Exploring cortical excitability and photosensitivity in neurological disorders using pupillary response to sparse multifocal stimuli
Creators: name: Ali, Eman
Publisher: name: The Australian National University
Year: 2016
Subjects: Migraine
Epilepsy
Multifocal perimetry
cortical excitability
photo-sensitivity
Pupil

description: Exploring cortical excitability and photosensitivity in neurological disorders using pupillary response to sparse multifocal stimuli Abstract: Epilepsy and migraine are two distinct paroxysmal neurological disorders yet both disorders overlap in multiple aspects. The objective of this thesis was to study two of the phenomena shared by these disorders, namely photosensitivity and cortical hyperexcitability. For this purpose, I chose the multifocal objective pupillographic perimetry device (mfPOP) to study the largely subcortical part of the visual pathway responsible for the pupillary response. The main objectives were first, to examine whether the objective perimetry results differed from the general population in these two disorders, second to explore whether there were differences between sub-types of the disorders and, third, to estimate the safety and tolerability of the mfPOP protocols that involve light stimulation. We also examined the effects of treatments that might affect brain excitability. I then went further and analysed electroencephalograms (EEG) recorded from epilepsy subjects looking at changes in the alpha rhythm entrainment in response to photic stimulation as an added indicator of cortical excitability. These effects were correlated with the mfPOP results. Regarding photosensitivity, I found that the mfPOP device appeared to be safe when used in migraine subjects, even when a method designed specifically designed to stimulate the melanopsin containing retinal ganglion cells was used: these cells have been implicated in the mechanism of exacerbation of migraine headaches by light. Safety was also supported clinically and objectively for epilepsy patients by using EEGs and finding them to be clear of epileptiform activities during mfPOP testing. 7 Regarding cortical excitability, I found that this phenomena did indeed affect the pupil derived perimetry responses, with the responses being increased post-ictally and interictally in epilepsy patients while being normal in the inter-ictal period in migraineurs and decreased after migraine attacks. These changes were reversed by two distinct classes of medication, anti-epileptics in epilepsy and triptans in migraine patients. Some disease-specific differences in the location of visual field defects were observed, especially for response sensitivity. Disease dependent changes in mfPOP response delays were observed, which were more generalised across the visual fields more than the sensitivity changes. These findings were further supported by demonstrating that the alpha entrainment was more pronounced in epilepsy patients than the normal population and that it was also affected by medication use. These findings were consistent with the fact that both disorders have been shown to demonstrate an increase in cortical excitability in between attacks, this increase being more pronounced in epilepsy subjects. Medication consumption has a dampening effect on this excitability. During a migraine attack, this excitability is believed to transition to cortical spreading depression rather than to the hyper-synchronous activity that characterizes epilepsy. These results, combined with our earlier study of Multiple Sclerosis, demonstrate that mfPOP is a valuable tool in studying neurological disorders especially in populations with motor deficits. With its safety now relatively well established it can help shed a light on the pathophysiology of these disorders and aid in their diagnosis.