抗体特异性指数和脑脊液细胞学在部分病毒性脑炎诊断中的应用
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摘要
目的:评价抗体特异性指数在病毒性脑炎诊断中的意义,了解此种方法在病毒性脑炎诊断中的敏感性与特异性。期望为病毒性脑炎寻找一种具有理想的敏感性和高度特异性的病原学诊断方法,通过一种廉价、快捷、方便的方法来提高病毒性脑炎的诊断水平,为病毒性脑炎的临床治疗和发病机制研究提供帮助。并进一步研究不同类型中枢神经系统疾病的脑脊液细胞学特点。
方法:临床诊断的病毒性脑炎患者36例,入院三天内留取血清和第一份脑脊液标本,第二到第三周留取第二份脑脊液标本。所有标本冻存于-20oC低温冰箱,分批进行检测。用德国欧蒙公司提供的ELISA试剂盒,半定量检测标本中病毒特异性抗体IgG相对浓度。实验中,血清稀释404倍,脑脊液稀释2倍;通过四个标准液绘制标准曲线,标本酶标检测结果代入标准曲线计算病毒特异性抗体IgG浓度。免疫检验室通过散射速率比浊法分别检测脑脊液和配对血清中IgG总量。脑脊液中病毒特异性抗体占脑脊液总IgG比例与血清中病毒特异性抗体占血清总IgG比例之间的比值,即CSF/血清相对比值CSQrel(抗体特异性指数);此比值大于1.5视为阳性。实验中检测单纯疱疹病毒1型(HSV-1),EB病毒(EBV),人类巨细胞病毒(HCMV);通过病毒抗体特异性指数的阳性结果建立病毒性脑炎的病原学诊断。实验设立中枢神经系统非病毒性感染性疾病患者(结核性脑膜炎14例,化脓性脑膜炎2例,脑囊虫病4例),脱髓鞘疾病患者(多发性硬化5例,吉兰-巴雷综合征2例)为对照组。对两组患者病毒抗体特异性指数阳性率进行比较,来评价病毒抗体特异性指数作为病原学诊断方法的敏感性和特异性。动态观察两组患者的脑脊液细胞学,对两组患者的脑脊液细胞学进行分析比较,进一步探讨病毒性脑炎的脑脊液细胞学表现。对研究组和对照感染组(结核性脑膜炎,化脓性脑膜炎,脑囊虫病)的部分临床资料进行比较,分析病毒感染与其它类型感染在临床表现上的差异。统计学分析采用SPSS12.0软件,计数资料采用χ2检验,检验水准α=0.05。
结果:1在研究组36例中通过病毒抗体特异性指数诊断为单纯疱疹病毒性脑炎的6例(17%),EB病毒性脑炎3例(8%),巨细胞病毒性脑炎2例(6%),总体阳性率为31%。对照组27例中有一例临床诊断为结核性脑膜炎,但检测中EB病毒抗体特异性指数为阳性。在研究组中未见到多种抗体重叠阳性出现。两组抗体特异性指数阳性率比较,研究组为31%,对照组为4%,(χ~2=5.578,P=0.018)。此种方法诊断病毒性脑炎的特异性为91.7%。
2两组的脑脊液细胞学都有很高的异常率,研究组为86%,对照组为78%,两组间脑脊液细胞学的异常率无统计学差异。病毒性脑炎患者脑脊液细胞学以淋巴细胞反应为主,少数病例在早期见到嗜中性粒细胞增高现象。6例诊断为单纯疱疹病毒性脑炎的患者脑脊液细胞学全部异常,其中2例患者脑脊液细胞学检查见到红细胞;2例EB病毒性脑炎和巨细胞病毒性脑炎患者脑脊液细胞学有异常,但未发现与病毒性脑炎脑脊液细胞学的一般表现存在差异。
3研究组与对照感染组的部分临床资料存在差异,其中精神异常、脑膜刺激征的出现率和脑电图的异常率差异明显。
结论:病毒抗体特异性指数,反映抗体在中枢神经系统局部合成的情况,此指标大于1.5提示特异性抗体在病毒感染中枢神经系统后由鞘内合成;此方法在病毒性脑炎的诊断中有着比较理想的敏感性和很高的特异性,其意义值得重视。继续扩大研究的样本量,并增加检测的病毒抗体的种类,有可能提高此种方法检测结果的总体阳性率,近而得到一个更令人满意的敏感性。作为一种廉价、快捷、方便的病原学诊断方法,有可能为病毒性脑炎的临床治疗和研究带来巨大的帮助。流行病学资料和临床表现是病毒性脑炎的诊断基础,脑电图检查和脑脊液细胞学检测是重要的辅助检查措施,在病毒性脑炎的诊断中绝对不能疏漏。
Objective: To evaluate the sensitivity and particularity of the antibody specificity index in the diagnosis of viral encephalitis. Expected to find a good method of etiological diagnosis for viral encephalitis,which is cheap, convenient and has ideal sensitivity and particularity . The level of the diagnosis of viral encephalitis was expected to elevate. Wish it is helpful for the treatment and investigation. The feature of CSFC (cerebrospinal fluid cytology) in the central nervous system disease was studied further.
