Juvenile Myasthenia Gravis Patients Research Articles

Treatment of juvenile myasthenia gravis with tacrolimus: A cohort study.

We investigated the proper timing, efficacy and safety of tacrolimus for juvenile myasthenia gravis (JMG). We conducted a retrospective cohort study for JMG patients treated with tacrolimus at Xiangya Hospital, Central South University, Changsha, China from 2010 to 2023. The clinical information of patients with a follow-up of more than 1 year was collected. Comparisons of clinical features between groups of patients who achieved therapeutic goal and those who did not achieve therapeutic goal as well as between groups of patients treated with tacrolimus within or after 1 year from JMG onset was carried out. Forty-three patients were enrolled, of whom 28 achieved therapeutic goal. Tacrolimus reduced glucocorticoids (GC) dosages for the 28 cases and 15 cases discontinued GC completely. Generalized myasthenia gravis (GMG) subtype had an association with a group of patients who achieved therapeutic goal (p = 0.001). Median duration from JMG onset to tacrolimus use was 10.50 months for those who achieved therapeutic goal and 36.00 months for those who did not achieve therapeutic goal (p = 0.010). The median Myasthenia Gravis Activities of Daily Living (MG-ADL) score improved significantly (p = 0.003). The initiation of tacrolimus within 1 year of JMG onset showed an association with achievement of therapeutic goal (p = 0.026). GMG subtype showed an association with a group of patients who received tacrolimus within 1 year (p = <0.001). Tacrolimus side effects were tolerable. The provision of tacrolimus within 1 year of JMG onset is effective and safe.

Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Rituximab in juvenile myasthenia gravis-an international cohort study and literature review.

Juvenile myasthenia gravis (JMG) is a rare, antibody-mediated disorder of the neuromuscular junction. Treatment strategies in JMG are largely informed by adult MG treatments as the pathophysiology is similar. Rituximab is increasingly considered as a treatment option in refractory JMG but has not yet been systematically investigated in this patient group We conducted a retrospective study from five international centres with expertise in paediatric myasthenia. 10 JMG patients treated with rituximab were identified. Following rituximab treatment all patients had a reduction in JMG-related hospital admissions. At 24 month follow up, 6 patients (60%) had achieved complete stable remission or pharmacological remission and 7 patients were able to reduce immunomodulatory treatment(s). The main side-effect was infusion-related reactions (30%) which resolved in all patients with symptomatic treatment. We compared our cohort to previously reported JMG cases treated with rituximab and noted similar response rates but a slightly higher side-effect profile. Rituximab is a safe and effective treatment option in moderate to severe JMG and most patients have an improvement in MG symptoms post treatment.

Demographics and ocular findings in children with myasthenia.

To report the demographics and ocular features of myasthenia gravis in the paediatric population. Retrospective revision of the medical records of all patients younger than 18 years of age with myasthenia who were examined at Great Ormond Street Hospital between the 1st of January 2016 and 1st of January 2020. A total of 49 children were assessed during the 4-year period. There was a female predominance, with only 12 males (24.5%). 26 children (53.1%) had juvenile myasthenia gravis (JMG) while 18 (36.7%) had congenital myasthenic syndrome (CMS). 4 patients (8.2%) were diagnosed with probable CMS while 1 (2.0%) was classified as probable JMG. The mean age at diagnosis was 5.3 years old (SD 3.9) whereas the mean age at onset was 3.7 years old (SD 3.9). Almost half of the children (49%) had ocular involvement, present in 19 patients in the JMG group (70.4%) and in 5 children (22.7%) in the CMS cohort. Ptosis was the most common sign at presentation, seen in 32 patients (65.3%). Nine patients (18.4%) presented with a squint and another 7 (14.3%) developed it later on. Anti-acetylcholine receptor antibodies were positive in 18 of the 26 JMG patients (69.2%) whereas identifiable mutations were found in the 18 CMS patients (100%). Pyridostigmine was the drug of choice in our series, used by thirty-three patients (67.3%). The majority of the patients (73.5%) improved after treatment. JMG was the most common type of paediatric MG, specifically the ocular form. Ptosis was the most common sign at presentation. The majority of the patients improved after medical treatment.

