重症肌无力患者神经肌肉接头处的超微结构研究

目的探讨重症肌无力（ＭＧ）时神经肌肉接头（ＮＭＪ）突触后、前膜的变化及其意义。方法肋间内肌在辣根过氧化酶标记的α银环蛇毒素（ＨＲＰαＢｕＴｘ）标记后，用图形扫描及医学图像分析软件测量电镜照片中ＮＭＪ的各项指标，并与对照组比较分析。结果ＭＧ时突触后膜长度缩短，后、前膜长度比值变小，神经末端面积及其与突触后膜面积之比变小，突触后膜上的乙酰胆碱受体（ＡＣｈＲ）减少了３５．９％。结论ＭＧ时ＮＭＪ的变化主要存在于突触后膜。突触后、前膜长度之比对本病的诊断更有临床意义。     

大鼠实验性重症肌无力的免疫电镜研究

本文成功地制作了大鼠ＥＡＭＧ模型，在观察动物临床表现和检测血清ａｎｔｉ－ＡｃｈＲＡｂ的同时还对ＮＭＪ进行了电镜观察。ＥＡＭＧ急性期大鼠ＮＭＪ出现巨大吞噬细胞浸润，而突触前，后膜改变不明显；在慢性期ＮＭＪ与肌纤维间隙不规则，突触前、后膜间隙扩大，突触后膜上的ＡｃｈＲ明显减少，触脚亦减少，突触后膜变得简单化，而神经终未端内的囊泡和线粒体却基本保持完好。     

Reliability of SFEMG in diagnosing myasthenia gravis: Sensitivity and specificity calculated on 100 prospective cases

ObjectiveThe study aimed to determine the utility of single-fibre electromyography (SFEMG) in the diagnosis of myasthenia gravis (MG) in subjects with a clinical suspicion of the disease.MethodsWe performed a prospective, single-blinded study on 100 consecutive patients. SFEMG was not considered a criterion in making the MG diagnosis. For all cases, a different physician than the one performing SFEMG made the diagnosis of MG. All subjects underwent standard SFEMG of a single muscle, the orbicularis oculi.ResultsSFEMG was abnormal in 67 of 100 patients. A final diagnosis of definite MG was made in 54 patients (30 men/24 women). SFEMG was positive in 53 of 54 patients diagnosed with MG. The sensitivity of SFEMG in diagnosing MG was 98% (95% CI: 0.94–1.02), while the specificity was 70% (95% CI: 0.54–0.86), with a positive predictive value of 79% (95% CI: 0.74–0.79) and a negative predictive value of 97% (95% CI: 0.94–0.99).ConclusionsIn this cohort of patients, normal SFEMG findings were unlikely to occur in patients with MG.SignificanceSFEMG is not a confirmatory test for the diagnosis of MG, but it has a high negative predictive value in identifying patients without MG.     

Splenectomy in myasthenia gravis: a therapeutic concept?

Summary The case histories are presented of five patients with long-diagnosed myasthenia gravis (up to 15 years) who underwent splenectomy. A precondition for the decision to operate was muscle weakness that could not be controlled with standard therapy (e.g. anticholinesterase drugs, immunosuppressive measures). After splenectomy, a considerable improvement took place in three cases; in one case there was moderate improvement, and in another, no improvement. The alleviation of myasthenia gravis may be attributable to the reduction of either the number of immunocompetent lymphocytes in an important storage organ or of the total bulk of the immune system in an immune disease with raised autoantibody production. The acetylcholine receptor antibody titre was not affected by the operation in a consistent way. After splenectomy, immunosuppressive medication was tolerated better with respect to its haematological side-effects.     

