Opioid-induced leukoencephalopathy is a toxic leukoencephalopathy with distinct neuroimaging features, including diffuse, symmetric white matter hyperintensities on T2 and fluid-attenuated inversion recovery (FLAIR) sequences, which often affect the posterior cerebrum. Rarely, diffusion weighted imaging (DWI) restriction has been described and may not be present on initial neuroimaging.

A 61-year-old woman presented to the emergency department with three days of lethargy and unsteadiness. She remained unresponsive despite naloxone administration. Examination revealed reactive pupils, left arm extensor posturing, lower extremity rigidity with nonsustained right ankle clonus, and a positive right Babinski sign. Head computed tomography was normal, drug screen detected opioids, and laboratory studies were notable for hypercapnic respiratory failure requiring intubation. Despite treating the underlying disturbances, the patient remained unresponsive.

On day three, she developed left arm myoclonus. Electroencephalographic correlate and brain magnetic resonance imaging (MRI) were unremarkable. Anoxic brain injury was suspected based on presentation. Three days later, she developed facial myokymia. Repeat MRI revealed restricted diffusion of the splenium of the corpus collosum and centrum semiovale corresponding to regions of decreased signal on apparent diffusion coefficient (ADC), FLAIR and T2 hyperintensities of the splenium and centrum semiovale, and sparing of deep gray matter structures and subcortical U fibers. She was diagnosed with opioid-induced leukoencephalopathy, and ultimately transitioned to comfort care after discussion with the family.

Our case highlights the unique clinical and neuroimaging features observed in opioid leukoencephalopathy, such as hyperkinetic movement disorders, diffusion restriction, and FLAIR hyperintensities with sparing of the subcortical U-fibers. We emphasize the potential benefit of repeat imaging early in the course. With the increasing prevalence of opioid abuse, we hope this case raises awareness of opioid leukoencephalopathy, facilitating earlier detection and intervention opportunities.