Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics / Miastenia gravis triplo-soronegativa: características clínicas e epidemiológicas

Abstract Background Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG. Objective This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG. Methods This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile. Results The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment. Conclusion Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

Resumo Antecedentes A Miastenia gravis (MG) é uma desordem autoimune geralmente causada por anticorpos antirreceptores de acetilcolina (anti-RACh), tirosina quinase músculo-específica (anti-MuSK) ou proteína 4 relacionada ao receptor de lipoproteína de baixa densidade (anti-LRP4). No entanto, em uma parcela dos pacientes, nenhum destes três anticorpos pôde ser detectado, sendo estes casos denominados "triplo-soronegativos". Objetivo Descrever a frequência, bem como as características clínicas e epidemiológicas dos pacientes com MG triplo-soronegativa. Métodos Consiste em um estudo transversal e restrospectivo, realizado através da análise de prontuários médicos. Foi realizada análise estatística descritiva e analítica entre os subgrupos de pacientes, classificados de acordo com o perfil sorológico. Resultados A população consistiu de 93 pacientes com MG: 85 pacientes apresentavam positividade para anticorpos, sendo 80 (86%) com anticorpos anti-RACh, cinco (5,4%) com anti-MuSK, e não foram encontrados pacientes com anti-LRP4. Oito (8,6%) eram pacientes triplo-soronegativos, que apresentaram idade média de início da doença de 30 anos (21-45), e com sintomas iniciais mais comuns de ptose, diplopia e fraqueza generalizada. 75% dos pacientes triplo-soronegativos apresentaram resposta adequada ao tratamento. Conclusão O estudo demonstrou uma baixa frequência da pacientes com MG triplo-soronegativa na população brasileira. A MG triplo-soronegativa foi predominante nas mulheres, que se apresentaram com ptose, diplopia ou fraqueza generalizada, e a maioria dos pacientes apresentou resposta adequada ao tratamento imunossupressor. Não houve diferença significativa entre a MG triplo-soronegativa e os demais subgrupos.

Did the speech of patients with Myasthenia Gravis decline over 4 years? / Há declínio na fala de pacientes com Miastenia Gravis ao longo de 4 anos?

ABSTRACT Purpose To compare the speech and voice patterns of myasthenia gravis (MG) patients over four years, and correlate the results with clinical aspects of the disease. Methods Data was collected for 4 years. The clinical assessment tools included the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and the Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL). To assess speech, the recorded speaking tasks were analyzed acoustically and given auditory-perceptual ratings. Sex (equal distribution) and age (p=0.949) were used as matching criteria in the final sample, which consisted of 10 individuals in the MG group (MGG) and 10 individuals in the control group (CG). Results After 4 years, the MG participants presented stable health status, increased mild and moderate dysarthria (from 40% to 90% of the subjects), and a significant deterioration in the respiration, phonation, and articulation subsystems. The acoustic analysis showed a decline in articulatory patterns (speech rate p=0.047, articulation rate p=0.007, mean syllable duration p=0.007) and vocal quality (increased jitter p=0.022). In the follow-up comparison, there was a significant difference between the phonation variables (shimmer and harmonic-to-noise ratio) of the MGG and CG. Conclusion The MG patients presented a decline in speech over four years and an increase in mild and moderate dysarthria. Despite presenting stable health status, their respiratory, phonatory, and articulatory subsystems worsened. There was no correlation between speech patterns and clinical characteristics of the disease (severity and motor scale).

