可能为双硫仑样反应继发吉兰-巴雷综合征1例报道并文献复习

双硫仑样反应指在一定时间范围内,机体同时吸收乙醇及双硫仑药物后,导致体内乙醛、多巴胺代谢障碍的中毒反应,多表现为面部潮红、恶心呕吐、头晕头痛,严重者可致意识丧失、休克等[1]。而吉兰-巴雷综合征(Guillain‐Barrésyndrome)为一类免疫介导的急性炎性周围神经病,主要表现为多发脊神经根和周围神经损害[2]。吉兰-巴雷综合征的确切病因未明,主要有感染(空肠弯曲菌等)、免疫、接种疫苗等。但双硫仑样反应继发吉兰-巴雷综合征的病例国内外文献未见报道。现将近期我院收治的1例可能为双硫仑样反应继发吉兰-巴雷综合征患者的诊治情况汇报如下。     

头面部带状疱疹并发吉兰-巴雷综合征1例报告

<正>吉兰-巴雷综合征(GBS),是一种以急性对称性弛缓性肢体瘫痪为主要临床表现的自身免疫介导的周围神经病~([1])。典型的病理改变是周围神经组织中小血管周围淋巴细胞、巨噬细胞浸润以及神经纤维的脱髓鞘,严重时将出现继发性轴突变性。GBS发病的诱因主要是呼吸道和(或)胃肠道感染,2/3的病例出现上呼吸道感染或腹泻的症状~([2])。常见的前驱感染病原菌:空肠弯曲菌(CJ)、巨细胞病毒(CMV)、EB病毒(EBV)、单纯疱疹病毒(HSV)、风     

急性运动轴索性神经病的研究进展

急性运动轴索性神经病(AMAN)是吉兰-巴雷综合征(GBS)的主要亚型之一,与GBS主要亚型急性炎症性脱髓鞘性多发性神经病(AIDP)在临床表现、免疫病理生理机制、神经电生理检查、血清学抗体等方面均有不同。本文就AMAN相关研究进展做一综述。     

吉兰巴雷综合征的诊断与治疗

吉兰巴雷综合征(Guillain-Barrésyndrome,GBS)是一种急性发病,单时相、自限性免疫介导的周围神经病,在临床上主要表现为四肢特别是下肢弛缓性瘫,感觉障碍和自主神经功能障碍,也常累及脑神经。目前认为GBS包括,AIDP、急性运动性轴     

