海洛因海绵状白质脑病的长期随访研究

发布时间：2018-01-24 13:12

本文关键词： 海洛因海绵状白质脑病临床影像随访　出处：《南方医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：研究背景海洛因海绵状白质脑病(Heroin spongiform leukoencephalopathy, HSLE)是发生在吸嗜海洛因成瘾人群中的比较少见的中枢神经系统白质脑病,文献报道该病的总发病率约为0.32%。HSLE于1982年在荷兰阿姆斯特丹市由Wolters EC等首次发现。自此以后,欧洲、美国、台湾等地区有少数的个案报道。在国内,陆兵勋等在2000年3月首先报道了本病。由于本病为吸嗜海洛因成瘾者人群中出现的罕见疾病,专业教材中未提及,专著中也极少描述,病例少见,病例搜集难度大,除1982年荷兰和本研究组报道的大宗病例外,其余仅为少数个案报道,而且当时对本病尚缺乏足够的认识,加上科技水平等条件有限,均未能进行深入系统的临床研究。随着科学技术的进步,医学神经影像学技术取得了迅猛的发展,为进一步深入地研究疾病提供了很好的条件,有助于我们对疾病的了解和认识。截至目前,尚未见HSLE大宗病例的长期随访研究和结果,关于本病的长期预后、神经功能恢复以及影像学的预后情况仍不清楚,对本病的认识和疗效评定尚不够充分。而我们又拥有目前世界范围内最多的病例数,为我们对该病的长期随访研究提供了非常好的一次机会,有助于进一步加深我们对该病的了解和认识。目的本研究通过对HSLE患者的临床和多种影像学检查结果进行总结并进行长达13年的随访,对本病的临床、影像特点和预后进行深入地分析,为全面认识本病的特点和预后提供非常重要的依据。资料和方法 1、资料 50例南方医科大学南方医院神经内科2000年3月至2008年8月收治的诊断为海洛因海绵状白质脑病的患者,其中40例为住院病人,10例为门诊、流调病人。 2、方法一般资料收集：通过对病历进行回顾,收集记录所有患者的人口学资料,包括性别、年龄、籍贯、发病地区、吸毒时间、吸毒方式、吸毒量、戒毒次数、既往其他药物应用史、家族遗传病史等基本资料；记录患者的临床症状、体征等资料。实验室检查资料收集：收集患者的脑脊液常规、生化检查结果；病毒学检测的结果：人类免疫缺陷病毒(HIV)、EB病毒(EBV)、单纯疱疹病毒(HSV)、巨细胞病毒(CMV)等：细菌学检测结果：梅毒螺旋体、结核杆菌等；寄生虫检测结果：如弓形体等；血液生化、尿液吗啡试验结果。影像学资料收集：阅片收集记录患者的头颅CT、MRI、增强MRI、MRA、 DWI、MRS检查结果,记录病灶累及的部位、范围、信号变化特点、颅内血管情况、波谱特点等。组织活检资料收集：收集记录行尸检或脑组织活检患者的病理检查结果。长期随访：统一查体的标准,在规定的随访时间内对患者进行问卷和查体,记录一般随访调查表问卷情况、自行设计主要神经功能缺损情况量表、影像学的变化等结果。随访时间为治疗前、治疗后1月、治疗后6月、治疗后1年、治疗后2年、治疗后3年、治疗后5年、治疗后10年、治疗后13年。 3、统计学分析采用SPSS13.0软件对相关的数据进行统计学分析。计量资料用均数±标准差(x±s)表示；计数资料采用频数(n)或百分比(%)表示。P0.05定义为差异有统计学意义。结果 1、一般资料结果 50例患者中,男性45例,女性5例。年龄20-46岁,平均29.6±3.7岁。2000年收治26例,10例患者来自于广东省汕头市潮阳区；2004年收治10例,5例患者来自于广东省广州地区。全部患者均有烫吸海洛因史,吸毒时间最短为1年,最长10年,平均32.2±16.5月。每日吸毒量0.5-4.0g不等。其中24例兼有海洛因静注史。38例患者发病前有戒毒史,其中24例患者在戒毒开始2-14天发病,10例在戒毒后1-2个月发病,3例在戒毒后3-4个月发病,1例在戒毒后半年发病。3例发病后戒毒,戒毒的过程中病情进一步加重。患者所采用的戒毒方式不同,其中10例采用“冷火鸡法”戒毒,其余为药物(如美沙酮、硝基安定等)戒毒。15例在戒毒所戒毒,20例在医院或个体诊所戒毒,6例在家中自行戒毒。所有患者均无其它药物应用史和家族遗传史。 2、临床症状和体征患者的临床表现具有相似性。急性起病47例,亚急性起病3例,病情多在几天至十几天内达到高峰,少数病情进展达1月余。首发和突出的临床表现为小脑受损的的症状和体征,包括小脑性共济失调(走路不稳、动作迟缓、蹒跚步态甚至不能行走)和小脑性语言(吟诗样语言、爆破性语言、断续性语言、言语不清甚至不能言语)；若病情进展则出现皮质脊髓束受累,偏瘫或四肢瘫,病理征阳性,有些病人还可有头部或肢体震颤等锥体外系受累的表现；严重者出现意识障碍,出现去皮层状态、痉挛性四肢瘫、无动性缄默、抽搐、植物神经受损症状等。