Fusarium species central nervous system infection.

PURPOSE OF REVIEW: Fusarium species are an increasingly important cause of meningitis and invasive disease in immunocompromised patients as well as in otherwise healthy patients as observed in two recent healthcare-associated outbreaks. This review summarizes recently published information on treatment and diagnosis of this infection. RECENT FINDINGS: Incidence of Fusarium species meningitis and invasive fusariosis are increasing. Molecular techniques are improving the speed of diagnosis. New antifungal agents in development show good in vitro activity against some Fusarium species. New technologies, including cerebrospinal fluid (CSF) filtration, may play a role in treatment of central nervous system (CNS) disease. Due to the continued prime importance of the host immune system in recovery, immunomodulatory treatments may play a role in treatment. SUMMARY: The overall incidence of CNS fusariosis is increasing with a continued poor prognosis, but new diagnostic and treatment modalities are in development which may offer improvements.

Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review.

INTRODUCTION: Intracranial fungal infections' (IcFIs) varying clinical manifestations lead to difficulties in diagnosis and treatment. African populations are disproportionately affected by the high burden of the disease. There is a lack of clarity as to the diagnostic and treatment modalities employed across the continent. In this review, we aim to detail the management, and outcome of IcFIs across Africa. METHODS: This scoping review was conducted using the Arksey and O'Malley framework. MEDLINE, EMBASE, Cochrane Library, African Index Medicus, and African Journals Online were searched for relevant articles from database inception to August 10th, 2021. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews guidelines were used to report the findings of the review. RESULTS: Of the 5,779 records identified, 131 articles were included. The mean age was 35.6 years, and the majority (56.4%) were males. The majority (n = 8,433/8,693, 97.0%) of IcFIs presented as a meningitis, the most common communicable predisposing factor of IcFIs was HIV/AIDS (n = 7,815/8,693, 89.9%), and the most common non-communicable risk factor was diabetes mellitus (n = 32/8,693, 0.4%). Cryptococcus species was the most common (n = 8,428/8,693, 97.0%) causative organism. The most commonly used diagnostic modality was cerebrospinal (CSF) cultures (n = 4,390/6,830, 64.3%) for diffuse IcFIs, and MRI imaging (n = 12/30, 40%) for focal IcFIs. The most common treatment modality was medical management with antifungals only (n = 4,481/8,693, 51.6%). The most commonly used antifungal agent in paediatric, and adult patients was amphotericin B and fluconazole dual therapy (51.5% vs 44.9%). The overall mortality rate was high (n = 3,475/7,493, 46.3%), and similar for both adult and paediatric patients (47.8% vs 42.1%). CONCLUSION: Most IcFIs occurred in immunosuppressed individuals, and despite the new diagnostic techniques, CSF culture was mostly used in Africa. Antifungals regimens used was similar between children and adults. The outcome of IcFIs in Africa was poor for both paediatric and adult patients.

Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta-analysis.

BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.

Fungal Intracranial Infections (Central Nervous System-Invasive Fungal Disease) in Patients With Haematological Disorders-A Single-Centre Retrospective Study.

BACKGROUND: Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes. OBJECTIVES: To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder. PATIENTS AND METHODS: This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022. RESULTS: Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46). CONCLUSION: CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy.

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

Neuroparacoccidioidomycosis.

Paracoccidioidomycosis (PCM) is caused by a dimorphic fungus Paracoccidioides Brasiliensis and is endemic to subtropical areas of Central and South America. CNS involvement of PCM is extremely variable. NeuroPCM is found in 9.65% to 27.18% of PCM cases .Most neuro PCM patients presents with simultaneous involvement of other organ but isolated or initial CNS involvement may be a feature in 21%. Here we report a case of CNS PCM and this appears to be first reported case of PCM and CNS PCM in India.

First case of Rhinocladiella mackenziei brain abscess in Turkey: Case report and review of the literature.

Rhinocladiella mackenziei is a highly neurotropic fungus, mainly reported from the Middle East. However, in recent years, there have been some cases from outside this region. We described an additional fatal case of R. mackenziei cerebral infection for the first time from Turkey and made a literature review of all previously reported cases. During 34 years (1988-2022), there have been 42 R. mackenziei brain abscess cases. Most patients have been reported from Saudi Arabia (n = 14, 33.3%). It is noteworthy that 40.5% of patients, including our case, were immunocompetent at initial diagnosis and mostly presented with a single lesion (n = 10, 23.8%). The most frequent comorbidities were solid organ transplant (n = 9, 21.4%), diabetes mellitus (n = 6, 14.3%), malignancy (n = 6, 14.3%) and prior surgery (n = 3, 7.1%). The most commonly used initial antifungal regimen were amphotericin B together with itraconazole (n = 9, 21.4%), combinations of lipid preparations of amphotericin B, voriconazole and/or posaconazole (n = 9, 21.4%) and amphotericin B alone (n = 8, 19%). Although both surgical procedures and antifungal medication in the majority of patients were performed, mortality rates remained high (90.4%). The area at risk of R. mackenziei cerebral abscess cases extends to other countries. Clinicians should be aware of this emerging disease and take a detailed travel history in patients with atypical and undocumented brain abscesses. Our case confirms the hypothesis that this fungus might spread more widely than previously predicted regions.