Incidence and Ocular Features of Pediatric Myasthenias

To report the incidence, demographics, and ocular findings of children with myasthenia. Retrospective cohort study. The medical records of all children (<19 years) examined at Mayo Clinic with any form of myasthenia from January 1 1966, through December 31, 2015, were retrospectively reviewed. A total of 364 children were evaluated during the study period, of which 6 children were residents of the Olmsted County at the time of their diagnosis, yielding an annual age- and sex-adjusted incidence of 0.35 per 100 000<19 years, or 1 in 285 714<19 years. The incidence of juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS) was 0.12 and 0.23 per 100 000, respectively. Of the 364 study children, 217 (59.6%) had JMG, 141 (38.7%) had CMS, and 6 (1.7%) had Lambert-Eaton syndrome, diagnosed at a median age of 13.5, 5.1, and 12.6 years, respectively. A majority of the JMG and CMS patients had ocular involvement (90.3% and 85.1%, respectively), including ptosis and ocular movement deficits. Among children with at least 1 year of follow-up (JMG; median, 7.1 years, CMS; median, 7.0 years), improvement was seen in 88.8% of JMG patients (complete remission in 31.3%) and in 58.3% of CMS patients. Although relatively rare, myasthenia gravis in children has 2 predominant forms, CMS and JMG, both of which commonly have ocular involvement. Improvement is more likely in children with the juvenile form.

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.

Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset

BackgroundJuvenile myasthenia gravis (MG) is a rare autoantibody mediated autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark is muscle weakness and fatigability. Disease aetiology is complex, including both genetic and environmental factors. The involvement of genes in the human leukocyte antigen (HLA) is well established in adult MG. However, HLA associations in European juvenile MG have not been studied. This case-control study aimed to investigate and characterize genetic risk factors in prepubertal and postpubertal onset juvenile MG.Methodology/Principal findingsA population based Norwegian cohort of 43 juvenile MG patients (17 with prepubertal onset, 26 with postpubertal onset) and 368 controls were included. Next generation sequencing of five HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1) was performed, and a positive association was seen with HLA-B*08 (OR (95% CI) = 3.27 (2.00–5.36), Pc = 0.00003) and HLA-DRB1*04:04 (OR (95% CI) = 2.65 (1.57–4.24), Pc = 0.03). Stratified in postpubertal and prepubertal onset, HLA-DRB1*04:04 was only positively associated with the latter (P = 0.01). The HLA-B*08 allele (12.9% in the controls), previously described associated with early onset adult MG, was most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also increased among prepubertal onset MG (23.5%, P = 0.05).ConclusionThis study provides novel information about HLA susceptibility alleles in Norwegian juvenile MG where HLA-DRB1*04:04 was associated with prepubertal onset.

The effect of steroid treatment and thymectomy on bone age and height development in juvenile myasthenia gravis

Juvenile myasthenia gravis (JMG) is usually associated with growth retardation; however, no data have been published to date in this regard. The goal of this study was to analyze the developmental status of bone age (BA) and height in JMG patients and to subsequently identify the clinical factors, particularly thymectomy, associated with it to guide clinical practice. We conducted a cross-sectional study of 76 JMG patients to examine whether they had abnormalities of height and bone development according to the distribution of the height standard deviation score (Ht SDS) and BA. Correlation analysis and linear regression analysis were conducted to explore the related factors that may affect bone and height development. The mean BA was delayed 0.13 ± 1.42 years compared with the patients' chronological age (CA). The Ht SDS was also lower than the healthy peers. In multivariate analysis, the age at onset was negatively associated with delayed BA (R (2) = 0.08, p = 0.019), whereas the cumulative intake of prednisone was negatively associated with Ht CASDS (Ht SDS based on CA) (R (2) = 0.168, p = 0.003). There was no significant association between thymectomy and delayed BA and Ht CASDS. Delayed BA and growth retardation existed in JMG patients. The age at onset of JMG was a correlating factor for delayed BA and the cumulative prednisone use may be a determinant of height retardation. Thymectomy had no impact on the growth of bone and height. Monitoring BA and height should become routine care in JMG patients to take appropriate therapeutic interventions.

Invited Commentary

Juvenile myasthenia gravis (JMG) is a form of MG presenting before age 19 years and more common in Asian populations. The report from Cheng and colleagues [1Cheng C. Liu Z. Xu F. et al.Clinical outcome of juvenile myasthenia gravis after extended transsternal thymectomy in a Chinese cohort.Ann Thorac Surg. 2013; 95: 1035-1042Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar] is a retrospective analysis of 141 patients who underwent extended transsternal thymectomy in a Chinese hospital. The objective of the report was to identify factors associated with complete or pharmacologic remission, which occurred in approximately 46% of patients. The authors found that older age at operation (> 12 years) and a short waiting time from diagnosis (< 12 months) were associated with higher rates of complete remission. Approximately 70% of patients presented with ocular MG (OMG), a figure in line with the epidemiology of prepubertal JMG. In this pediatric population, OMG has been shown to have a higher rate of spontaneous remission and very low rate of progression to generalized MG compared with adults, in whom 80% of OMG will progress to generalized MG. Thymectomy remains a controversial treatment for JMG. On the one hand, thymectomy is justified in refractory cases because patients may be dependent on long-term immunosuppressant medications, with the resultant side effects, and because persistent amblyopia can result in children. On the other hand, thymectomy is not proven to reduce the risk of progression to generalized MG and caution needs to be taken in early childhood due to subsequent immunosuppression and high rates of spontaneous remission. The authors did not assess separately the outcome of patients with OMG and of those with generalized MG. Interestingly, older patients responded better to extended transsternal thymectomy, and this may be because they behave more similarly to adult MG patients. Nearly 50% of JMG patients are known to present without acetylcholine receptor antibody. A variable percentage of them (0% to 49%) have antibodies against another neuromuscular junction protein, muscle-specific kinase, which is associated with more generalized disease. Current evidence suggests that thymectomy is not recommended in muscle-specific kinase–positive disease because it is unclear whether thymectomy confers any benefit. Unfortunately, serology was not evaluated in this series, which would have contributed to a better understanding of the role of thymectomy in childhood. The use of corticosteroids was associated negatively with outcome in OMG. Because patients with refractory and more severe OMG had received corticosteroids, this result may be flawed by selection bias. A propensity score case-matched analysis between patients with and without steroids would have minimized this problem. The authors should be commended for analyzing the largest series of JMG ever reported in the literature and contributing to raise the interest for this pediatric disease in our community.

