{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:36:54Z","timestamp":1779935814893,"version":"3.53.1"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roche Farma Spain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Cognitive impairment has an impact upon the function and quality of life of patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression and are also associated with impaired cognitive performance. This study aimed to assess the attitudes of neurologists toward sNfL testing as regards making therapeutic decisions in clinically and radiologically stable patients experiencing cognitive decline. Methods: A web-based observational study was conducted among neurologists caring for patients with MS. The role of sNfL in therapeutic decisions was assessed through a simulated case scenario describing a 31-year-old woman with relapsing\u2013remitting MS for four years on glatiramer acetate. Her partner reported increased distractibility and difficulties in organizing daily activities over the past 18 months. There was no history of new relapses, and a follow-up brain MRI scan showed no new lesions. Her performance in the Symbol Digit Modalities Test decreased by 8 points from the previous year, with 46 correct answers. The patient had an sNfL level of 21 pg\/mL, with no other identified factors that could have altered this value. The participants were tasked with deciding to either escalate treatment or to continue the current treatment and schedule the patient for reassessment in 6\u201312 months (defined as decisions misaligned with emerging evidence [DMEE]). Multivariate regression analysis was conducted to determine factors associated with DMEE. Results: One hundred and sixteen neurologists participated in the study. Almost 50% of the participants (n = 57) opted not to escalate treatment despite high sNfL levels. This was more common among neurologists not fully dedicated to MS care (60.5% vs. 43.6%). The multivariate analysis showed that being a neurologist not fully dedicated to MS (odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.01\u20135.50; p = 0.04) and having a poor perception of sNfL benefits (OR = 1.02, 95% CI 1.00\u20131.04; p = 0.01) were associated with DMEE. Conclusions: Neurologists\u2019 lack of full dedication to MS care and limited perception of sNfL\u2019s clinical utility were key factors associated with suboptimal therapeutic decisions in a simulated case of cognitive decline with elevated sNfL. These findings underscore the need for increased education on the role of sNfL to improve evidence-based decision-making in MS management.<\/jats:p>","DOI":"10.3390\/jpm15020069","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T04:48:51Z","timestamp":1739508531000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Attitudes of Neurologists Toward Serum Neurofilament Light-Chain Testing in the Management of Relapsing\u2013Remitting Multiple Sclerosis with Cognitive Impairment"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-3652","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Garc\u00eda-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Department of Neurology, Hospital Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9858-3555","authenticated-orcid":false,"given":"Jorge","family":"Maurino","sequence":"additional","affiliation":[{"name":"Medical Department, Roche Farma, 28042 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 E.","family":"Meca-Lallana","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamberto","family":"Landete","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Dr. Peset, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Meca-Lallana","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2964-2045","authenticated-orcid":false,"given":"Elena","family":"Garc\u00eda-Arcelay","sequence":"additional","affiliation":[{"name":"Medical Department, Roche Farma, 28042 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-2054","authenticated-orcid":false,"given":"Eduardo","family":"Ag\u00fcera-Morales","sequence":"additional","affiliation":[{"name":"Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B.","family":"Caminero","sequence":"additional","affiliation":[{"name":"Department of Neurology, Complejo Asistencial de \u00c1vila, 05071 \u00c1vila, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mart\u00ednez-Y\u00e9lamos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitari de Bellvitge, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-8264","authenticated-orcid":false,"given":"Luis","family":"Querol","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Medrano","sequence":"additional","affiliation":[{"name":"Medical Department, Roche Farma, 28042 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9582-9230","authenticated-orcid":false,"given":"Roc\u00edo","family":"G\u00f3mez-Ballesteros","sequence":"additional","affiliation":[{"name":"Medical Department, Roche Farma, 28042 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9067-3668","authenticated-orcid":false,"given":"Luisa