Clinical differences of early and late-onset myasthenia gravis in 985 patients

Objective: The clinical differences of early-onset myasthenia gravis (EOMG) and late-onset MG (LOMG) have not been elucidated in China. In order to clarify this, a retrospective study was conducted in 985 MG patients, whose disease duration was longer than 3 years.

Methods: These patients were separated into EOMG and LOMG according to the onset age of 50 years. The clinical differences including demographics, clinical features, thymus abnormalities and comorbidities of EOMG and LOMG patients were analyzed.

Results: Results indicated that 485 were males and 500 were females, 714 were EOMG and 271 were LOMG. Female was more common in EOMG and male was more common in LOMG (p = 0.003). The peak onset age was 0–4 years in EOMG and 55–59 years in LOMG. Ocular MG (OMG) was more common in EOMG and generalized MG (GMG) was more common in LOMG (p = 0.004). The transformation rate of OMG to GMG was higher in LOMG (p = 0.002). The positive incidence of repetitive nerve stimulation (RNS) was higher in EOMG (p = 0.026). Thymoma was more frequent in LOMG (p = 0.017) and thymic hyperplasia was more frequent in EOMG (p < 0.001). Hyperthyroidism was more common in EOMG (p = 0.017) and diabetes was more common in LOMG (p < 0.001).

Conclusion: These results have potential significance for the recognition of clinical features and the determination of management strategies in EOMG and LOMG.     

Thymectomy in late-onset myasthenia gravis

Two cases of late-onset myasthenia gravis were successfully treated by thymectomy using a sternal splitting technique, in spite of the fact that no thymomas could be detected preoperatively. One patient was seriously ill, the other patient responded to medical treatment. Thymolipoma and malignant thymoma, respectively, were removed from the patients. It is stressed that not all thymomas produce antibodies to striated muscles and that CT-scan of the mediastinum is of limited value in the diagnosis of thymoma. It is suggested that patients with late-onset myasthenia gravis be offered thymectomy, even in the absence of detectable thymomas.     

Characteristics of late-onset myasthenia gravis

An increasing incidence of myasthenia gravis (MG) has been reported in the elderly, but the full clinical ramifications of late-onset myasthenia gravis (LOMG) remain unclear. We describe the clinical features of our cohort of patients with MG with an emphasis on an onset after the age of 50. This was a retrospective analysis of medical records of a cohort of patients followed in two tertiary neuromuscular clinics and comparison of early onset MG (EOMG) versus LOMG. There were 174 patients with a mean age of onset of 55.2?±?19.1?years, and 44 % were women. Late onset of myasthenia gravis after age 50 was reported in 114 patients (66 %). Anti-AChR antibody titers were elevated in 78 % of patients (65 % with EOMG vs. 85 % with LOMG; p?=?0.003), and frequency of elevated titers of anti-MuSK antibodies was similar in both groups (present in 38 % of all tested seronegative patients). Myasthenic crisis was equally common in generalized EOMG and LOMG (13 %). Ocular MG was more common in LOMG compared to EOMG (40 vs. 18 %, p?=?0.021). Diabetes was more prevalent with LOMG (27 vs. 5 %; p?=?0.0002). Overlapping clinical features of EOMG and LOMG are consistent with a continuous clinical spectrum of a single condition, with more frequent occurrence of seropositive and ocular MG with a late onset. A higher burden of comorbidities, such as diabetes mellitus, may warrant a modified approach to treatment of myasthenia in LOMG. However, overall disease severity may not be higher with aging. These observations have implications for design of MG clinical trials and outcomes studies.     

Clinical characteristics and prognosis of very late-onset myasthenia gravis in China

Alteration in onset-age distribution in myasthenia gravis (MG) and its increasing prevalence among the elderly underscores the need for a better understanding of the clinical course of MG and the establishment of personalized treatment. In this study we reviewed the demographics, clinical profile, and treatment of MG. Based on onset age, eligible patients were classified as early-onset MG (onset age ≥18 and <50 years), late-onset MG (onset age ≥50 and <65 years), and very late-onset MG (onset age ≥65 years). Overall, 1160 eligible patients were enrolled. Patients with late- and very late-onset MG showed a male predominance (P=0.02), ocular MG subtype (P=0.001), and seropositivity for acetylcholine receptors and titin antibodies (P<0.001). In very late-onset MG, a lower proportion of patients retained minimal manifestations status or better, a higher proportion of patients had MG-related deaths (P<0.001), and a shorter maintenance time of minimal manifestation status or better was seen at the last follow-up (P=0.007) than that in patients with early- and late-onset MG. Non-immunotherapy may associated with a poor prognosis in patients in the very late-onset group. Further studies on very late-onset MG patients should be performed to evaluate the relationship between immunotherapy and prognosis.     

Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis

Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late-onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma-like and others with early onset-like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non-acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non-thymectomized AChR antibody positive late-onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non-thymectomized cases showed an opposite trend. The three MG-related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non-thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late-onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies.     

晚发型重症肌无力临床研究

目的探讨晚发型重症肌无力(Myasthenia gravis,MG)患者的临床特点。方法回顾性研究40例晚发型MG的临床特点并与早发型MG比较。结果晚发型MG患者男/女比例高于早发型MG,为1.22:1。晚发型MG的症状由眼肌受累演变至全身症状(占67.5%)显著高于早发型MG(占38.7%)。晚发型MG的肌无力程度较早发型MG肌无力程度严重,而且血清乙酰胆碱受体(acetylcholine receptor,AchR)抗体阳性率及抗体水平均显著低于早发型MG低,但Titin抗体阳性率及抗体水平却显著高于早发型MG。胆碱酯酶抑制剂对晚发型MG的疗效不如早发型MG。结论晚发型MG是一个免疫异质性的MG亚群,它的临床表现以及血清免疫学特点不同于早发型MG。     

Clinical and immunological associations in myasthenia gravis. 2. Cell-mediated immunity

Myasthenic patients showed low absolute T cell counts and low spontaneous and phytohaemagglutinin-induced lymphocyte transformation responses. The abnormalities were particularly associated with late onset disease and female sex, but not with HLA phenotype or autoantibody production. Serum factors inhibitory to lymphocyte transformation occurred in some patients.     

Clinical and immunological associations in myasthenia gravis. 1: Autoantibodies.

Associations between female sex, HLA B8, positive anti-thyroid microsomal antibody and, to a lesser extent, antinuclear antibody were seen in 34 patients with myasthenia gravis. This supports the concept that the disease is heterogeneous. Anti-DNA antibodies, which were present in 62% of the patients, did not show such associations.     

Clinical, electrophysiological and immunological remissions after thymectomy in myasthenia gravis.

OBJECTIVES: Approximately 50% of patients treated with thymectomy have a chance for symptom-free life. However, immunological and neurophysiological abnormalities may be detected in patients with clinical remission. Although improvement usually parallels decrease in acetylcholine receptor antibody (AChRAb) levels and jitter values, there is a question what factors influence immunological and electrophysiological remission in a population of myasthenia gravis (MG) patients. METHODS: We analyzed retrospectively clinical data of 32 MG patients operated for generalized MG, followed-up at our department for 17.2 (4-31) years. They were in clinical remission for 12.8 (2-25) years. All of them had single fiber electromyograhy (SFEMG) of extensor digitorum communis muscle (EDC) muscle and estimation of AChRAb level at the end of follow-up. Their age at onset of MG was 17 years (6-48) and at thymectomy 19 (6.4-58) years. Tensilon test was positive in 30, repetitive nerve stimulation in 29 cases. RESULTS: Clinical remission was reached on average 4.2 years after thymectomy. SFEMG jitter value normalized in 60% of cases. AChRAb were negative only in 34% of patients. Jitter values correlated with AChRAb levels (P=0.006, r=0.5) but were not related to clinical factors. Only time to thymectomy correlated with time from thymectomy to clinical remission (P=0.001, r=0.5). CONCLUSIONS: Clinical remission is not always accompanied by normalization of SFEMG and AChRAb. Although normalization of neuromuscular transmission in patients with remission of MG is individual, short duration of MG before thymectomy increases the chance of early remission.     

Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis

The incidence of myasthenia gravis (MG) from 1970 through 1999 was studied in an area with 2.3 million inhabitants. The mean annual incidence rate of early-onset MG was constant at 3.5 x 10(-6). In late-onset MG, the rate increased from 4.7 to 20.8 x 10(-6). The two onset types of MG may thus be distinct disorders. The author hypothesized that late-onset nonthymoma anti-acetylcholine receptor antibody-seropositive MG may be provoked by environmental factors.     

HLA antigens and myasthenia gravis in Japan

Recent studies have noted an increased association of the histocompatibility antigen HLA-B8 with myasthenia gravis in Caucasian patients.The HLA types of 63 Japanese patients with myasthenia were compared to those of 271 controls. The present study was designed to assess correlations between HLA antigens, sex, age at onset, the presence of autoantibodies and thymic morphology.HLA-B12 was increased in Japanese patients, especially females with early age at onset, and in addition it was significantly correlated with thymic hyperplasia. HLA-B5 was frequently found in the patients with thymoma. Statistically the most frequent haplotype found in this disease was HLA-A10–HLA-B12.     

Paraneoplastic myasthenia gravis: immunological and clinical aspects

Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make‐up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late‐onset MG (age ≥ 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient’s immunological profile. Paraneoplastic MG causes a distinctive non‐limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre‐thymectomy plasmapheresis or iv‐IgG should be considered in these patients to minimize post‐thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non‐paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR‐related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.