{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:30:54Z","timestamp":1792603854346,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006401","name":"Fondation Charcot","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether serum creatine kinase activity (CK) and serum creatinine concentration (Crn) are prognostic and predictive biomarkers for disease severity, disease progression, and nusinersen treatment effects in adult patients with 5q\u2010associated spinal muscular atrophy (SMA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Within this retrospective, multicenter observational study in 206 adult patients with SMA, we determined clinical subtypes (SMA types, ambulatory ability) and repeatedly measured CK and Crn and examined disease severity scores (Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Patients were followed under nusinersen treatment for 18\u00a0months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CK and Crn differed between clinical subtypes and correlated strongly with disease severity scores (e.g., for Hammersmith Functional Motor Scale Expanded: (CK)<jats:italic>\u03c1<\/jats:italic>\u00a0=\u00a00.786\/ (Crn)<jats:italic>\u03c1<\/jats:italic>\u00a0=\u00a00.558). During the 18\u00a0months of nusinersen treatment, CK decreased (\u2206CK\u00a0=\u00a0\u221217.56%,<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001), whereas Crn slightly increased (\u2206Crn\u00a0=\u00a0+4.75%,<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Serum creatine kinase activity and serum creatinine concentration reflect disease severity of spinal muscular atrophy and are promising biomarkers to assess patients with spinal muscular atrophy during disease course and to predict treatment response. The decrease of creatine kinase activity, combined with the tendency of creatinine concentration to increase during nusinersen treatment, suggests reduced muscle mass wasting with improved muscle energy metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51340","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T04:41:36Z","timestamp":1617252096000},"page":"1049-1063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-6075","authenticated-orcid":false,"given":"Maren","family":"Freigang","sequence":"first","affiliation":[{"name":"Department of Neurology Universit\u00e4tsklinikum Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia D.","family":"Wurster","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-3450","authenticated-orcid":false,"given":"Tim","family":"Hagenacker","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Stolte","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weiler","sequence":"additional","affiliation":[{"name":"Department of Neurology Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kamm","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rostock Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Schreiber\u2010Katz","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-8423","authenticated-orcid":false,"given":"Alma","family":"Osmanovic","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Petri","sequence":"additional","affiliation":[{"name":"Department of Neurology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kowski","sequence":"additional","affiliation":[{"name":"Department of Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medicine G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabell","family":"Cordts","sequence":"additional","affiliation":[{"name":"Department of Neurology Klinikum Rechts der Isar Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Deschauer","sequence":"additional","affiliation":[{"name":"Department of Neurology Klinikum Rechts der Isar Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7096","authenticated-orcid":false,"given":"Paul","family":"Lingor","sequence":"additional","affiliation":[{"name":"Department of Neurology Klinikum Rechts der Isar Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Aust","sequence":"additional","affiliation":[{"name":"Department of Neurology Universit\u00e4tsklinikum Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Petzold","sequence":"additional","affiliation":[{"name":"Department of Neurology Universit\u00e4tsklinikum Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert C.","family":"Ludolph","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulm University Ulm Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Falkenburger","sequence":"additional","affiliation":[{"name":"Department of Neurology Universit\u00e4tsklinikum Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-7791","authenticated-orcid":false,"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neurology Translational Neurodegeneration Section \u201cAlbrecht\u2010Kossel\u201d University Medical Center Rostock University of Rostock Rostock Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Rostock\/Greifswald Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Department of Neurology Universit\u00e4tsklinikum Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2015.07.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807305788"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710504"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30037-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756286420907803"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190416"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190453"},{"key":"e_1_2_8_10_1","first-page":"CD006282","article-title":"Drug treatment for spinal muscular atrophy types II and III","volume":"1","author":"Wadman RI","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2020.05.002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09847-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10030075"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00898"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2014-001031"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09507-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12995"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00322"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1129"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa152"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"e1205","DOI":"10.1212\/WNL.0000000000007097","article-title":"Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy","volume":"92","author":"Lombardi V","year":"2019","journal-title":"Neurology"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.324"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008762"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000007926"},{"key":"e_1_2_8_25_1","first-page":"742","article-title":"The value of the determination of cretaine phosphokinase activity (CPK) in certain diseases of the muscles","volume":"7","author":"Hetnarska L","year":"1968","journal-title":"Pol Med J"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26099"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2004.02.007"},{"key":"e_1_2_8_28_1","first-page":"69","article-title":"Statistics corner: a guide to appropriate use of correlation coefficient in medical research","volume":"24","author":"Mukaka MM","year":"2012","journal-title":"Malawi Medical J"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1515\/JLM.2005.041"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.099648"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25430"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-0790-9"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2018.11.009"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007945"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09646-w"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21350"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26995"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033572"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.779"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-320033"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756286419846058"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09547-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215397"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14953"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105482"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318295d766"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)63356-X"},{"key":"e_1_2_8_49_1","first-page":"371","article-title":"Creatine kinase (CK) and creatine kinase isoenzyme (CK\u2010MB) activity in serum before and after intravenous salbutamol administration of patients with bronchial asthma","volume":"30","author":"Chazan R","year":"1992","journal-title":"Int J Clin Pharmacol Ther Toxicol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10223-9"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T08:15:42Z","timestamp":1724746542000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,31]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/acn3.51340"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51340","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,31]]},"assertion":[{"value":"2020-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}