Osserman Ⅴ型重症肌无力5例临床分析及文献复习

目的 对Osserman Ⅴ型重症肌无力（MG）的临床特点及诊治体会进行回顾性总结分析，以提高对此少见疾病中少见类型的认识。方法 对作者医院2004-11-2006-11期间收治的491例MG患者中所有Osserman Ⅴ型患者的临床特点和血清学检测结果进行回顾性分析。结果 491例MG患者中5例为Osserman Ⅴ型，在病程中先后出现不同程度舌肌、颞肌或上肢远端小肌肉萎缩。其中4例肌电图检查重频电刺激低频递减，血清乙酰胆碱受体抗体（AChR-Ab）阳性，另1例抗骨骼肌特异性受体酪氨酸激酶抗体（MuSK-Ab）阳性。5例患者均对溴吡斯的明对症治疗反应差，但对糖皮质激素和静脉丙种球蛋白（IVIG）治疗反应较好。半年后随访肌肉萎缩有不同程度改善。结论 Osserman Ⅴ型MG很罕见，肌肉萎缩的发病机制尚不清楚，部分患者可能与MuSK-Ab有关。血清学检测有助于对Osserman Ⅴ型MG确诊、避免误诊及改善预后。     

伴肌萎缩重症肌无力4例分析并文献复习

目的探讨伴肌萎缩重症肌无力(myasthenia gravis,MG)患者的临床特征、抗体及电生理特点,提高对此少见疾病的认识。方法回顾性分析作者医院2003—2016年收治的伴肌萎缩MG患者4例的临床资料,分析其临床特征、抗体、神经电生理检查、治疗及预后特点。结果 4例患者病程中出现不同程度的肌肉萎缩,1例为手肌(左侧大鱼际肌、小鱼际肌及第一骨间肌)萎缩,3例为舌肌萎缩(其中1例同时伴面肌萎缩);抗体检查显示乙酰胆碱受体抗体(AChR-Ab)阳性3例,1例为抗骨骼肌特异性受体酪氨酸激酶抗体(MuSK-Ab)阳性。4例患者低频重复神经刺激波幅均可递减,高频刺激波幅未见明显递增。伴手肌萎缩MG患者针极肌电图检查结果提示神经源性损害。结论伴肌肉萎缩MG较罕见,MuSK-Ab、AChR-Ab阳性MG患者均可出现肌肉萎缩,其机制有待进一步明确;早期行神经电生理检查、AChR-Ab及MuSK-Ab测定有助于明确诊断。     

斜方肌肌电图运动单位动作电位成人正常参考值的建立

目的 探讨不同血清抗体重症肌无力(MG)的临床特征.方法 用荧光免疫沉淀法(FIPA)和荧光免疫细胞染色法(CBA)检测119例MG患者血清乙酰胆碱受体抗体(AChR-Ab)和肌肉特异性受体酪氨酸激酶抗体(MuSK-Ab)水平.比较AChR-Ab阳性、MuSK-Ab阳性、血清抗体阴性MG的临床特征.结果 纳入119例患者中,90例AChR-Ab阳性(75.6%),29例阴性:其中5例MuSK-Ab阳性(17.2%),24例血清抗体阴性(82.8%).AChR-Ab阳性、MuSK-Ab阳性和血清抗体阴性MG 3组比较,男女比例和平均发病年龄差异均无统计学意义.3例MuSK-Ab阳性的患者主要表现为延髓肌受累;79.2%(19/24)的血清抗体阴性MG患者表现为美国MG协会(MGFA)Ⅰ型;2例MuSK-Ab阳性的患者MGFA≥Ⅲ型;MuSK-Ab滴度水平与患者病情严重程度相关(r=0.941,P=0.014);MuSK-Ab阳性的患者均未发现有胸腺的异常.结论 MuSK-Ab仅出现在AChR-Ab阴性患者的血清中.MuSK-Ab阳性的患者主要表现为延髓肌受累,病情较重且不伴有胸腺的病变.MuSK-Ab阳性的MG可能是不同于血清AChR-Ab阳性的MG的又一亚型.     