吉兰-巴雷综合征患者的流行病学特点及其预后:5年254例资料回顾

目的:回顾分析各型吉兰-巴雷综合征患者的临床特征及随访结果,为该病的合理治疗提供依据。方法:①选择2000-01/2005-01在哈尔滨医科大学第一临床医学院收治的吉兰-巴雷综合征患者254例男154例,女100例,平均(35±19)岁;符合Asbury和美国神经病学会制订的急慢性吉兰-巴雷综合征诊断标准的病历资料。②将全部病例的年龄、性别、发病月份、前驱病史、发病至高峰期及住院时间、首发症状、运动症状、感觉症状、波及颅神经、植物神经情况、辅助检查、治疗、随访等均列入Excel病例统计表进行分析统计。并根据吉兰-巴雷综合征电生理记载和临床表现,结合各型诊断标准对资料较为完整者进行分型。比较各型吉兰-巴雷综合征患者年龄、性别分布情况,发病月份分布,前驱病史,临床表现、实验室检查、用药情况和康复特点。③计数资料统计描述采用数字或率形式表示,计量资料以x±s表示,组间计量结果差异比较采用t检验。结果:①分型:经典吉兰-巴雷综合征即急性炎症性多发性神经病89例、吉兰-巴雷综合征变异型急性运动轴索型神经病32例、未分型急性炎症性多发性神经病或急性运动轴索型神经病72例、Fisher综合征14例、慢性吉兰-巴雷综合征34例、复发型吉兰-巴雷综合征5例、全植物神经功能不全3例。②年龄、性别分布:在各型中性别分布大部分为男多于女,仅复发性和植物神经型吉兰-巴雷综合征女>男。慢性吉兰-巴雷综合征及复发型吉兰-巴雷综合征患者年龄明显高于急性炎症性多发性神经病、急性运动轴索型神经病患者(P<0.05～0.01)。③发病月份分布:7,9,10月为吉兰-巴综合征发病高峰。④前驱病史:慢性吉兰-巴雷综合征有病前感染史比例(25%)明显低于急性吉兰-巴雷综合征(53.3%)。⑤临床表现:93%以上患者以四肢无力为主要症状;重者患者都迅速出现肢体瘫痪,需要辅助呼吸。⑥实验室检查结果:周围运动神经传导速度减慢为最主要神经电生理改变(72.4%),脑脊液常规检查可见蛋白-细胞分离现象(56.5%)。⑦治疗:目前吉兰-巴雷综合征病因治疗如应用静脉注射免疫球蛋白(39.0%)、血浆交换(2.36%)和激素治疗(30.7%),与1997/1999流行病学调查时(35.0%)相比静脉注射免疫球蛋白比例有上升趋势,而采用激素治疗所占比例(45%)有下降趋势。慢性吉兰-巴雷综合征患者中97%应用激素,而对激素反应好的占88.2%。⑧随访:早期静脉注射免疫球蛋白有利于病情早日康复,效果优于激素和单纯应用神经营养药物治疗。结论:①吉兰-巴雷综合征患者中男多于女。慢性吉兰-巴雷综合征及复发型吉兰-巴雷综合征患者年龄偏大。②7,9,10月为吉兰-巴雷综合征发病高峰月份。③急性吉兰-巴雷综合征患者有病前多有感染史。④治疗急性吉兰-巴雷综合征,应该在支持治疗基础上减少激素应用,提高静脉注射免疫球蛋白或血浆交换应用比例。而慢性吉兰-巴雷综合征应该继续应用激素治疗。⑤早期给予吉兰-巴雷综合征患者免疫球蛋白治疗,更有利于患者恢复健康。     

吉兰巴雷综合征患者的神经功能障碍特点:62例分析

背景:吉兰巴雷综合征(Guillainbarresyhdrome,GBS)又称急性炎症性脱髓鞘性多发性神经病,是以周围神经和神经根的脱髓鞘及小血管周围淋巴细胞及巨噬细胞的炎性反应为病理特点的自身免疫病。可见于任何年龄,但以青壮年男性多见,四季均有发病,夏,秋季节多见,起病呈急性或亚急性,少数起病较缓慢。目的:了解吉兰巴雷综合征患者的神经功能障碍特点及临床特点,为康复介入提供临床依据。设计:回顾性分析。单位:连云港市第一人民医院神经内科,苏州大学附属第一医院神经内科。对象:苏州大学附属第一医院1995-01/2002-07收治的吉兰巴雷综合征患者共62…     

空肠弯曲菌感染致人畜共患周围神经病的病原学分析

目的：寻找格林-巴利综合征(GBS)的病因及抗体检测。方法：对GBS患儿及其家庭成员和家禽家畜进行流行病学调查，分离培养大便中的空肠弯曲菌(CJ)和质粒分析及抗体测定。结果：10例GBS患儿中发现4例与CJ感染有关的人畜共患的周围神经病，分别在家禽家畜肢体瘫痪后1～3w出现GBS表现，大便培养CJ均为阴性，CJ抗体全部阳性；患者家禽家畜6份粪便CJ培养有5例阳性，血清抗体均阳性。结论：空肠弯曲菌感染可引起格林-巴利综合征，防止CJ感染是降低GBS发生的重要措施。     

抗体阳性的咽-颈-臂变异型吉兰-巴雷综合征1例

<正>吉兰-巴雷综合征(Guillain-Barrésyndrome,GBS)是一种急性周围神经病。80%～85%表现为急性炎性脱髓鞘性多发性神经病^[1]。咽-颈-臂(pharyngeal-cervical-brachial,PCB)变异型为GBS的一种特殊亚型,约占所有GBS的3%^[2],表现为快速进行性的咽喉、颈肩部及上肢肌肉无力。     

