Abstract

Lesions in the brainstem result in widespread damage to a number of sensorimotor systems including oculomotor and auditory neural circuits. Although these systems are spatially separate and highly specialised, they are also co-located. This thesis, investigates whether lesions in the oculomotor system will also cause co-morbid dysfunction in the auditory pathways. Specifically, we investigated the usefulness of the Auditory Brainstem Response (ABR) in two oculomotor conditions: slow saccades in Gaucher disease (GD) and opsoclonus in Dancing Eye Syndrome (DES). We present four empirical studies. In our first study we systematically investigated the ABR in GD. We found that multimodal testing can better delineate underlying neurological deficits in neuronopathic GD (nGD) and distinguish between phenotypes. In the second study we examined the ABR's utility as a longitudinal, objective marker of disease burden and in a randomised clinical control trial. ABRs continued to deteriorate regardless of treatment. In our third study we assessed audiological function in DES. We found that at least 43% of DES patients have hyperacusis. We also found subtle abnormalities in the auditory brainstem, as shown by the ABR. Our final study explored the onset-offset response in the ABR and assessed its utility as a clinical marker. Overall, this thesis provides new evidence that auditory pathways are also affected in diseases which are traditionally assumed to be ‘oculomotor’ in nature. We believe that there is sufficient evidence to warrant the inclusion of audiological testing, such as the ABR, as part of the standard assessment of newly diagnosed GD patients and that they undergo these tests prior to commencing treatment. These tests may also have a wider application as longitudinal outcome measures for use in clinical trials or as markers of neurological burden in GD and we believe may be useful in other metabolic diseases; we found that current therapies for GD have low efficacy. Understanding the underlying neurological deficits in these debilitating illnesses can only help to improve treatments and the long-term outlook for these patients.

Document Type

Thesis

Publication Date

2014-01-01

DOI

10.24382/4436

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