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Our approach to pharmacologic therapy in juvenile myasthenia gravis.
Source publication
Juvenile Myasthenia Gravis (JMG) is a rare disorder, defined as myasthenia gravis in children younger than 18 years of age. While clinical phenotypes are similar to adults, there are a number of caveats that influence management: broader differential diagnoses; higher rates of spontaneous remission; and the need to initiate appropriate treatment ea...
Citations
... Juvenile MG (JMG) corresponds to another distinct group of patients. Patients with MG onset before the age of 18 years account for 10-15% of the MG population 12 . This group of patients does not include neonatal MG affecting newborns and caused by the transfer of antibodies from a mother with MG to her baby during pregnancy. ...
... There is a wide range of variability in the presentation and severity of symptoms in juveniles, as in adult MG patients. However, JMG patients have a higher rate of spontaneous remission 12 . ...
... No differences were observed regarding the proportion of AChR + MG patients in both subgroups (Table 1). We did not compare the treatments and their impacts, but they typically involve a combination of symptomatic and immunosuppressive therapies, with thymectomy in appropriate cases 12,18 . Nevertheless, we analyzed the percentage of thymectomized patients and 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.
... MG is estimated to affect more than 700,000 people globally, with European incidence ranging between 0.63 and 2.9 per 100,000 person-years and prevalence ranging between 11.2 and 36.1 per 100,000 persons [3]. In children, MG is even more rare, with European incidence rates ranging between 0.09 and 0.43 per 100,00 person-years [4]. There is a peak in incidence from 60 to 70 years for both genders and an additional peak from 20 to 40 years in women [5]. ...
International guidelines on the treatment of myasthenia gravis (MG) have been published but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian MG experts for the practical management of MG in Belgium. It includes recommendations for treatment of adult patients with generalized myasthenia gravis (gMG) or ocular myasthenia gravis (oMG). Depending on the MG-related antibody a treatment sequence is suggested with therapies that can be added on if the treatment goal is not achieved. Selection of treatments was based on the level of evidence of efficacy, registration and reimbursement status in Belgium, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in February 2024. In addition to the treatment considerations, other relevant aspects in the management of MG are addressed, including comorbidities, drugs aggravating disease symptoms, pregnancy, and vaccination. As many new treatments might potentially come to market, a realistic future perspective on the impact of these treatments on clinical practice is given. In conclusion, these recommendations intend to be a guide for neurologists treating patients with MG in Belgium.
... In our study, we included patients with EOMG aged 1-18 years of age. MG in children and adolescents in China is mainly ophthalmo-type, which has a higher spontaneous remission rate (34,35). Moreover, patients with EOMG have few intercurrent diseases and can use steroids and other drugs in sufficient amounts, whereas those with LOMG may be limited in the use of drugs when taking steroids or other immunosuppressants due to concurrent diseases (such as diabetes, abnormal liver and kidney function, etc.), which affects the treatment effect. ...
Purpose
This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase.
Methods
A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group.
Results
Kaplan–Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05).
Conclusion
Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.
... As such, treatment has included steroids, immunosuppressive agents, and, more recently, various biological agents, which are more easily implemented in treatment and more effective. However, the use of such drugs in children is limited by the difficulty of conducting clinical trials to confirm their safety [136,137]. Immunosuppressive agents such as azathioprine and cyclophosphamide have been used for severe cases in Japan, but they are not actively used because they are not covered by insurance. Currently, tacrolimus and ciclosporin A are the two calcineurin inhibitors that are covered by insurance, and eculizumab, a biologic, has recently become available for use in pediatric patients. ...
The pathophysiology of myasthenia gravis (MG) has been largely elucidated over the past half century, and treatment methods have advanced. However, the number of cases of childhood-onset MG is smaller than that of adult MG, and the treatment of childhood-onset MG has continued to be based on research in the adult field. Research on pathophysiology and treatment methods that account for the unique growth and development of children is now desired. According to an epidemiological survey conducted by the Ministry of Health, Labour and Welfare of Japan, the number of patients with MG by age of onset in Japan is high in early childhood. In recent years, MG has been reported from many countries around the world, but the pattern of the number of patients by age of onset differs between East Asia and Western Europe, confirming that the Japanese pattern is common in East Asia. Furthermore, there are racial differences in autoimmune MG and congenital myasthenic syndromes according to immunogenetic background, and their pathophysiology and relationships are gradually becoming clear. In addition, treatment options are also recognized in different regions of the world. In this review article, I will present recent findings focusing on the differences in pathophysiology.
