Ruth Geraldes

Background: Real-world data are crucial to improving care for patients with rare diseases. Objectives: To develop the first global map of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD) patient registries/databases. Registries/databases were identified through rare disease portals, registry websites, and other sources, and surveyed. Results: Of the respondents ( N = 26), the majority were established within the past 15 years and reported being self-funded. Most collect diagnostic, clinical, and laboratory data. Major objectives included supporting scientific research and advancing disease understanding. Conclusions: Despite cost, time, resource, and data quality challenges, registries/databases provide important insights into addressing unmet needs in MOGAD and NMOSD.

Background and ObjectivesA proportion of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) experience relapses, but biomarkers predicting which patients are like...

Background: The effects of smoking and vascular risk factors (VRF) on relapse activity in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well understood. We aimed to investigate these. Methods: MOGAD patients in the Oxford National Neuromyelitis Optica (NMO) Service with known smoking or VRF (hypertension, hypercholesterolaemia, type 2 diabetes, elevated body mass index) status were considered for inclusion. Outcomes were time-to-relapsing course and relapse rate. Cox and negative binomial regression were utilised. Results: We included 172 patients. Current smokers had a 2.2 times higher relapse rate than never smokers (adjusted rate ratio 2.23 [95% CI = 1.35–3.68], p = 0.0017). Relapse rate was similar between past and never smokers (adjusted rate ratio 0.81 [0.51–1.29], p = 0.38). For time-to-relapsing course, multivariable analysis did not identify smoking as associated although univariable analysis showed a consistent trend with shorter time-to-relapse in current than never smokers (hazard ratio 1.76 [0.97–3.22], p = 0.06). There was no difference in either outcome by VRF status. Conclusion: Relapse rates were doubled in current than never smokers, whereas these were similar between past and never smokers. VRF did not associate with relapse risk. Smoking cessation should be encouraged in current smokers with MOGAD as past smokers were not observed with this poorer outcome.

The most common cause of convexity subarachnoid hemorrhage (cSAH) in younger patients (younger than 60 years) is reversible cerebral vasoconstriction syndrome (RCVS). Evidence on the long-term outcomes of future vascular events and functional outcome after cSAH due to RCVS is limited. We aimed to assess the rates and baseline predictors of our primary outcomes (cSAH, intracerebral hemorrhage (ICH), and ischemic stroke), functional outcome, and mortality after cSAH attributed to RCVS. Individual patient data pooled analysis in patients with cSAH attributed to RCVS. A systematic literature search was conducted in PubMed and EMBASE. Two independent reviewers screened studies and extracted data. Quality assessment was assessed using the Newcastle-Ottawa Scale. Early events during the accepted time frame of an RCVS episode (<3 months) were classified as progression rather than recurrence. Follow-up was truncated at 5 years. Primary outcomes were recurrent cSAH, ICH, and ischemic stroke. Secondary outcomes were mortality and functional status measured by modified Rankin Score (mRS). We identified 21 eligible cohorts finally including 138 patients from 9 collaborative centers, which provided individual patient data. The mean age was 49.3 ± 12.1 years, and 110 (79.7%) were female. During a mean follow-up of 1.8 years, annual rates were cSAH recurrence 0.81% (95% CI 0.1-2.91), ICH 0.81% (95% CI 0.1-2.91), and ischemic stroke 0.81% (95% CI 0.1-2.91). Progression during the initial episode (shortly after admission) occurred in 10 patients for cSAH, 2 for ICH, and 8 for ischemic stroke, respectively. Of 106 patients (76.8%) with available outcome data, 100 (94.3%) achieve a mRS of ≤1 at follow-up, indicating no significant disability. Two patients died (annual rate 0.5%, 95% CI 0.09-2.9): one within 10 days and the other within 2 months of the cSAH. Our data suggest a favorable prognosis for most patients after RCVS-associated cSAH with low rates of recurrent events and a high proportion achieving functional independence. Major limitations include retrospective data collection and potential selection bias from centers providing individual patient data. Nevertheless, these findings provide prognostic information to inform clinical practice.

Background: Smoking and vascular risk factors (VRFs) are reported to have adverse effects in multiple sclerosis but data are limited in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study aimed to measure their impact on disability. Methods: Smoking status was defined as never, past or current smokers and VRF comprised of ⩾1: hypertension, dyslipidemia, high body mass index or diabetes. Logistic regression models were fitted to predict their influence on recovery from onset attack and first optic neuritis (ON) attack. Results: A total of 442 patients were included. Current MOGAD smokers had a higher risk of disability from onset attack and first ON attack than never smokers (odds ratio (OR) 2.9, 95% confidence interval (CI) 1.3–6.9; OR 3.3, 95% CI 1.4–7.8). VRF in MOGAD was not predictive of disability. Current AQP4-NMOSD smokers and VRFs had a higher risk of residual disability from onset attacks (OR 7.5, 95% CI 2.1–27.7; OR 1.9, 95% CI 1.0–3.4). VRF was associated with higher risk of visual disability (OR 2.6, 95% CI 1.08–6.46) while smoking status was not. Conclusions: Current smoking status detrimentally influenced onset attack recovery in AQP4-NMOSD and MOGAD patients, including visual recovery in MOGAD. Non-smoking VRFs influenced clinical and visual outcomes in AQP4-NMOSD.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. Methods and analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0–6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate. The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression. Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. Ethics and dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration numbers: NCT03387670 ; ISRCTN82598726 .

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders.

Objectives: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Methods: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. Results: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00–4.06): 102 (2.13% 95% CI 1.73–2.56) with stroke and 81 (1.68% 95% CI 1.33–2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet’s disease (9.5%, 95% CI 5.79–14.37), polyarteritis nodosa (6.2%, 95% CI 3.25–10.61), and Takayasu’s arteritis (6.0%, 95% CI 4.30–8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09–3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20–3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05–9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01–2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. Conclusion: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet’s. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.