heroin and Canavan-Disease

To investigate whether microvascular damage is involved in the pathogenesis of heroin induced spongiform leukoencephalopathy (HSLE).. The brain tissues were collected from 4 HSLE patients and 5 controls and then fixed in 4% paraformaldehyde. The frontal lobe, corpus callosum and cerebellum were separated. The expressions of myelin base protein (MBP) and CD34 were detected by immunohistochemistry. TUNEL staining was applied to detect cell apoptosis. The correlation between microvascular changes and pathological vacuoles was evaluated.. No obvious abnormalities were found in the brain of controls. Immunohistochemistry for MBP showed the collapse and fracture of myelin sheath and vacuole formation in the subcortical white matter, corpus callosum, and cerebellar white matter of HSLE patients. TUNEL staining showed the number of apoptotic cells in the cerebellar white matter and corpus callosum of HSLE patients was significantly higher than that in controls (F = 389.451, P < 0.001). Masson's trichrome staining revealed vacuolar degeneration in the cerebral white matter of HSLE patients, and the vacuoles were distributed around the microvessels. Immunohistochemistry revealed CD34 positive cells were seldom found besides the vessels in the cerebellar white matter and corpus callosum of HSLE patients, but a variety of CD34 positive cells was found in the vascular wall of controls (F = 838.500, P < 0.001).. Apoptosis of oligodendrocytes may be related to the HSLE. Cerebral vascular injury and microcirculation dysfunction are involved in the pathogenesis of HSLE. The interrelation between apoptosis of oligodendrocytes and the microvascular damage are required to be studied in future investigations.

Topics: Adult; Antigens, CD34; Apoptosis; Canavan Disease; Cerebellum; Cerebrovascular Trauma; Corpus Callosum; Female; Frontal Lobe; Heroin; Heroin Dependence; Humans; Male; Microvessels; Middle Aged; Myelin Basic Protein; Oligodendroglia

To elucidate the relation between cytochrome P4502D6 (CYP2D6) gene polymorphism and the susceptibility of heroin spongiform leucoencephalopathy (HSLE).. With polymerase chain reaction-restriction fragment length polymorphism technique, the cytochrome P4502D6 gene polymorphisms were analyzed in HSLE cases and control subjects.. The frequencies of CYP2D6 (CYP2D6/C188, CYP2D6/L2938, CYP2D6/G4268) gene mutations were higher in HSLE patients than in the controls.. The CYP2D6 gene mutation is associated with a high risk of HSLE.

Topics: Adult; Canavan Disease; Cytochrome P-450 CYP2D6; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Mutation; Polymorphism, Restriction Fragment Length; Young Adult

To investigate the role of oligodendrocyte apoptosis under the regulation of the bcl-2/bax protein expression in brain white matter in the pathogenesis of heroin-induced spongiform leucoencephalopathy (HSLE).. Samples of frontal lobe, cerebellum, and corpus callosum were obtained from the brains during autopsy of 4 HSLE cases and 5 normal controls and underwent light microscopy and electron microscopy. Immunocytochemistry was used to detect the expression of myelin basic protein (MBP), caspase-3, bcl-2 protein, and bax protein.. Widespread demyelination was seen in the white matter of the frontal lobe, cerebellum and corpus callosum of the HSLE cases, most severely in the cerebellum. The levels of caspase-3 and bax expression of the HSLE group were significantly higher than those of the control group (both P <0.05) , however, the bcl-2 level of the HSLE group was no significantly different from that of the control group (P > 0.05).. Widespread demyelination in the white matter is a prevailed pathological change of HSLE. Oligodendrocyte apoptosis under induced by the decrease of bcl-2/bax ratio may contribute to the pathogenesis.

