本文關(guān)鍵詞： 海洛因 海綿狀白質(zhì)腦病 臨床 影像 隨訪　出處：《南方醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景 海洛因海綿狀白質(zhì)腦病(Heroin spongiform leukoencephalopathy, HSLE)是發(fā)生在吸嗜海洛因成癮人群中的比較少見的中樞神經(jīng)系統(tǒng)白質(zhì)腦病,文獻(xiàn)報(bào)道該病的總發(fā)病率約為0.32%。HSLE于1982年在荷蘭阿姆斯特丹市由Wolters EC等首次發(fā)現(xiàn)。自此以后,歐洲、美國(guó)、臺(tái)灣等地區(qū)有少數(shù)的個(gè)案報(bào)道。在國(guó)內(nèi),陸兵勛等在2000年3月首先報(bào)道了本病。 由于本病為吸嗜海洛因成癮者人群中出現(xiàn)的罕見疾病,專業(yè)教材中未提及,專著中也極少描述,病例少見,病例搜集難度大,除1982年荷蘭和本研究組報(bào)道的大宗病例外,其余僅為少數(shù)個(gè)案報(bào)道,而且當(dāng)時(shí)對(duì)本病尚缺乏足夠的認(rèn)識(shí),加上科技水平等條件有限,均未能進(jìn)行深入系統(tǒng)的臨床研究。 隨著科學(xué)技術(shù)的進(jìn)步,醫(yī)學(xué)神經(jīng)影像學(xué)技術(shù)取得了迅猛的發(fā)展,為進(jìn)一步深入地研究疾病提供了很好的條件,有助于我們對(duì)疾病的了解和認(rèn)識(shí)。 截至目前,尚未見HSLE大宗病例的長(zhǎng)期隨訪研究和結(jié)果,關(guān)于本病的長(zhǎng)期預(yù)后、神經(jīng)功能恢復(fù)以及影像學(xué)的預(yù)后情況仍不清楚,對(duì)本病的認(rèn)識(shí)和療效評(píng)定尚不夠充分。而我們又擁有目前世界范圍內(nèi)最多的病例數(shù),為我們對(duì)該病的長(zhǎng)期隨訪研究提供了非常好的一次機(jī)會(huì),有助于進(jìn)一步加深我們對(duì)該病的了解和認(rèn)識(shí)。 目的 本研究通過(guò)對(duì)HSLE患者的臨床和多種影像學(xué)檢查結(jié)果進(jìn)行總結(jié)并進(jìn)行長(zhǎng)達(dá)13年的隨訪,對(duì)本病的臨床、影像特點(diǎn)和預(yù)后進(jìn)行深入地分析,為全面認(rèn)識(shí)本病的特點(diǎn)和預(yù)后提供非常重要的依據(jù)。 資料和方法 1、資料 50例南方醫(yī)科大學(xué)南方醫(yī)院神經(jīng)內(nèi)科2000年3月至2008年8月收治的診斷為海洛因海綿狀白質(zhì)腦病的患者,其中40例為住院病人,10例為門診、流調(diào)病人。 2、方法 一般資料收集：通過(guò)對(duì)病歷進(jìn)行回顧,收集記錄所有患者的人口學(xué)資料,包括性別、年齡、籍貫、發(fā)病地區(qū)、吸毒時(shí)間、吸毒方式、吸毒量、戒毒次數(shù)、既往其他藥物應(yīng)用史、家族遺傳病史等基本資料；記錄患者的臨床癥狀、體征等資料。 實(shí)驗(yàn)室檢查資料收集：收集患者的腦脊液常規(guī)、生化檢查結(jié)果；病毒學(xué)檢測(cè)的結(jié)果：人類免疫缺陷病毒(HIV)、EB病毒(EBV)、單純皰疹病毒(HSV)、巨細(xì)胞病毒(CMV)等：細(xì)菌學(xué)檢測(cè)結(jié)果：梅毒螺旋體、結(jié)核桿菌等；寄生蟲檢測(cè)結(jié)果：如弓形體等；血液生化、尿液?jiǎn)岱仍囼?yàn)結(jié)果。 影像學(xué)資料收集：閱片收集記錄患者的頭顱CT、MRI、增強(qiáng)MRI、MRA、 DWI、MRS檢查結(jié)果,記錄病灶累及的部位、范圍、信號(hào)變化特點(diǎn)、顱內(nèi)血管情況、波譜特點(diǎn)等。 組織活檢資料收集：收集記錄行尸檢或腦組織活檢患者的病理檢查結(jié)果。 