Successful Therapy of CNS Tuberculosis With Granulomatous Inflammation in Immunodeficiency

Central nervous system (CNS) tuberculosis (TB) carries high mortality and neurologic sequelae, especially when unrecognized inborn errors of immunity are present. We report a young woman with refractory TB meningitis, multiple intracranial tuberculomas, hydrocephalus, and intracranial hypertension despite 10 months of standard anti-TB therapy and corticosteroids. Severe vomiting led to poor adherence and severe weight loss. As immunologic evaluation suggested atypical combined immunodeficiency (CID); monthly intravenous immunoglobulin (IVIG) was started. Neurosurgery did not give indication for shunt surgery. Given the severity and presumed impaired antimycobacterial immunity, adjuvant interferon-γ (IFN-γ; 50 µg/m² 3 times weekly) was added to therapy with steroids. Vomiting resolved, weight improved, and treatment was tolerated. Serial magnetic resonance imaging showed reduction in leptomeningeal enhancement and tuberculoma burden without surgery; no neurologic sequelae developed. Next-generation sequencing identified a homozygous NHEJ1 variant, not confirmed by Sanger, but findings supported CID. In refractory CNS-TB with suspected immunodeficiency, IFN-γ, steroids, IVIG in addition to anti-TB therapy may improve outcomes and avoid neurosurgical intervention. Early immunological evaluation and host-directed therapy should be considered.