Systematic review of neuroparacoccidioidomycosis: The contribution of neuroimaging.

BACKGROUND: Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques. OBJECTIVES: We believe a new systematic review is needed to summarise these advances. METHODS: We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI). RESULTS: Thirty-four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38-91) had hyperintensity on T1-weighted image; 84% (95%CI: 71%-92%) had hypointensity on T2-weighted image; 80% (95%CI: 66-89) had contrast enhancement with the classical ring-enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%). CONCLUSION: NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality.

Clinical characteristics of central nervous system candidiasis due to Candida albicans in children: a single-center experience.

BACKGROUND: Central nervous system candidiasis due to Candida albicans (CNSC) in children is easily misdiagnosed and is associated with poor outcomes and a high mortality rate. There is no big data research or systematic review of CNSC. METHODS: Patients diagnosed as CNSC with positive culture results of Candida albicans in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2019 were included. Patients receiving immunosuppressive therapy or transplantation, or with malignant tumours were excluded. We analysed the clinical characteristics, follow-up results, drug susceptibility tests and whole-exome sequencing (WES) results. RESULTS: Thirty-three definitive patients were enrolled, including 22 males and 11 females. Twenty-five patients suffered from CNSC when they were less than 1 year old, and a total of 29 patients had high-risk factors. The main clinical manifestations were fever, convulsions, and positive neurological signs. Twenty-two patients had CNS infections alone, and 11 patients had CNS infections combined with invasive infections involving multiple sites. Twenty-seven cases had a positive CSF and/or blood culture at our hospital. All strains were susceptible to fluconazole, and 2 strains had intermediate susceptibility to voriconazole. As for amphotericin B, all the strains were wild type (WT). WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before. CONCLUSION: CNSC mostly existed in children younger than 1 year old, who all had underlying risk factors. CNSC patients with onset at an older age or with recurrent superficial fungal infections might have primary immunodeficiency.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

The Impact of Paracoccidioides spp Infection on Central Nervous System Cell Junctional Complexes.

Paracoccidioidomycosis (PCM), a systemic mycosis caused by the fungus Paracoccidioides spp. is the most prevalent fungal infection among immunocompetent patients in Latin America. The estimated frequency of central nervous system (CNS) involvement among the human immunodeficiency virus (HIV)/PCM-positive population is 2.5%. We aimed to address the impact of neuroparacoccidioidomycosis (NPCM) and HIV/NPCM co-infection on the tight junctions (TJ) and adherens junction (AJ) proteins of the CNS. Four CNS formalin-fixed paraffin-embedded (FFPE) tissue specimens were studied: NPCM, NPCM/HIV co-infection, HIV-positive without opportunistic CNS infection, and normal brain autopsy (negative control). Immunohistochemistry was used to analyze the endothelial cells and astrocytes expressions of TJ markers: claudins (CLDN)-1, -3, -5 and occludin; AJ markers: ß-catenin and E-cadherin; and pericyte marker: alpha-smooth muscle actin. FFPE CNS tissue specimens were analyzed using the immunoperoxidase assay. CLDN-5 expression in the capillaries of the HIV/NPCM coinfected tissues (mixed clinical form of PCM) was lower than that in the capillaries of the HIV or NPCM monoinfected (chronic clinical form of PCM) tissues. A marked decrease in CLDN-5 expression and a compensatory increase in CLDN-1 expression in the NPCM/HIV co-infection tissue samples was observed. The authors suggest that Paracoccidioides spp. crosses the blood-brain barrier through paracellular pathway, owing to the alteration in the CLDN expression, or inside the macrophages (Trojan horse).

Intrathecal Antibacterial and Antifungal Therapies.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

[Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system].

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.

Central Nervous System Histoplasma-Associated Post-infectious Inflammatory Response Syndrome (Histo-PIIRS).

We present a case of central nervous system (CNS) histoplasmosis in a previously healthy adult with hepatitis C (HCV) presenting with neurological symptoms refractory to antifungal therapy and ventriculoperitoneal (VP) shunting 4 months after initial diagnosis. Persistent symptoms were thought to be inflammatory rather than infectious given negative cerebrospinal fluid (CSF) and serum fungal antigens. The patient promptly improved after initiation of corticosteroid therapy. Elevated CSF cytokines and regional enhancement on brain MRI resolved with corticosteroid treatment. This is the first case of Histoplasma-associated post-infectious inflammatory response syndrome (Histo-PIIRS) documented by CSF cytokine reduction in response to corticosteroid therapy.

