{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:39:55Z","timestamp":1790991595890,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"vor","delay-in-days":146,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence nationale de la recherche","doi-asserted-by":"publisher","award":["ANR-18-RHUS-0012"],"award-info":[{"award-number":["ANR-18-RHUS-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"LABEX CORTEX","award":["ANR-11-LABX-0042"],"award-info":[{"award-number":["ANR-11-LABX-0042"]}]},{"DOI":"10.13039\/501100006687","name":"Universit\u00e9 Claude Bernard Lyon 1","doi-asserted-by":"publisher","award":["ANR-11-LABX-0042"],"award-info":[{"award-number":["ANR-11-LABX-0042"]}],"id":[{"id":"10.13039\/501100006687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>While the spectrum of neurological immune checkpoint inhibitor-related adverse events is expanding, patients\u2019 outcomes are not well documented. This study aimed to assess outcomes of neurological immune-related adverse events and to identify prognostic factors. All patients experiencing grade \u22652 neurological immune-related adverse events identified at two clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; and OncoNeuroTox, Paris) over five years were included. Modified Rankin scores were assessed at onset, 6, 12, 18 months, and last visit. A multi-state Markov model was used to estimate the transition rates between minor disability (mRS &amp;lt;3), severe disability (mRS 3-5), and death (mRS 6), over the study period. The state-to-state transition rates were estimated using maximum likelihood and variables were introduced into the different transitions to study their effects. A total of 147 patients were included out of 205 patients with a suspicion of neurological immune-related adverse events. The median age was 65 years (range 20\u201387) and 87\/147 patients (59.2%) were male. Neurological immune-related adverse events involved the peripheral nervous system in 87\/147 patients (59.2%), the central nervous system in 51\/147 (34.7%), and both systems in 9\/147 (6.1%). Paraneoplastic-like syndromes were observed in 30\/147 patients (20.4%). Cancers included lung cancers (36.1%), melanoma (30.6%), urological cancers (15.6%), and others (17.8%). Patients were treated with programmed cell death protein (ligan) 1 (PD(L)1) inhibitors (70.1%), CTLA4 inhibitors (3.4%) or both (25.9%). Severe disability was reported in 108\/144 patients (75.0%) at onset and in 33\/146 patients (22.6%) at last visit (median follow-up duration: 12 months, range 0.5\u201350); 48\/147 (32.7%) patients died, from cancer progression (17\/48, 35.4%), neurological toxicity (15\/48, 31.2%), other causes (10\/48, 20.8%) or unknown causes (6\/48, 12.5%). The rate of transition from severe to minor disability independently increased with melanoma [compared to lung cancer, hazard ratio = 3.26, 95%CI (1.27; 8.41)] and myositis\/neuromuscular junction disorders [hazard ratio = 8.26, 95%CI (2.90; 23.58)], and decreased with older age [hazard ratio = 0.68, 95%CI (0.47; 0.99)] and paraneoplastic-like syndromes [hazard ratio = 0.29, 95%CI (0.09; 0.98)]. In patients with neurological immune-related adverse events, myositis\/neuromuscular junction disorders and melanoma increase the transition rate from severe to minor disability, while older age and paraneoplastic-like syndromes result in poorer neurological outcomes; future studies are needed to optimize the management of such patients.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad169","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T06:53:51Z","timestamp":1685170431000},"source":"Crossref","is-referenced-by-count":86,"title":["Neurological outcomes in immune checkpoint inhibitor-related neurotoxicity"],"prefix":"10.1093","volume":"5","author":[{"given":"Antonio","family":"Farina","sequence":"first","affiliation":[{"name":"Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Neurological Hospital , Bron 69677 , France"},{"name":"MeLiS - UCBL-CNRS UMR 5284\u2014INSERM U1314, Universit\u00e9 Claude Bernard Lyon 1 , Lyon 69008 , France"},{"name":"Department of Neuroscience, Psychology, Pharmacology and Child Health, University of Florence , Florence 50139 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Birzu","sequence":"additional","affiliation":[{"name":"Department of Neurology 2 Mazarin, Sorbonne University, Brain Institute, INSERM UMR 1127, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris 75013 , France"},{"name":"OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re et H\u00f4pital Percy , Paris 75561 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mad-H\u00e9l\u00e9nie","family":"Elsensohn","sequence":"additional","affiliation":[{"name":"Biostatistics\u2014Bioinformatics Department, Public Health Unit. Hospices Civils de Lyon , Lyon 69003 , France"},{"name":"Laboratory of Biometry and Evolutionary Biology, University Claude Bernard Lyon 1 , Villeurbanne 69622 , France"},{"name":"CNRS, UMR5558, Laboratory of Biometry and Evolutionary Biology, Biostatistics-Health Team , Villeurbanne 69622 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-5393","authenticated-orcid":false,"given":"Alberto","family":"Picca","sequence":"additional","affiliation":[{"name":"Department of Neurology 2 Mazarin, Sorbonne University, Brain Institute, INSERM UMR 1127, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris 75013 , France"},{"name":"OncoNeuroTox Group, Center for Patients with Neurological Complications of Oncologic Treatments Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re et H\u00f4pital Percy , Paris 75561 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[{"name":"Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Neurological Hospital , Bron 69677 , France"},{"name":"MeLiS - UCBL-CNRS UMR 5284\u2014INSERM U1314, Universit\u00e9 Claude Bernard Lyon 1 , Lyon 69008 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3652-7061","authenticated-orcid":false,"given":"Alberto","family":"Vogrig","sequence":"additional","affiliation":[{"name":"Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Neurological Hospital , Bron 69677 , France"},{"name":"MeLiS - UCBL-CNRS UMR 5284\u2014INSERM U1314, Universit\u00e9 Claude Bernard Lyon 1 , Lyon 69008 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Villagr\u00e1n-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Neurological Hospital , Bron 69677 , France"},{"name":"MeLiS - UCBL-CNRS UMR 5284\u2014INSERM U1314, Universit\u00e9 Claude Bernard Lyon 1 , Lyon 69008 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-4847","authenticated-orcid":false,"given":"Nicol\u00e1s Lundahl","family":"Ciano-Petersen","sequence":"additional","affiliation":[{"name":"Reference Centre for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Neurological Hospital , Bron 69677 , France"},{"name":"MeLiS - 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