RESUMO Objetivo Comparar o padrão de fala e voz de indivíduos com Miastenia Gravis (MG) em um intervalo de quatro anos e correlacionar com aspectos clínicos da doença. Método A coleta de dados foi realizada ao longo de 4 anos. A avaliação clínica foi composta pelo Quantitative Myasthenia Gravis Score (QMGS), pela Myasthenia Gravis Foundation of America Classification (MGFA) e pela escala de qualidade de vida para Miastenia Gravis (MG-QOL). A avaliação da fala foi composta por gravação de tarefas, análise perceptivo-auditiva e análise acústica. A amostra final foi composta por 10 indivíduos em MG e 10 indivíduos no grupo controle (GC), pareados por sexo (distribuição igualitária) e idade (p=0,949). Resultados Após 4 anos, os indivíduos com MG apresentaram estabilidade clínica, aumento do diagnóstico de disartria leve e moderada (de 40% para 90% dos sujeitos) e diminuição significativa no desempenho dos subsistemas da fala: respiração, fonação e articulação. Na análise acústica, houve declínio do padrão articulatório (taxa de fala p=0,047, taxa de articulação p=0,007, duração média das sílabas p=0,007) e qualidade vocal (jitter aumentado p=0,022). Houve diferença significativa nas variáveis fonatórias (shimmer e harmonic-to-noise ratio) entre os grupos MG e GC na comparação do seguimento. Conclusão Indivíduos com MG apresentaram declínio no padrão de fala em um intervalo de quatro anos, com aumento no número de disártricos (leve e moderado). Mesmo com a estabilidade da doença, houve piora dos subsistemas respiratório, fonatório e articulatório. Não houve correlação entre o padrão de fala e as características clínicas da doença (gravidade e escala motora).

Evaluación de la efectividad de la timectomía como tratamiento de la Miastenia Gravis

Objetivo: evaluar efectividad de timectomía como alternativa de tratamiento a la Miastenia Gravis (MG) en nuestro centro, entre 2007 y 2019, y cómo ha impactado en calidad de vida y manejo farmacológico. Material y Método: cohorte retrospectiva de pacientes sometidas a timectomía por equipo Cirugía Torácica del Hospital Gustavo Fricke (HGF) entre 2007 y 2019. Las variables fueron el tratamiento médico y dosis de anticolinesterásicos pre y post timectomía, y la calidad de vida medida a través de la encuesta MG-QOL15. Se utilizaron medidas de desviación estándar y comparaciones estadísticas para el análisis de estas variables, considerando estadísticamente significativo un p < 0,05. Resultados: total de 20 pacientes, mayoría mujeres jóvenes, timectomía vía transesternal. Dosis de anticolinesterásicos mostró disminución estadísticamente significativa de 5,05 a 3,06 pre y post timectomía respectivamente (p < 0,05). Encuesta MG-QOL15 media de 11,9 puntos. Discusión: Se ha demostrado que la timectomía cumple un rol importante en el manejo de la MG, otorgando una superioridad frente al tratamiento médico exclusivo. La Fundación Americana para Miastenia Gravis, recomienda el uso de la encuesta MG-QOL15 como herramienta para evaluar la calidad de vida. Existe poca literatura nacional en relación a este tema. Conclusión: La timectomía, es un procedimiento que mejora la calidad de vida de los pacientes con MG y permite reducir en forma significativa la dosis de fármacos utilizados.

Objective: To evaluate effectivity of thymectomy as an alternative treatment of MG in our center, between 2007 and 2019 and to know how it has impacted in life quality and pharmacological management. Material and Method: cohort study patients treated with thymectomy by Thoracic Surgical team from Gustavo Fricke Hospital between 2007 and 2019. The study variables were medical treatment and anticholinesterases doses before and after the thymectomy, and life quality measured through MG-QOL15 survey. Standard deviation measures and statistics comparisons were used for the analysis of these variables, considering statistically significant a p < 0.05. Results: total of 20 patients, mainly young women, thymectomy through a Trans-sternal approach. Anticholinesterase doses, showed a statistically significant decrease from 5.05 to 3.06 before and after thymectomy (p < 0.05). Discussion: It has been demonstrated that thymectomy plays an important role on the management of MG, giving a mastery against medical exclusive treatment, The American Foundation for Myasthenia Gravis recommends the use of MG-QOL15 survey as an important tool to evaluate life quality. There is a limited amount of national literature related to this topic. Conclusion: Thymectomy is a life quality changing procedure for MG patients and it helps to significantly reduce the drug doses used.

Electrophysiological evaluation of the neuromuscular junction: a brief review / Avaliação eletrofisiológica da junção neuromuscular: breve revisão

Abstract The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ("jiggle") due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.

