Brain biopsy is established for diagnosing non-resectable neoplastic lesions, with yields approaching 95%, and for documenting brain infections [1,2]. However, the indications and timing of brain biopsy in patients with neurological diseases of unknown etiology remain debatable [3–5]. The lack of biopsy guidelines reflects population heterogeneity, including immunocompetent and immunocompromised patients, isolated neurological presentations, systemic syndromes, and diagnoses, including tumors, infections, and inflammatory disorders.
