{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T19:57:08Z","timestamp":1779134228519,"version":"3.51.4"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T00:00:00Z","timestamp":1576281600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Acute disseminated encephalomyelitis is generally preceded by an infection, and it is usually self-limiting and non-recurrent. However, when there are multiple attacks of acute disseminated encephalomyelitis followed by optic neuritis, it is defined as acute disseminated encephalomyelitis-optic neuritis. To the best of our knowledge, there are no previous reports of acute disseminated encephalomyelitis and optic neuritis preceded by autoinflammation, triggered by periodic fever syndrome.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case summary<\/jats:title>\n<jats:p>We report on a case of acute disseminated encephalomyelitis with optic neuritis and periodic fever syndrome in a 12-year-old Ecuadorian Hispanic boy with several relapses over the past 10 years, always preceded by autoinflammatory manifestations and without evidence of infectious processes. Whole exome sequencing was performed, and although the results were not conclusive, we found variants in genes associated with both autoinflammatory (<jats:italic>NLRP12<\/jats:italic>) and neurological (<jats:italic>POLR3A<\/jats:italic>) phenotypes that could be related to the disease pathogenesis having a polygenic rather than monogenic trait.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>We propose that an autoinflammatory basis should be pursued in patients diagnosed as having acute disseminated encephalomyelitis and no record of infections. Also, we show that our patient had a good response after 1 year of treatment with low doses of intravenous immunoglobulin and colchicine.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13256-019-2305-3","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T01:02:24Z","timestamp":1576285344000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole exome sequencing in a child with acute disseminated encephalomyelitis, optic neuritis, and periodic fever syndrome: a case report"],"prefix":"10.1186","volume":"13","author":[{"given":"Pablo A.","family":"Ledesma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Carlos","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Burbano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricio","family":"Procel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Alberto","family":"Pedroza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,14]]},"reference":[{"key":"2305_CR1","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.autrev.2015.06.002","volume":"14","author":"S Esposito","year":"2015","unstructured":"Esposito S, Di Pietro GM, Madini B, et al. A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children. Autoimmun Rev. 2015;14:923\u20139. https:\/\/doi.org\/10.1016\/j.autrev.2015.06.002.","journal-title":"Autoimmun Rev"},{"key":"2305_CR2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/B978-0-323-53088-0.00018-X","volume":"87","author":"D Pohl","year":"2016","unstructured":"Pohl D, Alper G, Van Haren K, et al. Acute disseminated encephalomyelitis, Updates on an Inflammatory CNS syndrome. Neurology. 2016;87:38\u201345. https:\/\/doi.org\/10.1016\/B978-0-323-53088-0.00018-X.","journal-title":"Neurology"},{"key":"2305_CR3","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1177\/1352458515593404","volume":"21","author":"BH Ching","year":"2015","unstructured":"Ching BH, Mohamed AR, Khoo TB, et al. Multiphasic disseminated encephalomyelitis followed by optic neuritis in a child with gluten sensitivity. Mult Scler. 2015;21:1209\u201311. https:\/\/doi.org\/10.1177\/1352458515593404.","journal-title":"Mult Scler"},{"key":"2305_CR4","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/1471-2431-11-103","volume":"11","author":"MD Costanzo","year":"2011","unstructured":"Costanzo MD, Camarca ME, Colella MG, et al. Acute disseminated encephalomyelitis presenting as fever of unknown origin: case report. BMC Pediatr. 2011;11:103. https:\/\/doi.org\/10.1186\/1471-2431-11-103.","journal-title":"BMC Pediatr"},{"key":"2305_CR5","doi-asserted-by":"publisher","first-page":"e109","DOI":"10.1212\/NXI.0000000000000109","volume":"2","author":"E Schuh","year":"2015","unstructured":"Schuh E, Lohse P, Ertl-Wagner B, et al. Expanding spectrum of neurologic manifestations in patients with NLRP3 low-penetrance mutations. Neurol Neuroimmunol Neuroinflamm. 2015;2:e109. https:\/\/doi.org\/10.1212\/NXI.0000000000000109.