{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:57:06Z","timestamp":1789527426722,"version":"build-2803163510"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Ther"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1007\/s40120-025-00736-8","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T03:44:14Z","timestamp":1747021454000},"page":"1345-1353","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluating Cognitive Outcomes in Multiple Sclerosis: Real-World Impact of Ozanimod on Processing Speed Using BICAMS"],"prefix":"10.1007","volume":"14","author":[{"given":"Aurora","family":"Zangh\u00ec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Sofia","family":"Di Filippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Avolio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-9057","authenticated-orcid":false,"given":"Emanuele","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"issue":"10","key":"736_CR1","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","volume":"19","author":"RHB Benedict","year":"2020","unstructured":"Benedict RHB, Amato MP, DeLuca J, Geurts JJG. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol. 2020;19(10):860\u201371.","journal-title":"Lancet Neurol"},{"issue":"6","key":"736_CR2","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41582-020-0355-1","volume":"16","author":"J DeLuca","year":"2020","unstructured":"DeLuca J, Chiaravalloti ND, Sandroff BM. Treatment and management of cognitive dysfunction in patients with multiple sclerosis. Nat Rev Neurol. 2020;16(6):319\u201332.","journal-title":"Nat Rev Neurol"},{"issue":"4","key":"736_CR3","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1001\/jamaneurol.2020.4920","volume":"78","author":"E De Meo","year":"2021","unstructured":"De Meo E, Portaccio E, Giorgio A, Ruano L, Goretti B, Niccolai C, et al. Identifying the distinct cognitive phenotypes in multiple sclerosis. JAMA Neurol. 2021;78(4):414\u201325.","journal-title":"JAMA Neurol"},{"issue":"Suppl 2","key":"736_CR4","doi-asserted-by":"publisher","first-page":"S265","DOI":"10.1007\/s10072-010-0438-7","volume":"31","author":"F Patti","year":"2010","unstructured":"Patti F, Leone C, D\u2019Amico E. Treatment options of cognitive impairment in multiple sclerosis. Neurol Sci. 2010;31(Suppl 2):S265-9.","journal-title":"Neurol Sci"},{"issue":"1","key":"736_CR5","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/1471-2377-12-55","volume":"12","author":"RHB Benedict","year":"2012","unstructured":"Benedict RHB, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, et al. Brief International Cognitive Assessment for MS (BICAMS): international standards for validation. BMC Neurol. 2012;12(1):55.","journal-title":"BMC Neurol"},{"issue":"6","key":"736_CR6","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1177\/1352458511431076","volume":"18","author":"DW Langdon","year":"2012","unstructured":"Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, et al. Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Multiple Scler (Houndmills, Basingstoke, England). 2012;18(6):891\u20138.","journal-title":"Multiple Scler (Houndmills, Basingstoke, England)"},{"issue":"5","key":"736_CR7","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1177\/1352458517690821","volume":"23","author":"RH Benedict","year":"2017","unstructured":"Benedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler J. 2017;23(5):721\u201333.","journal-title":"Mult Scler J"},{"key":"736_CR8","doi-asserted-by":"crossref","unstructured":"Van Schependom J, D\u2019Hooghe M B, Cleynhens K, D\u2019Hooge M, Haelewyck MC, De Keyser J, et al. The Symbol Digit Modalities Test as sentinel test for cognitive impairment in multiple sclerosis. Eur J Neurol. 2014;21(9):1219\u201325, e71\u20132.","DOI":"10.1111\/ene.12463"},{"key":"736_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102950","volume":"51","author":"J Sandry","year":"2021","unstructured":"Sandry J, Simonet DV, Brandstadter R, Krieger S, Katz Sand I, Graney RA, et al. The Symbol Digit Modalities Test (SDMT) is sensitive but non-specific in MS: lexical access speed, memory, and information processing speed independently contribute to SDMT performance. Mult Scler Relat Disord. 