负性协同刺激分子PD-1在重症肌无力患者外周血中的表达

目的 观察重症肌无力(MG)患者外周血中负性协同刺激分子programmed death-1( PD-1)的表达情况,并探讨其与MG发病的关系。方法 采用免疫荧光标记、流式细胞仪检测45例MG患者和33名健康对照者外周血单个核细胞中PD-1及其配体PD-L1的表达,用ELISA法检测各组血浆中可溶性PD-1的水平。结果 (1)MG患者表达PD-1的CD4+T淋巴细胞比例增加,CD14+PD-L1+的单核细胞比例增加,但在不同性别及眼肌型与全身型间差异无统计学意义;在胸腺异常MG患者中CD4+PD-1+T细胞增加,CD14+ PD-L1+的单核细胞比例减少;早发型MG患者（年龄＜40岁）CD4+PD-1+T淋巴细胞比例明显低于晚发型（年龄≥40岁）。(2)MG患者血浆中sPD-1浓度为(6.92 +0.72) ng/ml,明显高于健康对照组的(3.28±0.42) ng/ml,但在性别、MG眼肌型与全身型不同类型间和有无胸腺异常各组间差异无统计学意义,且sPD-1与发病年龄呈负相关(r=-0.526,P=0.000)。结论 PD-1及PD-L1途径参与了MG的发病,异常升高的sPD-1可能干扰了正常的细胞膜上PD-1与PD-L1的结合,从而促使疾病进展。     

Influence of temperature on neuromuscular transmission in myasthenia gravis

Summary The effect of local cooling was studied in 28 patients with myastenia gravis. We stimulated the ulnar nerve with single stimuli and trains at 3/s for 2s and at 50/s for 1.5s. The compound muscle action potential (MAP), the muscle twitch and the isometric tetanic force of the adductor pollicis were registered. 1. At 3/s stimulation the pathological decrement of the MAP decreased after slight cooling. 2. The amplitude of the single MAP was higher at lower temperature when compared to normal temperature. The same increase is however to be found in healthy subjects. 3. After slight cooling, the maximum tetanic force was higher. However, the decrement of the force was higher also, therefore ruling out a practicable application of cooling for the patient. 4. After severe cooling (18–22°C) the tetanic force was much lower and in many cases a complete failure of the neuromuscular transmission occured.

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Zusammenfassung Der Einfluß lokaler Kühlung wurde an 28 Patienten mit Myasthenia gravis untersucht. Wir reizten den N. ulnaris mit einzelnen Impulsen und mit Serien von 3/s für 2s und von 50/s für 1.5s. Das Summenaktionspotential (MAP), die Muskelzuckung und die isometrische tetanische Kraft des Adduktor pollicis wurden registriert. 1. Bei Reizung mit 3/s war das pathologische Dekrement des MAP nach leichter Kühlung geringer. 2. Die Amplitude des MAP war größer. Diese Amplitudenzunahme tritt jedoch auch bei Gesunden nach Kühlung auf. 3. Nach leichter Kühlung war die maximale tetanische Kraft größer. Jedoch nahm die Kraft während der Reizung nach dem Maximum wieder schnell ab. Der praktische Nutzen einer Kühlung ist deshalb für den Patienten gering. 4. Nach starker Kühlung (18–22°C) war die maximale tetanische Kraft sehr niedrig. In vielen Fällen kam es zu einem vollständigen Versagen der neuromuskulären Impulsübertragung.

     

Thymectomy in the treatment of myasthenia gravis: report of 247 patients

Summary We made a retrospective assessment of the long-term outcome in 247 consecutive patients with myasthenia gravis (MG) who underwent thymectomy in the period January 1971–December 1985. In 84 cases a thymoma was found at surgery, while 163 patients had a non-neoplastic thymus. The duration of symptoms before surgery, the age at onset of the disease and the presence of germinal centres in the thymus did not appear to influence the prognosis. Patients with a non-neoplastic thymus showed a better response to thymectomy. Thymoma was associated with more severe disease and with a higher mortality; moreover, more thymoma patients required corticosteroid treatment in order to achieve good therapeutic results. In our opinion, thymectomy is indicated in the treatment of generalized MG, while ocular myasthenia seems not to be improved by the removal of the thymus.     

Decay and recovery of the stapedial reflex by prolonged stimulation in the diagnosis of myasthenia gravis

Summary The decay and recovery of stapedial reflex amplitude was investigated in 19 patients with myasthenia gravis and 30 control subjects. In 9 untreated patients the amplitude was reduced to less than 10% of the initial amplitude following continuous stimulation for 120 s, whereas the maximum decay in the control subjects was only 50%. In the group of treated patients the reflex decay showed individual variations. The rate of recovery after prolonged stimulation (5 min) was slower in the patient group, especially within the first 30 s of recovery. With increasing age, the rate of decay rose in the patient group as well as in the control group. The technical parameters necessary for obtaining information of clear diagnostic value are indicated, with which it was shown that the continuous prolonged stimulation of the stapedial muscle is a practical and valid method for the evaluation of patients with myasthenia gravis.     

