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.

Post covid cerebral phaeohyphomycosis by Rhinocladiella mackenziei: An unusual association.

Cerebral phaeohyphomycosis (CP) is a rare but a highly morbid fungal infection of the central nervous system caused by the fungi belonging to the order Chaetothyriales, which includes Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei (RM) etc. This disease is associated with poor clinical outcomes, with reported mortality of over 80%. We present the case of a 65-year gentleman who developed CP secondary to RM infection following COVID-19 and the associated challenges in his medical and surgical management.

Meningeal Whole Mounts for Imaging CNS Fungal Infection.

Invasive fungal infections may involve the brain and central nervous system (CNS), leading to often fatal meningitis in immunocompromised individuals. Recent technological advances have allowed us to move beyond studying the brain parenchyma to understanding the immune mechanisms of the meninges, the protective layer that surrounds the brain and spinal cord. Specifically, advanced microscopy techniques have enabled researchers to begin to visualize the anatomy of the meninges and the cellular mediators of meningeal inflammation. In this chapter, we describe how to make meningeal tissue mounts for imaging by confocal microscopy.

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).

Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa.

[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.

Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system / 中华预防医学杂志

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.

COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum.

AIMS: 1: Describe the epidemiology and determine risk factors for COVID-19 associated mucormycosis. 2: Elaborate the clinical spectrum of Rhino-Orbital-Cerebral Mucormycosis (ROCM), pattern of neuroaxis involvement and it's radiological correlates. METHODS: Observational study. Consecutive, confirmed cases of mucormycosis (N = 55) were included. A case of mucormycosis was defined as one who had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological examination (HPE). Data pertaining to epidemiology, risk factors, clinico-radiological features were analysed using percentage of total cases. RESULTS: Middle aged, diabetic males with recent COVID-19 infection were most affected. New onset upper jaw toothache was a striking observation in several cases. Among neurological manifestations headache, proptosis, vision loss, extraocular movement restriction; cavernous sinus, meningeal and parenchymal involvement were common. Stroke in ROCM followed a definitive pattern with watershed infarction. CONCLUSIONS: New onset upper jaw toothache and loosening of teeth should prompt an immediate search for mucormycosis in backdrop of diabetic patients with recent COVID-19 disease, aiding earlier diagnosis and treatment initiation. Neuroaxis involvement was characterized by a multitude of features pertaining to involvement of optic nerve, extraocular muscles, meninges, brain parenchyma and internal carotid artery.

Forensic Neuropathologic Phenotypes of Fungal Central Nervous System Infections: A Case Series.

ABSTRACT: Fungal infections of the central nervous system (FI-CNS) are life-threatening infections that most commonly affect immunocompromised individuals, but immunocompetent individuals may also be infected. Although FI-CNS are relatively rare, the prevalence of FI-CNS is on the rise because of the increasing number of transplant recipients, human immunodeficiency virus-infected individuals, and use of immunosuppressive therapies. Most cases of FI-CNS originate from outside the central nervous system. The etiologic fungi can be classified into 3 fungal groups: molds, dimorphic fungi, and yeasts. The clinical presentation of FI-CNS is highly variable and may be difficult to diagnose premortem. We present a case series of 3 patients, each infected by 1 representative species from each of the 3 fungal groups (Aspergillus species, Blastomyces species, Candida species) to illustrate different neuropathologic phenotypes of FI-CNS. All 3 patients had no history of immunodeficiency and were not suspected to have FI-CNS until they were diagnosed at autopsy. Fungal infections of the central nervous system are often fatal due to delayed diagnosis and diagnostic testing. Awareness of such poly-phenotypic manifestations of FI-CNS will be helpful in reducing delayed diagnosis. It is important for clinicians to include FI-CNS on the differential diagnosis when radiographic findings are nonspecific.

Disseminated Rhinocladiella mackenziei infection in a kidney transplant recipient: A case report and literature review.

Rhinocladiella mackenziei is a rare fungal pathogen which belongs to a large group of pigmented fungi causing phaeohyphomycosis. R. mackenziei primarily infects the brain and leads to high fatality rates among both immunocompetent and immunocompromised individuals. Among solid organ transplant recipients, the infection may disseminate to extra-neuronal sites, necessitating comprehensive radiologic imaging. Here we describe a new case of R. mackenziei infection in a renal transplant patient involving the brain and renal allograft. She received liposomal amphotericin B and voriconazole but no surgical intervention. Ultimately, the patient died after two months of hospital stay. A review of all reported cases of transplant patients infected with R. mackenziei is also presented.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study.

BACKGROUND: Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures. METHODS: 6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems ("skin-to-skin" and "OR entry to exit"). RESULTS: The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5-6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions. CONCLUSION: The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.

An unexpected intracerebral lesion - case report of a superinfected aspergillosis mimicking a brain metastasis.

BACKGROUND: Invasive aspergillosis of the central nervous system is a rare but increasingly prevalent disease. We present the unusual case of an immunosuppressed patient suffering from unexpected superinfected invasive aspergillosis with cerebral, pulmonal, and adrenal manifestations, mimicking a metastasized bronchial carcinoma. This report reveals the importance of including aspergillosis in the differential diagnosis of a cerebral mass lesion in the light of unspecific clinical findings. CASE PRESENTATION: A 58-year-old immunocompromised female presented to our emergency department with a single tonic-clonic seizure. Imaging showed a ring enhancing cerebral mass with perifocal edema and evidence of two smaller additional hemorrhagic cerebral lesions. In the setting of a mass lesion in the lung, and additional nodular lesions in the left adrenal gland the diagnosis of a metastasized bronchus carcinoma was suspected and the cerebral mass resected. However, histology did not reveal any evidence for a neoplastic lesion but septate hyphae consistent with aspergillus instead and microbiological cultures confirmed concomitant staphylococcal infection. CONCLUSIONS: A high index of suspicion for aspergillus infection should be maintained in the setting of immunosuppression. Clinical and radiological findings are often unspecific and even misleading. Definite confirmation usually relies on tissue diagnosis with histochemical stains. Surgical resection is crucial for establishing the diagnosis and guiding therapy with targeted antifungal medications.