Generalized Myasthenia Gravis Patients Research Articles

Efficacy of thymectomy in patients with non-thymoma myasthenia gravis

Objective: To compare the efficacy between thymectomy plus prednisone and prednisone alone in patients with non-thymoma myasthenia gravis (MG). Methods: Thirty generalized MG patients without thymoma who underwent thymectomy were collected as the operation group, and thirty-nine patients without thymectomy who were treated with prednisone alone were matched as the control group. The start point was the enrollment time and the endpoint event was the "clinical remission" (including complete stabilization remission, drug remission, and poor performance). The survival curve was used to analyze the difference of endpoint event time between the two groups. Besides, a 12-month follow-up study was conducted to compare relevant clinical indicators between the two groups. Results: There was no significant difference in the occurrence time of endpoint events between the two groups (P=0.614). After 6-month follow-up, no significant differences were found in clinical remission rate, the dosage of pyridostigmine bromide and prednisone, the peak dosage of prednisone, the use of other immunosuppressive medications and the rate of hospitalization for exacerbation of disease between the two groups (all P>0.05). After 12-month follow-up, the dosage of prednisone and pyridostigmine in the operation group was significantly lower than that in the control group (5(0,10)mg/d vs 7.5(5,10)mg/d and 30(0,105)mg/d vs 90(15,180)mg/d; P=0.038, 0.032). Conclusion: In patients with mild to moderate non-thymoma generalized MG, thymectomy does not achieve faster remission, but it does reduce the long-term dosage of prednisone and bromopyrazine.

Myasthenia Crisis Vs Cholinergic Crisis: Challenges in Crisis Management Without Plasmapheresis or Intravenous Immunoglobulin (IVIG)

Introduction: Myasthenia gravis (MG) is an acquired autoimmune disorder clinically characterized by skeletal muscle weakness & fatigability on exertion with prevalence as high as 2–7 in 10,000 and women are affected more frequently than men (~3:2). Over 12-16% of generalized MG patients experience crisis once in their lifetime. A serious complication of myasthenia gravis is respiratory failure. This may be secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment with excess doses of a cholinesterase inhibitor (cholinergic crisis). Case Report: Thirty-two years old woman refereed from a private hospital to ED for further treatment with myasthenia in crisis, after nine days of treatment in the previous ICU. Patient already in intubation with mechanical ventilation and history of the treatment of a high dose of multiple anticholinesterase drugs and steroids without plasmapheresis or immunoglobulin intravenous. During admission, diarrhea was present, with no sign of GI infection. On the third day of admission, the patient performed a Spontaneous Breathing Trial and was a success then extubated. Then two day after extubation, the patient falls to respiratory failure and need mechanical ventilation. Anticholinesterase test was performed, and it shows no improvement in clinical signs, and diagnose as Cholinergic Crisis. After re-adjustment of anticholinesterase drug with a lower dose, clinically, the respiratory condition improved, and on the 10th day of admission, the patient was succeed extubated. At 12nd days of ICU admission, patient discharge from ICU. Discussion: Myasthenia and Cholinergic Crisis is a severe and life-threatening condition characterized by generalized muscle weakness with a respiratory compromise that requires ventilatory support. Respiratory failure may be present in the cholinergic crisis without cholinergic symptoms (miosis, diarrhea, urinary incontinence, bradycardia, emesis, lacrimation, or salivation). The most important management aspect of Myasthenia patients in crisis is the recognition and treatment of myasthenia vs cholinergic crisis.

