A challenging presentation of central nervous system involvement in disseminated coccidioidomycosis: Insights from cases.

Background: Coccidioidomycosis is a fungal infection endemic to the southwestern United States that rarely involves the central nervous system (CNS) as a brain abscess or subdural empyema. These uncommon manifestations can mimic neoplastic or inflammatory lesions, making diagnosis particularly challenging. Case Description: We report two cases of disseminated coccidioidomycosis with atypical CNS presentations and imaging findings. In the first case, a patient with pulmonary sarcoidosis presented with a right parietal lesion and subdural empyema initially suspected to represent neurosarcoidosis or bacterial infection. In the second case, a patient with a history of resected CNS glioma developed a ring-enhancing lesion concerning for tumor recurrence. In both cases, the diagnosis of CNS coccidioidomycosis was established only after surgical intervention and histopathological examination. Both patients received prolonged antifungal therapy; however, outcomes differed, with one patient experiencing fatal disease progression and the other demonstrating neurological improvement. Conclusion: These cases highlight the diagnostic challenges of atypical CNS coccidioidomycosis and emphasize the importance of maintaining a high index of suspicion in endemic regions, particularly when imaging findings resemble neoplastic or inflammatory lesions. Early tissue diagnosis and multidisciplinary management are essential, and further studies are needed to optimize treatment strategies for these rare CNS manifestations.