Prognosis in substance abuse-related acute toxic leukoencephalopathy: A scoping review

  • Zachary A. Macchi
    Corresponding author at: Building 400, Mail Stop F429, 12469 E 17th Place, Aurora, CO 80045, USA.
    Department of Neurology, University of Colorado School of Medicine, 1635 Aurora Ct, Aurora, CO 80045, USA

    Behavioral Neurology Section, University of Colorado School of Medicine, 12649 E 17th Place, Aurora, CO 80045, USA
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  • Tara C. Carlisle
    Department of Neurology, University of Colorado School of Medicine, 1635 Aurora Ct, Aurora, CO 80045, USA

    Movement Disorders Center, University of Colorado School of Medicine, 12631 E 17th Ave, Aurora, CO 80045, USA
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  • Christopher M. Filley
    Department of Neurology, University of Colorado School of Medicine, 1635 Aurora Ct, Aurora, CO 80045, USA

    Behavioral Neurology Section, University of Colorado School of Medicine, 12649 E 17th Place, Aurora, CO 80045, USA

    Department of Psychiatry, University of Colorado School of Medicine, 1890 N Revere Ct, Suite 4020, Aurora, CO 80045, USA

    Marcus Institute for Brain Health, University of Colorado, 12348 E Montview Blvd, Aurora, CO 80045, USA
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Published:September 12, 2022DOI:


      • The course in toxic leukoencephalopathy (TL) from substance abuse is variable with a high rate of mortality and disability.
      • Across cases in the literature, the majority of cases of acute TL are associated with opiate abuse.
      • A subgroup of patients had partial or full recovery, suggesting that leukotoxic injury may be reversible in some cases.
      • Recovery is often protracted for survivors of acute TL, an important factor that influences shared medical decision-making.



      Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about recovery or prognosis in this condition. In light of the ongoing opiate epidemic in the United States, it is important to understand the natural history of patients who have acute neurological complications from illicit drug exposure. Our aim was to conduct a scoping review of the literature regarding prognosis in described cases of substance abuse-related TL.


      A strategic search of PubMed, Ovid, Cumulative Index to Nursing, and Allied Health Literature (CINAHL) databases yielded adult cases of acute TL from opiates, cocaine, or inhalants. Cases and case series were eligible for inclusion if they described acute leukoencephalopathy with a clear temporal association with opiate, cocaine, or inhalant abuse. Inclusion was contingent on availability of clinical descriptions until death or ≥ 4 weeks follow-up with neuroimaging consistent with TL.


      Among 52 cases from 14 articles, 21 (40.4%) individuals died with mean time to death of 28.2 days; with mean follow-up of 12.8 months, 10 (19.2%) survived with no recovery, 17 (32.7%) had partial recovery, and 4 (7.7%) individuals had full recovery.


      Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.


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