Practice Points
- The central vein sign (CVS) and paramagnetic rim lesions (PRL) can clarify complex diagnoses and lessen reliance on lumbar punctures, thereby reducing costs.
- Training for neurologists and radiologists should cover MRI protocols, image analysis, and how to provide emotional support when diagnosing multiple sclerosis (MS).
- Adoption of CVS/PRL would benefit from enhanced communication among neurologists, radiologists, and magnetic resonance physicists.
- People referred with potential MS want to be more involved in the diagnostic process and receive regular updates on referral status.
In the United Kingdom (UK), 150 people are diagnosed with multiple sclerosis (MS) every week.1 MS is a chronic inflammatory disease of the central nervous system, and timely diagnosis is critical to initiate immunosuppressive treatment and reduce long-term disability2; yet, on average, it takes 9 months from referral for people with MS to receive the diagnosis.3 These delays are not unique to the UK but represent an international challenge, partly due to the nonspecific nature of MS symptoms, exacerbated by lengthy diagnostic pathways.4 Prolonged waiting times have been highlighted as a significant contributor to patients’ emotional upheaval during the diagnostic process.5,6
The revised McDonald diagnostic criteria endorse the application of novel MRI biomarkers in clinical practice,7 offering MS services the opportunity to restructure their diagnostic pathway. One of the most significant updates is the inclusion of the central vein sign (CVS), a highly specific feature of MS lesions, which is visible on susceptibility-based sequences.8 This sign reflects the characteristic perivenular distribution of MS lesions.9 For a scan to be considered CVS-positive, 6 lesions are required to have a central vein; if there are fewer than 10 white matter lesions present on MRI, more than half must have a central vein.10 Application of the CVS as a biomarker has consistently shown a specificity of 85% to 98% for MS.11-13 This high specificity has led to the inclusion of the CVS as a tool supporting the diagnosis of MS, in both those presenting with clinical symptoms typical of MS and those solely with incidental imaging findings. A rarer but highly specific marker, paramagnetic rim lesions (PRLs), are thought to represent a ring of iron-rich macrophages and microglia around chronic lesions.14,15 PRLs have also been included in the revised criteria, albeit with a less prominent role.7
Previously, uncertain MS diagnoses would lead to a lumbar puncture (LP). Avoiding an LP and instead receiving an MRI scan for CVS/PRL analysis is highly preferred by most patients.16 LPs have a reported complication rate ranging from 8% to 60%, including a debilitating low-pressure headache in 5% to 36% of those who undergo the procedure.16,17 People who receive an LP require day-case hospital admission, time off from work, and additional recovery time. This also translates to an increased burden on health care professionals (HCPs) and systems. Replacing LPs with MRI scans, including susceptibility-based sequences, may not only facilitate a faster diagnosis, but also improve the experience for people who are ultimately diagnosed with MS.
The inclusion of CVS/PRL in international guidelines will not necessarily equate to changing clinical practice; previous literature suggests evidence can take up to 17 years to become routine.18 Implementing the revised MS guidelines is likely to take a prolonged period. A study’s results showed that just over half of MS specialist neurologists were correctly able to identify periventricular and juxtacortical lesions, highlighting the scale of the challenge to implement new radiological markers into clinical practice.19
To understand how CVS/PRL can be used in clinical practice to diagnose MS, theoretical frameworks such as normalization process theory (NPT) can be beneficial to identify what factors can contribute to ensuring this diagnostic criteria is applied within usual care.20 The 4 constructs of NPT (coherence, cognitive participation, collective action, and reflexive monitoring) can yield information on the barriers and facilitators to implementation in clinical practice.
This study sought to identify barriers and facilitators to implementing the CVS/PRL within an improved diagnostic pathway in the context of current broader challenges within the National Health Service (NHS) MS diagnostic pathway. We included the perspective of people with MS to ensure that any amendments to the diagnostic pathway considered their priorities. Although the study was based in the UK, this work provides insights for all centers considering the implementation of CVS/PRL to aid in the diagnosis of MS.
Methods
Ethics
This study was approved by the University of Nottingham Faculty of Medicine and Health Science Research Ethics Committee (FMHS 274-0824) and Nottingham University Hospitals NHS Trust (24-502C).
