Mysterious Amnesia Cases May Be Tied to Swelling Cerebellums

One memory-killing effect of opioid abuse may have a “swollen cerebellum” link.

Posted Mar 19, 2019

CLIPAREA l Custom media/Shutterstock
Cerebellum (Latin for "little brain") highlighted in anatomical illustration. Cerebellar means "relating to or located in the cerebellum."
Source: CLIPAREA l Custom media/Shutterstock

Over the past few years, newshounds have been following the developing story of mysterious amnesia cases involving people in Massachusetts going to emergency rooms because they suddenly lost their ability to form new memories. In recent weeks, there’s been an intriguing new development that involves the cerebellum. This is significant because many people still think of our "little brain" as only being involved in motor functions.

The possible involvement of the cerebellum in patients with instant-onset amnesia unearths a previously unrecognized way that the human cerebellum may play a role in cognition and nonmotor functions. 

Before diving into the latest March 18, 2019, cerebellum-related news report from Yale University Daily News, here’s a brief timeline of this developing cerebellar story:

On April 15, 2017, BuzzFeed published an article, “The Fourteen Who Forgot: 14 People in Massachusetts Suddenly Lost Their Memories, Could Heroin be the Culprit?” This story reported on a cluster of opioid addicts living in the Bay State who lost their ability to form new memories after “falling asleep” or overdosing on heroin that may have been laced with fentanyl.

Life Sciences Database/Wikipedia Commons
Hippocampus in red.
Source: Life Sciences Database/Wikipedia Commons

The first reported case of severe amnesia linked to opioid use was in 2012 when an MRI of a heroin addict—who had suffered instantaneous memory loss overnight—showed glowing white orbs on both sides of the brain where the bilateral “memory hubs” of the hippocampus are located. The sudden damage to hippocampal gray matter in a 22-year-old patient baffled neurologists.

After observing a few more isolated cases of sudden-onset amnesia, Massachusetts-based doctors alerted state officials about a handful of opioid-related drug overdoses that appeared to destroy the hippocampus and zap memory.

In 2015, the Massachusetts Department of Public Health (DPH) tagged this opioid-related phenomenon and gave it a more scientific name: “Unusual amnestic syndrome with acute, bilateral hippocampal damage.” The DPH also sent out an urgent request for emergency-room physicians, neurologists, and radiologists across the state to immediately report any information regarding additional cases to the Mass. Department of Health. Over the next two years, 14 people were diagnosed with this condition. 

On January 30, 2018, an article in The Atlantic, “The Link Between Opioid Overdoses and Amnesia Is Only Getting Stronger,” by Lauren Aguirre put this mysterious “amnestic” syndrome back in the national spotlight. This article is based on a case report published in the Annals of Internal Medicine which stated: “Between 2012 and 2016, a total of 14 persons in Massachusetts with a history of substance use developed an unusual amnestic syndrome that included acute, complete, and bilateral hippocampal lesions on magnetic resonance imaging.”

Unfortunately, because the Massachusetts DPH was the only state in the country that alerted doctors to be on the lookout for “unusual amnestic syndrome with acute, bilateral hippocampal damage,” there is very little nationwide information about this mysterious syndrome.

Yesterday, an online YaleNews article, “Potentially Deadly and Memory-Killing Effect of Opioid Abuse Explored,” reported that an assistant professor at Yale University, Adam Jasne, and colleagues had identified that swelling (i.e., edema) of the cerebellum might be an overlooked factor in the above-mentioned amnestic syndrome observed by doctors in Massachusetts from 2012 to 2016. 

Jasne and colleagues recently published this hypothesis in a Neurocritical Care paper, “Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted Diffusion (CHANTER) Syndrome." The seven-letter acronym “CHANTER” stands for Cerebellar Hippocampal And basal Nuclei Transient Edema with Restricted diffusion (CHANTER) syndrome.

In an email correspondence, Adam Jasne (who was affiliated with the University of Cincinnati prior to becoming an assistant professor at Yale) described his team’s process of discovery based on four patients in Cincinnati and two in Tennessee:

"Patients first came to our attention due to severe, unexplained cerebellar swelling. Looking at their imaging, bilateral hippocampal edema was also consistent, and there were several common features in their clinical histories, such as substance exposure. From there, we scoured the literature for similar cases, and that's how we made the connection to some cases of cerebellar injury (e.g., in the pediatric literature, reports of cerebellar swelling in kids' who got into a parent's methadone) and the pattern of hippocampal injury described by Jed Barash and Shamik Bhattacharyya et al., (2017), among others.”

In a statement to YaleNews, Jasne said, “We think this is killing people. When treating overdose patients, doctors generally don’t look for brain swelling, which can be treated if discovered early.”

In their paper, Jasne and co-authors emphasize the importance of raising awareness about CHANTER: “Given the potential for favorable outcome despite early obstructive hydrocephalus, early identification and treatment of this syndrome are critical. Further work is needed to better understand this syndrome, its risk factors, treatment, and outcomes."

In our email correspondence, Jasne clarified some nuances of his findings and reiterated the importance of spreading the word about CHANTER syndrome:

"We remain unsure if the syndrome is a direct opiate toxidrome, as suggested by Barash and Kofke (2018) recently, or an unusual pattern of hypoxic injury, perhaps moderated in some fashion by substance exposure. But because it is potentially fatal, and potentially treatable, we feel it is important to recognize and to spread awareness."

Until 1998, when Jeremy Schmahmann of Harvard Medical School published two landmark papers on “Dysmetria of Thought” and “Cerebellar Cognitive Affective Disorder,” most neurologists firmly believed that the cerebellum was only involved in motor functions and had nothing to do with cognition. Therefore, as part of a growing 21st-century timeline that includes multiple nonmotor functions attributed to the cerebellum, the possible involvement of cerebellar swelling in memory loss and sudden-onset amnesia is noteworthy.

The latest discovery that swelling of the cerebellum may somehow be associated with hippocampal damage and the inability to form new memories creates more questions than answers. The million-dollar question remains: How is cerebellar edema linked to the rare amnestic syndrome observed in a small handful of patients after an opioid overdose? More research and heightened awareness of this "sudden memory loss" phenomenon are needed at a global level.

References

Adam S. Jasne, Khalid H. Alsherbini, Matthew S. Smith, Abhi Pandhi, Achala Vagal, and Daniel Kanter. "Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion (CHANTER) Syndrome." Neocritical Care (First published online: February 20, 2019) DOI: 10.1007/s12028-018-00666-4

"Potentially Deadly and Memory-Killing Effect of Opioid Abuse Explored" by Bill Hathaway. (Published: March 18, 2019 in YaleNews) 

"14 People In Massachusetts Suddenly Lost Their Memories. Could Heroin Be The Culprit?" by Azeen Ghorayshi. Published: April 15, 2017 in BuzzFeed)

"The Link Between Opioid Overdoses and Amnesia Is Only Getting Stronger" by Lauren Aguirre. (Published: January 30, 2018 in The Atlantic

Uzoma B. Duru, Gauri Pawar, Jed A. Barash, Liv E. Miller, Indrani K. Thiruselvam, Marc W. Haut. "An Unusual Amnestic Syndrome Associated With Combined Fentanyl and Cocaine Use." Annals of Internal Medicine (First published: May 15, 2018) DOI: 10.7326/L17-0575