Myasthenia gravis and COVID-19: a systematic review of case reports and case series

Myasthenia gravis (MG) is an autoimmune disease involving neuromuscular transmission and possible respiratory failure when concomitant with COVID-19. The aim of this study was to analyze the need for ventilatory support (VS), length of hospital stay (LOS) and mortality in patients diagnosed with MG and COVID-19. In this systematic review, PubMed, SciELO, LILACS, MEDLINE and IBECS databases were searched for primary studies published from January 2010 to March 2021, with no language restrictions. Fourteen eligible studies were identified. The main factor associated with the need for VS was the use of antibiotics other than azithromycin (AZM) for the treatment of COVID-19 (RR 1.60; 95% CI 1.20­2.91; p = 0.009). Patients who used hydroxychloroquine (HCQ) and AZM had almost twice the risk of needing invasive ventilatory support (IVS) (RR 1.94; 95% CI 1.07-3.52; p = 0.16). There were nonsignificant trends towards less need for IVS in patients who used intravenous immunoglobulin (IVIg) and corticosteroid therapy (RR 0.54; 95% CI 0.09­3.26; p = 0.60). There was a trend towards shorter LOS in patients who received therapy with IVIg and corticosteroid therapy [8 (5 - 8) vs 19 (12.2­23.7); p = 0.007]. 10.3% (n = 4/39) died and 100% did not use IVIg or IVIg and prednisone. There was a non-significant trend towards higher mortality in patients who used AZM (RR 2.55; 95% CI 0.26­30.02; p = 0.60). IVIg and corticotherapy presented themselves as a favorable alternative in relation to the outcomes. KEY WORDS: Coronavirus infections; length of stay; Myasthenia gravis; Respiratory insufficiency.

Miastenia gravis: resultados inmediatos y alejados de la timectomía transesternal extendida / Results of extended transsternal thymectomy for Myasthenia gravis: experience with 58 patients

Background: Thymectomy improves clinical outcomes and decreases the need for medical treatment in patients with myasthenia gravis (MG). Aim: To describe the immediate and long-term results of extended transsternal thymectomy (ETT) in patients with MG. Material and Methods: A review of databases, surgical protocols, clinical records and interviews of patients subjected to extended transsternal thymectomy for MG between 1990 and 2016. Perioperative clinical characteristics, anticholinesterase treatment, immediate and remote surgical results were analyzed and patients were followed from one to 10years. Results: We studied 58 patients aged 35 ± 14years (72%) women. In the preoperative period, according to Osserman classification, nine patients (15,5%) were in grade I, eight (13,8%) in grade IIA 8 and 40 (69%) in grade IIB. The pathological study of the surgical piece showed thymic hyperplasia in 39 cases (67,2%). Four patients had postoperative complications but none died. In the Follow-up at 1, 3, 5, 8 and 10years the Masaoka palliation rate was 71.7, 77.5, 67.7, 70.0 and 70,6% respectively. The figures for remission rate were 13.0, 15.0,19.4, 35.0 and 35,3% respectively. The figures for Zielinski positive results were 79.6, 87.5, 87.1, 90.0 and 82,4% respectively. The DeFilippi score improved by 80.4, 87.5, 87.1, 90.0 and 82.4% respectively. The Myasthenia Gravis Foundation of America Post-Intervention State improved by 67.4, 77.5, 77.5, 75.0 and 70,6% respectively. Mean Myasthenia Gravis Activities of daily living (MGADL) and Myasthenia Gravis Quality of life scale 15 (MGQOL 15) were 1.65 and 6.31 respectively. Conclusions: In selected patients with MG, extended transsternal thymectomy in MG has good immediate and long-term results.