女性重症肌无力1316例临床特点分析

目的　研究女性重症肌无力 (MG)的临床特点及某些实验室指标。方法　回顾性分析1984～ 2 0 0 2年我院诊治的 1316例女性MG患者的临床资料 ,检测乙酰胆碱受体抗体和血清性激素水平 ,并与同期诊治的男性MG患者进行对比分析。结果　MG患者男女比例基本相同 (1∶1 0 1) ,但不同年龄段男女患者比例差异有显著意义 ;延髓肌型MG虽少见 ,但女性 (6 0例 )患者明显多于男性 (35例 ,P <0 0 5 ) ;女性MG患者病情加重或者发生危象存在特殊诱因 ;女性MG患者伴胸腺瘤者较男性低 ;女性MG患者合并其他自身免疫性疾病者更多 ;MG患者存在性激素水平异常 ,女性较男性为甚。结论　我国女性MG的临床特点与男性MG相比有其独特之处 ,充分认识这些特点将有利于指导临床的诊断和治疗。     

无创机械通气在重症肌无力危象治疗中的疗效

目的 研究应用双水平气道正压 通气(BiPAP)治疗重症肌无力所致急性呼吸衰竭的治疗作用。方法 回顾性分析2011-2013年收治的重症肌无力合并急性呼吸衰竭患者而使用双水平气道正压通气(BiPAP)治疗23例,比较他们BiPAP 治疗前、治疗后2 h的动脉血气分析数据的变化,心率、呼吸频率及治疗2周后症状改善情况(QMG评分),并进行统计学分析。结果 23例患者中有18例无创机械通气治疗前患者心率(HR),呼吸频率(RR),血浆pH值,动脉血氧分压(PaO₂),动脉血二氧化碳分压(PaCO₂)分别为(108.7±17.6)次/min,(25.8±5.3)次/min,7.31±0.04,(58.7±13.3)mmHg,(53.8±7.8)mmHg; 治疗后2小时患者HR、RR、血浆pH值PaO₂、PaCO₂分别为(83.4±15.9)次/min,(21.1±4.9)次/min,7.36±0.04,(83.4±15.7)mmHg,(38.6±7.0)mmHg,较治疗前均明显改善。(P<0.05),治疗前患者QMG评分为17.94±2.07分,治疗2周后患者QMG评分为(10.06±2.71)分,也较治疗前有显著改善。(P<0.01)。结论 BiPAP治疗对重症肌无力所致急性呼吸衰竭的有重要治疗价值,能有效改善患者的呼吸功能。     

延髓型重症肌无力166例的临床特点

目的 研究延髓型重症肌无力（MG）的临床特点。方法 回顾性分析1983年5月至2005年10月间我院诊治的166例延髓型MG患者的临床资料，并与本院MG资料库中其他类型的NG患者2722例进行比较。结果 延髓型MG在本组患者中的发生率为5．7％（166／2888）。女性多于男性（男：女=1：1．35），发病年龄高峰为20～40岁。危象发生率高（44／166，26．5％），18例（10．8％）延髓型MG患者半年内发生危象，总病死率达6．0％（10／166）。肺部感染发生率高（30／166，18．1％）。早期误诊率高达19．9％（33／166）。治疗相对困难，激素“中剂量冲击、小剂量维持”疗法和中剂量环磷酰胺疗法短期疗效较好，胸腺切除术远期缓解达80．0％（20／25）。结论 本组结果显示，延髓型MG具有不同于其他类型MG的临床特点，充分认识其临床特点有助于降低误诊率，提高诊断水平和治疗效果。     

Myasthenia gravis: the specificities of skeletal muscle and thymus antibodies

Antibodies against skeletal muscle antigens and against thymic myoid cells were examined in sera from 40 patients with myasthenia gravis (MG). Using an indirect immunofluorescence technique, antibodies against the surface of muscle cells were found in 23 sera, and antibodies against muscle cell cross-striations in 28 sera. Antibodies against thymic myoid cells were found in 27 sera, stained cells also occurring in fetal thymus from 14 weeks of gestation and in hyperplastic thymus from MG patients. Sera which stained myoid cells also stained muscle cell cross-striations. Sera from all the 20 patients with thymoma contained antibodies to a citric acid extract of skeletal muscle (CAE) as detected by indirect haemagglutination, whereas sera from 20 comparable patients without thymoma did not contain CAE antibodies. The myoid cell antibodies could be absorbed by homogenized muscle, but not by CAE-coated sheep erythrocytes. Different antibody patterns are seen among different MG patients; close associations were found between cross-striational and myoid cell antibodies, and between CAE-antibodies and a thymoma.     

