Serum neurofilament light chain (sNfL) levels reflect neuroaxonal damage and independently predict conversion to multiple sclerosis (MS) in individuals with radiologically isolated syndrome (RIS). This study aimed to assess how sNfL testing influences neurologists’ decisions regarding disease-modifying treatment (DMT) in the management of RIS.

 A noninterventional, web-based study was conducted among neurologists actively involved in MS care across Spain. Participants reviewed a simulated case of a 24-year-old woman diagnosed with RIS, characterized by a brain MRI showing 1 juxtacortical and 8 periventricular T2 hyperintense lesions, cerebrospinal fluid oligoclonal bands, and sNfL levels of 24 pg/mL. The neurologists had to decide whether to recommend initiating DMT or to schedule a reassessment in 6 to 12 months, with the latter considered a decision misaligned with emerging evidence (DMEE).

A total of 116 neurologists participated in the study (mean age, 41.9 years; 53.4% men). Overall, 58.6% (n = 68) opted against recommending the initiation of DMT. Lack of full dedication to MS care (OR, 2.52; 95% CI, 1.02-6.20; 

 = .045) and limited perception of sNfL benefits (OR, 1.03; 95% CI, 1.01-1.05; 

In a simulated high-risk RIS scenario with elevated sNfL levels, most neurologists refrained from recommending the initiation of DMT. These findings reinforce the need to increase awareness of prognostic factors for RIS-to-MS conversion and the utility of sNfL testing in guiding therapeutic decisions.

From the Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Department of Neurology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain (JEM-L); Universidad Católica San Antonio, Murcia, Spain (JEM-L); Division of Neurology, Department of Medicine, St Michael’s Hospital, University of Toronto, Toronto, Canada (GS); Clinical Outcomes and Decision Neuroscience Unit, Li Ka Shing Institute, University of Toronto, Toronto, Canada (GS); Medical Department, Roche Farma, Madrid, Spain (RG-B, NM, JM); Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain (JMG-D); Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (LQ); Department of Neurology, Hospital Universitario Doctor Peset, Valencia, Spain (LL); Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain (VM-L); Department of Immunology, Hospital Universitario Ramón y Cajal, Madrid, Spain (LMV); Department of Neurology, Hospital Universitario Reina Sofía, Córdoba, Spain (EA); Department of Neurology, Complejo Asistencial de Ávila, Ávila, Spain (ABC); Department of Neurology, Hospital Universitari de Bellvitge-Institut d’Investigació Biomèdica de Bellvitge, L’Hospitalet de Llobregat, Spain; (SM-Y); Departament of Clinical Sciences, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain (SM-Y); and the Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Red Española de Esclerosis Múltiple, Red de Enfermedades Inflamatorias, Universidad de Alcalá, Madrid, Spain (EM). 

: Jorge Maurino, Ribera del Loira 50, (28042), Madrid, Spain; 


* These authors contributed equally to this work.

 The authors are grateful to the Spanish Society of Neurology and all neurologists who participated in the study.

This study was funded by Roche Medical Department Spain (SL44806). The funding source had no role in the design, analysis, and interpretation of the data; review or approval of the manuscript; or decision to submit for publication.

The abstract of this article was presented at the 10th Congress of the European Academy of Neurology as a poster presentation with interim findings (EPV681); June 29-July 2, 2024; Helsinki, Finland.

José E. Meca-Lallana, MD, received meeting honoraria and participated in clinical trials and other research projects promoted by Alexion, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, and Sanofi. Gustavo Saposnik, MD, received consulting fees from Roche Farma Spain and is supported by the University of Toronto Scientific Merit award. José M. García-Domínguez, MD, received speaker, adviser, and researcher honoraria from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. Enric Monreal, MD, reported receiving research grants, travel support, or honoraria for speaking engagements from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, and Sanofi. Lamberto Landete, MD, received advisory board and scientific and educational activities honoraria from Almirall, Bayer, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi, Teva, and UCB. Virginia Meca-Lallana, MD, received consulting and speaking fees from Almirall, Biogen, Bristol Myers Squibb, Genzyme, Janssen, Merck, Novartis, Roche, Sanofi, Terumo, and Teva. Luis Querol, MD, received speaker honoraria from Biogen, CSL Behring, Grifols, Merck, Sanofi, and Roche; provided expert testimony for Annexon Pharmaceuticals, CSL-Behring, Grifols, Johnson & Johnson, Novartis, Sanofi, and Takeda; and received research funds from Grifols, Roche, and UCB. Eduardo Agüera, MD, received speaking honoraria from Biogen, Merck, Novartis, Roche, and Sanofi. Sergio Martínez-Yélamos, MD, received advisory board, consultant, and scientific communications; collaboration honoraria; research support; and funding for travel and congress expenses from Almirall, Bayer, Biogen Idec, Bristol Myers Squibb, Genzyme, Merck, Novartis, Roche, Sanofi, and Teva. Luisa M. Villar, PhD, reported receiving research grants and personal fees from Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi. Ana B. Caminero, MD, received courses and honoraria for her participation as speaker/meeting moderator/symposia organizer from Almirall, Alter, Bayer, Bial, Biogen, Bristol Myers Squibb, Lilly, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, Teva, and UCB; and support to attend scientific meetings from Bial, Biogen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Rocío Gómez-Ballesteros, MSc; Nicolas Medrano, MS; and Jorge Maurino, MD; are employees of Roche Farma Spain.

