重症肌无力患者血清连接素抗体与临床的关系

目的 探讨重症肌无力（MG）患者血清连接素抗体（Titin—Ab）水平与病情及胸腺异常的关系,以及其对诊断和预后判断的价值。方法 应用酶联免疫吸附法（ELISA）检测MG患者（MG组）52例、非MG（其他神经系统疾病）患者（NMG组）18例、健康对照者（NC组）50名血清中Titin—Ab水平,并对其中10例进行胸腺手术的MG患者随访。结果 MG组Titin—Ab阳性率为36．5％,NMG组和NC组均为阴性,MG组显著高于NC组和NMG组（均P〈0．01）;以MG伴胸腺瘤（MGT）组阳性率最高（83．3％）,MG伴胸腺萎缩（MGA）次之（37．5％）,胸腺正常的MG组为23．0％,MG伴胸腺增生组为阴性;Titin．Ab诊断MGT特异性高于胸腺CT（P〈0．05）。Titin—Ab阳性MG患者抗体水平与肌无力程度呈显著正相关（r=0．562,P〈0．01）;对10例不同胸腺病理类型的MG患者手术前后Titin—Ab测定显示差异具有显著性（P〈0．05）。结论 Titin—Ab阳性多见于MGT和MGA者,诊断MGT的特异性高于CT;Titin—Ab对MG的诊断、病情及预后判断均有帮助。     

重症肌无力患者血清titin抗体和乙酰胆碱受体抗体与疾病临床特征的关系

目的探讨重症肌无力(MG)患者血清titin抗体及乙酰胆碱受体(AChR)抗体与疾病临床特征的关系。方法采用酶联免疫吸附试验对90例MG患者和30例对照组成员进行titin抗体和AChR抗体的检测并进行比较。结果 MG患者AChR抗体、Titin抗体阳性率(76.7%,54.5%)明显高于对照组(10%,6.7%)(χ2=41.667,P=0.000;χ2=21.017,P=0.000)。titin抗体与AChR抗体检测MG的灵敏度分别为54.5%和76.7%,两种抗体并联试验灵敏度为89.4%。titin抗体在伴胸腺病变及晚发型MG患者中有较高阳性率,分别为80.0%和72.5%,明显高于非胸腺瘤组(47.1%,χ2=6.771,P=0.009)和早发型MG患者(40%,χ2=9.46,P=0.002)。全身型MG患者titin抗体与AChR抗体阳性率(69.2%,90.4%)显著高于眼肌型MG(34.2%,χ2=10.856,P=0.001;57.9%,χ2=12.956,P≤0.000)。甲亢组与非甲亢组MG患者titin抗体(33.3%,56.8%)与AChR抗体阳性率(55.6%,79%)差异性均无统计学意义(χ2=1.797,P=0.19;χ2=2.491,P=0.063)。结论 MG患者病情越重,titin抗体与AChR抗体阳性率越高。Titin抗体及AChR抗体能作为诊断MG的指标,联合检测能提高MG诊断的灵敏。然而MG患者血清titin抗体与AChR抗体并无一致性关系。     

Combined features of myasthenia gravis and Eaton-Lambert syndrome: anti-ganglioside antibodies in serum

We studied 2 patients with Eaton-Lambert syndrome showing some features of myasthenia gravis. Among 9 different glycolipid antigens examined, serum titers of IgG antibodies to GT1b, GD1a, and sialylparagloboside were increased. Those antibodies may be involved in the pathogenesis of the presynaptic neuromuscular block that was presumed to be present in these patients.     

联合检测重症肌无力的三种血清抗体诊断

目的对重症肌无力(MG)患者的乙酰胆碱受体抗体(Ach R-Ab)、连接素抗体(Titin-Ab)和肌肉特异性酪氨酸激酶抗体(Mu SK-Ab)评价该3种血清抗体联合检测对MG的诊断价值。方法选择MG组患者112例、其他疾病对照组53例和健康对照组56例,采用放射免疫法测定Ach R-Ab,ELISA法分别测定Titin-Ab和Mu SK-Ab,并对结果进行分析。结果 MG患者Ach R-Ab、Titin-Ab和Mu SK-Ab的阳性率分别为68.8%、54.5%和5.4%,明显高于对照组(P<0.05)。三种抗体联合检测,其敏感性和特异性分别为91.1%和89%。其中,Mu SK-Ab仅见于Ach R-Ab阴性的MG患者,主要表现为延髓肌受累,病情较重且不伴有胸腺病变。Titin-Ab多见于MG合并胸腺瘤(MGT)患者,其MGT组的阳性率高于未合并胸腺瘤的MG(NTMG)患者(P<0.05)。将MG患者根据Osserman评分进行分型,Titin-Ab阳性率与病情严重程度有关(P<0.05)。结论 Ach R-Ab、Titin-Ab、Mu SK-Ab三种抗体是MG的诊断性标记抗体,联合检测可以避免因单项检测出现的漏诊和误诊,此外,Titin-Ab对MG合并胸腺瘤具有显著相关性,还可作为判断MG病情严重程度的指标。     