Methods: Study group have 36 patients suffer from viral encephalitis which was clinical diagnosis. The serum and the first CSF sample were gathered in 3 days after they came in, the second CSF sample were gathered at the second or the third week. All the sample were preserved in cryogenic box at -20oC, and were treated in batch. The pathogen-specific antibody of the IgG class was quantitative in-vitor assayed by the ELISA test kit from EUROIMMUN Medizinische Labordiagnostika AG. In the assay, serum samples were diluted 1:404 in sample buffer, CSF samples were diluted 1:2 in sample buffer, standard curve was determined by the CSF calibrators(C A to C D), then the concentration of antibodies of IgG were obtained. The volume dose of the IgG was obtained from immunity laboratory by nephelometry. The quotient of the portion of pathogen-specific antibodies in total IgG of CSF and the portion of pathogen-specific antibodies in total IgG of serum is the relative CSF/serum quotient(CSQrel). A CSQrel above 1.5 is positive. In the study, the antibodies against HSV-1, EBV, HCMV were detected. A etiological diagnosis was made by the positive result. Total 27 patients suffer from others infective diseases of CNS (cerebral tubercu- losis14, suppurative meningitis2, brain cysticercosis4) and demyelinating diseases (multiple sclerosis5, Guillain-Barre syndrome2) composed control group. The positive rate of viral antibody specificity index was Compared; the sensitivity and particularity of the viral antibody specificity index in the diagnosis of viral encephalitis was evaluated. The CSFC of two groups was studied, and the appearance of CSFC of viral encephalitis was investigated. The clinical feature of the two infective groups was investigated to find the difference. Used SPSS12.0 for data analysis; enumeration data was treated byχ~2 test , size of testα=0.05.
Result: 1 In the study group 6 of the 36 patients (17%) were herpes simplex virus encephalitis, 3 (8%) were Epstein- Barr virus encephalitis, 2(6 % ) were human cytomegalovirus encephalitis. In the control group 1 of the 27 patients got a positive result of antibody specificity index, the antibody was against Epstein-Barr virus. There was not overlapped positive result in the study group. The positive rate of viral antibody specificity index in study group was 31%, in the control group was 4%; the particularity of this method was 92%in the diagnosis of viral encephalitis.
2 Most of the two group patients had abnormal cerebrospinal fluid cytology, in the study group was 86%, in the control group was 78%. The cerebrospinal fluid cytology of the most viral encephalitis patients was lymphocytic reaction; the quantity of neutrophilic leukocyte stepped up at nonage in minority patients. The cerebrospinal fluid cytology of the 6 patients suffer from herpes simplex virus encephalitis was abnormal,and red blood cell was find in the cerebrospinal fluid in two of them. The cerebrospinal fluid cytology of 2 Epstein-Barr virus encephalitis patients and 2 human cytomegalovirus encephalitis patients was abnormal.
3 Some clinical data of the study group and another infective group were discrepant; the emotionai disturbance, meningeal irritation sign and electroencephalogram were discrepant obviously.
Conclusion: Viral antibody specificity index is a value for the intrathecal pathogen-specific antibody production. The pathogen-specific antibody is produced intrathecally after the viral infection in central nervous system when the index is above 1.5.This method has ideal sensitivity and particularity, so we should pay close attention to it. A continuative study with larger sample size and more kinds of virus maybe raise the total positive rate, so that we can get a more satisfactory sensitivity. As a cheap and convenient method it may be very helpful for the treatment and investigation of viral encephalitis. Epidemiology data and clinical situation is the foundation for diagnosis of viral encephalitis. Electroencephalogram and cerebrospinal fluid cytology are important auxiliary examination, they should not be ignored.
