Central Nervous System Aspergillosis: Advances in Diagnosis, Therapeutics, and Multidisciplinary Management (2026 Update)

Abstract

BACKGROUND: Central nervous system (CNS) aspergillosis is a life-threatening infection with mortality rates exceeding 50%, especially in immunocompromised patients. Significant challenges persist due to limited antifungal drug penetration into the CNS, emerging resistance, and diagnostic delays, despite advancements in therapy and diagnostics. OBJECTIVE: This comprehensive review aims to synthesize pivotal advances in the management of CNS aspergillosis from 2020 to 2026 and to provide a multidisciplinary framework for addressing these ongoing challenges. METHODS: We conducted a comprehensive evaluation of the latest clinical data, pharmacokinetic studies, and expert recommendations from the specified period. The review critically appraises evidence on pharmacological therapies, diagnostic technologies, and adjunctive treatment strategies. FINDINGS: Key findings include: Pharmacotherapy: Voriconazole remains the cornerstone of therapy due to its superior CNS penetration (CSF:Plasma ratio ~50%). The roles of alternatives like isavuconazole, salvage combination regimens, and novel agents (e.g., olorofim, fosmanogepix) are evolving. DIAGNOSTICS: Cutting-edge tools such as AI-assisted imaging, metagenomic next-generation sequencing (mNGS), and MR spectroscopy for trehalose detection show significant potential for enabling earlier and more accurate diagnosis. Adjunctive Strategies: Neurosurgical intervention, immunomodulation, and therapeutic drug monitoring (TDM) are critical for optimizing outcomes. Emerging strategies like nanoparticle-based drug delivery and host-directed therapies (e.g., PD-1/PD-L1 blockade) offer promising avenues to overcome the blood-brain barrier. CONCLUSION: This review integrates the latest evidence to provide a timely and actionable resource for clinicians. It bridges gaps in existing guidelines by offering a multidisciplinary approach that addresses the complex management of CNS aspergillosis, with particular relevance for high-risk populations such as COVID-19 and immunocompromised patients.