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。     

Seronegative generalised myasthenia gravis: clinical features,antibodies, and their targets

Myasthenia gravis (MG) is a well-recognised disorder of neuromuscular transmission that can be diagnosed by the presence of antibodies to the acetylcholine receptor (AChR). However, some patients (about 15%) with generalised MG do not have detectable AChR antibodies. There is some evidence, however, that this "seronegative" MG is an antibody-mediated disorder. Plasma from patients with the disorder seems to contain various distinct humoral factors: IgG antibodies that reversibly inhibit AChR function; a non-IgG (possibly IgM) factor that indirectly inhibits AChR function; and an IgG antibody against the muscle-specific kinase (MuSK). The presence of antibodies against MuSK appears to define a subgroup of patients with seronegative MG who have predominantly localised, in many cases bulbar, muscle weaknesses (face, tongue, pharynx, etc) and reduced response to conventional immunosuppressive treatments. Moreover, muscle wasting may be present, which prevents complete response to these therapies.     

Frequency and clinical features of treatment-refractory myasthenia gravis

Journal of Neurology - To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort. Patient charts of 126 patients with...     

The coexistence of myasthenia gravis and myotonic dystrophy in one family

We are reporting the unique coexistence of two distinct neuromuscular diseases, myotonic dystrophy and the juvenile form of myasthenia gravis, occurring in one family. A 16-month-old previously healthy female presented with a two month history of bilateral varying drooping of both eyelids and bilateral external ophthalmoparesis. The acetylcholine receptor antibodies were elevated, and there was a dramatic response to edrophonium confirming the clinical impression of myasthenia gravis. Spontaneous remission of the ptosis was noted after six months with no specific treatment. Many other family members were examined; none of them had clinical or laboratory evidence of myasthenia gravis. The clinical examination of the mother and the maternal grandmother, neither of whom had any complaints, resulted in a definite diagnosis of myotonic dystrophy. The proband's father and a 3-year-old sister were examined and found to be normal. We studied the HLA antigens of all of the available family members; none were found to have the HLA antigens most commonly associated with myasthenia gravis. Secretor gene studies were not helpful in providing additional genetic identification. The question generated by the coexistence of these two uncommon disorders in one family is if there is a genetic or other relationship between them or if this was merely a coincidental occurrence. At this point in time the question remains unanswered and must await demonstration of additional similar circumstances.     

重症肌无力患者血清Titin抗体和AchR抗体检测的意义

目的 探讨重症肌无力(MG)患者血清Titin抗体及乙酰胆碱受体(AchR)抗体的检测意义.方法 采用酶联免疫吸附试验(ELISA)对81例MG患者和80例对照组成员进行Titin和AchR抗体的检测.结果 Titin抗体对MG具有特异性,它在合并胸腺瘤的MG(MGT)、晚发型MG患者中有较高的阳性率(分别为80%、69.4%)和抗体水平,明显高于早发型MG患者的阳性率(25%)和抗体水平,差异均有统计学意义(P<0.05).而早发型MG患者中AchR抗体阳性率比晚发型MG患者明显增高.并且早发型MG患者的AchR抗体水平也明显高于晚发型MG和MGT患者,差异均有统计学意义(P<0.05).结论 两种抗体检测为MG诊断和病因学研究提供了重要证据,联合检测可以提高MG诊断的灵敏度.     

伴自发电位重症肌无力的临床及电生理特点

目的探究伴自发电位重症肌无力患者的临床及电生理特点。方法收集重症肌无力住院患者共90例,均行重复神经电刺激、针电极肌电图检查,其中6例出现自发电位,回顾性分析6例病例临床及电生理特点。结果 6例患者均确诊为全身型重症肌无力,其中胸腺瘤合并率为3/6。乙酰胆碱受体抗体均阳性且多数滴度较高,其他重症肌无力抗体均阴性。针电极肌电图可见自发电位,均伴运动单位时限缩窄,重复神经电刺激均见低频波幅递减、高频未见递增。结论本研究揭示了全身型重症肌无力患者的一种少见电生理表现,即以正锐波及纤颤电位为主的自发电位,可为严重神经肌肉接头异常所致。     

218例重症肌无力危象的临床分析

目的总结重症肌无力危象的临床特点及急救和预防经验.方法回顾性分析1956～2004年诊治的218例患者369例次重症肌无力危象的病例资料.结果死亡51例,病死率23.39%;近十年(1994～2004年)死亡4人,病死率4.2%.结论综合利用气管切开正压辅助呼吸、激素冲击治疗、丙种球蛋白静滴及血浆交换可改善重症肌无力危象的预后,且明显降低病死率.     