自主神经功能不全为主的吉兰-巴雷综合征9例临床分析

吉兰一巴雷综合征（Guillain—Barresyndrome．GBS）或急性炎症性脱髓鞘性多发神经病是一种自身免疫性周围神经病,常累及脑神经,主要病理改变为周围神经组织小血管淋巴细胞、巨噬细胞浸润,神经纤维脱髓鞘,严重可继发轴突变性[1],其中自主神经常常受累[2],个别患者甚至以自主神经受损为首发症状。     

乙型脑炎继发神经节苷脂抗体阳性格林-巴利综合征1例

正格林-巴利综合征(Guillain-Barré Syndrome,GBS)是免疫介导的急性炎症性周围神经病,临床呈急性或亚急性起病,主要表现为四肢对称的迟缓性瘫,免疫治疗可缩短病程和改善症状。70%的GBS患者有前期感染,最常见的是空肠弯曲菌感染,占总数20%～30%;其他病原体包括疱疹病毒、细菌感染、肺炎支原体等~([1])。5%患者前期合并乙肝病毒感染~([2])。     

空肠弯曲菌感染与人格林-巴利综合征

弯曲菌是全球范围内主要的人兽共患性、细菌性肠道病原菌之一,对人致病的弯曲菌主要是空肠弯曲菌和结肠弯曲菌。特定血清型空肠弯曲菌引起的肠炎是人格林-巴利综合征(GBS)的重要前驱因子。本文对空肠弯曲菌引起GBS的流行病学与致病机制等研究情况及进展进行了综述。     

构建空肠弯曲菌致兔中枢神经系统病变的动物模型

背景:近年来,吉兰-巴雷综合征和眼肌麻痹-共济失调-无反射综合征屡有发现中枢神经系统受累,受累部位包括视神经、脑干和小脑。眼肌麻痹-共济失调-无反射综合征患者的脑干和脊髓小脑束发现MRI异常信号。因此建立空肠弯曲菌感染后脑炎的动物模型并通过影像学、免疫学及病理学等方法手段探讨其形成机制是实验出发点。目的:建立空肠弯曲菌Penner4型感染后中枢神经系统病变的动物模型。设计:随机分组设计、对照动物实验。单位:河北医科大学第二医院影像科、神经内科。材料:实验于2003-08/12在河北医科大学第二医院分子影像实验室完成。选择健康大耳白兔15只,随机分为实验组10只,对照组5只。方法:实验组于第1周将空肠弯曲菌灭活菌液与等体积的完全弗氏佐剂对抽充分乳化后,分别于双腋窝、双腹股沟及背部脊柱旁皮下多点注射免疫,每处1mL,每只总量5mL。以后每2周以单纯空肠弯曲菌灭活菌液腹腔注射加强免疫,每只每次总量5mL,共5次。对照组以相同体积的生理盐水代替空肠弯曲菌菌液,注射方法及时间与实验组完全相同。评价方法:①症状与体征:观察动物精神状态、饮食、尿便及肢体活动状况等。②血清学检查:用酶联免疫吸附法分别检测动物血清中抗空肠弯曲菌抗体、抗IgG型GM1抗体及髓鞘碱性蛋白含量。③影像学观察:使用TOSHIBA1.5T磁共振成像设备分别于每次免疫前随机抽取两组实验动物行MRI检查。扫描序列包括:自旋回波序列T1加权像,扫描参数为500/15ms(TR/TE);快速自旋回波序列T2加权像,4000/108ms(TR/TE);液体衰减反转恢复序列,参数为10000/120ms(TR/TE),翻转角90°,以上扫描层厚4.0mm,层间距0.8mm。④组织学检查:发病动物于初次免疫后4周经心脏灌注致死,立即开颅取视神经、部分白质、海马、脑干、小脑及颈、胸、腰各段脊髓,固定于40g/L甲醛溶液,分别行苏木精-伊红染色、坚固蓝染色及髓鞘碱性蛋白免疫组化染色。免疫后10周于实验组内随机选取5只及对照组5只以同样方法获得组织学标本。主要观察指标:症状与体征;动物血清中抗空肠弯曲菌抗体、抗IgG型GM1抗体及髓鞘碱性蛋白含量;影像学观察;组织学观察。结果:纳入动物15只,14只进入结果分析,实验组中1只动物于免疫后4周时死亡。①实验组1只动物于免疫后2周出现精神症状及肢体活动障碍。②实验组动物血清抗空肠弯曲菌-IgG抗体滴度在2～4周达到高峰,自第2周起,实验组动物血清A值显著大于对照组(实验组、对照组分别为1.923±0.403,0.973±0.633,P<0.05)。IgG型GM1(A值)在第8周时明显升高,但与对照组比较差异无显著性(实验组、对照组分别为0.115±0.042,0.097±0.039,P>0.05)。血清髓鞘碱性蛋白含量(A值)均在第8周时显著上升(0.134±0.041)。③影像学检查发现实验组动物在免疫后2～4周出现不同程度的颅脑MRI异常信号。④组织学改变见实验组动物脑干、延髓、颈髓、胸髓及腰髓等部位髓鞘肿胀,未见炎细胞浸润及髓鞘脱失。对照组上述部位均未见明显改变。结论:空肠弯曲菌Penner4型可诱发中枢神经系统病变。     