2021;51: 102950.","journal-title":"Mult Scler Relat Disord"},{"issue":"13","key":"736_CR10","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1177\/1352458518808204","volume":"25","author":"L Strober","year":"2019","unstructured":"Strober L, DeLuca J, Benedict RH, Jacobs A, Cohen JA, Chiaravalloti N, et al. Symbol Digit Modalities Test: a valid clinical trial endpoint for measuring cognition in multiple sclerosis. Multiple Scler (Houndmills, Basingstoke, England). 2019;25(13):1781\u201390.","journal-title":"Multiple Scler (Houndmills, Basingstoke, England)"},{"issue":"11","key":"736_CR11","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/S1474-4422(19)30239-X","volume":"18","author":"G Comi","year":"2019","unstructured":"Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009\u201320.","journal-title":"Lancet Neurol"},{"issue":"11","key":"736_CR12","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S1474-4422(19)30238-8","volume":"18","author":"JA Cohen","year":"2019","unstructured":"Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021\u201333.","journal-title":"Lancet Neurol"},{"issue":"9","key":"736_CR13","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1177\/1352458518789884","volume":"25","author":"JA Cohen","year":"2019","unstructured":"Cohen JA, Comi G, Arnold DL, Bar-Or A, Selmaj KW, Steinman L, et al. Efficacy and safety of ozanimod in multiple sclerosis: dose-blinded extension of a randomized phase II study. Multiple Scler (Houndmills, Basingstoke, England). 2019;25(9):1255\u201362.","journal-title":"Multiple Scler (Houndmills, Basingstoke, England)"},{"key":"736_CR14","doi-asserted-by":"crossref","unstructured":"Meadows KT, Akhtar MW, Brand M, Villescaz C, Clemons B, Lopez C, et al. Ozanimod (RPC1063) preserves central nervous system (CNS) Tissue in rodents by reducing neuronal breaks in vivo and modulating astrocyte activity in vitro (P5.027). Neurology. 2018;90(15_supplement):P5.027.","DOI":"10.1212\/WNL.90.15_supplement.P5.027"},{"key":"736_CR15","doi-asserted-by":"crossref","unstructured":"DeLuca J, Cohen J, Cree B, Comi G, Kappos L, Cheng C-Y, et al. Eight-point reliable change on symbol digit modalities test with ozanimod: findings from the phase 3 SUNBEAM and DAYBREAK extension trials (P6-6.015). Neurology. 2024;102(17_supplement_1):2760.","DOI":"10.1212\/WNL.0000000000204721"},{"issue":"2","key":"736_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162\u201373.","journal-title":"Lancet Neurol"},{"issue":"1","key":"736_CR17","doi-asserted-by":"publisher","first-page":"159","DOI":"10.2307\/2529310","volume":"33","author":"JR Landis","year":"1977","unstructured":"Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159\u201374.","journal-title":"Biometrics"},{"key":"736_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102673","volume":"48","author":"J DeLuca","year":"2021","unstructured":"DeLuca J, Schippling S, Montalban X, Kappos L, Cree BAC, Comi G, et al. Effect of ozanimod on symbol digit modalities test performance in relapsing MS. Mult Scler Relat Disord. 2021;48: 102673.","journal-title":"Mult Scler Relat Disord"},{"key":"736_CR19","doi-asserted-by":"crossref","unstructured":"DeLuca J, Cohen JA, Cree BAC, Cheng C-Y, Sheffield JK, Riolo JV, et al. Effects of ozanimod on cognitive processing speed: findings from the phase 3 SUNBEAM and DAYBREAK extension trials (P6-3.001). Neurology. 2023;100(17_supplement_2):2138.","DOI":"10.1212\/WNL.0000000000202342"},{"key":"736_CR20","unstructured":"DeLuca J, Gudesblatt M, Zivadinov R, et al. P323. Changes in Cognitive Functioning in Ozanimod-Treated Patients with Early Relapsing Multiple Sclerosis: Year 1 Interim Analysis of the ENLIGHTEN Study. Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm Beach, FL. ABSTRACT P323."},{"key":"736_CR21","doi-asserted-by":"crossref","unstructured":"Benedict RHB, Arnold DL, Cree BAC, Meng X, Schofield L, Boulos F, et al. Improved processing speed in multiple sclerosis during fingolimod therapy: oral Symbol Digit Modalities Test response in PREFERMS (P4.331). Neurology. 