Myasthenia Gravis In Children Research Articles

Targeted Treatments for Myasthenia Gravis in Children and Adolescents.

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

Immune mediated myasthenia gravis in children, current concepts and new treatments: A narrative review article.

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG.

Retracted: Clinical Efficacy of Immunoglobulin Combined with Glucocorticoids in the Treatment of Oculomotor Myasthenia Gravis in Children and the Effect on Serum Immunity.

[This retracts the article DOI: 10.1155/2022/1772881.].

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis.

Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.

Clinical Efficacy of Immunoglobulin Combined with Glucocorticoids in the Treatment of Oculomotor Myasthenia Gravis in Children and the Effect on Serum Immunity.

To investigate the effects of treatment with immunoglobulin on clinical outcomes and immune function in children with oculomotor myasthenia gravis. The clinical data of 100 pediatric patients with oculomotor myasthenia gravis treated in our hospital from January 2019 to December 2021 were selected as the subjects of this retrospective study and divided into a comparison group and a treatment group according to the different treatment methods. The comparison group was treated with glucocorticoids, and the treatment group was treated with immunoglobulin on the basis of the comparison group. The differences in the serum indexes, the effects of immune function, and the clinical efficacy of the two groups were observed and compared. It was found the comparison of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) after treatment was significantly different and lower in the treatment group than in the comparison group; the comparison of CD4+, CD3+, CD4+/CD8+, and NK cells after treatment was significantly different and higher in the treatment group than in the comparison group. The effective rate of 98.00% in the treatment group was significantly higher than that of 76.00% in the comparison group, and the difference was statistically significant. The clinical efficacy of the two groups showed that the fever, cough, sputum, myasthenia gravis crisis, and gastrointestinal reactions in the treatment group were significantly lower than those in the comparison group. The study indicates that comparative study of children with oculomotor myasthenia gravis treated with immunoglobulin combined with glucocorticoids is more effective, effectively improving the immune level of patients and reducing adverse reactions.

Anaesthetic Management of a Patient with Myasthenia Gravis Posted for Tonsillectomy- A Case Report

Myasthenia gravis is a chronic autoimmune disease of neuromuscular junction which causes skeletal muscle weakness and fatigability, characterised by decrement in postsynaptic acetylcholine receptor at neuromuscular junction caused by auto-antibodies destruction. There are three types of myasthenia gravis in children- transient neonatal, congenital and juvenile. Juvenile Myasthenia Gravis (JMG) is an autoimmune disorder that can affect the all skeletal muscles including extraocular muscles, which may lead to fatigability and generalised weakness. This report is about a case of seven-year-old patient weighing 25 kg presented with throat pain since one and half month. Patient was a known case of congenital myasthenia gravis and diagnosis was confirmed by Edrophonium test. He underwent tonsillectomy and was successfully managed under general anaesthesia with no muscle relaxant technique. Tonsillectomy in paediatric patients is not an uncommon surgical procedure. In spite of being a common surgery, it is still challenging to the surgeon as well as the anaesthesiologist as there is a shared airway between the two. Also, in the postoperative period there are chances of post-tonsillectomy bleeding causing airway obstruction, if not diagnosed and treated early could risk the life of the patient. Therefore, this surgery poses an increased risk of mortality and morbidity.

Childhood myasthenia gravis − clinical characteristics, diagnostic modalities, treatment strategies, and outcome

Background Childhood myasthenia gravis (CMG) is MG occurring in childhood or adolescence (i.e. <18 years of age). Aim The aim of the work was to identify different clinical presentations and classifications of CMG, current diagnostic modalities, treatment strategies, and outcome to provide a profile of CMG among a cohort of Egyptian children attending Alexandria University Children’s Hospital as a tertiary pediatric center. Patients and methods All children diagnosed as having CMG who attended Pediatric Neurology Clinic at Alexandria University Children’s Hospital from January 1, 2010 to December 31, 2019 were included. A questionnaire for parents or caregivers including demographic data was administered. Clinical examination, clinical scoring system for MG, MG Foundation of America (MGFA) clinical classification system, electrophysiological studies, laboratory investigations, and clinic records review were done. Results Male : female ratio was 1 : 2.75. Mean age at start of symptoms was 4.97±3.78 years. Ptosis was presented in all (100%) patients, swallowing difficulty and choking in 40% of the patients, generalized weakness in 40% of the patients, and slurred speech and nasal tone in 33.3% of the patients. Overall, 46.7% of the patients were classified as pure ocular myasthenia gravis (MGFA class I), 20.0% as MGFA class II (mild generalized), 26.7% as MGFA class III (moderate generalized), and 6.7% as MGFA class IV (severe generalized). Pyridostigmine was used by 100% of the patients, prednisolone by 60% of the patients, and azathioprine by four (26.7%) patients. Pyridostigmine was the commonest single drug used by 40% of the patients. The common combinations were pyridostigmine with prednisolone alone or with added azathioprine. The comparison between the MG-Activities of Daily Living scale profile scores in first and last visits for patients was statistically significant. There was a significant improvement in the class of diseases, with remission in 70% of the patients. Failure rate of management was found in 20% of the patients. Conclusion Ocular myasthenia gravis was the most common subclass of CMG; ptosis was the most common presenting symptom. All patients received pyridostigmine as the first-line treatment. Remission occurred in 70% of the patients.

