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.

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.

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.

[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.

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.

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.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

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.

Prolonged survival after disseminated Rhinocladiella infection treated with surgical excision and posaconazole.

Cerebral abscess due to pigmented molds is a rare but usually fatal infection occasionally seen in transplant recipients. A 67-year-old man of Iraqi origin underwent a deceased donation renal transplant for renal failure and 2 months later was diagnosed with an abscess in the left posterior frontal lobe of his brain. Subsequent biopsy proved this to be due to the mold Rhinocladiella mackenziei. Further interventions included two operations to aspirate the lesion, voriconazole, then liposomal amphotericin B, then a combination of posaconazole and flucytosine which he continued for over 4 years. He also suffered from right ankle pain and was diagnosed with septic arthritis; R mackenziei was isolated from pus aspirated from the ankle joint. He responded well to the treatment and has had little loss of function, and on CT, the cerebral lesion has stabilized. Beta-D-glucan, initially at very high levels proved useful to monitor response over the 5 years and the latest sample was negative (38 pg/mL). This case is notable for the first disseminated case of this infection, its favorable outcome on a novel antifungal combination and a new approach to monitoring the course of disease.

Central Nervous System Fungal Infection-Related Stroke: A Descriptive Study of Mold and Yeast-Associated Ischemic Stroke.

OBJECTIVE: Central nervous system (CNS) ischemic events caused by fungal infections are rare, and clinical characteristics of these ischemic events are largely unknown. The objective of this manuscript is to highlight characteristics of fungal-related strokes and describe possible mechanistic differences between CNS mold and yeast infection-related strokes. METHODS: We report a single-center retrospective case series of all adult patients who presented with concurrent CNS fungal infection and stroke between 2010 and 2018. Patients believed to have a stroke etiology due to cardioembolic, atheroembolic, or strokes nontemporally associated with a CNS fungal infection and those with incomplete stroke workups were excluded from analysis. RESULTS: Fourteen patients were identified with ischemic stroke and concurrent CNS fungal infection without other known ischemic stroke etiology. Eight patients had a CNS yeast infection, and 6 had a CNS mold infection. All patients presented with recurrent or progressive stroke symptoms. Six patients were immune-compromised. Four patients admitted to intravenous drug use. All yeast infections were identified by cerebrospinal fluid culture or immunologic studies while all but one of the mold infections required identification by tissue biopsy. Leptomeningeal enhancement was only associated with CNS yeast infections, while basal ganglia stroke was only associated with CNS mold infections. CONCLUSION: Ischemic stroke secondary to CNS fungal infections should be considered in patients with recurrent or progressive cryptogenic stroke, regardless of immune status and cerebrospinal fluid profile. CNS yeast and mold infections have slightly different stroke and laboratory characteristics and should have a distinct diagnostic method. Depending on clinical suspicion, a thorough diagnostic approach including spinal fluid analysis and biopsy should be considered.

Update on fungal infections of the central nervous system: emerging pathogens and emerging diagnostics.

PURPOSE OF REVIEW: Fungal infections of the central nervous system (CNS) are relatively uncommon but associated with significant morbidity and mortality. We reviewed recent literature highlighting new approaches to management of these complex patients. RECENT FINDINGS: Fungal infections are increasingly recognized as important causes of CNS disease in both immunocompromised and immunocompetent hosts. Globally, cryptococcal meningitis remains a leading cause of death in HIV-infected persons in resource-limited settings. Emerging fungal pathogens with increased virulence and resistance to numerous classes of antifungal agents have been identified and represent a management challenge. Newer diagnostic techniques focused on antigen detection or molecular amplification of fungal pathogens offer promise in the expediated diagnosis and treatment of CNS fungal infections. SUMMARY: Meningitis and brain abscess because of invasive fungal pathogens are frequently fatal infections. Newer laboratory tests allowing antigen detection or molecular amplification from cerebrospinal fluid are more sensitive than culture and allow earlier initiation of effective therapy.

Fungal Infections of the Central Nervous System.

Fungal central nervous system infections present in a myriad of clinical manifestation and remain a significant diagnostic challenge. Presenting symptoms, cerebrospinal fluid analysis, conventional fungal serum markers and imaging correlates of disease are seldom sensitive or specific; fungal culture growth or histopathologic analysis are often required for definitive diagnoses but limited by feasibility. Novel diagnostic tools (such as the cryptococcal antigen and next-generation sequencing) have increased diagnostic potency when available but require further studies to define their utility.Invasive fungal infections are an emerging health threat in the setting of increased immunomodulatory treatments, advancements in transplant medicine and increased world-wide travel. Therefore, strong clinical suspicion from epidemiologic clues, clinical progression and presence of CNS dissemination risk factors must be exercised to pursue broad diagnostic workups and rapidly initiate medical and surgical management. This article will describe the epidemiology, clinical presentations, diagnostic approach and therapeutic interventions for fungal infections in the central nervous system.

The Frozen Brain State of Cryptococcus gattii: A Globe-Trotting, Tropical, Neurotropic Fungus.

Initially reported in tropical regions, Cryptococcus gattii infection is now diagnosed globally. Methods: case report; Literature review. Although initial reports described outbreaks of pulmonary and central nervous system (CNS) disease in tropical regions such as Australia and New Guinea, it is now clear that Cryptococcus gattii is a global, neurotropic pathogen. In contrast with C. neoformans, C. gattii patients are more likely to present with cryptococcomas in the brain and lungs and are often HIV negative. Imaging findings can mimick cancer leading to delays in diagnosis and definitive treatment. Some experts have speculated that the spread of C. gattii is due to climate change, newly recognized genotypes that cause disease in temperate zones (genotype VGII), international travel, and improved awareness among physicians and veterinarians. We emphasize neurocritical and neurosurgical management, because patients with CNS involvement often have high intracranial pressures (ICP). Cryptococcus gattii patients often have elevated ICP without 'red flag' radiographic signs of elevated ICP such as ventriculomegaly, cerebral edema, or effaced basal cisterns. Therefore, diagnosis of high ICP should be suspected based on clinical symptoms such as incapacitating headaches, progressive visual loss and associated papilledema, and then confirmed by measuring the opening pressure with lumbar puncture (LP). Cerebral intraparenchymal deposition of the large cryptococcal polysaccharide capsule and cryptococcal organisms causes poor brain compliance leading to a 'frozen brain state.' Mortality rates and clinical outcomes are significantly improved with early diagnosis, antifungal therapies, steroids, and aggressive management of elevated ICP including cerebrospinal fluid (CSF) diversion by serial LP's, external ventricular drains and CSF shunts. Following institution of antifungal therapy, about 10% of patients can worsen due to immune reconstitution inflammatory syndrome which responds to steroids. We recommend neurocritical and neurosurgical management of C. gattii patients with CNS involvement and elevated ICP. There is often poor correlation between elevated ICP and neuroimaging due to the frozen brain state.

Cavernous sinus fungal infection: a rare case.

Intracranial fungal infection of the cavernous sinus is a condition that usually affects immunocompromised individuals and is rarely seen in immunocompetent individuals. It is a potentially life threatening condition which requires prompt treatment. Here we present a case of an immunocompetent patient with a fungal infection of the cavernous sinus.

Neuroinfections caused by fungi.

BACKGROUND: Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. METHODS: One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. RESULTS: The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. CONCLUSION: Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.