Partner Series
A Mysterious Infection Killed This Man. Here's How Doctors Finally Found the Cause
A man's mysterious symptoms were due to a brain infection with Powassan virus, a rare virus carried by ticks. Above, images from an MRI of the man's brain. On the left, fluid-filled cavities in the brain called ventricles (which look black) appear wider than usual. On the right, a brain area called the thalamus (also black) appears more extended than usual.
Credit: Reproduced with permission from JAMA Neurology. 2018. doi:10.1001/jamaneurol.2018.0132. Copyright©2018 American Medical Association. All rights reserved.

When a Massachusetts man arrived at the hospital, he had trouble speaking and walking. Doctors soon suspected that he had a potentially life-threatening condition: inflammation in his brain or the tissue surrounding it.

But to squelch the inflammation, they needed to know the cause. Tests for dozens of viruses, bacteria and fungi — typical culprits for brain inflammation — kept coming back negative.

Doctors didn't discover the cause until after the man's death, according to a new report of the case, published yesterday (March 19) in the journal JAMA Neurology. The culprit was the Powassan virus, a rare virus carried by ticks in the northeastern and Great Lakes regions of the United States. Just 100 cases of Powassan virus infections have been reported in the United States in the last 10 years, according to the Centers for Disease Control and Prevention (CDC).

The Powassan virus can infect the central nervous system and cause dangerous inflammation, the CDC says. About 10 percent of Powassan virus cases are fatal. 

Because the disease is so rare, there is no standard way of diagnosing it. This man's case was even more complicated because he was taking a cancer medication that affected his immune system. As a result, standard lab tests that look for antibodies against viruses wouldn't work, because the man wasn't producing those antibodies. [10 Bizarre Diseases You Can Get Outdoors]

But there is one genetic test that can be useful in these situations: a test that screens for potentially any virus, bacteria or other pathogen that may be causing an illness, rather than looking for a single microbe at a time, the researchers said. This test, known as an "unbiased sequencing assay," ultimately helped diagnose the man with Powassan virus, according to the report, led by Dr. Isaac Solomon, a neuropathologist at Brigham and Women's Hospital in Boston.

The man, who was in his 60s, had lymphoma, which is a cancer of the immune system. For treatment, he was taking a medication called rituximab, which acts on the immune system.

Problems began in December 2016, when the man went to the emergency room with a fever and pain in his testicles. Tests showed that he had orchiepididymitis, or inflammation in the testes. Doctors gave him an antibiotic and sent him home.

But three days later, he returned  to the hospital with speaking and walking problems and trouble using his arms. This time, doctors gave him three different antibiotics and an antiviral medication, suspecting that he had an infection causing inflammation in his brain (encephalitis) or the tissues surrounding his brain (meningitis).

A week later, the man's condition worsened, and he became much less alert. He appeared to have a severe brain injury; he wasn't opening his eyes in response to doctors' commands. An MRI showed that the man had excess fluid in his brain along with other signs of brain injury.

Doctors tested the man for numerous infectious diseases, including Lyme disease, syphilis, toxoplasmosis, herpes, mumps and West Nile virus infection. All the tests were negative.

Unfortunately, the man continued to get worse, and he died after two weeks in the hospital, according to the report.

After the man's death, the doctors continued to search for source of the mysterious ailment. Ultimately, they used several different tools to identify the Powassan virus. (The results of these tests weren't available until after the patient's death.)

One was called "metagenomic next-generation sequencing," a type of unbiased test in which researchers sequence all of the DNA and RNA in a sample. Given that most of this genetic material is from the patient himself, this approach is like looking for a needle in a haystack. (In this case, the "needle" is the strand of viral or bacterial DNA/RNA that's causing the disease.)

Eventually, the researchers found genetic material from the Powassan virus and concluded that the man had died from encephalitis caused by this virus.

The findings "support the utility of unbiased pathogen-detection assays capable of detecting a wide variety of infectious agents" in cases in which doctors can't seem to find the cause of a patient's encephalitis, the researchers wrote.

Original article on Live Science.