Myasthenia Crisis Vs Cholinergic Crisis: Challenges in Crisis Management Without Plasmapheresis or Intravenous Immunoglobulin (IVIG)

Introduction: Myasthenia gravis (MG) is an acquired autoimmune disorder clinically characterized by skeletal muscle weakness & fatigability on exertion with prevalence as high as 2–7 in 10,000 and women are affected more frequently than men (~3:2). Over 12-16% of generalized MG patients experience crisis once in their lifetime. A serious complication of myasthenia gravis is respiratory failure. This may be secondary to an exacerbation of myasthenia (myasthenia crisis) or to treatment with excess doses of a cholinesterase inhibitor (cholinergic crisis). Case Report: Thirty-two years old woman refereed from a private hospital to ED for further treatment with myasthenia in crisis, after nine days of treatment in the previous ICU. Patient already in intubation with mechanical ventilation and history of the treatment of a high dose of multiple anticholinesterase drugs and steroids without plasmapheresis or immunoglobulin intravenous. During admission, diarrhea was present, with no sign of GI infection. On the third day of admission, the patient performed a Spontaneous Breathing Trial and was a success then extubated. Then two day after extubation, the patient falls to respiratory failure and need mechanical ventilation. Anticholinesterase test was performed, and it shows no improvement in clinical signs, and diagnose as Cholinergic Crisis. After re-adjustment of anticholinesterase drug with a lower dose, clinically, the respiratory condition improved, and on the 10th day of admission, the patient was succeed extubated. At 12nd days of ICU admission, patient discharge from ICU. Discussion: Myasthenia and Cholinergic Crisis is a severe and life-threatening condition characterized by generalized muscle weakness with a respiratory compromise that requires ventilatory support. Respiratory failure may be present in the cholinergic crisis without cholinergic symptoms (miosis, diarrhea, urinary incontinence, bradycardia, emesis, lacrimation, or salivation). The most important management aspect of Myasthenia patients in crisis is the recognition and treatment of myasthenia vs cholinergic crisis.

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

Exosomal miRNA expression for myasthenia gravis (MG) has not been studied. Plasma samples from 92 patients with MG and 49 age-matched healthy controls (HCs) were screened (by means of deep sequencing and quantitative real-time polymerase chain reaction) for differentially expressed exosomal microRNA (miRNAs). miR-106a-5p was chosen to further verify because it is reportedly involved in MG pathogenesis. Spearman's correlation analysis was used to assess correlations between candidate miRNAs and patient quantitative MG scores (QMGSs). Area under the curve (AUC) of the receiver operating characteristic analysis was used to evaluate the diagnostic accuracy of the identified miRNAs for MG. miR-106a-5p levels were significantly decreased in MG patients compared with HCs, and were associated with patient QMGS. The AUC values for hsa-miR-106a-5p were 0.728 and 0.813 in ocular and generalized MG patients, respectively. Exosomal miR-106a-5p was expressed differently in different types of MG and was associated with MG severity.

Low-dose rituximab every 6 months for the treatment of acetylcholine receptor-positive refractory generalized myasthenia gravis.

In this prospective, open-label study we explore the effectiveness of low-dose rituximab every 6 months in treating refractory generalized myasthenia gravis (GMG). Twelve patients with acetylcholine receptor (AChR)-positive refractory GMG were enrolled for the study. The primary endpoint was the change in quantitative myasthenia gravis (QMG) score from baseline to the study end. Secondary endpoints included changes in manual muscle testing (MMT), MG-Related Activities of Daily Living (MG-ADL), and 15-item Quality-of-Life (MGQOL-15) scores, as well as prednisolone reduction. MG decreased from 18.25 ± 4.03 to 8.42 ± 3.99 (P = .0001), MMT from 27.50 ± 17.78 to 4.58 ± 4.34 (P = .0001), ADL from 8.50 ± 2.84 to 1.17 ± 1.27 (P < .0001), MGQOL-15 from 37.25 ± 13.78 to 17.50 ± 9.73 (P = .0015), and prednisolone dose from 29.38 ± 11.92 mg/day to 8.86 ± 1.88 mg/day (P ≤ .01). Low-dose rituximab every 6 months is effective in treating refractory GMG patients.

Upregulation of miR150-5p in generalized myasthenia gravis patients is associated with decreased serum levels of IL-17 and increased serum levels of IL-10.