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"5","key":"2305_CR6","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1073\/pnas.0708616105","volume":"105","author":"I J\u00e9ru","year":"2008","unstructured":"J\u00e9ru I, Duquesnoy P, Fernandes-Alnemri T, et al. Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci. 2008;105(5):1614\u20139. https:\/\/doi.org\/10.1073\/pnas.0708616105.","journal-title":"Proc Natl Acad Sci"},{"issue":"Suppl 1","key":"2305_CR7","doi-asserted-by":"publisher","first-page":"P262","DOI":"10.1186\/1546-0096-12-S1-P262","volume":"12","author":"G Volpe","year":"2014","unstructured":"Volpe G, Mauro A, Mellos A. NLRP12-associated autoinflammatory disorder: case report. Pediatr Rheumatol. 2014;12(Suppl 1):P262. https:\/\/doi.org\/10.1186\/1546-0096-12-S1-P262.","journal-title":"Pediatr Rheumatol"},{"issue":"3","key":"2305_CR8","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1002\/art.30170","volume":"63","author":"S Borghini","year":"2011","unstructured":"Borghini S, Tassi S, Chiesa S, et al. Clinical Presentation and Pathogenesis of Cold-Induced Autoinflammatory Disease in a Family With Recurrence of an NLRP12 Mutation. Arthritis Rheum. 2011;63(3):830\u20139. https:\/\/doi.org\/10.1002\/art.30170.","journal-title":"Arthritis Rheum"},{"issue":"6","key":"2305_CR9","doi-asserted-by":"publisher","first-page":"e0156981","DOI":"10.1371\/journal.pone.0156981","volume":"11","author":"X Xia","year":"2016","unstructured":"Xia X, Dai C, Zhu X, Liao Q, et al. Identification of a Novel NLRP12 Nonsense Mutation (Trp408X) in the Extremely Rare Disease FCAS by Exome Sequencing. PLoS One. 2016;11(6):e0156981. https:\/\/doi.org\/10.1371\/journal.pone.0156981.","journal-title":"PLoS One"},{"key":"2305_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/513782","volume":"2013","author":"Francesco Caso","year":"2013","unstructured":"Caso F, Rigante D, Vitale A, et al. Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and therapeutic issues. Int J Rheumatol. 2013; https:\/\/doi.org\/10.1155\/2013\/513782.","journal-title":"International Journal of Rheumatology"},{"key":"2305_CR11","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12969-015-0006-z","volume":"13","author":"C De Pieri","year":"2015","unstructured":"De Pieri C, Vuch J, De Martino E, et al. Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study. Pediatr Rheumatol Online J. 2015;13:11. https:\/\/doi.org\/10.1186\/s12969-015-0006-z.","journal-title":"Pediatr Rheumatol Online J"},{"key":"2305_CR12","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1007\/s10067-016-3410-y","volume":"36","author":"M Shen","year":"2017","unstructured":"Shen M, Tang L, Shi X, Zeng X, Yao Q. NLRP12 autoinflammatory disease: a Chinese case series and literature review. Clin Rheumatol. 2017;36:1661\u20137. https:\/\/doi.org\/10.1007\/s10067-016-3410-y.","journal-title":"Clin Rheumatol"},{"key":"2305_CR13","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/jnc","volume":"135","author":"P Nagy\u0151szi","year":"2015","unstructured":"Nagy\u0151szi P, Ny\u00fal-T\u00f3th \u00c1, Fazakas C, Wilhelm I, Kozma M, Moln\u00e1r J, Hask\u00f3 J, Krizbai IA. Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells. J Neurochem. 2015;135:551\u201364. https:\/\/doi.org\/10.1111\/jnc.","journal-title":"J Neurochem"},{"issue":"12","key":"2305_CR14","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/brainsci7020014","volume":"7","author":"Sulie Chang","year":"2017","unstructured":"Chang SL, Huang W, Mao X, Sarkar S. NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance. Brain Sci. 2017;7 https:\/\/doi.org\/10.3390\/brainsci7020014.","journal-title":"Brain Sciences"},{"key":"2305_CR15","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s12974-015-0414-5","volume":"12","author":"M Gharagozloo","year":"2015","unstructured":"Gharagozloo M, Mahvelati TM, Imbeault E, Gris P, Zerif E, Bobbala D, Ilangumaran S, Amrani A, Gris D. The nod-like receptor, Nlrp12, plays an anti-inflammatory role in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2015;12:198. https:\/\/doi.org\/10.1186\/s12974-015-0414-5.","journal-title":"J Neuroinflammation"},{"key":"2305_CR16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature09115","volume":"466","author":"I Surolia","year":"2010","unstructured":"Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu H, Bell DW, Driscoll DR, Diederichs S, Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, De Jager PL, Chretien Y, Varki A, MacDonald ME, Gillis T, Behrens TW, Bloch D, Collier D, Korzenik J, Podolsky DK, Hafler D, Murali M, Sands B, Stone JH, Gregersen PK, Pillai S. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature. 2010;466:243\u20137. https:\/\/doi.org\/10.1038\/nature09115.","journal-title":"Nature"},{"key":"2305_CR17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/ng.1037","volume":"44","author":"KA Hunt","year":"2011","unstructured":"Hunt KA, Smyth DJ, Balschun T, et al. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. Nat Genet. 2011;44:3\u20135. https:\/\/doi.org\/10.1038\/ng.1037.","journal-title":"Nat Genet"},{"key":"2305_CR18","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1212\/WNL.0000000000001002","volume":"83","author":"NI Wolf","year":"2014","unstructured":"Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M, Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S, Str\u00f8mme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, van der Knaap MS, Bernard G, 4H Research Group. Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations. Neurology. 2014;83:1898\u2013905. https:\/\/doi.org\/10.1212\/WNL.0000000000001002.","journal-title":"Neurology"},{"key":"2305_CR19","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.1172\/JCI92280","volume":"127","author":"B Ogunjimi","year":"2017","unstructured":"Ogunjimi B, Zhang SY, S\u00f8rensen KB, Skipper KA, Carter-Timofte M, Kerner G, Luecke S, Prabakaran T, Cai Y, Meester J, Bartholomeus E, Bolar NA, Vandeweyer G, Claes C, Sillis Y, Lorenzo L, Fiorenza RA, Boucherit S, Dielman C, Heynderickx S, Elias G, Kurotova A, Auwera AV, Verstraete L, Lagae L, Verhelst H, Jansen A, Ramet J, Suls A, Smits E, Ceulemans B, Van Laer L, Plat Wilson G, Kreth J, Picard C, Von Bernuth H, Fluss J, Chabrier S, Abel L, Mortier G, Fribourg S, Mikkelsen JG, Casanova JL, Paludan SR, Mogensen TH. Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections. J Clin Invest. 2017;127:3543\u201356. https:\/\/doi.org\/10.1172\/JCI92280.","journal-title":"J Clin Invest"},{"key":"2305_CR20","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/dmcn.13349","volume":"59","author":"J Gadian","year":"2017","unstructured":"Gadian J, Kirk E, Holliday K, Lim M, Absoud M. Systematic review of immunoglobulin use in pediatric neurological and neurodevelopmental disorders. Dev Med Child Neurol. 2017;59:136\u201344. https:\/\/doi.org\/10.1111\/dmcn.13349.","journal-title":"Dev Med Child Neurol"},{"key":"2305_CR21","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1177\/1352458516631038","volume":"22","author":"M Baumann","year":"2016","unstructured":"Baumann M, Hennes EM, Schanda K, Karenfort M, Kornek B, Seidl R, Diepold K, Lauffer H, Marquardt I, Strautmanis J, Syrbe S, Vieker S, H\u00f6ftberger R, Reindl M, Rost\u00e1sy K. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases. Mult Scler. 2016;22:1821\u20139. https:\/\/doi.org\/10.1177\/1352458516631038.","journal-title":"Mult Scler"},{"issue":"6","key":"2305_CR22","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.jaci.2009.11.001","volume":"124","author":"HM Hoffman","year":"2009","unstructured":"Hoffman HM. Therapy of autoinflammatory syndromes. J Allergy Clin Immunol. 2009;124(6):1129\u201338. https:\/\/doi.org\/10.1016\/j.jaci.2009.11.001.","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"2305_CR23","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1136\/annrheumdis-2011-201268","volume":"72","author":"N Haar","year":"2013","unstructured":"Haar N, Lachmann H, \u00d6zen S, et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis. 2013;72(5):678\u201385. https:\/\/doi.org\/10.1136\/annrheumdis-2011-201268.","journal-title":"Ann Rheum Dis"}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-019-2305-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13256-019-2305-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-019-2305-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T00:05:58Z","timestamp":1607817958000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-019-2305-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2305"],"URL":"https:\/\/doi.org\/10.1186\/s13256-019-2305-3","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"14 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was carried out in accordance with the recommendations of the Institutional Review Board from the Universidad San Francisco de Quito with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board from the Universidad San Francisco de Quito, with the protocol number: 2015-061\u2009T.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient\u2019s legal guardians for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"368"}}