Successful Therapy of CNS Tuberculosis With Granulomatous Inflammation in Immunodeficiency

Vollständiger Abstract

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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.