A 45-year-old female with a history of opioid use (morphine, oxycodone, heroin) presents with a 1-month history of altered mental status, bizarre behavior, and progressive cognitive decline. She had used opioids 2 months prior for 1 week, followed by a head injury 3 weeks later. Symptoms worsened over 1 month, including apraxia, aphasia, selective mutism, hyperreflexia, and wide-based gait. MRI brain showed bilateral white matter changes, and brain biopsy confirmed astrogliosis and microglial activation. The patient deteriorated rapidly and died 7 weeks after presentation.