肌肉特异性受体酪氨酸激酶抗体阳性重症肌无力

目的 探讨不同血清抗体重症肌无力(MG)的临床特征.方法 用荧光免疫沉淀法(FIPA)和荧光免疫细胞染色法(CBA)检测119例MG患者血清乙酰胆碱受体抗体(AChR-Ab)和肌肉特异性受体酪氨酸激酶抗体(MuSK-Ab)水平.比较AChR-Ab阳性、MuSK-Ab阳性、血清抗体阴性MG的临床特征.结果 纳入119例患者中,90例AChR-Ab阳性(75.6%),29例阴性:其中5例MuSK-Ab阳性(17.2%),24例血清抗体阴性(82.8%).AChR-Ab阳性、MuSK-Ab阳性和血清抗体阴性MG 3组比较,男女比例和平均发病年龄差异均无统计学意义.3例MuSK-Ab阳性的患者主要表现为延髓肌受累;79.2%(19/24)的血清抗体阴性MG患者表现为美国MG协会(MGFA)Ⅰ型;2例MuSK-Ab阳性的患者MGFA≥Ⅲ型;MuSK-Ab滴度水平与患者病情严重程度相关(r=0.941,P=0.014);MuSK-Ab阳性的患者均未发现有胸腺的异常.结论 MuSK-Ab仅出现在AChR-Ab阴性患者的血清中.MuSK-Ab阳性的患者主要表现为延髓肌受累,病情较重且不伴有胸腺的病变.MuSK-Ab阳性的MG可能是不同于血清AChR-Ab阳性的MG的又一亚型.     

AChR抗体阳性重症肌无力合并舌肌萎缩2例报道并文献分析

目的 探讨重症肌无力(MG)患者合并舌肌萎缩的发病特点及机制。方法 分析武汉同济医院神经内科住院部2例乙酰胆碱受体(AChR)抗体阳性MG患者合并舌肌萎缩的临床资料,检索MG合并舌肌萎缩的文献报道,总结此类疾病的特点、萎缩机制、治疗方法及预后。结果 在临床上MG合并舌肌萎缩并不多见,大多数患者伴有血清肌肉特异性酪氨酸肌酶(MuSK)抗体阳性,伴AChR抗体阳性者较为罕见,肌肉萎缩的发病机制具体不详; 该类患者除发病时间较长外,通常提示更严重的病情、更差的治疗反应、更不良的预后。结论 MG舌肌萎缩临床少见,严重影响着患者的言语、咀嚼和吞咽等功能,除病程较长外,其肌肉萎缩机制暂不清楚,有待临床进一步探索,以改善此类患者预后和生活质量。     

血清乙酰胆碱受体抗体、肌肉特异性酪氨酸激酶抗体浓度与重症肌无力患者临床分型和疾病转归的关系

目的探索血清乙酰胆碱受体抗体(AchR-Ab)、肌肉特异性酪氨酸激酶抗体(MuSK-Ab)浓度与重症肌无力(MG)患者临床分型和疾病转归的关系。方法收集2014年5月-2015年5月在本院神经内科住院治疗的MG患者43例(MG组)和同期在本院健康体检的正常人43例(N组),采用酶联免疫吸附(ELISA)法检测血清AChR-Ab、MuSK-Ab浓度,并计算MG组患者治疗前后的肌无力绝对评分,分析不同临床分型的MG患者治疗前的血清AChR-Ab、MuSK-Ab浓度,并对治疗前后肌无力绝对评分和治疗前后血清AChR-Ab、MuSK-Ab浓度变化进行相关性分析。结果 (1)治疗前,MG组和N组的血清AChR-Ab浓度分别为0.786±0.237ng·mL~(-1)、0.298±0.113ng·mL~(-1),差异有统计学意义(均P0.05),血清Mu SK-Ab浓度分别为0.322±0.128ng·mL~(-1)、0.281±0.123ng·mL~(-1),差异无统计学意义(均P0.05);(2)血清AChR-Ab和MuSK-Ab在不同临床分型MG患者中的浓度均没有明显差异(均P0.05);(3)治疗后肌力绝对评分和血清AChR-Ab浓度均显著下降(均P0.05),而血清MuSK-Ab浓度在治疗前后没有显著变化(P0.05),并且治疗后的血清AChR-Ab浓度和治疗后的肌无力绝对评分呈正相关(r=0.797,P0.05)。结论血清AChR-Ab和MuSK-Ab的浓度与MG的临床分型无明显相关性,血清AChR-Ab对疾病的转归有一定的预示作用。     