長(zhǎng)期隨訪：統(tǒng)一查體的標(biāo)準(zhǔn),在規(guī)定的隨訪時(shí)間內(nèi)對(duì)患者進(jìn)行問(wèn)卷和查體,記錄一般隨訪調(diào)查表問(wèn)卷情況、自行設(shè)計(jì)主要神經(jīng)功能缺損情況量表、影像學(xué)的變化等結(jié)果。隨訪時(shí)間為治療前、治療后1月、治療后6月、治療后1年、治療后2年、治療后3年、治療后5年、治療后10年、治療后13年。 3、統(tǒng)計(jì)學(xué)分析 采用SPSS13.0軟件對(duì)相關(guān)的數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示；計(jì)數(shù)資料采用頻數(shù)(n)或百分比(%)表示。P0.05定義為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果 1、一般資料結(jié)果 50例患者中,男性45例,女性5例。年齡20-46歲,平均29.6±3.7歲。2000年收治26例,10例患者來(lái)自于廣東省汕頭市潮陽(yáng)區(qū)；2004年收治10例,5例患者來(lái)自于廣東省廣州地區(qū)。全部患者均有燙吸海洛因史,吸毒時(shí)間最短為1年,最長(zhǎng)10年,平均32.2±16.5月。每日吸毒量0.5-4.0g不等。其中24例兼有海洛因靜注史。38例患者發(fā)病前有戒毒史,其中24例患者在戒毒開始2-14天發(fā)病,10例在戒毒后1-2個(gè)月發(fā)病,3例在戒毒后3-4個(gè)月發(fā)病,1例在戒毒后半年發(fā)病。3例發(fā)病后戒毒,戒毒的過(guò)程中病情進(jìn)一步加重�；颊咚捎玫慕涠痉绞讲煌�,其中10例采用“冷火雞法”戒毒,其余為藥物(如美沙酮、硝基安定等)戒毒。15例在戒毒所戒毒,20例在醫(yī)院或個(gè)體診所戒毒,6例在家中自行戒毒。所有患者均無(wú)其它藥物應(yīng)用史和家族遺傳史。 2、臨床癥狀和體征 患者的臨床表現(xiàn)具有相似性。急性起病47例,亞急性起病3例,病情多在幾天至十幾天內(nèi)達(dá)到高峰,少數(shù)病情進(jìn)展達(dá)1月余。首發(fā)和突出的臨床表現(xiàn)為小腦受損的的癥狀和體征,包括小腦性共濟(jì)失調(diào)(走路不穩(wěn)、動(dòng)作遲緩、蹣跚步態(tài)甚至不能行走)和小腦性語(yǔ)言(吟詩(shī)樣語(yǔ)言、爆破性語(yǔ)言、斷續(xù)性語(yǔ)言、言語(yǔ)不清甚至不能言語(yǔ))；若病情進(jìn)展則出現(xiàn)皮質(zhì)脊髓束受累,偏癱或四肢癱,病理征陽(yáng)性,有些病人還可有頭部或肢體震顫等錐體外系受累的表現(xiàn)；嚴(yán)重者出現(xiàn)意識(shí)障礙,出現(xiàn)去皮層狀態(tài)、痙攣性四肢癱、無(wú)動(dòng)性緘默、抽搐、植物神經(jīng)受損癥狀等。根據(jù)患者的意識(shí)狀態(tài)、小腦的癥狀和體征以及有無(wú)錐體束的損害,我們將此病分為三期,I期：小腦受累期(單純的小腦癥狀和體征)；Ⅱ期：錐體束受累期(小腦癥狀、體征合并有錐體束損害的癥狀)；III期：意識(shí)障礙期(昏迷、去皮層狀態(tài)、無(wú)動(dòng)性緘默、閉鎖綜合征等),合并錐體束損害的癥狀。 3、實(shí)驗(yàn)室結(jié)果 8例患者腦脊液常規(guī)出現(xiàn)少量白細(xì)胞計(jì)數(shù)增多,為1-10×106個(gè)/L,其余患者腦脊液常規(guī)正常；腦脊液生化：5例患者蛋白含量輕度升高,分別為0.46、0.48、0.50、0.56、0.60g/L,其余患者腦脊液蛋白質(zhì)均正常,葡糖糖和氯化物均正常；所有患者的HIV、EBV、CMV、HSV、梅毒螺旋體、結(jié)核桿菌、弓形體抗體結(jié)果均為陰性；血液生化檢查正常；除1例患者外,尿液?jiǎn)岱仍囼?yàn)均陰性。 4、影像學(xué)結(jié)果 CT結(jié)果：雙側(cè)小腦、基底節(jié)區(qū)、大腦皮層下白質(zhì)廣泛、對(duì)稱性低密度灶,尤以小腦中線兩旁、邊界清楚的對(duì)稱性“蝴蝶樣”低密度灶最為明顯；無(wú)占位效應(yīng)。 