根据患者的意识状态、小脑的症状和体征以及有无锥体束的损害,我们将此病分为三期,I期：小脑受累期(单纯的小脑症状和体征)；Ⅱ期：锥体束受累期(小脑症状、体征合并有锥体束损害的症状)；III期：意识障碍期(昏迷、去皮层状态、无动性缄默、闭锁综合征等),合并锥体束损害的症状。 3、实验室结果 8例患者脑脊液常规出现少量白细胞计数增多,为1-10×106个/L,其余患者脑脊液常规正常；脑脊液生化：5例患者蛋白含量轻度升高,分别为0.46、0.48、0.50、0.56、0.60g/L,其余患者脑脊液蛋白质均正常,葡糖糖和氯化物均正常；所有患者的HIV、EBV、CMV、HSV、梅毒螺旋体、结核杆菌、弓形体抗体结果均为阴性；血液生化检查正常；除1例患者外,尿液吗啡试验均阴性。 4、影像学结果 CT结果：双侧小脑、基底节区、大脑皮层下白质广泛、对称性低密度灶,尤以小脑中线两旁、边界清楚的对称性“蝴蝶样”低密度灶最为明显；无占位效应。 MIRI结果：双侧小脑半球、内囊后肢、胼胝体压部、大脑半球额、颞、顶、枕叶深部及脑干等处白质广泛、对称性异常信号改变,T1WI上呈低信号,T2WI上呈高信号,FLAIR序列上呈高信号改变,较T2WI稍减低。所有患者的小脑均受累及,而内囊前肢、大脑皮层则不受累及。 MRI增强扫描结果：4例患者行MRI增强扫描,增强病灶无强化。 MRA结果：8例患者行MRA扫描。4例患者MRA未见异常表现；3例患者MRA表现为血管分支减少、管径变细；1例患者MRA表现为血管分支减少,走行僵硬,管壁粗糙,粗细不均,呈“串珠样’改变。 DWI序列结果：8例行弥散加权成像,病灶呈高信号或明亮高信号,表观弥散系数(apparent diffusion coefficient,ADC)较正常脑组织降低。 MRS结果：4例患者行MRS检查,与正常脑组织相比,共同的特点是均有NAA含量的降低；2例Cho含量改变不明显,2例Cho含量降低；2例Cr含量改变不明显,2例Cr含量降低。 5、组织病理学结果病理结果提示该病的病理学特点为脑白质海绵状空泡样改变。 6、长期随访结果临床预后：患者的肌力恢复较早且完全,但是小脑症状的恢复较慢。肌力的恢复6个月内最快,5年随访时约89.4%患者的肌力恢复正常,10年随访时约92.3%患者的肌力恢复正常,13年随访时约94.1%患者的肌力恢复正常。多数患者的小脑症状在1年后恢复加快,但恢复较慢,5年随访时言语、行走完全恢复者仅占44.7%、47.3%,10年随访时言语、行走完全恢复的患者约53.8%、61.5%,13年随访时言语、行走完全恢复的患者约58.8%、70.5%。此外,7例Ⅲ期患者中5例死亡。影像学预后：颅内受累病灶可随着治疗和病情的好转而缩小,但是与临床症状和体征的恢复无明显相关性,头颅磁共振病灶信号的消退较临床症状和体征恢复的时间要延迟,甚至可能长期存在,病灶在DWI序列显像上仍可呈高信号改变。此外,部分患者出现脑萎缩改变。结论 (一)HSLE可能呈地区性、小规模、爆发性流行； (二)戒毒是HSLE的常见诱因； (三)HSLE最主要的病理学特点是脑白质海绵状空泡样变性； (四)HSLE的临床具有特点,临床分三期； (五)HSLE的影像学具有特点,对诊断有重要意义； (六)提出HSLE的诊断标准； (七)HSLE的病情进展与患者的年龄、毒龄、每日吸毒量、吸毒方式无关； (八)抗氧化剂和功能锻炼对患者功能的恢复具有重要的意义； (九)Ⅰ、Ⅱ期患者的预后较好,肌力的恢复较早、完全,但小脑症状的恢复较慢；Ⅲ期患者预后不良； (十)患者MRI的恢复与临床症状和体征的好转不一致。
[Abstract]:Research background
Heroin spongiform leukoencephalopathy (Heroin spongiform, leukoencephalopathy, HSLE) is addicted to heroin addiction in absorbing population in the relatively rare central nervous system leukoencephalopathy, the total incidence reported the disease rate is about 0.32%.HSLE in 1982 in Amsterdam, Holland by Wolters EC for the first time. Since then, the United States and Europe. Taiwan and other regions have reported a few cases. In China, the first reported in March 2000 in the aspects of this disease.
