Central nervous system (CNS) tuberculosis is associated with high mortality, neurological sequelae, diagnostic delay, and heterogeneous clinical spectrum. Beyond HIV infection, the role of broader immunosuppression and host inflammatory responses remains insufficiently characterized. In Tunisia, exposure to unpasteurized dairy and cattle raises concerns about possible zoonotic transmission.

All patients treated for CNS tuberculosis at La Rabta University Hospital (Tunis, Tunisia) from 2010 to 2023 were included. Patients were classified into mutually exclusive phenotypes using a hierarchical algorithm based on clinical, neuroimaging, and cerebrospinal fluid findings: meningeal, meningo-parenchymal, pseudotumoral, anergic (absence of cerebrospinal fluid pleocytosis), and other atypical phenotypes.

Overall, 168 patients were included (median age 41 years; 51% women), with 21% of immunosuppression cases and 13% of HIV co-infection cases. Tuberculosis exposure was reported in 58% of patients, mainly via unpasteurized dairy (46%). Clinical phenotypes were meningo-parenchymal (46%), meningeal (33%), pseudotumoral (9%), anergic (9%), and atypical (2%). In-hospital mortality was 26%, paradoxical reactions occurred in 18% of patients and neurological sequelae in 36% of survivors. Median treatment duration was 18 months; CNS recurrence was observed in 5% of patients and tuberculosis recurrence in 7%. HIV infection (OR 4.71) and disease severity (OR 3.40) were independently associated with mortality. The anergic phenotype was associated with minimal immunosuppression and lower mortality despite delayed diagnosis.

CNS tuberculosis in Tunisia shows heterogeneous phenotypes, frequent zoonotic exposure, high mortality, and substantial sequelae. The anergic phenotype may reflect a controlled host response. Improved molecular diagnostics and locally adapted treatment strategies are needed.