Resumo O nervo terminal e a membrana muscular compõem a junção neuromuscular. Após a abertura dos canais de cálcio dependentes de voltagem, os potenciais de ação do axônio motor provocam uma cascata de eventos que libera acetilcolina das vesículas para a fenda sináptica, ligando-se ao receptor na membrana muscular para despolarização. O potencial de ação muscular composto de baixa amplitude ocorre nas desordens pré-sinápticas, aumentando em mais de 100% após esforço de 10 segundos na síndrome miastênica de Lambert-Eaton e menos no botulismo. A eletromiografia pode mostrar potenciais de ação da unidade motora miopáticos e instabilidade morfológica ("jiggle") devido ao bloqueio do impulso. Estimulação nervosa repetitiva (ENR) de baixa frequência é útil nos distúrbios pós-sinápticos, como miastenia gravis e a maioria das síndromes miastênicas congênitas, quando há número reduzido de receptores de acetilcolina funcionantes. ENR de baixa frequência com decremento >10% é anormal comparando-se à amplitude do quarto com o primeiro potencial de ação muscular composto. ENR de alta frequência é útil nas doenças pré-sinápticas, como síndrome miastênica de Lambert-Eaton, botulismo e algumas síndromes miastênicas congênitas raras. ENR de alta frequência libera mais cálcio, aumenta acetilcolina, resultando em incremento do potencial de ação muscular composto. O eletrodo de agulha concêntrico registra potenciais de ação aparente de fibra única (PAAFU). Ativação voluntária mede jitter entre dois PAAFUs (duas junções neuromusculares). Ativação elétrica mede jitter de um PAAFU (uma junção neuromuscular). Jitter é o teste mais sensível para detectar disfunção de junção neuromuscular. A maioria dos distúrbios juncionais é responsiva ao tratamento.

Tratamento manipulativo osteopático em paciente com síndrome da pessoa rígida e miastenia gravis: relato de caso / Osteopathic manipulative treatment in person with stiff person syndrome and myasthenia gravis: case report

Introdução: Síndrome da Pessoa Rígida (SPR) é uma doença neurológica autoimune rara caracterizada pela rigidez e espasmos musculares episódicos dolorosos, especialmente no tronco e extremidades do corpo, gerando comprometimento funcional importante. Existe uma lacuna de conhecimento sobre os possíveis efeitos do tratamento manipulativo osteopático (TMO) nos sintomas motores de pessoas com SPR. Objetivos: Descrever os efeitos do TMO na tontura, equilíbrio e amplitude de movimento (ADM) cervical em uma pessoa com a SPR e miastenia gravis. Método: Relato de caso baseado no TMO em uma mulher com SPR e miastenia grave. As seguintes avaliações foram utilizadas: Inventário de Brazilian Version of the Dizziness Handicap Inventory (DHI), Fall Efficacy Scale (FES I ­ Brazil), Timed Get Up and Go Test (TUG), Teste de Sentar e Levantar 5 vezes, goniometria dos movimentos da coluna cervical. Resultados: Nenhum resultado expressivo foi obtido pela FES-I (-1,8%) e DHI (0%). Para os testes funcionais (TUG e Sentado para de pé 5 vezes) observamos melhora de 5,8% e 6,7%, respectivamente, após o tratamento. A ADM cervical melhorou substancialmente em todos os movimentos avaliados (flexão: 60%, extensão: 28%, rotação direita: 33%, rotação esquerda:38%, inclinação lateral direita: 77%, inclinação lateral esquerda: 87%). Conclusão: O TMO proposto pareceu ser importante para melhora da ADM cervical no caso relatado. Medo de quedas, impacto da tontura na qualidade de vida e funcionalidade de membros inferiores não demonstrou melhoras após o TMO.

Introduction: Stiff Person Syndrome (SPS) is a rare neurological autoimmune disease characterized by stiffness and painful episodic muscle spasms, especially in the trunk and extremities of the body, causing significant functional impairment in affected individuals. There is a gap in knowledge about the possible effects of an osteopathic manipulative treatment (OMT) on the motor symptoms of people with SPS. Objectives: To describe the effects of an OMT on dizziness, balance deficit, and cervical range of motion (ROM) in a patient with SPS and myasthenia gravis. Methods: This is a case report on an OMT intervention in a woman with SPS and myasthenia gravis. The following assessments were used: Brazilian Version of the Dizziness Handicap Inventory (DHI), Fall Efficacy Scale (FES I ­ Brazil), Timed Get Up and Go Test (TUG), Stand Up Test 5 times, goniometry of cervical movements. Results: No expressive results were obtained for FES I ­ Brazil (-1.8%) and DHI (0%). For the functional tests (TUG and Sit and stand up 5x) we observed an improvement of 5.8% and 6.7%, respectively, after treatment. The cervical ROM improved substantially in all movements tested (flexion: 60%, extension: 28%, right rotation: 33%, left rotation: 38%, right side bending: 77%, left side bending: 87%). Conclusion: The proposed OMT appears to be important for the improvement of cervical ROM in this case. Fear of falls, impact of dizziness on quality of life, and lower limb functionality did not demonstrate meaningful improvements after the OMT.

