{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:19:30Z","timestamp":1780647570445,"version":"3.54.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-18-RHUS-0012"],"award-info":[{"award-number":["ANR-18-RHUS-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006451","name":"Hospices Civils de Lyon","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006451","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Anti-IgLON5 disease presents with diverse symptoms, whose severity can be measured by the anti-IgLON5 disease composite score (ICS). This study applied the ICS to a retrospective anti-IgLON5 disease cohort (<jats:italic>n<\/jats:italic>\u2009=\u200952; median age 72\u00a0years, 63% male) diagnosed in the French Reference Center on Autoimmune Encephalitis (2016\u20132024), aiming to describe severity and clinical course, and to assess its potential to predict mortality. At diagnosis, the ICS distribution (median 18) aligned with previous publications and correlated with the time to diagnosis (median 19\u00a0months); all patients had symptoms in\u2009\u2265\u20092 ICS domains: bulbar (88%), sleep (84%), movement disorders (90%), cognition (64%), and\/or other (78%). Of 46 patients with follow-up data, 7 (16%) died shortly after diagnosis; for the others, changes in the ICS mirrored the clinical course: at last visit, it decreased in improving patients (16\/46, 35%; median 12 vs 17; <jats:italic>p<\/jats:italic>\u2009=\u20090.004), increased in worsening patients (11\/39, 24%; median 26 vs 21; <jats:italic>p<\/jats:italic>\u2009=\u20090.006) and did not change significantly in stable patients (12\/46, 26%; median 16 vs 15; <jats:italic>p<\/jats:italic>\u2009=\u20090.222). In the ROC analyses, 2-year mortality was predicted by the total ICS at diagnosis (AUC 69.51, 95% CI [50.19; 88.83]; optimal cut-off\u2009&gt;\u200920, sensitivity 59%, specificity 77%), and by the bulbar score at diagnosis (AUC 74.68, 95% CI [56.17, 93.19]; optimal cut-off\u2009&gt;\u20093, sensitivity 83%, specificity 62%). The ICS is a reproducible tool for assessing anti-IgLON5 disease severity and clinical course. Higher total and bulbar ICS at diagnosis are associated with increased mortality risk, underscoring the need for early and intensive management of bulbar dysfunction.<\/jats:p>","DOI":"10.1007\/s00415-025-13001-7","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T04:45:19Z","timestamp":1742359519000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Application of the anti-IgLON5 disease composite score to assess severity, clinical course, and mortality in a French cohort"],"prefix":"10.1007","volume":"272","author":[{"given":"Antonio","family":"Farina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Villagr\u00e1n-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Abichou-Klich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Benaiteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilien","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Campetella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Cluse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Desestret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Dumez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Fabien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goncalves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Picard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laurie","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Rogemond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Vogrig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien","family":"Joubert","sequence":"additional","affiliation":[],"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":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"13001_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S1474-4422(14)70051-1","volume":"13","author":"L Sabater","year":"2014","unstructured":"Sabater L, Gaig C, Gelpi E, Bataller L, Lewerenz J, Torres-Vega E, Contreras A, Giometto B, Compta Y, Embid C et al (2014) A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 13:575\u2013586","journal-title":"Lancet Neurol"},{"key":"13001_CR2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001271","author":"C Gaig","year":"2024","unstructured":"Gaig C, Sabater L (2024) New knowledge on anti-IgLON5 disease. Curr Opin Neurol. https:\/\/doi.org\/10.1097\/WCO.0000000000001271","journal-title":"Curr Opin Neurol"},{"key":"13001_CR3","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1002\/ana.25857","volume":"88","author":"J Landa","year":"2020","unstructured":"Landa J, Gaig C, Plagum\u00e0 J, Saiz A, Antonell A, Sanchez-Valle R, Dalmau J, Graus F, Sabater L (2020) Effects of IgLON5 antibodies on neuronal cytoskeleton: a link between autoimmunity and neurodegeneration. Ann Neurol 88:1023\u20131027","journal-title":"Ann Neurol"},{"key":"13001_CR4","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s12974-016-0689-1","volume":"13","author":"L Sabater","year":"2016","unstructured":"Sabater L, Planagum\u00e0 J, Dalmau J, Graus F (2016) Cellular investigations with human antibodies associated with the anti-IgLON5 syndrome. J Neuroinflamm 13:226","journal-title":"J Neuroinflamm"},{"key":"13001_CR5","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/cells10040837","volume":"10","author":"M Ryding","year":"2021","unstructured":"Ryding M, Gamre M, Nissen MS, Nilsson AC, Okarmus J, Poulsen AAE, Meyer M, Blaabjerg M (2021) Neurodegeneration induced by anti-IgLON5 antibodies studied in induced pluripotent stem cell-derived human neurons. Cells 10:837","journal-title":"Cells"},{"key":"13001_CR6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae048","author":"SM Yogeshwar","year":"2024","unstructured":"Yogeshwar SM, Mu\u00f1iz-Castrillo S, Sabater L, Peris-Sempere V, Mallajosyula V, Luo G, Yan H, Yu E, Zhang J, Lin L et al (2024) HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease. Brain. https:\/\/doi.org\/10.1093\/brain\/awae048","journal-title":"Brain"},{"key":"13001_CR7","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00401-023-02625-6","volume":"146","author":"E Berger-Sieczkowski","year":"2023","unstructured":"Berger-Sieczkowski E, Endmayr V, Haider C, Ricken G, Jauk P, Macher S, Pirker W, H\u00f6gl B, Heidbreder A, Schnider P et al (2023) Analysis of inflammatory markers and tau deposits in an autopsy series of nine patients with anti-IgLON5 disease. Acta Neuropathol 146:631\u2013645","journal-title":"Acta Neuropathol"},{"key":"13001_CR8","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1093\/brain\/awac090","volume":"146","author":"T Gr\u00fcter","year":"2023","unstructured":"Gr\u00fcter T, M\u00f6llers FE, Tietz A, Dargvainiene J, Melzer N, Heidbreder A, Strippel C, Kraft A, H\u00f6ftberger R, Sch\u00f6berl F et al (2023) Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease. Brain 146:600\u2013611","journal-title":"Brain"},{"key":"13001_CR9","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001137","volume":"9","author":"C Strippel","year":"2022","unstructured":"Strippel C, Heidbreder A, Schulte-Mecklenbeck A, Korn L, Warnecke T, Melzer N, Wiendl H, Pawlowski M, Gross CC, Kovac S (2022) Increased intrathecal B and plasma cells in patients with anti-IgLON5 disease: a case series. Neurol Neuroimmunol Neuroinflamm 9:e1137","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"13001_CR10","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1212\/WNL.0000000000003887","volume":"88","author":"C Gaig","year":"2017","unstructured":"Gaig C, Graus F, Compta Y, H\u00f6gl B, Bataller L, Br\u00fcggemann N, Giordana C, Heidbreder A, Kotschet K, Lewerenz J et al (2017) Clinical manifestations of the anti-IgLON5 disease. Neurology 88:1736\u20131743","journal-title":"Neurology"},{"key":"13001_CR11","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000385","volume":"4","author":"JA Honorat","year":"2017","unstructured":"Honorat JA, Komorowski L, Josephs KA, Fechner K, St Louis EK, Hinson SR, Lederer S, Kumar N, Gadoth A, Lennon VA et al (2017) IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm 4:e385","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"13001_CR12","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208101","volume":"102","author":"C Gaig","year":"2024","unstructured":"Gaig C, Gr\u00fcter T, Heidbreder A, Sabater L, Iranzo A, Santamaria J, Leypoldt F, Dalmau JO, Ayzenberg I, Graus F (2024) Development of a composite score for the clinical assessment of anti-IgLON5 disease. Neurology 102:e208101","journal-title":"Neurology"},{"key":"13001_CR13","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001009","volume":"8","author":"P Shambrook","year":"2021","unstructured":"Shambrook P, Hesters A, Marois C, Zemba D, Servan J, Gaymard B, Pico F, Delorme C, Lubetzki C, Arnulf I et al (2021) Delayed benefit from aggressive immunotherapy in waxing and waning anti-IgLON5 disease. Neurol Neuroimmunol Neuroinflamm 8:e1009","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"13001_CR14","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/bimj.201200045","volume":"55","author":"P Blanche","year":"2013","unstructured":"Blanche P, Dartigues J-F, Jacqmin-Gadda H (2013) Review and comparison of ROC curve estimators for a time-dependent outcome with marker-dependent censoring. Biom J 55:687\u2013704","journal-title":"Biom J"},{"key":"13001_CR15","doi-asserted-by":"publisher","first-page":"837","DOI":"10.2307\/2531595","volume":"44","author":"ER DeLong","year":"1988","unstructured":"DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837\u2013845","journal-title":"Biometrics"},{"key":"13001_CR16","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/aje\/kwj063","volume":"163","author":"NJ Perkins","year":"2006","unstructured":"Perkins NJ, Schisterman EF (2006) The inconsistency of \u201coptimal\u201d cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol 163:670\u2013675","journal-title":"Am J Epidemiol"},{"key":"13001_CR17","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000962","volume":"8","author":"J Werner","year":"2021","unstructured":"Werner J, Jelcic I, Schwarz EI, Probst-M\u00fcller E, Nilsson J, Schwizer B, Bloch KE, Lutterotti A, Jung H-H, Schreiner B (2021) Anti-IgLON5 disease: a new bulbar-onset motor neuron mimic syndrome. Neurol Neuroimmunol Neuroinflamm 8:e962","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"13001_CR18","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1378\/chest.127.6.2132","volume":"127","author":"E Farrero","year":"2005","unstructured":"Farrero E, Prats E, Povedano M, Martinez-Matos JA, Manresa F, Escarrabill J (2005) Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement. Chest 127:2132\u20132138","journal-title":"Chest"},{"key":"13001_CR19","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/jnnp.64.1.78","volume":"64","author":"PB Christensen","year":"1998","unstructured":"Christensen PB, Jensen TS, Tsiropoulos I, S\u00f8rensen T, Kjaer M, H\u00f8jer-Pedersen E, Rasmussen MJ, Lehfeldt E (1998) Mortality and survival in myasthenia gravis: a Danish population based study. J Neurol Neurosurg Psychiatry 64:78\u201383","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13001-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-025-13001-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13001-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T10:09:53Z","timestamp":1744970993000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-025-13001-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["13001"],"URL":"https:\/\/doi.org\/10.1007\/s00415-025-13001-7","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"25 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Macarena Villagr\u00e1n-Garc\u00eda is supported by a research grant from Fundaci\u00f3n Alfonso Mart\u00edn Escudero (Spain). Antonio Farina received a grant to perform research abroad by the European Academy of Neurology in 2022. The other authors report no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was approved by the institutional review board of the Hospices Civils of Lyon (N 23-5083). Written information was sent to all patients and none of them explicitly opposed his\/her participation in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards statement"}}],"article-number":"273"}}