重症肌无力患者血清四种抗体的检测及意义

目的探讨乙酰胆碱受体(AChR)抗体、乙酰胆碱酯酶(ACHE)抗体、Titin抗体、Ryanodine受体(RyR)抗体在重症肌无力(myasthenia gravis,MG)诊断中的临床意义。方法采用ELISA法检测89例MG患者、66例其他神经系统疾病患者和66名健康对照者上述血清4种抗体水平。结果 MG患者AChR抗体、AChE抗体、Titin抗体和RyR抗体的阳性率分别为53.9%、20.2%、64.0%和55.0%,明显高于对照组(P0.05)。4种抗体联合检测,其敏感度和特异度分别为94.4%和84.0%。AChE抗体多见于AChR抗体阴性且对新斯的明试验反应差的MG患者。Titin抗体在MG合并胸腺瘤(MGT)患者中的阳性率高于未合并胸腺瘤的MG(nMGT)患者(P0.05),其对MGT诊断的敏感度和特异度分别为82.2%和52.5%。晚发型MG患者血清Titin抗体和RyR抗体阳性率明显高于早发型MG(P0.05)。将MG患者根据Osserman评分进行分型,Titin抗体阳性率与病情严重程度有关(P0.05)。结论 AChR抗体、AChE抗体、Titin抗体和RyR抗体联合检测对诊断MG具有较高的敏感度和特异度。Titin抗体结合胸腺CT可能有助于提高MGT诊断的敏感度和特异度,Titin抗体多见于病情较重的患者。     

MuSK-Ab与血清学双阴性MG患者的检测及临床表现

目的探讨肌肉特异性酪氨酸激酶抗体(Mu SK-Ab)及血清学双阴性(d SN-MG)重症肌无力(MG)患者的临床特征。方法采用ELISA法检测108例MG患者、80例对照组的乙酰胆碱受体抗体(AchR-Ab)及Mu SK-Ab水平,并分析各型的临床特点。结果 108例MG患者中:AchR-Ab单阳性共计57例(占52.8%);AchRAb阴性的MG患者中Mu SK-Ab阳性的患者有5例(占10%),分型均为全身型。1例患者为AchR-Ab和Mu SK-Ab双阳性(d SP-MG)。共有45例血清双阴性MG(d SN-MG),占41.7%。胸腺异常者仅占24.4%且均未发生肌无力危象。除此之外,我们在疾病对照组中发现2例AchR-Ab阳性,1例Mu SK-Ab阳性。结论贵州省MG患者AchRAb及Mu SK-Ab阳性率同中国大陆、台湾地区的研究结果类似,低于欧美人种。Mu SK-Ab阳性的患者临床分型较重。d SN-MG也占有较大比例,其年龄组成及胸腺情况与其他两组均有差异。     