方法:临床诊断的病毒性脑炎患者36例,入院三天内留取血清和第一份脑脊液标本,第二到第三周留取第二份脑脊液标本。所有标本冻存于-20oC低温冰箱,分批进行检测。用德国欧蒙公司提供的ELISA试剂盒,半定量检测标本中病毒特异性抗体IgG相对浓度。实验中,血清稀释404倍,脑脊液稀释2倍;通过四个标准液绘制标准曲线,标本酶标检测结果代入标准曲线计算病毒特异性抗体IgG浓度。免疫检验室通过散射速率比浊法分别检测脑脊液和配对血清中IgG总量。脑脊液中病毒特异性抗体占脑脊液总IgG比例与血清中病毒特异性抗体占血清总IgG比例之间的比值,即CSF/血清相对比值CSQrel(抗体特异性指数);此比值大于1.5视为阳性。实验中检测单纯疱疹病毒1型(HSV-1),EB病毒(EBV),人类巨细胞病毒(HCMV);通过病毒抗体特异性指数的阳性结果建立病毒性脑炎的病原学诊断。实验设立中枢神经系统非病毒性感染性疾病患者(结核性脑膜炎14例,化脓性脑膜炎2例,脑囊虫病4例),脱髓鞘疾病患者(多发性硬化5例,吉兰-巴雷综合征2例)为对照组。对两组患者病毒抗体特异性指数阳性率进行比较,来评价病毒抗体特异性指数作为病原学诊断方法的敏感性和特异性。动态观察两组患者的脑脊液细胞学,对两组患者的脑脊液细胞学进行分析比较,进一步探讨病毒性脑炎的脑脊液细胞学表现。对研究组和对照感染组(结核性脑膜炎,化脓性脑膜炎,脑囊虫病)的部分临床资料进行比较,分析病毒感染与其它类型感染在临床表现上的差异。统计学分析采用SPSS12.0软件,计数资料采用χ2检验,检验水准α=0.05。
结果:1在研究组36例中通过病毒抗体特异性指数诊断为单纯疱疹病毒性脑炎的6例(17%),EB病毒性脑炎3例(8%),巨细胞病毒性脑炎2例(6%),总体阳性率为31%。对照组27例中有一例临床诊断为结核性脑膜炎,但检测中EB病毒抗体特异性指数为阳性。在研究组中未见到多种抗体重叠阳性出现。两组抗体特异性指数阳性率比较,研究组为31%,对照组为4%,(χ~2=5.578,P=0.018)。此种方法诊断病毒性脑炎的特异性为91.7%。
2两组的脑脊液细胞学都有很高的异常率,研究组为86%,对照组为78%,两组间脑脊液细胞学的异常率无统计学差异。病毒性脑炎患者脑脊液细胞学以淋巴细胞反应为主,少数病例在早期见到嗜中性粒细胞增高现象。6例诊断为单纯疱疹病毒性脑炎的患者脑脊液细胞学全部异常,其中2例患者脑脊液细胞学检查见到红细胞;2例EB病毒性脑炎和巨细胞病毒性脑炎患者脑脊液细胞学有异常,但未发现与病毒性脑炎脑脊液细胞学的一般表现存在差异。
3研究组与对照感染组的部分临床资料存在差异,其中精神异常、脑膜刺激征的出现率和脑电图的异常率差异明显。
结论:病毒抗体特异性指数,反映抗体在中枢神经系统局部合成的情况,此指标大于1.5提示特异性抗体在病毒感染中枢神经系统后由鞘内合成;此方法在病毒性脑炎的诊断中有着比较理想的敏感性和很高的特异性,其意义值得重视。继续扩大研究的样本量,并增加检测的病毒抗体的种类,有可能提高此种方法检测结果的总体阳性率,近而得到一个更令人满意的敏感性。作为一种廉价、快捷、方便的病原学诊断方法,有可能为病毒性脑炎的临床治疗和研究带来巨大的帮助。流行病学资料和临床表现是病毒性脑炎的诊断基础,脑电图检查和脑脊液细胞学检测是重要的辅助检查措施,在病毒性脑炎的诊断中绝对不能疏漏。
Objective: To evaluate the sensitivity and particularity of the antibody specificity index in the diagnosis of viral encephalitis. Expected to find a good method of etiological diagnosis for viral encephalitis,which is cheap, convenient and has ideal sensitivity and particularity . The level of the diagnosis of viral encephalitis was expected to elevate. Wish it is helpful for the treatment and investigation. The feature of CSFC (cerebrospinal fluid cytology) in the central nervous system disease was studied further.
