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Case Report: Longitudinal Imaging in a Patient With Opioid-associated Amnestic Syndrome

Key findings

  • This case report describes a 21-year-old female patient with opioid-associated amnestic syndrome (OAS) who was selected to test the hypothesis that OAS is associated with long-term changes in the hippocampi
  • Magnetic resonance spectroscopy of a region in the right hippocampus showed parameters suggesting possible toxic-metabolic changes
  • The patient's memory objectively improved by discharge on hospital day 8 after receiving inpatient and outpatient treatment with a multi-antioxidant regimen, which was continued as an outpatient
  • 53 months after presentation the patient showed none of the typical signs of hippocampal damage on MRI or tau positron emission tomography
  • It isn't certain that the antioxidant regimen influenced the course of this case, as the clinical resolution of OAS has been observed in other patients without treatment

Opioid misuse has been linked to a sudden-onset amnestic syndrome associated with bilateral hippocampal-restricted diffusion on MRI. In the rare cases where these individuals have been followed, long-term, repeat imaging has demonstrated persistent hippocampal abnormalities. In addition, autopsies in those with opioid use disorder have detected excessive tau deposition in the brain, including in the hippocampus.

Researchers at Massachusetts General Hospital now speculate that the damage in opioid-amnestic syndrome (OAS) might have a reversible, toxic–metabolic etiology. Michael H. Lev, MD, chief of the Division of Emergency Imaging in the Department of Radiology, Georges El Fakhri, PhD, director of the Gordon Center for Medical Imaging in the Department, and colleagues including Jed A. Barash, MD, of Veterans’ Home, Chelsea, Massachusetts, selected one patient for testing of that hypothesis and present the results in Cognitive and Behavioral Neurology.

Introduction to the Case

A 21-year-old woman was brought to Mass General because of acute memory loss. She had a history of attention-deficit hyperactivity disorder and substance use disorder, including opioids (intravenous heroin), benzodiazepines, marijuana, and infrequent cocaine.

The patient asked repetitive questions and could not recall any of three words at five minutes. Her recollection of events in the prior week was impaired, and she had difficulty spelling "world" in reverse. Toxicology screens showed the presence of opiates but no other drugs of abuse or ethanol.

Initial Imaging

Brain MRI demonstrated restricted diffusion and mildly prominent T2 and fluid-attenuated inversion recovery (FLAIR) signal throughout hippocampi and globi pallidi.

On hospital day 3, magnetic resonance spectroscopy of a right hippocampal region of interest showed a mild reduction of the N-acetyl aspartate/creatine ratio, slight elevation of the choline/creatine ratio, and the presence of lactate/lipid and glutamate/glutamine peaks, suggestive of possible toxic-metabolic changes.

Treatment and Follow-up

A 2015 paper published in Case Reports in Neurology describes a man recovering from an opiate overdose and aspiration pneumonia who developed delayed post-hypoxic leukoencephalopathy. His altered mental status was promptly reversed by improving in the setting of treatment with a multi-antioxidant regimen.

In the present case the inpatient team administered a similar regimen beginning on day 2 and continuing after discharge on day 8:

  • Vitamin B1—100 mg daily
  • Vitamin B2—100 mg daily
  • Vitamin B6—50 mg daily
  • Vitamin B12—1,000 mcg daily
  • Vitamin C—1,000 mg daily
  • Vitamin E—400 units daily
  • Coenzyme Q10—500 mg three times daily

At discharge, the patient could recall three of five words at five minutes.

About 4.5 months later, an MRI of the brain showed resolution of the restricted diffusion, although minimal anterior T2 and FLAIR hyperintense signal in the right hippocampus remained.

Fifty-three months after presentation, the patient underwent [18F]T807 positron emission tomography, which did not detect tau deposition in the hippocampi or elsewhere in the brain. MRI of the brain on the same day also revealed normal-appearing hippocampi.


The full resolution of restricted diffusion and FLAIR in this case, along with the magnetic resonance spectroscopy and PET findings, suggest the damage in OAS may manifest as a form of reversible metabolic injury.

Another possibility is an ischemic or anoxic mechanism. However, ischemia or anoxia severe enough to cause restricted diffusion typically involves the cortex more globally and at least some long-term minimal residual T2/FLAIR signal hyperintensity indicating gliosis or tissue injury.

Still, it isn't certain that the antioxidant regimen influenced the course of this case, as clinical resolution of OAS has been observed in other patients without such treatment. More research is needed to determine whether prognosis is related more to the degree of injury or other unidentified factors than to the effect of any particular intervention.

Learn more about the Division of Emergency Imaging

Learn more about the Gordon Center for Medical Imaging

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