"Chasing The Dragon": A Cause of Toxic Spongiform Leukoencephalopathy

My favorite case from the 2012 AANP Diagnostic Slide Session in Chicago last month featured an autopsy slide from the brain of a 25-year-old man with a history of polysubstance abuse found unresponsive at a New Year's Eve party. Toxicology screening was positive for methadone, lorazepam, and cocaine. The patient died after three weeks in the intensive care unit. Attendees were provided glass slides in advance of the session demonstrating the following findings:

Low Power: Marked white matter pallor

High Power: White matter virtually replaced by lipidized macrophages

Presenter Joshua Menke, MD of The Mayo Clinic (Rochester, MN) revealed that white matter damage was diffuse, including infratentorial structures. The subcortical U-fibers were relatively spared and myelin was disproportionately affected as compared to axons, as demonstrated in these photomicrographs from Dr. Menke's presentation:

LFB stain on left and neurofilament stain on right

Discussants included Drs. Tessa Hedley-Whyte, Craig Horbinski, Mark Cohen, and others. Before the diagnosis was revealed, Dr. Horbinski stated that he thought Delayed Hypoxic Leukoencephalopathy might be the best fit for this case. Dr. Cohen pointed out that Delayed Hypoxic Leukoencephalopathy tends spare the infratentorial regions, while the white matter damage is more diffusely distributed in toxic leukoencephalopathy. This case was ultimately revealed to be that of Toxic Spongiform Leukoencephalopathy.

Toxic leukoencephalopathy can be caused by a range of insults including radiation, chemotherapy, and drugs of abuse. Among the drugs of abuse that have been shown to cause toxic leukoencephalopathy are toluene, ethanol, cocaine, 3,4-methylenedioxy-methamphetamine, intravenous heroin, inhaled heroin pyrolysate, and psilocybin (Ref: Filley & Kleinschmidt-DeMasters NEJM 2001). Toxic spongiform leukoencephalopathy is a clinicopathologic entity first associated with the inhalation of pyrolysate heroin vapors, a practice which had its origins in Hong Kong in the 1950's and which came to be known colloquially as "chasing the dragon". Users typically "chase the dragon" by placing heroin on a creased piece of tin foil over a flame. As the drug sublimates, the user inhales the fumes. The pathophysiology of this form of leukoencephalopathy has not been clearly elucidated, but is thought to be related to a direct toxic effect of heroin on oligodendrocytes.