Undetected brain infections may explain some SIDS cases

Brain infections and inflammation may explain some cases of sudden infant death syndrome (SIDS), a small study hints.

The research pointed to a specific virus, called human parechovirus 3 (HPeV3),as potentially tied to the death of one child in the study; HPeV3 is known to cause both mild respiratory infections and severe nervous-system infections. At this point, the virus can't be definitively confirmed as the child's cause of death, but the study highlights the idea that some SIDS cases may stem from viral infections and that this notion bears further investigation.

"Our findings demonstrate proof of concept that undetected infections may contribute to risk of SIDS and that increased surveillance of HPeV3 in particular may be warranted," study co-author Ben Okaty, a geneticist at Harvard Medical School, told Live Science in an email. The team reported their findings Monday (Jan. 29) in the journal JAMA Neurology.

"It is likely that there might be other similar cases," specifically involving the HPeV3 virus, said Dr. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke, who was not involved in the study. "Patients should be investigated for that possibility," he told Live Science in an email.

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SIDS is the sudden death of a child younger than 1 year old that has no clear explanation, even after a thorough postmortem investigation. The cause of SIDS is thought to vary from case to case, but often, the deaths occur during sleep. The rate of SIDS dramatically declined in the 1990s in the U.S. following a government-led awareness campaign around safe sleeping practices for infants.

But since then, the rate of SIDS cases has remained fairly steady, suggesting factors besides sleep are at play.

Scientists have pinpointed potential differences in the genetics, nervous system function and enzyme activity of children who die of SIDS, compared with those who die of known causes or those who survive infancy. Some research has also pointed to neuroinflammation, meaning inflammation in the brain or spinal cord, as potentially involved in some SIDS cases.

To further investigate inflammation in SIDS, the study authors looked at clinical samples from 64 children who died of SIDS and 20 who died of known causes. They screened the clear fluid that surrounds the brain and spinal cord for signs of immune system activation and inflammation.

A compound called neopterin, which is produced by immune cells as they rev up in response to an infection, is one such sign of inflammation; it can be detected in various bodily fluids but doesn't point to a specific pathogen, only to general immune activation. Six of the children with SIDS had high neopterin levels in their samples, suggesting their nervous systems were inflamed.

To probe the causes of this inflammation, the researchers used a technique called metagenomic next-generation sequencing. 

"This type of screening isn't performed in a typical autopsy," study co-author Dr. Prashanth Ramachandran, an assistant professor of neurology at the University of California, San Francisco, told Live Science in an email.

Autopsies typically look at the shape and microscopic details of cells' structures, Nath said. Pathologists also sometimes test for specific pathogens in a tissue sample, but these tests look for known viruses and bacteria. The type of screening used in the study allowed the researchers to hunt for pathogens indiscriminately — "it provides an unbiased analysis," he said.

This screen turned up the HPeV3 in one child's fluid samples, as well as in tissues from the child's liver and several parts of the brain, such as the brainstem. HPeV3 can cause fairly mild respiratory and gastrointestinal infections, but in some cases, it can cause brain inflammation, or encephalitis.

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No specific pathogen was flagged in the other five children's samples. This may be because the concentration of pathogens was too low, or that the bug triggered detectable inflammation but was cleared away by the time of death, Nath wrote in a commentary, also published in JAMA Neurology. Or alternatively, because the screening looks for genetic material, it may be that the pathogen's genetic material degraded but the proteins it made persisted and drove inflammation, he wrote.

The researchers examined the gene activity in the HPeV3-positive child's brainstem and in those of several SIDS cases without signs of neuroinflammation. This analysis uncovered distinct differences in the HPeV3-positive child. These affected genes that are activated by immune signaling molecules, as well as genes involved in brain cell maturation.

Since the brainstem helps control involuntary and life-sustaining bodily functions, such as breathing, the researchers hypothesized that infection and dysfunction in the brainstem could have contributed to the child's SIDS. The infant had become fussy and developed a fever shortly before death, but no specific pathogen had been implicated at the time.

Still, "in cases such as this, it is really difficult to know whether the child died with or died of the viral infection," said co-senior study author Robin Haynes, a principal associate in pathology at Harvard Medical School. And at this point, "we do not know whether this virus might be implicated in more SIDS cases," Haynes told Live Science in an email.

More work needs to be done to understand the virus's path into and effects on the brain, and to investigate whether other pathogens could cause similar changes in the brainstem, Haynes said. In future investigations of SIDS, more pathologists should look for signs of brain inflammation and infection as potential factors, Nath wrote in a commentary, also published in JAMA Neurology.

In future research, "our goal is to strengthen the data linking infection, neuroinflammation, and brainstem abnormalities in SIDS in such a way that provides a better understanding of mechanisms underlying known risk factors for SIDS, including minor illness prior to death," Haynes said.

This article is for informational purposes only and is not meant to offer medical advice.