Quantitative Myasthenia Gravis Score Research Articles

Roles of IL-35-producing T and B cells in anti-acetylcholine receptor antibody-positive myasthenia gravis

BackgroundInterleukin 35 (IL-35) plays an anti-inflammatory in numerous autoimmune diseases. However, the potential roles of IL-35-producing T and B cells and serum IL-35 levels in the pathogenesis of myasthenia gravis (MG) and its association with disease activity in patients with MG remain unclear. MethodsThe percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells among peripheral blood mononuclear cells were determined in 37 patients with anti-acetylcholine receptor (AChR) antibody-positive MG and 35 healthy controls (HCs) by performing a flow cytometry analysis. Serum IL-35 levels in participants were determined using an enzyme-linked immunosorbent assay. Further, the correlations between IL35 levels and disease activity were analysed. ResultsThe percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells were significantly lower in patients with anti-AChR antibody-positive MG than in HCs (p = 0.001 and p = 0.002, respectively). Furthermore, patients with thymoma and patients with generalized MG had lower percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells than those without thymoma and those with ocular MG (p = 0.001 and p = 0.003; p = 0.008 and p = 0.001, respectively). Interestingly, the suppression of IL-35 secretion correlated negatively with the activities of daily living scores of patients with MG (r = -0.4774, p = 0.0028) and the quantitative MG scores (r = -0.4656, p = 0.0037). The proportions of IL-35-producing T cells and B cells and serum levels of IL-35 increased after treatment. ConclusionsIL-35 may represent a potential biomarker for the clinical evaluation of MG.

The feasibility of physical therapy in a patient with Parkinson’s Disease and Myasthenia Gravis: A case report

The occurrence for patients who have the co-existence of Parkinson’s Disease (PD) and Myasthenia Gravis (MG) is rare. This study attempted to investigate the feasibility of physical therapy on a patient with PD and MG. A 56-year-old male patient had MG for 42 years and PD for 10 years. He received physical therapy, including the 5-minute gait training and balance training, twice per week for 8 weeks. Quantitative Myasthenia Gravis Score (QMGs), Modified Barthel Index (MBI), Berg Balance Scale (BBS), and Parkinson’s Disease Questionnaire (PDQ-39) were used at baseline and post-intervention evaluation. The Unified Parkinson’s Disease Rating Scale (UPDRS) activities of daily living part (UPDRS-II) and motor part (UPDRS-III) were performed every two weeks until the end of intervention. After the intervention of 8 weeks, QMGs decreased by 3 (-43%), BBS increased by 4 (9%), MBI increased by 12 (14%), and PDQ-39 decreased by 5 (-11%). UPDRS-II, UPDRS-III and total UPDRS gradually decreased by 2 (-14%), 6 (-18%), and 8 (-17%) respectively during the intervention. With improved results of clinical scales, motor and ADL functions of this patient were enhanced. Our results suggested that physical therapy on the patient with PD and MG was feasible and effective, which deserves more attention and warrants further research. Keywords: Parkinson’s disease; Myasthenia gravis; physical therapy; UPDRS.

Analysis on the Clinical Effect of High-Dose Glucocorticoids Combined with Immunosuppressants on Patients with Myasthenia Gravis Undergoing Video-Assisted Thoracoscopic Surgery.

Objective The purpose of the study was to investigate the clinical effect of high-dose glucocorticoids (GCS) combined with immunosuppressants on the treatment of myasthenia gravis (MG) with video-assisted thoracoscopic surgery (VATS). Methods A total of 106 MG patients admitted to the neurology department of our hospital from February 2016 to February 2020 were selected as the study subjects and divided into experimental group (n = 53) and control group (n = 53). The patients in the control group underwent VATS, while the patients in the experimental group were treated with high-dose GCS combined with immunosuppressants on the basis of VATS treatment. The clinical efficacy of different MG treatment methods was analyzed. Results No significant differences were observed in visual analogue score (VAS) at T1 between the two groups (P > 0.05), while VAS scores at T2, T3, and T4 in the experimental group were significantly lower than those in the control group (P < 0.001). In the experimental group, the overall response rate was significantly higher than the control group (P < 0.05). Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) level in regulatory T (Treg) cells in experimental groups after treatment was significantly higher, compared to that in before treatment and the control group (P < 0.05). Similar results of each quantitative MG score were displayed in both groups after treatment, compared to before treatment and the control group (P < 0.05). Clinical performance of patients with lower incidence of adverse reactions in the experimental groups after treatment was significantly higher than those in the control group (P < 0.001). Conclusion GCS combined with immunosuppressants can effectively relieve patients' clinical symptoms and improve their quality of life, with significant clinical efficacy and high safety, which is worthy of application and promotion.

