Sarcoidosis is a granulomatous inflammatory multiorgan disorder where involvement of the central nervous system could be a diagnostic challenge.

40-year-old African American male presents with lethargy, seizure and personality changes. Physical examination revealed lethargy. MRI brain revealed increased T2 signaling in the frontal and temporal lobes with leptomeningeal enhancement. EEG was unremarkable. CSF analysis showed lymphocytic pleocytosis, hypoglycorrhachia and elevated protein. Autoimmune and infectious tests were negative but for positivity of EBV Real Time polymerase chain reaction. Intravenous ganciclovir therapy was started without clinical response. On repeated CSF analysis, an elevated serum angiotensin converting enzyme level of 9.8 U/L was found.  Due to diagnostic conundrum, brain biopsy was obtained which revealed granulomas with multinucleated giant cells surrounded by lymphocytes. Immunohistochemistry studies ruled out EBV brain invasion. Treatment of neurosarcoidosis with methotrexate and infliximab began. Four months later, leptomeningeal enhancement improved with return of baseline cognitive status.

This case underscores the importance of a high index of suspicion for neurosarcoidosis even in case of an atypical presentation such as concomitant intrathecal EBV reactivation.