Methods: Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR.
Results: The majority of multiple sclerosis patients were female (85.2%). The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct.
Conclusions: The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution.
OBJECTIVES/RESULTS: The authors put forward general principles for the ethical use of off-label DMTs for treating MS and a process to assess existing evidence and develop recommendations for their use.
CONCLUSION: The principles and process are endorsed by the World Federation of Neurology (WFN), American Academy of Neurology (AAN), European Academy of Neurology (EAN), Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) and Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), and we have regularly consulted with the Brain Health Unit, Mental Health and Substance Use Department at the World Health Organization (WHO).
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.
Patients and Methods: MS and NMOSD patients older than 40 were identified from neurology records from hospitals in Malaysia. The diagnoses were based on the Revised McDonald (2010) and Wingerchuk (2015) criteria. Controls were sampled from Malaysia's normal population. Individuals were interviewed telephonically or face-to-face. The age inclusion criterion (over 40) differentiated high or low lifetime risk of appendicitis, as appendicitis incidence is rare after 40.
Results: 49 MS, 71 NMOSD, and 880 controls met the inclusion criteria. Seventy-two individuals (9 MS, 4 NMOSD, 59 control) had undergone appendectomy. Appendectomy rates were 18.37% in the MS group (95% CI 7.5-29.2%), 5.6% in the NMOSD group (0.3%, 11%), and 6.7% among controls (5.1%, 8.4%), (MS vs NMOSD P = 0.036, MS vs controls P = 0.007). Binary regression analysis showed that MS was an independent risk factor for appendectomy (OR 2.938, 95% CI 1.302, 6.633, P = 0.009). NMOSD showed no association with appendectomy.
Conclusion: MS is positively associated with appendectomy, unlike ulcerative colitis, which is negatively associated. We hypothesize that there is a commonality in the microflora in persons who have had these two illnesses.
METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death).
RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group.
CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).
METHODS: The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA.
RESULTS: One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability.
DISCUSSION: These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.
METHODS: The Multiple Sclerosis International Federation third edition of the Atlas of MS was a survey that assessed the current global state of diagnosis including adoption of MS diagnostic criteria; barriers to diagnosis with respect to the patient, health care provider, and health system; and existence of national guidelines or national standards for speed of MS diagnosis.
RESULTS: Coordinators from 107 countries (representing approximately 82% of the world population), participated. Eighty-three percent reported at least 1 "major barrier" to early MS diagnosis. The most frequently reported barriers included the following: "lack of awareness of MS symptoms among general public" (68%), "lack of awareness of MS symptoms among health care professionals" (59%), and "lack of availability of health care professionals with knowledge to diagnose MS" (44%). One-third reported lack of "specialist medical equipment or diagnostic tests." Thirty-four percent reported the use of only 2017 McDonald criteria (McD-C) for diagnosis, and 79% reported 2017 McD-C as the "most commonly used criteria." Sixty-six percent reported at least 1 barrier to the adoption of 2017 McD-C, including "neurologists lack awareness or training" by 45%. There was no significant association between national guidelines pertaining to MS diagnosis or practice standards addressing the speed of diagnosis and presence of barriers to early MS diagnosis and implementation of 2017 McD-C.
DISCUSSION: This study finds pervasive consistent global barriers to early diagnosis of MS. While these barriers reflected a lack of resources in many countries, data also suggest that interventions designed to develop and implement accessible education and training can provide cost-effective opportunities to improve access to early MS diagnosis.
OBJECTIVE: Our study aimed to examine and contrast the clinical and radiological characteristics of TDL, high-grade gliomas (HGG) and primary CNS lymphoma (CNSL).
METHOD: This was a retrospective review of 66 patients (23 TDL, 31 HGG and 12 CNSL). Clinical and laboratory data were obtained. MRI brain at presentation were analyzed by two independent, blinded neuroradiologists.
RESULTS: Patients with TDLs were younger and predominantly female. Sensorimotor deficits and ataxia were more common amongst TDL whereas headaches and altered mental status were associated with HGG and CNSL. Compared to HGG and CNSL, MRI characteristics supporting TDL included relatively smaller size, lack of or mild mass effect, incomplete peripheral rim enhancement, absence of central enhancement or restricted diffusion, lack of cortical involvement, and presence of remote white matter lesions on the index scan. Paradoxically, some TDLs may present atypically or radiologically mimic CNS lymphomas.
CONCLUSION: Careful evaluation of clinical and radiological features helps in differentiating TDLs at first presentation from CNS neoplasms.