Brain Activity During Complex Walking in Atypical Parkinsonian Syndromes (NCT06906276)

Overview

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

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

• Wide-based, unsteady gait
• Cerebellar ataxia component (especially MSA-C)
• Orthostatic hypotension affecting walking
• Reduced balance reactions

• 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:

Scientific 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

• Inform deep brain stimulation target selection
• Guide rehabilitation strategies
• Identify novel therapeutic targets

• 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:

Why 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

• Spatiotemporal parameters (stride length, cadence, velocity)
• Joint angles and movement symmetry
• Center of mass trajectory

• 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

• 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

• Midbrain atrophy
• Globus pallidus degeneration
• Frontal lobe involvement
• Cerebellar output disruption

• 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

• 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

• 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

• Voxel-based morphometry (VBM)
• Cortical thickness measurements
• Region-of-interest volumetric analysis

• 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

• Timed Up and Go (TUG) test
• 10-Meter Walk Test
• 6-Minute Walk Test
• Gait variability parameters

• 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

• 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:

Clinical 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)

• 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

• 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

• APS subtypes have different pathology
• Disease stage affects findings
• Variable symptom presentation

• Need for age-matched controls
• Inclusion of PD patients for comparison
• Normal aging controls

Future Directions

Extension to Clinical Trials

This research could inform:

Personalized Medicine

Understanding individual neural patterns could guide:

• Individualized rehabilitation
• Targeted neuromodulation
• Precision medicine approaches

Related Pages

Related Conditions

• [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)

Related Topics

• [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

Related Hypotheses

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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: