The Prevalence, Demographics, Clinical Features, Neuroimaging, and Inter-ethnic Differences of MOGAD in Malaysia with Global Perspectives.

INTRODUCTION: CNS IIDDs1 tested positive for anti-MOG2 are known to have a distinct clinical profile with a better overall prognosis. OBJECTIVES: We aim to determine the prevalence, demographic and clinical characteristics of MOG antibody disease (MOGAD) specifically identifying any ethnic variations unique to our local population, with global perspectives. METHODS: This is a cross-sectional study conducted at the Neurology Department, Kuala Lumpur Hospital from January 2018 to January 2021. Out of 750 CNS IIDDs, seventy-eight consecutive anti-AQP4 antibody negative NMOSD/high risk undifferentiated relapsing or monophasic CNSIIDD subjects were tested for anti-MOG. RESULTS: Anti-MOG was positive in thirty six out of seventy-eight (%)(46.1%) seronegative patients. The prevalence of MOGAD in our Malaysian population is 0.12 per 100,000 persons with less marked female preponderance of 2:1 and younger age at onset of 23.8 ± 14.4 years. Despite a predominantly ethnic Malay population, a high proportion of our MOGAD patients were Indian (Proportion of Malay:Chinese:Indian:others; 16:9:10:1, prevalence 0.5 per 100,000 population for Indians) with favourable disease course in the most with minor exceptions. Monophasic and relapsing disease course was seen in 11.2% and 88.8% of patients respectively. However, fulminant aggressive disease can occur especially amongst the Chinese and paediatric cohorts. Optic neuritis, NMOSD and ADEM were the commonest presentations at onset and first relapse. EDSS at diagnosis, first relapse, and last follow-up were 4.5±2.5, 3±2.0, and 1.75(range 1-3). Neuroimaging showed large, fluffy, PRES- like supratentorial cortical, periventricular deep white matter ,diencephalon lesions,enhancing anterior optic nerve with or without chiasmal sparring lesions and cervical/cervicothoracic involvement. Area post rema lesions were rare. Threshold steroid levels exist relapsing on withdrawal some fulminantly requiring Immunosuppressants(rituximab) and intravenous immunoglobulins to maintain remission. CONCLUSION: Malaysian MOGAD profile was similar to its international descriptions of the disease with ethnic selectivity for Indians. Prolonged steroid maintenance is essential to prevent relapses. Fulminant aggressive cases of MOGAD especially amongst Paediatric patients and the Chinese cohort have been reported.

Clinical usefulness of anti-cell membrane DNA autoantibodies in serology negative systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) diagnosis is dependent on the detection of serum autoantibodies. To date, there is no autoantibody highly sensitive and specific enough to be considered as a gold standard. This study aimed to determine the diagnostic usefulness of anti-cmDNA antibodies which found to be associated with SLE. MATERIALS AND METHODS: Serum samples from 83 SLE, 86 other connective tissue diseases (OCTD) and 61 healthy subjects were randomly selected for the study. The OCTD cases included 56 rheumatoid arthritis, 12 scleroderma, 10 Sjogren's syndrome and 8 mixed connected tissue diseases. All samples were assayed for anti-cmDNA by indirect immunofluorescence assay (IFA) using Raji cells as substrate. SLE samples were also tested for antidsDNA and anti-Sm antibodies using enzyme-immunoassays. RESULTS: Anti-cmDNA positivity was highest in SLE (55.4%) compared to OCTD (9.3%) and healthy subjects (0%). It was 100% specific at differentiating SLE from healthy subjects and 90.7% specific at differentiating SLE from OCTD. There were no significant differences in the sensitivity (55.4%) of anti-cmDNA at differentiating SLE from OCTD and healthy groups. Anti-cmDNA was present in 52.9% of SLE samples negative for standard SLE-specific autoantibodies. It was detected in 7 (36.8%) of anti-dsDNA, 25 (52.1%) of anti-Sm and 5 (31.3%) of both anti-Sm and anti-dsDNA negative samples. Anti-cmDNA positive SLE was significantly associated with arthritis (p=0.019). CONCLUSION: The high specificity of anticmDNA detection by IFA makes it an excellent diagnostic test for SLE. Anti-cmDNA is also useful for identifying SLE with negative anti-dsDNA or/and anti-Sm antibodies.