Methods: Study group have 36 patients suffer from viral encephalitis which was clinical diagnosis. The serum and the first CSF sample were gathered in 3 days after they came in, the second CSF sample were gathered at the second or the third week. All the sample were preserved in cryogenic box at -20oC, and were treated in batch. The pathogen-specific antibody of the IgG class was quantitative in-vitor assayed by the ELISA test kit from EUROIMMUN Medizinische Labordiagnostika AG. In the assay, serum samples were diluted 1:404 in sample buffer, CSF samples were diluted 1:2 in sample buffer, standard curve was determined by the CSF calibrators(C A to C D), then the concentration of antibodies of IgG were obtained. The volume dose of the IgG was obtained from immunity laboratory by nephelometry. The quotient of the portion of pathogen-specific antibodies in total IgG of CSF and the portion of pathogen-specific antibodies in total IgG of serum is the relative CSF/serum quotient(CSQrel). A CSQrel above 1.5 is positive. In the study, the antibodies against HSV-1, EBV, HCMV were detected. A etiological diagnosis was made by the positive result. Total 27 patients suffer from others infective diseases of CNS (cerebral tubercu- losis14, suppurative meningitis2, brain cysticercosis4) and demyelinating diseases (multiple sclerosis5, Guillain-Barre syndrome2) composed control group. The positive rate of viral antibody specificity index was Compared; the sensitivity and particularity of the viral antibody specificity index in the diagnosis of viral encephalitis was evaluated. The CSFC of two groups was studied, and the appearance of CSFC of viral encephalitis was investigated. The clinical feature of the two infective groups was investigated to find the difference. Used SPSS12.0 for data analysis; enumeration data was treated byχ~2 test , size of testα=0.05.
Result: 1 In the study group 6 of the 36 patients (17%) were herpes simplex virus encephalitis, 3 (8%) were Epstein- Barr virus encephalitis, 2(6 % ) were human cytomegalovirus encephalitis. In the control group 1 of the 27 patients got a positive result of antibody specificity index, the antibody was against Epstein-Barr virus. There was not overlapped positive result in the study group. The positive rate of viral antibody specificity index in study group was 31%, in the control group was 4%; the particularity of this method was 92%in the diagnosis of viral encephalitis.
2 Most of the two group patients had abnormal cerebrospinal fluid cytology, in the study group was 86%, in the control group was 78%. The cerebrospinal fluid cytology of the most viral encephalitis patients was lymphocytic reaction; the quantity of neutrophilic leukocyte stepped up at nonage in minority patients. The cerebrospinal fluid cytology of the 6 patients suffer from herpes simplex virus encephalitis was abnormal,and red blood cell was find in the cerebrospinal fluid in two of them. The cerebrospinal fluid cytology of 2 Epstein-Barr virus encephalitis patients and 2 human cytomegalovirus encephalitis patients was abnormal.
