双重滤过血浆置换联合口服醋酸泼尼松治疗全身型重症肌无力：2例临床应用报告及文献复习

目的：报道2例双重滤过血浆置换（double filtration plasmapheresis,DFPP）联合口服小剂量醋酸泼尼松治疗全身型重症肌无力（myasthenia gravis,MG）的病例,旨在为MG临床治疗提供思路。方法：报道2例全身型MG患者的临床症状、辅助检查结果、诊疗经过以及预后,并结合相关文献复习,讨论不同治疗方法的作用。结果：病例1以“胸闷、气促3月余,加重伴双眼睑下垂、饮水呛咳1月”为主要临床表现,入院后完善相关检查,疲劳试验阳性,新斯的明试验阳性,四肢肌力4级,血清抗乙酰胆碱受体（acetylcholine receptor,Ach R）抗体阳性,重症肌无力评分（Quantitative MG Score,QMGS）为19分,MG日常生活质量（MG-activitie s of Daily Living Profile,MG-ADL）为13分。病例2因“吞咽乏力1月,加重伴四肢乏力1周余”入院诊治,查四肢肌力5级,洼田饮水试验3级,疲劳试验阳性。QMGS为6分,MG-ADL为11分,抗Ach R抗体>80 nmol/L。综合患者的临床表现和辅助检查结...     

抗体阴性重症肌无力的短程血浆置换疗法初探

血浆置换(plasma exchange,PE)在重症肌无力(MG)上的疗效已有报道,但缺乏明确一致的置换方案。我们对12例MG患者进行了37人次的短程PE,各例均在10d内行3～4次置换术,术前和术后第7天按Mantegazza肌力评分表进行临床疗效评定,结果除1例外,均获得肯定疗效,仅1人次发生较严重的副反应。4例抗体阴性病人置换后均获显著疗效,提示抗体阴性MG血浆中存在某些未知的致病因子。短程PE可供选择作为MG危象的治疗方案。     

血浆置换疗法抢救重症肌无力危象8例报告

我科1986～1990年收治重症肌无力危象40人次,其中8人次在综合抢救措施中,因常规抢救效果不佳,行血浆置换疗法(Plasma exchange简称PE)收到较好效果,报告如下。临床资料年龄与性别:17～60岁,平均41岁;男性5例,女性3例。病型与病程:均为全身型,发病至出现危象时间为3～60个月,平均21个月,其中5例在胸腺切除术后。诱发危象原因:感染5例,情绪激动、过劳2例,胸腺癌术后放疗1例;以感染诱发多见。     

小儿重症肌无力的免疫调节治疗

用肾上腺皮质激素，人血球蛋白、胸腺肽三者联合的免疫调节治疗方案治疗重症肌无力患者６８例，并观察了乙酰胆碱受体抗体及免疫球蛋白在治疗前后的变化，结果提示重症肌无力患儿体内免疫调节紊乱，本免疫调节疗法疗效满意，简便经济，且达到免疫调节目的。     

大剂量激素冲击联合小剂量血浆置换治疗重症肌无力的疗效

目的:观察大剂量激素冲击治疗以及联合小剂量血浆置换治疗重症肌无力的效果。方法;采用回顾性研究方法分析６７例患者用不同方法治疗的疗效,疗效判定用临床绝对评分和相对评分法,结果:各组治疗前后临床绝对评分有显著性差异,ｌ个月后,单用吡啶斯的明组、激素冲击治疗组、联合小剂量血浆置换组的相对评分分别为２７%、４８%、８１%。大剂量激素组、联合血浆置换组起效时间分别为２~３周、１~２周。结论:大剂量激素冲击治疗重症肌无力疗效肯定,如辅以小剂量血浆置换疗效更佳。     

血浆置换治疗在重症肌无力患者中的应用--附57例临床疗效分析

目的确定血浆置换（ＰＰ）治疗重症肌无力（ＭＧ）的起效时间、疗效,评价其疗效是否与降低血中乙酰胆碱受体抗体（ＡＣｈＲＡｂ）有关。方法ＰＰ第１周隔日１次,共３次,以后每周１次。用健康人血浆及血浆代用品进行ＰＰ,一般每次２０００ｍＬ（即７０６代血浆５００ｍＬ,血浆１５００ｍＬ）,置换当日及置换后每日于固定时间根据临床绝对记分法进行评分,同时每日晨取血查ＡＣｈＲＡｂ。结果痊愈、基本痊愈、显效、好转和无效分别为１、４、２３、２２和６例,总有效率８９．４７％。共有３５人、５２次在置换中出现不同程度副作用,包括口周麻木、四肢麻木、荨麻疹、寒战、发热和低血压等,经对症处理后好转。结论ＰＰ起效迅速,在肌无力危象抢救中有重要价值,但单独使用疗效不持久,应用得当可减少副作用。     

