{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:11:11Z","timestamp":1778310671821,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s10072-026-08961-1","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:48:58Z","timestamp":1776991738000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic alterations in cerebrospinal fluid of spinal muscular atrophy patients undergoing nusinersen therapy: a systematic review and meta-analysis of potential biomarkers of treatment response"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1115-4610","authenticated-orcid":false,"given":"Bassel","family":"Alrabadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Marouf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Bandak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel Rahman Bani","family":"Yassin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamen","family":"Refai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama Ziad","family":"Hammad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar M.","family":"Nashwan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Alomari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"8961_CR1","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1001\/archneurol.2011.74","volume":"68","author":"SJ Kolb","year":"2011","unstructured":"Kolb SJ, Kissel JT (2011) Spinal muscular atrophy: a timely review. Arch Neurol 68:979\u2013984. https:\/\/doi.org\/10.1001\/archneurol.2011.74","journal-title":"Arch Neurol"},{"key":"8961_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-017-0671-8","volume":"12","author":"IEC Verhaart","year":"2017","unstructured":"Verhaart IEC, Robertson A, Wilson IJ et al (2017) Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis 12:1\u201315. https:\/\/doi.org\/10.1186\/s13023-017-0671-8","journal-title":"Orphanet J Rare Dis"},{"key":"8961_CR3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.2174\/1566524016666161128113338","volume":"16","author":"LA Nash","year":"2016","unstructured":"Nash LA, Burns JK, Chardon JW et al (2016) Spinal muscular atrophy: more than a disease of motor neurons? Curr Mol Med 16:779\u2013792. https:\/\/doi.org\/10.2174\/1566524016666161128113338","journal-title":"Curr Mol Med"},{"key":"8961_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104870","volume":"140","author":"E Abati","year":"2020","unstructured":"Abati E, Citterio G, Bresolin N et al (2020) Glial cells involvement in spinal muscular atrophy: could SMA be a neuroinflammatory disease? Neurobiol Dis 140:104870. https:\/\/doi.org\/10.1016\/j.nbd.2020.104870","journal-title":"Neurobiol Dis"},{"key":"8961_CR5","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1006\/geno.1996.0147","volume":"32","author":"L B\u00fcrglen","year":"1996","unstructured":"B\u00fcrglen L, Lefebvre S, Clermont O et al (1996) Structure and organization of the human survival motor neurone (SMN) gene. Genomics 32:479\u2013482. https:\/\/doi.org\/10.1006\/geno.1996.0147","journal-title":"Genomics"},{"key":"8961_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072222","author":"S Messina","year":"2020","unstructured":"Messina S, Sframeli M (2020) New treatments in spinal muscular atrophy: positive results and new challenges. J Clin Med. https:\/\/doi.org\/10.3390\/jcm9072222","journal-title":"J Clin Med"},{"key":"8961_CR7","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s13311-014-0314-x","volume":"12","author":"MA Farrar","year":"2015","unstructured":"Farrar MA, Kiernan MC (2015) The genetics of spinal muscular atrophy: progress and challenges. Neurotherapeutics 12:290\u2013302. https:\/\/doi.org\/10.1007\/s13311-014-0314-x","journal-title":"Neurotherapeutics"},{"key":"8961_CR8","doi-asserted-by":"publisher","first-page":"453","DOI":"10.3233\/JND-190416","volume":"6","author":"MC Walter","year":"2019","unstructured":"Walter MC, Wenninger S, Thiele S et al (2019) Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3 - a prospective observational study. J Neuromuscul Dis 6:453\u2013465. https:\/\/doi.org\/10.3233\/JND-190416","journal-title":"J