José E. Meca-Lallana, MD

Gustavo Saposnik, MD

Rocío Gómez-Ballesteros, MSc

José M. García-Domínguez, MD

Luis Querol, MD

Lamberto Landete, MD

Virginia Meca-Lallana, MD

Luisa M. Villar, PhD

Eduardo Agüera, MD

Ana B. Caminero, MD

Sergio Martínez-Yélamos, MD

Nicolás Medrano, MD

Jorge Maurino, MD

Enric Monreal, MD

Serum neurofilament light chain (sNfL) measurement can help identify individuals with radiologically isolated syndrome (RIS) who are at high risk for multiple sclerosis (MS) conversion.

Despite evidence supporting early treatment in RIS, many neurologists hesitate to initiate disease-modifying therapy, revealing a limited
perception of the benefits of biomarkers like sNfL.

Neurologists not fully dedicated to MS are more likely to defer treatment initiation, emphasizing the need for specialized MS care.

Standardizing sNfL protocols, defining reference ranges, and raising awareness of clinical utility are key to improving RIS management.

The rising adoption of advanced brain imaging in medicine has led to the detection of incidental brain and spinal cord abnormalities, even in the absence of clinical symptoms.

 Radiologically isolated syndrome (RIS) describes individuals who exhibit focal white matter T2-hyperintense MRI lesions in the central nervous system that are highly suggestive of multiple sclerosis (MS), despite showing no symptoms and having a normal neurological examination.

Although RIS is relatively rare, with a cumulative incidence of 0.1%-0.7% according to Okuda criteria, between 30.7% and 51.2% of individuals develop MS within 3 years and 10 years following the initial detection of these incidental lesions, respectively.

 Young age; male sex; presence of oligoclonal bands (OCBs) in cerebrospinal fluid; and infratentorial, spinal cord, or gadolinium-enhancing lesions on the index MRI scan are associated with an increased risk of developing MS in individuals with RIS.

Serum neurofilament light chain (sNfL) concentrations serve as a biomarker of neuroaxonal damage in different inflammatory and neurodegenerative disorders and are increasingly used in MS care to predict clinical outcomes and monitor treatment response.

Elevated sNfL levels have been identified as a new independent risk factor of conversion to MS among individuals with RIS, with higher values correlating with a shorter time to first symptom.

 Testing of sNfL helps detect spinal cord lesions and/or OCBs and aids in discriminating individuals who have a high risk for clinical conversion from individuals with stable RIS.

The findings of 2 recent studies demonstrated that early treatment with disease-modifying therapies (DMT), such as dimethyl fumarate or teriflunomide, in patients with RIS significantly reduces the risk of developing the first clinical symptoms associated with MS.

 However, there is still uncertainty about whether all individuals should receive treatment.

 In this context, having a reliable and noninvasive biomarker of inflammatory activity like sNfL could aid neurologists in making prompt therapeutic decisions.

The aim of this study was to assess how sNfL testing influences neurologists’ decisions regarding the initiation of DMT in the management of RIS.

We conducted a noninterventional, cross-sectional, web-based study in collaboration with the Spanish Society of Neurology (SEN) as part of the NewFeeLs-MS project.

 This study aimed to evaluate neurologists’ perspectives on the utility of sNfL measurement in guiding treatment decisions in MS. Specifically, the present analysis examines choices regarding the initiation of DMT in individuals with RIS.

Neurologists actively involved in MS care completed a questionnaire and provided details about their demographic characteristics, professional background, clinical setting, and behavioral characteristics, including attitude toward evidence-based innovation, medical empathy, care-related regret, risk attitude at work, and occupational burnout. Participants were then provided with a simulated case scenario reflecting a common encounter with an individual with RIS to assess treatment initiation supported by sNfL levels. This case scenario was developed by the research team based on clinical practice and literature review.

Participants were invited to participate via e-mail from SEN. The study was approved by the Hospital Universitario Clínico San Carlos, Madrid, Spain, ethical review board (reference 23/471-E). All participants provided written informed consent and were recruited from August 28, 2023, to December 12, 2023.

The simulated case scenario described a 24-year-old woman diagnosed with RIS based on an incidental brain MRI performed for a headache episode that showed 1 juxtacortical and 8 periventricular white matter T2-hyperintense lesions highly suggestive of MS. The patient had OCBs in her cerebrospinal fluid and sNfL levels of 24 pg/mL. Participants were informed that there was no other neurological or nonneurological condition that could explain the radiological findings and sNfL levels. They then had to decide whether to recommend initiating treatment with teriflunomide or dimethyl fumarate, or to schedule the patient for a reassessment in 6 to 12 months.

