| Summary: | <p>In the past fifteen years two new antibody-mediated Central Nervous System (CNS) diseases, have been identified as distinct from multiple sclerosis (MS): Aquaporin-4-antibody (AQP4-Ab) and the more recently discovered myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD).
Although conventional brain MRI may help distinguish MS from antibody-mediated diseases, the use of quantitative and non-conventional imaging may give more pathological information and explain the clinical differences.
This thesis comprises a clinical study, describing the main clinical characteristics of MOGAD, and a cross-sectional MRI study that compares structural, quantitative and functional brain MRI findings across MOGAD, NMOSD-AQP4, MS and healthy controls. </p>
<p>The principal clinical finding is:</p>
<p>• MOGAD patients have a good recovery from visual and physical disability compared to NMOSD-AQP4, although some of them can be left with sphincter, erectile dysfunction, and cognitive impairment. </p>
<p>The main MRI study findings are:</p>
<p>• In MOGAD most of the white matter lesions tend to resolve, but patients are left with grey matter damage, and this may be related to persistent white matter lesions. Despite the greater residual disability, NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes. </p>
<p>• Non-lesional tissue fractional anisotropy (FA) was only reduced in MS, although focal reductions were noted in NMOSD-AQP4 patients, reflecting mainly optic nerve and corticospinal tract pathways. In MOGAD there is no abnormal non-lesional tissue FA. </p>
<p>• Disability (EDSS) in NMOSD-AQP4 is associated with NAWM FA alone, with deep grey matter atrophy and female sex in MS, and with brainstem volume in MOGAD. Visual acuity was associated with optic chiasm volume in NMOSD-AQP4 disease and with thalamic volume and female sex in MOGAD.</p>
<p>• in MOGAD, despite the good visual recovery, and the absence of structural and microstructural tissue damage, there is a reduced functional connectivity in the primary visual cortex. In NMOSD-AQP4 there is a broader involvement of the large brain networks (visual, salience, sensorimotor, default mode network), possibly related to the higher level of disability (and tissue damage), while in MS, a preferential involvement of subcortical network was found (i.e., basal ganglia). </p>
<p>• Cognitive performance is influenced by fatigue and depression in MOGAD and NMOSD-AQP4 but not in MS. Low cognitive score is associated with low deep grey matter volume in MOGAD and MS, while is mainly driven by cortical volume in NMOSD-AQP4. </p>
<p>The clinical and MRI studies from this thesis, represent some of the earliest studies directed at better understanding the MRI changes behind the clinical recovery and outcome in MOGAD. The comprehensive clinical and MRI approach, investigating not only physical disability, but also the often-neglected cognitive function, added novelty to this body of work and can open to future larger studies. </p>
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