Because this disease is a rare disease appear addicted to heroin addicts suck in the crowd, not mentioned in textbooks, monographs also rarely described, rare, difficult to collect cases, in addition to the bulk cases of Holland in 1982 and the study group report, the rest is only a few case reports of this disease, and that lack of adequate understanding, plus the technological level of the limited conditions, failed to conduct clinical research systematically and deeply.
With the progress of science and technology, medical neuroimaging technology has made rapid progress. It provides a good condition for further research of diseases, and helps us to understand and understand diseases.
As of now, no research and long-term follow-up results of HSLE of the bulk of cases, long-term prognosis of this disease, the prognosis of recovery of neurological function and imaging is still not clear, understanding and evaluation of curative effect of this disease is still not sufficient. And we have the most cases in the world, provides a a very good opportunity for us to the disease long-term follow-up study, help to further deepen our understanding of this disease.
objective
In this study, we summarized the clinical and imaging findings of HSLE patients and followed up for 13 years. We analyzed the clinical, imaging features and prognosis of this disease, providing a very important basis for a comprehensive understanding of the characteristics and prognosis of this disease.
Information and methods
1, information
50 cases of heroin spongiform encephalopathy diagnosed in the Department of Neurology of Nanfang Hospital, Southern Medical University from March 2000 to August 2008, including 40 inpatients and 10 outpatients, were enrolled in the Department of Neurology, Nanfang Hospital of Southern Medical University.
2, method
General data collection: through the review of medical records, collected demographic data of all patients, including gender, age, place of birth, onset time of drug abuse, drug abuse, drug abuse, drug treatment, other times, past history of drug use, the family history group; record the patient's clinical symptoms, signs and other information.
