{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T17:56:46Z","timestamp":1793987806100,"version":"4.8.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente funding scheme of the Italian Ministry of Health"],"award-info":[{"award-number":["Ricerca Corrente funding scheme of the Italian Ministry of Health"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Finalizzata bando 2021 (RF-2021-12373036)"],"award-info":[{"award-number":["Ricerca Finalizzata bando 2021 (RF-2021-12373036)"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009104","name":"Universit\u00e0 Degli Studi di Modena e Reggio Emila","doi-asserted-by":"publisher","award":["bando FAR 2021, Progetti di ricerca Interdisciplinari Mission Oriented, NEURALS project)"],"award-info":[{"award-number":["bando FAR 2021, Progetti di ricerca Interdisciplinari Mission Oriented, NEURALS project)"]}],"id":[{"id":"10.13039\/100009104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007386","name":"Fondazione Cassa di Risparmio di Modena","doi-asserted-by":"publisher","award":["Neurobiobanca di Modena"],"award-info":[{"award-number":["Neurobiobanca di Modena"]}],"id":[{"id":"10.13039\/100007386","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-94984-1","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T23:12:52Z","timestamp":1743462772000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen"],"prefix":"10.1038","volume":"15","author":[{"given":"Cecilia","family":"Simonini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Zucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gianferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Trojsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachele","family":"Piras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Giacchino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Banchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mandrioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"94984_CR1","unstructured":"Ruf, W. P. et al. Spectrum and frequency of genetic variants in sporadic amyotrophic lateral sclerosis. Brain Commun. 5, fcad152 (2023)."},{"key":"94984_CR2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jnnp-2016-315018","volume":"88","author":"Z-Y Zou","year":"2017","unstructured":"Zou, Z.-Y. et al. Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 88, 540\u2013549 (2017).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"94984_CR3","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1212\/01.wnl.0000343509.76828.2a","volume":"72","author":"M Saeed","year":"2009","unstructured":"Saeed, M. et al. Age and founder effect of SOD1 A4V mutation causing ALS. Neurology 72, 1634\u20131639 (2009).","journal-title":"Neurology"},{"key":"94984_CR4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41598-021-03891-8","volume":"12","author":"M Berdy\u0144ski","year":"2022","unstructured":"Berdy\u0144ski, M. et al. SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity. Sci. Rep. 12, 103 (2022).","journal-title":"Sci. Rep."},{"key":"94984_CR5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00401-003-0763-5","volume":"106","author":"T Arisato","year":"2003","unstructured":"Arisato, T. et al. Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families. Acta Neuropathol. (Berl.) 106, 561\u2013568 (2003).","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"94984_CR6","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/hmg\/ddm110","volume":"16","author":"D Sau","year":"2007","unstructured":"Sau, D. et al. Mutation of SOD1 in ALS: A gain of a loss of function. Hum. Mol. Genet. 16, 1604\u20131618 (2007).","journal-title":"Hum. Mol. Genet."},{"key":"94984_CR7","doi-asserted-by":"crossref","unstructured":"Bernard, E. et al. Clinical and molecular landscape of ALS patients with SOD1 mutations: Novel pathogenic variants and novel phenotypes. A single ALS center study. Int. J. Mol. Sci. 21, 6807 (2020).","DOI":"10.3390\/ijms21186807"},{"key":"94984_CR8","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","volume":"387","author":"TM Miller","year":"2022","unstructured":"Miller, T. M. et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N. Engl. J. Med. 387, 1099\u20131110 (2022).","journal-title":"N. Engl. J. Med."