全身型重症肌无力的临床和电生理特点分析

目的 探讨不同亚型全身型重症肌无力(Myasthenia gravis,MG)临床和电生理特点之间的区别,并分析电生理结果与疾病严重程度的相关性。方法 回顾性分析2016年7月至2020年7月在香港大学深圳医院神经内科就诊或住院的101例全身型MG患者的临床和电生理资料,按照其临床特点,分为早发乙酰胆碱受体(Acetylcholine receptor,AchR)抗体阳性全身型MG组(52例)、晚发AchR抗体阳性全身型MG组(23例)、胸腺瘤型MG组(22例)和肌肉特异性受体酪氨酸激酶(Muscle-specific receptor tyrosine kinase,MuSK)抗体阳性型MG组(4例),比较不同亚组MG患者的人口学特点、重症肌无力评分(Quantitative Myasthenia Gravis score,QMGs)、美国重症肌无力协会(MG Foundation America,MGFA)临床分级、重复神经电刺激(Repetitive nerve stimulation,RNS)结果,分析RNS结果与QMGs之间的相关性。结果 非MuSK抗体阳性全身型MG中,早发AchR抗体阳性全身型MG女性患者所占比率最高(71. 2%vs 65. 2%vs 36. 4%,P 0. 05),胸腺瘤型MG呼吸肌/球部肌肉受累为主患者所占比率最高(28. 8%vs 43. 5%vs 63. 6%,P 0. 05),早发AchR抗体阳性全身型MG被检肌肉RNS均为阳性患者所占比率最高(44. 2%vs 17. 4%vs 22. 7%,P 0. 05),QMGs与RNS最大波幅下降比率、RNS总波幅下降比率呈明显正相关关系(P 0. 01); MuSK抗体阳性全身型MG,其中重度受累患者所占比率、呼吸肌/球部肌肉受累为主患者所占比率均较高(均为75%),而被检肌肉RNS均为阳性患者所占比率较低(0%)。结论 不同亚型全身型MG的人群分布、性别占比、主要受累肌肉、受累肌肉受累程度及分布范围均具有显著的差别,这在全身型MG的分型诊断方面具有很大的参考价值;其RNS结果与疾病严重程度具有高度相关性,提示RNS在全身型MG的病情评估方面具有重要临床价值。     

血清CAE-Ab、nAchR-Ab检测对伴发胸腺瘤的重症肌无力患者早期诊断意义

目的探讨柠檬酸提取物抗体(CAE-Ab)及烟碱型乙酰胆碱受体抗体(nAchR-Ab)测定对临床早期诊断伴发胸腺瘤的重症肌无力(MG)患者的价值,与改良Osserman分型及病理分型的关系.方法采用酶联免疫吸附法检测20例伴发胸腺瘤的重症肌无力患者的血清CAE-Ab、nAchR-Ab.结果 CAE-Ab阳性率75%,nAchR-Ab阳性率60%,大多在Ⅱa型与Ⅱb型患者.上皮细胞为主型4例中Ⅱb型3例、CAE-Ab均阳性,术后发生肌无力危象2例,1例死亡.结论 CAE-Ab及nAchR-Ab检测可作为临床诊断 MG患者伴发胸腺瘤的筛选检查;术后病理分型可指导治疗和判断预后.     

重症肌无力三种突触前膜结合蛋白抗体的检测

应用选择性地作用于突触前膜的β-BGT,川楝素,β-AgTx以及选择性地作用于AChR的α-BGT,能与人骨骼肌提取的混合受体粗提液中各自的靶蛋白结合的特性,以ABC-ELISA方法检测了43例正常人和43例重症肌无力病人血清中的相应抗体。结果发现重症肌无力病人血清中存在抗突触膜上述数种蛋白成分的相应抗体。该结果提示某些重症肌无力病人的神经肌肉接头处存在多重免疫损伤。     

动态监测脑血管病患者抗心磷脂抗体及ENA多肽抗体的临床意义

采用酶联免疫吸附法与免疫印迹法动态监测５０例脑梗塞和４０例脑出血患者的抗心磷脂抗体及测定部分患者有ＥＮＡ多肽抗体。结果仅ＩｇＧ型ａＣｌ与ＥＮＡ多肽性在急性脑血管病患者显著升高，两者在ＣＩ与ＣＨ组的阳性率分别为１２．０％，１２．５％与３９．０％，４３．３％，与正常对照组０．０％及１６．％相比，Ｐ〈０．０５。     

噬菌体抗体库的构建及抗人脑胶质瘤单抗的筛选

目的采用噬菌体展示技术制备抗人脑胶质瘤单抗.方法以人脑胶质瘤细胞系SHG-44免疫小鼠,取其脾淋巴细胞,应用噬菌体展示技术构建噬菌体抗体库,并筛选抗人脑胶质瘤单抗.结果筛选得到的小鼠全套免疫球蛋白的重、轻链可变区基因片段分别为340bp和325bp,建成的抗体库库容为5.7×106,60/96克隆具有与肿瘤细胞结合活性,阳性率为62.5%,与正常人淋巴细胞则全部呈阴性反应.结论为胶质瘤单抗制备提供了一种新的方法.     