Aims of the Childhood Myasthenia Gravis Study Group in Japan

AbstractA Japanese epidemiological study about the age of onset of myasthenia gravis (MG) showed the highest peak at ages <5 years, besides the peak observed in adults, which was confirmed in east Asian populations, such as Korea, China and Hong Kong, and is different from that observed in white populations. The Childhood MG Study Group in Japan held an annual workshop for 12 years (from 2006 to 2017), in which the participants debated and obtained information about the clinical problems and related basic sciences of childhood MG. This workshop featured two kinds of presentations: research and clinical experiences. For the case presentation, 42 cases were reported, of which 14 were ocular MG and 28 were generalized MG, including nine cases of latent generalized MG. Seronegative MG was reported in eight cases, muscle‐specific receptor tyrosine kinase‐positive MG in one case and congenital myasthenic syndrome in four cases. Treatment of MG patients was various; tacrolimus was used for 23 cases, cyclosporine for two, a high dose of gamma‐globulin for 13 and thymectomy for 10. For the research presentation, various points of view were reported about the pathogenetic mechanism or treatment by top neurologists and scientists in Japan. This workshop will contribute to continued efforts of clinicians to treat patients, and researchers further progressing in their studies.

The correlation of neutrophil-to-lymphocyte ratio with the presence and short-time curative effect of myasthenia gravis in children: a retrospectively study

Objectives This study aimed to investigate the influence of neutrophil-to-lymphocyte ratio (NLR) on the severity and short-time curative effect of myasthenia gravis (MG) in children. Methods Data of 132 MG children were retrospectively analyzed, and data of 140 healthy controls (HC group) in the same period were collected. The data of both groups were compared and analyzed. Results NLR of MG group was significantly higher than that of HC group (Z = 2.644, p = 0.008). According to NLR level, patients were divided into 3 groups: N1 (NLR < 1.03), N2 (NLR 1.03-2.17), and N3 (NLR > 2.17). Significant differences in white blood cell counts, course of disease, uric acid, albumin and the time of hospital stay among the 3 groups were observed (p < 0.05, 0.01). The results of logistic regression revealed that NLR (adjusted OR = 3.874, 95% CI 1.359-11.045, p = 0.011) was the risk factor of MG, and it was risk factor of higher QMG during admission (adjusted OR = 2.989, 95% CI 1.247-7.160, p = 0.014) as well. Using the NLR level for the MG diagnostic test, the area under the receiver operating characteristic (ROC) curve was 0.765 [95%CI (0.710-0.820), p = 0.000], with a cut-off value of 1.39, sensitivity of 0.833, and specificity of 0.479. Cox regression analysis suggested that NLR (N1: Wald = 9.262, p = 0.010, N2: HR = 12.267, 95%CI 2.432-61.863, p = 0.000, and N3: HR = 8.142, 95%CI 1.209-77.754, p = 0.032) was associated with poor efficacy at discharge. Elevated NLR was considered as an independent risk factor of poor outcomes during discharge. Conclusion NLR could reflect disease severity and short time curative effect in children with MG to some extent. It may also be a potential marker in indicating diagnosis and severity of MG in children.