Brazilian-Portuguese translation, cross-cultural adaptation and validation of the Myasthenia Gravis Composite scale. A multicentric study / Tradução, adaptação cultural e validação da escala composta de Miastenia Grave para a lingua portuguesa do Brasil. Estudo multicêntrico

ABSTRACT Objective To perform the translation, cultural adaptation and validation of the Myasthenia Gravis Composite (MGC) scale in Brazil. Methods The study was conducted at three neuromuscular disease research centers in accordance with the international ethical standards, following a multi-modal approach and was conducted in three steps consisting of translation, cultural adaptation, and validation according to international guidelines. The final version of the MGC was applied in a sample of 27 MG patients and the total score was compared to a Portuguese version of the MG-QOL-15. Results The internal consistency verified by Cohen’s Kappa test was excellent (0.766). The correlation between the MGC and MG-QOL-15 was strong (R = 0.777; p = 0.000). No significant differences were found between the responses of patients in the first and second applications of the MGC. Conclusion The MGC scale, validated into Brazilian Portuguese, has proven to be a reliable instrument that is easy to use, and is highly reproducible.

RESUMO Objetivo Realizar a tradução e a adaptação transcultural da escala composta de Miastenia Grave (ECMG) Myasthenia Gravis Composite (MGC) no Brasil. Métodos O estudo foi realizado em três centros de investigação em doenças neuromusculares, de acordo com as normas éticas internacionais, consistindo em tradução, adaptação cultural e validação de acordo com as diretrizes internacionais. A versão final do MGC ECMG foi aplicada em vinte e sete pacientes com MG e a pontuação total foi comparada ao questionário MG-QOL 15. Resultados A consistência interna verificada pelo teste Kappa de Cohen foi excelente (0,766) e a correlação entre o a ECMG MGC e MG-QOL 15 foi positiva (R = 0,777; p = 0,000). Não foram encontradas diferenças entre as respostas dos pacientes na primeira e segunda aplicação da MGC. Conclusão A ECMG escala MGC validada para o Português do Brasil provou ser um instrumento confiável, de fácil aplicação e altamente reprodutível.

Determinants of quality of life in Brazilian patients with myasthenia gravis

OBJECTIVES: The aims of the current study were 1) to evaluate the reliability and validity of the Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale and 2) to investigate the quality of life of Brazilian patients with myasthenia gravis and its determinants. METHODS: This cross-sectional study included 69 patients with myasthenia gravis who underwent neurological evaluation and completed questionnaires regarding quality of life (the 36-item Short Form of the Medical Outcomes Study and the 15-item Myasthenia Gravis Quality of Life Scale), anxiety and depressive symptoms. RESULTS: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale showed high internal consistency and good concurrent validity with the 36-item Short Form of the Medical Outcomes Study and its subscales. Determinants of quality of life in Brazilian patients with myasthenia gravis included the current status of myasthenia gravis as assessed by the Myasthenia Gravis Composite, the current prednisone dose and the levels of anxiety and depression. CONCLUSION: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale is a valid instrument. Symptom severity, prednisone dosage and anxiety and depression levels impact the quality of life of patients with myasthenia gravis.

Clinical profile of patients with myasthenia gravis followed at the University Hospital, Federal University of Minas Gerais / Perfil clínico de pacientes com miastenia gravis em acompanhamento no Hospital das Clínicas, da Universidade Federal de Minas Gerais

Summary Objective: to determine the clinical profile of patients with myasthenia gravis (MG); followed at the Neuromuscular Diseases Clinic of the University Hospital, Federal University of Minas Gerais, Brazil, and to compare it with other Brazilian case series. Methods: sociodemographic and clinical data were collected from patients, and a systematic literature review performed, focusing on national studies on the clinical profile of MG patients. Results: sixty nine patients were enrolled in the study. Fifty five (91%) subjects were female and the mean age (SD) was 37.6 (±11.4) years. The mean disease duration was 14.1 years. Regarding treatment, prednisone was the most used strategy (64%), followed by the use of azathioprine (43%). There was no difference between thymectomized (42) and non-thymectomized (27) patients regarding disease severity and medication use. Conclusion: clinical and socio-demographic features of this MG sample from a University-based clinic resemble those reported in other Brazilian series and in the international literature. .