Quantitative evaluation of drug efficacy in the treatment of myasthenia gravis

ABSTRACT Objectives This study aimed to quantitatively evaluate placebo effect and drug efficacy characteristics and identify associated factors that affect quantitative myasthenia gravis (MG) score (QMGs) and MG activities of daily living score (MG-ADLs) in patients with MG. Methods Randomized placebo-controlled clinical trials were comprehensively searched in public databases (PubMed, EMBASE, and Cochrane Library databases). A model-based meta-analysis was developed to describe time-course about drug efficacy and placebo effect. Results Twelve articles including 13 trials (673 participants) that were eligible for this study evaluated four immunosuppressants (tacrolimus, cyclosporine, prednisone, and mycophenolate mofetil) and five targeted therapy drugs (eculizumab, belimumab, zilucoplan, efgartigimod, and iscalimab). The pharmacodynamic model showed that eculizumab had the highest efficacy in reducing QMGs scores (3.66 points), and efgartigimod had the highest efficacy in reducing MG-ADLs scores (1.97 points). The placebo effect of QMGs and MG-ADLs increased apparently with time and reached 52% and 90% of their maximum effect in 12 weeks, respectively. In addition, this study found that the activities of daily living ability increased with the increase of the proportion of patients undergoing thymectomy. Conclusion This study analyzed the efficacy characteristics of nine drugs. The present findings provide necessary quantitative information for drug development of MG.

Methotrexate as a Steroid-Sparing Agent in Myasthenia Gravis: A Preliminary Retrospective Study.

Treatment approach of myasthenia gravis (MG) is still debated; corticosteroids alone or in combination with immunosuppressive agents are the most used drugs. Azathioprine (AZA) has been shown to be effective for MG with a significant steroid-sparing activity, although burdened by side effects. Few studies on methotrexate (MTX) administration showed controversial results. In this cohort, we evaluated the role of MTX as a effective steroid-sparing agent. Fifteen MG patients treated with MTX, previously treated with AZA for at least 12 months, with poor benefits and uncomfortable side effects AZA related, have been selected. Each patient was evaluated through MG-Activity of Daily Living and Quantitative MG scores 5 times/yr. Patients treated with MTX had a significant improvement of MG-Activity of Daily Living and Quantitative MG scores. Furthermore, all patients reduced prednisone dosage, and none complained of side effects. We suggest MTX is effective and well tolerated and could be considered as a steroid-sparing agent in MG treatment.

A Critical Examination for the Pricing of Eculizumab and Efgartigimod in Myasthenia Gravis.

The purpose of this commentary is to focus on the downside of assumption-driven simulation modeling, the potential creation of a multitude of competing models, the mathematically impossible quality adjusted life year (QALY) and the failure to observe the axioms of fundamental measurement in mapping ordinal EQ-5D-5L preferences from the ordinal Quantitative Myasthenia Gravis (QMG) score. A second aspect of this commentary is to propose standards that should be set for the creation and evaluation of value claims in health technology assessment, in particular need fulfillment quality of life (QoL), that meet the demarcation test to distinguish science from non-science. The result is that the present ICER pricing claims for eculizumab and efgartigimod in myasthenia gravis should not be applied without consideration of more relevant evidence.

Factors affecting improvement of neurologic status evaluated by Quantitative Myasthenia Gravis Score for patients with thymomatous myasthenia gravis after extended thymectomy

BackgroundThe length of time for clinical improvement of patients with thymomatous myasthenia gravis (MG) after extended thymectomy is not clear. The purpose of this study was to determine the length of time after thymectomy in patients with thymomatous MG to achieve a 3-point reduction of Quantitative Myasthenia Gravis Score (QMGS), and identify variables associated with a failure to achieve the reduction.MethodsThe records of patients with thymomatous MG who underwent extended thymectomy from January 2005 to December 2018 were retrospectively reviewed. The primary end point was a reduction of 3 points of QMGs and the secondary end point was another reduction of 3 points of QMGs.ResultsA total of 481 patients were included in the analysis, the mean age of the patients was 41.63 ± 8.55 years, and approximately 60% were male. The median time to achieve a 3 point decrease in QMGS was 6 months, and the median time to achieve another 3 point decrease was 30 months. Multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a 3 point decrease in QMGS (HR = 0.55 and 0.65, respectively). Likewise, multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a second 3 point decrease in QMGS (HR = 0.53 and 0.53, respectively).ConclusionsIn patients with thymomatous MG who receive thymectomy, age ≥ 42 years and Masaoka-Koga stage > I are associated with a worse prognosis and failure to achieve a 3 point decrease in QMGS.