Before starting the experiment, participants were shown a screen with the following instructions: “We invite you to participate in a short survey to understand how sNfL testing influences decisions regarding the initiation of disease-modifying treatment in the management of RIS. We will present a case as a hypothetical situation in which the decision to treat should not be conditioned by hospital protocols, drug access, or costs. Responses should not be conditioned by reasons other than clinical judgment. The pathological cutoff point for sNfL levels will be 10 pg/mL.”

The primary outcome was decisions misaligned with emerging evidence (DMEE), defined as not recommending the initiation of DMT despite an elevated sNfL level.

Participants’ perceptions regarding the benefits of sNfL measurement were assessed by level of agreement with the following statement: “On a scale of 1% to 100%, what is your expectation of the usefulness of the sNfL determination in defining treatment for this patient?” The Evidence-Based Practice Attitude Scale (EBPAS) is a validated 15-item instrument designed to evaluate health care professionals’ openness to embracing new evidence-based treatments, interventions, and practices.

 Scores on the EBPAS range from 0 to 4, with higher scores reflecting a more favorable attitude toward health care innovations. Empathy levels among health care professionals were measured using the 20-item Jefferson Scale of Empathy-Health Professionals.

 This scale produces a continuous variable score ranging from 20 to 140, with higher scores indicating a greater degree of empathy toward patients. A previous experience involving regret related to caring for a patient was evaluated using the 10-item Regret Intensity Scale.

 A cutoff score of greater than 3 indicates the presence of care-related regret. The risk attitude at work was assessed using a single question from the German Socio-Economic Panel, a validated survey that measures willingness to take risks across various domains.

 Respondents were asked to rate their inclination to take risks in their work on a scale of 0 (not at all) to 10 (extremely). Occupational burnout was assessed using a single-item measure derived from the Physician Worklife Study.

 This measure utilizes a 5-category ordinal scale, where a cutoff score of greater than or equal to 3 indicates the presence of burnout.

Descriptive statistics were calculated for all variables. Continuous variables were summarized using measures of central tendency (mean and median) and variability/dispersion (SD and IQR). Categorical variables were described using absolute and relative frequencies (percentages).

Logistic regression models were used to evaluate the relationship between participants’ characteristics and the primary binary outcome of interest. The explanatory variables included in the model were predefined based on conceptual and clinical relevance, ensuring a balance between empirical and conceptual justification: age, sex, years of professional practice, years caring for patients with MS, practice setting (academic vs nonacademic), full or partial dedication to MS care, number of people with MS seen weekly, access to sNfL testing, participation in MS clinical trials (yes or no), burnout (yes or no), empathy, attitude toward innovation, care-related regret, and risk attitude at work. All variables were included simultaneously in the multivariable model to assess their independent associations with DMEE. Responses were mandatory, resulting in no missing data. Model fit was evaluated using the Hosmer-Lemeshow test and the C statistic.

121 completed the survey (completion rate, 89.6%). After excluding 5 participants who did not meet the inclusion criteria, the final analysis included 116 neurologists. The participants had a mean age of 41.9 years (SD, 10.1), and 53.4% were men. Seventy-eight (67.2%) neurologists were fully dedicated to the care of demyelinating disorders and managed a median of 16.0 (IQR, 10.0-25.0) patients with MS per week. Although 94.8% (n = 110) worked in academic hospitals, only 34.5% (n = 40) had access to sNfL testing at their hospitals. The 

Participant Demographic, Professional, and Behavioral Characteristics

Overall, 58.6% of participants (n = 68) showed DMEE. Participants’ overall expectations regarding the benefits of sNfL testing in this case were moderate, with a median of 60.5 (IQR, 40.0, 77.8). Participants with DMEE cared for fewer patients with MS per week (

= .01), participated less frequently in clinical trials (

= .01), and reported a lower willingness to adopt innovations compared with their counterparts (

= .03). The multivariable analysis, which was adjusted for age, years of experience, number of patients per week, EBPAS score, and global perception of sNfL value (as continuous variables), as well as sex, participation in clinical trials, and full or partial dedication to MS care (as dichotomous variables), indicated 2 significant associations with DMEE. Being a neurologist not exclusively dedicated to MS care (OR, 2.52; 95% CI, 1.02-6.20; 

= .04) and having a low perception of the clinical utility of sNfL (OR, 1.03; 95% CI, 1.01-1.05; 

< .001) were associated with DMEE. Participants’ demographic and behavioral characteristics, type of hospital, number of patients with MS, or access to sNfL tests were not associated with DMEE. There was no evidence of collinearity. The models demonstrated good fit, as indicated by the Hosmer-Lemeshow test (

Longitudinal studies assessing individuals with RIS found that over 50% will experience the first clinical event of MS within 10 years after the detection of incidental lesions.

