Myelin-oligodendrocyte glycoprotein associated disease (MOGAD) is a recently described inflammatory demyelinating disorder of the central nervous system. It has been shown to be distinct from both aquaporin-4 (AQP4) antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Spinal cord involvement is a hallmark feature of all three diseases and a central cause of disability, and so, is an important phenotype to study. This thesis consists of a retrospective clinical study and then a cross-sectional research MRI study that compares structural, quantitative and resting-state functional MRI scans across MOGAD, AQP4-NMOSD, MS and healthy volunteers (HV). The principal clinical research findings are: • MOGAD myelitis presents more frequently with short cord lesions, multiple cord lesions, conus lesions and involvement of either the brain or optic nerves at the time of the acute attack; these MRI lesions are likely to resolve at follow-up. • MOGAD myelitis results in significant sphincter dysfunction, despite good motor recovery. Conus lesions are associated the need for long term catheter dysfunction and the presence of a brainstem lesion during the acute attack may predict higher long term disability. The principal research MRI findings are: • AQP4-NMOSD myelitis shows the most severe, localised damage in areas of the cord involved during the acute episode. In MS, metrics show significant differences compared to HV but the relationship with lesion location is not as pronounced. In MOGAD, metrics are comparable to HV after recovery from myelitis but localised grey matter atrophy is noted in the affected area of the cord. • Patients with relapsing MOGAD show significantly more thoracic cord atrophy than monophasic MOGAD, even where the relapse occurred outside of the spinal cord. This may indicate that relapsing MOGAD denotes a more severe phenotype. • Non-conventional MRI metrics show clinical relevance: cervical cord cross-sectional area associates with disability outcomes and spinothalamic fractional anisotropy with pain scores, independent of disease type. • Distinct and robust functional networks exist in the spinal cord without a particular task. Damage in the spinal cord may lead to either a compensatory increase or a decrease in connectivity related to atrophy and cord lesions. The publications from this work, which form part of this thesis, have added to the growing body of research into the study of MOGAD. Additionally, advanced spinal cord imaging techniques were used, which add novelty to the research and its conclusions.
