大剂量免疫球蛋白及肾上腺皮质激素治疗重症？…

目的 为研究免疫球蛋白对重症肌无力（ＭＧ）的治疗效果。对６２例ＭＧ患者进行了免疫球蛋白及肾上腺皮质激素治疗的对比研究,方法 ３２例ＭＧ患者静脉注射大剂量免疫球蛋白（ＩＶＩｇ）３０列ＭＧ患者应用了肾上腺皮质激素（ＡＣＳ）冲击治疗。临床绝对评分及相对评分作为治疗前后疗效判定标准,结果 ６２例ＭＧ患者治疗前后评分有明显差异（Ｐ〈０．０１）,ＡＣＳ治疗前后差值较ＩＶＩｇ明显加大（Ｐ〈０．０１）。结论 ＩＶ     

癫痫患儿的免疫功能及免疫球蛋白辅助治疗的初步研究

目的：探讨癫痫患儿的免疫功能状态及免疫球蛋白辅助治疗的疗效。方法：测定５４例癫痫患儿血中ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｓ３及Ｔ细胞亚群，与正常对照组比较；对１４例常规抗癫痫治疗效果不佳者加用免疫球蛋白辅助治疗，观察疗效。结果：癫痫患儿血清ＩｇＧ降低（Ｐ＜０．０５），ＩｇＡ降低（Ｐ＜０．０１），ＩｇＭ及Ｃ３正常，ＣＤ３、ＣＤ４降低（Ｐ＜０．０５），ＣＤ８升高（Ｐ＜０．０１），ＣＤ４／ＣＤ８降低（Ｐ＜０．０５），免疫球蛋白辅助治疗有效率５７．２％。结论：癫痫患儿存在免疫功能紊乱，提示免疫机制参与了癫痫发病机制；免疫球蛋白辅助治疗癫痫有效。     

抗心磷脂抗体与偏头痛的关系

采用酶联免疫吸附法（ＥＬＩＳＡ）检测８９例偏头痛患者和６２例健康人血清中ＩｇＧ、ＩｇＡ和ＩｇＭ３种类型抗心磷脂抗体（ＡＣＬ）。结果表明患者组３种类型ＡＣＬ指数均显著高于对照组（Ｐ＜０．０５，Ｐ＜０．０１），其中３５例具有一种类型以上ＡＣＬ阳性（３９．３％），以ＩｇＧ型阳性为主。而且女性患者ＡＣＬ阳性率显著高于男性。提示偏头痛的发病与ＡＣＬ生成有一定关系。     

低能量氦氖激光血管内照射疗法对急性脑梗塞患者血清免疫球蛋白含量的影响

选择发病后２ｈ至７ｄ内入院的急性脑梗塞患者３０例，依据入院翌日晨检测的血清免疫球蛋白含量分为低免疫球蛋白组和高免疫球蛋白组，并设立对照组。３组均仅接受低能量氦氖激光血管内照射治疗。疗程结束后复查ＩｇＧ、ＩｇＡ、ＩｇＭ，进行低能量激光治疗前后的比较。结果显示：低能量激光治疗前，与对照组相比，低免疫球蛋白组ＩｇＧ降低，高免疫球蛋白组ＩｇＧ升高，有显著性差异（Ｐ＜０．０１）；治疗前后各组相比，低免疫球蛋白组ＩｇＧ升高，高免疫球蛋白组ＩｇＧ降低，有显著性差异（Ｐ＜０．００１），对照组治疗前后ＩｇＧ改变无统计学意义；低能量激光治疗后，低免疫球蛋白组ＩｇＧ高于对照组（Ｐ＜０．０５），高免疫球蛋白组ＩｇＧ和对照组相比无显著性差异。３组间ＩｇＡ、ＩｇＭ治疗前后均无统计学意义。本研究结果表明，低能量氦氖激光血管内照射疗法具有免疫调节功能，对进一步探讨急性脑血管病的危险因素及其治疗有积极意义。     