The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.     

A bacterium lipopolysaccharide that elicits Guillain-Barre syndrome has a GM1 ganglioside-like structure

There is a strong association between Guillain-Barre syndrome (GBS) and Penner's serotype 19 (PEN 19) of Campylobacter jejuni. Sera from patients with GBS after C. jejuni infection have autoantibodies to GM1 ganglioside in the acute phase of the illness. Our previous work has suggested that GBS results from an immune response to cross-reactive antigen between lipopolysaccharide (LPS) of the Gram-negative bacterium and membrane components of peripheral nerves. To clarify the pathogenesis of GBS, we have investigated whether GM1-oligosaccharide structure is present in the LPS of C. jejuni (PEN 19) that was isolated from a GBS patient. After extraction of the LPS, the LPS showing the binding activity of cholera toxin, that specifically recognizes the GM1- oligosaccharide was purified by a silica bead column chromatography. Gas-liquid chromatography-mass spectrometric analysis has shown that the purified LPS contained Gal, GalNAc, and NeuAc, which are sugar components of GM1 ganglioside. 1H NMR methods [Carr-Purcell-Meiboom- Gill (CPMG), total correlation spectroscopy (TOCSY), and nuclear Overhauser effect spectroscopy (NOESY)] have revealed that the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4(NeuAc alpha 2- 3)Gal beta] protrude from the LPS core. This terminal structure [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] is identical to the terminal tetrasaccharide of the GM1 ganglioside. This is the first study to demonstrate the existence of molecular mimicry between nerve tissue and the infectious agent that elicits GBS.     

格林-巴利综合征患者血清中髓鞘脂自身抗体水平的测定

应用免疫学方法检测了格林－巴利综合征（ＧＢＳ）病人和正常对照组各３０例的血清中髓鞘脂自身抗体含量，并进行了动态观察。结果显示，ＧＢＳ病人血清中髓鞘脂自身抗体水平明显高于正常对照组（Ｐ〈０．０１），ＧＢＳ患者髓鞘脂自身抗体出现的阳性率为２０％。动态观察发现，ＧＢＳ患者血清中髓鞘脂自身抗体水平的下降与临床症状的改善相一致。     

急性运动性轴索神经病冷冻复型超微结构观察

应用冷冻复型电镜技术对急性运动性轴索神经病（ＡＭＡＮ）周围神经病变特征与经典型格林－巴利综合征（ＧＢＳ）进行了对照研究．观察到前者以脊髓前根和远端周围运动纤维轴索不同程度病变为主，早期表现为神经微丝、微管数量较正常人和经典型ＧＢＳ者明显增多，经统计学处理有显著性差异（Ｐ＜０．０１）；经典型ＧＢＳ则以脊髓前、后根和远端周围神经纤维出现程度不等的髓鞘病变为主要特征，其早期病变者雪旺细胞核膜凹凸不平，核孔及核膜蛋白颗粒（ＩＭＰ）数量减少，并且板层粗糙或ＩＭＰ大小不一，分布不均。以上从亚细胞水平说明ＡＭＡＮ和经典型ＧＢＳ表现不同，为研究ＡＭＡＮ的特征提供了新的资料．     

