A multimodal MRI study of the human brain investigating neuromyelitis optica spectrum disorders

Abstract

Study 1 A multicentre longitudinal MRI study of MOG-antibody associated central nervous system inflammation Introduction Myelin oligodendrocyte glycoprotein antibodies (MOG-ab) cause a primary demyelinating illness targeting oligodendrocytes. Some patients fulfil the diagnostic criteria of NMOSD according to the IPND 2015(1); however, there are differences (2-5). Here, we investigate the epidemiology clinical Spectrum and longitudinal MRI characteristics in MOG-ab demyelinating disease (MOGAD) in a multicenter cohort. Methodology 1.5 and 3T MRI scans of 56 MOG-antibody positive patients from the U.K. and India were retrospectively reviewed, and MOG-ab tested, using live CBA IgG1 secondary Ab. The brain, spinal cord, and optic nerve scans were assessed for previously reported NMOSD and MS related changes by three reviewers trained by the Neuroradiologist (MB) (AA, DW, SH). Then, all the results were reviewed by the Neuroradiologist (MB). Longitudinal MRI scans were reviewed for temporal changes. Results MRI brain scans showed lesions in 32% brain stem, hemispheric white matter lesion 29%, u-fibre 20%, Corticospinal tract lesion 21%, Periependymal 14%, Cortical, Temporal, and Cerebellar lesion in 13%. The spinal cord MRI scans showed that 69% have LETM. Optic nerve scans showed 33% had bilateral optic neuritis, 61% long segment lesions, and orbital/ canalicular lesions, 83%. Longitudinal results showed that asymptomatic patients (13, median follow-up 16.5 months) (69%) who were off treatment showed improvement, and 31% were unchanged. In the follow up Patients (29, median follow-up 14 months), 55% showed improvement regardless of treatment, 21% resolution of lesions, 17% unchanged, and only 7% showed progression. Conclusion MOG-ab associated central nervous system inflammation can be associated with a wide range of MRI appearances; however, none seem exclusive for it. In a third of the MRI scans reviewed, brain stem and hemispheric lesions were detected. There was no corpus callosum Dawson’s fingers lesions seen in this cohort, and the AQP4-NMOSD typical lesions were not uncommon. The MRI showed mostly long cervicothoracic myelitis in the spinal cord, and in the optic nerve, long anterior lesions were most common. Reviewing the longitudinal scans showed no lesion accruing overtime in asymptomatic patients, and a variable degree of atrophy was associated with the lesion resolution. Study 2 Multimodal MRI Study investigating AQP4-NMOSD and MOGAD brain differences Introduction Neuromyelitis Optica Spectrum Disorders (NMOSD) are rare, relapsing, inflammatory disorders of the central nervous system, mainly targeting the spinal cord and optic nerves (1, 11). Although less well studied, it is increasingly recognised that the brain is also commonly affected (12, 13). Antibodies to aquaporin-4 (AQP4-ab), and more recently, antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) have been identified in the sera of individuals with NMOSD (2, 14-16). In our research, I aim to test the hypothesis that the inflammatory process in the brain is different between AQP4-ab positive NMOSD (AQP4-NMOSD) and MOG-ab positive (MOGAD) patients. Using conventional MRI scans limits the ability to detect brain microstructural changes. In this thesis, Diffusion tensor imaging - Tract based spatial statistics analysis (TBSS), Voxel based Morphometry (VBM), Freesurfer - are used to detect differences in the AQP4-NMOSD and MOGAD positive patients, and directly compare them to each other and healthy controls. Methodology 40 participants scanned (20 AQP4-NMOSD, 20 MOGAD). All participants were in remission for at least six-months. 32 healthy controls were also scanned for comparison. Brain MRIs were obtained for each participant using 3-T MRI. Automated Lesion Segmentation (LST) was used to extract and investigate lesion volume and count. White matter diffusion tracts were analysed using DTI metrics (Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity(AD)) perceived from TBSS with free water correction to increase the analysis sensitivity. VBM and Freesurfer were used to investigate grey matter differences. Correlation with neurostatus scores and patients’ clinical demographics was also performed.