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Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been described in patients with neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 antibodies (AQP4-IgG). We aimed to identify the proportion of AQP4-IgG-negative NMOSD patients who are seropositive for MOG-IgG. In a cross sectional study, we reviewed all patients seen in the National NMO clinic over the last 4 years (after the availability of MOG-IgG testing), including clinical information, MRI, and antibody tests. 261 unique patients were identified. 132 cases satisfied the 2015 NMOSD diagnostic criteria. Of these, 96 (73%) were AQP4-IgG positive and 36 (27%) were AQP4-IgG negative. These 36 patients were tested for MOG-IgG and 15/36 (42%) tested positive. 20% (25/125) of the patients who did not satisfy NMOSD criteria had MOG-IgG. Approximately half of seronegative NMOSD is MOG-Ig seropositive and one in five of non-NMOSD/non-MS demyelination is MOG-IgG positive. Since MOG-associated demyelinating disease is likely different from AQP4-IgG disease in terms of underlying disease mechanisms, relapse risk and possibly treatment, testing for MOG-IgG in patients with AQP4-IgG-negative NMOSD and other non-MS demyelination may have significant implications to management and clinical trials.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case–control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases). Among the 651 patients, [362 (55%) cases and 289 (45%) controls], a higher proportion of cases had impairment in ADLs (199 [68.9%] vs 101 [51.8%], OR 2.06, p < 0.0002) and reported symptoms impacting employment (159 [58.2%] vs 69 [35.6%] OR 2.53, p < 0.0001). There was no significant difference in the proportion with depression or anxiety between case and control groups overall. For cases, impairment of ADLs was associated with increased risk in female sex, age > 50 years and hypertension (OR 5.43, p < 0.003, 3.11, p = 0.02, 3.66, p = 0.04). Those receiving either statins or angiotensin converting enzyme (ACE) inhibitors had a lower risk of impairment in ADLs (OR 0.09, p = 0.0006, 0.17, p = 0.03). Patients with neurological or psychiatric complications of COVID-19 had worse functional outcomes than those with respiratory COVID-19 alone in terms of ADLs and employment. Female sex, age > 50 years, and hypertension were associated with worse outcomes, and statins or ACE inhibitors with better outcomes.

Introduction and objectives: neuromyelitis optica (NMO) is an autoimmune inflammatory disease that affects the central nervous system. It was thought to be a subclass of multiple sclerosis (MS); however, keen clinical observation, advances in imaging and diagnostic immunology have proved it to be a separate disorder. The discovery of antibodies to aquaporin-4 antigen (AQP4-IgG) has further advanced the field. The spectrum of disorders that are categorised under this name has widened and a new criterion has evolved. While we now have a fair understanding of aquaporin-4 NMO spectrum disorders (NMOSD), there is now an increased need to understand NMOSD without antibodies to aquaporin-4, including the disease associated with the new antibody to myelin oligodendrocytes glycoprotein (MOG-IgG).Hypothesis: neuromyelitis optica without AQP4-IgG antibodies is a different disease from that observed in neuromyelitis optica with AQP4-IgG antibodies.Aims: To study the widening spectrum of NMOSD, and to describe the role of other antibodies in seronegative NMOSD, namely antibodies to MOG. Specifically, I have studied three questions:1. What is the effect of the 2015 criteria for diagnosis of neuromyelitis optica spectrum disorders on diagnostic rates?2. What proportion of AQP4-IgG-negative NMO spectrum-disorder patients are MOGIgG positive?3. How common is the occurrence of seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease compared with figures for aquaporin 4 IgG disease?Methods: I conducted the study in the NMO and non-MS central nervous system (CNS) demyelination clinic, part of the UK NMO service at the Walton Centre NHS Foundation Trust. After an initial detailed review, prospective follow-up was performed with imaging and additional investigations that included new antibody tests as indicated, based on new information from the rapidly evolving field. All patients were tested for AQP4-IgG and MOGIgG antibodies at the Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, through use of the best available cell-based assay. Clinical and paraclinical information was gathered between 2013 and 2016 and analysed according to the study questions. Statistical analysis included demographic data, percentages, mean, median, interquartile range and Fisher test. This study formed part of the UK NMO study (MREC 02/8/082, Northwest Medical Research Ethics Committee).Results:1. Application of the new NMOSD criteria has led to a significant increase in the numbers of diagnoses of NMOSD by 76% and has widened the spectrum of the disease.2. MOG-IgG is present in 42% of patients who satisfy the clinical criteria for NMOSD but lack AQP4-IgG. However, some cases with MOG-IgG (20%) do not satisfy NMOSD criteria.3. Seizures occur in about 14% of MOG-IgG-positive NMOSD patients compared with 1% in AQP4-IgG positive.Conclusion: The ongoing research, which includes this work, has changed our understanding of NMOSD significantly in the last few years. The criteria that were introduced by the 2015 International Panel for NMO Diagnosis (IPND) bring a significant change in the approach to the diagnosis and classification of demyelinating syndromes that are not typical MS. The study of AQP4-IgG-negative NMOSD reveals that a significant group of patients have a different antibody (MOG-IgG) and exhibit unique clinical features including seizures. MOGIgG disease now is considered a different disease entity. It is expected that these observations will lead to a revision of the IPND criteria. These revised criteria could influence future clinical trials.