Fig. 1.

Overview of specimen types and modalities for diagnosing CNS infection. Panel (A) represents key anatomic compartments for sampling. Panel (B) provides an overview of the major diagnostic modalities. (I) Indirect evidence of infection can be provided by pathogen-specific antibody responses. Illustrated is a generic ELISA. (II) Gram stain and culture are performed for bacterial and fungal pathogens. (III) Pathogen antigen detection is most often performed by a modification of the ELISA assay. (IV) PCR detects nucleic acid from a prespecified target. (V) Multiplex PCR expands (IV) to examine a set of predetermined targets. (VI) Metagenomic sequencing amplifies all nucleic acid directly from a biological sample, including bacteria, fungi, and viruses, as well as human nucleic acid and microbes present in reagent or laboratory environment. Bioinformatic analyses are used to identify potential pathogens. CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction.