Management of Juvenile Myasthenia Gravis

Abstract

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 early, to avoid the long-term physical and psychosocial morbidity. Current practice is taken from treatment guidelines for adult MG or individual experience, with considerable variability seen across centers. We discuss our approach to treating JMG, in a large specialist JMG service, and review currently available evidence and highlight potential areas for future research. First-line treatment of generalized JMG is symptomatic management with pyridostigmine, but early use of immunosuppression, where good control is not achieved is important. Oral prednisolone is used as first-line immunosuppression with appropriate prevention and monitoring of side effects. Second-line therapies including azathioprine and mycophenolate may be considered where there is: no response to steroids, inability to wean to a reasonable minimum effective dose or if side-effects are intolerable. Management of ocular JMG is similar, but requires close involvement of ophthalmology in young children to prevent amblyopia. Muscle-specific tyrosine kinase (MuSK)-JMG show a poorer response to pyridostigmine and anecdotal evidence suggests that rituximab should be considered as second-line immunosuppression. Thymectomy is indicated in any patient with a thymoma, and consideration should be given in acetylcholine receptor (AChR) positive JMG allowing time for spontaneous remission. The benefit is less clear in ocular JMG and is not advised in MuSK-JMG. Children experiencing a myasthenic crisis require urgent hospital admission with access to the intensive care unit. PLEX is preferred over IVIG due to rapid onset of action, but this needs to be balanced with feasibility in very young children. Key questions remain in the management of JMG: when to initiate both first- and second-line treatments, choosing between steroid-sparing agents, and determining the optimal dose and treatment duration. We feel that given the rarity of this disease, the establishment of national registries and collaboration across groups will be needed to address these issues and facilitate future drug trials in JMG.

Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

“…Generalization of symptoms occurs less often compared to adult MG patients. Moreover, the rate of spontaneous remissions is much higher than in adults [ 55 , 56 , 57 ]. Similar to the adult-onset MG, AChR Ab are mostly detected in both ocular and generalized MG [ 55 , 58 ].…”

Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies

“…Accurate antibodies detection is crucial for diagnosis and prognosis, together with other factors, such as thymus histology, age and clinical features. For instance, AChR antibody-positive patients tend to have follicular hyperplasia of the thymus and practically all cases of thymoma are AChRAbs positive, thus thymectomy (surgical removal of thymus) is a first-line treatment choice in AChR MG, excluding patients with only OMG ( 29 , 92 – 94 ). In addition, refractory AChR-MG is usually present in patients with thymoma.…”

“…The disease has two typical peaks of onset; early-onset MG (EOMG, <50 years), with a predominance of females and late-onset MG (LOMG, >50 years), that have a larger proportion of males (18,24). In contrast, neonatal and juvenile MG is relatively uncommon and symptoms are usually less severe and limited to OMG form (18, [27][28][29][30]. Genetic studies have revealed strong relationship between human leukocyte antigen, HLA-DQA1, DQB1 with thymoma, while HLA-DQB1and DRB1alleles were associated with EOMG, LOMG and OMG (31,32).…”

Developing outcome measures of disease activity in pediatric myasthenia

“…Juvenile myasthenia gravis (JMG) is an autoimmune disorder with an immune response directed against the neuromuscular junction, whereas congenital myasthenic syndrome (CMS) refers to a group of genetic disorders affecting proteins expressed at the neuromuscular junction 1‐3 . Neonatal myasthenia gravis may occur in 10% to 20% of infants born to women with myasthenic syndrome (MG) due to transplacental transfer of acetylcholine receptor antibodies, but is not suitable for evaluation using the scales under investigation in this study 2,4 …”

“…[1][2][3] Neonatal myasthenia gravis may occur in 10% to 20% of infants born to women with myasthenic syndrome (MG) due to transplacental transfer of acetylcholine receptor antibodies, but is not suitable for evaluation using the scales under investigation in this study. 2,4 JMG and CMS have fluctuating courses, although treatment can improve disease course and well-being of patients. 5 History and neurological examination at a single office visit is limited in assessing disease course and response to therapy due to recall bias, physician variability, and the variable symptoms of the disease.…”