Myasthenia gravis in children; Issues and challenges

AbstractAutoimmune myasthenia gravis (MG) occurs in children, as well as in adults. Childhood myasthenia gravis is characterized by its distinct clinical features. Epidemiological studies have shown the high frequency of onset before the age of 5 years in Japan. Similar results have been reported from China. Clinical types are divided into pure ocular, latent generalized and generalized. In general, childhood myasthenia gravis is milder, mainly with ocular symptoms. Anti‐acetylcholine receptor antibody is often negative (seronegative). The responsiveness to treatment is generally good, and almost 90% of patients can achieve complete remission. Early diagnosis and adequate treatments are important.

Approach to the unraveled questions over neuromuscular junction diseases

This focused review series should be very useful to the readers, covering the various unraveled questions about neuromuscular disorders, such as anti‐low‐density lipoprotein receptor‐related protein 4, animal models and childhood myasthenia gravis.

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.

Analysis for the effect of different regimens on ocular myasthenia gravis in children

To evaluate the efficacy, recurrent risk factors and transferable ratio of treatments with 3 different regiments on children with systematic myasthenia gravis (MG). Methods: The data of 104 children with ocular MG from June 2010 to March 2014 were collected from Department of Pediatric Neurology of Xiangya Hospital and they were retrospectively studied. The patients were divided into 3 groups: a methylprednisolone group (n=44), a prednisone group (n=48) and a bromine pyridostigmine group (n=12). Evaluative system from American MG foundation was used to evaluate the efficacy of treatment and the ratio of ocular MG transformed into systematic MG. Results: The efficacy in the methylprednisolone group was better than that in the prednisone group, and both of them were better than that in the bromine pyridostigmine group (both P<0.05).Methylprednisolone, prednisone combined with bromine pyridostigmine could reach a better long-term efficacy in children with ocular MG. Early treatment with glucocorticoid could reduce clinical relapse. Conclusion: A treatment with high-dose methylprednisolone pulse can improve early clinical remission in children with ocular MG. However, there is a similar efficacy in the long run of different glucocorticoid therapeutic regiments. A relatively order onset age, infection and thyroid dysfunction are recurrent risk factors in children with ocular MG.

Effect of Jianpiyiqi granule on ocular myasthenia gravis in children prepared with a formula from Traditional Chinese Medicine

ObjectiveTo investigate the effect of Jianpiyiqi granule, prepared according to a Traditional Chinese Medicine (TCM) formula, on the ocular type of myasthenia gravis (MG) caused by a defect in synaptic transmission at the neuromuscular junction. MethodsA total of 155 children with ocular MG were recruited from January 2008 to January 2015. All individuals received ineffective glucocorticoid treatment prior to admission, and were given Jianpiyiqi granules (two doses per day) for 12 months. Plasma levels of acetylcholine receptor autoantibodies (AChR-Ab), cytokines, immune parameters and clinical score were analyzed. ResultsAfter intervention with Jianpiyiqi granule for 12 months, the levels of cytokines [including interleukin (IL)-6, IL-12, IL-17], immune parameters [including immunoglobulin G (IgG), IgM, free triiodothyronine, free thyroxine] and AChR-Ab were significantly decreased (P = 0.042, P = 0.049, P = 0.011, P = 0.02, P = 0.04, P = 0.03, P = 0.01; F = 21.60, P = 0.000). In contrast, IL-4 levels were significantly increased (P = 0.049). The absolute clinical score after treatment declined significantly compared with before treatment (F = 33.24, P = 0.000). The effective cure rate and the total effective rate gradually increased to a maximum of 149 (96.2%) and 151 (97.4%) in MG patients after 12 months of treatment, respectively. ConclusionThe Jianpiyiqi granule treatment lowered AChR-Ab levels and improved cytokine and other immune parameter levels, which suggests that the granule could be an ancillary treatment for ocular MG in children caused by a defect in synaptic transmission at the neuromuscular junction.

Meet the experts : therapy of myasthenia gravis in childhood

Meet the experts : therapy of myasthenia gravis in childhood

Clinical characteristics and therapeutic evaluation of childhood myasthenia gravis.

This study aimed to analyze the clinical characteristics, classification and treatment of childhood myasthenia gravis (MG) and address the prognosis through follow-up. The clinical data of 135 children with MG were grouped according to clinical type and therapeutic drugs, retrospectively analyzed and prospectively monitored. Of the 135 MG patients, 85.2% had type I (ocular type), with only 4.2% progressing to systemic MG; 13.4% had type II (general type); and 1.5% had type III (fulminating type). Relapse occurred in 46.1% of the 102 patients that were followed up. The positive rate for the primary acetylcholine receptor antibody was 40.19%, without significant differences among clinical subtypes. The positive rate of the repetitive nerve stimulation frequency test by electromyography was 37.97%. Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the patients. Thymic hyperplasia was present in 5.93% of the patients, while 1.48% had thymoma. Steroid treatment was effective in the majority of the patients. Ocular type MG was common in this cohort of patients. The incidence and mortality of myasthenia crisis were low, the presence of concurrent thymoma was rare and only a limited number of children developed neurological sequelae.

