsons-disease) but exhibit distinct patterns that reflect their underlying pathology[@gilman2008]:
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
Impact on Quality of Life
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, depressionScientific Rationale
Why Study Neural Correlates?
Understanding the neural basis of gait dysfunction in APS offers several benefits[@snijders2011]:
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
Complex Walking Tasks
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 stairsWhy Complex Tasks Matter:
- More demanding neural control
- Earlier detection of dysfunction
- Better correlates with real-world mobility
- Greater impact on daily function
Study Objectives
Primary Endpoints
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
Secondary Endpoints
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
Relevance to Specific Conditions
PSP
PSP presents with distinctive gait abnormalities that reflect midbrain and basal ganglia pathology[@hoglinger2017]:
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
MSA gait reflects both parkinsonian and cerebellar involvement[@gilman2008]:
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
CBS typically presents with asymmetric gait disturbance[@armstrong2013]:
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
Assessment Methods
Neuroimaging Techniques
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
Clinical Measures
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 Gait Interference
What is Dual-Task Interference?
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)[@delval2014]:
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
Neural Mechanisms
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 areaClinical Implications
Deep Brain Stimulation
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
Rehabilitation
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
Biomarker Development
The study may identify imaging biomarkers for:
- Disease progression
- Treatment response
- Clinical trial endpoints
- Prognostication
Research Challenges
Methodological Considerations
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
Future Directions
Extension to Clinical Trials
This research could inform:
Patient selection: Identify neural phenotypes for trials
Endpoint development: Imaging biomarkers as endpoints
Mechanistic studies: Understand drug effects on neural circuitsPersonalized Medicine
Understanding individual neural patterns could guide:
- Individualized rehabilitation
- Targeted neuromodulation
- Precision medicine approaches
Related Pages
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
- [Multiple System Atrophy](/diseases/multiple-system-atrophy)
- [Corticobasal Syndrome](/diseases/corticobasal-syndrome)
- [Atypical Parkinsonian Syndromes](/diseases/atypical-parkinsonian-syndromes)
- [Gait Analysis in Neurological Disease](/diagnostics/gait-analysis)](/diagnostics)
- [Parkinsonian Gait](/symptoms/parkinsonian-gait)](/proteins/parkin)
- [Postural Instability](/symptoms/postural-instability)
Research Methods
- [Functional MRI](/techniques/functional-mri)
- [Diffusion Tensor Imaging](/techniques/diffusion-tensor-imaging)
- [Motion Analysis](/techniques/motion-analysis)
External Links
- [ClinicalTrials.gov - NCT06906276](https://clinicaltrials.gov/study/NCT06906276)
- [CurePSP Foundation](https://curepsp.org/)
- [MSA Trust](https://www.msatrust.org.uk/)](/institutions/msa-trust)
- [Corticobasal Degeneration International](https://www.cbdinternational.org/)
References
[NCT06906276 - Brain Activity During Complex Walking (n.d.)](https://clinicaltrials.gov/study/NCT06906276)
[Höglinger et al., Clinical diagnosis of progressive supranuclear palsy (2017)](https://pubmed.ncbi.nlm.nih.gov/28692957/)
[Gilman et al., Consensus criteria for MSA (2008)](https://pubmed.ncbi.nlm.nih.gov/18695218/)
[Armstrong et al., Corticobasal syndrome (2013)](https://pubmed.ncbi.nlm.nih.gov/23439137/)
[Snijders et al., Neuroimaging of gait (2011)](https://pubmed.ncbi.nlm.nih.gov/22051924/)
[Delval et al., Gait and cognition (2014)](https://pubmed.ncbi.nlm.nih.gov/25063503/)From the [SciDEX Exchange](/exchange) — scored by multi-agent debate
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Pathway Diagram
The following diagram shows the key molecular relationships involving Brain Activity During Complex Walking in Atypical Parkinsonian Syndromes (NCT06906276) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)