2012, EN, English, Thesis edition: Neurophysiological biomarkers in amyotrophic lateral sclerosis Cheah, Benjamin, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW

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Physical Description
  • Thesis
  • PhD Doctorate
Published
  • Awarded By:University of New South Wales. Clinical School - Prince of Wales Hospital, 2012
Language
  • EN
  • English

Edition details

Title
  • Neurophysiological biomarkers in amyotrophic lateral sclerosis
Author
  • Cheah, Benjamin, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW
Other Contributors
  • Matthew, Kiernan, Faculty of Medicine, UNSW
  • Arun, Krishnan, Faculty of Medicine, UNSW
  • David, McKenzie, Faculty of Medicine, UNSW
Published
  • Awarded By:University of New South Wales. Clinical School - Prince of Wales Hospital, 2012
Physical Description
  • Thesis
  • PhD Doctorate
Subjects
Summary
  • This thesis examines the pathophysiology of amyotrophic lateral sclerosis (ALS) and role of neurophysiological biomarkers in understanding and diagnosing this neurodegenerative disease. One of the rationales for the thesis was to expand the utilisation of threshold-tracking transcranial magnetic stimulation and axonal excitability techniques in ALS clinical trials. Development of such biomarkers may facilitate patient enrollment and expedite completion of clinical trials in ALS. Given that ALS is a disorder affecting the entire neural axis, from upper motor neuron through to lower motor neuron, the present thesis drew upon multiple neurophysiological techniques in an attempt to better understand ALS pathophysiology. To clarify the development of central dysfunction in ALS, correlations between short interval intra-cortical inhibition and magnetic SR curve were initially investigated. Corticomotoneuronal hyperexcitability was identified during the progressive disintegration of inhibitory circuits in the motor cortex in ALS. Furthermore, the severity of motor cortical hyperexcitability appeared to correspond to the clinical phenotype of ALS. Neurophysiological subtypes including the relatively inexcitable motor cortex were also investigated, with the latter associated with young age, poor fine motor function, and prominent UMN dysfunction. Given that motor cortical hyperexcitability may be specific for ALS, results were compared to patients with an ALS-mimic disorder, acquired autoimmune neuromyotonia, and it was determined that acquired neuromyotonia patients retained normal cortical excitability. Threshold-tracking transcranial magnetic stimulation was subsequently shown to be clinically useful in identifying ALS across a mixed neuromuscular cohort. In addition, the test shortened diagnostic time by approximately eight months, potentially enabling earlier enrollment of ALS patients into clinical trials. In terms of identifying lower motor neuron involvement, axonal excitability studies were undertaken at baseline and at 12 weeks follow-up to ascertain the longitudinal changes in axonal function that may develop in ALS patients. Progressive axonal dysfunction became apparent, consistent with the development of axonal hyperpolarisation, that overall was more profound in ALS patients who demonstrated weakness and functional impairment.
Terms of Use
Language
  • EN
  • English
Related Resource
  • SHELF:T/​2011/​438 (Ask at Level 2 Information Desk, UNSW Library)
Identifier
  • oai:unsworks.unsw.edu.au:unsworks:10192

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