Treatment Of Myasthenia Gravis Patients Research Articles

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia.

This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4-5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. A total of 75 MG patients with insomnia were included in this study. After 4-5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.

TREATMENT OF MYASTHENIA GRAVIS PATIENTS WITH COVID-19: REVIEW OF THE LITERATURE.

SUMMARYCoronavirus disease 2019 (COVID-19), caused by the late 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a respiratory disease which could put myasthenia gravis (MG) patients at a greater risk of developing severe disease course, since infections and some drugs are a well-recognized trigger of symptom exacerbation in MG patients. Out of ten most commonly used past and present drugs used in COVID-19 treatment, two (quinolone derivatives and azithromycin) are known to worsen MG symptoms, whereas another two (tocilizumab and eculizumab) might have positive effect on MG symptoms. Colchicine, remdesivir, lopinavir, ritonavir and favipiravir seem to be safe to use, while data are insufficient for bamlanivimab, although it is also probably safe to use. Considering MG treatment options in patients infected with SARS-CoV-2, acetylcholine esterase inhibitors are generally safe to use with some preliminary studies even demonstrating therapeutic properties in regard to COVID-19. Corticosteroids are in general safe to use, even recommended in specific circumstances, whereas other immunosuppressive medications (mycophenolate mofetil, azathioprine, cyclosporine, methotrexate) are probably safe to use. The only exception is rituximab since the resulting B cell depletion can lead to more severe COVID-19 disease. Concerning plasmapheresis and intravenous immunoglobulins, both can be used in COVID-19 while taking into consideration thromboembolic properties of the former and hemodynamic disturbances of the latter. As current data suggest, all known COVID-19 vaccines are safe to use in MG patients.

Aims of the Childhood Myasthenia Gravis Study Group in Japan

AbstractA Japanese epidemiological study about the age of onset of myasthenia gravis (MG) showed the highest peak at ages &lt;5 years, besides the peak observed in adults, which was confirmed in east Asian populations, such as Korea, China and Hong Kong, and is different from that observed in white populations. The Childhood MG Study Group in Japan held an annual workshop for 12 years (from 2006 to 2017), in which the participants debated and obtained information about the clinical problems and related basic sciences of childhood MG. This workshop featured two kinds of presentations: research and clinical experiences. For the case presentation, 42 cases were reported, of which 14 were ocular MG and 28 were generalized MG, including nine cases of latent generalized MG. Seronegative MG was reported in eight cases, muscle‐specific receptor tyrosine kinase‐positive MG in one case and congenital myasthenic syndrome in four cases. Treatment of MG patients was various; tacrolimus was used for 23 cases, cyclosporine for two, a high dose of gamma‐globulin for 13 and thymectomy for 10. For the research presentation, various points of view were reported about the pathogenetic mechanism or treatment by top neurologists and scientists in Japan. This workshop will contribute to continued efforts of clinicians to treat patients, and researchers further progressing in their studies.

Correlation of blood concentration with efficacy and safety of tacrolimus in treatment of myasthenia gravis patients

Objective To investigate the relationship of blood concentration of tacrolimus with efficacy and safety in treatment of patients with myasthenia gravis. Methods The clinical data of 74 patients with myasthenia gravis admitted in our hospital from January 2013 to December 2015 were analyzed retrospectively. The blood concentrations of tacrolimus were determined by chemiluminescence microparticle immunoassay. Treatment effects were evaluated with clinical relative scoring in China. Results There were 41 men and 33 women in 74 patients with the mean age of (56.7±15.8) years. According to the Osserman classification, there were 7 cases of type Ⅰ, 18 cases of type Ⅱb, 27 cases of type Ⅱa, 5 cases of type Ⅲ and 17 cases of type Ⅳ. Forty seven patients underwent thymectomy, including 9 cases of thymoma and 38 cases of hyperplasia. Patients were followed up for (28.1±14.5)days, and the effective rate was 74 %(55/74). There was no significant correlation between tacrolimus blood concentration and clinical efficacy. The incidence of adverse reaction of tacrolimus was 22%(16/74), and the incidence of adverse reactions increased with the increase of blood concentration. Conclusion Tacrolimus is effective in treatment of myasthenia gravis. The correlation of blood concentration of tacrolimus with the clinical efficacy needs to be further studied, but certainly, the monitoring of blood concentration can reduce the incidence of adverse reactions. Key words: Myasthenia gravis; Tacrolimus; Drug monitoring; Adverse drug reaction

Analysis of change in anti-acetylcholine receptor antibody and effect on myasthenia gravis symptoms by adjusting tacrolimus dosage according to the blood concentration

