MRI features of spongiform leukoencephalopathy following heroin inhalation

Abstract

Abstract-The authors studied seven patients with mitochondrial DNA (mtDNA) myopathy. Over time, there was a progressive depletion of mtDNA, which preferentially affected wild-type mitochondrial genomes. This suggests that loss of wild-type mtDNA is a major feature of mtDNA myopathy, and preventing wild-type mtDNA depletion has treatment implications. NEUROLOGY 2006;67:502-504 Steve E. Durham Most patients with multisystem mtDNA disease harbor both wild-type and mutated mtDNA (heteroplasmy). High percentage levels of mutated mtDNA are associated with a biochemical defect at the cellular level and severe disease in patients. However, it is not clear whether the pathology is primarily due to high amounts of mutated mtDNA, 3 low amounts of wild-type mtDNA, 4 or a combination of both. To develop our understanding of this issue, we followed mtDNA disease progression in seven subjects, correlating the absolute amount of mutated and wild-type mtDNA with the histochemical defect. Methods. Patients and histochemistry.We studied seven patients over a 4-to 14-year period (mean follow-up 7.3 years, 42.8% men; table). All patients were independently ambulant at the time of both biopsies. Four patients had a large-scale single deletion of mtDNA, and three had mtDNA point mutations previously shown to be pathogenic. Muscle biopsies were taken from different regions of the same muscle and snap frozen in supercooled isopentane and stored in liquid nitrogen at Ϫ196°C. Sequential COXsuccinate dehydrogenase histochemistry was performed on cryostat sections, and the percentage of COX-deficient fibers and ragged-red fibers (RRFs) was determined from a field of more than 200 muscle fibers.Molecular genetics. Total genomic DNA was extracted from each biopsy. The percentage deleted mtDNA was determined by Southern blot analysis. PCR amplification of the major arc confirmed that each deletion did not involve the mtDNA ND1 gene. For the point mutations, the percentage mutated mtDNA was determined by restriction fragment length polymorphism analysis of last-hot cycle radiolabeled PCR products. The relative amount of mtDNA was determined by real-time PCR using iQ Sybr Green on the BioRad ICycler (BioRad, CA) of an mtDNA target template spanning from nt 3459 to nt 3569 in the mtDNA ND1 gene, and nt 804 to nt 903 of the nuclear DNA (nDNA) reference gene GAPDH. Each reaction was optimized and confirmed linear over an appropriate concentration range using genomic DNA standards. Samples were analyzed in triplicate for both assays, enabling calculation of the average mtDNA:nDNA ratio.Results. There were no major histologic differences between the serial muscle biopsies taken from the same individual (figure E-1 on the Neurology Web site at www.neurology.org). There was histochemical evidence of progression in six of the seven patients. In four patients (57.1%), there was an increase in the percentage of COXnegative fibers, and in six (85.7%), there was an increase in the percentage of RRFs. The percentage of mutated mtDNA increased in four indi...

Methadone-Induced Toxic Leukoencephalopathy: MR Imaging and MR Proton Spectroscopy Findings

“…[8][9][10] The imaging findings in our patient are similar, though not identical, to previously reported MR imaging and spectroscopic white matter changes observed in heroin-vapor-inhalation toxicity (a practice known as "chasing the dragon"). [2][3][4]6,7 In general, the different case reports mention similar symmetric and confluent high-signal-intensity changes in the cerebral white matter observed on T2-weighted and FLAIR images with, as also observed in our patient, sparing of the subcortical U-fibers. In our patient, there was no evidence of heroin abuse in any form or involvement of any other recreational drug.…”

“…The proton MR spectroscopy findings revealed a decreased NAA peak and an increase in the lactate peak, similar to findings in previous reports of inhaled heroin neurotoxicity. 6,7 As stated by Vella et al, 13 these findings may indicate a mixed pathologic process of hypoxia and mitochondrial damage, with axonal injury but without demyelination.…”

“…1 Most of the available literature on imaging of illicit substances deals with the neurotoxic changes induced by heroin, a morphine agonist, administered either intravenously or through (repeated) inhalation. [2][3][4][5][6][7] There are only a few reported cases of severe methadone-induced toxic leukoencephalopathy that include imaging findings. [8][9][10] The imaging findings in our patient are similar, though not identical, to previously reported MR imaging and spectroscopic white matter changes observed in heroin-vapor-inhalation toxicity (a practice known as "chasing the dragon").…”

Toxic Leukoencephalopathy after Heroin Abuse without Heroin Vapor Inhalation

“…Subsequent reports have been described across Europe [2,3,5,7,9,14,[20][21][22][24][25][26][27][28][29][30], in the USA [6,12,17], Austra- lia [23], Canada [8,11,13,16], as well as a few cases from Taiwan [10,18,19] and Hong Kong [15]. However, reports of heroin-associated leukoencephalopathy remain seldom considering the large number of heroin addicts.…”

“…Inhalation of heroin vapor known as "chasing the dragon" or "chinesing" in particular leads to characteristic imaging and brain biopsy features [1][2][3][4][5][6][7][8][9]. Magnetic resonance imaging (MRI) shows symmetric white matter hyperintense signal changes in the cerebellum, the posterior cerebrum, the posterior limb of the internal capsule, the splenium of the corpus callosum, the medial lemniscus and the lateral brainstem [4,6,[8][9][10][11][12][13][14][15].…”