{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:13:50Z","timestamp":1791566030131,"version":"4.3.4"},"reference-count":85,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Paraneoplastic neurological syndromes (PNSs) are immune-mediated disorders caused by an antitumor response that cross-reacts with the nervous system, leading to severe and often irreversible neurological disability. Once considered exceedingly rare, PNSs are now increasingly recognized owing to the identification of novel neural autoantibodies, wider use of commercial testing, and the emergence of immune checkpoint inhibitor (ICI)-related neurotoxicity that phenotypically overlaps with classic PNS. In this narrative review, we performed a structured search of PubMed\/MEDLINE, Scopus, Web of Science, and Google Scholar, without date restrictions, to summarize contemporary advances in the epidemiology, pathogenesis, diagnosis, and management of PNS. Population-based data show rising incidence, largely reflecting improved ascertainment and expanding indications for ICIs. Pathogenetically, we distinguish T-cell-mediated syndromes associated with intracellular antigens from antibody-mediated disorders targeting neuronal surface proteins, integrating emerging concepts of molecular mimicry, tumor genetics, and HLA-linked susceptibility. The 2021 PNS-Care criteria are also reviewed, which replace earlier \u201cclassical\/non-classical\u201d definitions with risk-stratified phenotypes and antibodies, and demonstrate superior diagnostic performance while underscoring that \u201cprobable\u201d and \u201cdefinite\u201d PNS should be managed with equal urgency. Newly described antibodies and methodological innovations such as PhIP-Seq, neurofilament light chain, and liquid biopsy are highlighted, which refine tumor search strategies and longitudinal monitoring. Management principles emphasize early tumor control, prompt immunotherapy, and a growing repertoire of targeted agents, alongside specific considerations for ICI-associated neurological syndromes. Remaining challenges include diagnostic delays, limited high-level evidence, and the paucity of validated biomarkers of disease activity. Future work should prioritize prospective, biomarker-driven trials and multidisciplinary pathways to shorten time to diagnosis and improve long-term outcomes in patients with PNS.<\/jats:p>","DOI":"10.3390\/antib15010008","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"8","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Paraneoplastic Neurological Syndromes: Advances and Future Perspectives in Immunopathogenesis and Management"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0559-8506","authenticated-orcid":false,"given":"Stoimen","family":"Dimitrov","sequence":"first","affiliation":[{"name":"Clinic of Rheumatology, University Multiprofile Hospital for Active Treatment \u201cSt. Marina\u201d, 9010 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-3962","authenticated-orcid":false,"given":"Mihael","family":"Tsalta-Mladenov","sequence":"additional","affiliation":[{"name":"Second Clinic of Neurology with ICU and Stroke Unit, University Multiprofile Hospital for Active Treatment \u201cSt. Marina\u201d, 9010 Varna, Bulgaria"},{"name":"Department of Neurology and Neuroscience, Faculty of Medicine, Medical University \u201cProf. Paraskev Stoyanov\u201d\u2014Varna, 9010 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-0577","authenticated-orcid":false,"given":"Plamena","family":"Kabakchieva","sequence":"additional","affiliation":[{"name":"Clinic of Internal Diseases, Naval Hospital Varna, Military Medical Academy, 9010 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1652-4648","authenticated-orcid":false,"given":"Tsvetoslav","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Clinic of Rheumatology, University Multiprofile Hospital for Active Treatment \u201cSt. Marina\u201d, 9010 Varna, Bulgaria"},{"name":"First Department of Internal Medicine, Faculty of Medicine, Medical University \u201cProf. Paraskev Stoyanov\u201d\u2014Varna, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silva","family":"Andonova","sequence":"additional","affiliation":[{"name":"Second Clinic of Neurology with ICU and Stroke Unit, University Multiprofile Hospital for Active Treatment \u201cSt. Marina\u201d, 9010 Varna, Bulgaria"},{"name":"Department of Neurology and Neuroscience, Faculty of Medicine, Medical University \u201cProf. Paraskev Stoyanov\u201d\u2014Varna, 9010 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/practneurol-2021-003073","article-title":"Paraneoplastic Neurological Syndromes: A Practical Approach to Diagnosis and Management","volume":"22","author":"Binks","year":"2022","journal-title":"Pract. 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