 Elevated levels of sNfL have been identified as an independent risk factor for clinical conversion within 3 years of RIS diagnosis, with a hazard ratio of 2.8 (95% CI, 1.2-6.6; 

 Further, randomized, double-blind clinical trials showed that dimethyl fumarate and teriflunomide significantly delay the time to the first clinical event in individuals with RIS, with a risk reduction of 80% and 72%, respectively, vs placebo.

 In this context, RIS still presents a clinical dilemma for neurologists, balancing the potential benefits of early initiation of DMT to prevent conversion to MS against the risk of adverse events in asymptomatic individuals.

In our study, nearly 60% of participants in a survey organized in collaboration with the SEN chose not to initiate any DMT in a simulated case of RIS with an elevated sNfL level, despite the high risk of MS conversion. The lack of full dedication to MS care and a limited perception of sNfL benefits were associated with suboptimal decisions in this scenario. Notably, neurologists who managed neurological disorders other than MS were 2.5 times more likely to refrain from recommending the initiation of treatment. These findings suggest that although sNfL is a valuable prognostic biomarker, there may be areas where neurologists’ confidence or perception of its clinical utility in guiding therapeutic decisions for high-risk RIS patients could be further developed.

Neurologists’ decision-making process regarding whether to treat individuals with RIS has been explored in a few studies, all predating the outcomes of clinical trials involving dimethyl fumarate and teriflunomide and the availability of sNfL testing.

 In general, although there were variations among neurologists in Europe, the United States, and Latin America, the prevailing tendency was not to initiate DMT in cases of RIS.

 Follow-up MRI played a crucial role in this decision, particularly if gadolinium-enhanced lesions and/or new or enlarging T2 lesions were detected.

The likelihood of experiencing a first clinical event increases gradually as the number of risk factors rises.

 The emergence of ultrasensitive single-molecule detection technologies has enabled the measurement of sNfL as a marker of ongoing inflammatory disease activity in different neurological disorders.

 Measuring sNfL appears to be a reliable and easy-to-implement additional tool for identifying high-risk individuals with RIS in the context of the treatment decision-making process.

 Rival et al found that 84% of a sample of 57 individuals with RIS and OCBs, spinal cord lesions, and sNfL levels greater than 5 pg/mL at diagnosis experienced clinical conversion within 3 years, compared with 34% in the remaining cases where no association of these factors was observed.

 In our simulated case scenario, there were 3 risk factors associated with MS: being younger than 37 years, the presence of OCBs, and an elevated sNfL determination.

Physicians’ decisions to adopt or reject a new diagnostic tool are perceptual phenomena influenced by a combination of objective knowledge and emotional factors.

 These factors include demographic elements (eg, age, sex, and practice setting) and behavioral elements (eg, risk preferences and personal approach). In addition, considerations related to the innovation itself, such as ease of use, perceived usefulness, potential risks, and financial implications, also play a role. The moderated recognition of the benefits of sNfL in our study can be attributed to several factors. These may include its lack of specificity; susceptibility to confounding factors such as age, sex, renal function, or body mass index; and the absence of standardized measurement techniques and reference ranges across different neurological populations and diseases.

Our study’s findings align with previous research, showing that general neurologists or those not exclusively focused on managing demyelinating diseases are more likely to make suboptimal medical decisions when compared with MS specialists.

 Multidisciplinary MS care units provide a comprehensive and specialized approach to managing demyelinating diseases, ultimately leading to improved patient outcomes and enhanced quality of life, as well as cost-effective care.

 In today’s MS care landscape, management has become increasingly complex due to the diverse array of diagnostic and follow-up techniques available, as well as the varying efficacy and safety profiles of treatment options. This dynamic environment demands a comprehensive approach that integrates evolving treatments, outcomes assessment, and biomarker utilization to optimize care delivery and patient outcomes. Consequently, neurologists who are not exclusively focused on managing demyelinating diseases may find it challenging to fully integrate the wide variety of factors that affect current MS care. Given the complexity of RIS management, we suggest that patients with RIS be treated by neurologists with greater clinical and radiological expertise to optimize outcomes. Future research could explore the impact of specialist care on RIS outcomes.

The emergence of sNfL testing as a promising biomarker in the context of RIS management presents both opportunities and challenges. Although sNfL measurement holds potential for identifying high-risk individuals and informing treatment decisions, its integration into clinical practice requires careful consideration of various factors, including standardization of measurement techniques, establishment of reference ranges, and enhancement of neurologists’ awareness and understanding of its clinical implications.

Our study has some limitations. First, we included 3 risk factors associated with conversion to MS.

