{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:41:02Z","timestamp":1791265262520,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:label\/>\n                  <jats:p>Though candidiasis is the most frequent invasive fungal infection, Candida spp. central nervous system (CNS) infections are rare but severe. To further describe clinico-patho-radiological presentations of this entity, we report a retrospective study from January 2005 to December 2018 including patients aged\u00a0\u2265\u00a028 days with proven or probable CNS candidiasis in France. Twenty-four patients were included. Seventeen patients (70%) had CNS localization secondary to disseminated candidiasis (10 with hematologic malignancies [HM]; the seven other patients had infective endocarditis [IE]). Among patients with HM, seven previously had lumbar puncture for intrathecal chemotherapy, the three others had IE. Among patients with disseminated infection, magnetic resonance imaging (MRI) evidenced meningitis (17%), micro-abscesses (58%), or vascular complications (67%). Seven patients (30%) had isolated CNS involvement related to neurosurgery (n\u00a0=\u00a02), CARD9 deficiency (n\u00a0=\u00a02), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n\u00a0=\u00a01 each). All evaluated patients with isolated CNS involvement had meningitis on cerebrospinal fluid (CSF) and intracranial hypertension. For the latter patients, MRI evidenced meningitis (71%) or abscesses (57%). Among all patients, cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. CSF \u03b2DGlucan or mannan Ag were positive in respectively 86% and 80% of cases. Mortality attributed to CNS candidiasis was 42%: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection. CNS candidiasis are isolated or occur during disseminated infection in patients with HM and lumbar puncture for intrathecal chemotherapy or during IE. Clinical, radiological finding and outcome highly vary according to CNS localized versus disseminated candidiasis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lay Summary<\/jats:title>\n                  <jats:p>Candida is a yeast and is the most common cause of fungal infections worldwide.<\/jats:p>\n                  <jats:p>Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged\u00a0\u2265\u00a028 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n\u00a0=\u00a02), CARD9 deficiency (n\u00a0=\u00a02), intravenous drug use (n\u00a0=\u00a01), diabetes mellitus (n\u00a0=\u00a01), or no identified risk factor (n\u00a0=\u00a01).<\/jats:p>\n                  <jats:p>During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/mmy\/myaa051","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T19:18:32Z","timestamp":1591384712000},"page":"266-277","source":"Crossref","is-referenced-by-count":31,"title":["Central nervous system candidiasis beyond neonates: Lessons from a nationwide study"],"prefix":"10.1093","volume":"59","author":[{"given":"H\u00e9l\u00e8ne","family":"Chaussade","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, Service de maladies infectieuses, h\u00f4pital Universitaire Necker-Enfants malades, Assistance Publique \u2013 H\u00f4pitaux de Paris, IHU Imagine, Paris, France"},{"name":"Service de m\u00e9decine interne et maladies infectieuses, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Cazals","sequence":"additional","affiliation":[{"name":"Service de neuroradiologie, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Desoubeaux","sequence":"additional","affiliation":[{"name":"Service de parasitologie \u2013 mycologie \u2013 m\u00e9decine tropicale, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Jouvion","sequence":"additional","affiliation":[{"name":"Unit\u00e9 histopathologie humaine et mod\u00e8les animaux, Institut Pasteur, Paris, France"},{"name":"Universit\u00e9 de la Sorbonne, INSERM, Maladies g\u00e9n\u00e9tiques d'expression p\u00e9diatrique, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Armand-Trousseau, UF G\u00e9n\u00e9tique mol\u00e9culaire, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Elisabeth","family":"Bougnoux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Unit\u00e9 de Parasitologie-mycologie, H\u00f4pital Necker, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Lefort","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne, H\u00f4pital Beaujon, Clichy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Rivoisy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Service de maladies infectieuses, h\u00f4pital Universitaire Necker-Enfants malades, Assistance Publique \u2013 H\u00f4pitaux de Paris, IHU Imagine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Desnos-Ollivier","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Mycologie Mol\u00e9culaire, UMR 2000, CNR des Mycoses Invasives et antifongiques, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Chretien","sequence":"additional","affiliation":[{"name":"Unit\u00e9 histopathologie humaine et mod\u00e8les animaux, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taieb","family":"Chouaki","sequence":"additional","affiliation":[{"name":"Laboratoire de mycologie et parasitologie, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9reng\u00e8re","family":"Gruson","sequence":"additional","affiliation":[{"name":"Service d'h\u00e9matologie, Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Bernard","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine interne et maladies infectieuses, Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lortholary","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Service de maladies infectieuses, h\u00f4pital Universitaire Necker-Enfants malades, Assistance Publique \u2013 H\u00f4pitaux de Paris, IHU Imagine, Paris, France"},{"name":"Institut Pasteur, Unit\u00e9 de Mycologie Mol\u00e9culaire, UMR 2000, CNR des Mycoses Invasives et antifongiques, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Lanternier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Service de maladies infectieuses, h\u00f4pital Universitaire Necker-Enfants malades, Assistance Publique \u2013 H\u00f4pitaux de Paris, IHU Imagine, Paris, France"},{"name":"Institut Pasteur, Unit\u00e9 de Mycologie Mol\u00e9culaire, UMR 2000, CNR des Mycoses Invasives et antifongiques, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the French Mycosis study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"2021030816511881600_bib1","first-page":"12","article-title":"Mycoses invasives en France m\u00e9tropolitaine, PMSI 2001\u20132010: Incidence, l\u00e9talit\u00e9 et tendances","author":"Bitar","year":"2013","journal-title":"BEH"},{"key":"2021030816511881600_bib2","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00134-014-3408-3","article-title":"Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002\u20132010)","volume":"40","author":"Lortholary","year":"2014","journal-title":"Intensive Care Med"},{"key":"2021030816511881600_bib3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/ajcp\/70.1.31","article-title":"The emergence of candidosis: the dominant postmortem cerebral mycosis","volume":"70","author":"Parker","year":"1978","journal-title":"Am J Clin Pathol"},{"key":"2021030816511881600_bib4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0002-9343(84)90757-5","article-title":"Candidal infection in the central nervous system","volume":"76","author":"Lipton","year":"1984","journal-title":"Am J Med"},{"key":"2021030816511881600_bib5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12281-018-0316-y","article-title":"Candidiasis of the central nervous system in neonates and children with primary immunodeficiencies","volume":"12","author":"Drummond","year":"2018","journal-title":"Curr Fungal Infect Rep"},{"key":"2021030816511881600_bib6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/13693786.2013.789566","article-title":"Candida cerebral abscesses: a case report and review of the literature","volume":"51","author":"Fennelly","year":"2013","journal-title":"Med Mycol"},{"key":"2021030816511881600_bib7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1469-0691.2012.03764.x","article-title":"Diagnosis, management and outcome of Candida endocarditis","volume":"18","author":"Lefort","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"2021030816511881600_bib8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s007010050009","article-title":"Candida infection of cerebrospinal fluid shunt devices: report of two cases and review of the literature","volume":"142","author":"Montero","year":"2000","journal-title":"Acta Neurochir"},{"key":"2021030816511881600_bib9","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.jaci.2014.12.1930","article-title":"Inherited CARD9 deficiency in otherwise healthy adults with invasive candidiasis of the central nervous system","volume":"135","author":"Lanternier","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"2021030816511881600_bib10","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s10096-008-0466-x","article-title":"Candida infective endocarditis","volume":"27","author":"Baddley","year":"2008","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2021030816511881600_bib11","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/cid\/cix913","article-title":"Prosthetic valve Candida spp. endocarditis: new insights into long-term prognosis-The ESCAPE study","volume":"66","author":"Rivoisy","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib12","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"De Pauw","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib13","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1086\/313753","article-title":"Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis","volume":"30","author":"Li","year":"2000","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib14","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/eurheartj\/ehv319","article-title":"2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM)","volume":"36","author":"Habib","year":"2015","journal-title":"Eur Heart J"},{"key":"2021030816511881600_bib15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0732-8893(00)00140-1","article-title":"The central nervous system and infection by Candida species","volume":"37","author":"S\u00e1nchez-Portocarrero","year":"2000","journal-title":"Diagn Microbial Infect Dis"},{"key":"2021030816511881600_bib16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/clinids\/19.1.60","article-title":"Chronic candidal meningitis: an uncommon manifestation of candidiasis","volume":"19","author":"Voice","year":"1994","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib17","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1086\/513746","article-title":"Candidal Meningitis in HIV-Infected Patients: Analysis of 14 Cases","volume":"25","author":"Casado","year":"1997","journal-title":"Clin Infect Dis."},{"key":"2021030816511881600_bib18","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s00134-017-4743-y","article-title":"The risk and clinical outcome of candidemia depending on underlying malignancy","volume":"43","author":"Lortholary","year":"2017","journal-title":"Intensive Care Med"},{"key":"2021030816511881600_bib19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fmicb.2018.02434","article-title":"Frequency and geographic distribution of CARD9 mutations in patients with severe fungal infections","volume":"9","author":"Vaezi","year":"2018","journal-title":"Front Microbiol"},{"key":"2021030816511881600_bib20","doi-asserted-by":"crossref","first-page":"e1005293","DOI":"10.1371\/journal.ppat.1005293","article-title":"CARD9-dependent neutrophil recruitment protects against fungal invasion of the central nervous system","volume":"11","author":"Drummond","year":"2015","journal-title":"PLoS Pathog"},{"key":"2021030816511881600_bib21","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1056\/NEJMoa0810719","article-title":"A homozygous CARD9 mutation in a family with susceptibility to fungal infections","volume":"361","author":"Glocker","year":"2009","journal-title":"N Engl J