Neuromuscul Dis"},{"key":"8961_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11040206","author":"L Deutsch","year":"2021","unstructured":"Deutsch L, Osredkar D, Plavec J, Stres B (2021) Spinal muscular atrophy after Nusinersen therapy: improved physiology in pediatric patients with no significant change in urine, serum, and liquor 1H-NMR metabolomes in comparison to an age-matched, healthy cohort. Metabolites. https:\/\/doi.org\/10.3390\/metabo11040206","journal-title":"Metabolites"},{"key":"8961_CR10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. https:\/\/doi.org\/10.1136\/bmj.n71","journal-title":"BMJ"},{"key":"8961_CR11","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","volume":"25","author":"A Stang","year":"2010","unstructured":"Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603\u2013605. https:\/\/doi.org\/10.1007\/s10654-010-9491-z","journal-title":"Eur J Epidemiol"},{"key":"8961_CR12","doi-asserted-by":"publisher","first-page":"280","DOI":"10.7326\/0003-4819-158-4-201302190-00009","volume":"158","author":"JA Hayden","year":"2013","unstructured":"Hayden JA, van der Windt DA, Cartwright JL et al (2013) Assessing bias in studies of prognostic factors. Ann Intern Med 158:280\u2013286. https:\/\/doi.org\/10.7326\/0003-4819-158-4-201302190-00009","journal-title":"Ann Intern Med"},{"key":"8961_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12206696","author":"M Beaudin","year":"2023","unstructured":"Beaudin M, Kamali T, Tang W et al (2023) Cerebrospinal fluid proteomic changes after Nusinersen in patients with spinal muscular atrophy. J Clin Med. https:\/\/doi.org\/10.3390\/jcm12206696","journal-title":"J Clin Med"},{"key":"8961_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094329","author":"L Bianchi","year":"2021","unstructured":"Bianchi L, Sframeli M, Vantaggiato L et al (2021) Nusinersen modulates proteomics profiles of cerebrospinal fluid in spinal muscular atrophy type 1 patients. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms22094329","journal-title":"Int J Mol Sci"},{"key":"8961_CR15","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16393","author":"G Musso","year":"2024","unstructured":"Musso G, Bello L, Capece G et al (2024) Neurofilament light chain and profilin-1 dynamics in 30 spinal muscular atrophy type 3 patients treated with nusinersen. Eur J Neurol. https:\/\/doi.org\/10.1111\/ene.16393","journal-title":"Eur J Neurol"},{"key":"8961_CR16","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1007\/s00415-019-09389-8","volume":"266","author":"B Olsson","year":"2019","unstructured":"Olsson B, Alberg L, Cullen NC et al (2019) NFL is a marker of treatment response in children with SMA treated with nusinersen. J Neurol 266:2129\u20132136. https:\/\/doi.org\/10.1007\/s00415-019-09389-8","journal-title":"J Neurol"},{"key":"8961_CR17","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1002\/mus.27731","volume":"66","author":"R Orbach","year":"2022","unstructured":"Orbach R, Sagi L, Sadot E et al (2022) Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy. Muscle Nerve 66:762\u2013766. https:\/\/doi.org\/10.1002\/mus.27731","journal-title":"Muscle Nerve"},{"key":"8961_CR18","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-024-05426-6","author":"C Panicucci","year":"2024","unstructured":"Panicucci C, Sahin E, Bartolucci M et al (2024) Proteomics profiling and machine learning in nusinersen-treated patients with spinal muscular atrophy. Cell Mol Life Sci. https:\/\/doi.org\/10.1007\/s00018-024-05426-6","journal-title":"Cell Mol Life Sci"},{"key":"8961_CR19","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1002\/psp4.12890","volume":"12","author":"A Paris","year":"2023","unstructured":"Paris A, Bora P, Parolo S et al (2023) A pediatric quantitative systems pharmacology model of neurofilament trafficking in spinal muscular atrophy treated with the antisense oligonucleotide nusinersen. CPT: Pharmacometrics & Systems Pharmacology 12:196\u2013206. https:\/\/doi.org\/10.1002\/psp4.12890","journal-title":"CPT: Pharmacometrics & Systems