Myasthenia gravis (MG) is an archetypal autoimmune disorder of the neuromuscular junction. The imbalance of inflammatory cytokines are involved in the pathogenesis of MG. IL-33, a member of the IL-1 family, plays a key immune-modulation role in several autoimmune disease. However, its regulatory role in MG remains unclear. Here, we demonstrated that IL-33 expression in the serum of MG patients was significantly increased. We further proved that the serum levels of IL-33 were significantly negative correlated with the expression levels of TSLP. Increased serum IL-33 levels positively correlated with the upregulation of IL-17A levels and the quantitative myasthenia gravis (QMG) score in MG patients. Our findings indicate that IL-33 plays a potent immuno- enhancing role in the pathogenesis of MG by downregulating TSLP, consequently affecting the development of Th17 cells in MG.

Objective To investigate the clinical significance of needle electrode electromyography (NEMG)test for myasthenia gravis (MG).Methods This retrospective study analyzed the results of NEMG and clinical data of 335 inpatients with definite MG who were treated at the 309th hospital of Chinese PLA between 2011 and 2013. The patients enrolled were divided into 2 groups according to whether the results of NEMG showed myopathic damage. And the clinical character of the 2 groups were compared.Results NEMG demonstrated that 29 patients (8.7%)showed myopathic changes,and none had spontaneous potentials. The myogenic damage only presented shorter durations and lower amplitude of motor unit potentials (MUP). Patients with myogenic damage had higher clinical absolute scores (20.8±7.3)than those without such changes (14.9± 9.0,t = 1.79,P < 0.05 ). Patients without myogenic damage usually got initial symptoms only involving extraocular muscles (85.62%) but limbs and bulbar muscles (14.38%). While, the ratio of extraocular muscles onset was relatively low (55.17%)in patients with myogenic damage,and most patients involved limbs and bulbar muscles at the onset of the disease (44.83%). There was statistical difference between the 2 groups (χ2 =9.79,P <0.01). Otherwise,there was no statistical difference in gender,ages at onset,course of disease,Osserman classification or thymus types. Conclusions Some patients with MG may show myogenic damage in NEMG test. Patients with myogenic damage showed more sever clinical symptoms. Electrophysiological tests can indicate MG severity to some extent.

The study evaluated the efficacy of low-dose tacrolimus for treating Myasthenia Gravis (MG). Data were collected from 97 patients treated with low-dose tacrolimus from February 2011 to April 2015. Metabolic analysis was performed to determine more accurate tacrolimus dosing and patients were followed-up within clinic every 6 months for up to 4 years. The myasthenia gravis-specific activities of daily living scale was used to assess MG symptoms and their effects on patients’ daily activities. All side effects and adverse reactions were thoroughly documented. At the end of follow-up, 6 patients were in complete stable remission, 17 patients were in pharmacological remission, 26 patients were in minimal manifestation status, 32 patients were improved, 2 patients were unchanged, 11 patients had worsening symptoms, and 3 patients died. Side effects were reported and/or observed in 24 patients, of which 7 patients experienced elevated blood glucose, 2 patients developed neoplasms, 3 patients developed gastrointestinal symptoms, 3 showed mild increases in aminotransferases, 3 patients suffered from bone marrow suppression, 2 patients suffered from skin rashes and erythema, and 1 patient required discontinuation of therapy. Transient renal insufficiency was also observed in 1 patient and 3 other patients had minor miscellaneous side effects. This study adds some knowledge on the efficacy and side effects of low-dose tacrolimus in the treatment of MG. Tacrolimus immunotherapy is a valid option for the management of MG, and can be gradually reduced in dose once symptoms are improved until complete withdrawal is achieved.

目的 总结SNEDDON综合征(SS)的临床特点,提高其诊治水平.方法 分析1例SS病人的临床资料并复习相关文献.结果 病人双手出现网状青斑,伴有后循环短暂性脑缺血,既往有脑梗死病史,颅脑MRI检查可见多发腔隙性梗死,诊断SS,经抗血小板等治疗后好转.结论 SS是主要累及中小血管的系统性血管疾病,病因尚不明确,临床表现为广泛皮肤网状青斑并缺血性脑卒中,多伴其他脏器损害.早期诊治可防止严重神经功能缺损的发生.