Timectomía toracoscópica en pacientes con Miastenia Gravis juvenil

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.

Objective: To describe the post-surgical clinical evolution of a case series of patients with juvenile myasthenia gravis (JMG) treated with right video-assisted thoracoscopic (TVA) thymectomy. Materials and Methods: Retrospective study that included 13 pediatric patients with JMG who underwent right TVA thymectomy at the Siglo XXI National Medical Center of Mexico between March 2016 and April 2022. Patients were clinically characterized, and the disease was classified according to Osserman's criteria. Post-surgical evolution was evaluated using the DeFilippi classification to determine the proportion of patients with improvement and complete remission. Results: The included patients were mostly women (84.6%) with a mean age at diagnosis of 11.1 ± 3.1 years. The four MG classifications were included, with the highest proportion of mild generalized MG (38.5%), followed by ocular (23.1%) and moderate-severe generalized (23.1%). The evaluation of post-surgical progression showed that after three months of follow-up, 92.3% presented improvements, including a decrease in the use of medications. Complete remission was only recorded in one of the patients. Patients who underwent surgery before 12 months of evolution of JMG had better results after TVA thymectomy. Conclusion: The usefulness of TVA thymectomy in Mexican pediatric patients with JMG was demonstrated. Our experience adds evidence that pediatric patients benefit from thymectomy by improving their clinical status and decreasing the use of medications and complications of the disease.

Crisis Miasténica: Reporte de Caso y Revisión de la Literatura / Myasthenic Crisis: Case Report and Literature Review

Introducción. La crisis miasténica es la complicación más grave que sufren los pacientes con Miastenia Gravis. Esta enfermedad se caracteriza clínicamente por debilidad muscular generalizada, que particularmente mejora con el reposo y empeora con el ejercicio debido al agotamiento de la conducción nerviosa a nivel post sináptico. El manejo de la crisis miasténica tiene como piedra angular tratar la causa desencadenante, así como utilizar los fármacos de acción rápida y los descritos en la literatura para enfrentar este escenario, como la plasmaféresis, inmunoglobulinas o terapia biológica. Además, es crucial tener un adecuado manejo desde el punto de vista ventilatorio manteniendo la protección pulmonar y sobre todo diafragmática, con las herramientas disponibles en la actualidad al lado de la cama del paciente. Asimismo, el weaning o destete del ventilador mecánico debe llevarse a cabo de manera objetiva y bajo evaluaciones específicas para lograr un desenlace optimo.

Introduction. Myasthenic crisis is the most serious complication suffered by patients with Myasthenia Gravis. This disease is clinically characterized by generalized muscle weakness, which particularly improves with rest and worsens with exercise due to depletion of nerve conduction at the post-synaptic level. The cornerstone of managing myasthenic crisis is treating the triggering cause, as well as using fast-acting drugs and interventions described in the literature to deal with this scenario, such as plasmapheresis, immunoglobulins, or biological therapy. In addition, it is imperative to ensure adecuate management from the ventilatory perspective, preserving lung function and safeguarding the diaphragm with the tools currently available at the patient's bedside. Likewise, weaning from the mechanical ventilator must be conducted objectively and guided by specific evaluations to achieve an optimal outcome.

Myasthenia gravis in the complex scenario of LRBA-related immune dysregulation / Miastenia gravis no cenário clínico complexo das imunodesregulações relacionadas ao gene LRBA

Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.

