Longitudinal Imaging in a Patient With Opioid-associated Amnestic Syndrome

Abstract

Since 2012, individuals with a history of opioid misuse have infrequently been observed to develop a sudden-onset amnestic syndrome associated with bilateral hippocampal-restricted diffusion on MRI. Follow-up imaging of this opioid-associated amnestic syndrome (OAS) has revealed persistent hippocampal abnormalities. Given these observations, as well as neuropathological studies demonstrating excessive tau deposition in the hippocampi and other brain regions of individuals with opioid misuse, we describe longitudinal imaging of a patient with a history of OAS from presentation through 53 months later, when tau positron emission tomography (PET) was performed. Our patient was a 21-year-old woman with a history of attention-deficit hyperactivity disorder and substance use disorder, including opioids (intravenous heroin), who was hospitalized for acute-onset, dense anterograde amnesia. Her urine toxicology screen was positive for opiates. On presentation, her brain MRI showed restricted diffusion as well as T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensity of the hippocampi and globi pallidi. On day 3, magnetic resonance spectroscopy of a right hippocampal region of interest showed a mild reduction of N-acetyl aspartate/creatine, slight elevation of choline/creatine, and the appearance of lactate/lipid and glutamate/glutamine peaks. At 4.5 months, there was resolution of restricted diffusion on MRI, although a minimal anterior T2 and FLAIR hyperintense signal in the right hippocampus persisted. However, by 53 months, when mild memory loss was reported, the hippocampi appeared normal on MRI, and [ 18 F]T807 (tau) PET showed no uptake suggestive of tau deposition. This case report supports the investigation into the hypothesis that OAS may follow a trajectory of reversible metabolic injury.

FIGURE 1.

MRI of our patient’s brain on presentation. A. Bilateral hippocampal-restricted diffusion with hyperintense signal on DWI. B. Corresponding dark signal on apparent diffusion coefficient weighted MRI sequences (yellow arrows), consistent with restricted diffusion. C. FLAIR sequences showing bilateral hippocampal hyperintensity (yellow arrows); similar changes were observed in the globi pallidi (not shown). D. Magnetic resonance spectroscopy of a right hippocampal region of interest on the third day showing a pattern of mild reduction of the NAA/Cr ratio, slight elevation of the Cho/Cr ratio, and appearance of lactate/lipid peaks (yellow arrow) and Glx peaks (blue arrow), suggestive of mild-to-moderate toxic-metabolic versus ischemic change, but with differential diagnosis including excitotoxic seizure activity and carbon monoxide intoxication. ADC = apparent diffusion coefficient. Cho = choline. Cr = creatine. DWI = diffusion weighted imaging. FLAIR = fluid-attenuated inversion recovery. Glx = glutamate-glutamine. NAA = N-acetyl aspartate.

FIGURE 2.

MRI of our patient’s brain at ~4.5 months after presentation. A. Complete resolution of the previously noted bilateral hippocampal-restricted diffusion on DWI. B. Minimal right anterior T2 hyperintense signal remains (yellow arrow). DWI = diffusion weighted imaging.

FIGURE 3.

[¹⁸F]T807 PET performed at 53 months from presentation showing no uptake suggestive of tau deposition in the hippocampi or other regions of the brain. PET = positron emission tomography.