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Intracranial Caseating Granulomas with No Infectious Organism Detected

Abstract: Background: Caseating granuloma is a classic histopathological feature of mycobacterial infections. Occasionally, no infectious organism is demonstrated despite extensive examination of intracranial caseating granulomas. The pathogenesis and optimal management strategy for patients with such intracranial caseating granulomas with no detectable infectious organism (ICGNs) remain unclear. Methods: The study was a retrospective case-series design in a referral hospital setting. Patients with intracranial caseating granulomas in whom no infectious etiology was identified after appropriate investigations were reviewed. Results: Eight patients with ICGN (four females and four males) were identified in an eight-year-period. Average age on presentation was 46 years (range 21-69 years). Cerebrospinal fluid showed lymphocytic pleocytosis, elevated protein and decreased glucose. Neuroimaging showed multiple or single intraparenchymal and meningeal enhancements. Intracranial ICGN were demonstrated on biopsy. Immunomodulation was tried and resulted in improvement in five out of eight patients. In four patients, anti-mycobacterial treatment resulted in no improvement or worsening of clinical or radiological features. Conclusions: The response to therapy of intracranial caseating granulomas where no organism is identified after thorough investigations hints to non-infectious causes, and suggests current dogma regarding the significance of necrosis in granulomatous diseases should be re-evaluated. Our retrospective series suggests that patients may benefit from an early trial of immunomodulation therapy, a hypothesis to be tested in a randomized trial.