3 Some clinical data of the study group and another infective group were discrepant; the emotionai disturbance, meningeal irritation sign and electroencephalogram were discrepant obviously.
Conclusion: Viral antibody specificity index is a value for the intrathecal pathogen-specific antibody production. The pathogen-specific antibody is produced intrathecally after the viral infection in central nervous system when the index is above 1.5.This method has ideal sensitivity and particularity, so we should pay close attention to it. A continuative study with larger sample size and more kinds of virus maybe raise the total positive rate, so that we can get a more satisfactory sensitivity. As a cheap and convenient method it may be very helpful for the treatment and investigation of viral encephalitis. Epidemiology data and clinical situation is the foundation for diagnosis of viral encephalitis. Electroencephalogram and cerebrospinal fluid cytology are important auxiliary examination, they should not be ignored.
引文
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27 邵新华,吴杰,汪梅先.小儿病毒性脑炎与抗病毒抗体IgM 的临床意义.湖南医学,2004,15,9:50-51
28 秦琴保,潘小平,李蒙燕,雷秀霞,陈少辉,杨银梅.脑 脊液单纯疱疹病毒和抗体及细胞学检查的意义. 实 用医学杂志, 2003,19,9:974-976
29 Lakeman FD, Koga J, Whitley RJ. Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex virus encephalitis. Infect Dis, 1987, 155:1172
30 董万利,徐培锡,许丽珍.用斑点免疫渗虑试验诊断单纯疱疹病毒性脑炎.中国神经免疫学和神经病学杂志,1997,4,4:221-223
31 Mitchell PS, Epsy MJ, Smith TF, et al. Laboratory diagnosis of central nervous system infection with herpes simplex virus by PCR performed with CSF specimens. Clin Microbiol, 1997,35,11:2873-2877
32 Tebas P, Nease RF, Storch GA. Use of the polymerase chain reaction in the diagnosis of herpes simplex encephalitis: a decision analysis model. Am J Med, 1998,105,287-295
33 Vahey M, Nau ME, Barrick S, et al. Performance of the Affymetrix genechip PRT440 platform forantiretroviral drug resistance genotype of human immunodeficiency virus type 1 cades and viral isolates with length polympirphisms. Clin Microbiol, 1999, 37, 8:2533-2537
34 Dopakta H.D., Schuy W.: Compact Epstein-Barr virus diagnosis based on a defined antigen mix and specific igA.Res.Virol.1996,147:53-66
35 Felgenhauer K, Beuche W. Labordiagnostik neurol- ogischer Erkrankungen.Georg Thieme Verlag, Stuttart, 1999,8,1
36 Reiber H. The hyperbolic function: a mathemation of the protein flux/CSF flow model for blood-CSF barrier funceion. J Neurol Sci , 1994, 126:243-245
37 沈霞.中枢神经系统疾病的免疫学检验.检验医学,2006,21,4:434-436
38 蒋莉,蔡方成.病毒性脑炎的诊断及鉴别诊断.小儿急救医学杂志,1998,5,1:3-5
39 张建,王得新,赵伟秦等.单纯疱疹病毒脑炎的临床研究.中风与神经疾病杂志,2002,19,6:350-352
40 Rantnlaiho T, Farkkila M, Vaheri A, etal. Acute enc- ehalitis from 1967 to 1991. Neurol Sci, 2001, 184, 2:169-177
1 Griffin DE, Hardwick JM. Regulatators of apoptosis on the road to persistent alphavirus infection. Annu Rev microl, 1997, 51, 563-592
2 何俊瑛, 何红彦, 孙伟等. 石家庄地区中枢神经系统感染的住院资料分析. 中华神经科杂志,2007,40,10: 671-674
3 Chaudhuri A , Kennedy P G E. Diagnosis and treatment of viral encephalitis. Postgrad. Med. 2002, 78: 575-583
