A neurologist in Massachusetts noticed the pattern about a year ago. He had seen four patients come in with amnesia—three who tested positive for opioids (heroin or prescription painkillers) and a fourth with a history of heroin use. Memory loss from drug use is not unusual, but when he peered inside their brains with an MRI scan, he saw something really strange.
All four patients had the same problem: Little or no blood was flowing to their hippocampi, two slivers of tissue deep in brain, one on the left and one right, involved in memory. And the effect was symmetrical. Whatever had damaged the brains of these patients seemed to specifically attack the hippocampus neurons. With their hippocampi impaired, the patients couldn’t form new memories. This is not how opioids are supposed to work. Could this be a rare undiscovered effect from existing opioids or a new effect of a novel synthetic drug?
The neurologist, Jed Barash, then at Lahey Hospital and Medical Center, wrote up the four cases and reported them to the Massachusetts Department of Public Health. This prompted doctors in the state to dig through their patient records for more cases of amnesia with a history of opioid use.
Eventually, they found 10 more, bringing the total to 14 in the last several years in Massachusetts. Doctors were only able to follow up with MRIs in three of the cases; one patient’s hippocampi recovered to normal, but the other two others continued to have shrunken hippocampi. The results were published last week in the CDC’s Morbidity and Mortality Weekly Report. “We wanted to put it to wider attention,” says Alfred DeMaria, Jr., an epidemiologist with the Massachusetts Department of Public Health. He hopes that more doctors will look out for the phenomenon, so they can get to the bottom of it.
The pattern of blood flow is confounding other brain experts, too. “I don’t think anybody really knows how the vasculature can lead to reduced blood flow in the hippocampus, rather specifically and bilaterally,” says Michael Bennett, a neuroscientist at Albert Einstein College of Medicine. That’s because blood vessels in the brain generally start in the center and radiate to the front and back. If the blood in the brain is somehow disrupted—by stimulants like meth that cause blood vessels to spasm, or by an overdose where patients stop breathing—the front and back of the brain tend to bear the brunt of the damage. “Those areas are most affected because they’re the very end of the distribution of the arteries.” says Thomas Kosten, a psychiatrist at Baylor.
That’s why DeMaria fears the effect on the hippocampus may be specific to the opioid that those patients took. Synthetic opioids like fentanyl have fueled the opioid epidemic in the U.S. Perhaps a new synthetic drug can specifically affect the neurochemistry of neurons in the hippocampus.
Kosten hypothesizes it could also be the effect of opioids combined with another drug that is a stimulant. In several of the cases, the patients did report using cocaine, amphetamines, or benzodiazepines as well as opioids.
Whatever the explanation, doctors were only able to pick up this relatively rare amnesia cluster because so many patients are turning up with opioid overdoses. As the opioid crisis continues, scientists are going to learn a lot more about how opioids affect the brain. “There’s a lot we don’t know,” says Kosten, particularly about synthetic opioids like fentanyl. There’s a lot to know, and a lot to have to know, now that so many patients are turning up with a history of opioid use.