Nikos Evangelou

The central vein sign (CVS) was included in 2024 McDonald criteria but remains underutilized in clinical practice. Implementation of CVS may reduce the requirement for lumbar punctures (LPs). At Nottingham, UK academic multiple sclerosis (MS) center, we implemented a fast-track (FT) pathway incorporating CVS analysis for people referred with imaging suggestive of MS as part of a quality improvement project. We retrospectively reviewed consecutive patients diagnosed with MS referred between March 1, 2024, and July 31, 2025. Data from 59 consecutive patients were analyzed. The mean time to diagnosis was 2.9 months in FT pathway and 5.6 months in usual outpatient pathway (Student t test mean 83-day difference, p = 0.003). No people with MS in FT pathway received a LP. The mean cost per patient was £707 (FT) vs £999 (outpatient). Routine application of CVS within a structured diagnostic pathway accelerated diagnosis, eliminated LPs, and reduced costs. Our findings support a broader adoption of CVS to streamline MS workup.

Background: Vocational rehabilitation (VR) interventions aimed at optimising job retention could help people with multiple sclerosis (MS) stay employed longer and prevent premature job loss. Currently, there is a lack of specialist services providing these types of interventions in the United Kingdom, and existing healthcare services are overstretched, hindering the introduction of a new service. This study aims to report on the adaptation of an MS-specific VR intervention for implementation within charities supporting those living with MS. Methods: Semi-structured interviews with people with MS, employers, and employees from charities, and informal communication with stakeholders from national charities supporting employment for people with disabilities. This study used the ADAPT guidance and normalisation process theory (NPT), which together informed the design, stakeholder engagement, and data analysis using framework analysis. Results: We conducted semi-structured interviews with 26 participants (11 people with MS, 12 MS charity employees, and three employers), and informal conversations with six stakeholders [charity employment specialists ( n = 3), disability advisors ( n = 2), charity CEO ( n = 1)]. Four themes mapped to the core NPT constructs were identified to explain the implementation process, including service structure, training non-specialists, intervention components, and service promotion. Recommended adaptations include providing guidance on structured intervention sessions, collaborations with external organisations, and monitoring intervention delivery and performance to maximise the use of the limited resources available. Conclusion: The adaptations identified can facilitate the delivery of the VR intervention within charities. Providing mentoring support, upskilling staff, and strategic collaborations are essential for the long-term sustainability of the intervention in this new context.

Background: Cognitive difficulties are common in people with multiple sclerosis (pwMS), yet access to neuropsychological rehabilitation is often limited or only provided to those with more severe impairments. The NEuRoMS intervention provides brief, tailored neuropsychological rehabilitation for pwMS with mild-to-moderate cognitive difficulties. Objectives: To evaluate feasibility and acceptability of the intervention and test procedures for a definitive trial. Methods: A mixed-methods, multi-centre feasibility randomised controlled trial (RCT) was conducted. Feasibility outcomes were recruitment, retention, outcome completion, randomisation, intervention delivery and fidelity. Quantitative data were collected at baseline, 3- and 6-months, supplemented by interviews with pwMS and healthcare providers. Results: Seventy-nine participants were randomised (mean age = 54.5 ( SD = 11.5); 70% women) from three UK MS clinics. Most feasibility criteria were met: retention (>80%) and outcome-measure completion (81%–89%) were high, and trial procedures were acceptable. Intervention delivery was feasible and delivered as intended, but staffing-related recruitment challenges need addressing in future trials. Preliminary signal of efficacy was observed, with 3.42-point difference (effect size = 0.48) in the planned primary outcome (MS psychological impact) favouring the intervention, supported by qualitative evidence of sustained behaviour change. Conclusion: The NEuRoMS intervention and trial procedures were feasible and acceptable, with early indication of efficacy. A definitive RCT is underway. Trial registration: ISRCTN11203922; https://doi.org/10.1186/ISRCTN11203922

