{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:40:10Z","timestamp":1783446010499,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p &lt; 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p &lt; 0.0001) and correlated with treatment yield. A strong negative correlation (r = \u22120.633) was observed for SMA type 1 and a very strong negative correlation (r = \u22120.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102074","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T04:09:36Z","timestamp":1664424576000},"page":"2074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Mihaela","family":"Axente","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"National University Center for Children Neurorehabilitation \u201cDr. Nicolae Robanescu\u201d, 44 Dumitru Minca Street, 041408 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada","family":"Mirea","sequence":"additional","affiliation":[{"name":"National University Center for Children Neurorehabilitation \u201cDr. Nicolae Robanescu\u201d, 44 Dumitru Minca Street, 041408 Bucharest, Romania"},{"name":"Faculty of Midwifery and Nursing, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-9690","authenticated-orcid":false,"given":"Corina","family":"Sporea","sequence":"additional","affiliation":[{"name":"National University Center for Children Neurorehabilitation \u201cDr. Nicolae Robanescu\u201d, 44 Dumitru Minca Street, 041408 Bucharest, Romania"},{"name":"Faculty of Midwifery and Nursing, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"P\u0103dure","sequence":"additional","affiliation":[{"name":"National University Center for Children Neurorehabilitation \u201cDr. Nicolae Robanescu\u201d, 44 Dumitru Minca Street, 041408 Bucharest, Romania"},{"name":"Faculty of Midwifery and Nursing, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6568-6846","authenticated-orcid":false,"given":"Cristina Manuela","family":"Dr\u0103goi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020956 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Crengu\u021ba","family":"Nicolae","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020956 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Adriana","family":"Ion","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, National Institute for Infectious Diseases Prof. Dr. Matei Bal\u0219, Carol Davila University of Medicine and Pharmacy, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fneur.2019.00898","article-title":"Biomarkers and the development of a personalized medicine approach in spinal muscular atrophy","volume":"10","author":"Kariyawasam","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.braindev.2012.03.009","article-title":"Peripheral nerve abnormalities in pediatric patients with spinal muscular atrophy","volume":"35","author":"Yonekawa","year":"2013","journal-title":"Brain Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/TACG.S239603","article-title":"Spinal Muscular Atrophy: Mutations, Testing, and Clinical Relevance","volume":"14","author":"Keinath","year":"2021","journal-title":"Appl. Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3233\/JND-200534","article-title":"Measuring Outcomes in Adults with Spinal Muscular Atrophy\u2013Challenges and Future Directions\u2013Meeting Report","volume":"7","author":"Sansone","year":"2020","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pediatrneurol.2019.06.007","article-title":"From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1","volume":"100","author":"Mendell","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chabanon, A., Seferian, A.M., Daron, A., P\u00e9r\u00e9on, Y., Cances, C., Vuillerot, C., De Waele, L., Cuisset, J.-M., Laugel, V., and Schara, U. (2018). Prospective and longitudinal natural history study of patients with type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201004"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/mus.21838","article-title":"Compound muscle action potential and motor function in children with spinal muscular atrophy","volume":"42","author":"Lewelt","year":"2010","journal-title":"Muscle Nerve"},{"key":"ref_10","unstructured":"(2021, May 15). A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants with Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (NURTURE), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02386553."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Arnold, W.D., Simard, L.R., Rutkove, S.B., and Kolb, S.J. (2017). Development and testing of biomarkers in spinal muscular atrophy. Spinal Muscular Atrophy, Elsevier.","DOI":"10.1016\/B978-0-12-803685-3.00024-0"},{"key":"ref_12","unstructured":"European Medicines Agency (2021, May 17). Annex 1. Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/spinraza-epar-product-information_en.pdf."},{"key":"ref_13","unstructured":"American Society of Health-System Pharmacists (2021, May 17). Spinraza (nusinersen) Approved. Available online: https:\/\/www.ahfsdruginformation.com\/spinraza-nusinersen-approved\/."},{"key":"ref_14","unstructured":"European Medicines Agency (2021, May 17). EU\/3\/12\/976: Orphan Designation for the Treatment of 5q Spinal Muscular Atrophy. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/orphan-designations\/eu312976."