Objetivo: determinar o perfil clínico dos pacientes com miastenia gravis (MG) atendidos na Clínica de Doenças Neuromusculares do Serviço de Neurologia do Hospital das Clínicas da Universidade Federal de Minas Gerais, e comparar com outras séries de casos brasileiras. Métodos: foram coletados dados clínicos e sociodemográficos dos pacientes, e realizada revisão sistemática de literatura, focando em estudos nacionais sobre o perfil clínico de pacientes com MG. Resultados: sessenta e nove pacientes participaram do estudo, sendo 55 (91%) do sexo feminino, e a média de idade (desvio-padrão) de 37,6 (±11,4) anos. O tempo médio de doença foi de 14,1 anos. Em relação ao tratamento, o uso isolado de prednisona foi a estratégia mais adotada (64%), seguida do uso de azatioprina (43,3%). Não houve diferença entre os pacientes timectomizados (47) e não timectomizados (22) no que diz respeito à gravidade da doença e ao tratamento. Conclusão: as características clínicas e sociodemográficas da presente amostra de pacientes com MG de um serviço universitário assemelham-se às características de outras séries brasileiras e da literatura internacional. .

Myasthenia Gravis in South Trinidad / Miastenia Gravis en el sur de Trinidad

OBJECTIVE: There is no previous research on Myasthenia Gravis (MG) in Trinidad and Tobago. This study sought to determine the prevalence and to characterize MG in South Trinidad. METHODS: A cross-sectional study was performed over 30 months in South Trinidad to identify, interview and statistically analyse data on MG cases. RESULTS: Among 36 prevalent patients, female:male ratio was 1.6:1. Estimated MG point prevalence in South Trinidad on March 31, 2010 was 78 per million. Mean age ofprevalent patients was 50.5 years. Mean age of onset was 35 years. A higher prevalence was detected in Africans than East Indians (178 vs 68 per million; p = 0.003). Ocular and extremity muscle weakness were the most common initial symptoms. Autoimmune conditions (mainly thyroid disease) co-existed in 25.7%. Treatment involved pyridostigmine and/or immunosuppressants for all except two that went into remission with just steroids. Generalized MG occurred in 60%; 42.9% expressed social and/or professional handicap. One case with suggestive clinical features tested positive for muscle specific tyrosine kinase antibody. CONCLUSIONS: While many features of MG in South Trinidad were similar to international data, the unique, statistically significant higher prevalence in Africans than East Indians warrants further research, given the paucity of reports from Africa and India. Patients with MG suffered a diminished quality of life, necessitating improved health planning.

OBJETIVO: No existen investigaciones previas sobre la miastenia gravis (MG) en Trinidad y Tobago. Este estudio tuvo por objeto determinar la prevalencia y caracterización de la MG en el sur de Trinidad. MÉTODOS: Se realizó un estudio transversal por espacio de más de 30 meses en el sur de Trinidad, con el fin de identificar, entrevistar, y analizar estadísticamente los datos sobre los casos de MG. RESULTADOS: Entre los 36 pacientes prevalentes, la proporción hembra:varón fue 1.6:1. La prevalencia puntual estimada MG en el sur de Trinidad el 31 de marzo de 2010, fue 78 por millón. La edad promedio de los pacientes prevalentes fue 50,5 años. La edad promedio al inicio de la enfermedad fue de 35 años. Se detectó una mayor prevalencia en los africanos que en los indios orientales (178 vs 68 por millón; p = 0. 003). La debilidad del músculo ocular y las extremidades fueron los síntomas iniciales más comunes. Las condiciones autoinmunes (principalmente la enfermedad de tiroides) coexistían en 25,7%. El tratamiento implicó la administración depiridostigmina y/o inmunosupresores para todos, excepto dos que entraron en remisión con esteroides solamente. La MG generalizada se produjo en un 60%; el 42,9% expresaron sus handicaps sociales y profesionales. Un caso con características clínicas sugestivas resultó positivo en la prueba de anticuerpos de tirosina quinasa específica del músculo. CONCLUSIONES: Si bien muchas características de la MG en el sur de Trinidad fueron similares a las que aparecen en los datos internacionales, la prevalencia única, y según las estadísticas significativamente mayor en los africanos que en los indios orientales, indica la necesidad de que se realicen investigaciones ulteriores, dada la escasez de informes procedentes de Africa y la India. Los pacientes con MG sufrieron una disminución en la calidad de vida, lo cual requiere una planificación para mejorar la salud.

