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      Juvenile Myasthenia Gravis in a 14-year-old adolescent masked by mood disorder: the complex balance between neurology and psychiatry

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          Abstract

          Juvenile Myasthenia Gravis (JMG) is a neuromuscular disease, often characterized at onset by fatigue and fluctuating weakness. We report a case of a girl affected by severe mood disorder, in which the diagnosis of JMG and its treatment were challenged by the concomitant psychiatric condition. A 14-year-old girl, with a history of severe mood disorder and emotional dysregulation, had been treated with benzodiazepines, sertraline, and antipsychotics, reporting generalized fatigability, weakness, and drowsiness, first ascribed to her psychiatric condition and therapy. After a suicide attempt, she was hospitalized and a neurological assessment revealed a fluctuating ptosis and facial weakness, that improved with rest. The diagnosis of JMG was confirmed by repeated nerve stimulation test, and by the response to pyridostigmine. Antibodies anti-AChR and anti-MuSK were negative. JMG diagnosis may be harder in adolescents with psychiatric comorbidity. Moreover, the neurological condition limits the choice of the appropriate psychopharmacotherapy.

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          Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update

          Myasthenia gravis (MG) is an autoimmune neuromuscular disorder which is characterized by presence of antibodies against acetylcholine receptors (AChRs) or other proteins of the postsynaptic membrane resulting in damage to postsynaptic membrane, decreased number of AChRs or blocking of the receptors by autoantibodies. A number of drugs such as immune checkpoint inhibitors, penicillamine, tyrosine kinase inhibitors and interferons may induce de novo MG by altering the immune homeostasis mechanisms which prevent emergence of autoimmune diseases such as MG. Other drugs, especially certain antibiotics, antiarrhythmics, anesthetics and neuromuscular blockers, have deleterious effects on neuromuscular transmission, resulting in increased weakness in MG or MG-like symptoms in patients who do not have MG, with the latter usually being under medical circumstances such as kidney failure. This review summarizes the drugs which can cause de novo MG, MG exacerbation or MG-like symptoms in nonmyasthenic patients.
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            Pediatric Myasthenia Gravis.

            Myasthenia gravis is a disorder of neuromuscular transmission that leads to fatigue of skeletal muscles and fluctuating weakness. Myasthenia that affects children can be classified into the following 3 forms: transient neonatal myasthenia, congenital myasthenic syndromes, and juvenile myasthenia gravis (JMG). JMG is an autoimmune disorder that has a tendency to affect the extraocular muscles, but can also affect all skeletal muscles leading to generalized weakness and fatigability. Respiratory muscles may be involved leading to respiratory failure requiring ventilator support. Diagnosis should be suspected clinically, and confirmatory diagnostic testing be performed, including serum acetylcholine receptor antibodies, repetitive nerve stimulation, and electromyography. Treatment for JMG includes acetylcholinesterase inhibitors, immunosuppressive medications, plasma exchange, intravenous immunoglobulins, and thymectomy. Children with myasthenia gravis require monitoring by a pediatric ophthalmologist for the development of amblyopia from ptosis or strabismus.
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              Management of Juvenile Myasthenia Gravis

              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.
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                Author and article information

                Journal
                Acta Myol
                Acta Myol
                AM
                Acta Myologica
                Pacini Editore Srl
                1128-2460
                2532-1900
                30 September 2022
                2022
                : 41
                : 3
                : 126-129
                Affiliations
                [1 ] Section of Child and Adolescent Neuropsychiatry, Department of Public Health, and Paediatric Sciences, Università degli Studi di Torino , Turin, Italy
                [2 ] Neuromuscular Unit, Department of Neurosciences RLM, University of Turin , Turin, Italy
                Author notes
                Correspondence Rossella D’Alessandro Section of Child and Adolescent Neuropsychiatry, Department of Public Health and Paediatric Sciences, University of Turin, Regina Margherita Hospital, piazza Polonia 94, 10126 Turin, Italy. Tel.: +39 011 3135248. Fax: +39 011 3135387. E-mail: rosselladalessandro@ 123456live.com
                Author information
                https://orcid.org/0000-0002-6358-5937
                Article
                10.36185/2532-1900-079
                9628800
                6912f9e4-9221-4a8b-b9fb-6cf1ec9b9be8
                ©2022 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy

                This is an open access article distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license. The article can be used by giving appropriate credit and mentioning the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en

                History
                : 29 August 2022
                : 19 September 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 10, Pages: 4
                Categories
                Case Report

                Plant science & Botany
                juvenile myasthenia gravis,psychiatric comorbidities,mood disorder
                Plant science & Botany
                juvenile myasthenia gravis, psychiatric comorbidities, mood disorder

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