{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:24:27Z","timestamp":1791246267256,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"EU programme Horizon2020","award":["681094"],"award-info":[{"award-number":["681094"]}]},{"DOI":"10.13039\/501100007352","name":"Swiss State Secretariat for Education, Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032605","name":"Swiss Paraplegic Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032605","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CeNeReg of Wyss Zurich"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["P500PB_214416"],"award-info":[{"award-number":["P500PB_214416"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Health Research BC","doi-asserted-by":"publisher","award":["RT-2023-3173"],"award-info":[{"award-number":["RT-2023-3173"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"publisher","award":["MFE 194028"],"award-info":[{"award-number":["MFE 194028"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There are no approved interventional therapies, aside from neurorehabilitation, that enhance neurological recovery after acute traumatic spinal cord injury. A key challenge is the lack of biomarkers surpassing clinical standards for optimal stratification. We evaluated electrophysiological markers of preserved neuronal function to improve enrichment strategies over clinical measures. We hypothesized that participants with preserved electrophysiological markers would achieve greater neurological and functional recovery in response to a plasticity-inducing intervention.<\/jats:p>\n                  <jats:p>We conducted a retrospective stratification analysis of data from the recently completed randomized, placebo-controlled, phase 2b Nogo Inhibition in spinal cord injury (NISCI) trial (NCT03935321) investigating the efficacy of NG101, a recombinant human antibody that neutralizes the neurite outgrowth-inhibiting protein Nogo-A. Participants aged 18\u201370 years with acute (4\u201328 days) cervical spinal cord injury were eligible. At screening, all participants underwent clinical neurological examination and electrophysiological recordings (i.e. somatosensory evoked potentials). Treatment effect sizes for the recovery of upper extremity motor scores and spinal cord independence measure of self-care (6-month change) between NG101 and placebo groups were compared for stratification based on clinical versus electrophysiological criteria. Power analyses were conducted to estimate the required sample sizes needed for each method.<\/jats:p>\n                  <jats:p>The cohort included 116 participants (45.5 \u00b1 16.8 years old, 74 NG101 and 41 placebo). Clinical stratification showed greater functional recovery in motor-incomplete participants treated with NG101 versus placebo [estimate 0.02 (95% confidence interval: 0.006\u20130.038), P = 0.007]. Electrophysiological stratification revealed greater functional recovery in participants with preserved somatosensory evoked potentials treated with NG101 versus placebo [0.04 (0.015\u20130.054), P &amp;lt; 0.001]. Effect sizes were large for electrophysiological stratification (Cohen\u2019s d = 0.94) but small for clinical stratification (Cohen\u2019s d = 0.46). Power analyses demonstrated smaller required sample sizes for electrophysiological stratification (required n = 32) versus clinical stratification (required n = 120).<\/jats:p>\n                  <jats:p>This study shows the value of electrophysiology in comparison to clinical measures for biomarker-driven enrichment and improved power in acute spinal cord injury trials. We emphasize the importance of functionally spared neuronal pathways in promoting recovery in response to plasticity-inducing interventions, such as anti-Nogo-A antibodies.<\/jats:p>","DOI":"10.1093\/brain\/awaf354","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T11:55:58Z","timestamp":1758628558000},"page":"908-917","source":"Crossref","is-referenced-by-count":6,"title":["Enhanced clinical trial stratification in spinal cord injury: the value of electrophysiology"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-0133","authenticated-orcid":false,"given":"Paulina S","family":"Scheuren","sequence":"first","affiliation":[{"name":"International Collaboration on Repair Discoveries, University of British Columbia , Vancouver, BC , V5Z 1M9","place":["Canada"]},{"name":"Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, BC , V6T 1Z3","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schubert","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich , Zurich 8008 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Hubli","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich , Zurich 8008 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine R","family":"Jutzeler","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, ETH Zurich , Zurich 8092 ,","place":["Switzerland"]},{"name":"Swiss Institute of Bioinformatics (SIB) , Lausanne 1015 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Rupp","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Heidelberg University Hospital , Heidelberg 69120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Abel","sequence":"additional","affiliation":[{"name":"Clinic for Paraplegia, Klinikum Bayreuth GmbH , Bayreuth 95445 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Maier","sequence":"additional","affiliation":[{"name":"Spinal Cord Injuries, Berufsgenossenschaftliche Unfallklinik Murnau , Murnau 82418 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"R\u00f6hl","sequence":"additional","affiliation":[{"name":"Spinal Cord Injuries, Berufsgenossenschaftliche Unfallklinik Murnau , Murnau 82418 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Baumberger","sequence":"additional","affiliation":[{"name":"Swiss Paraplegic Centre , Nottwil 6207 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margret","family":"Hund-Georgiadis","sequence":"additional","affiliation":[{"name":"Clinic of