重症肌无力患者若干临床问题探讨（附10例分析）

报告１０例ＭＧ病人均检测了周围血淋巴细胞计数、血清免疫球蛋白（ＩｇＧ、ＩｇＡ、ＩｇＭ）、补体Ｃ３、ＣＨ５０、Ｅ－玫瑰花结试验（ＥＲＦＴ）和淋巴细胞转换试验（ＬＴＴ），同时还测定血丙酮酸及酶谱（ＧＯＴ、ＬＤＨ、ＣＰＫ），并设３０例正常对照。ＭＧ组与对照组比较，除ＥＲＦＴ（Ｐ＜０．００１）、ＧＯＴ（Ｐ＜０．０１）、ＣＰＫ（Ｐ＜０．０１）、及ＬＤＨ（Ｐ＜０．０５）有差异外，余诸项均无统计学意义、提示一般血清免疫学或补体测定对ＭＧ诊断无特异性意义，结合文献复习对ＭＧ患者若干临床问题分别进行讨论。     

精神分裂症患者的脑脊液免疫球蛋白含量分析

作者对３４例精神分裂症患者的脑脊液中的免疫球蛋白（Ｉｇ）含量进行了测定分析。结果显示：精神分裂症患者脑脊液中ＩｇＣ（Ｐ＜０．００１）、ＩｇＡ（Ｐ＜０．０５）、ＩｇＭ（Ｐ＜０．０１）含量显著高于正常人对照组。这提示精神分裂症患者确有免疫学方面的异常。     

格林—巴利综合征患者血清和脑脊液中的抗硫脂抗体

探讨抗硫脂抗体与格林－巴利综合征（ＧＢＳ）的关系。方法采用固相酶联免疫吸附法对急性期ＧＢＳ患者血清和脑脊液（ＣＳＦ）中抗硫脂ＩｇＧ和ＩｇＭ抗体进行检测。结果ＧＢＳ患者血清和ＣＳＦ中抗硫脂ＩｇＧ及ＩｇＭ抗体的阳性率均明显高于正常对照组；血清中抗硫脂ＩｇＭ抗体滴度与标本收集时患者发病天数呈负相关（Ｐ＜０．０５），而血清中抗硫脂ＩｇＧ抗体滴度与临床分级（Ｐ＜０．０１）、ＣＳＦ中抗硫脂ＩｇＧ抗体滴度（Ｐ＜０．０１）呈正相关；血清中抗硫脂ＩｇＧ或ＩｇＭ阳性的ＧＢＳ患者，体检时有不同程度的感觉障碍患者为５６％，而血清中抗硫脂抗体阴性患者仅为１６％，两者之间差异有显著意义（Ｐ＜０．０５）。结论抗硫脂抗体可能在ＧＢＳ的病理过程中起重要作用     

多发梗塞性痴呆患者血浆和脑脊液中若干神经肽含量的变化

用放射免疫法测定了３０例多发梗塞性痴呆（ＭＩＤ）、３５例无痴呆多发脑梗塞患者（ＭＣＩ）及３０名健康人的血浆生长抑素（ＳＳ）、精氨酸加压素（ＡＶＰ）及β－内啡肽（β－ＥＰ）含量，同时测定了部分ＭＩＤ和ＭＣＩ患者脑脊液（ＣＳＦ）中ＳＳ、ＡＶＰ、β－ＥＰ含量。发现ＭＩＤ患者血浆ＳＳ、ＡＶＰ含量比ＭＣＩ组和健康对照组均降低（Ｐ＜０．０５），且随痴呆程度的加重，其含量有递减趋势。而血浆中β－ＥＰ在这三组间差异无显著性意义（Ｐ＞０．０５）。ＭＩＤ组ＣＳＦ中ＳＳ、β－ＥＰ含量低于ＭＣＩ组（Ｐ＜０．０５），而ＣＳＦ中ＡＶＰ含量在两组间无差异（Ｐ＞０．０５），ＣＳＦ中ＡＶＰ含量与痴呆的关系有待进一步研究。     

