NMDAR抗体水平对脑炎的鉴别诊断及病情评估作用

发布时间：2018-05-24 21:32

本文选题：抗NMDAR脑炎 + 病毒性脑炎　；参考：《重庆医科大学》2017年硕士论文

【摘要】：研究背景:自身免疫性脑炎是泛指一组由自身免疫抗体介导的神经功能损伤的疾病,是迄今较为新型的脑炎分类。10年前Dalmau等人首先发现并报道了卵巢畸胎瘤相关的副肿瘤性抗N-甲基-D-天冬氨酸受体脑炎,该报道称的上是自身免疫脑炎范畴的转折点。随着这一敲门砖似的研究成果及抗体检测深入,近年来各种新型的自身免疫性脑炎被陆续发现并报道,主要可分为两大类:抗神经元细胞内抗原抗体、抗神经细胞表面/突触蛋白抗体。而NMDAR脑炎是自身免疫性脑炎中最常见、最典型的类型,约占自身免疫性脑炎患者的80%,好发于青年女性和儿童,与畸胎瘤关系较密切,与其他恶性肿瘤相关性较小。这种亚型的自身免疫性脑炎是由免疫球蛋白G攻击神经元细胞表面的N-甲基-D-天冬氨酸受体谷氨酸的N1亚基使神经元产生炎症反应,导致神经细胞功能紊乱而产生一系列的临床症状,主要可表现为发热、头痛等前驱症状、精神行为异常、不自主运动、癫痫、近期记忆力下降、自主神经功能紊乱等。如果能够早期治疗,这种功能紊乱是可逆的。但是如果没有的到及时的治疗,长期的炎症反应和N-甲基-D-天冬氨酸介导的谷氨酸兴奋性毒性可能造成神经元细胞永久性破坏。对于NMDAR脑炎患者而言,早期的诊断及治疗可拥有相对较好的预后,可以恢复到患病前基本生活功能状态,而且后续复查影像学检查既往异常的病灶也可能会完全吸收、消失。所以早期的诊断及治疗对于抗NMDAR脑炎患者而言极其重要,直接关系的抗NMDAR脑炎患者的治疗效果及预后。脑炎的主要致病原因可分为两大类,即自身免疫性和感染性。由于自身免疫性脑炎相关抗体检测在国内可能比较容易得到,近年来发现并确诊的自身免疫性脑炎的病例量大幅度上升,可能会给临床医生带来一种错觉认为自身免疫性脑炎比感染性脑炎更多见,这可能是因为感染性的病原体检测尤其是病毒PCR检测的不全面或技术限制,导致了病毒性脑炎的诊断不足。事实上自身免疫性脑炎约占脑炎的10%-20%,较病毒性脑炎患病比例低。因此,对于自身免疫性脑炎和病毒性脑炎早期的鉴别诊断就显得格外重要,直接关系到治疗方案的制定、治疗效果及患者远期的预后。目的:抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate recep-tor,NMDAR)脑炎是自身免疫性脑炎中最常见的类型,临床表现多样化,好发于青年女性及儿童;病毒脑炎为临床上常见脑炎类型,临床特点可与抗NMDAR脑炎相似,本文主要探讨NMDAR抗体水平对抗NMDAR抗体脑炎和病毒性脑炎的鉴别诊断及抗NMDAR抗体水平对抗NMDAR脑炎病情评估作用。方法:回顾性分析重庆医科大学附属第一医院2014年3月-2016年3月期间诊断为抗NMDAR脑炎和病毒性脑炎患者。其中抗NMDAR脑炎患者53例为研究组(11例重症患者和42例普通患者),病毒性脑炎患者22例作为对照组。对两组患者的一般情况、临床资料及血清、脑脊液的NMDAR抗体水平进行分析。结果:1、抗NMDAR脑炎患者中男性21例、女性32例,平均(45.12±10.13)岁;22例病毒性脑炎中男性7例、女性15例,平均年龄(47.22±12.49)岁;两组间在性别与平均年龄差异不具有统计学意义。2、抗NMDAR脑炎患者中有前驱感染史12例(22.6%)、发热24例(45.3%),意识障碍27例(50.9%)、癫痫发作32例(60.4%)、不自主运动21例(39.6%)、头痛23例(43.4%)、精神行为异常39例(78.1%)。病毒性脑炎患者中有前驱感染史14例(63.6%)、发热21例(95.5%),意识障碍3例(13.6%)、癫痫发作1例(4.6%)、不自主运动2例(9.1%)、头痛14例(63.6%)、精神行为异常0例(0)。抗NMDAR脑炎相比病毒性脑炎患者在以下临床表现中存在显著差异:有前驱感染史(X2=11.54,P=0.00)、发热(X2=16.31,P=0.00)、意识障碍(X2=9.02,P=0.00)、癫痫发作(X2=19.67,P=0.00)、不自主运动(X2=6.82,P=0.00)、精神异常(X2=27.44,P=0.00)。3、抗NMDAR脑炎组患者血清中抗NMDAR抗体浓度平均含量为14.03±5.62ng/ml、脑脊液中抗NMDAR抗体浓度平均含量为29.31±4.37ng/ml;病毒性脑炎组患者血清中抗NMDAR抗体浓度平均含量为3.94±2.97ng/ml、脑脊液中抗NMDAR抗体浓度平均含量为12.34±3.19ng/ml。两组血清(t=7.95,P=0.00)、脑脊液(t=16.46,P=0.00)中NMDAR抗体含量差异显著,且均脑脊液含量显著高于血清含量;4、11例抗NMDAR脑炎重症患者血清中抗NMDAR抗体浓度为高水平者9例、脑脊液中中抗NMDAR抗体浓度为高水平者10例,;42例抗NMDAR脑炎普通组患者血清中抗NMDAR抗体浓度为高水平者2例、脑脊液中抗NMDAR抗体浓度为高水平者2例。抗NMDAR脑炎重症和普通患者血清(X2=31.47,P=0.00)、脑脊液(X2=36.94,P=0.00)中NMDAR抗体高和低水平构成的差异有统计学意义。结论:1、抗NMDAR脑炎和病毒性脑炎患者在临床表现上存在一定差别,且存在统计学意义。前驱感染史、发热、意识障碍、癫痫发作、不自主运动、精神异常多见于自身免疫性脑炎患者。2、抗NMDAR脑炎患者的抗NMDAR抗体浓度均高于病毒性脑炎患者;且两组患者脑脊液的抗NMDAR抗体浓度均较血清中抗NMDAR抗体浓度高。提示抗NMDAR抗体在脑脊液中更为敏感,且血清、脑脊液中NMDAR抗体浓度和具体水平可作为鉴别诊断要点。3、抗NMDAR脑炎重症患者的血清及脑脊液中抗NMDAR抗体浓度较抗NMDAR脑炎普通患者高,且抗体浓度差异存在统计学意义,提示血清、脑脊液中抗NMDAR抗体水平越高,病情可能越严重。
[Abstract]:Background: autoimmune encephalitis is a group of diseases characterized by neurologic impairment mediated by autoantibodies. It is a new type of encephalitis that Dalmau et al..10 years ago first discovered and reported the paraneoplastic anti N- methyl -D- aspartate receptor encephalitis associated with ovarian teratoma. This report is called the autoimmune brain. In recent years, a variety of new autoimmune encephalitis has been discovered and reported in succession, with two major categories: anti neuronal cell antigen antibody, anti nerve cell surface / synaptic protein antibody, and NMDAR encephalitis is the most important of autoimmune encephalitis. The most common, typical type, about 80% of the patients with autoimmune encephalitis, is