目的 评价免疫抑制剂环孢素A(Cyclosporine A,CsA)治疗全身型重症肌无力(myasthenia gravis,MG)的疗效及其不良反应.方法 回顾性分析51例全身型MG患者接受CsA治疗前及治疗后1、3、6、12个月时MG严重程度评分及不良反应,并通过监测患者服药1个月后血CsA浓度,分析CsA血药浓度与临床疗效的相关性.结果 接受CsA治疗1、3、6、12个月时的总有效率(临床相对评分≥25％)分别为78.4％、80.4％、84.3％、90.2％,且随服用CsA时间的延长,MG临床绝对评分进一步下降(P＜0.05).临床显效及好转组患者血CsA浓度[(97.3±25.4) ng/ml,(85.3 ±-32.4) ng/ml]与无效组[(86.3±27.9)ng/ml]比较差异无统计学意义(P＞0.05).CsA主要不良反应为肾功能损伤6例(11.8％),肝功能损伤3例(5.9％),胃肠道反应8例(15.7％).结论 CsA治疗全身型MG,起效快,临床疗效确切.

OBJECTIVE:To evaluate the therapeutic effects of thymectomy in myasthenia gravis (MG) patients with thymoma.METHODS:A total of 178 MG patients with thymectomy between July 2008 and December 2010 were included. All the subjects were received either cyclophosphamide alone or in combination with radiotherapeutic treatment after surgery. The MG absolute and relative clinical scores were used to assess the effectiveness of long-term treatments. Clinical evaluations were conducted before, and at 1 , 6, 12 and 24 months after operation. A comparative analysis on the inter-relationships among MG clinical presentation, WHO histology and Masaoka stage was also conducted.RESULTS:(1) Of the 178 thymoma-patients, 103 were male and 75 were female, with a mean age of (43.7 +/- 12.5)-years old. One hundred and twelve cases were taken cyclophosphamide, and 58 cases with invasive thymoma (stages II , III and IV or WHO type B3 ) were taken cyclophosphamide in combination with radiotherapy. Five patients refused cyclophosphamide or radiotherapy and 3 did not finish treatment. (2) The muscular strength improved obviously in 32.8% (58/177) of the patients after 1 month after thymectomy, and 59.8% (101/169), 69.7% (115/165) and 81.5% (132/162) after 6 months, 1 year and 2 years, respectively with MG score for disease severity decreased significantly with time. (3) No significant differences of the improvement rates were observed in patients within different WHO histology category. However, the rates were much higher in patients with Masaoka stage I (91.4%) and stage I (89.8%) than those in patients with stage III (45.5%) and IV (28.6%) (all P < 0.001) .CONCLUSIONS:The remission rate of MG patients with thymomas increase after thymectomy plus cyclophosphamide or in combination with radiotherapy and reached 81.5% after 2 years. The remission rate is associated with Masaoka stage, but not with WHO histology.

Objective To evaluate the efficacy of tacrolimus in patients with prednisone-dependent generalized myasthenia gravis(MG). Methods A total of 74 patients with prednisone-dependent generalized MG received either tacrolimus(FK506)(n=34) or azathioprine(n=40) for more than 12 months. The daily dosage and adverse reaction of tacrolimus or azathioprine used in these two groups were recorded, and the therapeutic effect of the drugs and the clinical scores of MG were evaluated and compared between the two groups before treatment and at 1, 3, 6 and 12 months after treatment. Results Compared with that of before treatment(18.2±9.1), clinical relative scores of MG decreased significantly in tacrolimus group at 1, 3, 6 and 12 months after its treatment(13.4±6.5, 10.7±4.6, 8.7±3.7 and 5.3±2.1, respectively)(P0.01). W hile in azathioprine group, the significant differences in efficiency appeared only 6 and 12 months after azathioprine treatment(P0.05). The total clinical efficacy(clinical relative score ≥25%) in tacrolimus group were 65.3%, 77.6%, 81.2% and 85.8%, respectively at 1, 3, 6 and 12 months after treatment, and it was significantly higher than that in azathioprine group(12.3%, 25.4%, 56.7% and 75.6%, respectively). Prednisone decrement rate in tacrolimus group was 8.8%, 32.4% and 70.6%, respectively at 3, 6 and 12 months after treatment, and the rate of prednisonerelated adverse effects decreased from 94.1% at baseline to 14.7% at the final visit(P0.01). Conclusion The therapeutic effect of tacrolimus is clearly superior to that of azathioprine for the prednisone-dependent generalized MG patients, and it significantly reduces the dependence of patients on prednisone.

