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.).
MATERIALS AND METHODS: Therefore, based on current evidence and expert opinion, Malaysian expert panels from various disciplines have gathered to discuss the management of ESUS patients with PFO. This consensus sought to educate Malaysian healthcare professionals to diagnose and manage PFO in ESUS patients based on local resources and facilities.
RESULTS: Based on consensus, the Malaysian expert recommended PFO closure for embolic stroke patients who were younger than 60, had high RoPE scores and did not require long-term anticoagulation. However, the decision should be made after other mechanisms of stroke have been ruled out via thorough investigation and multidisciplinary evaluation. The PFO screening should be made using readily available imaging modalities, ideally contrasttransthoracic echocardiogram (c-TTE) or contrasttranscranial Doppler (c-TCD). The contrast-transesophageal echocardiogram (c-TEE) should be used for the confirmation of PFO diagnosis. The experts advised closing PFO as early as possible because there is limited evidence for late closure. For the post-closure follow-up management, dual antiplatelet therapy (DAPT) for one to three months, followed by single antiplatelet therapy (APT) for six months, is advised. Nonetheless, with joint care from a cardiologist and a neurologist, the multidisciplinary team will decide on the continuation of therapy.
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: 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.
METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays.
RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis.
CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.
METHODS: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.
RESULTS: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.
CONCLUSION: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.
TRIAL REGISTRATION: NCT01892345 (ClinicalTrials.gov).