{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:58:59Z","timestamp":1776416339632,"version":"3.51.2"},"reference-count":125,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":67,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Paraneoplastic motor neuron disease is an uncommon paraneoplastic neurologic syndrome whose existence has fallen into ambiguity. Epidemiologic studies that have addressed the association between cancer and motor neuron disease have provided conflicting results. Case studies that report motor neuron disease presentation at the time of active malignant disease, in the presence of another paraneoplastic neurologic syndrome or onconeural antibody or with neurologic response to antineoplastic treatment provide strong evidence for paraneoplastic motor neuron disease. However, conclusive evidence about the existence and the clinical and laboratory profiles of this neurologic syndrome is lacking. In this study, we report four new cases of paraneoplastic motor neuron disease, two of whom with expression of Sry-like high mobility group box 1 (SOX1) antibody. We also present a systematic review of all cases of paraneoplastic motor neuron disease reported to date that fulfill prespecified inclusion criteria with individual participant data meta-analysis of the demographic, clinical and laboratory features of the disease. Our data demonstrate that motor neuron disease can present as a paraneoplastic neurologic syndrome. Paraneoplastic motor neuron disease spans the whole motor neuron disease phenotypic spectrum, and it is associated with a wide variety of neoplastic diseases, onconeural antibodies and it may present concurrently with other well-recognized paraneoplastic neurologic syndromes. Paraneoplastic motor neuron disease may be clinically indistinguishable from idiopathic motor neuron disease. Its only distinctive clinical feature is the rapidly progressive course. A subset of cases display immune derangements in cerebrospinal fluid, including increased white cell count, elevated protein, albumin index, IgG index and\/or oligoclonal band expression. Cancer-induced inflammatory pathways may trigger the disease in genetically predisposed individuals harboring amyotrophic lateral sclerosis-causing genetic deficits. A thorough evaluation for neoplastic diseases should be carried out upon strong suspicion of this rare paraneoplastic neurologic syndrome to increase the diagnostic yield for this entity. Paraneoplastic motor neuron disease apparently results from complex interactions between degenerative and immune pathways and its pathophysiology may elucidate previously unresolved aspects of idiopathic motor neuron disease pathogenesis.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag024","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:49:26Z","timestamp":1772628566000},"source":"Crossref","is-referenced-by-count":0,"title":["Motor neuron disease can present as a paraneoplastic neurologic syndrome with various phenotypes"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8537-4471","authenticated-orcid":false,"given":"Eleftheria","family":"Koropouli","sequence":"first","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0016-7991","authenticated-orcid":false,"given":"Stavros","family":"Bellos","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavroula","family":"Aristeidou","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariadne","family":"Daponte","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Gklinos","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fotios","family":"Athanasopoulos","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonis","family":"Tsionis","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Andreadou","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Zouvelou","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michail","family":"Rentzos","sequence":"additional","affiliation":[{"name":"First Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens School of Medicine , Vasilissis Sofias Avenue 72-74, Athens 11528 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"2026041703582910700_fcag024-B1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1097\/00000441-194407000-00009","article-title":"Primary and symptomatic amyotrophic lateral sclerosis. 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