Study Aim and Objectives
Our aim was to learn how to successfully implement CVS/PRL into the MS diagnostic pathway. To do this, we sought to understand the challenges within the current MS diagnostic pathway, including the perspectives of people with MS and their priorities for improving the pathway; identify barriers and facilitators to implementing a new diagnostic pathway using CVS/PRL; and consider the utility of CVS/ PRL in cases of diagnostic uncertainty, including where individuals are referred with a preliminary nonspecific MRI suggestive of demyelination.
Study Design
Semistructured interviews and focus groups with people with MS and HCPs were conducted online using Microsoft Teams from October 2024 to February 2025. Interviewers (C.C.S.S, C.G., T.P.) received training from experienced qualitative researchers (B.D.P., L.T.). Interviewer characteristics are in Table 1.
Two participant groups were recruited: people with MS and HCPs. Eligibility criteria for the MS group were as follows: diagnosed in the last 10 years, 18 years or older, able to communicate in English, and able to provide consent. The inclusion criteria for HCPs were staff currently involved in the MS diagnostic pathway.
Participants were purposefully recruited to promote diversity in experiences and professional backgrounds. People with MS and HCPs were recruited through advertisements (University of Nottingham, social media), patient and public involvement networks, previous research studies, and personal contacts of the research team. Prior to the study, both groups of participants received an information sheet stating the study aim and provided written informed consent.
Data Collection
Participants had the choice of an interview or focus group based on availability. Only interviewers and participants were present during the interviews. Interviews and group discussions were video- and audio-recorded, and the team took field notes during the sessions. No repeat interviews were undertaken, and no participants left the study.
Topic guides were underpinned by NPT21 and an intervention logic model (Figure S1; all supplemental figures are available in a PDF at the end of the online paper). The interview topic guides were developed in collaboration through an iterative process with 3 authors (T.P., C.G., B.D.P.), but were not pilot tested with participants. Separate topic guides were developed for HCPs and people with MS (see Figures S2 and S3) to support semistructured interviews. Interviewers used these guides to tailor each interview to the specific expertise of the participant.
Researchers stopped collecting data when data saturation was reached. This was recognized when no new ideas were identified in data collection. Transcripts and results were not presented to participants for feedback.
Data Analysis
Interviews and focus groups were transcribed verbatim and analyzed using a framework (Table 2) in NVivo 15.0.
The framework method is a systematic approach to data analysis and coding that allowed us to identify barriers and facilitators within pathways. The framework was structured around NPT, enabling efficient categorization of relevant ideas based on factors influencing implementation. Initial coding themes were identified in advance based on the framework and revised through analysis. Data from both participant groups were analyzed separately and then synthesized to identify areas of synergy and dissonance.
Transcripts were independently coded by 3 researchers (C.C., C.G., T.P.). Disagreements were discussed with an experienced qualitative researcher (B.D.P.).
The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was used to ensure comprehensive reporting (Figure S4).
Results
Nineteen participants (9 people with MS; 10 HCPs) were recruited. All HCPs participated in a semistructured individual interview, whereas people with MS participated in either an interview (n = 2) or a focus group (n = 7) (Tables 3 and 4). Interviews and focus groups lasted between 30 and 75 minutes. Four themes with 12 subthemes were identified (Figure 1, Table 5).
Theme 1: Current Challenges in the Diagnostic Pathway
Inequality of Care
People with MS and HCPs identified disparities in the diagnostic experience, including variations in facilities and clinical expertise between MS centers and district general hospitals. HCPs specifically described discrepancies in access to advanced scanners and specialist neuroradiologists. Both groups highlighted differences based on the place of initial presentation: Acute services typically support faster diagnoses compared with waiting for outpatient appointments and investigations.
Inefficiencies
Both participant groups stated that diagnostic delays arose from long waiting times for appointments and scans. HCPs described how not all hospitals perform the MRI sequences required for CVS/PRL analysis, requiring neuroimaging to be repeated after referral to specialist centers. HCPs reported that initial consultations with MS specialists are often considered inefficient, as additional paraclinical data are required before a diagnosis is made; they described how delays in MRI and LPs being performed and then reported led to inefficiencies.
Communication
Both groups agreed that ineffective communication among HCPs caused delays, often due to scarce referral information. HCPs described how MRI scans are not always protocolled as requested, sometimes due to insufficient information being provided to radiologists. The pathway for communicating scan reports to neurologists is not streamlined in Nottingham; digitization is not optimally utilized, as radiology reports are still printed and manually transferred between secretaries and consultants. People with MS reported insufficient clarity on investigation timelines and experienced difficulties contacting the neurology team, which increased their distress. They wanted more detailed information at diagnosis and easy access to their medical records.
