Plasma Microbial Cell-Free DNA (CF-DNA) Next-Generation Sequencing in Diagnosing Intracranial Abscesses: Pathophysiology and a Scoping Review of the Literature

Abstract

Plasma microbial cell-free DNA (cf-DNA) from next-generation sequencing (NGS) provides improved sensitivity and specificity compared to standard microbial blood cultures. cf-DNA sequencing also has an improved turnaround time (TAT) and allows quicker commencement of antibiotics in life-threatening infections such as a brain abscess. Brain abscesses carry significant morbidity and mortality. Empiric treatment and management are critical in improving functional neurological outcomes. Reported here is the case of a severe central nervous system (CNS) infection with multiple ring-enhancing lesions seen throughout the cerebrum on magnetic resonance imaging (MRI). Standard microbial blood cultures were inconclusive and definitive identification of the pathogen was achieved through microbial cf-DNA NGS. Brain abscesses develop in four distinct phases: early cerebritis, late cerebritis, early capsule formation, and late capsule formation. The pathogenesis of cerebral abscess involves direct parenchymal inflammation of the pathogen, the recruitment of inflammatory CNS cell types (microglia, inflammatory astrocytes, etc), and the chemotaxis of immune cells. cf-DNA is released into the bloodstream in response to pathogen opsonization and immune-mediated cell death. A scoping literature review includes cases of intracranial abscesses diagnosed via cf-DNA NGS.