Clinical Outcome of Juvenile Myasthenia Gravis After Extended Transsternal Thymectomy in a Chinese Cohort

The role of surgical treatment for juvenile myasthenia gravis (MG) remains unclear. Here, we performed a retrospective study to evaluate the predictors of clinical outcome of juvenile MG treated with extended transsternal thymectomy. A total of 141 consecutive juvenile MG patients underwent extended transsternal thymectomy at an academic hospital over a 20-year period were reviewed. Thymectomy was performed in patients resistant to pyridostigmine therapy, with generalized symptoms or ocular MG with partial response to pyridostigmine for more than 2 years. Variables potentially affecting responses to extended transsternal thymectomy were evaluated using Kaplan-Meier analysis and Cox regression modeling. Complete stable remission (CSR) is defined as asymptomatic without medication for more than 12 months. There were 96 patients with ocular MG and 45 generalized MG, the median age at disease onset was 6 years and that at operation was 12 years. Among 135 patients with complete postoperative follow-up, 34 (25.2%) achieved CSR, 28 (20.7%) experienced pharmacologic remission, 61 (45.2%) improved, 5 (3.7%) remained stable, and 7 (5.2%) deteriorated. The results indicated the disease-onset age greater than 6 years and age at operation greater than 12 years were both positively associated with CSR responses. Postoperative steroid treatments in ocular MG and preoperative disease duration in generalized MG (>12 months) were negatively associated with CSR responses. Extended transsternal thymectomy for Chinese juvenile MG patients has an efficacy comparable with reports from other ethnicities. Juvenile patients with disease-onset age greater than 6 years, age at operation greater than 12 years, and shorter disease duration of generalized MG are associated with favorable clinical outcomes.

Myasthenia gravis in an 22 months-old girl - impressing improvement due to early adaequate therapy

Aims: Infantile Myasthenia gravis (MG) is a rare autoimmune disease, antibodies against the nicotinic acetylcholine receptor (AChR) can be found in 50% off all cases. Others as antibodies to muscle-specific kinase (MuSK) are less frequent. The prevalence of MG in infants below 1 year of age is approximately 1.1/106. If antibodies are missing, a congenital myasthenic syndrome (CMS) has to be taken into account. Therapeutical options are the treatment with acetylcholinesterase inhibitors and often also immunosuppression. Depending on clinical severity a plasmapheresis or intravenous immunoglobulin could be indicated. A thymectomy could increase the probability of remission. Methods: We report on a 22-months-old girl with an uneventful neurological development. At the age of 20 months she showed a one-sided ptosis, in further course of both sides with a significant strength reduction in a context of a febrile common cold. First examinations without abnormal results in brain-MRI or blood. No elevation of AChR-antibodies at the beginning. Because of the typical clinical symptoms a therapy with pyridostigmine was started with only mild improvement. A few weeks later slightly elevated temperature due to a common cold, markedly reduced strength, serious ptosis, cough insufficiency; unable to sit, stand or walk. A slightly elevated AChR-antibodies-level was found (0.83 nmol/l), the repetitive nerve stimulation showed a decrement more than 10%. Results: In addition to the treatment with pyridostigmine (5mg/kgBW/day) we started a therapy with steroids and thereafter also with azathioprine. An impressing improvement could be demonstrated even after reduction of steroids. The girl actually shows a stable status. Conclusion: There are only few reports on infantile and juvenile MG patients and their therapy, evidence based recommendations for medical treatment do not exist. However a consequent drug therapy with acetylcholinesterase inhibitors, steroids and azathioprine reached a dramatic improvement in our patient and held it until now. Depending on clinical course and age a thymectomy have to be considered.