Effects of hospital-family multidisciplinary 5E rehabilitation model on patients with myasthenia gravis / 中国实用护理杂志

Objective:To explore the effects of hospital-family multidisciplinary 5E rehabilitation model on clinical status, athletic ability, respiratory muscle strength, quality of life and psychological states of patients with myasthenia gravis (MG).Methods:This was a quasi-experimental study. According to the convenient sampling method, patients with type 2 MG treated in the First Affiliated Hospital of Harbin Medical University from January 2020 to September 2021 were divided into intervention group and control group. The control group was treated with routine nursing methods, and the intervention group was treated with hospital-family multidisciplinary 5E rehabilitation model for 12 weeks. The effects of intervention were compared by using Myasthenia Gravis Composite (MGC), 6-minute walking test (6MWT), maximum inspiratory pressure (MIP), Fatigue Scale-14 (FS-14), Myasthenia Gravis Quality of Life-15(MGQOL-15), Herth Hope Level Scale(HHI) and Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6C).Results:Repeated measurement analysis of variance showed that there were significant differences between 6MWT score and MGQOL-15 score twelve weeks after intervention, the intervention group scores were (477.95 ± 29.23), (6.25 ± 3.40) points, the control group scores were(435.85 ± 19.82), (9.95 ± 3.22) points, the differences were statistically significant ( t= 4.51, -3.58, both P<0.05). Besides, the differences of MIP, FS-14 score, SES6C score and HHI score were also statistically significant, the intervention group scores were (102.09 ± 19.56), (2.56 ± 1.31), (34.78 ± 8.68), (33.43 ± 6.39) points, the control group scores were (90.85 ± 12.25), (4.65 ± 2.50), (24.15 ± 6.62), (25.90 ± 8.30)points, the differences were statistically significant ( t values were -4.46-3.35, all P<0.05). Repeated measurement analysis of variance showed that there were significant differences in the time effect and interaction effect of MGQOL-15 score between the two groups ( F=28.28, 22.01, both P<0.05), there were also significant differences in the group effect, time effect, and interaction effect of 6MWT between the two groups ( F=13.94, 8.24, 12.85, all P<0.05). Conclusions:The rehabilitation of patients with MG could be promoted by the hospital-family multidisciplinary 5E rehabilitation model. Detailed research should be further strengthened to lay a foundation for the development of rehabilitation guidelines for patients with MG.

Update in immunomodulatory drug therapy for myasthenia gravis / 中华实用儿科临床杂志

Myasthenia gravis (MG) is an acquired autoimmune neuromuscular junction disease mediated primarily by anti-acetylcholine receptor antibody.Muscle-specific receptor tyrosine kinase antibody, low density lipoprotein receptor-associated protein 4 antibody and ranine receptor can also reduce the stability of acetylcholine receptors in the postsynaptic membrane and cause disease.The treatment of myasthenia gravis mainly includes symptomatic therapy, immunosuppressive therapy, immunoregulation and thymotomy.Immunosuppressive therapy is the main treatment of MG, but the long-term use of glucocorticoid (a hormone steroid) or a nonsteroidal immunosuppressant can bring about unwanted side effects and adverse events.To solve this problem, research progress of immunosuppressive drugs for treating MG was summarized in this paper.This article aims at finding the right treatment plan and explore the application value of new biological agents in MG treatment.

Cogan's sign in a patient with suspected post-COVID-19 vaccine-associated myasthenia gravis

ABSTRACT The Cogan's sign is indicative of myasthenia gravis. This is the first report of neurological signs in a patient with post-COVID-19 vaccine-associated myasthenia gravis in Brazil. In this case, a previously healthy 68-year-old woman presented with proximal limb weakness, left ptosis, and diplopia 1 month after receiving her fourth dose of the COVID-19 vaccine. Neurological examination revealed the presence of Cogan's sign, and she recovered rapidly after treatment. To our knowledge, this is the first reported case of myasthenia gravis associated with the COVID-19 vaccine in Brazil.

Recent Advances in Post-operatively New Onset Myasthenia Gravis in Thymoma Patients / 肿瘤防治研究

Patients with thymoma without preoperative myasthenia gravis may develop symptoms of myasthenia gravis after tumor resection. A comprehensive understanding toward this rare clinical phenomenon is lacking. Recent studies indicate that post-operatively new onset myasthenia gravis (ponoMG) is the result of multiple mechanisms and their interactions, which may be related to the thymoma-mediated production, release and long-term presence of abnormal T cells and autoimmune antibodies in the periphery, as well as the presence of ectopic thymus and late recurrence of thymoma. Preoperative antibody titer is the main predictor. The treatment strategy is based on anticholinesterase drugs and hormonal therapy. In this study, we review the incidence, pathogenesis, predictors, and prevention and treatment strategies of ponoMG.