Theme 2: Barriers to Future CVS/PRL Implementation
Financial Constraints
HCPs highlighted how limited NHS funding may broadly hinder investment in improving the diagnostic pathway. For example, participants believed that scheduling CVS/PRL neuroimaging early in the diagnostic pathway could impact costs, including administrator support, extra neuroimaging in some cases, clinician time reorganization, and further HCP training. These could be challenging barriers to overcome in future implementation.
Capacity
HCPs were concerned that CVS/PRL analysis could increase demand on neurology and radiology services, potentially exposing weaknesses in the existing MS diagnostic pathway, including operational oversights and human errors. HCPs observed how all specialties would prefer their scans to be prioritized. They noted that if CVS/PRL imaging were to replace LPs, staffing requirements and financial costs may shift from neurology to radiology services.
Clinician Hesitancy With Revised Diagnostic Criteria
HCPs highlighted potential reluctance to change current practices. Neurologists acknowledged current misapplication of diagnostic criteria and misdiagnosis rates in MS. Some expressed concern that the updated MS diagnostic criteria could increase the risk of misdiagnosis, either through misclassification of CVS/PRLs or by enabling earlier diagnoses that may lack clinical certainty.
Theme 3: Suggestions for Overcoming Barriers and Improving the Diagnostic Pathway
Training, Awareness, and Guidance for HCPs on Applying CVS/PRL
HCPs discussed how the implementation of CVS/PRL into clinical practice would require greater awareness and targeted teaching. They suggested specific training on the necessary MR sequences and on how to interpret them. Hospital MS administrators wanted education on any improvements so they could support effective implementation and answer patient queries. The necessity of accurate neuroradiology reports was emphasized, and widespread dissemination was called for to ensure external radiology reporters are also skilled in CVS/PRL interpretation. Endorsement by relevant professional bodies would support broad implementation by providing clear standards to follow, which would increase clinician confidence.
Enhancing Interdisciplinary Communication
HCPs believed that enhanced dialogue between neurologists and neuroradiologists could facilitate a smoother diagnostic pathway. This might include discussions between the specialties on the desired MRI sequences for CVS/PRL analysis and their reporting. HCPs also felt they would benefit from enhanced access to neuroradiologist support in cases of diagnostic uncertainty, especially during multidisciplinary team meetings. Regarding the diagnostic pathway more generally, neurologists thought consultations could be improved by working more closely with MS nurses.
Providing Emotional and Practical Support
HCPs and people with MS suggested neurologists could benefit from specialized training on delivering emotional support at diagnosis. People with MS also emphasized the importance of a dedicated hospital contact throughout their diagnostic journey to address concerns about appointments and scans. They valued access to MS nurses to address their questions and concerns, and HCPs praised nurses' input. HCPs described how the presence of an MS nurse could improve the appointment during which the diagnosis is explained.
Evaluating the Impact of Improvements
Feedback from people with MS and quantitative audits could assess the impact of improvements. Outcome measures identified by HCPs included time to diagnosis and number of appointments in the improved pathway, patients’ experience of the pathway, and interpretation of CVS/PRL in radiology reports.
Theme 4: Benefits of Applying CVS/PRL Within the Diagnostic Pathway
Avoid Lumbar Punctures
HCPs and people with MS agreed that reducing LPs would improve the patient experience while still meeting the revised diagnostic criteria. Both groups preferred MRI scans as a primary diagnostic method. HCPs further suggested that reducing LP use would alleviate strain on hospital services.
Provide Clarity for Complex Diagnoses
In circumstances where it is difficult to distinguish MS from other conditions, HCPs suggested that the use of the CVS/PRL could reduce uncertainty. They believed CVS/PRL inclusion could expedite diagnostic decisions for complex cases.
Discussion
There are significant challenges to improving MS diagnostic care within the NHS. Similar to other nations, the UK health care system has financial constraints, with taxpayer funding allocated through a competitive commissioning process.22 This is exacerbated by an aging population, placing an increased demand on thinly spread services.23 In addition to these financial and capacity constraints, HCPs in our study cited concerns about regional inequality in service provision. People with MS described their practical experience of this, with long delays throughout their diagnostic journeys compounding the emotional strain associated with diagnosis. Tackling these challenges requires solutions that minimize additional workload for clinicians while reducing costs.