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1101\/gad.1941310","article-title":"Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model","volume":"24","author":"Hua","year":"2010","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100771","DOI":"10.1016\/j.spen.2019.08.007","article-title":"Neuromuscular Diseases of the Newborn","volume":"32","author":"Fay","year":"2019","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.31925\/farmacia.2022.3.24","article-title":"Assessing legal responsibility in romanian pharmaceutical practice","volume":"70","author":"Banu","year":"2022","journal-title":"Farmacia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2329048X211008725","DOI":"10.1177\/2329048X211008725","article-title":"Spinal muscular atrophy: The use of functional motor scales in the era of disease-modifying treatment","volume":"8","author":"Pierzchlewicz","year":"2021","journal-title":"Child Neurol. Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ejpn.2011.07.014","article-title":"Nerve conduction studies and needle EMG in very small children","volume":"16","author":"Pitt","year":"2012","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nmd.2009.11.014","article-title":"The Children\u2019s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP INTEND): Test development and reliability","volume":"20","author":"Glanzman","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kichula, E., Duong, T., Glanzman, A., Pasternak, A., Darras, B., Finkel, R., De Vivo, D., Zolkipli-Cunningham, Z., and Day, J. (2018). Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Feasibility for Individuals with Severe Spinal Muscular Atrophy II (S46. 004), AAN Enterprises.","DOI":"10.1212\/WNL.90.15_supplement.S46.004"},{"key":"ref_22","unstructured":"(2021, May 29). CHOP INTEND (Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders). Available online: https:\/\/smauk.org.uk\/files\/files\/Research\/CHOPINTEND.pdf."},{"key":"ref_23","unstructured":"Physical Assessments for Individuals with Spinal Muscular Atrophy (SMA) (2021, June 25). Biogen. Together in SMA. Available online: https:\/\/www.togetherinsma.com\/en_us\/home\/introduction-to-sma\/physical-assessment.html?tabKey=tab21."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.nmd.2007.05.009","article-title":"An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients","volume":"17","author":"Glanzman","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1177\/0883073811420294","article-title":"Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III","volume":"26","author":"Glanzman","year":"2011","journal-title":"J. Child Neurol."},{"key":"ref_26","unstructured":"(2021, May 29). HFMSE\u2014Hammersmith Functional Motor Scale\u2014Expanded. Spinal Muscular Atrophy UK. Available online: https:\/\/smauk.org.uk\/files\/files\/Research\/HFMSEscale.pdf."},{"key":"ref_27","unstructured":"(2021, May 29). Hammersmith Functional Motor Scale Expanded for SMA (HFMSE). Available online: http:\/\/columbiasma.org\/docs\/HFMSE_2019_Manual.pdf."},{"key":"ref_28","unstructured":"(2021, May 29). Six Minute Walk Test. Available online: https:\/\/www.physio-pedia.com\/Six_Minute_Walk_Test_\/_6_Minute_Walk_Test."},{"key":"ref_29","unstructured":"Williams, F., and Monge, P. (2001). Reasoning with Statistics: How to Read Quantitative Research, Harcourt College Publishers. [5th ed.]."},{"key":"ref_30","unstructured":"(2021, June 17). Pearson\u2019s Correlation Coefficient. Available online: https:\/\/www.statisticssolutions.com\/free-resources\/directory-of-statistical-analyses\/pearsons-correlation-coefficient\/."},{"key":"ref_31","first-page":"179","article-title":"Physical Therapy and Nusinersen Impact on Spinal Muscular Atrophy Rehabilitative Outcome","volume":"27","author":"Mirea","year":"2022","journal-title":"FBL"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7S29","DOI":"10.1016\/S0929-693X(20)30274-8","article-title":"Respiratory management of children with spinal muscular atrophy (SMA)","volume":"27","author":"Fauroux","year":"2020","journal-title":"Arch. P\u00e9diatrie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/ppul.24664","article-title":"Impact of scoliosis surgery on pulmonary function in patients with muscular dystrophies and spinal muscular atrophy","volume":"55","author":"Farber","year":"2020","journal-title":"Pediatr. Pulmonol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1007\/s00586-020-06564-8","article-title":"Impact of growth friendly interventions on spine and pulmonary outcomes of patients with spinal muscular atrophy","volume":"30","author":"Swarup","year":"2021","journal-title":"Eur. Spine J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mirea, A., Shelby, E.-S., Axente, M., Badina, M., Padure, L., Leanca, M., Dima, V., and Sporea, C. (2021). Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235540"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41436-020-00987-w","article-title":"CMAP changes upon symptom onset and during treatment in spinal muscular atrophy patients: Lessons learned from newborn screening","volume":"23","author":"Weng","year":"2021","journal-title":"Genet. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/10\/2074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:39Z","timestamp":1760143299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/10\/2074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["pharmaceutics14102074"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14102074","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]}}}