Pharmacology"},{"key":"8961_CR20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ejpn.2022.12.003","volume":"42","author":"FEV Scheijmans","year":"2023","unstructured":"Scheijmans FEV, Cuppen I, Zwartkruis MM et al (2023) Inflammatory markers in cerebrospinal fluid of paediatric spinal muscular atrophy patients receiving nusinersen treatment. Eur J Paediatr Neurol 42:34\u201341. https:\/\/doi.org\/10.1016\/j.ejpn.2022.12.003","journal-title":"Eur J Paediatr Neurol"},{"key":"8961_CR21","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1111\/ene.15331","volume":"29","author":"DC Schorling","year":"2022","unstructured":"Schorling DC, K\u00f6lbel H, Hentschel A et al (2022) Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy. Eur J Neurol 29:2084\u20132096. https:\/\/doi.org\/10.1111\/ene.15331","journal-title":"Eur J Neurol"},{"key":"8961_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215397","author":"A Totzeck","year":"2019","unstructured":"Totzeck A, Stolte B, Kizina K et al (2019) Neurofilament heavy chain and tau protein are not elevated in cerebrospinal fluid of adult patients with spinal muscular atrophy during loading with nusinersen. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms20215397","journal-title":"Int J Mol Sci"},{"key":"8961_CR23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s13311-022-01305-9","volume":"20","author":"S Verma","year":"2023","unstructured":"Verma S, Perry K, Razdan R et al (2023) CSF IL-8 associated with response to gene therapy in a case series of spinal muscular atrophy. Neurotherapeutics 20:245\u2013253. https:\/\/doi.org\/10.1007\/s13311-022-01305-9","journal-title":"Neurotherapeutics"},{"key":"8961_CR24","doi-asserted-by":"publisher","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 KG (2022) Biochemical and clinical biomarkers in adult SMA 3\u20134 patients treated with nusinersen for 22 months. Ann Clin Transl Neurol 9:1241\u20131251. https:\/\/doi.org\/10.1002\/acn3.51625","journal-title":"Ann Clin Transl Neurol"},{"key":"8961_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncel.2022.982760","volume":"16","author":"S Bonanno","year":"2022","unstructured":"Bonanno S, Cavalcante P, Salvi E et al (2022) Identification of a cytokine profile in serum and cerebrospinal fluid of pediatric and adult spinal muscular atrophy patients and its modulation upon nusinersen treatment. Front Cell Neurosci 16:1\u201315. https:\/\/doi.org\/10.3389\/fncel.2022.982760","journal-title":"Front Cell Neurosci"},{"key":"8961_CR26","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-12909-4","volume":"272","author":"M Zandl-Lang","year":"2025","unstructured":"Zandl-Lang M, Z\u00fcllig T, Holzer M et al (2025) Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients. J Neurol 272:183. https:\/\/doi.org\/10.1007\/s00415-025-12909-4","journal-title":"J Neurol"},{"key":"8961_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fneur.2024.1394001","volume":"15","author":"M Brku\u0161anin","year":"2024","unstructured":"Brku\u0161anin M, Kosa\u0107 A, Brankovi\u0107-Sre\u0107kovi\u0107 V et al (2024) Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia. Front Neurol 15:1\u201311. https:\/\/doi.org\/10.3389\/fneur.2024.1394001","journal-title":"Front Neurol"},{"key":"8961_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fped.2023.1294405","volume":"11","author":"L Chen","year":"2023","unstructured":"Chen L, Liu F, Fang D, Li J (2023) Study on the efficacy, safety, and biomarkers of nusinersen in type II and III spinal muscular atrophy in children. Front Pediatr 11:1\u20138. https:\/\/doi.org\/10.3389\/fped.2023.1294405","journal-title":"Front Pediatr"},{"key":"8961_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00018-023-04885-7","volume":"80","author":"I Faravelli","year":"2023","unstructured":"Faravelli I, Gagliardi D, Abati E et al (2023) Multi-omics profiling of CSF from spinal muscular atrophy type 3 patients after nusinersen treatment: a 2-year follow-up multicenter retrospective study. Cell Mol Life Sci 80:1\u201318. https:\/\/doi.org\/10.1007\/s00018-023-04885-7","journal-title":"Cell