Effect of acyclovir and phosphonoformate on cytomegalovirus infection in guinea pigs

Adult Hartley guinea pigs infected with guinea pig cytomegalovirus (CMV) develop a mononucleosis syndrome with a brief viremia, splenomegaly, lymphadenopathy, and peripheral lymphocytosis with circulating atypical lymphocytes. The present study used this experimental model to evaluate in vivo the therapeutic efficacy of acyclovir (ACV) and phosphonoformate (PFA) during CMV infection. Guinea pigs were treated with ACV or PFA from day 3 to day 7 postinoculation. The course of the mononucleosis syndrome and the spread of virus in various tissues were similar in drug- and sham-treated infected guinea pigs. Infected animals treated with ACV or PFA developed disseminated CMV disease with severe interstitial pneumonia, whereas sham-treated infected and drug-treated noninfected animals did not. In addition, mortality rates in infected animals treated with ACV were significantly higher than those in sham-treated animals. Furthermore, the normal lymphoproliferative response to CMV infection appeared to be reduced in ACV-treated as compared to sham-treated animals, with fewer peripheral lymphocytes, less lymphoid tissue in the spleen and lymph nodes, and less mononuclear inflammation around the inclusion-containing cells of the liver and salivary gland. These results show that ACV and PFA are not useful in the treatment of CMV infection in guinea pigs but instead may have harmful effects.     

Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.     

人类去细胞同种异体神经移植物化学萃取方法的研究

背景研究表明应用化学消化剂处理同种异体神经可以有效地清除细胞、髓鞘而不出现宿主免疫排斥反应,但目前这种方法仅在小动物及低等哺乳类实验中取得成功,离临床应用尚有差距.目的清除人类周围神经中的细胞和髓鞘,萃取粗大和长段的去细胞神经移植物.设计非随机非对照实验研究.地点和对象实验在解放军第三○四医院骨科完成,对象为急性脑外伤死亡者,男,26岁,体质量75 kg,死者家属同意遗体捐献.干预切取年轻男性遗体捐献者的长段尺神经,以Triton X-100和脱氧胆酸钠溶液按一定浓度和程序进行化学处理.萃取神经及新鲜神经行HE染色、髓鞘染色及纤维素染色,以观察细胞、髓鞘及神经基底膜;免疫组织化学染色以显示许旺细胞基底板层;行半薄切片及超薄切片透射电镜检查,观察超微结构.主要观察指标去细胞神经的物理形状,组织学观察和超微结构.结果去细胞神经的延展性及神经外膜的韧弹性良好.细胞和髓鞘被彻底清除,神经基底膜被保留;许旺细胞基底板层保留完好;去细胞神经为一种没有细胞髓鞘及其碎片的空的神经基质管.结论Triton X-100及脱氧胆酸钠化学处理方法,可有效清除人类周围神经中的细胞及髓鞘,萃取粗大和长段的去细胞神经;该神经移植物保持了网管柱状组织结构,保留了许旺细胞基底板层及其主要成分一板层素.     

Overview of new research findings

The understanding on the pathophysiology of Guillain-Barré syndrome (GBS) has been significantly advanced for the past few years, and the contribution of Japanese researchers to it is worth mentioning. In axonal GBS (AMAN), transmission failure of a peripheral nerve occurs when anti-ganglioside antibody which is specifically formed based on the polymorphism of C. jejuni enters through the blood-nerve barrier and damages the node of Ranvier and its surrounding structures. Electrophysiologically, patients with AMAN demonstrate distal conduction failure, but that finding may improve rapidly by immunomodurating therapy suggesting distal conduction failure. The mainstream therapy of GBS is still intravenous immunoglobulin (IVIg) and plasma exchange. However, clinical trials to assess effectiveness of other immunotherapy have been actively conducted.