Myasthenia gravis (MG) is an organ-specific autoimmune disease. The imbalance of T helper type 17 cells (Th17) plays a key role in the pathogenesis of thymomatous MG. But the regulatory mechanism for Th17 cell development in MG-related thymoma remains undefined. Here we demonstrated that thymic stromal lymphopoietin (TSLP) is significantly decreased in thymomas. We also proved that TSLP was post-trancriptionally regulated by microRNA-19b. The expression of microRNA-19b was negatively correlated with the expression of TSLP mRNA and protein in thymomas. This study indicated that the elevation of microRNA-19b suppressed TSLP expression and then influenced T cell development in thymomatous MG.

Objective To measure the clinical significance of serum Titin antibody measurement in patients with myasthenia gravis (MG) crisis.Methods Twenty six patients with MG crisis,30 patients with other neurologieal diseases (ONDs) and 30 health controls,collected in our hospital from July 2008 to August 2010,were chosen in our study; the sera level oftitin antibody was deetected by enzyme-linked immunosorbentassay (ELISA); correlations of titin antibody level with the clinical features and prognosis of the patients with MG crisis were analyzed.Results The positive rate of titin antibodies in MG crisis group and ONDs group was 73.1％ and 3.3％,and it was negative in health control group; significant differece was noted (x2=51.922,P=0.000).The positive rate of titin antibodies in patients older than 50 years of the MG crisis group was signifcantly higher than that in patients younger than 50 years (x2=5.052,P=0.014); the positive rate of titin antibodies in MG crisis group was negatively correlated to the gender of the patients,the types of Osserman and the pathological types (P＞0.05).The titin antibody titer after treatment was significantly decreased as compared with that before treatment (P＜0.05).Conclusion Positive titin antibody is mostly found in MG crisis and it's level is related to the severity of MG crisis,indicating that it might be beneficial for evaluating prognosis of MG patients.

目的 评价优化后急性缺血性脑卒中临床路径管理模式的优越性.方法 随机选取医院实施急性缺血性脑卒中治疗临床路径管理优化前后收治的急性脑梗塞患者各200例,采用回顾性分析比较各组患者的相关指标.结果 路径优化管理后.患者诊疗等待时间缩短,疾病规范诊疗比率进一步提高,医护工作量大大减少,患者满意度进一步提高.结论 实施临床路径能够改善医疗质量,更好地利用医疗资源.临床路径优化后医疗质量进一步提高.

Objective To investigate clinical manifestation, image of cerebral venous thrombosis complicated essential thrombocytosis.Methods Clinical and image data were analyzed with a literature review. Results Headache was the common symptom of onset in this two cases, while the initial clinical symptoms was not obvious, in addition to platelets significantly increased, WBC count were mildly increased, JAK2 V617F mutation-positive, venous sinus was not develop by cerebral angiography, and the prognosis was favorable. Conclusion Cerebral venous thrombosis complicated essential thrombocytosis is rare, this disease should be considered if patient with headache and platelet increased.

Objective To investigate the regulatory T cells(Treg) and its influencing factors in the thymomas complicated with myasthenia gravis(MG). Methods The numbers of FoxP3+Treg cells were detected by immunohistochemical analysis, and the transcriptional levels of FoxP3 mRNA and thymic stromal lymphopoietin(TSLP) mRNA were quantitatively analyzed by real-time reverse transcription polymerase chain reaction(real-time RT-PCR). Results CD4+FoxP3+nTreg cells in thymomas were significantly decreased compared with normal thymus(P < 0.01) and the standard values of FoxP3 mRNA and TSLP mRNA were significantly decreased in thymomas(P < 0.01). Among the types of thymomas, the numbers of FoxP3+Treg cells, standard values of FoxP3 mRNA and TSLP mRNA were higher in B1 organoid thymomas than other types of thymomas. There was a strong positive correlation between the FoxP3 mRNA transcriptional levels and the TSLP mRNA transcriptional levels. Conclusion These results suggest that there is decreased number of CD4+FoxP3+Treg cells in thymomas in patients with MG and the decreased transcriptional levels of FoxP3 may be regulated by the decreased transcription of TSLP. The decrease of CD4+FoxP3+Treg cells may interfere with the immune tolerance of patients with thymomas.

