Plasmapheresis therapy in myasthenia gravis

Plasmapheresis in the treatment of myasthenia gravis has led to disparate results when applied by different investigators because of considerable differences in the volume, number, and tempo of plasmaphereses and in the type and amount of concomitant immunosuppressive drug therapy. Used as short-term crisis intervention, plasmapheresis produces temporary clinical improvement and reduction in titer of antibody to acetylcholine receptor, even without accompanying drug therapy. When applied as long-term primary therapy under optimal conditions, plasmapheresis is capable of generating stable improvement in most patients. This response appears to result from a synergistic action with immunosuppressive drugs, since it is characterized by a sustained reduction in titer of antibody to acetylcholine receptor. Where clinical circumstances warrant cytotoxic immunosuppression in patients with myasthenia gravis, consideration should be given to the simultaneous employment of plasmapheresis, in order to maximize benefit to the patient from a given exposure to drug therapy.     

非手术免疫抑制疗法治疗伴胸腺瘤的重症肌无力患者的远期疗效观察

目的评价非手术的免疫抑制疗法对伴有胸腺瘤的重症肌无力（MG）的远期疗效。方法采用类固醇、化学疗法、放射疗法治疗84例MG伴胸腺瘤患者,作回顾性研究,经诊断治疗后1－21年（平均4．8年）长期随访,评价其远期有效率、存活率和存活质量。结果远期有效率为86．9％（73／84）,即31例（36．9％）获完全缓解,37例（44．0％）获药物缓解,5例（6．0％）获明显改善。5年存活率76．5％,10年存活率54．5％。完全缓解期0．5－20．0年（平均4．6年）。总病死率为13．1％（11／84）。结论非手术免疫抑制疗法治疗MG伴胸腺瘤患者远期疗效良好,从远期存活率和存活质量来看并不亚于手术疗法。死因大多仍为危象,不是瘤转移。     

Monitoring azathioprine therapy in myasthenia gravis

Azathioprine (AZA) is used increasingly in the treatment of selected patients with myasthenia gravis (MG). The "usual" dose is 2 to 3 mg/kg/d, but guidelines do not exist to determine a specific dose for an individual patient. We reviewed our previously reported MG patients to determine what laboratory studies correlated with therapeutic efficacy. Among the studies examined, red cell mean corpuscular volume (RBC MCV) was the most useful: in 10 patients who responded to AZA, MCV increased by 15 +/- 2 fl (mean +/- SD), while in 6 nonresponders, MCV increased by only 4.5 +/- 6 fl (p less than or equal to 0.01). RBC MCV may be helpful in monitoring AZA therapy in patients with MG.     

Electroconvulsive therapy in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a neuromuscular disease sometimes associated with severe psychiatric complications. The use of electroconvulsive therapy (ECT) in MG raises certain challenges. METHODS: We describe a patient with MG and a steroid-induced major depressive episode with psychotic features treated with ECT. We also review the literature on similar cases and on the safety of ECT with muscle relaxation in this condition. RESULTS: The use of ECT in patients with MG is a viable therapeutic option when psychiatric complications secondary to MG or its treatment do not respond to psychotropic medications. CONCLUSION: ECT with muscle relaxants could be administered safely, with appropriate precautions kept in mind.     

Immunosuppressive drug therapy in myasthenia gravis

We reviewed the records of 37 patients with myasthenia gravis treated with azathioprine (n = 10) or cyclophosphamide (n = 27). All patients had received prednisone and anticholinesterase therapy, and most had undergone thymectomy prior to immunosuppressive therapy. Thirty patients (81%) responded to treatment. Both azathioprine and cyclophosphamide were found to be effective in the treatment of myasthenia gravis. The degree of improvement was more pronounced in patients with thymoma.     

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     

Tacrolimus in refractory patients with myasthenia gravis: coadministration and tapering of oral prednisolone.

We prospectively investigated therapeutic and adverse effects of tacrolimus in seven patients with myasthenia gravis (MG) who were resistant to conventional therapies or could not be treated with thymectomy because of complications. Within two months of initiation of tacrolimus all the patients subjectively showed improvement of clinical symptoms, while both the quantitative MG score for disease severity and MG-activities of daily living profile were significantly decreased (p<0.05) 3 and 6 months after commencement compared with before. Nine months after initiation and later, MG temporarily exacerbated in two patients with rapid tapering of oral prednisolone and one non-thymectomized one. This drug is useful in the treatment of refractory patients with MG irrespective of thymectomy, particularly in the early phase after commencement. When tacrolimus is additionally used for treatment of MG, preceding drugs, particularly corticosteroids such as oral prednisolone, should be carefully tapered if necessary in order to prevent clinical exacerbation.     

Intermittent long-term adrenocorticosteroid treatment of myasthenia gravis

Summary It is widely accepted that a long-term, alternate-day administration of adrenal corticosteroids after thymectomy is one of the most effective treatments of myasthenia gravis. However, some patients with myasthenia gravis show a tendency to develop steroid dependency, and require extremely prolonged administration of fairly high doses of steroids. Various types of adverse reactions to steroids are likely to occur in such cases. To avoid this, intermittent, single-dose administration of steroids was performed on a trial basis in the present study. Prednisolone, in doses of 50–100 mg, was given once every 3–7 days in three steroid-dependent myasthenic patients, in one case for up to 6 years. The effects of the intermittent treatment were as good as, and adverse effects less frequently found than in single-dose, alternate-day administration.     