Reduction in peripheral regulatory T cell population in childhood ocular type myasthenia gravis.

Myasthenia gravis (MG) is a T-cell dependent and antibody mediated autoimmune disease. Recent studies of adult patients and animal models have shown that regulatory T cells (Tregs) play an important role in the pathogenesis of MG, but little is known about MG in children. This study evaluated the role of peripheral blood Tregs in childhood ocular MG and assessed if Tregs could be an index for estimating immunological status. Clinical data and peripheral lymphocytes were obtained from 13 children with serum AChR antibody-positive ocular type MG and 18 age-matched controls. Committed cells from MG patients were divided into two clinical stages: active (n=12) and remission (n=11). Tregs and Th17 cells were analyzed by flow cytometric analysis based on CD4(+)CD25(+) intracellular Foxp3(+) and CD4(+) intracellular IL-17A(+) fractions, respectively. The percentage of Tregs among peripheral blood CD4(+) T cells in active stage, remission stage, and control groups was 3.3±1.3%, 4.8±1.7%, and 5.0±0.6%, respectively. The Treg population was significantly lower in the active stage than in the remission stage and controls. Furthermore, Treg percentage was significantly lower during relapse of myasthenia symptoms. We witnessed no remarkable associations between the percentage of Tregs and immune suppressant dosages. A significant reduction in the peripheral Treg population is considered to contribute to the pathophysiology of ocular type childhood MG and may be a marker of immunological state in these patients.

Thymectomy for myasthenia gravis in children: A comparison of open and thoracoscopic approaches

PurposeThymectomy is an accepted component of treatment for myasthenia gravis (MG), but optimal timing and surgical approach have not been determined. Though small series have reported the feasibility of thoracoscopic resection, some studies have suggested that minimally invasive methods are suboptimal compared to open sternotomy owing to incomplete clearance of thymic tissue. Here we report the largest series of thymectomies for pediatric myasthenia gravis in the literature to date. MethodsA retrospective review of patients undergoing thymectomy for MG between 1990 and 2013 in a tertiary referral hospital was performed. Twelve patients who underwent thoracoscopic thymectomy were compared to 16 patients who underwent open thymectomy via median sternotomy. Postoperative outcomes were determined by electronic chart review in consultation with the treating pediatric neurologist. Disease severities were graded according to a modified Myasthenia Gravis Foundation of America (MGFA) Quantitative MG (QMG) score. ResultsOverall, thoracoscopic resections tended to be performed on patients with earlier and less severe disease than open surgeries. Inpatient length of stay was significantly shorter after thoracoscopic surgery (mean 1.8 vs 8.0 days, p=0.045). The preoperative and postoperative MGFA QMG scores were equivalent between the two groups. Both groups experienced a decrease in disease severity (p<0.001) after median follow-up time of 23 months in the thoracoscopic group and 44 months in the open group. ConclusionsMinimally invasive thymectomy for MG in children has increased in popularity as surgeons and neurologists compare the risks and benefits of surgery against other therapies. This analysis suggests that thoracoscopic thymectomy is not inferior to median sternotomy in terms of disease control in this small series, and that the morbidity of the thoracoscopic approach appears sufficiently low to be considered for early stage disease. Low perioperative morbidity and shortened hospital course make thoracoscopic thymectomy an attractive option in centers with sufficient medical and surgical experience.

Prognosis and therapy of myasthenia gravis in children and adolescents

Prognosis and therapy of myasthenia gravis in children and adolescents

Increased subsequent risk of myasthenia gravis in children with allergic diseases

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction. The initiating factors of MG remain unclear. However, allergy has been regarded as a potential risk factor. We included 410 children with MG diagnosed between 2000 and 2008, as well as 1640 randomly selected controls. The odds ratios of MG were calculated to determine the association between MG and preexisting allergic diseases. The children with allergic diseases were at increased subsequent risk of MG, which was associated with the cumulative effect of the concurrent allergic diseases and the frequency of seeking medical care.