{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:25:01Z","timestamp":1793823901310,"version":"4.6.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"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":["J Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment with significant improvements in survival rates. With the increase in ICI use in the clinical setting, several case reports and series have described neurological adverse events associated with it. We conducted this systematic review and meta-analysis to estimate the incidence of neurological adverse events among ICI clinical trials.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 25, 2025, using ICI and clinical trial as keywords along with their related MeSH terms. The inclusion criteria involved clinical trials investigating the efficacy or safety of any ICI as the only systemic therapy among never treated patients with cancer. To eliminate the impact of other systemic therapies, trials that used ICIs as an adjuvant to another systemic treatment or included patients previously treated with any systemic therapies were excluded. The incidence and its 95% confidence interval (95%CI) were used as the effect measures in the analysis. Subgroup analyses were conducted based on the type of cancer and number of ICIs used in the trial.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We included a total of 8,826 patients with cancer from 31 clinical trials. The pooled incidence of neurological adverse events was 1.78\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n % (95%CI 1.06\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %-2.78\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %). There was no difference (\n p<\/jats:italic>\n \u2009=\u20090.481) in the incidence of neurological side effects between trials that used one ICI (1.83\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.81\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20133.22\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %) compared to those that used two ICIs (0.90\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.01\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20132.64\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %). There was also no significant difference (\n p<\/jats:italic>\n \u2009>\u20090.622) in the incidence among patients with hepatocellular carcinoma (HCC) (1.20\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.01\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20133.67\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), non-small cell lung carcinoma (NSCLC) (1.83\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.01\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20136.0\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), and melanoma (1.16\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.22\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20132.71\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %). The most common neurological adverse events were peripheral neuropathy (1.34\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.61\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20132.3\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), myositis (0.78\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.29\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20131.49\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), aseptic meningitis (0.71\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.25\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20131.40\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), autoimmune demyelinating polyneuropathy (0.66\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.21\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20131.32\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), epilepsy (0.66\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.21\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20131.32\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %), and myasthenia gravis (0.66\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %; 95%CI 0.21\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %\u20131.32\u2009\u00d7\u200910\n \u20133<\/jats:sup>\n %).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Taken all together, the incidence of ICI-related neurological adverse events among patients with cancer is low and estimated at 1 in 5000 patients. Individual data analysis of ICI clinical trials is needed to examine the factors associated with ICI-related neurological adverse events.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00415-026-13925-8","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T16:29:26Z","timestamp":1780763366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The neurological adverse events of immune check point inhibitors in the treatment of cancer"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-9728","authenticated-orcid":false,"given":"Ahmad A.","family":"Toubasi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuraya N.","family":"Al-Sayegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"issue":"16","key":"13925_CR1","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","volume":"381","author":"J Larkin","year":"2019","unstructured":"Larkin J et al (2019) Five\u00a0year survival with combined Nivolumab and Ipilimumab in advanced melanoma. 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The manuscript was conducted in concordance with the declaration of Helsinki and the common ethical practices.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"373"}}