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（Transmissible
Spongiform 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。
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
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