MiR150-5p has been reported to be involved in generalized myasthenia gravis, in which different cytokines play critical roles. The regulatory network of cytokines in generalized myasthenia gravis has not been fully elucidated. Our study aimed to investigate the interactions between miR150-5p and different cytokines in generalized myasthenia gravis. Serum levels of miR150-5p and different cytokines including IL-2, IL-17, IL-10, IL-19, IL-20 and IL-35 were detected by qRT-PCR and ELISA, respectively. ROC curve analysis was performed to evaluate the diagnostic value of miR150-5p for generalized myasthenia gravis. Correlation between serum levels of miR150-5p and different cytokines were analyzed by Pearson correlation coefficient. Compared with healthy controls, decreased serum levels of IL-2 and IL-17 and increased serum levels of miR150-5p, IL-10, IL-19, IL-20 and IL-35 were observed in patients with generalized myasthenia gravis. Serum levels of miR150-5p were positively correlated with IL-10 and negatively correlated with IL-17. After treatments, serum levels of miR150-5p and IL-10 decreased, while serum levels of IL-2 and IL-17 increased. Upregulation of miR150-5p is involved in generalized myasthenia gravis patients and is associated with decreased serum levels of IL-17 as well as increased serum levels of IL-10.

Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis.

Background:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily.Methods:A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1, 2012 and February 28, 2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude.Results:The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1% (46/85) in the ALS group, and the results of different nerves were 54.1% (46/85) of the accessory nerve, 8.2% (7/85) of the ulnar nerve and 0% (0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100% (41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave.Conclusions:Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.

MiR-30e-5p as predictor of generalization in ocular myasthenia gravis.

ObjectiveTo determine a predictive factor for the risk of conversion from ocular myasthenia gravis (OMG) to generalized MG (GMG) in a prospective study.Methods RNA was isolated from serum samples and detection of microRNA (miRNA) expression analyzed with qPCR. In the discovery set, 179 human miRNAs were assayed for profiling of five OMG patients and four age‐ and gender‐matched healthy controls. Based on the specific accumulation pattern of 19 miRNAs from the discovery set, in addition to miRNAs previously found elevated in generalized MG (GMG; miR‐150‐5p and miR‐30e‐5p), 21 miRNAs were subsequently analyzed in a validation cohort of 83 OMG patients (82 immunosuppression treatment naive; 49 male) within 3 months of diagnosis and at a follow‐up visit (median duration 28 months from first visit).ResultsThirteen patients generalized 14.8 ± 12.0 months after the diagnosis and the majority (85%) belonged to the late onset MG group. Two miRNAs were significantly higher in secondary GMG (SGMG) patients compared to OMG patients with late onset MG: miR‐30e‐5p (9.1 ± 0.5 vs. 6.3 ± 0.9; P < 0.0001) and miR‐150‐5p (7.4 ± 1.1 vs. 6.4 ± 1.1; P = 0.01). The sensitivity for miR‐30e‐5p in differentiating OMG and SGMG was 96% in all OMG patients and 100% in late onset OMG patients.InterpretationThis is the first study to describe a potential predictive factor associated with the risk of generalization for patients with OMG. Raised levels (>8) of miR‐30e‐5p at initial presentation in patients with ocular MG symptoms, give a predictive cut‐off for subsequent generalization of 96–100%.

Satisfactory Response With Achieving Maintenance Low-Dose Prednisone in Generalized Myasthenia Gravis.

To estimate the satisfactory response rate (SR%) with achieving maintenance, low-dose prednisone in acetylcholine receptor antibody-positive generalized myasthenia gravis. In this retrospective study, we estimate the SR% as defined by (remission/minimal manifestations status for at least 6 months using 7.5 mg or less of prednisone daily, for maintenance treatment at 2, 4, and 6 years after symptoms onset) for patients who were not taking steroid-sparing immunosuppressant (SSI) as a primary outcome and for patients taking an SSI as a secondary outcome. Forty-five patients were not taking an SSI at 2 years, 34 patients at 4 years, and 17 patients at 6 years; SR% was 44.4%, 64.7%, and 58.8%, respectively. Thirty-six patients were taking an SSI at 2 years, 22 patients at 4 years, and 15 patients at 6 years; the SR% was 50.0%, 45.4%, and 66.7%, respectively. Nearly half of the generalized myasthenia gravis patients who were not taking an SSI achieved an SR.

