Clinical and imaging biomarkers of audiovestibular function in infratentorial superficial siderosis

Disabling hearing loss is known to affect over 400 million people worldwide while the lifetime prevalence of dizziness can be as high as 40%. Rare causes for hearing and balance impairment are often understudied. Infratentorial (classical) superficial siderosis (iSS) is a rare but sometimes disabling complex neurological condition most often associated with hearing and balance impairment, and myelopathy. Olfactory loss has been reported but not yet systematically studied. iSS results from a chronic low-grade and low volume bleeding into the cerebrospinal fluid and the deposition of iron-degradation products (predominantly haemosiderin) in the subpial layers of the central nervous system, with predilection for the cerebellum and the vestibulocochlear nerves. Magnetic resonance imaging (MRI) allows haemosiderin to be visualised in-vivo and is the mainstream diagnostic modality. Due to the assumed rarity of iSS (prevalence of 0.03-0.14%), our research opportunities are limited. Few dedicated studies describe iSS-related audiovestibular (AV) findings, often limited to case-series, with mixed findings. There is currently no robust evidence that the radiological haemosiderin appearances correlate with the objective clinical tests. This project focuses on phenotyping the AV function in iSS and identifies predominantly retrocochlear hearing loss with features suggestive of central auditory dysfunction, and mixed vestibular (predominantly cerebellar) dysfunction. This work introduces and validates an imaging rating scale aiming to capture the anatomical extent of haemosiderin deposits visualised on MRI in a standardised and reproducible way. The scale demonstrates excellent reliability and good validity, with the scores correlating with hearing thresholds. This project estimates the prevalence of MRI-defined iSS in a large UK Biobank sample, similar to other rare neurootological disorders. Using patient/self-report measures, this work captures markedly low health-states of individuals with iSS and identifies possible iSS-specific auditory characteristics. Finally, the work identifies high prevalence of olfactory dysfunction in individuals with iSS