Myasthenia gravis and thymus: long-term follow-up screening of thymectomized and non-thymectomized patients / Miastenia gravis e timo: investigacao no seguimento de longo prazo em pacientes timectomizados e nao timectomizados

Thymoma screening is recommended at the onset of myasthenia gravis (MG) or when patients with MG present with clinical deterioration or a progressive increase of anti-acetylcholine receptor antibody. However, it is unknown if it is necessary to repeat the screening of thymoma at fixed intervals, even in the absence of MG deterioration, when the initial screening is negative. We analyzed the recurrence rate and incidence of new thymoma in a series of patients with well-controlled MG. The sample consisted of 53 patients, aged 17 to 72 years, and the follow-up varied between 75 and 472 months. The chest computerized tomography detected thymus abnormalities in eight patients at the initial screening and no abnormalities in all patients at a second screening after five years. The findings of this study support the classical opinion that screening for thymoma should be recommended only if there is clinical deterioration due to the disease.

A investigação de timoma é recomendada em pacientes com miastenia gravis (MG) no início da doença, em caso de haver piora clínica ou aumento dos níveis do anticorpo antirreceptor de acetilcolina. Contudo, não foi estabelecido se é necessário repetir a investigação de timoma em intervalos fixos, na ausência de piora clínica, quando a investigação inicial foi negativa. A taxa de recorrência e a incidência de novo timoma foram analisadas em uma série de pacientes com MG bem controlada. A amostra consiste de 53 pacientes, idade entre 17 e 72 anos, com tempo de acompanhamento variando entre 75 e 472 meses. A primeira tomografia computadorizada de tórax detectou anormalidades no timo em oito pacientes durante a investigação inicial da doença e nenhuma anormalidade no segundo exame, após cinco anos de doença, em todos os pacientes. Os achados desse estudo corroboram a clássica opinião de que a investigação de timoma deveria ser recomendada somente se houver piora clínica da doença.

Resultado de la timectomía en los tumores epiteliales / Result of thymectomy in epithelial tumors

Introducción: el timoma describe las neoplasias que no presentan atipia manifiesta del componente epitelial, cuando se exhibe claramente atipia citológica se le conoce como carcinoma tímico, y la cirugía es el tratamiento de elección. Nuestro objetivo es evaluar la eficacia de la timectomía en los enfermos con tumores epiteliales del timo (timoma, carcinoma tímico). Métodos: se estudiaron 26 enfermos entre enero 2007 a enero 2012 que, con este diagnostico, fueron operados en nuestro centro. Resultados: la miastenia gravis estuvo presente en 16 (61,5 por ciento) pacientes, de ellos en el posoperatorio se extubaron 11 (68,7 por ciento) después de 12 horas. La esternotomía total fue el abordaje principal 13 (50 por ciento), cuando la lesión era superior a los 7 centímetros fue más probable la ampliación a un hemitórax. Cuando se necesitó resección de pulmón, pericardio o ambos, el tiempo quirúrgico fue superior a los 120 minutos. Se complicaron 7 (29,6 por ciento), de ellos 5 (71,4 por ciento) de causa respiratoria. En 19 (73,9 por ciento) los tumores se clasificaron como estadio I de Masaoka y en 6 (23,1 por ciento) hubo carcinoma tímico.Tuvimos 1 fallecido (3,8 por ciento). Todos los miasténicos tuvieron remisión completa o farmacológica, en 2 hubo recidiva local y en ninguno fallecimiento durante el seguimiento. Conclusiones: la timectomía transesternal es el tratamiento de elección, y se necesita ampliar a un hemitórax cuando la lesión es más de 7 cm con resección de pericardio, pulmón o ambos. En este caso, se obtendrán resultados favorables en los miasténicos y en el control del tumor durante el seguimiento(AU)

