Acute Amnestic Syndrome associated with Fentanyl Overdose is an increasingly recognized clinic-radiological entity. We aim to present a case of opioid related amnestic syndrome with transient hyperintensities of bilateral hippocampi in neuroimaging who later developed diffuse leukoencephalopathy.

A 44-year-old female initially presented after being found unresponsive due to a fentanyl overdose. After improved level of awareness following administration of Narcan, acute anterograde amnesia was noticed. At that time the patient also had septic shock due to MSSA bacteremia secondary to right shoulder septic arthritis. Brain MRI with contrast revealed bilaterally symmetric restricted diffusion involving hippocampal heads, bodies, and tails regions with periventricular subependymal gray matter heterotopia. Executive functioning improved over time, however her short term memory remained mildly impaired.  Four weeks after initial insult she presented due to intermittent confusion, further decline in orientation, short-term and working memories was noticed during hospital admission. Examination revealed patient was disoriented to person, place, date, situation, and impaired delayed recall was noticed.  Patient exhibited inability to remember her healthcare providers and recent events throughout the hospital admission. Serum chemistries, including urine drug and ethanol levels were unremarkable.  Due to concern for metabolic/infectious insult a lumbar puncture was performed but was not suggestive of infection, JC virus, and MS panel was unremarkable.  Repeated brain MRI with and without contrast demonstrated resolution of the restricted diffusion in the hippocampal area and interval development of diffuse leukoencephalopathy sparing the cerebellar and brainstem white matter.

Delayed leukoencephalopathy has been described after hypoxic brain injury secondary to opioid overdose, however to our knowledge this entity has not been previously described following an opioid-related amnestic syndrome. The pathophysiology of these conditions is still uncertain, potential explanations include cerebral ischemia/hypoxemia or excitotoxicity secondary to neuronal hypermetabolism.