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.     

Comparative efficacy of low dose,daily versus alternate day plasma exchange in severe myasthenia gravis

Abstract Objective To evaluate the comparative efficacy of low dose daily versus alternate day plasma exchange in patients with severe myasthenia. Methods Thirty three patients with myasthenia gravis (Osserman's stage II b and III) were randomized to receive alternate day (n = 17) or daily low dose plasma exchange (n = 16). Plasma exchange were carried on each patient, number of exchanges varying subject to their requirements and 20-25 ml/kg plasma was removed during each session. Myasthenia gravis disease scale (MGDS) score was evaluated before and after the procedure. Time to wean off ventilator, removal of nasogastric tube and total duration of hospital stay were also assessed. Results There was no statistically significant difference between daily vs. alternate day group with regards to change in MGDS score, percentage change in MGDS score, and complication rates. A decreased hospital stay was observed in patients on daily plasma exchange which almost reached statistical significance. Conclusion We conclude from our study that daily and alternate day plasma exchange are similar in their efficacy and complication rates, however the daily schedule could be a preferred modality due to decreased hospital stay.     

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.     

Safety of plasma exchange therapy in patients with myasthenia gravis

Introduction: Plasma exchange (PLEX) is effective in myasthenia gravis (MG), but there are concerns about its safety. Methods: We collected data prospectively from 42 patients randomized to PLEX treatment in a comparison study with intravenous immunoglobulin (IVIg). Detailed information on the PLEX treatment methodology and adverse events are reported. Results: Forty of 42 patients completed PLEX. Ninety percent were treated in an outpatient setting. Fifty‐five percent had no complications, and 45% had mild–moderate reactions that did not require stopping treatment; the majority were citrate reactions and peripheral vascular issues that were easily treated. Fifty‐seven percent of patients responded to treatment, and 83% completed PLEX via peripheral venous access. Two patients had severe adverse events: 1 related and 1 unrelated to PLEX. Comorbid disease and age did not predict reactions. Conclusion: PLEX is safe, effective, and well tolerated in patients with MG. Our results do not raise concerns about the safety of PLEX in patients with moderate–severe MG. Muscle Nerve 47: 510–514, 2013     

Plasma exchange in myasthenia gravis: effect on anti-AChR antibodies and other autoantibodies

Plasma exchange (PE) was performed in 6 patients with myasthenia gravis (MG). Acetylcholine receptor (AChR) antibodies and other MG-correlated antibodies were quantified each day before, during and after PE. The antibody concentrations decreased during PE with a consisting increase between two exchanges. Repeated PE induced a transient decline in the AChR antibody concentration. The clinical improvement was maximal during the week after PE and correlated in time with increasing concentrations of AChR antibodies.     

Plasma exchange in myasthenia gravis: changes in serum complement and immunoglobulins

Serum concentrations of C4, IgG, IgA, and IgM were followed in 8 selected patients with myasthenia gravis (MG) during a 5-day course of plasma exchange (PE), using donor plasma as a replacement solution. C3 activation products (C3b, iC3b and C3c) and the terminal SC5b-9 complement complex were measured in 4 of the patients. All patients improved during the treatment, including 2 patients without detectable antibodies to AChR in serum. The main findings of the study were marked complement activation and an approximately 50% fall in the serum concentrations of IgM and C4 during PE, independent of the concentrations in the donor plasma. The concentrations of IgG and IgA did not change significantly. The fall in C4 during PE is presumably caused by C4 consumption. We postulate that the fall in IgM is an effect of a complement-induced vasodilatation and that PE-induced complement consumption may influence the effect of PE in patients with MG.     

Outcome of plasmapheresis in myasthenia gravis: delayed therapy is not favorable

Introduction: The purpose of this study was to compare the in‐hospital mortality and complication rates after early and delayed initiation of plasma exchange (PLEX) in patients with myasthenia gravis (MG). Methods: Our cohort was identified from the Nationwide Inpatient Sample database for the years 2000 through 2005. Early treatment was defined as therapy with PLEX administered within the first 2 days from hospital admission. Univariate and multivariate analyses were employed. Results: One thousand fifty‐three patients were treated and included in the analysis. A delay in receiving PLEX was associated with higher mortality (6.56% vs. 1.15%, P < 0.001) and increased complications (29.51% vs. 15.29%, P < 0.001). Adjusted analysis showed increased mortality [odds ratio (OR) 2.812; 95% confidence interval (CI) 1.119–7.069] and complications (OR 1.672; 95% CI 1.118–2.501) with delayed PLEX therapy. Conclusions: Delaying PLEX therapy for MG by more than 2 days after admission may lead to higher mortality and complication rates, and thus prompt therapy is warranted. Muscle Nerve 43: 578–584, 2011     

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.     