Mol Life Sci"},{"key":"8961_CR30","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/mus.27212","volume":"63","author":"A Introna","year":"2021","unstructured":"Introna A, Milella G, D\u2019Errico E et al (2021) Is cerebrospinal fluid amyloid-\u03b242 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients? Muscle Nerve 63:905\u2013909. https:\/\/doi.org\/10.1002\/mus.27212","journal-title":"Muscle Nerve"},{"key":"8961_CR31","doi-asserted-by":"publisher","first-page":"8419","DOI":"10.1111\/jcmm.16802","volume":"25","author":"J Johannsen","year":"2021","unstructured":"Johannsen J, Weiss D, Daubmann A et al (2021) Evaluation of putative CSF biomarkers in paediatric spinal muscular atrophy (SMA) patients before and during treatment with nusinersen. J Cell Mol Med 25:8419\u20138431. https:\/\/doi.org\/10.1111\/jcmm.16802","journal-title":"J Cell Mol Med"},{"key":"8961_CR32","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/jnc.14953","volume":"153","author":"T Kessler","year":"2020","unstructured":"Kessler T, Latzer P, Schmid D et al (2020) Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy. J Neurochem 153:650\u2013661. https:\/\/doi.org\/10.1111\/jnc.14953","journal-title":"J Neurochem"},{"key":"8961_CR33","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1111\/ene.15382","volume":"29","author":"I Magen","year":"2022","unstructured":"Magen I, Aharoni S, Yacovzada NS et al (2022) Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients. Eur J Neurol 29:2420\u20132430. https:\/\/doi.org\/10.1111\/ene.15382","journal-title":"Eur J Neurol"},{"key":"8961_CR34","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.4103\/NRR.NRR-D-24-00067","volume":"20","author":"X Xing","year":"2025","unstructured":"Xing X, Liu X, Li X et al (2025) Insights into spinal muscular atrophy from molecular biomarkers. Neural Regen Res 20:1849\u20131863. https:\/\/doi.org\/10.4103\/NRR.NRR-D-24-00067","journal-title":"Neural Regen Res"},{"key":"8961_CR35","doi-asserted-by":"crossref","unstructured":"Mousele C, Holden D, Gnanapavan S (2024) In: Makowski GSBT-A in CC (ed) Chapter Two - Neurofilaments in neurologic disease. Elsevier, pp 65\u2013128","DOI":"10.1016\/bs.acc.2024.06.010"},{"key":"8961_CR36","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1093\/hmg\/11.12.1439","volume":"11","author":"C Cifuentes-Diaz","year":"2002","unstructured":"Cifuentes-Diaz C, Nicole S, Velasco ME (2002) Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model. Hum Mol Genet 11:1439\u20131447. https:\/\/doi.org\/10.1093\/hmg\/11.12.1439","journal-title":"Hum Mol Genet"},{"key":"8961_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.689938","volume":"15","author":"A Yuan","year":"2021","unstructured":"Yuan A, Nixon RA (2021) Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front Neurosci 15:689938. https:\/\/doi.org\/10.3389\/fnins.2021.689938","journal-title":"Front Neurosci"},{"key":"8961_CR38","doi-asserted-by":"publisher","first-page":"6038","DOI":"10.1523\/JNEUROSCI.3716-14.2015","volume":"35","author":"N Miller","year":"2015","unstructured":"Miller N, Feng Z, Edens BM et al (2015) Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy. J Neurosci 35:6038\u20136050. https:\/\/doi.org\/10.1523\/JNEUROSCI.3716-14.2015","journal-title":"J Neurosci"}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-08961-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-026-08961-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-08961-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T06:31:39Z","timestamp":1778308299000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-026-08961-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["8961"],"URL":"https:\/\/doi.org\/10.1007\/s10072-026-08961-1","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"30 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No ethical approval or consent to participate was needed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors report no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"458"}}