Thymoma complicated with polymyositis and myasthenia gravis: A case report / 中国胸心血管外科临床杂志

@#Thymoma complicated with polymyositis and myasthenia gravis is a rare case, which can be clearly diagnosed and given symptomatic treatment according to its own diagnostic criteria, imaging and laboratory examinations. This paper reports the clinical data of a thymoma patient with polymyositis and myasthenia gravis admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University, and discusses the possible pathogenesis and treatment methods.

Expression and function of α7 nicotinic acetylcholine receptor in thymocytes of myasthenia gravis patients / 中国胸心血管外科临床杂志

@#Objective    To investigate the expression of α7 nicotinic acetylcholine receptor (α7 nAChR) in thymocytes of patients with myasthenia gravis (MG) and its effect on cytokine secretion and T cell proliferation. Methods    Patients with MG who underwent expanded thoracoscopic thymectomy in the Comprehensive Diagnosis and Treatment Center of the Henan Provincial People’s Hospital from June 2021 to June 2022 were selected and allocated to a MG group. Patients who underwent partial thymectomy to expose the surgical field during the cardiac disease surgery from June 2021 to September 2022 in the Department of Adult Cardiac Surgery of Fuwai Huazhong Cardiovascular Hospital were selected as the control group. Thymic single cell suspensions were prepared from MG and control groups, and the expression of α7 nAChR in thymocytes of the two groups was detected by real-time polymerase chain reaction and Western blotting. Then CD3/CD28 monoclonal antibody coupled with magnetic beads was used to induce T cell activation, and the levels of cytokines interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, IL-17, and IL-21 in thymocytes of the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The activated T cells of the MG group were divided into a blank control group, an α7 nAChR antagonist group, and an α7 nAChR agonist group according to different treatment methods. After 72 hours of culture, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, and IL-21 expression levels in the culture supernatant were measured by ELISA. Afterwards, CD4-PE and CD8-APC antibodies were added, and the proliferation of T cell subsets was detected by flow cytometry. Results    A total of 10 MG patients were collected, including 3 males and 7 females with an average age of 19.25±6.28 years; and 15 control patients were collected, including 6 males and 9 females with an average age of 26.18±6.77 years. Compared with the control group, the mRNA and protein levels of α7 nAChR in the thymocytes of MG group were decreased, and the expression levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-21 in the supernatant were increased (P<0.05), but there was no statistical difference in the expression of IL-10 and IL-17 (P>0.05). The cell-culture experiment showed that compared with the blank control group, the levels of IFN-γ, TNF-α, IL-6 and IL-21 secreted by T cells in the α7 nAChR antagonist group were increased (P<0.05), while they were decreased in the α7 nAChR agonist group (P<0.05). There was no statistical difference in the secretion levels of IL-4, IL-10 or IL-17 among the three groups (P>0.05). CD4+ T and CD8+ T cells in the α7 nAChR agonist group were significantly less than those in the blank control group and α7 nAChR antagonist group (P<0.001), while they were significantly more in the α7 nAChR antagonist group than those in the blank control group (P<0.001). Conclusion    The expression of α7 nAChR in thymocytes of MG patients is decreased, and α7 nAChR may be involved in the inflammatory response in thymocytes and thus in thymic function.

Application of new surgical clinical classification and staging of myasthenia gravis in the perioperative period / 中国胸心血管外科临床杂志

@#Objective     To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods     The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results     Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion     The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.

Long-term efficacy and influencing factors of extended thymectomy for myasthenia gravis with thymic atrophy / 中国胸心血管外科临床杂志

