Background: Inhalation of heated heroin vapor ("chasing the dragon"), which is gaining popularity among drug users seeking to avoid the risks of parenteral drug administration, can produce progressive spongiform leukoencephalopathy. Methods. We studied the clinical phenotype and course, MRI, MRS, and brain pathology in the first American patients described with this syndrome. Results: Two of the three heroin users studied inhaled heroin pyrolysate together daily over the course of 2 weeks. They developed ataxia, dysmetria, and dysarthria. Patient 1 progressed to an akinetic mute state with decorticate posture and subsequent spastic quadriparesis. Patient 2 developed a mild spastic quadriparesis and gait freezing. Patient 3 was asymptomatic following less heroin exposure. Brain MRI showed diffuse, symmetrical white matter hyperintensities in the cerebellum, posterior cerebrum, posterior limbs of the internal capsule, splenium of the corpus callosum, medial lemniscus, and lateral brainstem. MRS showed elevated lactate. Brain biopsy (Patient 1) showed white matter spongiform degeneration with relative sparing of U-fibers; electron microscopy revealed intramyelinic vacuolation with splitting of intraperiod lines. Progressive deterioration occurred in Patients 1 and 2 over 4 weeks. Both were treated with antioxidants including oral coenzyme Q, and clinical improvement occurred. Patient 1 recovered nearly completely over 24 months. Patient 2 improved, but developed a delayed-onset cerebellar hand tremor. Both still have white matter abnormalities on MRI and MRS. Conclusions: Elevated lactate in white matter and the possible response to antioxidants suggests mitochondrial dysfunction in progressive spongiform leukoencephalopathy following inhalation of heated heroin vapor.
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