Although Amyotrophic Lateral Sclerosis (ALS) is considered a motor system degeneration, up to 70% of patients also experience clinically significant cognitive and behavioural change. Motor decline is measured using a semi-quantitative scale- the ALS Functional Rating Scale (ALSFRSR), the slope of which is used as a primary endpoint in clinical trials. However, despite its clinical importance, decline in cognition/behaviour has not been established as primary/secondary outcome in trials, as current assessment instruments (Edinburgh Cognitive & Behavioural ALS Screen, and the Beaumont Behavioural Index (BBI) are of limited utility, particularly for those with behavioural impairment, as the assessment relies on proxy reporting. There is an urgent need for reliable quantitative measures of cognitive/behavioural change in ALS. While high-density electroencephalography (HD-EEG) is a promising quantitative neurophysiology-based assessment, this technology has yet to be incorporated into a clinical trial setting.
This proposal uses quantitative EEG (resting state and bespoke evoked potential recordings with source localisation) as a nested exploratory outcome measure of cognitive and behavioural change in an ongoing investigator-led phase 3 placebo-controlled clinical trial.The objectives are (1) To assess the feasibility of incorporating quantitative EEG as an objective measure of network disruption in ALS in a clinical trial setting; (2) To learn how to correlate observed network impairment with current neuropsychological assessment (ECAS and BBI); and (3) To evaluate the acceptability of EEG measurement for participating patients within a clinical trial setting.
As the study is blinded, and segregation based on treatment or placebo arm will not be possible as part of the summer studentship. However, that data will be collated at the end of the clinical trial, and I will be invited to participate in additional analyses following unblinding.