转移因子治疗重症肌无力中免疫作用的探讨

本文用转移因子(TF)配合抗胆碱酯酶药物治疗重症肌无力(MG)73例,其中16例用ELISA法测定了抗乙酰胆碱受体抗体(AchR-Ab)水平。结果表明:(1)治疗组较对照组症状缓解率明显提高、复发率明显下降(P<0.01)。且未见肌无力危象发生。(2)MG患者血清AChR-Ab水平明显高于正常对照组,经TF治疗后随着临床症状的缓解其AchR-Ab水平也明显下降(P<0.01)。(3)患者外周血淋巴细胞经丝裂原(PHA和PWM)刺激后其产生的AChR-Ab与正常对照组对比无明显差异(P>0.05)。     

血浆置换治疗在重症肌无力患者中的应用：附57例临 …

目的 确定血浆置换（ＰＰ）治疗重症肌无力（ＭＧ）的起效时间,疗效,评价其疗效是否与降低血中乙酰胆碱受体抗体（ＡＣｈＲＡｂ）有关。方法 ＰＰ第１周隔日１次,共３次,以后每周１次,用健康人血浆及血浆代用品进行了ＰＰ,一般每次２０００ｍＬ（即７０６代血浆５００ｍＬ,血浆１５００ｍＬ）置换当日及置换后每日于固定时间根据临床绝对记法分进行了评分,同时每日晨取血查ＡＣｈＲＡｂ。结果 痊愈,基本痊愈,显效,好转     

乙酰胆碱受体抗体测定对儿童重症肌无力的诊断价值

重症肌无力(MG)是累及神经肌肉接头突触后膜乙酰胆碱受体的自身免疫性疾病,免疫学研究已发现,患者血清中针对靶细胞的抗乙酰胆碱受体抗体(AchRsb)滴度增加,并认为AchRab是MG的主要致病因子。故检测患儿血清AchRab具有诊断MG的特异性价值。本文应用ELASA法对63例MG患儿进行了血清AchRab测定,发现大多数患儿抗体滴度明显升高,能反映临床情况,具有很高的实验诊断价值。     

重症肌无力免疫疗法新进展

重症肌无力(MG)是以乙酰胆碱受体抗体(AchRab)为主要致病因素的自身免疫性疾病,其治疗方法很多,但都以免疫疗法降低AchRab 为主。本文就免疫抑制剂、血液疗法、手术疗法和放射治疗等方面的新进展进行介绍。     

双重血浆置换与常规疗法治疗急性吉兰-巴雷综合征的随机对照研究

目的 比较双重血浆置换（double filtration plasmapheresis，DFPP）与常规疗法治疗急性吉兰一巴雷综合征（Guillain-Barre syndrome，GBS）的临床疗效。方法 将60例急性GBS患者随机分为DFPP组及常规治疗组，观察治疗前后神经功能改善状况，并检测治疗前后血液中免疫系列、补体系列及总蛋白水平。结果两组MRC（medical research council）评分于治疗1个月后、Hughes评分于治疗半年后比较差异有统计学意义，治疗后DF-PP组血液中免疫球蛋白IgG、IgA及补体C3明显低于常规治疗组，总蛋白无明显变化。结论 DFPP是治疗急性GBS较为有效的方法，可明显改善患者神经功能缺损状况，其机制可能与降低血液中免疫球蛋白及补体有关。     

Double filtration plasmapheresis in myasthenia gravis - analysis of clinical efficacy and prognostic parameters

OBJECTIVES: The aim of this study was to evaluate the efficacy of double filtration plasmapheresis (DFP) in the treatment of patients with myasthenia gravis (MG) and to analyze the possible prognostic factors related to responsiveness to DFP. MATERIALS AND METHODS: We treated 45 MG patients, 26 women and 19 men aged 21-72 years, with DFP for 5 consecutive sessions. All were affected by severe generalized or respiratory weakness with an Osserman's classification of group 2 or 3 and had not responded to previous treatments. RESULTS: Thirty-eight out of 45 patients (84%) achieved significant improvements after DFP. The baseline MG score and removal rate for immunoglobulin G (IgG) were significantly higher in the patients with good response than in the other response groups. Poor responders were more likely to have thymoma and a longer interval among sessions of DFP. Better response in patients with age at onset of less than 40 years was associated with higher MG score. Serum concentration of all proteins tested fell as follows (mean +/- SD): IgM, 88+/-7%; IgA, 71+/-11%; IgG, 59+/-14%; globulin, 52+/-11%; AchRAb, 47+/-14%; and albumin, 27+/-10%. All the patients tolerated plasmapheresis well except for 2.2% who experienced hypotension. CONCLUSION: In this study, DFP was effective and safe in the treatment of patients with severe generalized MG. The factors correlating with the better clinical response were high MG score, a thymic pathology of non-thymoma, daily apheresis, young age at onset, and high removal rate for IgG.     

