Abstract
Delayed leukoencephalopathy in the aftermath of toxic exposure and cerebral hypoxia-ischemia is known as "delayed post-hypoxic leukoencephalopathy" (DPHL) but the name "delayed toxic-hypoxic leukoencephalopathy" (DTHL) may be more accurate if toxic and hypoxic mechanisms are both involved in the pathogenesis of delayed leukoencephalopathy. DTHL is characterized by initial recovery from toxic exposure and cerebral hypoxia-ischemia, clinical stability over a few weeks, and subsequent neurological deterioration with the sudden emergence of diffuse white matter disease. A 46-year-old man suffered respiratory failure and hypotension as a result of opioid overdose. Brain MRI showed watershed infarcts and EEG showed diffuse theta-delta slowing consistent with global cerebral hypoperfusion. He recovered fully and was discharged with intact cognitive function. Three weeks later, he presented with abulia and psychomotor retardation. MRI revealed extensive white matter hyperintensity and EEG showed diffuse polymorphic delta activity. DTHL was diagnosed based on classic MRI features, history of opioid overdose and hypoxic brain injury, and negative test results for etiology of white matter disease. He developed akinetic mutism prompting administration of methylprednisolone 1000-mg IV q24h for five days. He also received amantadine 100-mg PO q12h. His cognition, motivation, and psychomotor function slowly improved and returned to baseline about two months after the overdose. Clinic reassessment two and a half months after the overdose revealed normal cognitive function, slight residual MRI hyperintensity, and mild EEG slowing anteriorly. Toxic-metabolic myelinopathy causing diffuse demyelination in the deep white matter is a perfect explanation for the patient's neurological symptoms, MRI changes, EEG findings, and time course of recovery.