Decreased expression of circulating Aire and increased Tfh/Tfr cells in myasthenia gravis patients.

Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells (we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T-follicular helper (cTfh) and T-follicular regulatory (cTfr) cells in MG patients. In our research, we found that the acetylcholine receptor (AChR) Ab level is higher in generalized MG (GMG) than that in ocular MG (OMG). Compared with the control group (CG), lower expression of Aire was found in MG patients, especially in GMG. The ratio of Tfh/Tfr was higher in GMG patients, and then in the OMG patients, and lowest in CG. All these differences above were statistically significant. Negative relation was discovered between expression of Aire in circulating blood and ratio of Tfh/Tfr, so did it exist between Aire expression and the severity of MG. Meanwhile, positive relation was discovered between ratio of Tfh/Tfr and the severity of MG. However, no significant relation was manifested in our study between the subset age of MG and Aire level. Overall, these findings imply circulating Aire might play a role in the imbalance of cTfh and cTfr cells and participate in the pathogenesis of MG.

Predictive score for oral corticosteroid-induced initial worsening of seropositive generalized myasthenia gravis

BackgroundInitial worsening of symptoms after the start of corticosteroid administration is a major concern in the treatment of myasthenia gravis (MG). However, the risk factors or specific patient backgrounds related to this issue have not been fully understood. We aimed to determine the risk factors and developed a scoring system for predicting initial worsening in generalized MG. MethodsWe enrolled 62 generalized MG patients with anti-acetylcholine receptor antibody. Initial worsening was defined as an increment of three points in the Quantitative MG score within 2 weeks after the start of steroid treatment. A multivariate logistic regression model was used to determine the risk factors, and predictive scores were assigned. Bootstrap resampling was applied to evaluate the risk score model's internal validity. ResultsSteroid-induced initial worsening occurred in 26% of MG patients and was correlated with thymoma-associated or early-onset MG (p = 0.018), initial prednisolone doses ≥40 mg/day (p = 0.029), and upper limb weakness (p = 0.039). Stepwise multivariate logistic regression identified these three clinical factors for predicting initial worsening in MG. A predictive score of 0–3 points had a bootstrapping area under the curve of 0.770 (0.625–0.878). ConclusionsOur scoring system based on three clinical characteristics can predict the likelihood of steroid-induced initial worsening in MG.

Clinical Characteristics of Juvenile Myasthenia Gravis in Southern China.

To describe the clinical profile, clinical outcomes and factors that may affect the outcome of juvenile myasthenia gravis (JMG) patients in southern China. We reviewed information relating to JMG patients treated and evaluated at the First Affiliated Hospital, Sun Yat-sen University, between 1998 and 2015. The study involved 327 JMG patients who had been followed up for ≥1 year. Overall, 77.4% patients showed initial symptoms in the prepubertal period (<12 years). 306 patients showed only ocular symptoms at onset. By the final follow-up, 61 ocular myasthenia gravis (OMG) patients (61/306, 19.9%) had developed generalized myasthenia gravis (GMG). Anti-acetylcholine receptor antibodies (AChR-Ab) titer was an independent risk factor for generalization. Eleven patients (3.4%) experienced spontaneous remission, but four relapsed. Low-dose oral prednisone (0.25 mg/kg) was administered when symptoms did not significantly improve after pyridostigmine treatment. Immunosuppressants were administered when prednisone was unsatisfactory. Optimal outcome was achieved in 59.6% of patients. Specifically, 60 patients (18.3%) attained complete stable remission (CSR), 12 (3.7%) attained pharmaceutical remission (PR), and 123 (37.6%) attained minimal manifestation (MM). In total, 53 OMG patients (21.5%) attained CSR, a significantly higher proportion than among the GMG patients (8.6%, P = 0.009). Moreover, 67.2% of patients with duration <2 years showed significant clinical improvement compared with 46.3% of those with duration >2 years (P < 0.001). Thymectomy did not exhibit definite efficacy for JMG patients. There was a low frequency of cases positive for AChR-Ab in the Chinese population. AChR-Ab titer was revealed as an independent risk factor for generalization. Low doses of prednisone could treat JMG effectively with few side effects.

Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis.

Neostigmine test (NT) is a pharmacological test, demonstrating a clinical improvement in patients affected by myasthenia gravis (MG). We aim to compare clinical evaluation and neurophysiological recordings by concentric-needle single-fiber electromyography (CN-SFEMG) in response to acute administration of neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10 with ocular MG and 13 with generalized MG) were evaluated before and after 90min neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered analysis of mean value of consecutive differences (MCD), single-pair jitter, and blocks. MGC scores significantly improved after NT in generalized MG patients (MGC 11.1 ± 7.6 vs 9.1 ± 6.7, p = 0.02), whereas the improvement was not significant in the ocular group. CN-SFEMG recordings significantly improved after NT in generalized MG patients (MCD 58.9 ± 18.8 vs 45.9 ± 23.2μs, p = 0.003; single-pair jitter 49.8 ± 26.9 vs 24.1 ± 26.7%, p = 0.0001; blocks 6.2 ± 9.5 vs 2.6 ± 7.4%, p = 0.03) as well as in ocular MG patients (MCD 50.8 ± 22.7 vs 40.1 ± 22.9μs, p = 0.01; single-pair jitter 35.9 ± 23.7 vs 20.0 ± 25.1%, p = 0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to acute administration of neostigmine in MG. Moreover, neurophysiological modifications to NT could show subclinical improvement in ocular MG better than that of the clinical scale.

Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity

AimTo assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. BackgroundIL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. Patients and methodsSera of 42 seropositive MG patients (66.7% women), mean age 50.6±23.7 years) have been tested by ELISA for IL-15 levels. ResultsThere were no statistically significant differences between IL-15 serum levels in MG patients in comparison with controls as well as between subgroups of MG patients (early vs. late onset and thymoma MG). Mean/median IL-15 serum levels were similar in MG patients treated with corticosteroids (CS) and CS naïve. Outliers (very high values) were seen only in untreated generalized MG patients. ConclusionsSerum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity.

Palpebral portion of the orbicularis oculi muscle to repetitive nerve stimulation testing: A potential assessment indicator in patients with generalized myasthenia gravis

Repetitive nerve stimulation (RNS) is a valuable diagnostic method for myasthenia gravis (MG). However, its association with clinical severity was scarcely studied. We reviewed medical records and retrospectively enrolled 121 generalized MG patients. Sensitivity of different muscles to RNS and clinical scoring systems was evaluated. RNS testing revealed facial muscles have the highest positive rate, followed by proximal muscles and distal muscles, with the palpebral portion of the orbicularis oculi muscle most sensitive. Amplitude decrement of compound muscle action potential (CMAP) in the palpebral portion of the orbicularis oculi muscle is related to quantitative myasthenia gravis (QMG) scores, MG-specific manual muscle testing (MMT) scores and myasthenia gravis-related activities of daily living (MG-ADL) scores. We suggest that RNS testing of the palpebral portion of the orbicularis oculi muscle is a potential assessment indicator in patients with generalized MG.