Introduction: Thymomea describes the neoplasias that do not present evident atypia of the epithelial component; the clear cytological atypia indicated thymic carcinoma and surgery is the treatment of choice. The objective of this paper was to evaluate the efficacy of thymectomy aimed at patients with epithelial tumors in the thymus (thymoma, thymic carcinoma). Methods: Twenty six patients under study from January 2007 to January 2012, they were operated on after this diagnosis. Results: Myasthenia gravis was present in 16 patients (61.5 percent), 11 of them (68.7 percent) were removed their intubation after 12 hours of surgery. Total sternotomy was the main approach in 13 patients (50 percent); in case of an over 7cm long injure, the approach was extended to hemithorax. Resection of lung, pericardium or both required more than 120min surgical time. Seven patients (29.6 percent) suffered complications, 5 of them (71.4 percent) respiratory complications. Nineteen patients (73.9 percent) had Masaoka's staging I tumors whereas 6 (23.1 percent) had thymic carcinoma. One patient died (3.8 percent). All these patients with myasthenia gravis showed complete or pharmacological remission, 2 experienced local relapse and no patient died in the follow-up period. Conclusions: Transsternal thymectomy is the treatment of choice. It is required to extend it to hemithorax when there is an over 7 cm long injure, with resection of the pericardium, the lung or both. In this case, the favorable results will be achieved in myasthenic patients and in the tumor control during the follow-up phase(AU)

Disfonia como principal queixa num quadro de miastenia grave: diagnóstico e fonoterapia / Dysphonia as the primary complaint in a case of myasthenia gravis: diagnosis and speech therapy

Miastenia grave é uma doença autoimune que se manifesta por fraqueza e fadiga muscular progressivas. São frequentes os sintomas oculares e bulbares, dentre eles, a disfonia. Este artigo relata um caso de disfonia, cuja avaliação fonoaudiológica contribuiu com o diagnóstico de miastenia grave e seu tratamento. A paciente em questão procurou o atendimento fonoaudiológico com diagnóstico otorrinolaringológico de presbifonia. A avaliação perceptivo-auditiva e acústica da voz identificou alterações em respiração, fonte glótica e filtro/ressonância. Como alguns dados obtidos com a anamnese e observados nas provas vocais não se relacionavam diretamente com a presença de presbifonia, houve a necessidade de discussão do caso com o médico, quando ambos concluíram a necessidade de encaminhar a paciente para avaliação neurológica. O neurologista consultado levantou a hipótese diagnóstica de miastenia grave e solicitou exames. A paciente seguiu em acompanhamento fonoaudiológico e medicamentoso. Na reavaliação vocal, ocorrida cerca de dois meses após o início do tratamento, foi constatada melhora na qualidade vocal, com grande impacto na qualidade de vida. Este trabalho evidencia a importância da avaliação fonoaudiológica detalhada e da participação do fonoaudiólogo na equipe interdisciplinar.

Myasthenia gravis is an autoimmune disease, manifested by progressive muscular weakness and fatigue. There are frequent ocular and bulbar symptoms, among them, dysphonia. This article reports a case of dysphonia that contributed to the diagnosis of myasthenia gravis through a speech evaluation. The patient sought speech therapy with the ENT diagnosis of presbyphonia. The perceptual voice assessment and acoustic analysis pointed out respiration, glottal voice source and resonance affections. Considering that some of the data obtained from anamnesis and vocal assessments were not directly related to presbyphonia, the speech therapist discussed the case with the physician and they both concluded it was necessary to refer the patient to a neurological evaluation. The neurologist then raised the diagnostic hypotheses of myasthenia gravis and requested further examinations. The patient underwent speech therapy and drug treatment. A vocal reassessment, which occurred two months after the initial treatment, showed improvement in voice quality, with great impact on quality of life. This article shows the importance of detailed clinical speech evaluation and participation of a speech therapist in an interdisciplinary team.