4 李效兰,岳伟,张辰昊. 病毒性脑炎脑电图, CT, MRI 检 查阳性检出率对比分析.中国综合临床, 2004, 20, 7: 603-604
5 罗敏,肖家和.病毒性脑炎的 CT, MRI 诊断. 临床放射 学杂志,2000, 19, 3: 133-136
6 黄仲奎,邓德茂, 龙莉玲, 秦宇红. DWI 在散发性脑炎 与急性脑梗死鉴别诊断价值. 实用放射学杂志, 2005, 21, 2: 120-122
7 李富康,钟春梅,郭毅,付学军,马可夫.CT, MRI,EEG 对病毒性脑炎的诊断价值. 中国实用神经疾病杂志, 2006, 9,3:7-9
8 喻红霞. 脑电图检查在小儿病毒性脑炎诊治中的价 值.实用神经疾病杂志,2005, 8, 5: 87
9 张玉珍, 于志远, 李璐. 单纯疱疹病毒性脑炎的 EEG 及脑 CT 分析.山东医药,1999, 39, 13: 30
10 Simko JP, Caliendo AM, Hogle K, Versalovic J. Diffe- rences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) docu- mented by detection of HSV DNA.Clin Infect Dis, 2002,35,4:414-419
11 王蘋, 毕建忠. 42 例病毒性脑炎患者的脑脊液细胞 学特点与其临床分型分析.山东医药, 2004, 44, 22: 35-36
12 粟秀初,赵钢,杨毅宁. 单纯疱疹病毒性脑炎 30 例脑 脊液细胞学结果分析. 中国神经精神杂志, 1999, 25, 2: 108
13 何俊瑛,孔繁元,郭力. 临床脑脊液细胞学诊断. 河北 科技出版社.2007,8:131
14 黄刚,张昆南, 高幼奇等. 40 例病毒性脑膜脑炎脑脊 液细胞学观察.实用临床医学, 2006, 7,1: 49-50
15 唐金荣,侯熙德,王颖等.单纯疱疹病毒性脑炎脑脊液 细胞学诊断.中风与神经疾病杂志, 1998, 15,6:363- 364
16 Tang YW, Mitchell PS, Epsy MJ, et al. Molccular dia- gnosis of herpes simplex virus infection in the central nervous system. Jclin Microbiol, 1999,37, 2: 2127- 2136
17 李海波,常桂芬, 梁东等. 检测病毒性脑炎患儿脑脊 液中单纯疱疹病毒IgM抗体的临床应用. 吉林医学,2000,21,1:13-14
18 邵新华,吴杰, 汪梅先. 小儿病毒性脑炎与抗病毒抗 体 IgM 的临床意义. 湖南医学, 2004, 15, 9: 50-51
19 张辉,王廷骇,徐云鹤,樊征鸿. 病毒性脑炎患儿肠道 病毒特异性 IgM 抗体快速检测.中国实用儿科杂志 1999, 14, 11: 659-660
20 秦琴保, 潘小平, 李蒙燕等. 脑脊液单纯疱疹病毒 和抗体及细胞学检查的意义. 实用医学杂志, 2003, 19, 9: 974-976
21 Lakeman FD,Koga J,Whitley RJ.Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex virus encephalitis.Infect Dis, 1987, 155: 1172
22 董万利,徐培锡, 许丽珍. 用斑点免疫渗虑试验诊断 单纯疱疹病毒性脑炎. 中国神经免疫学和神经病学 杂志, 1997, 4, 4: 221-223
23 Mitchell PS, Epsy MJ, Smith TF, et al. Laboratory dia- gnosis of central nervous system infection with herpes simplex virus by PCR performed with CSF specimens . Clin Microbiol, 1997, 35, 11: 2873-2877
24 Tebas P, Nease RF, Storch GA. Use of the polymerase chain reaction in the diagnosis of herpes simplex ence- phalitis: a decision analysis model. Am J Med, 1998, 105, 287-295
25 Vahey M, Nau ME, Barrick S, et al. Performance ofthe Affymetrix genechip PRT440 platform for antiret- roviral drug resistance genotype of human immunod- eficiency virus type1 clades and viral isolates with length polympirphisms. Clin Microbiol, 1999, 37, 8: 2533-2537
26 张芙蓉,张秋萍. 病毒性脑炎患儿脑脊液白细胞介素 和肿瘤坏死因子-α变化及意义.华中医学杂志,2005, 29, 1: 23-24
27 王振海,吴庆秋,吕洁, 谢鹏, 孔繁元. 病毒性脑炎患 者 S-100 蛋白浓度与临床的相关性. 中华微生物学 和免疫学杂志,2006, 26, 3: 263-266
28 李光乾, 焦颖, 林忠东等. 病毒性脑炎患儿血清和 脑脊液神经生化标志物的测定. 中华传染病杂志, 2004, 22, 6: 398-401
29 郑庭亮, 张金池, 林文杰等.脑脊液乳酸脱氢酶,β2- 微球蛋白检测对小儿化脓性脑炎与病毒性脑炎的 鉴别诊断.国际检验医学杂志,2006 , 27, 4: 307-308
2 Hinson VK, Tyor WR. Update of viral encephalitis; Inflammatory diseases; Curr. Opin Neurol. 2001, 14: 369-374
3 孟家眉.神经内科临床新进展.北京出版社,1994: 288
4 潘小玲, 梁国栋. 病毒性脑炎. 中华试验和临床病毒学杂志,2006,20,3:288-291
5 王得新.病毒性脑膜炎.见:王得新,主编.神经病毒学-基础与临床 . 第 1 版 ,北 京: 人 民 卫 生 出 版 社 , 2004,369-372
6 赵宇红,申昆玲.病毒脑炎病 原学及诊断技术研究进展.医学综述,2004,10,4:232-234
7 Tsuchiya K, Katase S, Yoshino A, et al. Diffusion weig- hed MR imaging of enc ephalitis. AJR, 1999, 173, 4:1097-1099