Med"},{"key":"2021030816511881600_bib22","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1182\/blood-2012-08-450551","article-title":"Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency","volume":"121","author":"Drewniak","year":"2013","journal-title":"Blood"},{"key":"2021030816511881600_bib23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/cid\/ciu215","article-title":"CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy","volume":"59","author":"Gavino","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s10875-016-0255-8","article-title":"Chronic and invasive fungal infections in a family with CARD9 deficiency","volume":"36","author":"Alves de Medeiros","year":"2016","journal-title":"J Clin Immunol"},{"key":"2021030816511881600_bib25","first-page":"1","article-title":"Intradural cauda equina Candida abscess presenting with hydrocephalus: case report","volume":"30","author":"Argersinger","year":"2019","journal-title":"J Neurosurg Spine"},{"key":"2021030816511881600_bib26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41590-019-0377-2","article-title":"CARD9+ microglia promote antifungal immunity via IL-1\u03b2- and CXCL1-mediated neutrophil recruitment","volume":"20","author":"Drummond","year":"2019","journal-title":"Nat Immunol"},{"key":"2021030816511881600_bib27","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0732-8893(94)90016-7","article-title":"Candida cerebrospinal fluid shunt infection: report of two new cases and review of the literature","volume":"20","author":"S\u00e1nchez-Portocarrero","year":"1994","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2021030816511881600_bib28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.4103\/2156-7514.184244","article-title":"Fungal infections of the central nervous system: a pictorial review","volume":"6","author":"Gavito-Higuera","year":"2016","journal-title":"J Clin Imaging Sci"},{"key":"2021030816511881600_bib29","first-page":"1115","article-title":"Diffusion-weighted imaging of fungal cerebral infection","volume":"26","author":"Gaviani","year":"2005","journal-title":"Am J Neuroradiol"},{"key":"2021030816511881600_bib30","first-page":"1","article-title":"Neurocandidiasis: a case report and consideration of the causes of restricted diffusion","volume":"7","author":"Lin","year":"2013","journal-title":"J Radiol Case Rep"},{"key":"2021030816511881600_bib31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00234-007-0242-0","article-title":"Fungal versus bacterial brain abscesses: is diffusion-weighted MR imaging a useful tool in the differential diagnosis","volume":"49","author":"Mueller-Mang","year":"2007","journal-title":"Neuroradiology"},{"key":"2021030816511881600_bib32","doi-asserted-by":"crossref","first-page":"e0152475","DOI":"10.1371\/journal.pone.0152475","article-title":"Magnetic resonance imaging of cerebral aspergillosis: imaging and pathological Ccorrelations","volume":"11","author":"Marzolf","year":"2016","journal-title":"PLoS ONE"},{"key":"2021030816511881600_bib33","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S1413-8670(10)70123-9","article-title":"Candida tropicalis as an emerging pathogen in Candida meningitis: case report and review","volume":"14","author":"Goldani","year":"2010","journal-title":"Braz J Infect Dis."},{"key":"2021030816511881600_bib34","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1093\/cid\/cit808","article-title":"Utility of (1-3)-\u03b2-D-glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of fungal meningitis and other infections","volume":"58","author":"Litvintseva","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib35","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1128\/JCM.02952-14","article-title":"(1,3)-\u03b2-d-glucan in cerebrospinal fluid for diagnosis of fungal meningitis associated with contaminated methylprednisolone injections","volume":"53","author":"Malani","year":"2015","journal-title":"J Clin Microbiol"},{"key":"2021030816511881600_bib36","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1128\/JCM.42.2.867-870.2004","article-title":"Detection of the Candida antigen mannan in cerebrospinal fluid specimens from patients suspected of having Candida meningitis","volume":"42","author":"Verduyn Lunel","year":"2004","journal-title":"J Clin Microbiol"},{"key":"2021030816511881600_bib37","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2021030816511881600_bib38","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1086\/315643","article-title":"Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system","volume":"182","author":"Groll","year":"2000","journal-title":"J Infect Dis"},{"key":"2021030816511881600_bib39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/00002826-199504000-00001","article-title":"Therapy of fungal meningitis","volume":"18","author":"Slavoski","year":"1995","journal-title":"Clin Neuropharmacol"},{"key":"2021030816511881600_bib40","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/j.1468-1293.2009.00778.x","article-title":"Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV-associated cryptococcal meningitis-infected patients","volume":"11","author":"Manosuthi","year":"2010","journal-title":"HIV Medicine"},{"key":"2021030816511881600_bib41","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1086\/375080","article-title":"Caspofungin","volume":"36","author":"Saravolatz","year":"2003","journal-title":"Clin Infect Dis"}],"container-title":["Medical Mycology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/3\/266\/36330150\/myaa051.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/3\/266\/36330150\/myaa051.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T16:52:00Z","timestamp":1615222320000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mmy\/article\/59\/3\/266\/5861672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,23]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,23]]},"published-print":{"date-parts":[[2021,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/mmy\/myaa051","relation":{},"ISSN":["1369-3786","1460-2709"],"issn-type":[{"value":"1369-3786","type":"print"},{"value":"1460-2709","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2020,6,23]]}}}