Central nervous system infections after solid organ transplantation.

PURPOSE OF REVIEW: Significant advances to our understanding of several neuroinfectious complications after a solid organ transplant (SOT) have occurred in the last few years. Here, we review the central nervous system (CNS) infections that are relevant to SOT via a syndromic approach with a particular emphasis on recent updates in the field. RECENT FINDINGS: A few key studies have advanced our understanding of the epidemiology and clinical characteristics of several CNS infections in SOT recipients. Risk factors for poor prognosis and protective effects of standard posttransplant prophylactic strategies have been better elucidated. Newer diagnostic modalities which have broad clinical applications like metagenomic next-generation sequencing, as well as those that help us better understand esoteric concepts of disease pathogenesis have been studied. Finally, several studies have provided newer insights into the treatment of these diseases. SUMMARY: Recent findings reflect the steady progress in our understanding of CNS infections post SOT. They provide several avenues for improvement in the prevention, early recognition, and therapeutic outcomes of these diseases.

Neuroradiology of infectious diseases.

PURPOSE OF REVIEW: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions. RECENT FINDINGS: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed. SUMMARY: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.

Central nervous system candidiasis beyond neonates: Lessons from a nationwide study.

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 ≥ 28 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 = 2), CARD9 deficiency (n = 2), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n = 1 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 ßDGlucan 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. LAY SUMMARY: Candida is a yeast and is the most common cause of fungal infections worldwide. 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 ≥ 28 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 = 2), CARD9 deficiency (n = 2), intravenous drug use (n = 1), diabetes mellitus (n = 1), or no identified risk factor (n = 1).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.

Challenging diagnosis of chronic cerebral fungal infection: Value of (1→3)-ß-D-glucan and mannan antigen testing in cerebrospinal fluid and of cerebral ventricle puncture.

Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture.

Central nervous system blastomycosis clinical characteristics and outcomes.

Blastomycosis is a local or systemic infection, caused by Blastomyces dermatitidis (B. dermatitidis) or B. gilchristii. Blastomycosis has been described as "the great pretender," alluding to the fact that it manifests in a wide range of symptoms and disease severity. Central nervous system (CNS) involvement, although rare, carries significant mortality. Due to the limited published reports of CNS blastomycosis, we present an updated cohort with eight cases of proven or probable CNS blastomycosis describing presentation, diagnosis, treatment and outcomes. Headache was the most common presenting symptom. Magnetic resonance imaging (MRI) proved to be the superior imaging study. All patients in our cohort were diagnosed by histopathological staining or cultures of tissue or fluid obtained from CNS or extra-CNS lesions. All patients that received treatment with Liposomal amphrotericin B for at least 10 days followed by a prolonged azole therapy did not have relapse. Two patients with late diagnoses died during hospitalization. Our findings confirm the importance of timely diagnosis and treatment of CNS blastomycosis to improve outcomes especially with an azole that have a high CNS penetration and a good intrinsic activity for B. dermatitidis such as voriconazole.

Survival case of rhinocerebral and pulmonary mucormycosis due to Cunninghamella bertholletiae during chemotherapy for acute myeloid leukemia: a case report.

A 42-year-old man diagnosed with acute myeloid leukemia complained of progressive swelling of the right side of his face with pain 11 days after the third cycle of consolidation therapy with high-dose arabinosylcytosine-cytarabine. Head and neck magnetic resonance imaging showed a mass lesion in his right maxillary sinus with parapharyngeal involvement, which included the right masseter muscle, intraorbital involvement, and an abscess in his brain. Chest computed tomography revealed peribronchial small nodules in his right upper lobe and a necrotic tumor in his right lower lobe. Molds identified as Cunninghamella bertholletiae were isolated from the necrotic ulcer. According to these results, chemotherapy for leukemia was discontinued. High-dose liposomal amphotericin (10 mg/kg/day) was initiated. Because renal dysfunction occurred, the dosage was decreased to 6 mg/kg and combined with 150 mg/day micafungin. Debridement of necrotic tissue in the right maxillary sinus and establishment of the fenestration between the sinus and oral cavity were performed. Subsequently, brain and lung lesions were surgically removed. Rhinocerebral mucormycosis was successfully treated without relapse over 3 years by a 112-day course of intravenous anti-fungal therapy and 223-day course of terbinafine and partial surgical removal, respectively, to maintain masticatory and ocular functions. To our knowledge, there has been no other report of a long-term survival case of rhinocerebral mucormycosis due to C. bertholletiae.