8 Lim CC T,Lee KE,Lee WL,et al Nipah virus enc- ephalitis serial MR study of an emerging disease.Radiology, 2002,222,11:219-226
9 王得新.病毒病的发病机制和持续感染.见:王得新, 主编,神经病毒学-基础与临床.第 1 版,北京:人民 卫 生出版社.2004:42-61
10 徐平,谢鹏.中枢神经病毒感染的病理及生物化学机 制.中华神经医学杂志,2003,2,4:315-317
11 Griffin DE, Hardwick JM. Regulatators of apoptosis on the road to persistent alphavirus infection. Annu Rev microl, 1997,51,563-592
12 Chaudhuri A , Kennedy P G E. Diagnosis and treat- ment of viral encephalitis. Postgrad Med: 2002, 78: 575-583
13 李效兰,岳伟,张辰昊.病毒性脑炎脑电图,CT,MRI 检查 阳 性 检 出 率 对 比 分 析 . 中 国 综 合 临床,2004,20,7:603-604s
14 罗敏,肖家和.病毒性脑炎的 CT, MRI 诊断.临床放射学杂 志, 2000,19,3:133-136
15 黄仲奎,邓德茂,龙莉玲,秦宇红.DWI 在散发性脑炎与 急 性 脑 梗 死 鉴 别 诊 断 价 值 . 实 用 放 射 学 杂志,2005,21,2:120-122
16 李富康,钟春梅,郭毅,付学军,马可夫.CT, MRI,EEG 对病毒性脑炎的诊断价值.中国实用神经疾病杂志, 2006,9,3:7-9
17 喻红霞.脑电图检查在小儿病毒性脑炎诊治中的价值.实用神经疾病杂志,2005,8,5:87
18 张玉珍,于志远,李璐.单纯疱疹病毒性脑炎的EEG及脑 CT 分析.山东医药,1999,39,13:30
19 Simko JP,Caliendo AM,Hogle K,Versalovic J. Dif- ferences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA. Clin Infect Dis. 2002,35,4:414-419
20 王蘋,毕建忠.42 例病毒性脑炎患者的脑脊液细胞学特点与其临床分型分析.山东医药,2004,44,22:35-36
21 粟秀初,赵钢,杨毅宁.单纯疱疹病毒性脑炎30例脑脊液 细 胞 学 结 果 分 析 . 中 国 神 经 精 神 杂志,1999,25,2:108
22 何俊瑛,孔繁元,郭力.临床脑脊液细胞学诊断.河北科技出版社.2007,8:131
23 黄刚,张昆南,高幼奇,曹文锋,吴晓敏.40 例病毒性脑膜 脑 炎 脑 脊 液 细 胞 学 观 察 . 实 用 临 床 医学,2006,7,1:49-50
24 唐金荣,侯熙德,王颖,陈光辉,吴文涛.单纯疱疹病毒性脑炎脑脊液细胞学诊断.中风与神经疾病杂志,1998,15,6:363-364
25 Tang YW, Mitchell PS, Epsy MJ, et al. Molccular diagnosis of herpes simplex virus infection in the central nervous system. Jclin Microbiol, 1999, 37,2:2127-2136
26 李海波,常桂芬,梁东,梁志学.检测病毒性脑炎患儿脑脊液中单纯疱疹病毒 IgM 抗体的临床应用.吉林医学,2000,21,1:13-14
27 邵新华,吴杰,汪梅先.小儿病毒性脑炎与抗病毒抗体IgM 的临床意义.湖南医学,2004,15,9:50-51
28 秦琴保,潘小平,李蒙燕,雷秀霞,陈少辉,杨银梅.脑 脊液单纯疱疹病毒和抗体及细胞学检查的意义. 实 用医学杂志, 2003,19,9:974-976
29 Lakeman FD, Koga J, Whitley RJ. Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex virus encephalitis. Infect Dis, 1987, 155:1172
30 董万利,徐培锡,许丽珍.用斑点免疫渗虑试验诊断单纯疱疹病毒性脑炎.中国神经免疫学和神经病学杂志,1997,4,4:221-223
31 Mitchell PS, Epsy MJ, Smith TF, et al. Laboratory diagnosis of central nervous system infection with herpes simplex virus by PCR performed with CSF specimens. Clin Microbiol, 1997,35,11:2873-2877
32 Tebas P, Nease RF, Storch GA. Use of the polymerase chain reaction in the diagnosis of herpes simplex encephalitis: a decision analysis model. Am J Med, 1998,105,287-295
33 Vahey M, Nau ME, Barrick S, et al. Performance of the Affymetrix genechip PRT440 platform forantiretroviral drug resistance genotype of human immunodeficiency virus type 1 cades and viral isolates with length polympirphisms. Clin Microbiol, 1999, 37, 8:2533-2537
34 Dopakta H.D., Schuy W.: Compact Epstein-Barr virus diagnosis based on a defined antigen mix and specific igA.Res.Virol.1996,147:53-66
35 Felgenhauer K, Beuche W. Labordiagnostik neurol- ogischer Erkrankungen.Georg Thieme Verlag, Stuttart, 1999,8,1
36 Reiber H. The hyperbolic function: a mathemation of the protein flux/CSF flow model for blood-CSF barrier funceion. J Neurol Sci , 1994, 126:243-245
37 沈霞.中枢神经系统疾病的免疫学检验.检验医学,2006,21,4:434-436
38 蒋莉,蔡方成.病毒性脑炎的诊断及鉴别诊断.小儿急救医学杂志,1998,5,1:3-5