3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS.MethodsWe searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis.ResultsSix randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity.ConclusionsThe pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

Changes in Physical Fitness and Body Composition Associated with Physical Exercise in Patients with Myasthenia Gravis: A Longitudinal Prospective Study.

There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity remains unknown. In this prospective study, we enrolled 34 patients with MG with stable condition and evaluated the disease severity, physical fitness parameters, and body composition (measured using whole-body dual-energy X-ray absorptiometry (DXA)), before and after conducting a 24-week physical exercise regimen of aerobic and resistance strength training. The outcomes were measured by DXA, quantitative MG (QMG) score, quality of life score, handgrip strength and walking speed. During the training regimen, participants were free to decide how many exercise sessions per week and regularly reported their weekly exercise time. The physical exercise program was well tolerated by the participants, the parameters of the QMG score and handgrip strength improved, and participants’ body composition did not change significantly. The high exercise group experienced greater deterioration in muscle mass in the arms, but exhibited a greater improvement in forced vital capacity, walking speed, and symptom severity. The group with low QMG scores improved more in terms of physical fitness, including walking speed. These findings indicate that physical exercise is well tolerated by patients with MG, and is accompanied by improved muscular and physical functions. We propose that physical exercise is safe, effective, and appropriate for patients with well-regulated MG.

Characteristics of low frequency repetitive nerve stimulation in patients with myasthenia gravis and its correlation with clinical features

Objective: To investigate the characteristics of low frequency repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) and analyze the correlation between RNS results and clinical characteristics. Methods: The clinical and electrophysiological data of 107 MG patients who were admitted to Guangdong Provincial People's Hospital and underwent electromyography (EMG) between September 2015 to September 2020 were retrospectively reviewed. The characteristics of low frequency RNS in ocular MG and generalized MG patients were analyzed. Patients were divided into RNS-negative group and RNS-positive group according to the RNS results. The clinical features, serological and thymic CT findings, thymic pathology were collected and compared. Binary logistic regression analysis was used to analyze the related factors of low frequency RNS. Results: Generalized MG (73.0%, 46/63) showed a lower positive rate of low frequency RNS compared to ocular MG (34.1%, 15/44) (P<0.001). In generalized MG, the positive rate of low frequency RNS in accessory nerve (68.3%, 43 cases) and facial nerve (52.4%, 33 cases) was higher than that in ulnar nerve (14.3%, 9 cases) (P<0.001). The decrease rate of compound muscle action potential (CMAP) in facial nerve (32%±11%) was higher than that in ocular muscle type (22%±7%) in RNS-positive group (P=0.011). Patients with positive facial nerve RNS were more likely to involve the throat muscles than those with negative result [22 cases (52.4%) compared with 17 cases (26.2%), P=0.006]. RNS-positive group showed a significantly higher quantitative myasthenia gravis (QMG) score than that of negative group (P<0.001). In ocular MG, patients with positive RNS showed a later onset (P=0.021), higher acetylcholine receptor (AChR) antibody-positive rate (P=0.03) and QMG score (P<0.001). Additionally, In generalized MG, patients with positive RNS showed a significantly higher AChR antibody-positive rate (P=0.023) and QMG score (P<0.001). The logistic regression analysis showed that QMG score [OR(95%CI)=1.66(1.36-2.03), P<0.001] and positive AChR antibody [OR(95%CI)=5.45(1.28-23.14), P=0.022] were independently related to abnormal RNS. Conclusions: Low frequency RNS is more sensitive in generalized MG. The stimulation of facial and accessory nerves increases the positive rate of RNS in MG patients. Abnormal results of low frequency RNS tend to be combined with positive AChR antibody and higher QMG score, reflecting the severity of muscle weakness. Therefore, serological examination and early intervention are required for those with abnormal RNS.