Early fast-acting treatment strategy against generalized myasthenia gravis

Introduction In this study we sought to clarify the effects of early fast-acting treatment (EFT) strategies on the time course for achieving the treatment target in generalized myasthenia gravis (MG). Methods This retrospective study of 923 consecutive MG patients analyzed 688 generalized MG patients who had received immunotherapy during the disease course. The time to first achieve minimal manifestations (MM) or better while receiving prednisolone at ≤5 mg/day for ≥6 months (MM-or-better-5mg) up to 120 months after starting immunotherapy was compared between EFT and non-EFT patients. Results Achievement of MM-or-better-5mg was more frequent and earlier in the EFT group (P = 0.0004, Wilcoxon test; P = 0.0001, log-rank test). Multivariate Cox regression analysis calculated a hazard ratio of 1.98 (P < 0.0001) for utilization of EFT. Dosing regimens of oral steroids in EFT produced no differences in the time course. Conclusions EFT strategies are advantageous for early achievement of MM-or-better-5mg. Muscle Nerve 55: 794–801, 2017

Peripheral NK and B regulatory cell frequencies are altered with symptomatic exacerbation in generalized myasthenia gravis patients

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Clinical significance of serum resistin in patients with generalized myasthenia gravis

Objective: To detect the serum resistin levels in patients with generalized myasthenia gravis (GMG) and evaluate the clinical values of resistin. Methods: We detected the serum resistin levels in 58 patients with GMG and 58 healthy controls (HC) from January 2013 to December 2015 in Tianjin medical university general hospital.Then we analyzed the correlation of the serum resistin levels with the clinical features. Results: The serum resistin levels in patients with GMG, (8.26±4.27) ng/ml, was significantly higher than in HC, (4.12±1.36) ng/ml, (P<0.001). There was no statistical difference of the serum resistin levels between female or male patients with GMG (P=0.589). The serum resistin levels in patients with GMG was positively correlated with the quantitative MG score for disease severity (QMG) (r=0.446, P<0.001), but not correlated with age (r=0.168, P=0.206). The patients with higher resistin levels took higher risk of combining with thymoma (P=0.002), 56.5%, and these patients had higher QMG, 11(5) (P=0.001); and the ratio and QMG in the patients with lower resistin levels were 17.1%, 7(5), respectively.The GMG patients with thymoma (TGMG+ ) had remarkably higher serum resistin levels, (10.7±5.3) ng/ml (P=0.010) and the QMG score, 11(5) (P<0.001) than the GMG patients without thymoma (TGMG-) with (7.0±3.1) ng/ml and 8(5). Conclusion: Resistin is probably associated with the severity of the disease of MG, and maybe a potential biomarker of MG combined with thymoma.

Survey of epidemiology, clinical picture and current treatments for elderly‐onset (≥ 65 years) patients with myasthenia gravis in Nagano Prefecture, Japan

AbstractBackgroundOur previous population‐based study in 1982–2001, Nagano Prefecture, Japan, showed increased numbers of patients with elderly‐onset (≥ 65 years) myasthenia gravis.AimWe carried out a retrospective survey in 2002–2012 in the same area, and investigated the epidemiology, clinical picture and treatments for myasthenia gravis.MethodsQuestionnaires were sent to 23 hospitals and patient records were reviewed. Patients were classified into the non‐elderly‐onset (15–64 years, n = 136) or elderly‐onset (≥ 65 years, n = 78) group. The questionnaires included details of sex, age/date of onset, initial symptoms, disease severity, association with thymoma and treatments. Post‐intervention status and maximum/maintenance dose of prednisolone were investigated.ResultsThe rate of elderly‐onset myasthenia gravis patients increased in 2002 – 2012 despite correction for increases in the elderly population. The ratio of Myasthenia Gravis Foundation of America class I was higher, and that of class IIb was lower, and the thymectomy rate in non‐thymomatous generalized myasthenia gravis patients was lower in the elderly‐onset group. There was no marked difference in the rate of intensive treatments (plasma exchange, intravenous immunoglobulin etc.) between the groups. Immunosuppressive therapies (prednisolone, calcineurin inhibitors) were applied frequently in both groups, whereas calcineurin inhibitor use rate and mean maximal dose of prednisolone were lower, and the “minimum manifestation status with prednisolone ≤ 5 mg” rate was higher in the elderly‐onset group.ConclusionThis study suggested that a low or moderate dose of prednisolone can be fully effective in many elderly‐onset myasthenia gravis patients, and some might not require calcineurin inhibitors or thymectomy to reduce prednisolone dose.

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.