... However, purely ocular cases have a higher chance of being seronegative. 18 Three of our four patients had positive AChR antibodies, whereas none was positive for MuSK antibody. Interestingly, our two-and-a-half-year-old child (Case 4), arrived in the emergency department with respiratory crises, and had a prolonged PICU stay; she did not respond to IVIG but showed a dramatic response to plasmapheresis. ...
Myasthenia in the infancy and toddler age group is rare and often presents a challenge to treating pediatric neurologists. Our report addresses the challenges encountered when distinguishing myasthenia in infants and toddlers from similar illnesses, as well as the differentiation between congenital myasthenia, transient myasthenia, and autoimmune myasthenia. We present four cases of myasthenia between the ages of 10 and 30 months. The diagnosis and management of these cases were challenging due to the variability in clinical presentation. Four cases of myasthenia were diagnosed, with three having autoimmune myasthenia and one having congenital myasthenic syndrome. One patient initially tested negative for acetylcholine receptor antibodies, but later tested positive after 4 months and had a rare facial diplegia finding. The patient with congenital myasthenic syndrome had a novel genetic mutation, DPAGT1 homozygous variants, and also had false positive acetylcholine receptor antibodies. These cases highlight the importance of genetic testing for all infants and toddlers suspected of having myasthenia.
... La timectomía está indicada en cualquier paciente con un timoma, y se debe considerar en MGJ con AChR positivo, dando tiempo para la remisión espontánea 10,11 . La MGJ presenta buena tasa de remisión ante el tratamiento quirúrgico e incluso presenta remisión espontánea en el 14,3-45% 8 . ...
Objetivo:
Describir la evolución clínica postquirúrgica de una serie de casos de pacientes con Miastenia Gravis juvenil (MGJ) tratados con timectomía por toraoscópica videoasistida (TVA) derecha.
Materiales y Métodos:
Estudio retrospectivo que incluyó 13 pacientes pediátricos con diagnóstico de MGJ sometidos a timectomía toracoscópica derecha en la Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI de México, entre marzo de 2016 y abril de 2022. Los pacientes fueron caracterizados clínicamente y la enfermedad fue clasificada de acuerdo a los criterios de Osserman. La evolución postquirúrgica se evaluó con la clasificación de DeFilippi para determinar la proporción de pacientes con mejoría y la remisión completa.
Resultados:
Los pacientes incluidos fueron, en su mayoría, mujeres (84,6%) con edad promedio al diagnóstico fue de 11,1 ± 3,1 años. Las cuatro clasificaciones de MG fueron incluidas, con mayor proporción de MG generalizada leve (38,5%), seguida de ocular (23,1%) y generalizada moderada grave (23,1%). La evaluación de la progresión postquirúrgica demostró que a los tres meses de seguimiento 92,3% presentó mejorías, incluyendo la disminución del uso de medicamentos. La remisión total solo se registró en uno de los pacientes. Los pacientes que tuvieron cirugía antes de los 12 meses de evolución de la MGJ presentaron mejores resultados post timectomía por TVA.
Conclusión:
Se demostró la utilidad de timectomía por TVA en pacientes pediátricos mexicanos con MGJ. Nuestra experiencia agrega evidencia de que los pacientes pediátricos se benefician de la timectomía, mejorando su estado clínico y disminuyendo el uso de medicamentos y complicaciones e la enfermedad.
... There is a bimodal distribution in the onset of myasthenia gravis, with increased incidence in younger ages, peaking in the second decade of life, and another peak in the sixth decade of life. 3 Juvenile myasthenia gravis is defined as onset of myasthenia gravis before 18 years of age 5 , though some studies place this cut off at 19 years of age. 6 JMG age of onset can be as young as 12-24 months, up to an adolescent onset. ...