Clinical Evaluation of the Efficacy and Safety of Co-Administration of Wuzhi Capsule and Tacrolimus in Adult Chinese Patients with Myasthenia Gravis.

BackgroundTacrolimus has been recommended as an effective immunosuppressant for patients with myasthenia gravis (MG), while the high price, variable bioavailability, and narrow therapeutic window restrict its clinical application. Wuzhi capsule (WZC) could improve tacrolimus blood concentration by inhibiting the metabolism of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). There are few studies focused on the coadministration of WZC and tacrolimus in autoimmune diseases. This study was aimed at quantifying the efficacy and safety of coadministration of WZC and tacrolimus in adult Chinese patients with MG.MethodsIn this retrospective study, 122 patients with MG on tacrolimus were enrolled. The initial tacrolimus dose was 2 mg/d. Patients with standard initial tacrolimus concentration were classified into group A (standard-dose group). Those failed to reach target concentration were divided into group B (high-dose group) and group C (co-administering WZC group), according to treatment adjustment of increasing tacrolimus dose and co-administration of WZC, respectively. A logistic analysis was used to identify factors associated with clinical outcome. Adverse drug reactions (ADRs) were recorded for safety analysis.ResultsThe tacrolimus concentration after coadministration of WZC was remarkably increased. It was higher compared with simply increasing the tacrolimus dose (p<0.001). The multivariate logistic analysis indicated that the baseline quantitative MG score was a predictive factor for clinical outcomes (OR=0.189; 95% CI 0.082–0.436; p<0.001). Fourteen patients (11.5%) reported ADRs after tacrolimus therapy. ADRs incidence was not related to WZC coadministration.ConclusionThe coadministration of WZC and tacrolimus can substantially elevate the tacrolimus concentration. It is a safe and economic treatment for adult Chinese patients with MG. Patients with a worse disease condition tend to present a better clinical outcome after tacrolimus therapy.

Validation of Spanish version of 15-item myasthenia gravis quality-of-life questionnaire.

The aim of this study was to achieve the translation and cross-cultural adaptation of the MG-QOL15R questionnaire into Spanish and the analysis of its psychometric properties. We recruited patients with MG, ≥18years old, whose mother tongue was Spanish. After the translation and cross-cultural adaptation of the MG-QOL15-R, the following tests were performed: internal consistency using the Cronbach-α coefficient and corrected item-total correlations; reproducibility with a test-retest analysis using intraclass correlation coefficients; and concurrent validity using Spearman's correlation coefficient of the Spanish language MG-QOL15R-S, Myasthenia Gravis Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As an approximation to construct validity, the nonparametric Mann-Whitney U test was performed between MG-QOL15R-S scores according to the Myasthenia Gravis Foundation of America classification. A total of 83 MG patients were enrolled, mean age 48.19±17.25years; 58 (69.9%) were women. The mean MG-QOL15R-S score was 11.3±7.1. Cronbach-α coefficient was 0.92. Item-total correlation ranged between 0.43 and 0.75. Intraclass correlation coefficient was 0.80. The Spearman correlation coefficient was 0.637 (p-value<.001) for MG-ADL and 0.487 (p-value<.001) for QMG. Mann-Whitney U tests of the mean MG-QOL15R-S scores were significantly different according to the clinical severity (p-value<.001). The Spanish version of the MG-QOL15R is a valid and reliable instrument and potentially useful for measuring health-related quality of life in Spanish-speaking MG patients.

Swallowing dysfunction in myasthenia gravis patients examined with high-resolution manometry

ObjectiveTo prospectively compare oropharyngeal swallowing dysfunction in myasthenia gravis (MG) patients presenting with difficulty in swallowing between the neutral and chin-down positions, based on the results of high-resolution manometry (HRM) examination. MethodsWe prospectively compared the HRM results of swallowing studies of seven MG patients showing difficulty in swallowing (neutral and chin-down positions) at the Department of Neurology of our institution during the period February–December 2018. The HRM assessment parameters were as follows: maximum swallowing pressure (SP) at the soft palate, meso‑hypopharynx, and upper esophageal sphincter (UES), and the duration of relaxation pressure at the UES. These parameters were compared between the two positions and their correlations with the results of neurological evaluations, such as the Quantitative Myasthenia Gravis (QMG) score (total and neck muscles alone), and grip strength, were also analyzed. ResultsIn comparison with the neutral position, in the chin-down position the maximum SP at the meso‑hypopharynx was significantly increased (p < 0.05), the maximum SP at the UES was significantly decreased (p < 0.05), and the duration of relaxing SP at the UES was significantly increased (p < 0.05). Interestingly, there were no correlations between the SP at any location and the results of the neurological evaluations. ConclusionsThe chin-down position appears useful for improving pharyngeal clearance in MG patients, by promoting increased SP at the meso‑hypopharynx, relaxing SP at the UES, and increasing the duration of relaxation pressure at the UES.

