Developing Novel Non-invasive Electrophysiological Biomarkers of Dysfunction in Spinal and Cortical Pathways and Sensorimotor Impairments in Motor Neurone Disease
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- Non-invasive recording of the SC functional neuro-electric activity
Study Overview
Brief Summary
Substantial variability exists in the onset, and rate of degeneration across individuals with Motor Neurone Disease (MND) or Amyotrophic Lateral Sclerosis (ALS). This variability requires biomarkers that accurately classify and reliably track clinical subtypes as the disease progresses. Degeneration occurs in the brain and spinal cord, however, non-invasive diagnosis of spinal cord function remains highly challenging due to its unique alignment in spine. Disruption of complex spinal and cortical circuits that transmit and process neural signals for position sense and movement has not been adequately captured in the neurophysiological profiling of ALS patients. The overarching aim of this study is to reveal and quantify the extent of change in the sensorimotor integration and its potential contribution to network disruption in ALS.
Detailed Description
Background:
Substantial variability exists in the onset, and rate of degeneration across individuals with Motor Neurone Disease (MND) or Amyotrophic Lateral Sclerosis (ALS). This variability requires biomarkers that accurately classify and reliably track clinical subtypes as the disease progresses. Degeneration occurs in the brain and spinal cord, however, non-invasive diagnosis of spinal cord function remains highly challenging due its unique alignment in the spine. Disruption of complex spinal and cortical circuits that transmit and process neural signals for position sense and movement has not been adequately captured in the neurophysiological profiling of ALS patients.
Aim:
To develop, test, and employ non-invasive techniques to explore (dys)function between motor, sensory brain, and spinal networks in ALS. The project will address if the electrical activity of the cortical-spinal network by the of use peripheral stimulation (vibration, electrical nerve stimulation) to probe and reveal the normal or abnormal communication between brain and spinal networks. It is expected to reveal novel neurophysiological signatures in ALS patients compared to healthy controls.
Study Design & Data Analysis:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy Volunteers:
- •age and gender matched to patient groups
- •intact physical ability to take part in the experiment.
- •Diagnosis of ALS, PLS, PMA, SMA, Polio or MS
- •capable of providing informed consent.
Exclusion Criteria
- •Healthy Controls:
- •History of neuromuscular
- •neurological or active psychiatric disease disease
- •history of reaction or allergy to recording environments, equipment and the recording gels.
- •presence of active psychiatric disease
- •any medical condition associated with severe neuropathy (e.g. poorly controlled diabetes).
- •History of reaction or allergy to recording environments, equipment and the recording gels.
Outcomes
Primary Outcomes
Non-invasive recording of the SC functional neuro-electric activity
Time Frame: Baseline
Understanding the role of spinal cord (SC) in neuromuscular physiology (in both impaired and healthy individuals) and will also assist in discovering biomarkers in Brain-SC Peripheral connections. This is a perspective outcome that will be future based upon the inferences gained by the first two outcomes.
Biomarker of sensorimotor integration
Time Frame: Baseline to 2-years after baseline
A viable biomarker of sensorimotor integration for reliable and early distinction between healthy people and Motor Neuron Disease patient sub-phenotypes. This will be achieved by comparing connectivity measures between EEG, Non-cortical CNS, and EMG electrophysiological signals. The integration will also be seen in spectral analysis measures.
Determination of the feasibility of sensorimotor signatures as reliable biomarkers of ALS
Time Frame: Baseline
The sensorimotor integration and signature biomarkers achieved during outcome 1 will be correlated with the clinical scores and will be statistically tested for reliability and robustness. The effect sizes of these statistical and correlation matrices will be used to evaluate the feasibility of the signatures as reliable biomarkers for motor neuron conditions like ALS.
Secondary Outcomes
No secondary outcomes reported
Investigators
Orla Hardiman
Professor of Neurology
University of Dublin, Trinity College