The high prevalence of antiphospholipid antibodies in refractory focal epilepsy is related to recurrent seizures

Background:  Previous studies have shown the association between antiphospholipid antibodies with epilepsy but there are no studies addressing the effect of seizure frequency, duration of epilepsy, epilepsy type and aetiology on the prevalence of these antibodies in well-evaluated refractory epilepsy.
Methods:  Anticardiolipin, anti-β2-glycoprotein I and antinuclear antibody levels were measured in 105 well-evaluated patients with refractory focal epilepsy. Clinical determinants included the patient history, electroclinical classification and high resolution brain magnetic resonance imaging.
Results:  Patients with seizures during the month prior to sampling (recent seizures) had increased prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (29%) compared with healthy controls [13%; age-adjusted odds ratio (OR): 3.09, 95% confidence interval (CI): 1.30–7.34] and patients with no recent seizures (11%; age-adjusted OR: 4.00, CI: 0.84–19.02). The patients with recent seizures had increased prevalence of moderate positive IgG class anticardiolipin antibodies (12%) compared with the controls (4%) and the patients with no recent seizures (0%; age-adjusted OR: 4.45, CI: 1.14–17.36). The prevalence of IgG class anticardiolipin antibodies was not associated with epilepsy type, duration or aetiology.
Conclusion:  The presence of antiphospholipid antibodies is associated with recurrent seizures in patients with refractory focal epilepsy. The measurement of these antibodies may be useful in evaluating the outcome of epilepsy.     

多发性肌炎合并间质性肺病17例分析

目的:通过对17例多发性肌炎合并间质性肺病患者临床资料的分析以探讨其临床特点。方法:采用回顾性研究方法。结果:多发性肌炎合并间质性肺病者发热、咳嗽咳痰及关节痛出现率高,血沉明显增快,血抗核抗体(ANA)及抗Jo-1抗体的检出率高,肺部有特殊影像学改变,激素及免疫抑制剂有效。有半数以间质性肺病为首发症状。结论:多发性肌炎合并间质性肺病有特殊的临床表现,治疗效果不差。     

抗谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体与难治性癫痫的相关性研究

目的探讨抗谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体与成人难治性癫痫发病机制的相关性。方法本研究分为3组,即正常对照组(NC组)、可控性癫痫组(NE组)以及难治性癫痫组(IE组)各30例,其中NC组来自医院体检中心的健康体检人员;NE组及IE组来自吉林大学第一医院神经内科癫痫诊疗中心。以酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测3组的血清抗谷氨酸脱羧酶抗体、抗心磷脂抗体及抗神经节苷脂抗体数值,采用正态性检验,两组间定量资料比较。结果 IE组的血清3种抗体水平显著高于NE组及NC组,NE组和NC组的抗体浓度比较无统计学意义;3种抗体检测对于难治性癫痫的诊断具有高度一致性。结论成人难治性癫痫中谷氨酸脱羧酶抗体、抗神经节苷脂抗体和抗心磷脂抗体的检测对于难治性癫痫的诊断、治疗及预后判断具有指导作用。     

Immunohistochemical localization of serotonin and choline acetyltransferase in sensory neurones of the locust

Sensory neuronal cell bodies in the leg of locust, Schistocerca gregaria, were visualized with antibodies to locust choline acetyltransferase and with antibodies to serotonin by the avidin-biotin peroxidase technique. Two groups of sensory cells react with the antibody to choline acetyltransferase: One group is associated with external mechanoreceptors (i.e., hair-plate hairs and campaniform sensilla) and the other with internal proprioceptors (i.e., chordotonal organs and multiterminal receptors). Sensory cells which react with the antibody to serotonin are associated only with internal proprioceptors being found in both chordotonal organs and multiterminal receptors. In the metathoracic femoral chordotonal organ indirect evidence suggests that some sensory cells are reactive to both antibodies. Some multiterminal receptors react with anti-choline-acetyltransferase, while others react with antiserotonin. These results support the conclusion that most insect sensory neurones are cholinergic but some are serotoninergic.     