},{"key":"94984_CR9","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1007\/s13311-022-01237-4","volume":"19","author":"M Benatar","year":"2022","unstructured":"Benatar, M. et al. Design of a randomized, placebo-controlled, phase 3 trial of tofersen initiated in clinically presymptomatic SOD1 variant carriers: The ATLAS study. Neurotherapeutics 19, 1248\u20131258 (2022).","journal-title":"Neurotherapeutics"},{"key":"94984_CR10","doi-asserted-by":"crossref","unstructured":"Wiesenfarth, M. et al. Effects of tofersen treatment in patients with SOD1-ALS in a \u201creal-world\u201d setting\u2014A 12-month multicenter cohort study from the German early access program. eClinicalMedicine 69, 102495 (2024).","DOI":"10.1016\/j.eclinm.2024.102495"},{"key":"94984_CR11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/mus.27818","volume":"67","author":"T Meyer","year":"2023","unstructured":"Meyer, T. et al. Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice. Muscle Nerve 67, 515\u2013521 (2023).","journal-title":"Muscle Nerve"},{"key":"94984_CR12","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12437-7","author":"M Sabatelli","year":"2024","unstructured":"Sabatelli, M. et al. Long-term treatment of SOD1 ALS with tofersen: A multicentre experience in 17 patients. J. Neurol. https:\/\/doi.org\/10.1007\/s00415-024-12437-7 (2024).","journal-title":"J. Neurol."},{"key":"94984_CR13","doi-asserted-by":"crossref","unstructured":"Meyer, T. et al. Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS\u2014A multicenter observational study over 18 months. Muscle Nerve (2024).","DOI":"10.1002\/mus.28182"},{"key":"94984_CR14","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1212\/WNL.0000000000009559","volume":"95","author":"M Benatar","year":"2020","unstructured":"Benatar, M. et al. Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology 95, e59\u2013e69 (2020).","journal-title":"Neurology"},{"key":"94984_CR15","doi-asserted-by":"crossref","DOI":"10.1111\/ene.16379","volume":"31","author":"T Meyer","year":"2024","unstructured":"Meyer, T. et al. Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study. Eur. J. Neurol. 31, e16379 (2024).","journal-title":"Eur. J. Neurol."},{"key":"94984_CR16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/21678421.2024.2423707","volume":"26","author":"TJ Simkins","year":"2025","unstructured":"Simkins, T. J. et al. Plasma neurofilament analysis in VITALITY-ALS. Amyotroph. Lateral Scler. Front. Degener. 26, 103\u2013112 (2025).","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"94984_CR17","doi-asserted-by":"crossref","DOI":"10.1111\/ene.16054","volume":"31","author":"I Martinelli","year":"2024","unstructured":"Martinelli, I. et al. SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study. Eur. J. Neurol. 31, e16054 (2024).","journal-title":"Eur. J. Neurol."},{"key":"94984_CR18","doi-asserted-by":"crossref","DOI":"10.1016\/j.jns.2024.123112","volume":"463","author":"C Ros\u00e9n","year":"2024","unstructured":"Ros\u00e9n, C. et al. High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS. J. Neurol. Sci. 463, 123112 (2024).","journal-title":"J. Neurol. Sci."},{"key":"94984_CR19","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1007\/s10072-024-07301-5","volume":"45","author":"A Xu","year":"2024","unstructured":"Xu, A. et al. Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: A systematic review and meta-analysis. Neurol. Sci. 45, 2489\u20132503 (2024).","journal-title":"Neurol. Sci."},{"key":"94984_CR20","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1002\/acn3.51625","volume":"9","author":"B De Wel","year":"2022","unstructured":"De Wel, B., De Schaepdryver, M., Poesen, K. & Claeys, K. G. Biochemical and clinical biomarkers in adult SMA 3\u20134 patients treated with nusinersen for 22 months. Ann. Clin. Transl. Neurol. 9, 1241\u20131251 (2022).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"94984_CR21","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s13023-021-01961-8","volume":"16","author":"M Freigang","year":"2021","unstructured":"Freigang, M. et al. Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy. Orphanet J. Rare Dis. 16, 330 (2021).","journal-title":"Orphanet J. Rare Dis."},{"key":"94984_CR22","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1136\/jnnp-2019-321916","volume":"91","author":"L Vu","year":"2020","unstructured":"Vu, L. et al. Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes. J. Neurol. Neurosurg. Psychiatry 91, 350\u2013358 (2020).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"94984_CR23","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1007\/s00415-024-12442-w","volume":"271","author":"X Yao","year":"2024","unstructured":"Yao, X. et al. Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: A multi-center disease registry in China. J. Neurol. 271, 5378\u20135391 (2024).","journal-title":"J. Neurol."},{"key":"94984_CR24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12974-014-0165-8","volume":"11","author":"M Gold","year":"2014","unstructured":"Gold, M. et al. \u03b11-antitrypsin modulates microglial-mediated neuroinflammation and protects microglial cells from amyloid-\u03b2-induced toxicity. J. Neuroinflammation 11, 165 (2014).","journal-title":"J. Neuroinflammation"},{"key":"94984_CR25","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.bbrc.2010.01.110","volume":"393","author":"F Zsila","year":"2010","unstructured":"Zsila, F. Inhibition of heat- and chemical-induced aggregation of various proteins reveals chaperone-like activity of the acute-phase component and serine protease inhibitor human \u03b11-antitrypsin. Biochem. Biophys. Res. Commun. 393, 242\u2013247 (2010).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"94984_CR26","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1111\/j.1471-4159.2007.04677.x","volume":"102","author":"Q Xiao","year":"2007","unstructured":"Xiao, Q. et al. Mutant SOD1 G93A microglia are more neurotoxic relative to wild-type microglia. J. Neurochem. 102, 2008\u20132019 (2007).","journal-title":"J. Neurochem."},{"key":"94984_CR27","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/acn3.51112","volume":"7","author":"G Tondo","year":"2020","unstructured":"Tondo, G. et al. 11 C-PK11195 PET\u2013based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol. 7, 1513\u20131523 (2020).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"94984_CR28","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s11481-013-9489-x","volume":"8","author":"W Zhao","year":"2013","unstructured":"Zhao, W., Beers, D. R. & Appel, S. H. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J. Neuroimmune Pharmacol. 8, 888\u2013899 (2013).","journal-title":"J. Neuroimmune Pharmacol."},{"key":"94984_CR29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000493986","volume":"18","author":"E Zucchi","year":"2018","unstructured":"Zucchi, E. et al. Cerebrospinal fluid neurofilaments may discriminate upper motor neuron syndromes: A pilot study. Neurodegener. Dis. 18, 255\u2013261 (2018).","journal-title":"Neurodegener. Dis."},{"key":"94984_CR30","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-024-04311-4","author":"M Vinceti","year":"2024","unstructured":"Vinceti, M. et al. Changes in cerebrospinal fluid concentrations of selenium species induced by tofersen administration in subjects with amyotrophic lateral sclerosis carrying SOD1 gene mutations. Biol. Trace Elem. Res. https:\/\/doi.org\/10.1007\/s12011-024-04311-4 (2024).","journal-title":"Biol. Trace Elem. Res."},{"key":"94984_CR31","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1007\/s00415-023-12130-1","volume":"271","author":"P Reilich","year":"2024","unstructured":"Reilich, P. et al. Myelitis as a side effect of tofersen therapy in SOD1-associated ALS. J. Neurol. 271, 2114\u20132118 (2024).","journal-title":"J. Neurol."},{"key":"94984_CR32","doi-asserted-by":"crossref","unstructured":"Moshe\u2010Lilie, O., Riccelli, L. P. & Karam, C. Possible recurrent aseptic meningitis associated with nusinersen therapy. Muscle Nerve 62, (2020).","DOI":"10.1002\/mus.27042"},{"key":"94984_CR33","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.1038\/s41467-022-34620-y","volume":"13","author":"S Opie-Martin","year":"2022","unstructured":"Opie-Martin, S. et al. The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration. Nat. Commun. 13, 6901 (2022).","journal-title":"Nat. Commun."},{"key":"94984_CR34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3389\/fneur.2020.00377","volume":"11","author":"N Gaur","year":"2020","unstructured":"Gaur, N., Perner, C., Witte, O. W. & Grosskreutz, J. The Chitinases as biomarkers for amyotrophic lateral sclerosis: Signals from the CNS and beyond. Front. Neurol. 11, 377 (2020).","journal-title":"Front. Neurol."