 This suggests that our results might have been more pronounced (meaning that a larger number of participants might have deferred treatment initiation) if we had included a simulation of elevated sNfL levels in isolation. Second, the study did not collect the participants’ level of knowledge about sNfL in demyelinating disorders, a factor potentially impacting their perception of the utility of this assessment. Third, our exclusive focus on practicing neurologists from Spain might limit the generalizability of our findings to other cultural contexts and health care systems. Fourth, this study did not investigate the financial implications or the practical ease of obtaining sNfL testing, nor the current lack of funding of DMT in the RIS indication, for health care systems in Spain, factors that could impact real-world treatment decisions despite being explicitly removed from our simulated scenario. Fifth, although our study demonstrated that elevated sNfL levels did not uniformly lead to treatment initiation in our simulated scenario, a limitation is that the study design did not include a direct comparison with a hypothetical case with low sNfL levels. Such a comparison could further elucidate the precise weight neurologists attribute to this biomarker in guiding therapeutic decisions, providing a clearer understanding of whether a low sNfL would indeed lead to a different recommendation. Finally, our study was conducted before the release of the 2024 revision of the McDonald MS diagnostic criteria, which introduced a major change by reclassifying RIS as MS for individuals meeting specific criteria, such as the presence of dissemination in space and time and OCBs in the cerebrospinal fluid.

 This update is expected to significantly influence clinical decision-making, as it expands the definition of MS to include a subset of individuals previously categorized as having RIS. Consequently, neurologists may now be more likely to initiate treatment in such cases. As a result, our findings, which are based on the prior classification system, may not fully reflect current therapeutic strategies, highlighting the need for future studies to explore the impact of these updated criteria on clinical practice. Despite these limitations, a strength of our study is its representation of neurologists managing MS and other demyelinating disorders in Spain, with our sample comprising approximately 58% of this group, according to SEN data.

Despite the recognized association between elevated sNfL levels and an increased risk of conversion to MS, more than 50% of neurologists made decisions misaligned with emerging evidence by not recommending the initiation of DMT in a simulated case of RIS with high sNfL levels. Neurologists not exclusively dedicated to MS care and those with a limited perception of sNfL benefits were more likely to defer treatment initiation, highlighting potential gaps in knowledge and practice patterns. Efforts led by scientific societies are essential to develop evidence-based guidelines and educational initiatives that enhance neurologists’ understanding of sNfL testing and other risk factors relevant to caring for patients with RIS.

Gibson LM, Paul L, Chappell FM, et al. Potentially serious incidental findings on brain and body magnetic resonance imaging of apparently asymptomatic adults: systematic review and meta-analysis. 

Lebrun-Frénay C, Okuda DT, Siva A, et al. The radiologically isolated syndrome: revised diagnostic criteria. 

. 2023;146(8):3431-3443. doi:10.1093/brain/awad073

Okuda DT, Lebrun-Frénay C. Radiologically isolated syndrome in the spectrum of multiple sclerosis. 

. 2024;30(6):630-636. doi:10.1177/13524585241245306

Preziosa P, Rocca MA, Filippi M. Radiologically isolated syndromes: to treat or not to treat? 

. 2024;271(5):2370-2378. doi:10.1007/s00415-024-12294-4

Maunula A, Martola J, Atula S, et al. Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis: a data lake cohort study. 

. 2023;30(8):2376-2384. doi:10.1111/ene.15849

Lebrun-Frénay C, Rollot F, Mondot L, et al. Risk factors and time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome. 

. 2021;4(10):e2128271. doi:10.1001/jamanetworkopen.2021.28271

Amato MP, De Stefano N, Inglese M, et al. Secondary prevention in radiologically isolated syndromes and prodromal stages of multiple sclerosis. 

. 2022;13:787160. doi:10.3389/fneur.2022.787160

Moura J, Granziera C, Marta M, et al. Emerging imaging markers in radiologically isolated syndrome: implications for earlier treatment initiation. 

. 2024;45(7):3061-3068. doi:10.1007/s10072-024-07402-1

Mato-Abad V, Labiano-Fontcuberta A, Rodríguez-Yáñez S, et al. Classification of radiologically isolated syndrome and clinically isolated syndrome with
machine-learning techniques. 

. 2019;26(7):1000-1005. doi:10.1111/ene.13923

Rojas JI, Pappolla A, Blaya P, et al. Accumulative risk of clinical event in high-risk radiologically isolated syndrome in Argentina: data from the nationwide registry RelevarEM. 

. 2022;269(4):2073-2079. doi:10.1007/s00415-021-10791-4

Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders - towards clinical application. 

. 2024;20(5):269-287. doi:10.1038/s41582-024-00955-x

Monreal E, Ruiz PD, San Román IL, et al. Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis. 

 2024;12:1397845. doi:10.3389
/fpubh.2024.1397845

Kölliker Frers RA, Otero-Losada M, Kobiec T, et al. Multidimensional overview of neurofilament light chain contribution to comprehensively understanding multiple sclerosis. 