高血压合并急性脑血管病的心率变异性改变

对原发性高血压（ＥＨ）合并急性脑血管病（ＡＣＶＤ）患者３０例进行２４小时动态心电图心率变异性（ＨＲＶ）测定，并与３０例无ＡＣＶＤ的ＥＨ患者进行对比。结果显示，合并ＡＣＶＤ组最小心率及平均心率明显高于对照组（Ｐ＜０．０１、＜０．００１）；ＳＤＮＮ、ｒＭＳＳＤ、ＰＮＮ５０比对照组明显减低（Ｐ＜０．００１、＜０．０１、＜０．００１）。提示合并ＡＣＶＤ的ＥＨ患者ＨＲＶ减低，其主要原因可能是自主神经中枢损害。     

格林—巴利综合征患者血清和脑脊液中白细胞介素6检测及其意义

采用生物学方法检测了３０例ＧＢＳ患者血清及脑脊液中ＩＬ－６水平，结果表明ＧＢＳ患者血清及脑脊液中ＩＬ－６检出率及水平明显高于非炎症性神经病组及正常对照组（均Ｐ＜０．０１）；１４例血清和脑脊液均可检出ＩＬ－６的ＧＢＳ患者中，血清ＩＬ－６水平与脑脊液中ＩＬ－６水平之间无相关性（Ｐ＞０．０５）；血清ＩＬ－６检测阳性的ＧＢＳ患者中，血清免疫球蛋白水平（ＩｇＧ、ＩｇＭ、ＩｇＡ）明显高于血清ＩＬ－６检测阴性的ＧＢＳ患者及正常对照组（均Ｐ＜０．０１），而血清ＩＬ－６检测阴性的ＧＢＳ患者血清免疫球蛋白水平与正常对照组比较无明显差别（Ｐ＞０．０５）。提示ＩＬ－６与ＧＢＳ发病有关。     

Intravenous immunoglobulin for prophylaxis of acute exacerbation in Myasthenia Gravis

Intravenous immunoglobulin (IVIg) treatment for acute exacerbations of Myasthenia Gravis (MG) was shown in several open-label studies. There are only two studies demonstrating the efficiency of regular intermittent IVIg therapy on MG patients who are not in their acute attack periods. Thirteen patients who had displayed an inadequate clinical response to immunosuppressive treatments, or who were not appropriate for immunosuppressive treatment due to the age factor and thus were given regular IVIg therapy, were retrospectively investigated. Moreover, the pre- and post-treatment attack frequencies were also evaluated. The mean number of attacks was 0.0960 attacks/year before IVIg therapy, and 0.0056 attacks/year after IVIg therapy (p = 0.002). The number and severity of the attacks were decreased in all patients. Eight patients (62 %) had used steroids; among them, steroid was completely stopped in two patients following the regular IVIg therapy, and the dose was decreased by 50 % in the other six patients. The requirement for pyridostigmine did not decrease in four patients, whereas this need decreased by 20–50 % in nine patients. IVIg can produce repeated beneficial effects in patients with MG and may be useful as an adjunct in the management of MG. IVIg has minimal adverse effects and ability to reduce corticosteroid dose. These results suggest that intravenous immunoglobulin maintenance therapy is a valid modality in patients with resistant treatment MG.     

静脉注射人免疫球蛋白治疗全身型重症肌无力的短期疗效观察

目的观察静脉注射人免疫球蛋白(intravenous immunoglobulin, IVIg)治疗全身型重症肌无力(myasthenia gravis, MG)的短期临床疗效、安全性。方法纳入2016年1月至2019年9月期间北京医院就诊的58例Osserman分型Ⅱb及以上的全身型MG患者。收集患者一般信息、入院诊断、治疗用药情况,采用许氏绝对与相对评分法(the absolute and relative score of MG,ARS-MG)评估患者IVIg治疗前及治疗后7、14 d临床症状的改善情况,并比较不同年龄(<60岁和≥60岁)、病程(≤1年和>1年)以及有无构音障碍、咀嚼障碍、呼吸困难者间IVIg疗效的差异。结果 58例MG患者IVIg治疗后第7天许氏评分较治疗前降低[(17.21±10.52)分比(23.22±10.45)分,P<0.01]。IVIg治疗7 d时其总有效率为48.28%(n=58),治疗后14 d其总有效率为59.46%(n=37)。不同年龄、病程以及有无构音障碍、咀嚼障碍、呼吸困难者间IVIg疗效比较无统计学差异(均P>0...     

IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory myopathies: current status

Intravenous immunoglobulin (IVIg) is an effective tool for the treatment of diseases with immune pathogenesis. This article reviews the current knowledge of the benefits of treating with IVIg patients with myasthenia gravis (MG), Lambert Eaton myasthenic syndrome (LEMS), dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Myasthenia gravis: Treatment of MG with IVIg was reported to be beneficial in a number of case series and two randomised controlled trials, in which efficacy was measured by clinical improvement using myasthenic muscle score and decrease in anti-acetylcholine receptor antibodies (AchRAb). According to the results, IVIg could be recommended for crisis and severe exacerbation. In many other clinical conditions, such as response to treatment of mild or moderate exacerbation, changes in steroid dosage and before thymectomy, IVIg has also been reported to be helpful, but no controlled trials to confirm its efficacy have been performed. Lambert-Eaton myasthenic syndrome: A placebo-controlled crossover study reported a significant clinical improvement in the amplitude of the resting CMAP following IVIg treatment. Further experience from case reports also indicates that IVIg is useful in patients with LEMS, both as a short- and long-term treatment, especially when immunosuppressive drugs are not fully effective. Inflammatory myopathies/dermatomyositis: In a double-blind placebo-controlled crossover trial in patients with DM resistant to other treatments, IVIg was shown to produce a significant increase of muscle strength as well as a marked improvement in immunopathological parameters in repeated muscle biopsies (before and after IVIg). Thus, IVIg is an important therapy in patients with DM resistant to other conventional therapies. Polymyositis: No randomised trials have been undertaken. One study showed clinical improvement and a reduction in the need of prednisone in patients with chronic refractory PM. Inclusion body myositis: Three controlled trials showed some muscle strength improvement, although the changes did not reach statistical significance. However improvement in swallowing was repeatedly observed, suggesting that some patients with severe dysphagia may derive a modest benefit from IVIg therapy. CONCLUSION: Controlled trials indicate that in MG, LEMS, and DM, IVIg at a total dose of 2 g/kg is a highly useful therapy. Uncontrolled trials and case reports indicate benefit in many different clinical situations, but further clinical investigation is required.     

Intravenous immunoglobulin in the preparation of thymectomy for myasthenia gravis

OBJECTIVES: A clinical trial including six patients was conducted to assess the effect of intravenous immunoglobulin (IVIg) in the preparation of thymectomy for patients with myasthenia gravis (MG). MATERIAL AND METHODS: Six consecutive patients of type IIB MG treated with IVIg at a dose 0.4 g/kg daily for 5 days before thymectomy were enrolled in this study. RESULTS: All patients responded positively to this treatment. Improvement began to occur 1-9 days after starting the injection (mean 3.33 days), and reached a maximum in 3-19 days (mean 6.50 days). Thymectomy was performed 9-13 days (mean 11.20 days) after starting the injection in five of the six patients with uneventful post-operative courses. CONCLUSION: IVIg might be an alternative to plasmapheresis (PE) in the prethymectomy preparation of MG patients, and thymectomy should be performed within 2 weeks after IVIg treatment to minimize the perioperative complications. Controlled trial vs PE enrolling more patients is needed to assess the significance of the IVIg in the preparation of thymectomy for patients of MG.     

High-dose intravenous immunoglobulin therapy for myasthenia gravis

The objective of this open, retrospective study was to investigate whether intravenous immunoglobulin (IVIg) could induce a clinically obvious improvement in patients with generalized myasthenia gravis (MG), as judged by MG functional status. Fourteen patients with generalized MG were treated during at least one episode with 0.4 g IVIg per kilogram body weight per day for 5 consecutive days. Patients with confounding variables were excluded; this left 11 patients (16 episodes) to be further analysed. We defined improvement as at least a one-step improvement in MG functional status (according to the University of Virginia’s Modification of Osserman’s classification). Of the treatment episodes, 56% were classified as positive responses. If improvement occurred, onset of improvement started after 3 (1–12) days and peak effect was reached after 7 (4– 30) days (median and range). All four patients who required artificial ventilation could be weaned from it 8.5 (6–11) days after the start of IVIg (median and range). Of the patients treated on two occasions, only one patient had a positive response during both. In MG functional status 5, improvement was observed during five of seven episodes. None of the patients with MG functional status 3 responded. Patients with an acute relapse of MG seemed to respond equally well to IVIg compared with patients with subacute deterioration/ chronic-static state (50% versus 60%). The MG functional status at the start of IVIg and on the day of maximal improvement was compared for all episodes together, and significant improvement was noted (P = 0.0052). We did not see any serious side-effects after IVIg treatment. This retrospective analysis suggests that high-dose IVIg is an effective therapy in some patients with deterioration of generalized MG. If improvement occurs, it starts within a few days of the onset of IVIg and the effect seems to peak within 2 weeks. Received: 4 March 1997 Received in revised form: 28 August 1997 Accepted: 1 September 1997     

