Survival analysis of myasthenia gravis patients at a Referral Center in Pará, Brazil (2005-2020) / Análise de sobrevivência de pacientes com miastenia ravis em um Centro de Referência no Pará, Brasil (2005-2020)

Objective: To evaluate the profile and survival of patients diagnosed with Myasthenia Gravis, by reviewing medical records of neurological consultations at a referral service in the interior of Pará (Brazil), between 2005 and 2020. Methods: a historical, observational and retrospective cohort study. 36 participants were included. Survival analysis methods were used to identify prognostic factors for disease remission at the observation time of 36 months. The correlation between the variables and the death outcome was performed using the chi-square test. Results: Most patients were women (66.6%) and had the generalized form of the disease (86.1%). The most prevalent symptoms were: ophthalmoparesis (97.2%), fatigability (75%) and dysphagia (72.2%). Among the complications, 19.4% had myasthenic crisis. The dosage of antiacetylcholine receptor (AChR) antibody was positive in 58.3% and 69.4% underwent electroneuromyography, and 72% of them had electrodecrement. Most of the patients responded to the staggered standard treatment and achieved remission (83.3%), while 16.6% died. Survival analysis showed through Kaplan-Meier curves and Log-rank test that the variables related to poor control were male gender (p=0.01), thymus disease (p=0.02) and use of cyclosporine (p=0.02). The factors that influenced the death outcome were male gender, cyclosporine and thymectomy. Conclusion: The study showed that the evolution of people with Myasthenia Gravis over 15 years and the poor prognostic factors were equivalent to the international literature.

Objetivo: Avaliar o perfil e a sobrevida de pacientes com diagnóstico de Miastenia Gravis, por meio da revisão de prontuários de consultas neurológicas em um serviço de referência no interior do Pará (Brasil), entre 2005 e 2020. Métodos: estudo de coorte histórico, observacional e retrospectivo. 36 participantes foram incluídos. Métodos de análise de sobrevivência foram utilizados para identificar fatores prognósticos para remissão da doença no período de observação de 36 meses. A correlação entre as variáveis e o desfecho de óbito foi realizada por meio do teste qui-quadrado. Resultados: A maioria dos pacientes eram mulheres (66,6%) e apresentavam a forma generalizada da doença (86,1%). Os sintomas mais prevalentes foram: oftalmoparesia (97,2%), fadiga (75%) e disfagia (72,2%). Dentre as complicações, 19,4% tiveram crise miastênica. A dosagem do anticorpo anti-receptor de acetilcolina (AChR) foi positiva em 58,3% e 69,4% realizaram eletroneuromiografia, sendo que 72% deles apresentaram eletrodecremento. A maioria dos pacientes respondeu ao tratamento padrão escalonado e obteve remissão (83,3%), enquanto 16,6% morreram. A análise de sobrevivência mostrou através de curvas de Kaplan-Meier e teste Log-rank que as variáveis relacionadas ao mau controle foram sexo masculino (p=0,01), doença do timo (p=0,02) e uso de ciclosporina (p=0,02). Os fatores que influenciaram no desfecho óbito foram sexo masculino, ciclosporina e timectomia. Conclusão: O estudo mostrou que a evolução das pessoas com Miastenia Gravis ao longo de 15 anos e os fatores de mau prognóstico foram equivalentes à literatura internacional.

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).

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.

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.

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.

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.

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.

Manifestaciones neurológicas en una paciente con lupus eritematoso sistémico / Neurological manifestations in a patient with systemic lupus erythematosus

El lupus eritematoso sistémico es una enfermedad inflamatoria sistémica cuyo proceso inflamatorio genera un importante número de manifestaciones clínicas articulares y extraarticulares. Entre las manifestaciones extraarticulares destaca la afectación neurológica, y el compromiso puede ser tanto a nivel del sistema nervioso central o periférico. El objetivo de la presente investigación es presentar el caso de una paciente de 56 años de edad, con diagnóstico de lupus eritematoso sistémico de 18 años de evolución quien presentó un cuadro crónico de cefalea, neuropatía periférica y miastenia gravis como manifestaciones neurológicas de la enfermedad. Con el tratamiento de ciclofosfamida y el aumento de la dosis de esteroide, en la actualidad la paciente se encuentra estable. El reporte de este caso hace hincapié en la importancia que revisten las manifestaciones neurológicas como parte de las manifestaciones extraarticulares de esta enfermedad, ya que este tipo de afección es determinante en el curso del lupus eritematoso sistémico y en la calidad de vida de los pacientes(AU)