Psychiatric disorders in myasthenia gravis / Transtornos psiquiátricos na miastenia gravis

OBJECTIVE: To investigate the prevalence of psychiatric disorders in patients with myasthenia gravis (MG). METHOD: Forty-one patients with MG answered to a structured psychiatric interview (MINI-Plus). RESULTS: Eleven (26.1 percent) patients were diagnosed with a depressive disorder and 19 (46.3 percent) were diagnosed with an anxiety disorder. Patients with dysthymia were older (p=0.029) and had longer disease duration (p=0.006). Patients with social phobia also had longer disease duration (p=0.039). CONCLUSION: Psychiatric disorders in MG are common, especially depressive and anxiety disorders.

OBJETIVO: Investigar a prevalência de transtornos psiquiátricos em pacientes com miastenia gravis (MG). MÉTODO: Quarenta e um pacientes com MG responderam a uma entrevista psiquiátrica estruturada (MINI-Plus). RESULTADOS: Onze (26,1 por cento) pacientes foram diagnosticados com transtorno depressivo e 19 (46,3 por cento) foram diagnosticados com um transtorno de ansiedade. Pacientes com distimia eram mais velhos (p=0,029) e tinham maior tempo de doença (p=0,006). Os pacientes com fobia social também tiveram maior tempo de doença (p=0,039). CONCLUSÃO: Transtornos psiquiátricos na MG são bastante comuns, principalmente transtornos depressivos e de ansiedade.

The cost-effectiveness of open or thoracoscopic thymectomy compared to medical treatment in managing Myasthenia gravis without thymomas / Costo efectividad de timectomía abierta y toracoscópica frente al tratamiento médico, en el manejo de Miastenia gravis sin timoma

Objective Assessing the cost-effectiveness of open or thoracoscopic thymectomy compared to medical therapy in managing myasthenia gravis not associated with thymoma. Methods A Markov model was designed for evaluating three strategies' cost-effectiveness. Transition probabilities were taken from the pertinent literature; the costs were estimated from official tariff manuals. Incremental cost-effectiveness ratios were estimated and probabilistic and deterministic sensitivity analysis was used for clinical variables, costs and the model's assumptions. Results Thoracoscopic thymectomy was the most effective and least costly strategy and dominated the other two alternatives. The cost per life year gained was Col § 1 129 531 without discount and Col § 805 179 with discount. Univariate sensitivity analysis showed that the main variables affecting the results were the effects' discount rate, the cost of a myasthenic crisis and the probability of complete remission. Thoracoscopy thymectomy was the most cost-effective strategy for different thresholds of willingness to pay in probabilistic analysis. Conclusions Thoracoscopic thymectomy is a cost-effective strategy in the treatment of MG without thymoma.

Objetivo Evaluar la costo efectividad de las timectomía abierta y toracoscópica frente a la terapia mé,dica en el manejo de miastenia gravis sin timoma. Mé,todo Se construyó un modelo de Markov para evaluar la costo efectividad de las 3 estrategias. Las probabilidades de transición se obtuvieron de la literatura. Los costos se estimaron a partir de las tarifas oficiales. Se calculó la costo-efectividad incremental. Se realizaron análisis de sensibilidad probabilísticos y determinísticos para las variables clínicas, los costos supuestos del modelo. Resultados La timectomía toracoscópica es la estrategia más efectiva y menos costosa, y domina a las otras dos alternativas. El costo por año de vida ganado fue de § 1 129 531 y § 805 179 pesos colombianos, con y sin descuento. El análisis de sensibilidad univariado mostró que las principales variables que afectan los resultados son la tasa de descuento, el costo de una crisis miasté,nica y la probabilidad de remisión completa. En el análisis de sensibilidad probabilístico, la timectomía toracoscópica es la estrategia costo-efectiva para los diferentes umbrales de disponibilidad a pagar. Conclusiones La timectomía toracoscópica es una estrategia costo-efectiva en el tratamiento de miastenia gravis sin timoma.