Triggers and outcomes in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and MOG antibody-associated disease: the unanswered questions

Thesis

Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD) are antibody-mediated autoimmune inflammatory CNS syndromes (AICS). The precipitants of attacks are unknown. There is some evidence that infection or vaccination can trigger MOGAD.

Like multiple sclerosis, both can result in cerebral inflammation. Cognitive impairment in multiple sclerosis is well-documented, but whether it is a feature of NMOSD and MOGAD is debated. Studies attempting to resolve this question are flawed by small samples, inadequate control groups, erroneous statistical methods and, in the case of NMOSD, mixed seropositive and seronegative samples.

The large cohort of patients with AQP4+ NMOSD and MOGAD under the care of the John Radcliffe Hospital enabled an adequately powered study of cognitive outcomes in adults with these diseases. This is the first study to compare cognitive performance of patients with AQP4+ NMOSD and MOGAD to that of controls with a chronic autoimmune disease that spares the central nervous system. 

This work confirms significantly poorer attention and processing speed in AQP4+ NMOSD compared with controls and identifies paediatric onset as a risk factor for impairment. The findings refute reports of cognitive impairment in MOGAD.

The SARS-CoV-2 pandemic delayed the study of cognition in adults with NMOSD and MOGAD. However, the mass SARS-CoV-2 vaccination programme afforded an unparalleled opportunity to research vaccinerelated autoimmune phenomena.

This study used clinic-based observational, epidemiological and laboratory-based approaches to analyse associations between SARSCoV-2 vaccination and onset of AICS, including AQP4 and MOGAD. The multimodal approach provides evidence that ChAdOx1S can trigger onset of MOGAD. 

Research presented here highlights the importance of screening for cognitive impairment in young people with AQP4+ NMOSD and offering educational support if needed. It also demonstrates a role of vaccineassociated antigens and/or vaccine-induced immune pathways in development of MOGAD, which could provide the basis for further study of disease risk factors and, potentially, future treatments. 

Authors: Francis, A

• DOI: 10.5287/ora-bxyy9q5dx
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: NMOSD; Neuromyelitis optica spectrum disorder; vaccine; cognition; MOG
• Subjects: Neurology