},{"key":"94984_CR35","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3390\/biomedicines10040819","volume":"10","author":"G Gianferrari","year":"2022","unstructured":"Gianferrari, G. et al. Epidemiological, clinical and genetic features of ALS in the last decade: A prospective population-based study in the Emilia Romagna Region of Italy. Biomedicines 10, 819 (2022).","journal-title":"Biomedicines"},{"key":"94984_CR36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/21678421.2016.1270325","volume":"18","author":"A Fasano","year":"2017","unstructured":"Fasano, A. et al. Percutaneous endoscopic gastrostomy, body weight loss and survival in amyotrophic lateral sclerosis: a population-based registry study. Amyotroph. Lateral Scler. Front. Degener. 18, 233\u2013242 (2017).","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"94984_CR37","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1007\/s10072-015-2343-6","volume":"36","author":"J Mandrioli","year":"2015","unstructured":"Mandrioli, J. et al. Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy. Neurol. Sci. 36, 2243\u20132252 (2015).","journal-title":"Neurol. Sci."},{"key":"94984_CR38","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1212\/WNL.0000000000001642","volume":"84","author":"C-H Lu","year":"2015","unstructured":"Lu, C.-H. et al. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84, 2247\u20132257 (2015).","journal-title":"Neurology"},{"key":"94984_CR39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/21678421.2016.1267768","volume":"18","author":"MJ Strong","year":"2017","unstructured":"Strong, M. J. et al. Amyotrophic lateral sclerosis\u2014Frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria. Amyotroph. Lateral Scler. Front. Degener. 18, 153\u2013174 (2017).","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"94984_CR40","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","volume":"44","author":"H Ashkenazy","year":"2016","unstructured":"Ashkenazy, H. et al. ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res. 44, W344-350 (2016).","journal-title":"Nucleic Acids Res."},{"key":"94984_CR41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003440","volume":"10","author":"J Bendl","year":"2014","unstructured":"Bendl, J. et al. PredictSNP: robust and accurate consensus classifier for prediction of disease-related mutations. PLoS Comput. Biol. 10, e1003440 (2014).","journal-title":"PLoS Comput. Biol."},{"key":"94984_CR42","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.4103\/1673-5374.361535","volume":"18","author":"I Martinelli","year":"2023","unstructured":"Martinelli, I. et al. The landscape of cognitive impairment in superoxide dismutase 1-amyotrophic lateral sclerosis. Neural Regen. Res. 18, 1427 (2023).","journal-title":"Neural Regen. Res."},{"key":"94984_CR43","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.3390\/biomedicines9111623","volume":"9","author":"C Simonini","year":"2021","unstructured":"Simonini, C. et al. CSF heavy neurofilament may discriminate and predict motor neuron diseases with upper motor neuron involvement. Biomedicines 9, 1623 (2021).","journal-title":"Biomedicines"},{"key":"94984_CR44","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/ana.27054","volume":"96","author":"S Witzel","year":"2024","unstructured":"Witzel, S. et al. Population-based evidence for the use of serum neurofilaments as individual diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis. Ann. Neurol. 96, 1040\u20131057 (2024).","journal-title":"Ann. Neurol."},{"key":"94984_CR45","doi-asserted-by":"crossref","unstructured":"Fazeli, B. et al. Quantification of blood glial fibrillary acidic protein using a second-generation microfluidic assay. Validation and comparative analysis with two established assays. Clin. Chem. Lab. Med. 62, 1591\u20131601 (2024).","DOI":"10.1515\/cclm-2023-1256"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-94984-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-94984-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-94984-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T23:14:15Z","timestamp":1743462855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-94984-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["94984"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-94984-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"assertion":[{"value":"13 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Each patient\u2019s EAP for tofersen administration was approved by the local Ethical Committees of all the participating centers prior to enrolment,while this observational study received approval from the Ethics Committee of Area Vasta Emilia Nord (file number: 63\/2022).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"11034"}}