Delayed posthypoxic leukoencephalopathy following a morphine overdose

J Clin Neurosci. 2012 Jul;19(7):1060-2. doi: 10.1016/j.jocn.2012.01.001. Epub 2012 May 1.


We describe one patient and review the literature to define delayed posthypoxic leukoencephalopathy, its etiology, pathophysiology and prognosis. We present a 54-year-old man with confusion and diffuse rigidity following a morphine overdose that had required intubation three weeks previously. A brain CT scan showed bilateral globi pallidi hypodensities and diffusion-weighted brain MRI (DWI) was consistent with acute cerebral anoxia. On day 20 after the initial presentation, the patient insidiously progressed to a state of "akinetic mutism". The brain MRI showed diffuse hyperintensity of the white matter on T2-weighted fluid-attenuated inversion recovery sequences. These areas were bright on DWI and were hypointense on the apparent diffusion coefficient map. An extensive autoimmune, metabolic, toxicological, and infectious work-up included arylsulfatase A enzyme levels, which were unremarkable. Therapy with levodopa was initiated with subsequent improvement of the diffuse rigidity. At discharge, the patient continued to be lethargic with moderate rigidity but began to display signs of recovery. He eventually fully recovered with residual mild confusion. Thus, delayed hypoxic leukoencephalopathy is a rare complication of hypoxic-ischemic encephalopathy, occurring in 2.75% of victims of carbon monoxide poisoning. It typically manifests two to 40 days after apparent recovery from an obtunded state. Prognosis is variable, but recovery can be complete. This report brings to light an important syndrome that can easily be misdiagnosed. Patients who present with these clinical and radiographic features should be treated fully and given time to recover without abrupt withdrawal of care.

Publication types

  • Case Reports

MeSH terms

  • Diffusion Magnetic Resonance Imaging
  • Drug Overdose
  • Humans
  • Hypoxia, Brain / chemically induced*
  • Hypoxia, Brain / complications
  • Hypoxia, Brain / diagnosis
  • Leukoencephalopathies / chemically induced*
  • Leukoencephalopathies / complications
  • Leukoencephalopathies / diagnosis
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Morphine / adverse effects*


  • Morphine