Laboratory data collection: routine cerebrospinal fluid were collected, biochemical examination results; virological testing results: human immunodeficiency virus (HIV), EB (EBV) virus, herpes simplex virus (HSV), cytomegalovirus (CMV): bacteriological detection results: syphilis helicoid, tuberculosis; parasite detection results: such as toxoplasmosis; blood biochemistry, urine morphine test results.
Imaging data collection: read and collect CT, MRI and MRI, MRA, DWI and MRS results of patients, record the location, range, characteristics of signal changes, intracranial blood vessels, and spectral characteristics.
Biopsy data collection: a pathological examination of the patients who were recorded for autopsy or biopsy of the brain.
Long term follow-up: the unified examination standard, questionnaire and examination of patients during the follow-up time, recorded follow-up questionnaire questionnaire and self-designed scale mainly neurological function, imaging changes. Results follow-up before treatment, after treatment after treatment in January, June, for 1 years. After 2 years of treatment, 3 years after treatment, 5 years after treatment, 10 years after treatment, 13 years after treatment.
3, statistical analysis
SPSS13.0 software was used for statistical analysis of the relevant data. The measurement data were expressed by mean + standard deviation (x + s). Counting data were represented by frequency (n) or percentage (%),.P0.05 was defined as the difference was statistically significant.
Result
1, general data results
In 50 patients, 45 males and 5 females. The age of 20-46 years old, average 29.6 + 3.7 years.2000 years were 26 cases, 10 patients from Chaoyang District of Guangdong city in Shantou province; 10 cases from 2004, 5 patients from Guangzhou area of Guangdong province. All patients had chaising heroin history, smoking poison is the shortest time for 1 years, the longest 10 years, an average of 32.2 + 16.5 months. The daily amount of drugs ranging from 0.5-4.0g. Among them 24 cases with intravenous injection of heroin have history of drug history before the onset of.38 patients, 24 patients started 2-14 days at the onset of drug among them, 10 cases in treatment 1-2 months after onset, 3 in cases of drug treatment for 3-4 months after the onset, 1 cases in treatment six months after onset of.3 patients after drug treatment, drug treatment in the process of further aggravated. Patients with drug treatment in different ways, of which 10 cases were treated with "cold turkey" drug, for the rest of the drug (such as methadone, nitrazepam) drug.15 cases in drug rehab 20 cases were detoxification at hospital or individual clinic, and 6 cases were detoxification at home. All patients had no other history of drug use and family history.
2, clinical symptoms and signs
The clinical manifestations of patients with acute onset of similarity. In 47 cases, 3 cases of subacute onset disease, multi peak in a few days to ten days, a progression of up to 1 more than a month. The first clinical manifestation and prominent cerebellar damage symptoms and signs, including cerebellar ataxia (walking instability, slow movement can not even walk, staggering gait) and cerebellar language (like poetry language, blasting language, intermittent language, slurred speech or even speech); if there is progression of corticospinal tract involvement, hemiplegia or quadriplegia, positive pathological signs, some patients may also have head or limb tremor and other extrapyramidal the involvement of the performance; severe disturbance of consciousness, appear to cortex, spastic quadriplegia, akinetic mutism, convulsions, autonomic nerve damage symptoms. According to the patient's state of consciousness, cerebellar symptoms and signs as well as there is no cone The beam damage, we will divided into three periods: period of stage I cerebellar involvement (pure cerebellar symptoms and signs); II: pyramidal period (cerebellar symptoms, signs and symptoms of pyramidal damage); III: disturbance of consciousness (coma period, decorticate state, no movement silence, etc.), with locked in syndrome of pyramidal tract symptoms.
3, laboratory results
8 cases of cerebrospinal fluid in patients with conventional small white blood cell count increased, 1-10 * 106 /L, the cerebrospinal fluid of patients with normal cerebrospinal fluid; biochemical: 5 cases of patients with mild elevated protein content, respectively 0.46,0.48,0.50,0.56,0.60g/L, the rest of the patients had normal cerebrospinal fluid protein, glucose and chloride were normal in all patients; HIV, EBV, CMV, HSV, syphilis, tuberculosis, Toxoplasma antibody were negative; blood biochemical examination was normal; except for 1 patients, the urine morphine test were all negative.