OBJECTIVE:To evaluate the efficacy and safety of tacrolimus in patients with generalized myasthenia gravis (MG).METHODS:A total of 69 cases admitted to our hospital were given 2-6 mg/day tacrolimus (FK506) for 12 months. The MG absolute and relative clinical scores were used to monitor the efficacy of tacrolimus. Clinical evaluation was conducted at month 1, 3, 6, and 12, while the serum concentration of FK506 was measured at one month after administration of tacrolimus for one month.RESULTS:The therapeutic response presenting as improved muscular strength showed within one month after administration of tacrolimus. The overall response rates (MG relative clinical score ≥ 25%) at month 1, 3, 6 were 81.2%, 87.6%, 92.2% respectively. It reached 93.8% by the final visit at month 12. MG score to evaluate disease severity decreased significantly as the subjects continued to take tacrolimus. Statistic analysis suggested that the serum concentration of FK506 was correlated with its therapeutic effect. Serum trough levels in remission and response groups [(7.1 ± 3.9) µg/L and (6.3 ± 3.8) µg/L, respectively] were significantly higher than that of no response group [(3.4 ± 1.3) µg/L]. The most common adverse effects included hyperglycemia (5 cases), myelosuppression (3 cases), and dizziness tinnitus (3 cases), majority of which were temporary and manageable.CONCLUSIONS:Our study has shown that tacrolimus significantly improved muscular strength of generalized MG patients. The treatment is well tolerated. The therapeutic effect of tacrolimus is observed within 1 month after initial use. Adverse events were manageable and not common.

Acquired myasthenia gravis is an autoimmune disease that affects the neuromuscular junctions.The target of the autoimmune attack in most cases is the skeletal muscle acetylcholine receptor(AChR).The final result remains muscle endplate dysfunction and muscle weakness.Most of patients with myasthenia gravis need a certain immune therapy in different courses of disease to induce a completed remission or near remission of symptoms and maintain it.In this review,the conventional methods and new progresses of management of myastheia gravis will be reviewed,including acetylcholinesterase inhibitors,immune modulationg therapy and thymectomy.The dosage,usage,course of treatment,indication,side effect of drugs and measures to side effect will be introduced.The primary aim of treatment of myasthenia gravis is induction and maintenance of clinical or pharmacologic remission while minimizing adverse effects of therapy.Treatment decisions must be individualized based on clinical classification,severity and coexisting disease,and patient participation in these decisions is essential to successful management.During the past decade,the prognosis of myasthenia gravis was improved significantly as which the imm une therapies,especiall y newly immunosuppressant was used in treatment of myasthenia gravis.So,newly immunosuppressant such as cycloporine,mycophenolate mofetil,tacrolimus,rituxmiab and their pharmacological mechanisms will be focused on in this review.

Objective To evaluate the benefit of thymectomy in children with myasthenia gravis(MG).Methods Over a period of 2 years from 2008 to 2011,the data of a total of 83 children(5～14 years)with MG were collected,including 38 patients with thymectomy and 45 with drug treatment.Thymectomy versus drug treatment for the rates of remission,improvement,no change and deterioration(remission and improvement were regarded as effective)were compared.The percentages of CD4+ and CD8+ T cells at different period after thymectomy or drug treatment were also measured.Results The children who underwent thymectomy had significantly higher rate of remission and more effective compared with drug treatment during a mean follow-up period of 24 months.There were no significant changes in the rates of no change and deterioration after the two approaches of treatment for MG.The percentage of CD8+ T cells was significantly decreased and the ratio of CD4+/CD8+ T cells was increased in the MG group compared to the controls while there was no statistically significant difference in the percentage of CD4+ T cells between the two groups.The ratio of CD4+/CD8+ T cells was decreased at the 1 year follow-up in children with MG received thymectomy.Conclusion Thymectomy appears to provide a high rate of remission and improvement in children with MG.It suggests that MG can be actively managed in children using thymectomy,with better chance for a good outcome.

Clinical classification and age distribution in myasthenia gravis (MG) cases seem different between Oriental and Caucasian populations, but there have rarely been any clinical studies on MG patients from mainland China. The goal of the current study was to perform a comprehensive survey of myasthenia gravis in a hospital in China, establishing contemporary cohort data and clinical features. 1,108 unselected patients with MG attending the 309th Hospital of PLA, Beijing, China were studied during a 36-month period from July 2008 to June 2011. The sex ratio was 1:1 (F:M). 62.5 % of patients presented as adolescents and adults. Ocular MG cases accounted for 65.6 % childhood MG patients. A positive response was observed in 96.8 % of the patients for neostigmine tests, whereas a positive decremental response to low frequency repetitive nerve stimulation (RNS) was observed in 77.4 % of the patients. The highest stimulating positive rate was 65.3 % in stimulated facial nerve. Thymoma was significantly increased in those patients with severe MG, especially in the cohort involving the respiratory muscles (p < 0.001). The study revealed higher frequency of ocular and childhood MG compared to other studies in USA and European countries, which can be a result of optimum case ascertainment, increased disease duration, or application of complex diagnostic tests. The relative increase in the prevalence of ocular myasthenia can be attributed to the impact of an aging population.