2017;88(16_supplement):P4.331.","DOI":"10.1212\/WNL.88.16_supplement.P4.331"},{"issue":"3","key":"736_CR22","doi-asserted-by":"publisher","first-page":"e376","DOI":"10.1212\/WNL.0000000000011275","volume":"96","author":"RHB Benedict","year":"2021","unstructured":"Benedict RHB, Tomic D, Cree BA, Fox R, Giovannoni G, Bar-Or A, et al. Siponimod and cognition in secondary progressive multiple sclerosis: EXPAND secondary analyses. Neurology. 2021;96(3):e376\u201386.","journal-title":"Neurology"},{"issue":"2","key":"736_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s40263-015-0297-0","volume":"30","author":"SF Hunter","year":"2016","unstructured":"Hunter SF, Bowen JD, Reder AT. The Direct effects of fingolimod in the central nervous system: implications for relapsing multiple sclerosis. CNS Drugs. 2016;30(2):135\u201347.","journal-title":"CNS Drugs"},{"key":"736_CR24","doi-asserted-by":"publisher","unstructured":"D'Amico E, Patti F, Zangh\u00ec A, Zappia M. A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives. Int J Mol Sci. 2016;17(10):1725. https:\/\/doi.org\/10.3390\/ijms17101725","DOI":"10.3390\/ijms17101725"},{"issue":"10","key":"736_CR25","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1177\/1352458519860319","volume":"26","author":"VM Leavitt","year":"2020","unstructured":"Leavitt VM, Brandstadter R, Fabian M, Katz Sand I, Klineova S, Krieger S, et al. Dissociable cognitive patterns related to depression and anxiety in multiple sclerosis. Mult Scler. 2020;26(10):1247\u201355.","journal-title":"Mult Scler"},{"key":"736_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fnimg.2022.970385","volume":"1","author":"MN Uddin","year":"2022","unstructured":"Uddin MN, Figley TD, Kornelsen J, Mazerolle EL, Helmick CA, O\u2019Grady CB, et al. The comorbidity and cognition in multiple sclerosis (CCOMS) neuroimaging protocol: study rationale, MRI acquisition, and minimal image processing pipelines. Front Neuroimag. 2022;1: 970385.","journal-title":"Front Neuroimag"},{"key":"736_CR27","doi-asserted-by":"publisher","first-page":"204062232098312","DOI":"10.1177\/2040622320983121","volume":"12","author":"A Zangh\u00ec","year":"2021","unstructured":"Zangh\u00ec A, D\u2019Amico E, Lo Fermo S, Patti F. Exploring polypharmacy phenomenon in newly diagnosed relapsing-remitting multiple sclerosis: a cohort ambispective single-centre study. Ther Adv Chron Dis. 2021;12:2040622320983121.","journal-title":"Ther Adv Chron Dis"},{"issue":"1","key":"736_CR28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/13524585221129964","volume":"29","author":"D Bourdette","year":"2022","unstructured":"Bourdette D, Herink M. Polypharmacy in multiple sclerosis: more is not necessarily better. Mult Scler J. 2022;29(1):3\u20135.","journal-title":"Mult Scler J"}],"container-title":["Neurology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-025-00736-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40120-025-00736-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-025-00736-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T14:35:52Z","timestamp":1757169352000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40120-025-00736-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["736"],"URL":"https:\/\/doi.org\/10.1007\/s40120-025-00736-8","relation":{},"ISSN":["2193-8253","2193-6536"],"issn-type":[{"value":"2193-8253","type":"print"},{"value":"2193-6536","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"8 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Aurora Zangh\u00ec has nothing to disclose related to the submitted manuscript. Paola Sofia Di Filippo has nothing to disclose related to the submitted manuscript. Carlo Avolio has nothing to disclose related to the submitted manuscript. Emanuele D\u2019Amico has nothing to disclose related to the submitted manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study protocol was approved by the local ethics committee (Comitato Etico Bari). All patients signed a written informed consent to participate in the study. The current report does not contain any individual or identifying information. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}