Prognosis of myasthenia gravis: a retrospective study of 380 patients

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission. Received: 27 October 1994 Received in revised form: 30 June 1997 Accepted: 10 July 1997     

Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis

Myasthenia gravis (MG) is a chronic autoimmune disorder with a fluctuating clinical course. The aim of immunotherapy is to bring about long-term remission. We evaluated the safety and efficacy of cyclophosphamide in generalized MG. We also highlight the limitations of cyclophosphamide therapy in inducing long-term remission. Data from 22 patients with generalized MG who received cyclophosphamide therapy were analyzed in terms of its safety and outcome. Twelve patients completed at least six pulses of intravenous cyclophosphamide therapy, and all improved symptomatically at 6 months. At 1 year, only seven patients reported sustained benefit and five had discontinued oral pyridostigmine. During a follow-up period of 56.67 months, all but one patient relapsed and required alternative immunomodulatory therapy. The average time to remission after the initiation of intravenous pulse cyclophosphamide (n = 12) was 3.6 months (standard deviation [SD] 1.6 months, range 1–6 months), while the mean duration of remission was 20.3 months (SD 8.8 months, range 12–39 months). Forty-six adverse events were documented in 11 patients over 127 cyclophosphamide pulses. Most of the adverse events were managed symptomatically. In four patients, cyclophosphamide had to be discontinued due to adverse events. Intravenous pulse cyclophosphamide is effective in the management of MG; however remission may be short, necessitating long-term follow-up and alternative immunomodulation. Careful monitoring for adverse events should be mandatory.     

伴胸腺瘤的重症肌无力患者治疗和预后

目的：研究伴有胸腺瘤的重症肌无力（MG）患者的治疗方法和影响预后的因素。方法回顾性研究103例经手术证实的MG伴胸腺瘤患者,给予皮质类固醇,化学疗法,放射疗法等治疗,观察患者的远期疗效和生存率。结果：MG总有效率为78．6％,其中完全缓解23例（22．3％）,药物缓解26例（25．2％）,部分缓解32例（31．3％）,5年和10年生存率分别为77．8％和48．5％,其中淋巴细胞为主型分别为88．9％和72．7％,混合型为83．3％和58．3％,上皮细胞为主型为55．6％和10．0％;按Masaoka分期标准,I期和II期患者的5,10年生存率分别为89．8％和76．2％,Ⅲ期和Ⅳ期为35．7％和0％,皮质类固醇和放疗等综合治疗患者5年和10年生存率分别达到88．9％和57．1％,结论：MG伴胸腺瘤患者手术后应给予皮质类固醇,放疗和化疗等综合, 提高疗效和和者生存,上皮细胞胞型胸腺瘤和Masaoka分期Ⅲ期和Ⅳ期患者预后较差。     

胸腺切除治疗重症肌无力围术期处理及疗效评价

目的对行胸腺切除术治疗的重症肌无力病人按围术期处理，进行疗效评估。方法应用胸腺切除术治疗的６４例重症肌无力病人，手术前后口服皮质类固醇、胆碱酯酶抑制剂，静脉滴注丙种球蛋白，并行血浆置换等以缓解肌无力症状。测定外周血乙酰胆碱受体抗体（ＡＣｈＲａｂ）和胸腺瘤相关抗体（ＣＡＥａｂ）的滴度。结果病人组术后ＡＣｈＲａｂ滴度明显下降，而ＣＡＥａｂ则无明显变化。术后随访１～１０年，总缓解率为８１．３％。结论所有重症肌无力病人，只要手术前后应用皮质类固醇调整免疫功能以及胆碱酯酶抑制剂、大剂量丙种球蛋白和血浆置换疗法等缓解症状，均可接受胸腺手术治疗，不受年龄、性别和病程的限制。