EEG and TMS-based Biomarkers of ALS, MS and FTD

Conditions: Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Multiple Sclerosis

Interventions: Procedure: 128 electrode electroencephalography (EEG)
Procedure: Transcranial magnetic stimulation (TMS)

Brief Summary: The purpose of this observational study is to improve understanding of the biology of why ALS, MS and FTD have different effects on different people and facilitate better measurement of the disease in future drug testing. To do this, brain and spinal cord neural network functionality will be measured over time, in addition to profiling of movement and non-movement symptoms, in large groups of patients, as well as in a population-based sample of the healthy population. Patterns of dysfunction which relate to patients' diagnosis and coinciding and future symptoms which align with categories of patients with similar prognoses will be investigated and their ability to predict incident patients' symptoms in future will be measured.

Detailed Description: The aim of this project is to characterize spatiotemporal patterns of central nervous system dysfunction that correlate with clinical features of ALS, MS and FTD, to provide non-invasive electrophysiological measurements that can be used in a clinical setting to inform stratification of patients in clinical trials, and to provide data driven diagnostic and prognostic biomarkers and objective clinical trial outcome measures. Such dysfunction will be investigated by recording single- and paired-pulse transcranial magnetic stimulation (TMS)-associated electromyography (EMG) during rest and by recording electroencephalography (EEG) during rest and during cognitive-motor tasks.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Amyotrophic lateral sclerosis patients	128 electrode electroencephalography (EEG)	-
Controls	128 electrode electroencephalography (EEG)	Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis
Multiple sclerosis patients	Transcranial magnetic stimulation (TMS)	-
Frontotemporal dementia patients	128 electrode electroencephalography (EEG)	-
Frontotemporal dementia patients	Transcranial magnetic stimulation (TMS)	-
Amyotrophic lateral sclerosis patients	Transcranial magnetic stimulation (TMS)	-
Controls	Transcranial magnetic stimulation (TMS)	Individuals from the Irish population with no psychiatric, psychological, neurological or muscular disease diagnosis
Multiple sclerosis patients	128 electrode electroencephalography (EEG)	-

Primary Outcome Measures

Name	Time	Method
Diagnosis-related changes in EEG or TMS measurements	Baseline to final visit assessed up to 2 years after baseline	Differences in rate of change (slope) across time of single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between those within each patient cohort relative to controls
Diagnosis-related difference in EEG or TMS measurements	Baseline recording	Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between those within each patient cohort and controls
Prognosis-related EEG or TMS measurements	Baseline recording	Patient cohort single or paired pulse TMS measures or time and/or frequency domain EEG characteristics which show significant correlation to cognitive, behavioural, motor and/or sensory task performance, to disease duration or to survival time
Prognosis-related changes in EEG or TMS measurements	Baseline to final visit assessed up to 2 years after baseline	Rates of change (slope) across time of patient cohort single or paired pulse TMS measures or time and/or frequency domain EEG characteristics which show significant correlation to cognitive, behavioural, motor and/or sensory task performance, to disease duration or to survival time

Secondary Outcome Measures

Name	Time	Method
Diagnosis-specific changes in EEG or TMS measurements	Baseline to final visit assessed up to 2 years after baseline	Differences in rate of change (slope) across time of single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between patient cohorts
Diagnosis-specific difference in EEG or TMS measurements	Baseline recording	Differences in single or paired pulse TMS measures or time and/or frequency domain EEG characteristics between patient cohorts

Locations (1): Academic Unit of Neurology, Trinity College Dublin, The University of Dublin
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Dublin, Leinster, Ireland