A comparison of multiple sclerosis disease characteristics across three genetically diverse Asian racial groups in Singapore.

Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups-Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.

The burden of psychiatric morbidity in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD before and after neurological diagnosis.

BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients. METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed. RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689). CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.

COVID-19 infection after SARS-CoV-2 mRNA vaccination in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD patients during the Omicron subvariant BA.1/2 wave in Singapore.

BACKGROUND: The SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore. METHODS: This was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination. RESULTS: Two hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy. CONCLUSIONS: The Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.

COVID-19 infection after two doses of SARS-CoV-2 mRNA vaccine in multiple sclerosis, AQP4-antibody NMOSD and MOGAD.

BACKGROUND: In pre-vaccinated people with multiple sclerosis (MS), certain disease-modifying therapies (DMTs), particularly the anti-CD20 treatments, appear to be associated with an increased risk of COVID-19 infection and indeed with severe infection. It is still not known if such observations extend to vaccinated individuals and there have been considerably fewer studies in aquaporin-4-antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) patients. In this study, we investigated the rates of symptomatic COVID-19 infection in adult patients with MS, AQP4-NMOSD and MOGAD who had received 2 doses of SARS-CoV-2 mRNA vaccine. METHODS: This was a prospective observational study conducted at the 2 main neuroimmunology referral centres in Singapore. Only patients on active follow-up were recruited to ensure robust data collection. Data on demographics, disease history, DMTs and SARS-CoV-2 mRNA vaccinations were recorded, and for those infected with COVID-19, data on COVID-19 infection was collected. RESULTS: Nineteen (13 MS, 5 AQP4-NMOSD, 1 MOGAD) out of 365 (231 MS, 106 AQP4-NMOSD, 28 MOGAD) patients had COVID-19 infection despite 2 doses of SARS-CoV-2 mRNA vaccine. Amongst the infected patients, 11 patients were on DMTs (3 rituximab, 2 interferons, 1 azathioprine, 1 mycophenolate, 1 prednisolone, 1 cladribine, 1 alemtuzumab, 1 fingolimod), while 8 patients were untreated. The crude infection rate was calculated using time-at-risk analysis, revealing that rituximab had the highest infection rate amongst all the DMTs. A lower crude infection rate was observed in patients who received a third vaccination. The majority of infections were mild and no patients required oxygen supplementation. CONCLUSION: Our findings suggest that patients on rituximab are still at risk of COVID-19 infection after 2 vaccinations and the receipt of a third vaccination may help to prevent infection. Future large scale studies will be required to better delineate the infection risk of different DMTs after the second and subsequent vaccinations.

Asian and African/Caribbean AQP4-NMOSD patient outcomes according to self-identified race and place of residence.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence. METHODS: This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three. RESULTS: Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups. CONCLUSION: This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors.