{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:59:40Z","timestamp":1792803580554,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute - Ricerca Corrente 2022-2024","award":["RRC2024-23684441"],"award-info":[{"award-number":["RRC2024-23684441"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Rare side effects of immune-checkpoint inhibitors (ICIs) are known as neurological immune-related adverse events (n-irAEs). Typically, n-irAEs affect the peripheral nervous system, primarily presenting as myositis, polyradiculoneuropathy, or cranial neuropathy. Less commonly, they impact the central nervous system, resulting in encephalitis, meningitis, or myelitis. High-grade n-irAEs managing and recognizing remains challenging, considering the risk of mortality and long-term disability. To date, strong scientific data are lacking to support the management of high-grade clinical forms. We performed a systematic literature search, selecting all articles describing high-grade steroid-resistance n-irAEs. and we reported them in a practical review. Specifically, current recommendations advise stopping ICI use and beginning corticosteroid treatment. Our findings highlighted that in steroid-resistant n-irAEs, it should be recommended to quickly escalate to plasma exchange (PLEX) and\/or intravenously immunoglobulins (IVIg), usually in association with other immunosuppressants. Furthermore, newer evidence supports the use of drugs that may specifically block inflammation without reducing the anti-tumour effect of ICIs. In this practical review, we provide new evidence regarding the therapeutic approach of high-grade n-irAEs, particularly in steroid-resistant cases. We would also stress the importance of informing the scientific community of the discrepancy between current guidelines and clinical evidence in these rare forms of pathology.<\/jats:p>","DOI":"10.3390\/brainsci14080764","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T11:11:25Z","timestamp":1722337885000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Unravelling the Acute, Chronic and Steroid-Refractory Management of High-Grade Neurological Immune-Related Adverse Events: A Call to Action"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-0890","authenticated-orcid":false,"given":"Antonio","family":"Malvaso","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Neuroimmunology Research Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Giglio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"},{"name":"Neuroncology Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pace","sequence":"additional","affiliation":[{"name":"IRCCS Regina Elena, Istituto Nazionale Tumori, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bini","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-8128","authenticated-orcid":false,"given":"Enrico","family":"Marchioni","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation\u2014National Neurological Institute, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The Blockade of Immune Checkpoints in Cancer Immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. 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