Pediatric myasthenia gravis (MG) is a relatively rare, but very treatable condition. Prognosis in pediatric myasthenia gravis is favorable for minimal manifestation status (MMS) or remission when compared to adults. Ocular only presentations are more common, though severe refractory generalized MG presentations also occur. An observational examination is key to the diagnosis and follow-up of pediatric MG patients in the clinic setting. Treatment options are limited by side effect and growth considerations, as well as lack of approved MG medications in the pediatric population. Multidisciplinary care should be considered for pediatric MG, similar to other neuromuscular conditions seen in specialty care settings.
... Juvenile myasthenia gravis (JMG) is a rare subtype of early-onset myasthenia gravis (≤18 years old). According to the current data, JMG was more prevalent in China than in western countries, 38 accounting for around 45% and 5% of MG cases, respectively. 39,40 Although JMG in China was mainly reported to be ocular myasthenia gravis and often had good prognosis, about half of patients exhibited elevated acetylcholine receptor antibodies, which were considered to be associated with increased risk of generalization. ...
Objective:
As a potentially life-threatening condition, myasthenia gravis (MG) has limited epidemiological studies on mortality. We aim to provide demographic distribution, geographical variation, and temporal trend of MG-related mortality in China.
Methods:
The national population-based analysis was conducted based on records derived from the National Mortality Surveillance System of China. All deaths related to MG were identified from 2013 to 2020, and MG-related mortality was evaluated by sex, age, location, and year.
Results:
A total of 4224 deaths were related to MG during 2013-2020, and the median age at death of MG was 59.45 years, significantly lower than that in the general population (75.47 years, P < 0.05). In 2020, the age-standardized mortality rate of MG was 1.86 per million people and markedly higher in males than in females (2.37 vs. 1.31 per million). The mortality rate per million was lower than 1 in young children, peaking at 2.83 only in males (vs. 0.36 in females) aged 10-19 years, and substantially increased with age, reaching the highest rate of 13.31 for males and 10.58 for females aged 80 years and older. Geographical disparity across China was observed with the highest age-standardized mortality rate in Southwest (2.53 per million). From 2013 to 2020, MG-related mortality rate showed an increasing trend with the average annual percentage change of 3.5% (95% CI, 1.4-5.6). The notable increases occurred in age 10-19 years and over 70 years.
Interpretation:
In China, MG-related mortality was notably high among adolescent males and the elderly. The increasing death burden due to MG highlight challenges to disease management.
... In addition, since the expression of target receptor β(3) is limited to the bladder, the inherent cardiovascular safety profile of mirabegron contributes to its superiority in comparison to antimuscarinic drugs [14]. Myasthenia gravis (MG) is a chronic, autoimmune and neuromuscular transmission disease characterized by an autoantibody reaction to the structures of the neuromuscular junction, resulting in impaired synaptic transmission and the consequent fatigability and weakness of skeletal muscles [15]. The disease's prevalence is higher in women (approximately 70%), and the varying severity of symptoms and degree of muscular involvement directly impact the patient's quality of life [16]. ...
... MG mainly affects acetylcholine receptors and disturbs their mechanism (O'Connell et al., 2020). In most MG cases, the first symptoms are the weakness of extraocular muscles and ocular misalignment, F I G U R E 2 Forest plot of the prevalence of depression in MG patients. ...
Objective
Myasthenia gravis (MG) people experience adverse psychiatric outcomes, which may impact on their life and disturb their daily activity. Depression and anxiety are identified as significant psychiatric problems that MG people face. However, there is no sufficient epidemiological information about depression and anxiety‐based publication. Due to this limitation, the aim of this study was to review the prevalence of depression and anxiety in MG patients.
Methods
Original and international databases were searched to find papers about the estimation of anxiety and depression. Random‐effects analysis was used for calculating the proportions of anxiety and depression. For estimating anxiety and depression based the severity, instruments, type of studies, and study regions, subgroup analysis was performed.
Results
38 studies met inclusion criteria and entered study. The pooling of the prevalence of depression was found at 36%, (95% CI 28% to 45%). Also, prevalence of anxiety was found at 33%, (95% CI 25% to 42%). Prevalence of depression based on mild, moderate, and severe level was 27%, 14%, and 9%, respectively.
Conclusions
Anxiety and depression are a major concern among MG individuals. The estimation of both anxiety and depression are high even when compared to other autoimmune diseases. It seems depression and anxiety are important issues and more attention needs to be paid to these psychiatric disorders.