Long-term results of corticosteroid therapy in patients with myasthenia gravis.

We studied the long-term outcome of prednisone therapy in 104 patients with myasthenia gravis (MG). At the end of the follow-up period, good therapeutic results were recorded in 85 patients (81.7%), poor results in 13 (12.5%) and no significant change of MG status in 6 (5.8%). We found a correlation between the duration of treatment and the incidence of steroid side effects. The presence of thymoma and severe forms of MG were associated with relapsing disease requiring prolonged corticosteroid regimens. The age at the start of therapy did not influence significantly the response to treatment.     

Immunoadsorption therapy for myasthenia gravis.

The results of a multicentre trial were analysed to evaluate the efficacy of immunoadsorption therapy for severe generalised myasthenia gravis. Twenty patients with myasthenia gravis who were concurrently receiving high dose prednisolone and azathioprine therapy were treated with an affinity-type adsorbent, using tryptophan-linked polyvinyl alcohol gel (IM-TR), according to a standardised treatment protocol. The 20 patients received five adsorption treatments within a period of 10 days. In 11, pronounced improvement of myasthenic weakness was seen and long-term remission was maintained. The treatment was especially effective in patients with thymic hyperplasia. Circulating acetylcholine receptor (AChR) antibodies were reduced by about 60% by treating one plasma volume. There was no difference in the rate of removal of the AChR antibodies between patients with thymic hyperplasia and patients with thymoma. No serious complications occurred during 100 procedures. It was concluded that the immunoadsorption therapy with IM-TR is useful in controlling symptoms in patients with severe myasthenia gravis who are otherwise unresponsive.     

Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up

We previously reported that prednisone reduced the frequency of generalized myasthenia (GMG) and controlled diplopia without major adverse effects at 2 years in patients with ocular myasthenia gravis (OMG). Questions remain as to whether study subjects had long-standing disease, biasing results towards a steroid benefit, and if prednisone merely delayed GMG onset. Here, we performed a record review of a referral neuro-ophthalmology service OMG database for patients who were followed-up for ≥4 years or until GMG developed. We studied the effect of prednisone on GMG incidence and control of ocular symptoms. Generally, patients with diplopia were recommended for prednisone therapy. Most remained on daily 2.5–10 mg for diplopia control. We compared the results for prednisone-treated and “untreated” (pyridostigmine only) patients. Of 87 patients, 55 were in the prednisone-treated and 32 were in the untreated groups. GMG developed in 7 (13%) of the prednisone-treated (OR 0.41; 95% CI 0.22–0.76) and in 16 (50%) of the untreated (OR 2.78; 95% CI 1.68–4.60) patients. After OMG onset, GMG developed at a mean 5.8 and 0.22 years in prednisone and untreated groups. Diplopia was present at the last exam in 27% of the prednisone-treated (mean 7.2 years) and in 57% of the untreated (mean 4.6 years) OMG patients. For 48 prednisone-treated patients who did not develop GMG, OMG treatment failure occurred in 13. Thus, prednisone delays the onset of GMG and has sustained benefit in reducing the incidence of GMG and controlling diplopia. Without prednisone, GMG develops in 50% of OMG patients, typically within 1 year.     

Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis

OBJECTIVE: To investigate effectiveness of long-term treatment of myasthenia gravis (MG) with intravenous immunoglobulin (IVIG). BACKGROUND: There are no definitive studies showing effectiveness of IVIG therapy in long-term treatment of MG. Most studies have investigated the acute treatment of MG with IVIG. We describe our experience with long-term treatment of MG with IVIG in six patients. METHODS: Acute treatment of MG by IVIG therapy has been well established in the literature. We describe six patients who were treated on a long-term basis with IVIG therapy. All of these patients had positive acetylcholine receptor antibody titers. They all received initial infusion for 5 days of IVIG at a dose of 400 mg/kg/day followed by maintenance therapy of 400 mg/kg for 1 day every 3-4 months. These patients were followed for 2 years. All other medications, including prednisone and cholingeric drugs such as Mestinon, were gradually weaned. For the last years, each of these patients maintained better than functional class 2 on an average of 1.5-2.2+/-0.5 grades on the University of Virginia modification of Ossermann's classification scale for MG. They were solely treated with IVIG infusion every 3-4 months without any other concomitant medications. Three of the patients had previously undergone thymectomies. None of the patients noticed any worsening in their scores on the University of Virginia modification of Ossermann's classification worse than Grade II in the last 2 years. There were no complications related to IVIG therapy, and all patients tolerated a single infusion of IVIG every 3-4 months at 400 mg/kg for 1 day. RESULTS: Our study demonstrates that IVIG maintenance is effective treatment of MG in selected patients and it is well tolerated. CONCLUSIONS: IVIG therapy is a convenient, effective therapy when used selectively for treatment of MG on a long-term basis without any significant side effects.     

Plasma C3c changes in myasthenia gravis patients receiving high-dose intravenous immunoglobulin during crisis

Fast-migrating C3c, a sensitive index of complement activation, was assayed in the plasma of 2 myasthenia gravis (MG) patients in crisis who received high-dose IV immunoglobulin therapy. Dramatic responses were observed in both patients. Clinical improvement paralleled a decrement in C3c levels, suggesting that regulation of complement activation may be one possible mechanism of IV immunoglobulin treatment in MG.