The inclusion of CVS/PRL imaging and analysis into the MS diagnostic pathway may help alleviate these pressures on NHS services. Until recently, more than 80% of people with suspected MS underwent LPs, which are costly (£505 per procedure in the NHS Payment Scheme) and associated with complications such as pain, hospital admissions, and missing days of work.24-26 Given that a head MRI is essential as part of the diagnostic work-up in all circumstances (£122 per scan), integrating CVS/PRL analysis may significantly reduce service costs by reducing LPs. HCPs discussed how early identification of CVS/PRL, even prior to a neurology consultation, could reduce the need for repeated MRIs and lower the average of 3 clinical appointments for an MS diagnosis (with first-time appointments costing £325 and later follow-ups £236).25,26 Further, the high specificity of CVS/PRL may help reduce the rate of MS misdiagnosis, estimated at 15%, with consequences including inappropriate treatment.4,27
Efforts must therefore be turned to supporting the rollout of these new MRI biomarkers. For successful implementation of the new diagnostic pathway, HCPs require training. Unfortunately, the provision of education in the NHS tends to follow a rigid approach with clear boundaries between different jobs and professional backgrounds that hamper the interaction between all HCPs involved in the care of people with a certain health condition.28 For the successful implementation of an improved MS diagnostic pathway, the training must include neurologists, MS nurses, radiographers, and others on the MS care team to ensure they all work toward the same goal.
Even though training is a core method for health care improvements,29 we need to understand how best to strike the balance between local implementation and global dissemination across different settings and regions. Didactic approaches are easier to disseminate at scale, whereas interactive training is more effective but resource-intensive.30 In this case, broad dissemination is essential to ensure that externally employed reporting radiologists receive training. An optimal strategy may blend national resources with local dissemination, codesigned with end users to ensure suitability in practice.
HCPs further stressed that adoption of CVS/PRL should be endorsed by national organizations to mitigate medico-legal risk for clinicians.31 Enhancing interdisciplinary collaboration between neurologists and radiologists was also highlighted, echoing broader literature that identifies communication as pivotal to sustaining health care innovation.32,33
Incorporating CVS/PRL analysis into diagnostic pathways presents an opportunity to improve overall care more broadly. An area relatively neglected in the pathway is the provision of emotional support at the time of diagnosis. One recommendation34 was for MS nurses to be present at diagnostic appointments, where feasible. This aligns with a recent study demonstrating the feasibility of an emotional support program delivered by nurses to address the concerns of people with MS.35 Providing emotional support at the time of diagnosis could be beneficial, given the complex psychological process of adjustment and the high levels of anxiety and depression experienced by people with MS.36
Two further technical themes not identified by our stakeholders must be considered. First, the variability in susceptibility-based sequence quality across MR scanners is a potential barrier to implementation. Although scanners can support CVS/PRL acquisition, image clarity varies, limiting diagnostic utility at some centers.37 Collaborations with MR vendors may be critical to optimize sequences before scaling training efforts. Second, automated CVS/PRL detection tools may support adoption by reducing the time for radiologist reporting. Promising initial studies have demonstrated that these tools perform with similar accuracy to clinicians.38,39 There are significant barriers to the use of artificial intelligence in the NHS; these include governance, medico-legal responsibilities, and cost. However, prior uptake of such tools in stroke care offers a precedent for future adoption in MS care.40
It is important to consider why these technical concerns were not revealed in our interviews. Automated detection tools may simply not have been prominent in the considerations of our participants (ie, availability bias), as they are still being validated and have not yet entered clinical practice. However, this may also reflect the key limitation of our study, that HCPs were recruited from a single academic center. Although HCPs discussed how services differ at other centers, unique challenges were not captured. The next step, therefore, is to expand this work by exploring barriers to implementation nationally and internationally with clinicians from a wide range of health care settings. A strength of our study is its rigorous qualitative methodology, with interview questions guided by NPT. We also capture previously overlooked perspectives by including a diverse range of stakeholders, such as administrators, MR physicists, and MS nurses.
Conclusions
Our study explores current challenges and perceived barriers and facilitators to implementing CVS/PRL within MS diagnostic pathways at an NHS MS center. Despite systemic pressures, stakeholders recognized the potential for these biomarkers to reduce the need for LPs, shorten diagnostic delays, and improve diagnostic clarity. Effective implementation would be supported by widespread staff training, efforts to enhance interdisciplinary communication, and endorsement from national bodies. CVS/PRL assessment offers the hope of improving patient care and cost-effectiveness; implementation must deliver this.
