Pathology of toxic leucoencephalopathy in drug abuse supports hypoxic‐ischemic pathophysiology/etiology

Abstract

The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes. The histological characteristics of leucoencephalopathy vary with survival period. Prominent axonal injury and axonal spheroids were observed with shorter survival and spongiform changes becoming apparent with longer survival (acute and chronic incomplete infarct pattern). Necrosis was present in all cases and its appearance changed with longer survival (acute and chronic complete infarct pattern). Significant primary demyelination was not observed. These observations suggest that the primary defect in this leucoencephalopathy is hypoxic-ischemic injury, predominantly in the white matter. Spongiform leucoencephalopathy likely represents the longer-survival incomplete infarct pattern and is observed with polydrug abuse.

Transient Hypothyroidism During Lactation Arrests Myelination in the Anterior Commissure of Rats. A Magnetic Resonance Image and Electron Microscope Study

“…No relevant changes in T 2 r were observed after P100 in MMI and C rats, suggesting that changes in myelinated axon number are undetectable with currently available MRI technique. This is the case of patients who suffer toxic leucoencephalopathy associated with the use of drugs such as opioids and cocaine ( Buttner and Weis, 2006 ; Alturkustani et al, 2017 ) in which demyelination of commissural and white matter axons in the cerebral cortex becomes detectable in MRI scans at an advanced stage of the disease ( Phan-Ba et al, 2012 ). Diffusion image measurements of amygdala-lesioned young monkeys are relatively insensitive to white matter changes during recovery ( Grayson et al, 2017 ).…”

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing the Role of Neuroinflammation and Brain Edema

“…Poor outcome in TL has be attributed to ischemic/ hypoxic injury of the white matter resulting in demyelination and axonal degeneration. 24,25 In light of the mild electroclinical abnormalities and rapid clinical recovery (5 weeks), ischemic/hypoxic white matter injury is not a suitable explanation for TL in our patient. The best pathophysiologic explanation is cocaine-induced white matter inflammation and edema that was not severe enough to cause significant ischemic/hypoxic injury of the white matter, thus sparing our patient persistent neurological deficits.…”

Spongiform leukoencephalopathy: A unique case of biopsy confirmed leukoencephalopathy secondary to toxic, non-inflammatory exposure

“…5 One current hypothesis is that the spongiform leukoencephalopathy is consistent with an incomplete infarct pattern, which may be the result of a partial hypoxic injury commonly seen with poly-drug abuse. 5 The white matter tracts themselves are thought to be exceedingly susceptible to such injury, largely due to their relatively high metabolic requirement and vastness. 3 The prevalence and incidence of toxin-induced leukoencephalopathy are not readily available in the current literature.…”