4, imaging results
CT results: bilateral cerebellum, basal ganglia, subcortical white matter were widely distributed, symmetric low density foci, especially in the central line of cerebellum, the boundary was clear, symmetrical, "butterfly like" low density foci were most obvious, no occupying effect.
MIRI results: bilateral cerebellum, posterior limb of the internal capsule, corpus callosum, brain hemisphere frontal, temporal, occipital top, deep white matter and brain stem at the extensive, symmetrical abnormal signal change, T1WI showed low signal, T2WI showed high signal, FLAIR sequence showed high signal changes, T2WI is diminished low. All patients were involved and the cerebellum, anterior limb of the internal capsule, cerebral cortex is not involved.
MRI enhanced scan results: 4 patients underwent enhanced MRI scan, and the enhancement was not enhanced.
MRA results: 8 patients underwent MRA scan, and.4 showed no abnormal expression in MRA. In 3 patients, MRA showed a decrease in blood vessel branches and a smaller diameter. In 1 patients, MRA showed a decrease in vascular branches, rigidity and rough wall thickness.
DWI sequence results: 8 cases were diffusion-weighted imaging, the lesions were hyperintense or bright high signal, and the apparent diffusion coefficient (apparent diffusion coefficient (ADC)) was lower than that of normal brain tissue.
MRS results: 4 patients underwent MRS examination. Compared with normal brain tissue, the common characteristics were the decrease of NAA content, 2 cases of Cho content change was not obvious, 2 cases of Cho content decreased, 2 cases of Cr content change was not obvious, 2 cases Cr content decreased.
5, histopathological results
Pathological findings suggest that the pathological features of the disease are cavernous vacuoles like changes in the white matter.
6, long-term follow-up results
The clinical prognosis of patients with muscle recovery: early and complete, but slower recovery of cerebellar symptoms. Muscle recovery within 6 months of the fastest 5 years follow-up, approximately 89.4% of patients with normal muscle recovery, 10 years follow-up of about 92.3% patients returned to normal muscle strength, 13 years follow-up, approximately 94.1% of patients with normal muscle recovery. Cerebellar symptoms of most patients in 1 years after the recovery speed, but the recovery was slow, 5 years follow-up speech, walking recovery accounted for only 44.7%, 47.3%, 10 years follow-up speech, walking about 53.8% patients recovered completely, 61.5%, 13 years follow-up speech, walking about 58.8% patients recovered completely, in addition to 70.5%. 7 cases of stage III patients, 5 patients died.
The prognosis of intracranial involvement: imaging lesions can be narrowed with treatment and the improvement of the disease, but with clinical symptoms and signs of recovery have no obvious correlation, regression of MRI signal lesions than the clinical symptoms and signs of recovery time will be delayed, and may still exist for a long time, lesion in DWI sequence imaging showed high signal change. In addition, some patients with cerebral atrophy.
conclusion
(1) HSLE may be regional, small and explosive.
(2) drug abstinence is a common cause of HSLE.
(three) the main pathological feature of HSLE is cavernous vacuolated degeneration of white matter.
(four) the clinical features of HSLE were divided into three stages.
(five) the imaging features of HSLE are of great significance to the diagnosis.
(six) put forward the diagnostic criteria of HSLE;
(seven) the progression of HSLE was not related to the age of the patients, the age of the drug, the daily drug use, and the way of drug use.
(eight) antioxidants and functional exercise are of great significance to the recovery of the patient's function.
(nine) the prognosis of patients in stage I, stage II is better, the recovery of muscle strength is early, complete, but the recovery of cerebellar symptoms is slow, and the prognosis of stage III patients is bad.
(ten) the recovery of MRI in patients is not consistent with the improvement of clinical symptoms and signs.

【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742

【参考文献】