@#Objective    To analyze the surgical efficacy and influencing factors of myasthenia gravis (MG) patients with thymic atrophy after thymectomy. Methods    The clinical data of MG patients with thymic atrophy undergoing thymectomy between October 2014 and May 2018 in Daping Hospital of Army Medical University and Shijiazhuang People Hospital were retrospectively analyzed. Results    A total of 71 patients were collected, including 40 males and 31 females with a mean age of 45.17±12.42 years. All patients received the surgery successfully. After the surgery, 20 (28.17%) patients were stable remission, 12 (16.90%) patients were minimal manifestation status,19 (26.76%) patients were improved, 5 (7.04%) patients showed no change, 3 (4.23%) patients were worsened, 10 (14.08%) patients were exacerbated and 2 (2.82%) patients were dead. Multivariate logistic regression analysis showed that the preoperative illness duration (OR=4.61, 95%CI 1.13-18.85, P=0.03), and postoperative pyridostigmine combined with immunosuppressive (OR=0.12, 95%CI 0.03-0.45, P=0.00) were independent risk factors for long-term efficacy of thymectomy for MG patients with thymic atrophy. Conclusion    Early surgery after diagnosis of MG and postoperative pyridostigmine combined with immunosuppressive treatment is beneficial to the prognosis of MG patients with thymic atrophy.

Subxiphoid versus intercostal video-assisted thoracoscopic extended thymectomy for myasthenia gravis: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To compare the clinical efficacy of subxiphoid video-assisted thoracoscopic surgery (XVATS) and conventional intercostal VATS (CVATS) extended thymectomy for myasthenia gravis (MG). Methods    The clinical data of MG patients who underwent extended thymectomy in the Department of Thoracic Surgery of Xuzhou Central Hospital from October 2016 to October 2021 and finished the follow-up were retrospectively reviewed. They were divided into an XVATS group and a CVATS group according to the procedure. The perioperative variables and clinical efficacy of the two groups were compared. Results    A total of 84 patients were collected, including 43 males and 41 females, with a mean age of 52.3 years. There were 41 patients in the XVATS group and 43 patients in the CVATS group. There was no mortality, cardiopulmonary thrombosis, prolonged air leak, or mediastinal infection. Additionally, the CVATS group recorded 5 (11.6%) patients of conversion to open thoracotomy, 1 (2.3%) patient of postoperative MG crisis, 1 (2.3%) patient of bleeding in thorax, and 1 (2.3%) patient of chylothorax. The operation time (127.4±50.4 min vs. 122.9±38.6 min), intraoperative bleeding [46.9 (25.7, 79.2) mL vs. 45.7 (21.9, 92.1) mL], incidence of complications [0 vs. 7.0% (3/43)], chest tube duration (4.3±1.9 d vs. 4.8±2.8 d), follow-up time (19.1±8.5 months vs. 22.5±13.7 months), the proportion of residual mediastinal fat tissue [12.2% (5/41) vs. 4.7% (2/43)], and total MG remission rate [29.3% (12/41) vs. 51.2% (22/43)] were not statistically different between the two groups (P>0.05). However, the two groups showed  significantly different incidence of conversion to open thoracotomy [0 vs. 11.6% (5/43), P=0.024], postoperative hospital stay time (8.2±3.3 d vs. 11.4±5.8 d, P=0.003) and total drainage volume [396.7 (173.8, 542.5) mL vs. 218.8 (102.1, 430.0) mL, P=0.038]. Conclusion    XVATS extended thymectomy is technically safe and feasible; however, more evidence is warranted before the recommendation of this approach for the treatment of MG.

Subxiphoid and subcostal arch thoracoscopic versus median sternotomy enlarged thymectomy for the treatment of myasthenia gravis complicated with thymoma: A propensity score matching study / 中国胸心血管外科临床杂志

@#Objective    To compare clinical effects of enlarged thymectomy for the treatment of myasthenia gravis (MG) complicated with thymoma via subxiphoid and subcostal arch thoracoscopic resection versus median sternotomy resection. Methods    We retrospectively analyzed the clinical data of patients with MG complicated with thymoma admitted in Tangdu Hospital of the Air Force Military Medical University between December 2011 and December 2021. Patients who underwent subxiphoid and subcostal arch thoracoscopic enlarged thymectomy were allocated to a SR group, and patients who underwent median sternotomy enlarged thymectomy were allocated to a MR group. Perioperative outcomes were compared between the two groups. Results    A total of 456 patients were collected. There were 51 patients in the MR group, including 30 males and 21 females aged 23-66 (49.5±11.8) years. There were 405 patients in the SR group, among whom 51 patients were matched to the MR group by propensity score matching, including 28 males and 23 females aged 26-70 (47.2±12.2) years. The operations were accomplished successfully in all patients, and no conversion to thoracotomy occurred in the SR group. The SR group had advantages in the operation time, intraoperative blood loss,  chest drainage duration, hospital stay time, patients’ satisfaction level, pain score and complications (all P<0.05). No statistical difference was found in the number of intraoperative lymph node dissection stations, number of intraoperative lymph nodes dissected or remission of MG between the two groups (P>0.05). Conclusion    Subxiphoid and subcostal arch thoracoscopic enlarged thymectomy and lymphadenectomy is a safe, effective and feasible minimally invasive procedure for the treatment of MG complicated with thymoma.