High-dose intravenous immunoglobulin for the treatment of MuSK antibody-positive seronegative myasthenia gravis

We treated two patients with anti-muscle specific tyrosine kinase (MuSK)-antibody positive seronegative myasthenia gravis (MG) with high-dose intravenous gammaglobulin (IVIg) and evaluated their clinical courses. Both patients were Japanese women, MuSK-positive seronegative MG, and were unresponsive to conventional treatments, including thymectomy, steroids, and tacrolimus. The patients required frequent hospitalization for plasmapheresis. In case 1, a 45-year-old woman, it was difficult to obtain blood access for plasmapheresis. High-dose IVIg, 400 mg/kg per day for 5 days, was administered in cases 1 and 2. In both cases, clinical improvement was observed 3 days after the start of IVIg therapy and lasted for 2 to 3 months. We propose that IVIg therapy is an effective treatment for MuSK-positive seronegative MG, when conventional treatments have failed.     

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。     

IVIg in other autoimmune neurological disorders: current status and future prospects

A number of autoimmune disorders have been identified in which IVIg treatment may be beneficial. Evidence for the use of IVIg in inflammatory myopathies comes from controlled trials in dermatomyositis (DM) and sporadic-inclusion body myositis (s-IBM). In DM, muscle strength was increased and neuromuscular scores and skin rashes improved. Results for s-IBM have not been as encouraging as those observed for DM. Subsequently, IVIg should be recommended as a second-line therapy in DM and used for life-threatening dysphagia in s-IBM. Using an animal model of experimental autoimmune myasthenia gravis (MG), studies also indicate that IVIg can significantly improve clinical symptoms and affect pathogenic idiotypic antibodies. In human MG, studies indicate that IVIg exhibited equal efficacy compared to plasmapheresis. IVIg can therefore be recommended for use in an MG crisis or in lieu of plasmapheresis. The role of IVIg in the chronic management of MG has not been studied. IVIg has also been investigated in autoimmune CNS disorders. In a controlled study in patients with stiff person syndrome IVIg was effective, with improvements in the distribution of stiffness index and heightened sensitivity scores. For neurodegenerative diseases such as Alzheimer's disease, post-polio syndrome, pain, fibrosis, and autoimmune sleep disorders, some early promising results for the use of IVIg are emerging, but remain to be fully investigated. In conclusion, IVIg appears to be an effective treatment for a number of autoimmune disorders, however, optimal dosing and pharmacogenetic studies are necessary.     

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.     

Intravenous immune globulin usage for neurological and neuromuscular disorders: an academic centre, 4 years experience

Intravenous immune globulin (IVIg) use for labeled and unlabeled indications has grown in the last years. Aim of this study was to evaluate the IVIg usage profile for neurological inpatients in a single academic medical centre, over a long period of time. We retrospectively reviewed all approved IVIg transfusions for neurological disorders at Careggi Hospital from 2003 to 2006. The pharmacy records were then cross-referenced with patient medical records to determine the indication for IVIg administration. From 2003 to 2006 we observed a tremendous increase in IVIg administration, in the annual number of treated patients and in the mean annual courses. Fifty-seven patients (24%) received a long-term IVIg treatment, which accounted for 61% of the total IVIg consumption. The use of IVIg continues to expand despite concerns on future availability and long-term safety; alternative treatment strategies in chronic neurological disorders which require long-term, potentially indefinite therapy are warranted.