No correlation between acetylcholine receptor antibody concentration and individual clinical symptoms of myasthenia gravis: A systematic retrospective study involving 67 patients.

ObjectiveTo investigate the correlation between acetylcholine receptor antibodies (AChR‐Ab) concentration levels and individualized clinical symptoms in patients with AChR myasthenia gravis (AChR‐MG) in China.MethodsELISA was used to determine the concentration of AChR‐Ab in patients with MG. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, Quantitative Myasthenia Gravis (QMG) score, and MG‐specific activities of daily living (MG‐ADL) scoring systems were used to evaluate the clinical status of patients. Spearman correlation analysis was used to determine the correlation between the AChR‐Ab concentration and clinical score. The changes in the antibody concentration and clinical score are shown in MGFA‐antibody concentration–treatment plots.ResultsAutoantibody detection tests were performed in 67 patients, and their clinical scores were recorded. Forty‐nine patients received immunosuppressive therapy, 17 patients received pyridostigmine only, and 1 patient under thymectomy without any medication. The AChR‐Ab concentration correlated with the MGFA Classification in 5 (29.4%) patients in the pyridostigmine‐only group and 15 (30.6%) patients in the immunosuppressive drug group. The changes in the MGFA Classification preceded the changes in the AChR‐Ab concentration in 4 (23.5%) patients treated with pyridostigmine and 10 (20.4%) patients on immunosuppressive drugs. In patients on oral non‐steroidal immunosuppressants, the AChR‐Ab concentration changed by more than 50%, whereas the MGFA Classification did not increase. The AChR‐Ab concentration decreased in 17/32 (53.1%) patients after thymectomy, and then increased, whereas the AChR‐Ab concentration increased in 15/32 (46.9%) patients and the MGFA Classification decreased in 27/32 (81.8%) patients after thymectomy. The AChR‐Ab concentration presented a slight correlation with the corresponding MGFA, QMG, and MG‐ADL in patients with thymoma.DiscussionIn the Chinese AChR‐MG population, the Changes in the AChR‐Ab concentration in individuals with AChR‐MG did not consistently correlate with the severity of clinical symptoms.

Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses.

ObjectiveGeneralized myasthenia gravis (gMG) is an autoimmune disease that causes disabling weakness via damage to the neuromuscular junction. In most patients, the disease is mediated by autoantibodies to the acetylcholine receptor, which activate the complement cascade. Our objective was to analyze response profiles in adult patients with anti‐acetylcholine receptor antibody‐positive refractory gMG treated with eculizumab—a terminal complement inhibitor—in the REGAIN study or its open‐label extension (OLE).MethodsWe retrospectively analyzed Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) scores recorded during REGAIN and its OLE. Early/late responses were defined as improvement in MG‐ADL score (≥3 points) or QMG score (≥5 points) at ≤12 or >12 weeks, respectively, after eculizumab initiation.ResultsThe analysis included 98 patients. By Week 12 and conclusion of the OLE, MG‐ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively, and QMG response by 56.1% and 71.4%, respectively. Response was observed over multiple consecutive assessments for most patients. At Week 130, the least‐squares mean percentage changes (95% CI) from baseline in MG‐ADL score were −61.9% (−69.9%, −53.9%) and −47.5% (−59.0%, −36.0%) in early and late MG‐ADL responders, respectively; the least‐squares mean percentage changes from baseline in QMG score were −40.8% (−48.3%, −33.4%) and −55.5% (−68.4%, −42.7%) in early and late QMG responders, respectively.InterpretationThe findings suggest that, although most patients with refractory gMG will achieve clinical response by Week 12 of eculizumab treatment, first responses can be observed with longer‐term treatment.

