Comparative epidemiology and quantitative neuroimaging of neuromyelitis optica spectrum disorder and multiple sclerosis

Background: Central Nervous System (CNS) inflammatory syndromes represent a spectrum of diseases caused by infiltration of inflammatory cells into the tissue of the brain and spinal cord. They comprise a group of diseases that can be acute or chronic, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO) and its spectrum disorders (NMOSD), clinically isolated syndrome (CIS) and multiple sclerosis (MS). MS is the most common one while NMO/NMOSD is relatively rare although the exact population-based epidemiological parameters are lacking. The distinction of MS and NMO/NMOSD in adult patients and of MS and ADEM in paediatric patients is important for considerations of prognosis and treatment. This thesis aims to differentiate NMO/NMOSD from MS using epidemiology analyses and quantitative magnetic resonance imaging at 7 Tesla. The hypothesis of the thesis is that NMO/NMOSD can be differentiated from MS by disease incidence, prevalence, severity, and the quantitative characteristics of the lesion and non-lesion white matter of the brain. Methods: The thesis firstly employed a comparative epidemiological study to estimate incidence and prevalence of MS and NMO/NMOSD, and to estimate risks for associated comorbidities and mortality between NMO/NMOSD and MS. The thesis then applied two quantitative techniques to compare the white matter lesions and non-lesion white matter (so-called normal-appearing white matter [NAWM]) of both NMO/NMOSD and MS. Results: The results are presented in seven chapters. Chapter 1 provides a general review of CNS inflammatory syndromes. Chapter 2 shows the estimated incidence and prevalence of CNS inflammatory diseases in 2012 using the Clinical Practice Research Datalink (CPRD). MS is estimated to be the most prevalent and the NMO/NMOSD the rarest. Chapter 3 shows the case-controlled analytic results on the impact of the burden of comorbidity in MS. The burden is cumulative after MS diagnosis and impacts on patient survival compared to non-MS patients. With an interest of new-onset epilepsy in the course of MS compared to non-MS controls, chapter 4 shows that MS patients have a higher risk of having the first medical recorded epilepsy at and after MS diagnosis. Chapter 5 shows the comorbidity burden in NMO/NMOSD, and estimates the risk for mortality between NMO/NMOSD and age- and gender-matched MS populations. Chapter 6 compares in vivo white matter lesions and NAWM of the brain between adult patients with NMO/NMOSD or MS and healthy subjects using quantitative T1 relaxation time and magnetisation transfer ratio (MTR) magnetic resonance imaging at 7 Tesla. The results show that myelin content of white matter lesions is relatively better-preserved in NMO/NMOSD than that in MS; and they also show some changes in the NAWM of NMO/NMOSD, despite the fact that the metrics of the histogram of both sequences are not different to those in MS. Conclusions: In the UK, NMO/NMOSD is rare with a higher disease severity compared to MS, which is the most prevalent inflammatory disease. In vivo, using T1 relaxation time and MTR imaging at 7 Tesla, the white matter lesions of the brain have more preserved myelin in patients with NMO/NMOSD than in those with MS. There is at least a small proportion of intracranial NAWM having subtle changes in patients with NMO/NMOSD that is detectable, but the changes could not be differentiated from MS in the current study. This thesis helps to better understand the epidemiology of NMO/NMOSD and MS, and MRI detectable changes of lesions and NAWM in NMO/NMOSD