Anti-neuroblastoma antibodies in myasthenia gravis: clinical and immunological correlations

Forty-four of 109 myasthenia gravis (MG) patients (40%) had serum antibodies against human neuroblastoma cells (NBL). Anti-NBL antibodies were most frequent in the sera of MG patients who had either a hyperplastic thymus or a thymoma, clinically mild to moderately severe generalized MG, and a long disease duration (greater than or equal to 11 years). No correlation between individual anti-NBL antibody and anti-acetylcholine receptor (AChR) antibody titers was observed. Seven of the 19 patients negative for anti-AChR antibodies (37%) had anti-NBL antibodies in their sera. These findings provide further evidence for immunological heterogeneity in MG. In addition to the typical autoantibodies to the AChR, autoimmunization against neural antigens can frequently be detected in these patients.     

Antivirus antibodies in myasthenia gravis

Serum antibodies to influenza A, measles, rubella, cytomegalovirus, varicella zoster, herpes simplex type 1, and mumps have been assayed in 104 patients with myasthenia gravis, grouped according to clinical features plus thymus pathology, and compared with matched controls. No significant differences in incidence or antibody titer were detected. In 37 patients with recent onset of symptoms, the incidence of antibody to coxsackieviruses B1-B6 was less than in controls. Juvenile-onset cases also demonstrated antibody to Epstein-Barr virus at the expected frequency. These results weaken the case for any of these common viruses, or the response to them, contributing to the pathogenesis of myasthenia gravis.     

Striational antibodies in myasthenia gravis: reactivity and possible clinical significance

Myasthenia gravis is an autoimmune disease caused, in most cases, by antibodies attaching to the acetylcholine receptor. Some myasthenia gravis patients have antibodies that bind in a cross-striational pattern to skeletal and heart muscle tissue sections (striational antibodies). These antibodies react with epitopes on the muscle proteins titin and ryanodine receptor, are found mainly in sera of patients with thymoma and late-onset myasthenia gravis, and may correlate with myasthenia gravis severity. Their presence may predict an unsatisfactory outcome after thymectomy. The detection of titin and ryanodine receptor antibodies provides more specific clinical information than the immunofluorescent demonstration of striational antibodies.     

重症肌无力患者血清IgG-乙酰胆硷受体抗体亚型研究

目的 探讨重症肌无力（ＭＧ）患者血清ＩｇＧ－乙酰胆硷受体抗体（ＡＣｈＲＡｂ）亚型的分布规律及其临床意义。方法 采用ＡＢＣ－ＥＬＩＳＡ法检测４３例ＭＧ组和２５例临床对照组、２０例正常对照组血清中ＩｇＧ－ＡＣｈＲＡｂ亚型ＩｇＧ１－４。结果 ＭＧ组与两对照组相比ＩｇＧ１和ＩｇＧ４亚型抗体无显著差别,ＩｇＧ２亚型抗体显著升高（Ｐ〈０．０５）,ＩｇＧ３亚型抗体显著降低（Ｐ〈０．０５）;ＭＧ组各临床类型间各亚型抗体无显著差别。结论 ＩｇＧ－ＡＣｈＲＡｂ亚型以ＩｇＧ２活性为主,但未显示与ＭＧ临床类型有关。     

Muscle antibodies in the cerebrospinal fluid from patients with myasthenia gravis

IgG antibodies to nicotinic acetylcholine receptor (AChR) and to a muscle antigen extracted by citric acid, were quantified in serum and cerebrospinal fluid (CSF) from 28 patients with myasthenia gravis, and the serum:CSF ratios compared with those of total IgG. Agarose-electrophoresis and calculations of the IgG index and Tourtellotte's formula were performed. No evidence of intrathecal antibody synthesis was demonstrated. Compared to the total IgG concentrations in serum and CSF, the CSF concentrations of IgG AChR antibodies were lower than expected.     

Anti-acetylcholinesterase antibodies associate with ocular myasthenia gravis

In MG, anti-AChR or anti-MuSK abs impair neuromuscular transmission. Partial inhibition of AChE can ameliorate symptoms, while a complete block causes a cholinergic blockade. We found anti-AChE abs in 115/240 MG patients, with no correlation with sex, age at onset, thymus pathology, presence of anti-AChR or anti-MuSK antibodies. We found a correlation with the ocular form of the disease, and with milder forms of MG not requiring immunosuppressants; moreover, when we considered only those patients who were off AChEI therapy, we found that ocular patients were positive for anti-AChE abs, while generalized patients were negative. According to an experimental model, we hypothesize that anti-AChE abs could contribute to ptosis through an inhibition of the sympathetic innervation of the tarsal muscle.     

Prevalence,clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand

A small but variable subgroup of patients with myasthenia gravis (MG) who have antibodies to muscle-specific kinase (MuSKAb-MG) can present with distinct phenotypes and are often treatment-resistant. The prevalence, clinical phenotypes and outcomes of treatment of patients with MuSKAb-MG in Thailand were determined. Eight (16.3%) of the 49 patients with generalized MG who were negative for acetylcholine receptor antibodies (AChRAb) were positive for muscle-specific kinase antibodies. Most patients had predominant oculobulbar features and respiratory failure occurred in three. At follow up, three out of the seven patients who underwent thymectomy were in complete stable remission and four had improved and were on reduced immunosuppression medication, suggesting a possible benefit of thymectomy.