. 2022;13:912005. doi:10.3389/fimmu.2022.912005

Freedman MS, Gnanapavan S, Booth RA, et al. Guidance for use of neurofilament light chain as a cerebrospinal fluid and blood biomarker in multiple sclerosis management. 

. 2024;101:104970. doi:10.1016/j.ebiom.2024.104970

Rival M, Thouvenot E, Du Trieu de Terdonck L, et al. Neurofilament light chain levels are predictive of clinical conversion in radiologically isolated syndrome. 

. 2022;10(1):e200044. doi:10.1212/NXI
.0000000000200044

Okuda DT, Kantarci O, Lebrun-Frénay C, et al. Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome. 

. 2023;93(3):604-614. doi:10.1002/ana.26555

Lebrun-Frénay C, Siva A, Sormani MP, et al. Teriflunomide and time to clinical multiple sclerosis in patients with radiologically isolated syndrome: the TERIS randomized clinical trial. 

. 2023;80(10):1080-1088. doi:10.1001/jamaneurol.2023.2815

Smets I. Presymptomatic MS or radiologically isolated syndrome (RIS) should be actively monitored and treated - NO. 

. 2023;29(7):795-797. doi:10.1177/13524585231172945

Amato MP, Portaccio E. A first step towards preventive medicine in multiple sclerosis. 

. 2023;19(3):134-135. doi:10.1038/s41582-022-00769-9

Saposnik G, Monreal E, Medrano N, et al. Does serum neurofilament light chain measurement influence therapeutic decisions in multiple sclerosis? 

 2024;90:105838. doi:10.1016/j.msard.2024.105838

García-Domínguez JM, Maurino J, Meca-Lallana JE, et al. Attitudes of neurologists toward serum neurofilament light-chain testing in the management of relapsing-remitting multiple sclerosis with cognitive impairment. 

Monreal E, Fernández-Velasco JI, García-Sánchez MI, et al. Association of serum neurofilament light chain levels at disease onset with disability worsening in patients with a first demyelinating multiple sclerosis event not treated with high-efficacy drugs. 

. 2023;80(4):397-403. doi:10.1001/jamaneurol.2023.0010

Melas CD, Zampetakis LA, Dimopoulou A, et al. Evaluating the properties of the Evidence-Based Practice Attitude Scale (EBPAS) in health care. 

. 2012;24(4):867-876. doi:10.1037/a0027445

Hojat M, DeSantis J, Shannon SC, et al. The Jefferson Scale of Empathy: a nationwide study of measurement properties, underlying components, latent variable structure, and national norms in medical students. 

. 2018;23(5):899-920. doi:10.1007/s10459-018-9839-9

Saposnik G, Bueno-Gil G, Sempere ÁP, et al. Regret and therapeutic decisions in multiple sclerosis care: literature review and research protocol. 

. 2021;12:675520. doi:10.3389/fneur.2021.675520

Dohmen T, Falk A, Huffman D, et al. Individual risk attitudes: measurement, determinants, and behavioral consequences. 

. 2011;9:522-550. doi:10.1111/j.1542-4774.2011.01015

Dolan ED, Mohr D, Lempa M, et al. Using a single item to measure burnout in primary care staff: a psychometric evaluation. 

. 2015;30(5):582-587. doi:10.1007/s11606-014-3112-6

Inglese M, Amato MP. Presymptomatic MS or radiologically isolated syndrome should be actively monitored and treated: commentary. 

. 2023;29(7):797-798. doi:10.1177/13524585231172941

Tornatore C, Phillips JT, Khan O, et al. Consensus opinion of US neurologists on practice patterns in RIS, CIS, and RRMS: evolution of treatment practices. 

. 2016;6(4):329-338. doi:10.1212/CPJ.0000000000000254

Fernández O, Delvecchio M, Edan G, et al. Survey of diagnostic and treatment practices for multiple sclerosis in Europe. 

. 2017;24(3):516-522. doi:10.1111/ene.13236

Carnero Contentti E, Pettinicchi JP, Caride A, et al. Decision-making on radiologically isolated syndrome among Argentinean neurologists: a survey based on clinical experience. 

. 2019;27:61-64. doi:10.1016/j.msard.2018.09.030

Rauner Y, Stummer H. Adoption processes of innovations in health systems: the example of telemedicine in Germany. 

. 2024;12(2):129. doi:10.3390/healthcare12020129

Saposnik G, Camacho A, Díaz-Abós P, et al. Therapeutic decision-making under uncertainty in the management of spinal muscular atrophy: results from DECISIONS-SMA study. 

. 2022;11(3):1209-1219. doi:10.1007/s40120-022-00366-4

Fortea J, García-Arcelay E, Terrancle Á, et al. Attitudes of neurologists toward the use of biomarkers in the diagnosis of early Alzheimer’s disease. 

. 2023;93(1):275-282. doi:10.3233/JAD-221160

Moccia M, Terracciano D, Brescia Morra V, et al. Neurofilament in clinical practice: is the multiple sclerosis community ready? 