39 张建,王得新,赵伟秦等.单纯疱疹病毒脑炎的临床研究.中风与神经疾病杂志,2002,19,6:350-352
40 Rantnlaiho T, Farkkila M, Vaheri A, etal. Acute enc- ehalitis from 1967 to 1991. Neurol Sci, 2001, 184, 2:169-177
1 Griffin DE, Hardwick JM. Regulatators of apoptosis on the road to persistent alphavirus infection. Annu Rev microl, 1997, 51, 563-592
2 何俊瑛, 何红彦, 孙伟等. 石家庄地区中枢神经系统感染的住院资料分析. 中华神经科杂志,2007,40,10: 671-674
3 Chaudhuri A , Kennedy P G E. Diagnosis and treatment of viral encephalitis. Postgrad. Med. 2002, 78: 575-583
4 李效兰,岳伟,张辰昊. 病毒性脑炎脑电图, CT, MRI 检 查阳性检出率对比分析.中国综合临床, 2004, 20, 7: 603-604
5 罗敏,肖家和.病毒性脑炎的 CT, MRI 诊断. 临床放射 学杂志,2000, 19, 3: 133-136
6 黄仲奎,邓德茂, 龙莉玲, 秦宇红. DWI 在散发性脑炎 与急性脑梗死鉴别诊断价值. 实用放射学杂志, 2005, 21, 2: 120-122
7 李富康,钟春梅,郭毅,付学军,马可夫.CT, MRI,EEG 对病毒性脑炎的诊断价值. 中国实用神经疾病杂志, 2006, 9,3:7-9
8 喻红霞. 脑电图检查在小儿病毒性脑炎诊治中的价 值.实用神经疾病杂志,2005, 8, 5: 87
9 张玉珍, 于志远, 李璐. 单纯疱疹病毒性脑炎的 EEG 及脑 CT 分析.山东医药,1999, 39, 13: 30
10 Simko JP, Caliendo AM, Hogle K, Versalovic J. Diffe- rences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) docu- mented by detection of HSV DNA.Clin Infect Dis, 2002,35,4:414-419
11 王蘋, 毕建忠. 42 例病毒性脑炎患者的脑脊液细胞 学特点与其临床分型分析.山东医药, 2004, 44, 22: 35-36
12 粟秀初,赵钢,杨毅宁. 单纯疱疹病毒性脑炎 30 例脑 脊液细胞学结果分析. 中国神经精神杂志, 1999, 25, 2: 108
13 何俊瑛,孔繁元,郭力. 临床脑脊液细胞学诊断. 河北 科技出版社.2007,8:131
14 黄刚,张昆南, 高幼奇等. 40 例病毒性脑膜脑炎脑脊 液细胞学观察.实用临床医学, 2006, 7,1: 49-50
15 唐金荣,侯熙德,王颖等.单纯疱疹病毒性脑炎脑脊液 细胞学诊断.中风与神经疾病杂志, 1998, 15,6:363- 364
16 Tang YW, Mitchell PS, Epsy MJ, et al. Molccular dia- gnosis of herpes simplex virus infection in the central nervous system. Jclin Microbiol, 1999,37, 2: 2127- 2136
17 李海波,常桂芬, 梁东等. 检测病毒性脑炎患儿脑脊 液中单纯疱疹病毒IgM抗体的临床应用. 吉林医学,2000,21,1:13-14
18 邵新华,吴杰, 汪梅先. 小儿病毒性脑炎与抗病毒抗 体 IgM 的临床意义. 湖南医学, 2004, 15, 9: 50-51
19 张辉,王廷骇,徐云鹤,樊征鸿. 病毒性脑炎患儿肠道 病毒特异性 IgM 抗体快速检测.中国实用儿科杂志 1999, 14, 11: 659-660
20 秦琴保, 潘小平, 李蒙燕等. 脑脊液单纯疱疹病毒 和抗体及细胞学检查的意义. 实用医学杂志, 2003, 19, 9: 974-976
21 Lakeman FD,Koga J,Whitley RJ.Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex virus encephalitis.Infect Dis, 1987, 155: 1172
22 董万利,徐培锡, 许丽珍. 用斑点免疫渗虑试验诊断 单纯疱疹病毒性脑炎. 中国神经免疫学和神经病学 杂志, 1997, 4, 4: 221-223
23 Mitchell PS, Epsy MJ, Smith TF, et al. Laboratory dia- gnosis of central nervous system infection with herpes simplex virus by PCR performed with CSF specimens . Clin Microbiol, 1997, 35, 11: 2873-2877
24 Tebas P, Nease RF, Storch GA. Use of the polymerase chain reaction in the diagnosis of herpes simplex ence- phalitis: a decision analysis model. Am J Med, 1998, 105, 287-295
25 Vahey M, Nau ME, Barrick S, et al. Performance ofthe Affymetrix genechip PRT440 platform for antiret- roviral drug resistance genotype of human immunod- eficiency virus type1 clades and viral isolates with length polympirphisms. Clin Microbiol, 1999, 37, 8: 2533-2537
26 张芙蓉,张秋萍. 病毒性脑炎患儿脑脊液白细胞介素 和肿瘤坏死因子-α变化及意义.华中医学杂志,2005, 29, 1: 23-24
27 王振海,吴庆秋,吕洁, 谢鹏, 孔繁元. 病毒性脑炎患 者 S-100 蛋白浓度与临床的相关性. 中华微生物学 和免疫学杂志,2006, 26, 3: 263-266
28 李光乾, 焦颖, 林忠东等. 病毒性脑炎患儿血清和 脑脊液神经生化标志物的测定. 中华传染病杂志, 2004, 22, 6: 398-401
29 郑庭亮, 张金池, 林文杰等.脑脊液乳酸脱氢酶,β2- 微球蛋白检测对小儿化脓性脑炎与病毒性脑炎的 鉴别诊断.国际检验医学杂志,2006 , 27, 4: 307-308