{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T21:31:32Z","timestamp":1792359092195,"version":"4.4.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fingolimod (Gilenya\u00ae), a first-in-class sphingosine-1-phosphate receptor modulator is approved for the treatment of relapsing-remitting multiple sclerosis. Fingolimod-induced selective immunosuppression leads to an increased risk of opportunistic infections such as cryptococcosis. So far, a total of 8 cases of fingolimod-related cryptococcal meningoencephalitis have been published.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 49-year-old female with relapsing-remitting multiple sclerosis presented with cephalgia, fever, confusion and generalized weakness. She had been on fingolimod therapy for the past 5.5\u2009years. Clinical examination suggested meningoencephalitis and laboratory findings showed an IgG\n                      <jats:sub>2<\/jats:sub>\n                      deficiency. Initially no pathogen could be detected, but after 4 days\n                      <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                      was found in the patient\u2019s blood cultures leading to the diagnosis of cryptococcal meningoencephalitis. After antimycotic therapy, her symptoms improved and the patient was discharged.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MS patients on immunomodulatory \u00a0therapy are at constant risk for opportunistic infections. Cephalgia, fever and generalized weakness in combination with fingolimod-induced lymphopenia should be considered a red flag for cryptococcosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12883-020-01741-0","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T08:08:41Z","timestamp":1587974921000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cryptococcal meningoencephalitis in an IgG2-deficient patient with multiple sclerosis on fingolimod therapy for more than five years \u2013 case report"],"prefix":"10.1186","volume":"20","author":[{"given":"Tobias","family":"Wienemann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kristin","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"MacKenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Bielor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"Weyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan","family":"Aktas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"issue":"10","key":"1741_CR1","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1001\/jamaneurol.2015.1746","volume":"72","author":"L Achtnichts","year":"2015","unstructured":"Achtnichts L, et al. Cryptococcal Meningoencephalitis in a patient with multiple sclerosis treated with Fingolimod. JAMA Neurol. 2015;72(10):1203\u20135.","journal-title":"JAMA Neurol"},{"issue":"11","key":"1741_CR2","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1212\/WNL.0000000000001929","volume":"85","author":"D Huang","year":"2015","unstructured":"Huang D. Disseminated cryptococcosis in a patient with multiple sclerosis treated with fingolimod. Neurology. 2015;85(11):1001\u20133.","journal-title":"Neurology"},{"key":"1741_CR3","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.msard.2016.07.015","volume":"9","author":"E Grebenciucova","year":"2016","unstructured":"Grebenciucova E, Reder AT, Bernard JT. Immunologic mechanisms of fingolimod and the role of immunosenescence in the risk of cryptococcal infection: a case report and review of literature. Mult Scler Relat Disord. 2016;9:158\u201362.","journal-title":"Mult Scler Relat Disord"},{"issue":"22","key":"1741_CR4","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.2169\/internalmedicine.55.7255","volume":"55","author":"H Seto","year":"2016","unstructured":"Seto H, et al. Disseminated Cryptococcosis in a 63-year-old patient with multiple sclerosis treated with Fingolimod. Intern Med. 2016;55(22):3383\u20136.","journal-title":"Intern Med"},{"key":"1741_CR5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.msard.2016.06.007","volume":"9","author":"MD Ward","year":"2016","unstructured":"Ward MD, Jones DE, Goldman MD. Cryptococcal meningitis after fingolimod discontinuation in a patient with multiple sclerosis. Mult Scler Relat Disord. 2016;9:47\u20139.","journal-title":"Mult Scler Relat Disord"},{"key":"1741_CR6","doi-asserted-by":"publisher","unstructured":"Pham C, Bennett I, Jithoo R. Cryptococcal meningitis causing obstructive hydrocephalus in a patient on fingolimod. BMJ Case Rep. 2017;2017. https:\/\/doi.org\/10.1038\/s41423-018-0026-y.","DOI":"10.1038\/s41423-018-0026-y"},{"key":"1741_CR7","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.inat.2017.10.005","volume":"12","author":"TI Anene-Maidoh","year":"2018","unstructured":"Anene-Maidoh TI, Paschall RM, Graham SR. Refractory cryptococcal meningoencephalitis in a patient with multiple sclerosis treated with fingolimod: a case report. Interdiscip Neurosurg. 2018;12:8\u20139.","journal-title":"Interdiscip Neurosurg"},{"key":"1741_CR8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.clinimag.2018.11.005","volume":"54","author":"I Chong","year":"2019","unstructured":"Chong I, Wang KY, Lincoln CM. Cryptococcal meningitis in a multiple sclerosis patient treated with Fingolimod: a case report and review of imaging findings. Clin Imaging. 2019;54:53\u20136.","journal-title":"Clin Imaging"},{"key":"1741_CR9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1086\/313603","volume":"30","author":"RJ Graybill","year":"2000","unstructured":"Graybill RJ, Sobel JD, Saag MS. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Clin Infect Dis. 2000;30:47\u201354.","journal-title":"Clin Infect Dis"},{"key":"1741_CR10","first-page":"61","volume":"124","author":"PG Pappas","year":"2013","unstructured":"Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013;124:61\u201379.","journal-title":"Trans Am Clin Climatol Assoc"},{"issue":"3","key":"1741_CR11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1086\/649858","volume":"50","author":"JR Perfect","year":"2010","unstructured":"Perfect JR, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291\u2013322.","journal-title":"Clin Infect Dis"},{"issue":"12","key":"1741_CR12","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1086\/599112","volume":"48","author":"PG Pappas","year":"2009","unstructured":"Pappas PG, et al. A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis. 2009;48(12):1775\u201383.","journal-title":"Clin Infect Dis"},{"issue":"1","key":"1741_CR13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1093\/cid\/cir745","volume":"54","author":"A Loyse","year":"2012","unstructured":"Loyse A, et al. Comparison of the early fungicidal activity of high-dose fluconazole, voriconazole, and flucytosine as second-line drugs given in combination with amphotericin B for the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis. 2012;54(1):121\u20138.","journal-title":"Clin Infect Dis"},{"issue":"6","key":"1741_CR14","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1586\/eri.12.48","volume":"10","author":"KA Marr","year":"2012","unstructured":"Marr KA. Cryptococcus gattii as an important fungal pathogen of western North America. Expert Rev Anti-Infect Ther. 2012;10(6):637\u201343.","journal-title":"Expert Rev Anti-Infect Ther"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-01741-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-020-01741-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-01741-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T19:10:34Z","timestamp":1619464234000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-020-01741-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,27]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1741"],"URL":"https:\/\/doi.org\/10.1186\/s12883-020-01741-0","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,27]]},"assertion":[{"value":"27 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"A written consent has been obtained from the patient for the publication of her course of disease as a case report in a peer-reviewed medical journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author(s) declared the following potential conflicts of interest with respect to the research, authorship and\/or publication of this article: T.W., A.K.M, C.B., V.W. and C.M. have no disclosures. D.K. received compensation for speaking from Grifols SA. H.-P.H. received compensation for consulting, speaking, and serving on steering committees from Bayer Healthcare, Biogen, Celgene Receptos, GeNeuro, MedImmune, MedDay, Merck, Novartis, Roche, Sanofi Genzyme, and TG Therapeutics with approval by the Rector of Heinrich Heine University. Orhan Aktas has received grant support from Bayer, Biogen, Novartis, and Sanofi and consultancy or speaking fees and fees for serving on steering committees from Bayer, Biogen, Celgene, Medimmune, Merck, Novartis, Roche, Sanofi, and Teva.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"158"}}