抗N-甲基-D-天冬氨酸受体脑炎的抗体检测及临床意义

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的抗体检测意义及临床特征。方法选取本院收治的脑炎病人35例及对照组30例,分析临床资料,采用转染细胞间接免疫荧光法检测两组患者其血清及脑脊液抗NMDAR机体结果抗NMDAR抗体检测仅1例边缘叶脑炎患者结果阳性,该患者腑脊液细胞数增多、蛋白轻度升高、脑电图见双侧慢波、其余检查无异常。精神症状及意识水平障碍明显,免疫治疗有效。结论抗NMDAR脑炎发病率低,临床表现复杂多样,怀疑该病时需行抗NMDAR抗体检测。     

Elevated Levels of Smooth Muscle Autoantibodies in Patients with Acromegaly

Screening of sera from patients with central nervous system (CNS) tumors for serum antibodies to tumor and normal tissue antigens revealed that the sera from a significant percentage of patients with pituitary adenoma demonstrated reactivity for smooth muscle antibodies (SMA) at a serum titer (1/25) at which other CNS tumors are devoid of this reaction. The sera were assessed by an indirect inlmunofluorescent antibody assay on fresh cryostat sections of rat kidney, liver, diaphragm, and stomach tissue. Absorption of SMA-positive sera with extracts containing smooth muscle tissue abolished the reaction.

The overall incidence of SMA among patients harboring pituitary tumors was 30% (12/40). Assessment of the functional types of the tumor revealed a distinct predilection for such findings among patients with clinical acromegaly. Among patients with hypersecretion of growth hormone (CA) 90% (9/10) have SMA (both IgG and IgM type) whereas SMA was positive in only 10% (3/30) of corresponding group of patients with pituitary tumors resulting in hypercortisolemia or those that did not result in a hyperfunctional endocrine state.     

A study of circulating gliadin antibodies in schizophrenia among a Chinese population

The present work measured circulating antibodies against native gliadins, deamidated gliadin-derived epitopes, and transglutaminase 2 (TGM2) in 473 patients with schizophrenia and 478 control subjects among a Chinese population. The results showed that 27.1% of patients with schizophrenia were positive for the IgA antibody against native gliadins compared with 17.8% of control subjects (χ(2) = 11.52, P = .0007, OR = 1.72, 95% CI 1.25-2.35), although this significant difference appeared to be due mainly to low IgA gliadin antibody levels in female controls. A total of 27.6% of female patients were positive for IgA gliadin antibodies compared with 13.9% of female controls (χ(2) = 10.46, P = .0012, OR = 2.36, 95% CI 1.39-4.01), and 26.4% of male patients were positive for IgA antibodies compared with 19.8% of male controls (χ(2) = 3.26, P = .071, OR = 1.46, 95% CI 0.97-2.19). Of 128 patients who were positive for the IgA antibody against native gliadins, 8 were positive for the IgA antibody against deamidated gliadin epitopes and 1 was positive for IgA anti-TGM2 antibody. However, quantitative analysis demonstrated that the mean levels of IgA antibodies against deamidated gliadin epitopes and TGM2 were significantly lower in patients with schizophrenia than the control subjects (P < .001 and P = .008, respectively). The prevalence of IgG antibodies against native gliadins was not significantly different between the patient group and the control group (χ(2) = 2.25, P = .134, OR = 1.32, 95% CI 0.92-1.88). This study suggests that specific gliadin-derived epitopes may be involved in schizophrenia.