Systemic lupus erythematosus is a systemic inflammatory disease whose inflammatory process generates a significant number of articular and extra-articular clinical manifestations. Within the extra-articular manifestations, neurological involvement stands out, among others, the commitment can be both at the level of the central or peripheral nervous system. The objective of the present investigation is to present the case of a 56-year-old patient, diagnosed with systemic lupus erythematosus of 18 years of evolution and who has presented chronic symptoms of headache, peripheral neuropathy and myasthenia gravis as neurological manifestations of the illness. The report of this case is considered important to publicize the importance of neurological manifestations as part of the extra-articular manifestations of this disease; this type of condition is decisive in the course of the disease and in the quality of life of patients(AU)

Myasthenia gravis in clinical practice / Miastenia gravis na prática clínica

ABSTRACT Background: Myasthenia gravis is largely a treatable disease, but it can result in significant morbidity and even mortality, which can usually be avoided, or at least mitigated, with timely diagnosis and appropriate treatment of the disease. Objective: this review aims to summarize the main practical aspects of the diagnostic approach, treatment and care of myasthenic patients. Methods: The authors performed a non-systematic critical review summarizing the main practical aspects of myasthenia gravis. Results: Most patients with myasthenia have autoantibodies targeted at acetylcholine receptors or, less commonly, muscle-specific kinase - MuSK. Electrophysiology plays an important role in the diagnosis of neuromuscular junction dysfunction. The central clinical manifestation of myasthenia gravis is fatigable muscle weakness, which can affect eye, bulbar, respiratory, and limb muscles. With rare exceptions, patients have a good response to symptomatic treatment, but corticosteroids and/or immunosuppressants are usually also necessary to obtain good control of the manifestations of the disease. Conclusion: Knowledge of the peculiar aspects of their clinical and electrophysiological presentations is important for the diagnosis. Likewise, specific treatment and response time to each drug are crucial for proper care.

RESUMO Antecedentes: A miastenia gravis é, em grande parte, uma doença tratável, mas pode resultar em significativa morbidade e até mortalidade, que geralmente pode ser evitada, ou pelo menos atenuada, com diagnóstico oportuno e tratamento adequado da doença. Objetivo: Esta revisão visa resumir os principais aspectos práticos da abordagem diagnóstica, do tratamento e dos cuidados de pacientes miastênicos. Métodos: Os autores realizaram uma revisão crítica não sistemática, resumindo os principais aspectos práticos da miastenia gravis. Resultados: A maioria dos pacientes com miastenia apresenta autoanticorpos direcionados aos receptores de acetilcolina ou, menos comumente, quinase músculo-específica - MuSK. A eletrofisiologia desempenha um papel importante no diagnóstico da disfunção da junção neuromuscular. A manifestação clínica central da miastenia gravis é a fraqueza muscular fatigável, que pode afetar os músculos oculares, bulbares, respiratórios e dos membros. Com raras exceções, os pacientes respondem bem ao tratamento sintomático, mas geralmente também são necessários corticosteroides e/ou imunossupressores para se obter um bom controle das manifestações da doença. Conclusão: O conhecimento dos aspectos peculiares de suas apresentações clínicas e eletrofisiológicas é importante para o diagnóstico. Da mesma forma, o tratamento específico e o tempo de resposta a cada medicamento são cruciais para o cuidado adequado.

Congenital myasthenic syndrome in a cohort of patients with 'double' seronegative myasthenia gravis / Síndrome miastênica congênita em uma série de pacientes com miastenia gravis duplo soronegativa

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of 'double' SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in 'double' SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with 'double' SNMG in whom differential diagnosis is recommended.

RESUMO Antecedentes: As síndromes miastênicas congênitas (SMC) podem ter sobreposição fenotípica com a miastenia gravis soronegativa (MG-SN). Objetivo: Estabelecer a prevalência mínima de SMC diagnosticada inicialmente como MG duplo soronegativa em uma série de casos brasileiros. Métodos: A análise genética das mutações mais comuns nos genes CHRNE, RAPSN e DOK7 foi usada como o principal exame de triagem. Resultados: Vinte e dois pacientes com diagnóstico prévio de MG-SN foram geneticamente analisados, sendo que uma paciente foi confirmada com SMC devido a presença de variante em heterozigose composta no gene CHRNE (c.130insG/p.Cys210Phe). Conclusões: O presente estudo confirma que SMC devido mutação no gene CHNRE pode ser inicialmente diagnosticada como MG-SN. O estudo estimou como 4,5% a prevalência de diagnóstico de SMC entre nossos pacientes préviamente diagnosticados como MG-SN. Com base nesse estudo, a análise genética pode ser recomendada para investigação do diagnóstico diferencial em pacientes com MG-SN.