Multiple sclerosis and neuromyelitis optica spectrum disorders in Malaysia: A comparison in different ethnic groups.

We performed a retrospective observational analytical study looking at the frequencies and characteristics of multiple sclerosis(MS) and neuromyelitis optica spectrum disorders(NMOSD) in consecutive patients with idiopathic inflammatory demyelinating disease (IIDDs) attending three centers (2009-2017). Of 523 patients with IIDDs, there were 173 patients with NMOSD and 230 patients with MS. The percentage of NMOSD: IIDDs was 33%. The percentage of NMOSD:Total MS and NMOSD cohort was 43%. Of 141 seropositive NMOSD patients, 134(95%) were from the three main ethnic groups. The percentage of seropositive NMOSD to IIDDs and to combined MS and NMOSD was 26.9% and 35% respectively. Ratios of MS to NMOSD were nearly equal at 1.3 to 1.0, reinforcing the high ratio of NMOSD to MS in Asia. Nearly half of the Chinese cohort were seropositive ie; 71/141 (50%) with the remainder being Malays; 56/141 (39.7%) and Indians; 7/141 (5%). Amongst the other indigenous groups seropositivity was seen in 2 each of Iban, Bajau, Kadazan descent as well as one of Bidayuh origin. Comparatively, seropositivity in NMOSD is commoner amongst the Chinese compared to the Malays (p ≤ 0.005) and Indians, p ≤ 0.05 with ratios as high as 10:1. In the MS group of 230 subjects, 123(53.5%) were Malays (ratio of MS:NMOSD of 2:1), 41(17.8%) were Chinese, (ratio of MS:NMOSD of 0.5:1.0) and 54 (23.5%)were Indians (ratios of MS:NMOSD of 5:1 amongst the Indians). The remainder from East Malaysia were made up of 2 each of Kadazans, Ibans and Bajaus including 3 each of Bidayuh and Eurasian descent. Comparatively, in the NMOSD and MS cohorts a female preponderance was noted more so amongst Chinese NMOSD patients, with rare familial occurrence in both but more in Malay MS/NMOSD patients. This study also highlighted some of the inter-ethnic differences in presentation of MS and NMOSD amongst the 3 main ethnic races in Malaysia and confirms indigenous races having MS/NMOSD which needs further research. It also reviewed current literature on similar inter-ethnic differences world wide. To conclude, MS and NMOSD are the commonest demyelinating diseases seen in Malaysia with interesting inter-ethnic differences and similarities.

Antiphospholipid antibodies among women experiencing fetal loss.

The presence of antiphospholipid antibodies (aPLs) is closely associated with thrombotic events and pregnancy complications such as recurrent pregnancy loss, preeclampsia and placental insufficiency. We investigated the presence of aPLs and its frequency among female patients with a history of fetal loss in a Malaysia population. Serum samples were collected from 108 patients who had (1) one or more unexplained deaths of morphologically normal fetuses at or beyond the 22nd week of gestation, or (2) one or more premature births of morphologically normal neonates at or before the 24th week of gestation due to eclampsia or preeclampsia, or recognized features of placental insufficiency, or (3) three or more unexplained, consecutive, spontaneous miscarriages before the 20th week of gestation. Serum was tested for aPLs subtypes: anticardiolipin (aCL), anti-beta-2- glycoprotein I (aß2GPI), anti-beta-2-glycoprotein I dependent cardiolipin (aß2GPI dependent CL), anti-phosphatidylcholine (aPC), anti-phosphatidylethanolamine (aPE), anti-phosphatidylinositol (aPI), anti-phosphatidylserine (aPS) and anti-sphingomyeline (aSph) by using the enzyme-linked immunosorbent assay (ELISA) method. The mean age of patients was 30±5. Four patients (3.7%) were found positive for at least one aPLs subtype. Four aPLs subtypes were detected. The most common subtypes was aß2GPI dependent CL (3.7%), followed by aCL (2.7%), aß2GPI (0.9%), and aPE(0.9%). In conclusion, frequency of aPLs among women with fetal loss (3.7%) in Malaysia was low with subtype aß2GPI dependent CL being the most prevalent aPLs.