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Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPP\u03b2, A\u03b240, A\u03b242, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM (p = 0.04) and HFMSE (p = 0.05) at 24 months. A reduction in sAPP\u03b2 levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, A\u03b240, and A\u03b242) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings.<\/jats:p>","DOI":"10.3390\/ijms25073810","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T06:33:16Z","timestamp":1711693996000},"page":"3810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neurodegeneration Biomarkers in Adult Spinal Muscular Atrophy (SMA) Patients Treated with Nusinersen"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3000-0338","authenticated-orcid":false,"given":"Pol","family":"Andr\u00e9s-Benito","sequence":"first","affiliation":[{"name":"Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Francisco","family":"V\u00e1zquez-Costa","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit and ERN-NMD Group, Department of Neurology, Hospital Universitario y Polit\u00e9cnico La Fe and IIS La Fe, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46026 Valencia, Spain"},{"name":"Department of Medicine, University of Valencia, 46021 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy Carolina","family":"\u00d1ungo Garz\u00f3n","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit and ERN-NMD Group, Department of Neurology, Hospital Universitario y Polit\u00e9cnico La Fe and IIS La Fe, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0106-0956","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Colomina","sequence":"additional","affiliation":[{"name":"Anesthesia and Critical Care Department, Bellvitge University Hospital-University of Barcelona, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6330-1376","authenticated-orcid":false,"given":"Carla","family":"Marco","sequence":"additional","affiliation":[{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Terrafeta","sequence":"additional","affiliation":[{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain"},{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain"},{"name":"Neuropathology Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain"},{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Povedano","sequence":"additional","affiliation":[{"name":"Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain"},{"name":"CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain"},{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","unstructured":"Darras, B.T., Jones, H.R., Ryan, M.M., and De Vivo, D.C. (2015). Neuromuscular Disorders of Infancy, Childhood, and Adolescence, Elsevier BV."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(80)90847-8","article-title":"CLASSIFICATION OF SPINAL MUSCULAR ATROPHIES","volume":"315","author":"Pearn","year":"1980","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/S0140-6736(08)60921-6","article-title":"Spinal muscular atrophy","volume":"371","author":"Lunn","year":"2008","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s13311-014-0314-x","article-title":"The Genetics of Spinal Muscular Atrophy: Progress and Challenges","volume":"12","author":"Farrar","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.nmd.2018.05.010","article-title":"Nusinersen in type 1 SMA infants, children and young adults: Preliminary results on motor function","volume":"28","author":"Pane","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s10072-018-3622-9","article-title":"Intrathecal nusinersen treatment for SMA in a dedicated neuromuscular clinic: An example of multidisciplinary and integrated care","volume":"40","author":"Sansone","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_9","first-page":"e413","article-title":"Nusinersen in adult patients with spinal muscular atrophy","volume":"95","author":"Visser","year":"2020","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1111\/ene.15542","article-title":"Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy","volume":"29","author":"Povedano","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1111\/ene.15501","article-title":"Nusinersen in adult patients with 5q spinal muscular atrophy: A multicenter observational cohorts\u2019 study","volume":"29","author":"Povedano","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s13311-022-01200-3","article-title":"Nusinersen in Adults with 5q Spinal Muscular Atrophy: A Systematic Review and Meta-analysis","volume":"19","author":"Gavriilaki","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer Dement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.jalz.2018.01.010","article-title":"CSF biomarkers of Alzheimer\u2019s disease concord with amyloid-\u03b2 PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts","volume":"14","author":"Hansson","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","first-page":"681","article-title":"The Concept of Prodromal Parkinson\u2019s Disease","volume":"5","author":"Mahlknecht","year":"2015","journal-title":"J. Park. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaat7108","DOI":"10.1126\/scitranslmed.aat7108","article-title":"Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington\u2019s disease","volume":"10","author":"Byrne","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1212\/01.wnl.0000437313.80913.2c","article-title":"Basal ganglia involvement in amyotrophic lateral sclerosis","volume":"81","author":"Bede","year":"2013","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S1474-4422(08)70293-X","article-title":"Biomarkers in amyotrophic lateral sclerosis","volume":"8","author":"Turner","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.nbd.2009.10.005","article-title":"Inflammation in ALS and SMA: Sorting out the good from the evil","volume":"37","author":"Papadimitriou","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0188-4409(01)00316-2","article-title":"The Molecular Bases of Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"32","author":"Maccioni","year":"2001","journal-title":"Arch. Med. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","article-title":"Prevalence, incidence and carrier frequency of 5q\u2013linked spinal muscular atrophy\u2014A literature review","volume":"12","author":"Verhaart","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1111\/ene.14902","article-title":"Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen","volume":"28","author":"Meyer","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1474-4422(20)30037-5","article-title":"Nusinersen in adults with 5q spinal muscular atrophy: A non-interventional, multicentre, observational cohort study","volume":"19","author":"Hagenacker","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1136\/jnnp-2020-323822","article-title":"Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3","volume":"91","author":"Maggi","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.parkreldis.2008.05.001","article-title":"Levels of brain related proteins in cerebrospinal fluid: An aid in the differential diagnosis of parkinsonian disorders","volume":"15","author":"Constantinescu","year":"2009","journal-title":"Park. Relat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1212\/WNL.0b013e31821432ff","article-title":"Neurofilament heavy chain in CSF correlates with relapses and disability in multiple sclerosis","volume":"76","author":"Kuhle","year":"2011","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1177\/1352458512443092","article-title":"Neurofilaments as biomarkers in multiple sclerosis","volume":"18","author":"Teunissen","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1136\/jnnp-2013-306789","article-title":"Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients","volume":"85","author":"Gresle","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ana.24552","article-title":"Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis","volume":"79","author":"Weydt","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xu, Z., Henderson, R.D., David, M., and McCombe, P.A. (2016). Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164625"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yuan, A., Rao, M.V., and Nixon, R.A. (2017). Neurofilaments and Neurofilament Proteins in Health and Disease. Cold Spring Harb. Perspect. Biol., 9.","DOI":"10.1101\/cshperspect.a018309"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/acn3.779","article-title":"Neurofilament as a potential biomarker for spinal muscular atrophy","volume":"6","author":"Darras","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s00415-019-09389-8","article-title":"NFL is a marker of treatment response in children with SMA treated with nusinersen","volume":"266","author":"Olsson","year":"2019","journal-title":"J. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1002\/acn3.51625","article-title":"Biochemical and clinical biomarkers in adult SMA 3\u20134 patients treated with nusinersen for 22 months","volume":"9","author":"Poesen","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Totzeck, A., Stolte, B., Kizina, K., Bolz, S., Schlag, M., Thimm, A., Kleinschnitz, C., and Hagenacker, T. (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., 20.","DOI":"10.3390\/ijms20215397"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3233\/JND-210735","article-title":"Neurofilament Levels in CSF and Serum in an Adult SMA Cohort Treated with Nusinersen","volume":"9","author":"Rich","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2217\/17520363.2.4.363","article-title":"Tau as a biomarker of neurodegenerative diseases","volume":"2","author":"Sergeant","year":"2008","journal-title":"Biomark. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1001\/jamaneurol.2018.4666","article-title":"Assessment of Plasma Total Tau Level as a Predictive Biomarker for Dementia and Related Endophenotypes","volume":"76","author":"Pase","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_39","first-page":"1152","article-title":"Brain-derived tau: A novel blood-based biomarker for Alzheimer\u2019s disease-type neurodegeneration","volume":"146","author":"Turton","year":"2022","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e20200861","DOI":"10.1084\/jem.20200861","article-title":"Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer\u2019s disease","volume":"217","author":"Horie","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1212\/WNL.0000000000003246","article-title":"Plasma tau in Alzheimer disease","volume":"87","author":"Mattsson","year":"2016","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/alzrt163","article-title":"Plasma tau levels in Alzheimer\u2019s disease","volume":"5","author":"Zetterberg","year":"2013","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fnagi.2019.00222","article-title":"Age-Dependent Relationship Between Plasma A\u03b240 and A\u03b242 and Total Tau Levels in Cognitively Normal Subjects","volume":"11","author":"Lue","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s40261-021-01071-0","article-title":"Cerebrospinal Fluid and Clinical Profiles in Adult Type 2\u20133 Spinal Muscular Atrophy Patients Treated with Nusinersen: An 18-Month Single-Centre Experience","volume":"41","author":"Milella","year":"2021","journal-title":"Clin. Drug Investig."},{"key":"ref_45","first-page":"e14051","article-title":"Total tau in cerebrospinal fluid detects treatment responders among spinal muscular atrophy types 1\u20133 patients treated with nusinersen","volume":"30","author":"Kutija","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.18632\/aging.101551","article-title":"YKL40 in sporadic amyotrophic lateral sclerosis: Cerebrospinal fluid levels as a prognosis marker of disease progression","volume":"10","author":"Colomina","year":"2018","journal-title":"Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-017-0226-4","article-title":"YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias","volume":"12","author":"Llorens","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1159\/000444855","article-title":"Chitinase 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications","volume":"83","author":"Malaguarnera","year":"2016","journal-title":"Pathobiology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11882-016-0637-2","article-title":"New Insights Into the Relationship Between Chitinase-3-Like-1 and Asthma","volume":"16","author":"Komi","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e227","DOI":"10.1038\/tp.2013.11","article-title":"Soluble amyloid precursor protein \u03b2 as blood-based biomarker of Alzheimer\u2019s disease","volume":"3","author":"Perneczky","year":"2013","journal-title":"Transl. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1212\/WNL.0000000000004088","article-title":"CSF sAPP\u03b2, YKL-40, and neurofilament light in frontotemporal lobar degeneration","volume":"89","author":"Alcolea","year":"2017","journal-title":"Neurology"},{"key":"ref_52","first-page":"e1619","article-title":"CSF sAPP\u03b2, YKL-40, and NfL along the ALS-FTD spectrum","volume":"91","author":"Alcolea","year":"2018","journal-title":"Neurology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fneur.2018.00384","article-title":"A Role for GDNF and Soluble APP as Biomarkers of Amyotrophic Lateral Sclerosis Pathophysiology","volume":"9","author":"Stanga","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/42257","article-title":"Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E","volume":"388","author":"Barger","year":"1997","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/nature07767","article-title":"RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases","volume":"457","author":"Nikolaev","year":"2009","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/mus.27212","article-title":"Is cerebrospinal fluid amyloid-\u03b242 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?","volume":"63","author":"Introna","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3233\/JND-190416","article-title":"Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3\u2014A Prospective Observational Study","volume":"6","author":"Walter","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_58","first-page":"676","article-title":"Ultrasound-guided lumbar puncture for nusinersen administration in spinal muscular atrophy patients","volume":"28","author":"Aparici","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rencher, A.C., and Christensen, W.F. (2012). Methods of Multivariate Analysis, Wiley Editorial. 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