大剂量丙球蛋白抢救重症肌无力危象的临床研究

目的:探讨大剂量丙球蛋白(Ig)在抢救重症肌无力危象的临床疗效。方法:根据Qsseman分型,Ⅱa型2例、Ⅱb型8例、Ⅲ型13例、Ⅳ型3例MG危象患者在综合抢救的同时联合应用大剂量Ig静脉注射为治疗组。Ⅱa型1例、Ⅱb型6例、Ⅲ型15例、Ⅳ型2例综合治疗患者为对照组。以临床绝对评分及临床相对评分作为治疗前、后疗效判定标准,于治疗前、后2周抽清晨空腹血查AChRAb,观察治疗前、后重症肌无力的免疫状态的变化。结果:治疗组治疗前、后AChRAb有明显差异(P<0.01)。对照组治疗前、后无明显差异。临床评分两组治疗前、后均有明显差异(P<0.05),但治疗组治疗前、后分值差明显大于对照组(P<0.01)。经治疗后两组危象持续时间及有效率有明显差异(P<0.01)。结论:大剂量Ig在抢救MG危象中疗效明显、安全、可靠,值得临床应用。     

Double filtration plasmapheresis in the treatment of myasthenic crisis--analysis of prognostic factors and efficacy

OBJECTIVES: To examine the prognostic factors and outcome of myasthenia gravis (MG) patients in crisis with double filtration plasmapheresis (DFP) treatment. MATERIAL AND METHODS: A total of 15 patients experienced 20 episodes of crisis during the study period. Plasmapheresis was carried out using a double filtration METHOD: Demographic information, clinical features of crisis, and associated complications were analyzed. RESULTS: The median duration of crisis was 9 days. Chest infection was the most common precipitant of crisis. Twelve out of the 20 episodes (60%) responded well to DFP and mechanical ventilation was discontinued after the third session of DFP in 8 of them. Three significant predictors for prolonged crisis were shorter intervals between the onset of MG and the first crisis (P=0.04), higher serum bicarbonate levels at baseline (P=0.03) and the thymic pathology of thymoma (P=0.03). CONCLUSION: DFP can ameliorate the profound weakness in crisis and seems to be a rational therapy for patients with myasthenic crisis.     

Predicting the course of myasthenic weakness following double filtration plasmapheresis

OBJECTIVE: To evaluate the clinical course of patients with myasthenia gravis (MG) up to 3 months after double filtration plasmapheresis (DFP). MATERIAL AND METHODS: We recorded the MG score and measured the level of acetylcholine receptor antibody (AchRAb) at baseline and day 1 (D1), week 1 (W1), 1 month (M1), 2 (M2) and 3 months (M3) after DFP in 16 MG patients. Based on the difference in score during follow-up, we divided our patients into clinical improvement (CI) and clinical worsening (CW) groups. RESULTS: The MG score decreased in all courses from a mean of 8.1 at baseline to 5.6 at D1, and to 4.7, 4.0, 3.8, and 3.7 at W1, M1, M2, and M3, respectively. In the CW group, AchRAb levels were significantly higher at M1 (P = 0.022). The AchRAb level at W1 correlated significantly with the MG score at M3 (P = 0.027) and the changes of MG score from W1 to M1 (P = 0.029). The ratio of AchRAb levels of M1 to W1 correlated well with MG score at W1 (P = 0.032), at M3 (P = 0.001), and the changes of MG score from W1 to M1 (P = 0.004). CONCLUSION: Excessive rebounds of AchRAb level at W1 may suggest clinical worsening and further increases in AchRAb level at M1 predict poorer outcome after DFP.     