MIRI結(jié)果：雙側(cè)小腦半球、內(nèi)囊后肢、胼胝體壓部、大腦半球額、顳、頂、枕葉深部及腦干等處白質(zhì)廣泛、對(duì)稱性異常信號(hào)改變,T1WI上呈低信號(hào),T2WI上呈高信號(hào),FLAIR序列上呈高信號(hào)改變,較T2WI稍減低。所有患者的小腦均受累及,而內(nèi)囊前肢、大腦皮層則不受累及。 MRI增強(qiáng)掃描結(jié)果：4例患者行MRI增強(qiáng)掃描,增強(qiáng)病灶無(wú)強(qiáng)化。 MRA結(jié)果：8例患者行MRA掃描。4例患者M(jìn)RA未見異常表現(xiàn)；3例患者M(jìn)RA表現(xiàn)為血管分支減少、管徑變細(xì)；1例患者M(jìn)RA表現(xiàn)為血管分支減少,走行僵硬,管壁粗糙,粗細(xì)不均,呈“串珠樣’改變。 DWI序列結(jié)果：8例行彌散加權(quán)成像,病灶呈高信號(hào)或明亮高信號(hào),表觀彌散系數(shù)(apparent diffusion coefficient,ADC)較正常腦組織降低。 MRS結(jié)果：4例患者行MRS檢查,與正常腦組織相比,共同的特點(diǎn)是均有NAA含量的降低；2例Cho含量改變不明顯,2例Cho含量降低；2例Cr含量改變不明顯,2例Cr含量降低。 5、組織病理學(xué)結(jié)果 病理結(jié)果提示該病的病理學(xué)特點(diǎn)為腦白質(zhì)海綿狀空泡樣改變。 6、長(zhǎng)期隨訪結(jié)果 臨床預(yù)后：患者的肌力恢復(fù)較早且完全,但是小腦癥狀的恢復(fù)較慢。肌力的恢復(fù)6個(gè)月內(nèi)最快,5年隨訪時(shí)約89.4%患者的肌力恢復(fù)正常,10年隨訪時(shí)約92.3%患者的肌力恢復(fù)正常,13年隨訪時(shí)約94.1%患者的肌力恢復(fù)正常。多數(shù)患者的小腦癥狀在1年后恢復(fù)加快,但恢復(fù)較慢,5年隨訪時(shí)言語(yǔ)、行走完全恢復(fù)者僅占44.7%、47.3%,10年隨訪時(shí)言語(yǔ)、行走完全恢復(fù)的患者約53.8%、61.5%,13年隨訪時(shí)言語(yǔ)、行走完全恢復(fù)的患者約58.8%、70.5%。此外,7例Ⅲ期患者中5例死亡。 影像學(xué)預(yù)后：顱內(nèi)受累病灶可隨著治療和病情的好轉(zhuǎn)而縮小,但是與臨床癥狀和體征的恢復(fù)無(wú)明顯相關(guān)性,頭顱磁共振病灶信號(hào)的消退較臨床癥狀和體征恢復(fù)的時(shí)間要延遲,甚至可能長(zhǎng)期存在,病灶在DWI序列顯像上仍可呈高信號(hào)改變。此外,部分患者出現(xiàn)腦萎縮改變。 結(jié)論 (一)HSLE可能呈地區(qū)性、小規(guī)模、爆發(fā)性流行； (二)戒毒是HSLE的常見誘因； (三)HSLE最主要的病理學(xué)特點(diǎn)是腦白質(zhì)海綿狀空泡樣變性； (四)HSLE的臨床具有特點(diǎn),臨床分三期； (五)HSLE的影像學(xué)具有特點(diǎn),對(duì)診斷有重要意義； (六)提出HSLE的診斷標(biāo)準(zhǔn)； (七)HSLE的病情進(jìn)展與患者的年齡、毒齡、每日吸毒量、吸毒方式無(wú)關(guān)； (八)抗氧化劑和功能鍛煉對(duì)患者功能的恢復(fù)具有重要的意義； (九)Ⅰ、Ⅱ期患者的預(yù)后較好,肌力的恢復(fù)較早、完全,但小腦癥狀的恢復(fù)較慢；Ⅲ期患者預(yù)后不良； (十)患者M(jìn)RI的恢復(fù)與臨床癥狀和體征的好轉(zhuǎn)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.

【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742

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