{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:29:13Z","timestamp":1785151753667,"version":"3.55.0"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012029","name":"Tsuchiya Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012029","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Immune\u2010related adverse events (irAEs) commonly involve the gastrointestinal tract, endocrine glands, skin, and liver, and rarely the nervous system. The pathomechanism of irAEs in the nervous system is unclear, and so characterizing these severe toxic effects is a priority, even if irAEs are uncommon in the nervous system. Our patient presented subacute muscle weakness and dysesthesia with colitis as irAEs caused by pembrolizumab, one of the anti\u2010programmed death\u20101 (PD\u20101) antibodies. Electromyography revealed abundant fibrillations and fasciculations of upper and lower extremities and severe reduction in motor unit potentials; however, antineutrophil cytoplasmic antibodies, rheumatoid factor, autoantibodies against Hu and Yo, and anti\u2010ganglioside antibodies, such as GQ1b, were undetectable in the serum. Although he was treated with high\u2010dose glucocorticoids, antibiotics, and a monoclonal anti\u2010tumor necrosis factor alpha (TNF\u03b1) antibody, he developed colonic perforation. The total colorectal resection was performed, and the resected colon showed mucosal defect and perforation. He died of lung aspergillosis. Postmortem examination revealed CD8\u2010positive lymphocyte infiltration around neurons of dorsal root ganglia. The sciatic nerve displayed the widening of myelin laminae and thinning of myelinated fibers but not a decrease in the density of myelinated nerve fibers. In the sural nerve, the density of myelinated fibers slightly decreased, and some fibers showed less densely myelinated laminae. Drug safety information, including previous randomized trials of anti\u2010PD\u20101 and anti\u2010cytotoxic T\u2010lymphocyte\u2013associated antigen\u20104 (CTLA\u20104) antibodies, showed that patients treated with anti\u2010PD\u20101 antibodies appeared to have more frequent and severe peripheral neuropathies compared to those in patients who received anti\u2010CTLA\u20104 antibodies (1.59% <jats:italic>vs<\/jats:italic>. 0.69%; Fisher exact test, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; three severe events <jats:italic>vs<\/jats:italic>. zero severe events). The present results and drug safety information suggest that the pathomechanism of irAEs caused by anti\u2010PD\u20101 antibodies is different from that by anti\u2010CTLA\u20104 antibodies. The neurological irAEs might be clues to solving the pathomechanism of irAEs.<\/jats:p>","DOI":"10.1111\/neup.12729","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T01:34:55Z","timestamp":1620092095000},"page":"266-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pembrolizumab\u2010caused polyradiculoneuropathy as an immune\u2010related adverse event"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-5979","authenticated-orcid":false,"given":"Takashi","family":"Kurashige","sequence":"first","affiliation":[{"name":"Department of Neurology National Hospital Organization Kure Medical Center and Chugoku Cancer Center  Kure, Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mineyo","family":"Mito","sequence":"additional","affiliation":[{"name":"Department of Respiratory National Hospital Organization Kure 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