Myasthenia gravis, an autoimmune disorder affecting neuromuscular transmission, is mainly sporadic while familial cases are very rare. Usually familial myasthenia gravis cases have uniform clinical symptoms as well as serum anti-acetylcholine receptor antibodies. Interestingly, in our cases varying clinical types of myasthenia gravis and seropositive/seronegative anti-acetylcholine receptor antibodies coexisted in the same family. The mother and her daughter both had ocular myasthenia gravis, detectable anti-acetylcholine receptor antibodies and non-detectable anti-muscle-specific kinase antibodies, and good responses to medications. The son displayed ocular symptoms at the onset, and then progressed into a generalized form after 1 year. His serum anti-acetylcholine receptor antibodies and anti-muscle-specific kinase antibodies were both negative. Neither corticosteroids nor thymectomy alleviated his symptoms. Human leukocyte antigen DQA1*0301 allele sharing by the three patients may be involved in their genetic susceptibility to myasthenia gravis, and subtle differences in human leukocyte antigen DQB1 alleles may be associated with their variations in clinical features and serum antibodies.

OBJECTIVE:To investigation the clinical characteristics in myasthenia gravis (MG) patients with thymomas.METHODS:A total of 856 MG patients admitted to the department during 2008.7 - 2010.12 were reviewed retrospectively. The patients with MG were divided into two groups based on thymic pathology, which were 162 cases with thymoma and 694 cases without thymoma. We compared the different clinical features including the gender, age of onset, MG symptoms and the incidence rate of myasthenia crisis. And the relationship between the WHO types, Maosaoka stages of thymoma and the severe of MG was also studied.RESULTS:The percentage of thymoma-associated MG patients was 18.9 percent of hospitalized MG patients at the same period. Of the 162 thymoma-associated patients, 94 were male and 68 were female, with a ratio of 1.38:1 and a mean age of (42.9 ± 12.4) years old. Thymoma was more frequent in middle-old aged patients than in children. Compared with non-thymoma MG, more thymomatous patients showed generalised MG, but not only ocular muscles weakness (90.1% vs 62.4%, P < 0.001). There were significant differences of the incidence rate of myasthenic crisis in the two groups (14.8% vs 2.3%). (2) WHO type B2 and Maosaoka I, II thymoma were the commonest types among all potentially MG-associated thymoma. No differences of Osserman MG classification was found in thymomatous patients with different pathologic changes.CONCLUSIONS:The thymomatous MG patients had its distinctive clinical features: thymomas occurred in about 19.7% of MG patients with more men than women, more common in generalized, higher incidence of myasthenia crisis, with B2 type thymic pathology and Maosaoka I, II stages. No correlation was found between pathologic and clinical stages.

患者女,17岁,主因头痛4d,加重伴恶心呕吐1d入院.入院前4d大便后突然出现右侧头痛,自服止痛药后症状无缓解.入院前1d头痛加重,伴眼眶周围痛、恶心、呕吐,呕吐物为胃内容物,就诊于外院行头颅CT示“右侧枕叶大片状高密度影”,诊断脑出血,量约48 ml,给予脱水、补液等治疗,为进一步治疗来我院.

OBJECTIVE:To investigate the immunoregulatory role of Th17 cell and the related cytokines in myasthenia gravis.METHODS:Totally 51 myasthenia gravis (MG) patients were divided into MG with thymomas (TM group) and the MG with normal thymus (NT group), as well as 22 healthy subjects as controls. Th17 cells from peripheral blood mononuclear cells were measured by flow cytometry. Th17 related cytokines were detected by ELISA and real-time quantitative-PCR.RESULTS:The quantity of Th17 cells in MG patients with thymomas (1.53 ± 0.59)% were significantly increased compared with that of healthy control (0.94% ± 0.32%, P < 0.05). There was no significant difference in the number of Th17 cells between healthy controls and NT group. The expression levels of IL-17 mRNA (23.7 ± 4.5) were up-regulated significantly versus those in healthy controls (13.4 ± 3.2, P < 0.01). The levels of mRNA expression of IL-1β, IL-6 and IL-23 were up-regulated significantly in TM group. The mean concentration of IL-17 was up-regulated significantly in TM group (30.4 ± 7.3) ng/L versus healthy controls [(19.2 ± 4.9) ng/L, P < 0.05]. Serum levels of IL-23 and IL-1β were always increased in TM group versus healthy controls.CONCLUSION:The elevated levels of IL-17 and other Th17 related cytokines in thymomas may aggravate the autoimmunity disorder.