{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:10:41Z","timestamp":1790831441533,"version":"4.1.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":237,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la recherche m\u00e9dicale","doi-asserted-by":"crossref","award":["DQ20170336751"],"award-info":[{"award-number":["DQ20170336751"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"name":"LABEX CORTEX","award":["ANR-11-LABX-0042"],"award-info":[{"award-number":["ANR-11-LABX-0042"]}]},{"name":"BETPSY","award":["ANR-18-RHUS-0012"],"award-info":[{"award-number":["ANR-18-RHUS-0012"]}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis (n = 105), cerebellar degeneration (n = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis (n = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma (n = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice. Overall, Kelch-like protein 11 antibodies were detected in 11 patients [11\/11, 100% were male; their median (range) age was 44 (35\u201379) years], 9 of them from the antibody-negative paraneoplastic neurological syndrome cohort, 1 from the antibody-positive (Ma2-Ab) cohort and 1 additional prospectively detected patient. All patients manifested a cerebellar syndrome, either isolated (4\/11, 36%) or part of a multi-system neurological disorder (7\/11, 64%). Additional core syndromes were limbic encephalitis (5\/11, 45%) and myelitis (2\/11, 18%). Severe weight loss (7\/11, 64%) and hearing loss\/tinnitus (5\/11, 45%) were common. Rarer neurologic manifestations included hypersomnia and seizures (2\/11, 18%). Two patients presented phenotypes resembling primary neurodegenerative disorders (progressive supranuclear palsy and flail arm syndrome, respectively). An associated cancer was found in 9\/11 (82%) patients; it was most commonly (7\/9, 78%) a spontaneously regressed (\u2018burned-out\u2019) testicular germ cell tumour. A newly designed clinical score (MATCH score: male, ataxia, testicular cancer, hearing alterations) with a cut-off \u22654 successfully identified patients with Kelch-like protein 11 antibodies (sensitivity 78%, specificity 99%). Pathological findings (three testicular tumours, three lymph node metastases of testicular tumours, one brain biopsy) showed the presence of a T-cell inflammation with resulting anti-tumour immunity in the testis and one chronic, exhausted immune response\u2014demonstrated by immune checkpoint expression\u2014in the metastases and the brain. In conclusion, these findings suggest that Kelch-like protein 11 antibody paraneoplastic neurological syndrome is a homogeneous clinical syndrome and its detection can be facilitated using the MATCH score. The pathogenesis is probably T-cell mediated, but the stages of inflammation are different in the testis, metastases and the brain.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab185","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T14:01:29Z","timestamp":1629986489000},"source":"Crossref","is-referenced-by-count":64,"title":["Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3652-7061","authenticated-orcid":false,"given":"Alberto","family":"Vogrig","sequence":"first","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"P\u00e9ricart","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHU de Toulouse, IUC-Oncopole, 31300 Toulouse, France"},{"name":"INSERM U1037, Cancer Research Center of Toulouse (CRCT), 31100 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laurie","family":"Pinto","sequence":"additional","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Rogemond","sequence":"additional","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Picard","sequence":"additional","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Selton","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHRU Nancy, 54035 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Mittelbronn","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch\/Alzette, Luxembourg"},{"name":"Luxembourg Center of Neuropathology (LCNP), L-1526 Luxembourg, Luxembourg"},{"name":"National Center of Pathology (NCP), Laboratoire National de Sant\u00e9 (LNS), 3555 Dudelange, Luxembourg"},{"name":"Department of Oncology (DONC), Luxembourg Institute of Health (LIH), L-1020 Luxembourg, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne-Marie","family":"Lanoisel\u00e9e","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHR d'Orl\u00e9ans, 45100 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Michenet","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHR d'Orl\u00e9ans, 45100 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Benaiteau","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHU de Toulouse, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Pariente","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHU de Toulouse, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Z\u00e9phir","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, CHU Lille, U1172 - Laboratory of neuroinflammation and Multiple Sclerosis, Lille Neuroscience & cognition, 59000 Lille, France"},{"name":"Department of Neurology, Centre de Ressources et Comp\u00e9tence SEP, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Giordana","sequence":"additional","affiliation":[{"name":"Department of Movement Disorders and Neurology, CHU Nice, 06003 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solveig","family":"Montaut","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHRU de Strasbourg, 67091 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayet","family":"Salhi","sequence":"additional","affiliation":[{"name":"Centre Expert Parkinson, H\u00f4pital Henri-Mondor, AP-HP, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Bachoumas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centre Hospitalier Public du Cotentin, 50100 Cherbourg-en-Cotentin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Montcuquet","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dupuytren Hospital, 87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Letovanec","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Uro-Coste","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHU de Toulouse, IUC-Oncopole, 31300 Toulouse, France"},{"name":"INSERM U1037, Cancer Research Center of Toulouse (CRCT), 31100 Toulouse, France"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier, 31062 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-5952","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Honnorat","sequence":"additional","affiliation":[{"name":"French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, H\u00f4pital Neurologique, 69677 Bron, France"},{"name":"NeuroMyoGene Institute, INSERM U1217\/CNRS UMR5310, 69008 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, Lyon, 69622 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"issue":"1","key":"2022020823032067200_fcab185-B1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1056\/NEJMoa1816721","article-title":"Kelch-like protein 11 antibodies in seminoma-associated paraneoplastic encephalitis","volume":"381","author":"Mandel-Brehm","year":"2019","journal-title":"N Engl J Med"},{"issue":"11","key":"2022020823032067200_fcab185-B2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1001\/jamaneurol.2020.2231","article-title":"Expanded clinical phenotype, oncological associations, and immunopathologic insights of paraneoplastic Kelch-like protein-11 encephalitis","volume":"77","author":"Dubey","year":"2020","journal-title":"JAMA Neurol"},{"issue":"3","key":"2022020823032067200_fcab185-B3","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000666","article-title":"Clinical significance of Kelch-like protein 11 antibodies","volume":"7","author":"Maudes","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"2022020823032067200_fcab185-B4","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000604","article-title":"Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors","volume":"6","author":"Vogrig","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"2022020823032067200_fcab185-B5","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1007\/s12311-015-0742-0","article-title":"Mapping Purkinje cell placement along the Purkinje cell layer: An analysis of postmortem tissue from essential tremor patients vs. controls","volume":"15","author":"Louis","year":"2016","journal-title":"Cerebellum"},{"issue":"6","key":"2022020823032067200_fcab185-B6","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000883","article-title":"Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France","volume":"7","author":"H\u00e9bert","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"1","key":"2022020823032067200_fcab185-B7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00415-019-09544-1","article-title":"Epidemiology of paraneoplastic neurological syndromes: A population-based study","volume":"267","author":"Vogrig","year":"2019","journal-title":"J Neurol"},{"issue":"3","key":"2022020823032067200_fcab185-B8","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000701","article-title":"Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes","volume":"7","author":"D\u00e9chelotte","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"4","key":"2022020823032067200_fcab185-B9","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001014","article-title":"Updated diagnostic criteria for paraneoplastic neurologic syndromes","volume":"8","author":"Graus","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"8","key":"2022020823032067200_fcab185-B10","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1136\/jnnp.2003.034447","article-title":"Recommended diagnostic criteria for paraneoplastic neurological syndromes","volume":"75","author":"Graus","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"2022020823032067200_fcab185-B11","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00415-018-9143-x","article-title":"Motor neuron involvement in anti-Ma2-associated paraneoplastic neurological syndrome","volume":"266","author":"Vogrig","year":"2019","journal-title":"J Neurol"},{"issue":"3","key":"2022020823032067200_fcab185-B12","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000699","article-title":"Clinical spectrum and diagnostic pitfalls of neurologic syndromes with Ri antibodies","volume":"7","author":"Simard","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"18","key":"2022020823032067200_fcab185-B13","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1212\/WNL.0000000000003887","article-title":"Clinical manifestations of the anti-IgLON5 disease","volume":"88","author":"Gaig","year":"2017","journal-title":"Neurology"},{"issue":"4","key":"2022020823032067200_fcab185-B14","doi-asserted-by":"crossref","first-page":"e371","DOI":"10.1212\/NXI.0000000000000371","article-title":"Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis","volume":"4","author":"Joubert","year":"2017","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"5","key":"2022020823032067200_fcab185-B15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s12311-020-01159-x","article-title":"Transient neurological symptoms preceding cerebellar ataxia with glutamic acid decarboxylase antibodies","volume":"19","author":"Mu\u00f1iz-Castrillo","year":"2020","journal-title":"Cerebellum"},{"issue":"5","key":"2022020823032067200_fcab185-B16","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1007\/s12311-019-01075-9","article-title":"Stroke-like presentation of paraneoplastic cerebellar degeneration: A single-center experience and review of the literature","volume":"18","author":"Vogrig","year":"2019","journal-title":"Cerebellum"},{"key":"2022020823032067200_fcab185-B17","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/brain\/121.4.561","article-title":"The cerebellar cognitive affective syndrome","volume":"121 (Pt 4","author":"Schmahmann","year":"1998","journal-title":"Brain"},{"key":"2022020823032067200_fcab185-B18","first-page":"1","article-title":"Spontaneous regression as a \u201cburned-out\u201d non-seminomatous testicular germ cell tumor: A case report and literature review","volume":"1","author":"Dorantes-Heredia","year":"2019","journal-title":"J Surg Case Rep"},{"key":"2022020823032067200_fcab185-B19","doi-asserted-by":"crossref","first-page":"1756286420932797","DOI":"10.1177\/1756286420932797","article-title":"Pathophysiology of paraneoplastic and autoimmune encephalitis: Genes, infections, and checkpoint inhibitors","volume":"13","author":"Vogrig","year":"2020","journal-title":"Ther Adv Neurol Disord"},{"issue":"2","key":"2022020823032067200_fcab185-B20","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.clindermatol.2012.08.017","article-title":"Immunology of melanoma","volume":"31","author":"Mukherji","year":"2013","journal-title":"Clin Dermatol"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcab185\/39961746\/fcab185.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/3\/fcab185\/42381467\/fcab185.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/3\/fcab185\/42381467\/fcab185.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:09:12Z","timestamp":1644361752000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcab185\/6358130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcab185","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021]]},"published":{"date-parts":[[2021]]},"article-number":"fcab185"}}