{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:47:13Z","timestamp":1793083633139,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients who develop chimeric antigen receptor (CAR) T-cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) frequently undergo evaluation with electroencephalography (EEG). We hypothesize that EEG features and Synek scale score, a measure of degree of EEG abnormality, are associated with ICANS severity. Here, we performed a retrospective review of 125 adult patients at Memorial Sloan Kettering Cancer Center (MSKCC) who received CAR-T cell therapy from 2010 to 2019, including 53 patients with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 72 patients with large B-cell lymphoma (LBCL) treated with the commercial CAR T products axicabtagene ciloleucel or tisagenlecleucel. We collected video EEG monitoring (27 with B-ALL and 20 with LBCL) and recorded daily EEG features, Synek scores, and ICANS grade for 47 eligible patients. Synek scale and ICANS grade were positively correlated (correlation coefficient 0.47, 95% CI: 0.31\u20130.60). This was further corroborated in the univariable model associating high Synek scale (3 or 4) with high ICANS grade (OR\u2009=\u200915.2; 95%CI:7.8\u201329.7, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). EEG features such as discontinuity, absence of posterior dominant rhythm, and presence of generalized sharp waves were statistically significantly associated with higher ICANS grade in univariable models. In the multivariable model, discontinuity (OR\u2009=\u20094.2 (95%CI:1.3\u201313.8, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) and absence of posterior dominant rhythm (OR\u2009=\u200910.5 (95%CI:4.6\u201323.9, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) were statistically associated with higher ICANS grade. Overall, EEG discontinuity and absence of posterior dominant rhythm were independently associated with higher severity of neurotoxicity. Further, our data suggest that Synek Scale, may be a severity marker for neurotoxicity.<\/jats:p>","DOI":"10.1038\/s41598-024-80566-0","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T17:21:34Z","timestamp":1732382494000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["EEG features and synek scale indicate severity of neurotoxicity in adult patients treated with CD19 CAR T-cell therapy"],"prefix":"10.1038","volume":"14","author":[{"given":"David","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne S.","family":"Reiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Pennisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel-Angel","family":"Perales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward K.","family":"Avila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca D.","family":"Santomasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"key":"80566_CR1","unstructured":"Investigators, J. S. SJ and Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma., N Engl J Med., vol. 380, no. 1, pp. 45\u201356, Jan 3. (2019)."},{"key":"80566_CR2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","volume":"396","author":"PMGL JS Abramson","year":"2020","unstructured":"JS Abramson, P. M. G. L. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 396, 839\u2013852 (2020).","journal-title":"Lancet"},{"key":"80566_CR3","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","volume":"377","author":"LFBN SS Neelapu","year":"2017","unstructured":"SS Neelapu, L. F. B. N. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory large B-Cell lymphoma. N Engl. J. Med. 377, 2531\u20132544 (2017).","journal-title":"N Engl. J. Med."},{"key":"80566_CR4","doi-asserted-by":"crossref","unstructured":"Wang, M. J. M, KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma., N Engl J Med, vol. 382, pp. 1331\u20131342., (2020).","DOI":"10.1056\/NEJMoa1914347"},{"key":"80566_CR5","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1126\/science.aar6711","volume":"359","author":"CH June","year":"2018","unstructured":"June, C. H., O\u2019Connor, R. S. & Kawalekar, O. U. CAR T cell immunotherapyfor human cancer. Science 359, 1361\u20131365 (2018 ).","journal-title":"Science"},{"key":"80566_CR6","first-page":"433","volume":"39","author":"BCWJR K","year":"2019","unstructured":"K., B. C. W. J. R. & Santomasso, S. E. The other side of CAR T-Cell therapy: Cytokine Release Syndrome, neurologic toxicity, and Financial Burden. Am. Soc. Clin. Oncol. Educ. Book. 39, 433\u2013444 (2019).","journal-title":"Am. Soc. Clin. Oncol. Educ. Book."},{"key":"80566_CR7","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1097\/PPO.0000000000000507","volume":"27","author":"SB Danish","year":"2021","unstructured":"Danish, S. B. Neurotoxicity Biology and Management. Cancer J. 27, 126\u2013133 (2021).","journal-title":"Cancer J."},{"issue":"8","key":"80566_CR8","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1158\/2159-8290.CD-17-1319","volume":"8","author":"BD Santomasso","year":"2018","unstructured":"Santomasso, B. D. & Jae, H. P. Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell therapy in patients with B-cell Acute Lymphoblastic Leukemia. Cancer Discov. 8(8), 958\u2013971 (2018).","journal-title":"Cancer Discov."},{"key":"80566_CR9","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1158\/2159-8290.CD-17-0698","volume":"7","author":"HKHL J Gust","year":"2017","unstructured":"J Gust, H. K. H. L. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov. 7, 1404\u20131419 (2017).","journal-title":"Cancer Discov"},{"key":"80566_CR10","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1182\/blood-2018-12-893396","volume":"133","author":"JJFD P Karschnia","year":"2019","unstructured":"P Karschnia, J. J. F. D. Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood 133, 2212\u20132221 (2019).","journal-title":"Blood"},{"key":"80566_CR11","doi-asserted-by":"crossref","unstructured":"Rubin, D. B. Neurological toxicities associated with chimeric antigen receptor T-cell therapy, Brain, vol. 142, no. 5, pp. 1334\u20131348, (2019).","DOI":"10.1093\/brain\/awz053"},{"key":"80566_CR12","unstructured":"D. S. B. L. F. e. a. Lee, ASTCT Consensus Grading for Cytokine Release Syndrome and neurologic toxicity Associated with Immune Effector cells. Biol. Blood Marrow Transpl., 25, 4, pp. 625\u2013638, (2019)."},{"issue":"7","key":"80566_CR13","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1038\/s41591-023-02404-6","volume":"29","author":"JH Park","year":"2023","unstructured":"Park, J. H. et al. CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: phase 2 trial interim results. Nat. Med. 29(7), 1710\u20131717 (2023).","journal-title":"Nat. Med."},{"issue":"2","key":"80566_CR14","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1097\/00004691-198804000-00003","volume":"5","author":"SVM Prognostically Important","year":"1988","unstructured":"Prognostically Important, S. V. M. EEG coma patterns in diffuse Axonic and traumatic encephalopathies in adults. J. Clin. Neurophysiol. 5(2), 161\u2013174 (1988).","journal-title":"J. Clin. 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Rep., 12, 20011, (2022).","DOI":"10.1038\/s41598-022-24010-1"},{"key":"80566_CR18","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1056\/NEJMoa1709919","volume":"378","author":"JH Park","year":"2018","unstructured":"Park, J. H. Long-term follow-up of CD19 CAR therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 378, 449\u2013459 (2018).","journal-title":"N. Engl. J. Med."},{"key":"80566_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/WNP.0000000000000806","volume":"38","author":"LJ Hirsch","year":"2021","unstructured":"Hirsch, L. J. American Clinical Neurophysiology Society\u2019s standardized. J. Clin. Neurophysiol. 38, 1\u201329 (2021).","journal-title":"J. Clin. Neurophysiol."},{"key":"80566_CR20","doi-asserted-by":"crossref","unstructured":"Kane, N. A revised glossary of terms most commonly used by clinical electroencephalographers and updated proposal for the report format of the EEG findings. Revision 2017, vol. 4, no. 2, pp. 170\u2013185, (2017).","DOI":"10.1016\/j.cnp.2017.07.002"},{"issue":"4","key":"80566_CR21","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1182\/bloodadvances.2019000952","volume":"4","author":"M Pennisi","year":"2020","unstructured":"Pennisi, M. et al. Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management. Blood Adv. 4(4), 676\u2013686 (2020).","journal-title":"Blood Adv."},{"key":"80566_CR22","doi-asserted-by":"crossref","unstructured":"Donnelly, E. M. & Blum, A. S. Focal and generalized slowing, coma, and Brain Death, in The Clinical Neurophysiology Primer, Humana, 127\u2013140. (2007).","DOI":"10.1007\/978-1-59745-271-7_9"},{"key":"80566_CR23","doi-asserted-by":"crossref","unstructured":"Smith, S. EEG in the diagnosis, classification, and management of patients with epilepsy, Journal of Neurology, Neurosurgery & Psychiatry vol. 76, 2005. (2005).","DOI":"10.1136\/jnnp.2005.069245"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80566-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80566-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80566-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T18:02:23Z","timestamp":1732384943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-80566-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,23]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["80566"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-80566-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,23]]},"assertion":[{"value":"15 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Perales reports honoraria from Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite\/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, and Sellas Life Sciences, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune, Omeros and OrcaBio. He has received institutional research support for clinical trials from Incyte, Kite\/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29090"}}