. 2024;30(6):643-645. doi:10.1177/13524585241246536

Fernández-Velasco JI, Goicochea-Briceño H, Rodríguez-Jorge F, et al. Establishing normal serum values of neurofilament light chains and glial fibrillary acidic protein considering the effects of age and other demographic factors in healthy adults. 

. 2024;25(14):7808. doi:10.3390/ijms25147808

Saposnik G, Andhavarapu S, Fernández Ó, et al. Factors associated with treatment escalation among MS specialists and general neurologists: results from an international cojoint study. 

. 2022;58:103404. doi:10.1016/j.msard.2021.103404

Soelberg Sorensen P, Giovannoni G, Montalban X, et al. The multiple sclerosis care unit. 

. 2019;25(5):627-636. doi:10.1177/1352458518807082

Zeydan B, Azevedo CJ, Makhani N, et al. Early disease-modifying treatments for presymptomatic multiple sclerosis. 

 2024;38(12):973-983. doi:10.1007/s40263-024-01117-9

Lebrun-Frenay C. The confavreux lecture: the radiologically isolated syndrome diagnosis, prognosis and perspectives. 

 2025;31(3):249-256. doi:10.1177/13524585241311217

Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. 

. 2025;24(10):850-865. doi:10.1016/S1474-4422(25)00270-4

Saposnik G, Sempere AP, Raptis R, et al. Decision making under uncertainty, therapeutic inertia, and physicians’ risk preferences in the management of multiple sclerosis (DIScUTIR MS). 

. 2016;16:58. doi:10.1186/s12883-016-0577-4

Attitudes of Neurologists Toward the Potential Role of Serum Neurofilament Light Chain Measurement in Treatment Decision-Making for People With Radiologically Isolated Syndrome

Comprehensive management of multiple sclerosis (MS) requires a multispecialty approach. Routine health care must not be neglected but maintained in consideration of the complexity and variety of consequences of the disease process. This study assesses the confidence of obstetric and gynecological providers (OBGYNs) when caring for people with MS.

OBGYNs, including doctors, physician assistants, and advanced nurse practitioners within Hackensack Meridian Health, completed a survey assessing their comfort level with and knowledge of how to care for patients with MS.

The survey was completed by 29.2% of eligible providers. Most reported that people with MS tend to have sexual and bladder dysfunction; contraceptive management does not change; and pregnancy influences the disease process. They were split regarding the risk of infertility in and the impact of menopause on people with MS. There were no statistically significant differences in the recommendations of providers of varying levels of experience on any topic.

Provider recommendations, regardless of their level of experience, highlight the gaps in the available literature, indicating a need for further research to guide clinical management. Dedicated education on existing guidelines for OBGYN care for people with MS is necessary to improve provider comfort.

From the Departments of Obstetrics and Gynecology (KLB, AFO) and the Department of Neurology (KP), Hackensack University Medical Center, Hackensack Meridian Health Network, Hackensack, NJ. 

 Krupa Pandey, MD, Director of the Clinical Research Division of the Neurosciences Institute, Director of MS Comprehensive Care Center, Neurosciences Institute at Hackensack University Medical Center, 360 Essex St, Suite 303, Hackensack, NJ 07601; 

Krupa Pandey, MD, has served as a consultant for Biogen, Bristol Myers Squibb, Genentech-Roche, and Sanofi-Genzyme and has served as a speaker for Alexion, Biogen, Bristol Myers Squibb, Genentech-Roche, Horizon Therapeutics, and Sanofi-Genzyme. All other authors have reported no relevant disclosures.

A portion of this manuscript’s data regarding menopause recommendations was presented as a poster at the 2023 Menopause Society Annual Meeting; September 27-30, 2023; Philadelphia, Pennsylvania.

Kelly L. Budge, MD, MRes

Antonia F. Oladipo, MD, MSci

Krupa Pandey, MD

Obstetric and gynecological providers (OBGYNs) treat people with multiple sclerosis (MS) but report overall poor confidence in their treatment, regardless of their number of years of experience.

OBGYN knowledge of treatment reflects current gaps in the literature, especially regarding family planning, sexually transmitted infections,
and menopause.

Multiple sclerosis (MS) is a chronic demyelinating disease affecting approximately 1 million people in the United States, with the highest incidence in the northeast of the country.

 Women of childbearing age (median age at diagnosis, 20-50 years) are mostly affected at a ratio of 3:1 compared to men.

 Therefore, the impact on decisions regarding medication and reproductive health can be significant for people with MS. Additionally, as the treatment armamentarium expands and efficacy improves, the number of people with MS who will need postmenopausal care will also rise.

Topics such as contraception; family planning; pregnancy; menopause; and pelvic, sexual, and bladder disorders are complex and require a thorough understanding of the most current literature, including the incorporation of existing guidelines. Literature is available regarding the impact of MS on fertility treatments,

 along with existing Centers for Disease Control guidelines for contraception use by people with MS.