more likely to occur in young women and children, closely related to teratoma and less associated with other malignant tumors. This subtype of autoimmune encephalitis is the N1 subunit of the immunoglobulin G that attacks the N- methyl -D- aspartic acid receptor of the neuron cell surface. An inflammatory response to a neuron resulting in a disorder of the nerve cell to produce a series of clinical symptoms, such as fever, headache and other precursory symptoms, abnormal mental behavior, involuntary movement, epilepsy, recent memory decline, and autonomic nervous dysfunction. If fruit can be treated early, this disorder is reversible. But such as Chronic treatment, chronic inflammatory response and N- methyl -D- aspartic glutamic acid induced excitotoxicity may cause permanent damage to neuron cells. For patients with NMDAR encephalitis, early diagnosis and treatment can have a relatively good prognosis and can be restored to the basic living condition before the disease. The early diagnosis and treatment are extremely important for the patients with anti NMDAR encephalitis, and the direct relation to the treatment effect and prognosis of anti NMDAR encephalitis patients. The main causes of encephalitis can be divided into two categories: autoimmune and infectious. The detection of autoimmune encephalitis related antibodies may be easier to be obtained in China. In recent years, the number of cases of autoimmune encephalitis found and confirmed has risen substantially. It may bring a illusions to clinicians and think that autoimmune encephalitis is more common than infectious encephalitis, which can be attributed to the detection of infectious pathogens. In fact, autoimmune encephalitis is about 10%-20% of encephalitis, which is lower than viral encephalitis. Therefore, the early differential diagnosis of autoimmune encephalitis and viral encephalitis is particularly important, which is directly related to the system of treatment. Objective: Anti N- methyl -D- aspartic acid receptor (N-methyl-D-aspartate recep-tor, NMDAR) encephalitis is the most common type of autoimmune encephalitis, and its clinical manifestations are diversified in young women and children; viral encephalitis is a common type of clinical encephalitis, and the clinical characteristics can be associated with anti NMDAR encephalitis. Similarly, this paper mainly discusses the differential diagnosis of NMDAR antibody level against NMDAR antibody encephalitis and viral encephalitis and the evaluation of anti NMDAR antibody level against NMDAR encephalitis. Methods: a retrospective analysis of the diagnosis of anti NMDAR encephalitis and viral encephalitis in the First Affiliated Hospital of Chongqing Medical University during the year of -2016 in March 2014. 53 cases of anti NMDAR encephalitis were studied in the study group (11 cases of severe and 42 cases) and 22 cases of viral encephalitis as a control group. The general situation, clinical data and serum and cerebrospinal fluid NMDAR antibody levels in two groups were analyzed. Results: 1, 21 men and 32 women with anti NMDAR encephalitis, average (45.12 + 10.13) years of age; 22 cases. There were 7 male and 15 women in viral encephalitis, with an average age of (47.22 + 12.49) years. The difference between sex and average age was not