Neurorehabilitation and Paraplegiology, REHAB Basel , Basel 4055 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Saur","sequence":"additional","affiliation":[{"name":"Orthop\u00e4dische Klinik , Hessisch Lichtenau 37235 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Benito-Penalva","sequence":"additional","affiliation":[{"name":"Institut Guttmann, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la UAB , Badalona 08916 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d'Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Rehahn","sequence":"additional","affiliation":[{"name":"Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin , Berlin 12683 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Aach","sequence":"additional","affiliation":[{"name":"Department of Spinal Cord Injuries, BG University Hospital Bergmannsheil , Bochum 44789 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Badke","sequence":"additional","affiliation":[{"name":"BG Clinic T\u00fcbingen , T\u00fcbingen 72076 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Kriz","sequence":"additional","affiliation":[{"name":"Spinal Cord Unit, Department of Rehabilitation and Sports Medicine, 2nd Faculty of Medicine, Charles University and University Hospital Motol , Prague 150 06 ,","place":["Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Freund","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich , Zurich 8008 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Weidner","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Heidelberg University Hospital , Heidelberg 69120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E","family":"Schwab","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine, University of Zurich , Schlieren 8952 ,","place":["Switzerland"]},{"name":"Wyss Zurich Translational Center, University and ETH Zurich , Zurich 8006 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L K","family":"Kramer","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries, University of British Columbia , Vancouver, BC , V5Z 1M9","place":["Canada"]},{"name":"Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, BC , V6T 1Z3","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Curt","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich , Zurich 8008 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"2026030512074926900_awaf354-B1","doi-asserted-by":"crossref","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2026030512074926900_awaf354-B2","doi-asserted-by":"crossref","first-page":"105381","DOI":"10.1016\/j.ebiom.2024.105381","article-title":"Next-gen spinal cord injury clinical trials: Lessons learned and opportunities for future success","volume":"109","author":"Scheuren","year":"2024","journal-title":"EBioMedicine"},{"key":"2026030512074926900_awaf354-B3","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1089\/neu.2023.0163","article-title":"Safety and efficacy of riluzole in acute spinal cord injury (RISCIS): A multi-center, randomized, placebo-controlled, double-blinded trial","volume":"1","author":"Fehlings","year":"2023","journal-title":"J Neurotrauma"},{"key":"2026030512074926900_awaf354-B4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1474-4422(24)00447-2","article-title":"Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: A randomised, double-blind, multicentre, placebo-controlled, phase 2b trial","volume":"24","author":"Weidner","year":"2025","journal-title":"Lancet Neurol"},{"key":"2026030512074926900_awaf354-B5","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1089\/neu.2020.7473","article-title":"Characterizing natural recovery after traumatic spinal cord injury","volume":"38","author":"Kirshblum","year":"2021","journal-title":"J Neurotrauma"},{"key":"2026030512074926900_awaf354-B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.46292\/sci2702-1","article-title":"International standards for neurological classification of spinal cord injury","volume":"27","author":"Rupp","year":"2021","journal-title":"Top Spinal Cord Inj Rehabil"},{"key":"2026030512074926900_awaf354-B7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/neu.2013.2982","article-title":"Spinal cord injury: How can we improve the classification and quantification of its severity and prognosis?","volume":"31","author":"Krishna","year":"2014","journal-title":"J Neurotrauma"},{"key":"2026030512074926900_awaf354-B8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s12916-022-02395-0","article-title":"International surveillance study in acute spinal cord injury confirms viability of multinational clinical trials","volume":"20","author":"Bourguignon","year":"2022","journal-title":"BMC Med"},{"key":"2026030512074926900_awaf354-B9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0003-9993(97)90007-1","article-title":"Ambulatory capacity in spinal cord injury: Significance of somatosensory evoked potentials and ASIA protocol in predicting outcome","volume":"78","author":"Curt","year":"1997","journal-title":"Arch Phys Med Rehabil"},{"key":"2026030512074926900_awaf354-B10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/sj.sc.3100809","article-title":"Electrophysiological recordings in patients with spinal cord injury: Significance for predicting outcome","volume":"37","author":"Curt","year":"1999","journal-title":"Spinal Cord"},{"key":"2026030512074926900_awaf354-B11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0003-9993(96)90219-1","article-title":"Traumatic cervical spinal cord injury: Relation between somatosensory evoked potentials, neurological deficit, and hand function","volume":"77","author":"Curt","year":"1996","journal-title":"Arch Phys Med Rehabil"},{"key":"2026030512074926900_awaf354-B12","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.clinph.2008.01.021","article-title":"Evolution of tibial SSEP after traumatic spinal cord injury: Baseline for clinical trials","volume":"119","author":"Spiess","year":"2008","journal-title":"Clinical Neurophysiology"},{"key":"2026030512074926900_awaf354-B13","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1089\/neu.2017.5576","article-title":"Electrophysiological multimodal assessments improve outcome prediction in traumatic cervical spinal cord injury","volume":"35","author":"Hupp","year":"2018","journal-title":"J Neurotrauma"},{"key":"2026030512074926900_awaf354-B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cophys.2019.11.001","article-title":"Recovery after spinal cord injury is enhanced by anti-Nogo-A antibody therapy\u2014from animal models to clinical trials","volume":"14","author":"Sartori","year":"2020","journal-title":"Curr Opin Physiol"},{"key":"2026030512074926900_awaf354-B15","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/ana.20627","article-title":"Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats","volume":"58","author":"Liebscher","year":"2005","journal-title":"Ann Neurol"},{"key":"2026030512074926900_awaf354-B16","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1177\/1545968313520413","article-title":"Identifying homogeneous subgroups in neurological disorders: Unbiased recursive partitioning in cervical complete spinal cord injury","volume":"28","author":"Tanadini","year":"2014","journal-title":"Neurorehabil Neural Repair"},{"key":"2026030512074926900_awaf354-B17","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1177\/1545968315570322","article-title":"Toward inclusive trial protocols in heterogeneous neurological disorders: Prediction-based stratification of participants with incomplete cervical spinal cord injury","volume":"29","author":"Tanadini","year":"2015","journal-title":"Neurorehabil Neural Repair"},{"key":"2026030512074926900_awaf354-B18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1177\/1545968318776371","article-title":"First-in-man intrathecal application of neurite growth-promoting anti-nogo-A antibodies in acute spinal cord injury","volume":"32","author":"Kucher","year":"2018","journal-title":"Neurorehabil Neural Repair"},{"key":"2026030512074926900_awaf354-B19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/1545968309348312","article-title":"Dermatomal somatosensory evoked potentials and electrical perception thresholds during recovery from cervical spinal cord injury","volume":"24","author":"Kramer","year":"2010","journal-title":"Neurorehabil Neural Repair"},{"key":"2026030512074926900_awaf354-B20","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1080\/09638280601046302","article-title":"The spinal cord independence measure (SCIM) version III: Reliability and validity in a multi-center international study","volume":"29","author":"Itzkovich","year":"2007","journal-title":"Disabil Rehabil"},{"key":"2026030512074926900_awaf354-B21","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.clinph.2020.01.017","article-title":"Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI","volume":"131","author":"Awad","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"2026030512074926900_awaf354-B22","doi-asserted-by":"crossref","first-page":"jrm00156","DOI":"10.2340\/16501977-2774","article-title":"Prevalence of discomplete sensorimotor spinal cord injury as evidenced by neurophysiological methods: A cross-sectional study","volume":"53","author":"Wahlgren","year":"2021","journal-title":"J Rehabil Med"},{"key":"2026030512074926900_awaf354-B23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1177\/0888439004267674","article-title":"Clinical neurophysiological assessment of residual motor control in post-spinal cord injury paralysis","volume":"18","author":"Mckay","year":"2004","journal-title":"Neurorehabil Neural Repair"},{"key":"2026030512074926900_awaf354-B24","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/cne.21321","article-title":"Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey","volume":"502","author":"Freund","year":"2007","journal-title":"J Comp Neurol."},{"key":"2026030512074926900_awaf354-B25","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nm1436","article-title":"Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates","volume":"12","author":"Freund","year":"2006","journal-title":"Nat Med"},{"key":"2026030512074926900_awaf354-B26","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.4103\/1673-5374.139470","article-title":"Cervical spinal cord injury: Tailoring clinical trial endpoints to reflect meaningful functional improvements","volume":"9","author":"Bond","year":"2014","journal-title":"Neural Regen Res"},{"key":"2026030512074926900_awaf354-B27","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41393-019-0276-2","article-title":"The challenge of recruitment for neurotherapeutic clinical trials in spinal cord injury","volume":"57","author":"Blight","year":"2019","journal-title":"Spinal Cord"},{"key":"2026030512074926900_awaf354-B28","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1001\/jamaneurol.2017.0318","article-title":"Challenges to translation and the Hippocratic oath by premature termination of spinal cord stem cell-based trials","volume":"74","author":"Curt","year":"2017","journal-title":"JAMA Neurol"},{"key":"2026030512074926900_awaf354-B29","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/s41393-020-00547-8","article-title":"Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system","volume":"58","author":"Mulcahey","year":"2020","journal-title":"Spinal Cord"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awaf354\/64374774\/awaf354.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/149\/3\/908\/64374774\/awaf354.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/149\/3\/908\/64374774\/awaf354.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T17:07:56Z","timestamp":1772730476000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/149\/3\/908\/8263041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9,24]]},"published-print":{"date-parts":[[2026,3,5]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awaf354","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,9,24]]}}}