【作者】 王为民；

【导师】 陆兵勋；

【作者基本信息】 第一军医大学 ， 神经病学， 2001， 硕士

【摘要】 背景与目的 海洛因海绵状白质脑病（Heroin Spongiform Leukoencephalopathy，HSLE）是一种与经鼻烫吸海洛因有关的，主要表现为走路不稳、言语不清等小脑受损症状，主要累及脑白质的神经系统疾病。1982年由Wolters等在荷兰首次发现，以后德国、意大利、比利时和美国等地陆续有个案报道。除1982年荷兰和我们2000年8月报道成批发生外，其它均为个案报道。HSLE的临床表现与急、慢性海洛因中毒完全不同，主要表现为小脑性共济失调。HSLE的发病机理不明。其脑部病理改变为脑白质的广泛空泡伏变性，与可传播性海绵状脑病（TransmissibleSpongiform Encephalopathy，TSE）的病理改变相似。TSE的诊断金标准是脑组织免疫组化PrP阳性，近年来发现脑脊液（CSF）14-3-3蛋白检测在诊断Creutzfeldt-Jacob病（CJD）方面的敏感性和特异性都很高，被认为是CJD的可靠生前诊断指标。为明确HSLE与TSE的关系，我们对收集到的29例HSLE患者进行血液和CSF检查、头颅影像学和脑组织病理、免疫组化研究，患者脑组织匀浆鼠脑内接种传递实验研究。 材料与方法 所有病例均为我科自2000年3月以来收治的HSLE患者，一共29例。所有病例进行脑电图、头颅影像学检查，3例尸检，11例脑组织活检，HE、刚果红、髓鞘染色及GFAP、PrP免疫组化。采集患者血液和CSF，进行CSF常规及细胞学、糖、蛋白质和氯化物；血液和CSF病毒学、弓形体、梅毒检测；CSF 14-3-3蛋白Western Blot检测。2例死亡患者脑组织匀浆进行Wistar大鼠脑内接种，观察期6个月。 结 果 所有患者HIV、HSV、MCV、EB、梅毒螺旋体、弓形体抗体检查均为阴性，无合并感染者CSF生化和常规检查正常。CSF14-3-3蛋白做stern Blot检坝均为阴性。 CT显示病变部位白质内界限清楚的对称低密度病灶，无水肿及占位效应。Mill示病变部位臼质广泛异常信号，呈长 TI长 TZ改变，FI。AIR序列成象显示白质高信号改变，病变范围基本同TZ加权像所见一致，增强无强化。 病理结果显示灰质神经细胞无明显减少，灰质无空泡形成。从灰白质交界处向白质空泡逐渐增多，白质区大量大小小均空泡形成，脑肉质呈海绵状改变。小血管周围无明显空泡改变，亦无水肿及炎性细胞浸炯。胶质增生不明显，少突胶质细胞相对少。未见缺血坏死病灶。PrP免疫组化可见神经元阳性反应。电镜：少突胶质细胞大量空泡退行性变，线粒体肿胀，内质网扩张，髓鞘有空泡，很多部位髓鞘被涡轮状空泡裂解。 脑内接种大鼠6个月内没有发病，脑组织病理检查无异常发现。 结论 1．HSLE是一种与经鼻烫吸海洛因有关的，主要表现为小脑受损症状，主要累及脑白质的系统性变性。 2．HSLE病理改变；灰质正常，白质海绵状空泡变性，电镜结果为少突胶质细胞大量空泡退行性变，线粒体肿胀，内质网扩张，髓鞘有空泡，很多部位髓鞘被涡轮状空泡裂解。 3．HSLE的CT表现为白质内界限清楚的对称低密度病灶，NlEl显示为界限清楚的长H长TZ病灶，FLAIR序列成象显示白质高信号改变，病变范围基本同TZ加权像所见一致，增强无强化。 4．HSLE与常见病毒、梅毒螺旋体、弓形体感染无关。 5．HSLE不是可传播性海绵状脑病。更多还原

【Abstract】 Background and Purpose Heroin Spongiform Leukoencephalopathy(HSLE) is a neurological disorder mainly affected brain white matter,which is related with inhalation of the pyrolysate of heroin.HSLE was firstly discovered in Netherlands in 1982. Since then, individual cases were reported in German, Italy, Belgium, the United States and Taiwan,except for the report of mass occurrence in the Netherlands( 1982) by Wolters and in the Chinese mainland by us(2000).The etiology and pathogenesis of HSLE are unknown.Clinical features of HSLE were different from acute or chronic heroin toxication absolutely. The main symptom of HSLE is cerebellar ataxia.The main pathological feature of lISLE was extensive vacuolation in white matter,which was like that of transmissible spongiform encephalopathy(T SE). The golden diagnostic standard of TSE is positive PrP immunohistochemistry reaction iii brain tissue.Recently, 14-3-3 protein in CSF was found to have high sensibility and specificity in CJD patients,and was regarded as a reliable premortem diagnostic standard of CJD.To make clear the relationship between HSLE and TSE,laboratory examination of blood and CSF, neurological imaging,brain tissue pathological and immunohistochemistry research were carried out in all the 29 cases of HSLE we collected and inoculation of homogenate of dead patientsrain to ratsrain to observed the transmisibility of HSLE were conducted. Materials and Methods The sum of cases of HSLE is 29.EEG,CT,MRI were carried out for each patient.Brain biopsy was conducted in 11 cases ,and necropsy was conducted in 3 dead cases.HE.,Congo red,myelin stains and GEAP,PrP immunohistochemistry stains were carried out.Blood and CSF of patients were collected for syphilis,toxoplasma gondii and routine,cytological, glycose,protein,chloride, virology examination and 14-3-3 protein Western Blot of CSF were were carried out too.Homogenate of 2 dead patients抌rain was inoculated in Wistar ratsrain,and the observation period was 6 months. Results I-LIVHSV,MCV,EB,toxoplasma gondii,syphilis examination were all negative.Routine and biochemistry examination of CSF were normal without infection.Immunoassay detection of 14-3-3 protein in CSF were negative. CT showed Symmetric low-density lesions with distinct boundaries in white matters,without effect of edema or mass.MRI showed extensive abnormal signals in white matters in lesion location with long TI and long T2.FLAJR images showed higher signals in white matters of lesion locations and their ranges mainly according with T2 images. The pathology character was spongiform vacuolar degeneration of white matter and neurons in grey matter did not decreased.There were no vacuole,edema and lymphoid infiltration in grey matter and small vessel periphery.There were no apparent reactive astroglial proliferation. o ligodendroglia relatively decreased. Positive reactivities of prion protein by immunohistochemistry were seen in neurons.Foci od ischemic necrosis were not found.Electron microscopy revealed a multivacuolar degeneration of the oligodendroglias. Swollen mitochondria and distended endoplasmic reticulum were found in the remaining cytoplasm.Ln many myelin sheaths vacuoles formed between the myelin lamellae by splitting of the intraperiod lines were observed.In some places continuity of the myelin sheath was interrupted by a ball of whorled myelin layer. The inoculated rats did not onset in 6 months,and the更多还原