statistically significant in two groups.2, 12 cases (22.6%), 24 fever (45.3%), 27 cases of consciousness disorder (50.9%), epileptic seizures (60.4%), autonomic movement and headache cases in the patients with anti NMDAR encephalitis. (43.4%) 39 cases of abnormal mental behavior (78.1%). There were 14 cases of predominant infection (63.6%), 21 fever (95.5%), 3 cases of disturbance of consciousness (13.6%), 1 cases of epileptic seizures (13.6%), 1 cases of epileptic seizures, 1 cases (9.1%), headache 14, and abnormality of sperm deity. The following clinical manifestations of anti NMDAR encephalitis were compared with those of viral encephalitis. There were significant differences: X2=11.54 (P=0.00), fever (X2=16.31, P=0.00), X2=9.02 (P=0.00), epileptic seizures (X2=19.67, P=0.00), involuntary movement (X2=6.82, P=0.00), and psychosis (X2=27.44, P=0.00). The average concentration of anti serum antibody in the serum of anti cerebrospinal meningitis group was 14.03 +. The average concentration of MDAR antibody was 29.31 + 4.37ng/ml, the average concentration of anti NMDAR antibody in the serum of the patients with viral encephalitis was 3.94 + 2.97ng/ml, the average concentration of anti NMDAR antibody in the cerebrospinal fluid was 12.34 + 3.19ng/ml. two groups (t=7.95, P=0.00), and the difference of NMDAR antibody in the cerebrospinal fluid (t=16.46, P=0.00) was significant, and the cerebrospinal fluid was all cerebrospinal fluid The content of the serum anti NMDAR antibody in the 4,11 patients with NMDAR encephalitis was high in 9 cases, and in the middle of the cerebrospinal fluid, the concentration of anti NMDAR antibody was high in 10 cases, and in the 42 patients with NMDAR encephalitis, the concentration of anti NMDAR antibody in the serum was high and the anti NMDAR antibody in the cerebrospinal fluid was high. There were 2 cases. There were significant differences in the high and low level of NMDAR antibodies in the serum (X2=31.47, P=0.00) and cerebrospinal fluid (X2=36.94, P=0.00) of the patients with NMDAR encephalitis and common patients. Conclusion: 1, there are some differences in the clinical manifestations of the patients with anti NMDAR encephalitis and viral encephalitis, and there are statistical significance. Obstruction, epileptic seizures, involuntary movement, abnormal psychosis in autoimmune encephalitis patients.2, anti NMDAR encephalitis patients with anti NMDAR antibody concentration is higher than viral encephalitis patients, and the two groups of cerebrospinal fluid anti NMDAR antibody concentration is higher than the serum NMDAR antibody concentration. Suggesting that anti NMDAR antibody in cerebrospinal fluid more sensitive, and blood The concentration and specific level of NMDAR antibody in cerebrospinal fluid can be used as the key point of differential diagnosis.3. The anti NMDAR antibody concentration in serum and cerebrospinal fluid of patients with anti NMDAR encephalitis is higher than that of anti NMDAR encephalitis, and the difference of antibody concentration is statistically significant. It suggests that the higher the level of anti NMDAR antibody in the cerebrospinal fluid, the more serious the disease may be.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.9

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