Topics: Adult; Aged; Apoptosis; Autopsy; bcl-2-Associated X Protein; Canavan Disease; Female; Heroin; Heroin Dependence; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Myelin Basic Protein; Oligodendroglia; Proto-Oncogene Proteins c-bcl-2

Topics: Canavan Disease; Hearing Loss, Sudden; Heroin; Humans; Male; Middle Aged

To investigate the regulation of cyclooxygenase (Cox)-2/2', 3'-cyclic nucleotide3' phosphohydrolase (CNPase) on the oligodendrocyte apoptosis in the pathogenesis of the heroin-induced spongiform leucoencephalopathy (HSLE).. Samples of frontal lobe, cerebellum, and corpus callosum were obtained from the brains during autopsy of 4 HSLE patients and 5 patients who died of diseases other than cerebral diseases (controls) and underwent light microscopy and electron microscopy. Immunocytochemistry was carried out to detect the expression of myelin basic protein (MBP), caspase-3, COX-2, and CNPase protein. Apoptosis was examined by TUNEL staining.. Widespread demyelination was seen in the white matter of the frontal lobe, cerebellum, and corpus callosum of the HSLE cases, most severely in cerebellum. In he HSLE group, the levels of caspase-3 and COX-2 expression were significantly higher, and the level of CNPase was significantly lower than those of the control group (all P < 0.05).. Widespread demyelination in the white matter is a prevailing pathological change of HSLE. Oligodendrocyte apoptosis is one of the causes of HSLE. The upregulation of COX-2 and downregulation of CNPase may contribute to the pathogenesis.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Adult; Aged; Apoptosis; Canavan Disease; Caspase 3; Cyclooxygenase 2; Female; Heroin; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Oligodendroglia

To understand the distribution and related risk factors of heroin spongiform leucoencephalopathy among drug users in coastland of Guangdong Province.. A cross-sectional study was conducted in four thousand four hundred and twenty eight drug users from eighteen detoxification organizations in six cities on coastland of Guangdong, using clustered random sampling methods. The six cities are Chaoyang (714), Heyuan (462), Shantou (572), Huidong (1286), Guangzhou (871) and Zhanjiang (523) and heroin abuse was considered serious in these cities. Questionnaire was used to collect the data on sex (man 3632, 82 percent; woman 795, 18 percent), age (minimum 15y, maximum 54y), duration of using heroin (minimum 1 month, maximum 150 months), daily dosage (minimum 0.02 g, maximum 6.0 g) and manner of using heroin. In addition, the neurological examination was taken in all of them and cerebral MRI was carried out in those with signs of cerebellar ataxia.. Results showed that the total incidence of heroin spongiform leucoencephalopathy in six cities is 3.16 per thousand. Poisson regression analysis showed that the incidence was related to residential areas. In comparison with other cities, there are higher incidences in Chaoyang and Heyuan. Our investigation also showed that all the patients with this disease used heroin by inhaling the pyrolysate. The incidence of heroin spongiform leucoencephalopathy was unrelated to the daily inhaling amount of heroin and the duration of inhaling heroin. No differences could be observed between the groups of different age and sex.. Spongiform leucoencephalopathy after inhalation of heroin is a rare complication and has never been reported in mainland of China before. The lesions are symmetrical and spongiform, but not necrotic and the cerebellum is invariably involved--a feature consistent with the clinical presentation that begins with ataxia. Cerebral CT showed symmetrical non-enhancing hypodense areas in both cerebellar hemispheres. Cerebral MRI showed the corresponding areas with decreased signal intensity on T1 weighted images and increased signal intensity on T2 weighted images. There was no contrast enhancement. When it occurs, several cases are affected as a small epidemic. It is suggested that the aetiology is related to the heroin batch and could perhaps be a toxic effect of a substance which came from heroin pyrolysis.

Topics: Administration, Inhalation; Adolescent; Adult; Canavan Disease; China; Cross-Over Studies; Female; Heroin; Heroin Dependence; Humans; Incidence; Male; Middle Aged

This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism.

Topics: Administration, Inhalation; Adult; Canavan Disease; Cerebellum; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotics; Tomography, X-Ray Computed; Volatilization