The 100 most cited studies on surgical treatment of myasthenia gravis: A bibliometric analysis / 中国胸心血管外科临床杂志

@#Objective    To analyze the research hotspots and progress of surgical treatment of myasthenia gravis. Methods    The top 100 most cited articles on surgical treatment of myasthenia gravis were identified by searching the Web of Science database, and a bibliometric analysis was conducted. Results    The publication year of the top 100 most cited articles ranged from 1939 to 2021, and the number of citations ranged from 55 to 850 per article. Most of the included articles were original research articles (75/100), which were mainly retrospective studies (64/75). The United States was the country with the most published articles and most citations, and Annals of Thoracic Surgery was the most sourced journal (n=20). Through VOSviewer analysis, high-density keywords were thymectomy, maximal thymectomy, extended thymectomy, transcervical thymectomy, thymoma, and autoantibodies. Conclusion    The scope of surgical resection, surgical approach and pathogenesis are the current hotspots in the field of surgical treatment of myasthenia gravis. It is hoped that this paper can provide references for future researches in this field.

Stimulation single fiber electromyography in orbicularis oculi in ocular myasthenia gravis / 中华神经科杂志

Objective:To establish the reference values of stimulation single fiber electromyography (SFEMG) in orbicularis oculi, and to explore its sensitivity in repetitive nerve stimulation (RNS) negative ocular myasthenia gravis (OMG) patients, and the relationship between jitter and various clinical parameters.Methods:Thirty-two healthy volunteers were included to establish the reference value of normal controls from January 2019 to December 2019. From December 2019 to January 2023, 36 OMG patients with negative RNS were collected. Quantitative MG score (QMGS) was performed, neostigmine test and antibody titers as well as thymus CT results were recorded. One side of the orbicularis oculi muscle was tested with a disposable concentric needle electrode in stimulation SFEMG, and the mean consecutive difference (MCD) value was calculated, which was compared with the average MCD value and upper limit of individual values in normal controls to evaluate whether the jitter was abnormal. Spearman correlation analysis of abnormal mean MCD values with QMGS and antibody titer was conducted.Results:Among the 32 healthy volunteers, there were 13 males and 19 females, the age was (46.8 ±18.7) years, and the MCD was (19.0 ±4.4) μs. The upper limit of the reference value was 27.7 μs for average MCD, and 37.4 μs for 10% individual values. Among 36 OMG patients negative at RNS tests, 20 were male and 16 were female, with a age of (37.2 ±17.0) years. The MCD was (29.9 ±14.7) μs, and Jitter was abnormal in 29 patients (81%). Among them, 20 (20/25) patients were antibody positive, 6 (6/26) patients had thymic hyperplasia, and 7 (7/26) patients had thymoma. The QMGS was 3(2, 4). There were 7 patients (19%) with normal jitter, whose QMGS was 3(2, 4). Among the patients with normal Jitter, 5 (5/5) patients were antibody positive, 2 (2/6) patients had thymic hyperplasia. There was no statistically significant difference in clinical indicators between the two groups of patients with abnormal or normal jitter. There was no significant correlation in antibody titer or QMGS with abnormal mean MCD value. Conclusions:The upper limit of the mean MCD value in the normal controls is 27.7 μs. The upper limit of a single value is 37.4 μs. Its sensitivity for OMG patients with RNS negative is 81%, and the abnormal mean MCD value does not show a significant correlation with various clinical indicators. Abnormal jitter indicates dysfunction of neuromuscular junction transmission, which is an important neuroelectrophysiological indicator for MG patients and is suitable for RNS negative patients. Orbicularis oculi muscle stimulation SFEMG provides a reliable and sensitive electrophysiological means for functional evaluation of neuromuscular junction.