静脉注射免疫球蛋白与血浆置换治疗重症肌无力的meta分析

目的系统评价静脉注射免疫球蛋白(IVIg)与血浆置换(PLEX)治疗重症肌无力(MG)的有效性和安全性。方法计算机检索Cochrane图书馆、Pubmed、Embase、CNKI及万方数据库,系统收集国内外有关这两种方式治疗MG的相关文献。按系统评价的方法,由2名研究员独立对文献进行质量评价和资料提取后,采用Rev Man 5.2软件进行Meta分析。结果共纳入9篇文献,合计2132例MG患者。Meta分析结果显示,IVIG与PLEX治疗MG的有效性无明显差异[OR=0.94,95%CI(0.57,1.32),P=0.79];IVIg与PLEX的治疗相关不良反应发生率也无明显差异[OR=0.91,95%CI(-0.37,2.21),P=0.83]。结论 IVIG与PLEX对MG的治疗效果以及治疗相关的不良反应发生率均无明显差异,因此,临床上可根据具体情况选择合适的治疗方式。     

A short plasma exchange protocol is effective in severe myasthenia gravis

Summary Plasma exchange has been reported to be a successful therapeutic procedure for the treatment of severely compromised myasthenic patients, but the optimal regimen in terms of costs or clinical benefit has not so far been determined. We have investigated the efficacy of a short plasmapheresis protocol of two exchanges 1 day apart in a series of 70 patients with severe forms of myasthenia gravis. Patients were evaluated before and 7 days after the first exchange. A positive outcome was observed in 70% of the plasma exchange cycles performed. Disease severity did not seem to be a negative prognostic factor for the efficacy of this short protocol, which was well tolerated by patients. In only 1 case were major side-effects observed. In spite of its short duration, the exchange treatment plus concomitant immunosuppressive drug therapy was not followed by early clinical deterioration.     

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     

A study of hand preference in myasthenia gravis

A recent study reported an association between left-handedness and some pathologies, such as autoimmune diseases, including myasthenia gravis (MG). We studied hand preference in 102 patients with a generalized autoimmune form of myasthenia gravis and in a control group of 178 subjects. We employed Oldfield's inventory with a few minor modifications. The questionnaire also asked the hand preference of patients' and controls' relatives. For each subject, the laterality quotient (LQ) was calculated and submitted to ANOVA. The frequency of left-handedness in controls was similar to that reported in the literature. Although left-handedness occurred less often in myasthenics, the difference between the two groups was not significant. Also the frequency of left-handedness in relatives of myasthenic patients did not differ from that observed in controls.     

Recovery from global amnesia during plasma exchange in myasthenia gravis: report of a case

A 47-year old thymectomized woman with myasthenia gravis, receiving prednisone therapy, developed amnesia for recent events during a benign acute febrile illness. Plasma exchange was performed 9 months later, and was followed by a dramatic improvement of the mnemonic dysfunction.     

Associated autoimmune diseases in myasthenia gravis A population-based study

During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe.     

A study of myasthenia gravis in patients with and without thymoma

This study was undertaken to compare the clinical, neurophysiological, radiological and prognostic features of myasthenia gravis with and without thymoma. 37 patients with myasthenia gravis (27 males, 10 females), with age range of 4.5 to 72 (mean 39) years, were managed at a tertiary care centre in India. Four patients were below 15 years of age and 6 above 55 years. Most of the patients were in stage II (34). There were 2 patients in stage III and 1 in stage I. 27 patients underwent thymectomy. Thymoma was detected in 10 cases. The decrement in patients with thymoma ranged between 11 and 62% (mean 27.9%) and nonthymoma group 10-75% (mean 28%). CT scan of thorax revealed mediastinal mass in 5 out of 10 cases of thymoma and 2 out of 27 patients without thymoma. Outcome of myasthenia gravis with thymoma was worse than without thymoma at 1 year followup. Severity of illness, extent of decrement, lack of facilitation, duration of illness and age of the patients were not related to the outcome. It is concluded the clinical and neurophysiological changes in myasthenia gravis with and without thymoma do not differ. However, patients with thymoma have a worse outcome.