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Pilot study successfully uses DNA sequencing to diagnose brain infections

In a proof-of-principle study, a team of physicians and bioinformatics experts at Johns Hopkins reports they were able to diagnose or rule out suspected brain infections using so called next-generation genetic sequencing of brain tissue samples.

The team says its study, described online in Neurology: Neuroimmunology & Neuroinflammation, demonstrates that using computers to rapidly analyze huge amounts of genetic and biological information could be a cost-effective addition to a pathology lab’s toolkit. More than 50 percent of inflammatory disorders and infections of the brain go undiagnosed, which can lead to treatments for individual symptoms that can do more harm than good.

“By incorporating modern genetic sequencing techniques into pathology diagnostics, we were able to investigate the potential presence of infection in 10 subjects and found appropriate explanations of clinical problems in eight out of 10 patient cases examined in this study,” says Carlos Pardo-Villamizar, M.D., associate professor of neurology at the Johns Hopkins University School of Medicine. “We hope to develop this technique further as a way to bring the diagnosis rate of inflammatory brain disorders and infections closer to 100 percent so we can treat patients more effectively.”

In the study, the researchers first identified 10 people at The Johns Hopkins Hospital – six males and four females between the ages of 16 and 68 – with clinical signs of a brain infection, such as fever and rapid onset of neurological symptoms, like weakness in limbs, partial paralysis numbness, headache or seizures.

Each patient had a biopsy of a brain lesion – an area of inflamed, damaged tissue – first identified by MRI. Using commercially available genetic sequencing technologies that read millions of pieces of DNA at once, the researchers sequenced the DNA of the brain tissue for each person and compared the results to a database containing human and nonhuman DNA sequences, 2,817 bacterial genomes, 4,383 viral genomes and 26 single-cell pathogen genomes.

After subtracting out the human DNA results, they ranked the top three other species found in each sample that were thought to be potential infectious organisms.

In three patients, they said genetic sequencing definitively identified the cause of the infection as Mycobacterium tuberculosis, the bacterium that causes tuberculosis and sometimes infects the brain; JC virus, which is found in most people but is only typically infectious in people with weakened immune systems; or Epstein-Barr virus, a herpes virus most commonly known to cause mononucleosis in humans.