Plasmapheresis combined with lymphocytapheresis and cytotoxic drugs as a therapeutic modality in neuroimmunological diseases

Rebound after plasmapheresis is thought to be due to enhanced antibody and/or immune complex production. To prevent rebound a combination of steroids and immunosuppressive drugs has been used: lymphocytapheresis was employed in most patients, for not more than 10 sessions. 50 patients with myasthenia gravis, inflammatory myopathy, chronic dysimmune polyneuropathy and immune complex polyneuropathy have been treated and longlasting benefits obtained in 35 patients. Rebound effects were observed only when cytotoxic drugs were not given or discontinued too soon. 8 patients who had been treated by plasmapheresis combined with steroids alone, after some recurrences of their disease, were switched to cytotoxic drugs, steroids and lymphocytapheresis combined with plasma exchange: in this group 7 patients eventually gained long lasting remissions. Our clinical experience strongly supports the hypothesis of a synergy between plasmapheresis and immunosuppressive measures.

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Sommario Si ritiene che il possibile effetto rebound che consegue alla plasmaferesi sia dovuto all'incremento di anticorpi e/o di immuno-complessi. Per prevenire tale effetto si utilizzano farmaci steroidei e immunosopressori; la linfocitoaferesi è stata applicata in diversi pazienti, ma per non più di 10 sedute. Gli AA. hanno trattato 50 pazienti affetti da miastenia, polimiosite, polineuropatie croniche disimmuni e polineuropatie da immuno-complessi con buoni risultati a distanza in 35 casi; un effetto rebound è stato osservato soltanto nei casi in cui non era stato instaurato o era stato interrotto inopportunamente un trattamento immunosoppressivo. In 8 pazienti che erano stati trattati con plasmaferesi associata a soli farmaci steroidei, dopo alcune recidive sintomatologiche della malattia, è stato instaurato uno schema terapeutico che prevedeva cortisonici, immunosopressori e linfocitoaferesi associati alla plasmaferesi: in 7 casi sono state così ottenute delle remissioni di lunga durata. Sulla scorta di tale esperienza clinica si ritiene fondata l'ipotesi di un sinergismo tra plasmaferesi e trattamento immunosoppressivo.

     

Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DR). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (IG), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P>0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P<0.05), while DF removed more IgA (72 % vs. 21 %, P< 0.05) and IgM (89 % vs. 57 %, P<0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG. Received: 10 September 1999, Received in revised form: 7 February 2000, Accepted: 24 February 2000     

Double filtration plasmapheresis benefits myasthenia gravis patients through an immunomodulatory action

Double filtration plasmapheresis (DFPP) is used to treat myasthenia gravis (MG). However, the definite mechanism is unclear. This study investigated whether DFPP improves MG through an immunomodulatory action. Thirty-five MG patients were randomly divided into two treatment groups: Group A (DFPP combined with oral methylprednisolone) and Group B (oral methylprednisolone alone). Their antibody levels, clinical scores, cytokine levels, and CD4⁺CD25^highFoxp3⁺ (regulatory T cell [Treg]) levels were then determined. Anti-titin antibody levels were significantly lower in Group A compared with Group B after treatment. The clinical remission rate in Group A was significantly higher than in Group B. The changes in cytokine levels (interleukin [IL]-2, IL-4, IL-10, and interferon-γ) in sera and the peripheral blood mononuclear cell culture supernatants did not significantly differ before and after the treatments in both groups (p < 0.05). The soluble intercellular adhesion molecule-1 (sICAM-1) levels were lower in Group A than in Group B (p < 0.05). MG patients exhibited a lower percentage of Treg cells than normal patients. DFPP combined with methylprednisolone treatment increased the Treg cell percentage more than treatment with methylprednisolone alone (p < 0.05). DFPP treatment more effectively lowers sICAM-1 and increases Treg cell expression, consequently benefiting MG patients.     

Plasmapheresis in myasthenia gravis. A comparative study of daily versus alternately daily schedule

OBJECTIVES: The aim of this study was to compare the efficacy of different protocols of plasmapheresis in the treatment of myasthenia gravis (MG). MATERIALS AND METHODS: We treated 30 MG patients with plasmapheresis on either a daily or alternately daily schedule for 5 consecutive sessions. Acetylcholine receptor antibody (AchRAb), serum proteins including albumin, globulin, immunoglobulin G (IgG), IgA, and IgM, and MG score were measured before and after the course of plasmapheresis in each group of patients. RESULTS: The mean percent reductions of serum proteins including IgA (81.5% vs 69.7%), IgM (95.6% vs 87.1%), and globulin (63.2% vs 50.1%) were significantly higher in the daily group. There were no significant differences in AchRAb and IgG levels after treatment between these 2 groups. However, the reduction of MG score was greater in the daily group. All the patients tolerated plasmapheresis well except for 2.7% of them who experienced hypotension. CONCLUSION: Our results suggest that daily plasmapheresis may be more effective in the treatment of patients with advanced MG.