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|Title: ||Cortical hyperexcitability in Amyotrophic Lateral Sclerosis: Diagnostic and pathophysiological biomarker|
|Authors: ||Geevasinga, Nimeshan|
|Issue Date: ||28-Dec-2015|
|Publisher: ||University of Sydney|
Sydney Medical School
|Abstract: ||Amyotrophic lateral sclerosis (ALS) is a progressive and degenerative disease of the motor system clinically defined by the presence of upper and lower motor neuron (UMN/LMN) signs. In this thesis the current diagnostic criteria were evaluated, both with a meta-analytical approach and a prospective multicenter design. The lack of an objective UMN biomarker resulted in a delayed diagnosis. Hence a novel threshold tracking transcranial magnetic stimulation (TMS) technique was utilised to measure cortical hyperexcitability, as a biomarker of UMN dysfunction. Cortical hyperexcitability facilitated an earlier diagnosis. This technique was then utilised to gain insights in familial ALS (c9orf72 repeat expansion). Cortical and peripheral nerve abnormalities were evident in familial ALS, but asymptomatic carriers had no evidence of cortical or peripheral nerve dysfunction. We then studied atypical ALS phenotypes such as the clinically UMN predominant variant, primary lateral sclerosis (PLS), reliably differentiating PLS from mimic disorders such as hereditary spastic paraparesis (HSP). In the lower motor neuron variant of ALS, termed flail leg syndrome, cortical hyperexcitability was only evident in patients with upper motor neuron signs. Taken together, these findings suggest that cortical hyperexcitability is a potentially robust diagnostic and pathophysiological biomarker in sporadic, familial and some atypical ALS variants.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
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|GEEVASINGA Nimeshan - Final Thesis.pdf||Thesis||2.89 MB||Adobe PDF|
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