Background Since its introduction, tacrolimus has been widely used in myasthenia gravis (MG) patients. However, the correlation between the blood concentration level of the drug, the change in anti-acetylcholine receptor (AChR) antibody and the effect of the drug has not been reported. Aim We sought to evaluate the correlation between the dose of tacrolimus and the blood concentration, change in anti-AChR antibody, and the effect on MG symptoms. Methods We retrospectively analyzed the data of 28 patients who were treated with tacrolimus. Steroid dose was not changed during the tacrolimus treatment. Change in the dose and the blood concentration of tacrolimus, the level of anti-AChR antibody, and Myasthenia Gravis Foundation of America Clinical Classification were analyzed. Results The anti-AChR antibody level decreased in 19 patients (19/26; 73%). There was a positive correlation between the dosage of tacrolimus and the blood concentration at the latest observation. The mean antibody level was reduced from 153.4 ± 278.2 nmol/L to 83.2 ± 148.7 nmol/L, (P = 0.013). Regarding the Myasthenia Gravis Foundation of America Clinical Classification, the score improved in 22 patients (22/28; 79%). There was a significant positive correlation between the change in the anti-AChR antibody titers and the change in Myasthenia Gravis Foundation of America Clinical Classification. Conclusion Tacrolimus is useful for treatment of MG patients. However, because the blood level of the drug at the same dosage varies among patients, a careful adjustment of the dose according to the blood concentration is necessary.

Treatment of myasthenia gravis patients with calcineurin inhibitors in Japan: A retrospective analysis of outcomes

AbstractObjectivesCalcineurin inhibitors (CNI) are approved for the treatment of myasthenia gravis (MG) in Japan. However, the extent to which CNI have been effective remains unclear. Here we report data regarding CNI use and outcomes of MG.MethodsWe evaluated 640 consecutive MG patients by a multicenter survey. Patients not receiving any immune treatment were excluded, and cross‐sectional and retrospective data of 515 patients receiving immune treatment with (n = 312) or without (n = 203) CNI were analyzed.ResultsCompared with patients treated without CNI, those treated with CNI had a higher frequency of MG Foundation of America Class III–V and higher severity disease at the worst clinical condition, and also had current higher severity, worse quality of life and higher daily doses of prednisolone, despite taking equivalent prednisolone dosages during the course of treatment. Achieving a treatment target was less frequent in the group treated with CNI. Onset age was not different between the two groups. Duration before CNI use after starting corticosteroids was 4.4 ± 6.3 years. Among those treated with CNI, late‐onset MG patients achieved a more favorable current condition than did those with early‐onset and thymoma‐associated MG, whereas there was no such difference without CNI treatment.ConclusionsCNI were given to severely ill MG patients with no attempt to select those more likely to respond, and failed to exert a strong impact on MG therapy. CNI should be given aggressively to patients with factors known to enhance susceptibility to these drugs, such as higher age at onset and early‐stage disease.

Serum proteomic, peptidomic and metabolomic profiles in myasthenia gravis patients during treatment with Qiangji Jianli Fang

BackgroundQiangji Jianli Fang (QJF) has been used for treatment of myasthenia gravis (MG) in China. However, our understanding of the effects of QJF against MG at the molecular level is limited. This study aims to investigate the effects of QJF treatment of MG patients on the protein, peptide and metabolite levels in serum.MethodsHigh-throughput proteomic, peptidomic and metabolomic techniques were applied to investigate serum samples from 21 healthy individuals and 47 MG patients before and after QJF treatment via two-dimensional gel electrophoresis, matrix-assisted laser desorption/ionization time of flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry, respectively.ResultsAfter QJF treatment, the expression levels of peptides m/z 1865.019, 2021.128 and 1211.668 of complement C3f increased (P = 0.004, P = 0.001 and P = 0.043, respectively), while that of peptide m/z 1739.931 of component C4b decreased (P = 0.043), in the serum of MG patients. The levels of γ-aminobutyric acid (P = 0.000) and coenzyme Q4 (P = 0.000) resumed their normal states.ConclusionQJF could inhibit the activity of the complement system and restore the normal levels of metabolites.

Diagnostic use of autoantibodies in myasthenia gravis

The diagnostic use of antibodies is dependent on sensitivity and specificity of the methods of antibody detection, which have been developed and improved over the years. Here, we review the different methods for the detection of acetylcholine receptor and muscle-specific kinase antibodies, which are, so far, the only antibodies recognised as pathogenic in myasthenia gravis (MG). Seronegative MG patients will benefit from more sensitive methods of antibody detection. The most recent developments in antibody detection assays, particularly those based on cells expressing target antigens, allow rapid and reliable identification of autoantibodies, improving the diagnosis and treatment of MG patients. The same approaches to antibody detection are now being applied to a wide range of other autoantigens and other autoimmune diseases.

Long-term effects of infrasternal mediastinoscopic thymectomy in myasthenia gravis

Background Endoscopic thymectomy is commonly used for treatment of myasthenia gravis (MG) patients due to its relatively low invasiveness. However, the long-term effects of endoscopic thymectomy have not been fully evaluated. Objective To assess the long-term effects of extended infrasternal mediastinoscopic thymectomy (IMT) in MG patients and compare them with those of extended transsternal thymectomy (TT). Methods Among 24 MG patients without thymoma who underwent thymectomy in our Institute between January 1997 and December 2000, 14 patients who received IMT and 10 who received TT were enrolled in the present study. Quantitative myasthenia gravis (QMG) score and anti-acetylcholine receptor antibody (anti-AChR) titers were evaluated before and at five years after surgery. Results After five years, QMG scores were reduced from 6.6 to 1.8 ( p < 0.01) in the IMT group, and from 7.6 to 2.7 ( p < 0.01) in the TT group. The anti-AChR titers were reduced from 75.2 to 40.1 ( p = 0.027) in the IMT group, and from 224 to 61.3 ( p = 0.020) in the TT group. Conclusion These data suggest that the long-term therapeutic effect of IMT is equivalent to TT, and is thus suitable for the treatment of MG patients.