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298

The genetic basis of multiple sclerosis (MS) susceptibility has been studied extensively in European (EUR) ancestry populations. The aim of our study was to determine the genetic architecture of MS susceptibility in people of South Asian (SAS) and African (AFR) genetic ancestral backgrounds. We recruited and genotyped a cohort of ancestrally diverse people with MS (pwMS) from across the United Kingdom. Cases were combined with controls from the UK Biobank (UKB). After genetic ancestry inference, we performed within-ancestry case-control genetic association studies of MS susceptibility, exploring single nucleotide variants and imputed classical human leukocyte antigen alleles. We analyzed genetic data from 676 pwMS from our cohort (median age = 45.7 years, 71.7% female genetic sex), 2,426 pwMS from the UKB (median age = 55.0 years, 72.3% female), and 27,640 UKB controls (median age = 54.0 years, 52.5% female). Genetic variants within the Major Histocompatibility Complex were associated with MS susceptibility across all ancestries (SAS: lead SNP chr6:32635095:G:C, odds ratio [OR] = 1.7, p = 4.2 × 10^-8, nearest gene HLA-DQA1; AFR: lead SNP chr6:32593550:T:C, OR = 1.7, p = 1.2 × 10^-5, nearest gene HLA-DRB1). EUR ancestry susceptibility alleles were over-represented in cases from both ancestries, with the degree of concordance stronger for the SAS (ρ = 0.46, p = 8.3 × 10^-9) than the AFR (ρ = 0.35, Spearman p = 2.5 × 10^-5) ancestry cohort. EUR-derived genetic risk scores performed better than chance but less well than in EUR ancestry cohorts, explaining 3.9% (SAS, p = 1.0 × 10^-4) and 1.9% (AFR, p = 2.0 × 10^-4) of the liability to MS, contrasting with 9.6% (empirical p = 1.0 × 10^-4) in the EUR cohort. Several classical human leukocyte antigen (HLA) alleles associated with MS in EUR ancestry populations show similar effects in SAS and AFR ancestry cohorts, including HLA-DRB1*15:01; however, the population-level risk explained by this allele is lower in SAS (8.8%) and AFR (2.9%) cohorts than in EUR cohorts due to allele frequency. We found some evidence for a protective role for the SAS-enriched HLA-A*33:03 allele in the SAS cohort, which has not been previously described. The genetic architecture of MS susceptibility shows strong concordance across ancestral groups suggesting shared disease mechanisms. Larger studies in diverse populations are likely to enhance our understanding of how genetic variation contributes to MS susceptibility in people of all ancestral backgrounds.

Background People with multiple sclerosis (MS) often leave the workforce prematurely due to MS symptoms and difficulties managing workplace relationships and performance. Vocational rehabilitation (VR) can improve job retention outcomes for people with MS, but there is a lack of evidence on the effectiveness of these interventions. Methods A multicentre, feasibility, parallel-group randomised controlled trial (RCT) comparing a job retention VR intervention plus usual care (n=30) with usual care alone (n=30). This study includes an embedded mixed-methods process evaluation. People with MS, aged 18-65 years, in paid employment will be recruited from MS charities. Participants with MS will be able to include their employers in the intervention to receive information about MS and employment. The intervention involves an initial interview and up to 10 hours of employment support for people with MS and up to four hours of support for employers, over six months. Employees from MS charities will be recruited and trained to deliver the MSVR intervention. Participants will be followed up by postal/telephone/online questionnaires at 6-, 9-, and 12-months post-randomisation. The aim is to ascertain the feasibility and acceptability of delivering the intervention within MS charities, and to determine parameters for future trial and explore the acceptability of the study intervention and procedures. Discussion This novel study will provide insight into how existing services from MS charities can fill a service gap by providing employment support to people with MS. Findings will inform the design of a future fully powered RCT. Trial Registration Number NCT06966115

Background: Job retention vocational rehabilitation (VR) interventions for people with multiple sclerosis (MS) can positively impact a person's independence and directly influence health and employment outcomes. However, evaluating the effectiveness of VR interventions can be challenging due to their highly individualised nature and the diverse range of potential health and employment outcomes that may be impacted.Aim: To identify the most important outcomes of a job retention VR intervention from the perspective of people with MS.Design: A nominal group technique (NGT) was conducted with people with MS using Microsoft Teams and Microsoft Forms. The study involved completing a demographic questionnaire, being introduced to VR, silently generating ideas, round‐robin discussions, ranking outcomes and reaching a consensus. NGT data were analysed using thematic analysis.Results: We conducted two NGTs involving 10 participants with MS. Nine outcomes were identified and ranked based on priority, relating to four themes: (1) Employer support and collaboration; (2) Empowerment; (3) Symptom management and progression and (4) Professional well‐being and performance.Conclusion: Improvements in employer support and symptom management were seen as key outcomes for VR interventions that could eventually lead to enhanced work performance and job retention for people with MS. Future research should explore how feasible it is to collect these outcomes to ascertain the impact of VR on employment over time. Due to the complexity of the outcomes identified, there may be a need to develop new outcome measures with improved validity and sensitivity to these interventions.Patient or Public Contribution: This study is part of a larger project co‐developed with three people MS. A lead patient and public involvement representative and lay co‐author reviewed the study topic guide to improve clarity and study focus and supported the group discussions and data analysis with input from the lead researcher.