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dc.contributor.authorGarg, Nidhi
dc.date.accessioned2019-04-09
dc.date.available2019-04-09
dc.date.issued2018-11-21
dc.identifier.urihttp://hdl.handle.net/2123/20260
dc.description.abstractThis thesis explores mechanisms of nerve dysfunction in the autoimmune neuropathies chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and the neuropathy associated with IgM antibodies against myelin-associated glycoprotein (MAG). Initially, the frequency of autoantibodies to nodal and paranodal proteins was established via serum assays. The clinical and neurophysiological features of patients with neurofascin-155 IgG4 antibodies were examined. In antibody-negative patients, axonal excitability studies revealed marked differences between CIDP and MMN patients with conduction block. CIDP with block was associated with paranodal dysfunction – evidenced by the excitability profile and serum binding to paranodes in teased nerve fibres. Excitability changes in MMN suggested a reduction in ion channel density along axons, potentially due to enlargement of motor units, prompting the subsequent study aimed at assessing motor unit properties in MMN. This study confirmed striking enlargement of motor units due to reinnervation, masking severe axonal loss and highlighting that assessment of motor unit numbers and size are critical in disease monitoring. Finally, studies in patients with anti-MAG neuropathy revealed a characteristic axonal excitability profile, consistent with an increase in juxtaparanodal fast potassium channel conductance, suggesting that nerve function may be improved by blockade of fast potassium channels. In summary, this thesis has demonstrated significant differences in molecular mechanisms across the immune-mediated neuropathies and provided new insights and tools to guide treatment approaches and monitor disease progression.en_AU
dc.rightsThe author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.en_AU
dc.subjectNeuropathyen_AU
dc.subjectNeurophysiologyen_AU
dc.subjectCIDPen_AU
dc.subjectMMNen_AU
dc.subjectImmunologyen_AU
dc.titleMechanisms Of Nerve Dysfunction Across The Spectrum Of Immunemediated Neuropathiesen_AU
dc.typeThesisen_AU
dc.type.thesisDoctor of Philosophyen_AU
usyd.facultyFaculty of Medicine and Health, Sydney Medical Schoolen_AU
usyd.degreeDoctor of Philosophy Ph.D.en_AU
usyd.awardinginstThe University of Sydneyen_AU


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