Determinants of quality of life changes with plasmapheresis in patients with myasthenia gravis

BackgroundImmunomodulation, including IVIG and plasma exchange, is useful for a crisis or severe exacerbation. Plasma exchange may be slightly faster and more effective in a myasthenic crisis than IVIG. The aim of the current study was to determine the changes in the quality of life (QOL) after plasmapheresis and factors influencing these changes.ResultsThis study was conducted on 98 MG patients diagnosed as moderate to severe myasthenia gravis (according to Myasthenia Gravis Foundation of America classification), 81 patients received alternate day 5 sessions plasmapheresis (TPE group) and 17 patients were on medical treatment only (control group). All patients were subjected to full history, through clinical neurological evaluation and scored with quantitative myasthenia gravis (QMG) score for MG severity at start and after 1 m. Both groups completed the QOL questionnaire at baseline and after 1 month. The MG-QOL-15 scores were computed and we analyzed the change in the QOL scores from baseline to after plasmapheresis groups and compared it with the results for the control group. The scores in QOL scales had significantly decreased after plasmapheresis, and the improvement in QOL scores had a good correlation with the decrease in QMGS. The improvement in QOL and QMG was significantly correlated with younger age, female gender, shorter duration of the illness, presence of AchR antibodies, antibody titer, and thymus hyperplasia.ConclusionPlasmapheresis is effective in improving quality of life in myasthenia gravis patients and this improvement influenced by age, gender, duration of illness, presence of AchR antibodies and their titer, and the thymus pathology.

Efficacy and safety of double-filtration plasmapheresis treatment of myasthenia gravis: A systematic review and meta-analysis.

Objectives:To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis.Methods:PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses.Results:Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97–9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51–11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma.Conclusion:This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.

Efficacy and safety of tacrolimus as long-term monotherapy for myasthenia gravis

The objective was to evaluate the long-term efficacy and safety of tacrolimus monotherapy in myasthenia gravis (MG) patients. Immunosuppressive drug-naïve MG patients were administered tacrolimus, followed by thymectomy in some of the cases according to the clinical guideline for MG. Additional aggressive immunosuppressive therapies were allowed if the patients without thymectomy did not achieve minimal manifestation (MM) or better status after 3 weeks of tacrolimus administration or in the thymectomized patients by 1–2 weeks after the operation (i.e., 1st evaluation). Of all 14 patients included in this study, 8 of them (57%) achieved MM or better status at the 1st evaluation, and the remaining 6 (43%), who had failed to gain MM or better status at the 1st evaluation, also achieved MM or better status with 1 course of aggressive immunosuppressive therapy. The quantitative MG (QMG) scores, MG-Activities of Daily Living (ADL) scales, and anti-acetylcholine receptor (AchR) antibody levels were significantly decreased at 6 months and maintained thereafter. At the end of the follow-up period (41–70 months), all patients were in MM or better status. None of the patients experienced severe adverse effects. Our small preliminary study indicates that long-term tacrolimus monotherapy is possibly effective and safe for MG patients.

Peripheral blood hsa-circRNA5333-4: A novel biomarker for myasthenia gravis

In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333–4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801–0.928, P < 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P < 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P < 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.

Calprotectin as potential novel biomarker in myasthenia gravis

Myasthenia gravis (MG) is the most common autoimmune disease affecting the neuromuscular junction by specific autoantibodies. The etiology of MG and its heterogeneity in clinical courses are poorly understood, although it was recently shown that gut microbial dysbiosis plays a critical role. Since levels of Calprotectin (CLP) seem to correlate with level of dysbiosis, we hypothesize that CLP may serve as potential disease activity biomarker in MG. Sera from 251 patients with MG and 90 controls were analyzed in an explorative, cross-sectional design. Prospectively, we tested CLP levels in MG patients up to 3 years. Association of CLP levels with socio-demographics, disease activity (quantitative myasthenia gravis (QMG) score, myasthenia gravis-specific Activities of Daily Living scale (MG-ADL)), antibody (Abs) status, history of myasthenic crisis, treatment regime, and history of thymectomy were investigated using univariate analysis. Mean baseline serum levels of CLP were significantly higher in MG patients compared to controls (4.3 μg/ml vs. 2.1 μg/ml; p < 0.0001). Higher levels of CLP were associated with a higher clinical disease severity measured by MGFA classification and QMG score. Nevertheless, the only weak correlation of CLP with clinical outcome parameters needs confirmation in future studies. Currently, there are no validated blood biomarkers for MG. The significantly elevated CLP and mild correlation with parameters of disease activity suggests that CLP holds promise as a biomarker for measurement of individual disease severity.