Jed Barash, a Boston neurologist, noticed something unusual in several patients. He had seen each of the four patients for anterograde amnesia. Their MRIs had something unusual in common: complete ischemia of the hippocampus. Dr. Barash notified the Massachusetts Department of Public Health, and an alert was sent to neurologists and other relevant specialists in the area. Ten more cases were soon uncovered.

Three of Dr. Barash’s four patients tested positive for opioids, and the fourth had a history of heroin use. Of the total, 13 patients either tested positive for opioids or reported a history of use. There were also reports of past use of benzodiazepines, LSD, MDMA, marijuana, PCP, and mushrooms among the group.

Bilateral ischemia to the hippocampus is a rare cause of memory loss. Past reported cases have been associated with toxin exposures including cocaine and carbon monoxide. The stand out feature of the cases in this particular cluster is the commonality of drug use, particularly opioids.

This series was reported in the January 27, 2017 Morbidity and Mortality Weekly Report (MMWR), but its meaning remains uncertain. Perhaps increased opioid use in recent years has caused a rare situation to appear more often and gain the attention it previously eluded. Alternatively, this is a new condition attributable to the increased use of synthetic drugs—both opioids such as fentanyl and synthetic marijuana. It’s possible they introduce patients to a novel toxin with more severe repercussions than their non-synthetic counterparts.

There is also the possibility that the decreased hippocampal blood flow is a result of overdose. This doesn’t explain the preferential effect on the hippocampus over the rest of the brain. One would expect a diminished blood flow to the brain as a result of overdose to have a more global impact.

Moving forward the hope is that giving these cases publicity will cause clinicians to be on the lookout for similar cases. The more cases are found and reported, the more closely the condition can be studied. In addition, researchers must look for similar changes on imaging in those who recover from overdose, whether or not they develop amnesia.

The MMWR report recommends MRI, toxicology screening, and neurology referral for any sudden-onset amnesia in adults. Advanced toxicology screening for synthetics may also be considered. One thing is for certain: as the opioid epidemic grows, clinicians must be prepared for not only the established effects of drug use, but also for the rare zebra that only appears when large numbers of individuals are affected.