 However, although neurologists may be aware of this body of information,

 it is unclear whether the obstetric and gynecologic provider (OBGYN) community is informed.

As management strategies of reproductive health issues differ among neurologists,

 there is likely a need for improvement in the field of OBGYN for the treatment of individuals with MS. We hypothesized that our hospital network, despite it being in a location with a higher incidence of MS, was not unique to these gaps in care, and we sought to understand providers’ specific discomforts in treating patients with MS. This study assesses OBGYN care providers’ confidence in treating patients with MS through a survey of providers within a single hospital network.

All OBGYNs (approximately 120 medical doctors [MDs], osteopathic doctors [DOs], physician assistants [PAs], and advanced practice nurses [APNs] within Hackensack Meridian Health, a single health network comprising 18 hospitals across the state of New Jersey, were contacted by email to complete a REDCap survey. The survey content was generated via a collaboration between a maternal-fetal medicine physician and a neurologist specializing in MS care. It assessed the OBGYNs’ knowledge of MS and the providers’ comfort level with caring for these patients (

, available as a PDF at the bottom of the online article), including providers’ standards of care for MS and routine care. Comfort level was assessed at the beginning and reassessed at the end of the survey to determine whether completion of the survey changed participants’ perspectives. Responses were collected over a period of 12 weeks and were anonymous. With a response rate of 29.2%, 35 OBGYNs participated. The margin of error is 14.0% with a 95% CI.

We used a 2-way analysis of variance (with Tukey test for post hoc pairwise differences) for multiple independent group comparisons. A 2-tailed 

 value less than .05 was regarded as statistically significant. All statistical analyses were performed using Prism, version 9, for Windows (GraphPad Software Inc).

The Hackensack University Medical Center Institutional Review Board (IRB) approved all procedures (Hackensack, NJ; IRB Pro2022-0237). A waiver of signed consent was obtained, as there was no more than minimal risk to participants and no identifiable information collected. No personal health information was collected, so no waiver of Health Insurance Portability and Accountability Act privacy authorization was required.

Of the 35 respondents, 85.7% were physicians, 5.7% were PAs, and 8.6% were APNs (

). The majority of respondents were general obstetricians and gynecologists (n = 27, 77.1%), but also included were maternal-fetal medicine specialists (n = 6, 17.1%) and reproductive endocrinology and infertility specialists (n = 2, 5.7%). Respondents fell into the end ranges of practice in the field, 0 to less than 5 years (n = 11, 31.4% and greater than 20 years (n = 12, 34.3%). Practice settings included inpatient (n = 25, 71.4%), outpatient (n = 21, 60%), academic hospital (n = 24, 68.6%), community hospital (n = 4, 11.4%), multispecialty group (n = 1, 2.9%), single-specialty group (n = 11, 31.4%), and solo private practice (n = 2, 5.7%). Most respondents practiced in small or large cities, with none from rural areas.

The majority of respondents reported having treated a patient with MS (n = 25, 71.4%), and 40% reported having treated a patient with MS within the past 6 months to 1 year. Self-reported confidence was assessed, with 17 (48.6%) reporting poor confidence, 16 (45.7%) somewhat confident, and 2 (5.7%) very confident. After completion of the survey, 1 respondent remained very confident (2.9%), 14 (40%) were somewhat confident, and 20 (57.1%) reported poor confidence in their knowledge of managing MS. There was no difference in provider confidence based on years of experience (

). There were also no statistically significant differences in recommendations among providers of varying levels of expertise on all topics (

Volume 27, Issue Q4

Attitudes of Neurologists Toward the Potential Role of Serum Neurofilament Light Chain Measurement in Treatment Decision-Making for People With Radiologically Isolated Syndrome

Clinical Care Gaps in the Management of Multiple Sclerosis Among Obstetric and Gynecologic Clinicians

“There’s No Magic Pill”: A Multimethods Qualitative Study Exploring Routine Fatigue Care in People With Multiple Sclerosis

Recruitment of African American Adults With Multiple Sclerosis Into Randomized Controlled Trials of Exercise Training: Lessons Learned From Project TEAAMS

The Impact of Attentional Focus on Gait in Adults With Multiple Sclerosis: A Preliminary Investigation

Occupational Therapy Interventions Addressing Activities of Daily Living and Sleep for People With Multiple Sclerosis: A Systematic Review

Ocrelizumab Wearing-Off Phenomenon: Prevalence, Predictors, and Outcomes After Intervention

Head Rotation Impairs Balance and Walking in People With Mild to Moderate Multiple Sclerosis: A Pilot Study

Rehabilitation in Multiple Sclerosis (RiMS) Network Is Key to the World Health Organization’s Rehabilitation 2030: A Call for Action for People With Multiple Sclerosis

Navigating the Unknown: A Qualitative Exploration of the Lived Experiences of People With Multiple Sclerosis During Pregnancy