In deep fungal infections, fungal infections of the central nervous system have three main characteristics, namely, the most serious disease, the most difficult diagnosis, and the most difficult treatment. The common pathogens are Cryptococcus, Candida and Aspergillus, followed by some endemic non-conditional pathogens such as Histoplasma, Bacillus dermatitidis, Coccidioides, etc. In addition, rare fungi such as Trichoderma caused by central nervous system infections have also been reported occasionally. The clinical features of cryptococcal meningitis are mostly seen in adults and can be primary or secondary to the lungs, skin, mucous membranes, bones, and liver and other tissues. The onset is often insidious, with a chronic or subacute course, with a few patients having an acute onset. Clinically, the presentation of patients with cryptococcal meningitis and the routine and biochemical changes in the cerebrospinal fluid are difficult to distinguish from tuberculous meningitis, viral meningitis or atypical cerebral, especially in the early stages of a few cases where the CSF sugar content can be normal and the protein mildly to moderately increased. However, CSF ink-stained smears often reveal neoplastic cryptococci, with a positive rate of 80% to 85%, and culture and latex agglutination tests also have a high positive rate for their polysaccharide podocyte antigens. In addition, tissue biopsy pathology and culture can also help to confirm the diagnosis. 2. Treatment of cryptococcal meningitis The drugs currently applied in the treatment of cryptocerebral include amphotericin B, flucytosine, fluconazole, itraconazole and lipid formulation of amphotericin B. Brain Aspergillosis 1. Clinical characteristics of brain Aspergillosis Most adults, and Aspergillus fumigatus is the most common. Secondary to immunodeficient patients, mostly due to blood-borne spread of pulmonary aspergillosis or direct spread of paranasal sinus aspergillosis infection; occurs in immunocompetent patients, mostly due to paranasal sinus infection. Diagnosis of cerebral aspergillosis is very difficult, blood and cerebrospinal fluid culture positive rate is low, involving the ventricles or meninges can occasionally be positive cerebrospinal fluid culture, confirming the diagnosis depends on histopathology and brain tissue biopsy specimens culture. If the intracranial infection of Aspergillus from sinus and mastoid origin, patients often have a history of sinusitis, otitis media, mastoiditis, and can cause destruction of adjacent parts of the skull base bone, imaging can be seen in the dural abscess and local dural enhancement. If the Aspergillus infection by pulmonary origin, there are mostly immunocompromised causes, and there are corresponding clinical symptoms and imaging changes in the lungs. 2. treatment of Aspergillus cerebri Currently, the effective antifungal drugs for Aspergillus cerebri are amphotericin B, lipid formulations of amphotericin B, itraconazole, voriconazole (Voriconazole), posaconazole (Posaconazole), ravuconazole (Ravuconazole), caspofungin (Caspofungin), etc., but only amphotericin However, only amphotericin B and its lipid formulation, as well as itraconazole, are approved for marketing in China, and caspofungin is also newly marketed. In vitro and in vivo clinical studies of voriconazole suggest that it has better efficacy against invasive Aspergillus, so the 2003 edition of the German guidelines for the treatment of invasive fungal infections in patients with hematological tumors recommends that voriconazole is preferred for cerebral Aspergillosis, followed by high-dose lipid formulations of amphotericin B and, if needed, combined with surgery. And amphotericin B can be the drug of choice only when imaging suggests Aspergillus infection, but there is no pathogenic basis yet, especially when jointed fungi (such as Trichoderma) cannot be excluded, priority is given to amphotericin B. Candida infection of the central nervous system 1. Clinical features of Candida meningitis Candida infection of the central nervous system in children is more often manifested as meningitis, often secondary to gastrointestinal or respiratory tract infection, caused by blood circulation or intravenous cannulation. In adults, it is more likely to present as a Candida brain abscess. The cerebrospinal fluid has a mildly increased cell count, a normal or low sugar content, and a significantly elevated protein content. Early examination of the cerebrospinal fluid does not easily detect the fungus, and multiple cerebrospinal fluid fungal cultures are required. 2. Treatment of Candida meningitis Currently, amphotericin B is mostly used to treat this type of meningitis. Because of the high concentration of fluconazole in the cerebrospinal fluid and the synergistic effect of the combination with amphotericin, the combination of the two is an optional treatment option for Candida meningitis, and retrospective analysis has shown that the combination of the two can significantly improve its cure rate. In the guidelines for the treatment of candidiasis published in the United States in 2004, amphotericin B 0.7-1 mg/(kg.d) combined with flucytosine 100 mg/(kg.d) is recommended as the preferred option, with fluconazole as a secondary option. The regimen is recommended to be discontinued at least 4 weeks after recovery of symptoms and signs. If there is an indwelling catheter, that catheter needs to be removed or replaced. It is clear that the “gold standard” for the diagnosis of CNS fungal infections is still the finding of fungi in brain tissue or cerebrospinal fluid specimens, but cerebrospinal fluid cultures are not always positive, and only 1/3 to 1/2 of patients have positive cerebrospinal fluid cultures. Therefore, in some patients with refractory chronic meningitis, when regular antibacterial and anti-TB therapy is ineffective and the disease is further aggravated, empirical antifungal therapy may be attempted even if the cerebrospinal fluid fungal smear and culture are negative. In addition, some new diagnostic methods, such as Aspergillus and other fungal-specific antigens, antibodies and nucleic acid detection, are also expected to be of great help in clinical diagnosis. In conclusion, fungal infections of the central nervous system, both diagnostic and therapeutic, remain a major challenge for us in the 21st century. However, with the improvement of fungal diagnostic techniques and the development and application of new antifungal drugs, it is believed that it provides greater possibilities for early diagnosis and treatment for our clinicians.