Ex Vivo Generated Regulatory T Cells Modulate Experimental Autoimmune Myasthenia Gravis

Naturally occurring CD4(+)CD25(+) regulatory T (Treg) cells are key players in immune tolerance and have therefore been suggested as potential therapeutic tools for autoimmune diseases. In myasthenia gravis (MG), reduced numbers or functionally impaired Treg cells have been reported. We have observed that PBL from myasthenic rats contain decreased numbers of CD4(+)CD25(high)Foxp3(+) cells as compared with PBL from healthy controls, and we have tested whether Treg cells from healthy donors can suppress experimental autoimmune MG in rats. Because the number of naturally occurring Treg cells is low, we used an approach for a large-scale ex vivo generation of functional Treg cells from CD4(+) splenocytes of healthy donor rats. Treg cells were generated ex vivo from CD4(+) cells by stimulation with anti-CD3 and anti-CD28 Abs in the presence of TGF-beta and IL-2. The obtained cells expressed high levels of CD25, CTLA-4, and Foxp3, and they were capable of suppressing in vitro proliferation of T cells from myasthenic rats in response to acetylcholine receptor, the major autoantigen in myasthenia. Administration of ex vivo-generated Treg cells to myasthenic rats inhibited the progression of experimental autoimmune MG and led to down-regulation of humoral acetylcholine receptor-specific responses, and to decreased IL-18 and IL-10 expression. The number of CD4(+)CD25(+) cells in the spleen of treated rats remained unchanged, but the subpopulation of CD4(+)CD25(+) cells expressing Foxp3 was significantly elevated. Our findings imply that Treg cells play a critical role in the control of myasthenia and could thus be considered as potential agents for the treatment of MG patients.

Safety of long‐term combined immunosuppressive treatment in myasthenia gravis – analysis of adverse effects of 163 patients

The aim of this study was to evaluate the long-term adverse effect (AE) profile of azathioprine (AZA) plus methylprednisolone combined immunosuppressive treatment in myasthenia gravis (MG) in a larger patient cohort. A prospective, open, observational study was conducted on 163 MG patients treated with combined immunosuppressive medication for a mean duration of 35.5 months (range 9-79 months). During the treatment course, AEs occurred in 61.4% of patients; 18% of these patients developed both steroid- and AZA-related AE, 15% had purely AZA-related AE and 67% had steroid-associated AEs. Severe AEs were encountered in only 6.7% of patients in whom treatment had to be discontinued. The clinical severity of MG at the start of the immunosuppressive treatment was positively correlated with the frequency and severity of AEs during the treatment, and patients with severe MG were found to be at higher risk of developing AEs during the combined immunosuppressive treatment. Combined immunosuppressive treatment of MG patients is well tolerated, and severe AEs requiring treatment cessation are rare. The incidence of steroid-related AEs is high during long-time therapy which underlines the importance of its combination with AZA. The probability of developing AEs seems to correlate with the severity of MG at the beginning of the treatment.

Clinical evaluation of a staphylococcal protein A immunoadsorption system in the treatment of myasthenia gravis patients.

The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Plasma antibody removal by conventional means, however, is nonselective and uses replacement fluids (chiefly, albumin solution) derived from human plasma. The Canadian Apheresis Group undertook a study at two Canadian apheresis centers to clinically evaluate a staphylococcal protein A immunoadsorption system (EXCORIM) in myasthenia gravis patients. The immunoadsorption system was safe and well tolerated. Ten of 12 patients had improvement in their neurologic status, as measured by a 20-point scoring system. The mean improvement in the weakness score was significant for the group (p = 0.0013). Patients with myasthenia gravis respond to treatment with plasma immunoadsorption. Further studies are required for a cost-benefit analysis.

Audiotympanometric findings in myasthenia gravis.

Myasthenia gravis can be a difficult diagnostic and therapeutic problem. Our study on six patients consisted of pure-tone audiograms, tympanometry, and acoustic reflex tests. Positive findings in the myasthenia gravis patients prior to medication included hyperacusis and increase in the intensity of sound required to elicit an acoustic reflex. Following medication, the hyperacusis lessened and the intensity of sound required to elicit the acoustic reflex decreased. During follow-up of two of the patients we encountered cholinergic (overdosage) crisis in one patient and myasthenic (underdosage) crisis in the other patient. Muscle weakness can be a common factor in both conditions. The acoustic reflex test can differentiate between the two types of crises. We believe audiotympanometric tests can aid in diagnosis and treatment of myasthenia gravis patients.