Next-generation sequencing of tissue

Abstract

In this issue of Neurology® Neuroimmunology & Neuroinflammation, Salzberg et al1 report on the results of a small prospective study of the application of next-generation sequencing (NGS) of RNA and DNA extracted from brain biopsy tissue specimens obtained from 10 patients with suspected neuroinfectious disease processes. In 3 patients, the NGS results, which included JC virus, Epstein-Barr virus, and Mycobacterium tuberculosis, were validated by other measures. Standard diagnostic methods would have led to the correct diagnosis in these patients; however, the NGS results showed that the same conclusions could have been drawn from a single assay that is able to detect bacteria, fungi, parasites, and viruses simultaneously. In 2 patients, the NGS results were indeterminate, but raised the possibility of infectious organisms that had not been suspected clinically: possible Delftia acidovorans in a 69-year-old man with Tolosa-Hunt syndrome and pachymeningitis and Elizabethkingia spp. from the brain mass of a 19-year-old man with Fanconi anemia.1 In 5 other cases, the investigators found NGS clinically useful, such as ruling out the presence of an infection in suspected cases of sarcoidosis or glial tumors,1 although the actual negative predictive value of a negative NGS result awaits definition in a larger prospective study.