M.","family":"Villar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Monreal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-9886","authenticated-orcid":false,"given":"Gustavo","family":"Saposnik","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, St. Michael\u2019s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","article-title":"Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues","volume":"19","author":"Benedict","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"De Meo, E., Portaccio, E., Bonacchi, R., Giovannoli, J., Niccolai, C., and Amato, M.P. (2025). An update on the treatment and management of cognitive dysfunction in patients with multiple sclerosis. Expert. Rev. Neurother., epub ahead of print.","DOI":"10.1080\/14737175.2025.2450788"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s00702-024-02786-y","article-title":"Cognitive impairment in multiple sclerosis: From phenomenology to neurobiological mechanisms","volume":"131","author":"Jellinger","year":"2024","journal-title":"J. Neural Transm."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Amato, M.P., Prestipino, E., Bellinvia, A., Niccolai, C., Razzolini, L., Past\u00f2, L., Fratangelo, R., Tudisco, L., Fonderico, M., and Mattiolo, P.L. (2019). Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors. PLoS. ONE, 14.","DOI":"10.1371\/journal.pone.0225494"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1177\/13524585241273037","article-title":"Progression independent of relapse activity in multiple sclerosis: Time to account for cognitive decline","volume":"30","author":"Tur","year":"2024","journal-title":"Mult. Scler."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1017\/S1355617715000053","article-title":"Perceived cognitive difficulties and cognitive test performance as predictors of employment outcomes in people with multiple sclerosis","volume":"21","author":"Honan","year":"2015","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41582-024-00955-x","article-title":"Neurofilaments as biomarkers in neurological disorders\u2014Towards clinical application","volume":"20","author":"Khalil","year":"2024","journal-title":"Nat. Rev. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101009","DOI":"10.1016\/j.lanepe.2024.101009","article-title":"Fluid biomarkers in multiple sclerosis: From current to future applications","volume":"44","author":"Gaetani","year":"2024","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Freedman, M.S., Gnanapavan, S., Booth, R.A., Calabresi, P.A., Khalil, M., Kuhle, J., Lycke, J., and Olsson, T. (2024). Guidance for use of neurofilament light chain as a cerebrospinal fluid and blood biomarker in multiple sclerosis management. EBioMedicine, 101.","DOI":"10.1016\/j.ebiom.2024.104970"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Monreal, E., Ruiz, P.D., Rom\u00e1n, I.L.S., Rodr\u00edguez-Antig\u00fcedad, A., Moya-Molina, M.\u00c1., \u00c1lvarez, A., Garc\u00eda-Arcelay, E., Maurino, J., Shepherd, J., and Cabrera, \u00c1.P. (2024). Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1397845"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1177\/1352458519881428","article-title":"Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study","volume":"26","author":"Jakimovski","year":"2020","journal-title":"Mult. Scler."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117229","DOI":"10.1016\/j.jns.2020.117229","article-title":"The relationship between neurofilament light chain and cognition in neurological disorders: A scoping review","volume":"420","author":"Ramani","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"fcac153","DOI":"10.1093\/braincomms\/fcac153","article-title":"Improved prediction of early cognitive impairment in multiple sclerosis combining blood and imaging biomarkers","volume":"4","author":"Brummer","year":"2022","journal-title":"Brain Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1177\/13524585221137697","article-title":"Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients","volume":"29","author":"Barro","year":"2023","journal-title":"Mult. Scler."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rademacher, T.D., Meuth, S.G., Wiendl, H., Johnen, A., and Landmeyer, N.C. (2023). Molecular biomarkers and cognitive impairment in multiple sclerosis: State of the field, limitations, and future direction\u2014A systematic review and meta-analysis. Neurosci. Biobehav. Rev., 146.","DOI":"10.1016\/j.neubiorev.2023.105035"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1007\/s00415-023-11676-4","article-title":"A multimodal marker for cognitive functioning in multiple sclerosis: The role of NfL, GFAP and conventional MRI in predicting cognitive functioning in a prospective clinical cohort","volume":"270","author":"Willemse","year":"2023","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1007\/s00415-021-10832-y","article-title":"Effects on cognition of DMTs in multiple sclerosis: Moving beyond the prevention of inflammatory activity","volume":"269","author":"Preziosa","year":"2022","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102673","DOI":"10.1016\/j.msard.2020.102673","article-title":"Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS","volume":"48","author":"DeLuca","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103959","DOI":"10.1016\/j.msard.2022.103959","article-title":"The effect of timing of high-efficacy therapy on processing speed performance in multiple sclerosis","volume":"64","author":"Monreal","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104952","DOI":"10.1016\/j.msard.2023.104952","article-title":"Managing cognitive impairment and its impact in multiple sclerosis: An Australian multidisciplinary perspective","volume":"79","author":"Agland","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fneur.2018.00174","article-title":"Therapeutic Inertia in the New Landscape of Multiple Sclerosis Care","volume":"9","author":"Saposnik","year":"2018","journal-title":"Front Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103176","DOI":"10.1016\/j.msard.2021.103176","article-title":"Therapeutic inertia in relapsing-remitting multiple sclerosis","volume":"55","author":"Rodrigues","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1037\/a0027445","article-title":"Evaluating the properties of the Evidence-Based Practice Attitude Scale (EBPAS) in health care","volume":"24","author":"Melas","year":"2012","journal-title":"Psychol. Assess."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s10459-018-9839-9","article-title":"The Jefferson Scale of Empathy: A nationwide study of measurement properties, underlying components, latent variable structure, and national norms in medical students","volume":"23","author":"Hojat","year":"2018","journal-title":"Adv. Health Sci. Educ. Theory Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/MLR.0b013e318280f02c","article-title":"Validation of a 10-item care-related regret intensity scale (RIS-10) for health care professionals","volume":"51","author":"Courvoisier","year":"2013","journal-title":"Med. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s11606-014-3112-6","article-title":"Using a single item to measure burnout in primary care staff: A psychometric evaluation","volume":"30","author":"Dolan","year":"2015","journal-title":"J. Gen. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1177\/13524585241256540","article-title":"Cognitive progression independent of relapse in multiple sclerosis","volume":"30","author":"Fuchs","year":"2024","journal-title":"Mult. Scler."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ncl.2023.06.004","article-title":"Highly Effective Therapy Versus Escalation Approaches in Early Multiple Sclerosis: What Is the Future of Multiple Sclerosis Treatment?","volume":"42","author":"Mowry","year":"2024","journal-title":"Neurol Clin."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Labiano-Fontcuberta, A., Monreal, E., and Benito-Le\u00f3n, J. (2022). Time to rethink the reported disease-modifying treatment effects on cognitive outcomes: Methods and interpretative caveats. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.995690"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1177\/13524585221114441","article-title":"Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial","volume":"28","author":"Williams","year":"2022","journal-title":"Mult. Scler."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s00415-020-09832-1","article-title":"Longitudinal serum neurofilament light chain (sNfL) concentration relates to cognitive function in multiple sclerosis patients","volume":"267","author":"Mattioli","year":"2020","journal-title":"J. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103404","DOI":"10.1016\/j.msard.2021.103404","article-title":"Factors associated with treatment escalation among MS specialists and general neurologists: Results from an International cojoint study","volume":"58","author":"Saposnik","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1177\/1352458518807082","article-title":"The Multiple Sclerosis Care Unit","volume":"25","author":"Giovannoni","year":"2019","journal-title":"Mult. Scler."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1177\/13524585241277044","article-title":"Impact of serum neurofilament light on clinical decisions in a tertiary multiple sclerosis clinic","volume":"30","author":"Wessels","year":"2024","journal-title":"Mult. Scler."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1177\/13524585241246536","article-title":"Neurofilament in clinical practice: Is the multiple sclerosis community ready?","volume":"30","author":"Moccia","year":"2024","journal-title":"Mult. Scler."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1177\/13524585241291452","article-title":"Using serum neurofilament-light in clinical practice: Growing enthusiasm that may need bridling","volume":"30","author":"Lycke","year":"2024","journal-title":"Mult. Scler."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/2\/69\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:34:13Z","timestamp":1760027653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/2\/69"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["jpm15020069"],"URL":"https:\/\/doi.org\/10.3390\/jpm15020069","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]}}}