Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Health and Rehabilitation Sciences

Supervisor

Dr. Timothy Doherty

Abstract

OBJECTIVES: The objectives of this thesis were to review the use of outcome measures systematically across amyotrophic lateral sclerosis (ALS) clinical trials, and evaluate the utility of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) as an outcome measure, with a particular focus on its application to the upper trapezius (UT).

METHODS: First, a systematic review quantified the frequency of use of outcome measures in ALS randomized controlled trials (Chapter 2). Next, the intra- and inter-rater reliability of DE-STA MUNE was evaluated in the UT of control subjects (Chapter 3), followed by the intra-rater reliability of the technique in the UT and biceps brachii of subjects with ALS (Chapter 4). To assess validity, the results of the technique in the UT were compared between subjects with ALS and control subjects (Chapter 4). The sensitivity to change of DE-STA MUNE in the UT was compared with that of various clinical outcome measures in a longitudinal study of subjects with ALS (Chapter 5). Finally, the influence of needle electrode depth on the results of the technique in the UT was evaluated in control subjects (Chapter 6).

RESULTS: The heterogeneity in the use of outcome measures across ALS randomized controlled trials was demonstrated, in addition to the infrequent use of MUNE. MUNE results demonstrated moderate intra- and inter-rater reliability for control subjects in the UT, although less favorable results were found overall for inter-rater reliability. Application of DE-STA MUNE to the UT in subjects with ALS demonstrated consistently high intra-rater reliability, the ability to detect the underlying pathophysiology of the disease, and a moderate degree of sensitivity to change for MUNE results. Further evaluation found needle electrode depth to significantly influence the results of the technique, with suggestions made for improved standardization of the protocol.

SIGNIFICANCE: These studies were novel in their evaluation of MUNE in the proximal, potentially clinically relevant UT. The studies mark the first evaluations of the reliability and sensitivity to change of DE-STA MUNE in subjects with ALS, finding application to the UT to be practical and promising for use as an outcome measure. Implementation of proposed improvements to the protocol may aid in further establishing DE-STA MUNE for use as an outcome measure in studies of ALS.


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