Miastenia gravis como síndrome paraneoplásico en un tumor de ovario. Reporte de caso y revisión de la bibliografía / Myasthenia gravis as a paraneoplastic syndrome in a ovarian tumor. Case report and review of the literature

Resumen INTRODUCCIÓN: Los síndromes paraneoplásicos son manifestaciones a distancia de las neoplasias, que se originan por mecanismos secundarios pero no por invasión tumoral. Son poco frecuentes, anteceden a la manifestación propia del tumor y desaparecen con su curación. Si bien la miastenia gravis tradicionalmente se ha relacionado con timomas, aquí se busca reportar un caso de miastenia gravis como síndrome paraneoplásico de un tumor de ovario y hacer una revisión de la bibliografía disponible referente a su diagnóstico. CASO CLÍNICO: Paciente de 46 años, con múltiples episodios de debilidad generalizada e insuficiencia ventilatoria que requirió ventilación mecánica y estancia en cuidados intensivos. Se estableció el diagnóstico clínico de miastenia gravis. A pesar del adecuado tratamiento y de la timectomía, las crisis persistieron. Al poco tiempo se le diagnosticó un adenocarcinoma seroso de ovario que se trató con cirugía y quimioterapia. Con esto desaparecieron los síntomas neurológicos, con una remisión total después de cuatro años de seguimiento, sin tratamiento médico. Para la revisión bibliográfica se emprendió una búsqueda en Medline, Cochrane, LILACS, Google Scholar y literatura gris con los términos "myasthenia gravis AND ovarian cancer". Se encontraron 18 artículos de los que se incluyeron solo dos publicaciones para la revisión completa. CONCLUSIONES: Los síndromes neurológicos, entre estos la miastenia gravis, asociados con tumores de ovario a modo de síndromes paraneoplásicos son poco frecuentes y plantean la necesidad de incluir el estudio ginecológico en pacientes con miastenia gravis de manifestación atípica.

Abstract BACKGROUND: Paraneoplastic syndromes are distant manifestations of neoplasms originated by secondary mechanisms but not by tumor invasion. They are infrequent, precede the manifestation of the tumor itself and disappear when the tumor is cured. Although myasthenia gravis has traditionally been related to thymomas, here we report a case of myasthenia gravis as a paraneoplastic syndrome of an ovarian tumor and review the available literature on its diagnosis. CLINICAL CASE: 46-year-old patient with multiple episodes of generalized weakness and ventilatory failure requiring mechanical ventilation and intensive care stay. The clinical diagnosis of myasthenia gravis was established. Despite adequate treatment and thymectomy, the crises persisted. Soon after, she was diagnosed with serous adenocarcinoma of the ovary, which was treated with surgery and chemotherapy. With this, the neurological symptoms disappeared, with total remission after four years of follow-up, without medical treatment. For the literature review a search was undertaken in Medline, Cochrane, LILACS, Google Scholar and grey literature with the terms "myasthenia gravis AND ovarian cancer". Eighteen articles were found of which only two publications were included for the full review. CONCLUSIONS: Neurological syndromes, among this myasthenia gravis, associated with ovarian tumors as paraneoplastic syndromes are rare and raise the need to include gynecological study in patients with myasthenia gravis of atypical manifestation.

Tratamiento de la eclampsia y miastenia gravis: reporte de un caso y revisión de la literatura / Eclampsia treatment and myasthenia gravis: case report and review of literature

OBJETIVO: Reportar el caso de una gestante con miastenia grave (MG) más preeclampsia-eclampsia y crisis miasténica en el puerperio mediato, y realizar una revisión de la literatura sobre el manejo farmacológico. MÉTODO: Se presenta el caso de una mujer de 26 años con MG, primigesta de 36 semanas de gestación, quien cursó con eclampsia y recibió fenitoína por 24 horas. Tuvo parto espontáneo sin complicaciones y crisis miasténica al día 11 del puerperio asociada a infección de vías urinarias y sepsis. Se realiza revisión de la literatura en PubMed, Cochrane, Embase, LILACS y Scopus, empleando los términos "Hypertension, Pregnancy-Induced", "Preeclampsia" y "Eclampsia", combinados con "Myasthenia Gravis", durante el periodo de publicación de 1960 a junio 2020, en inglés y español. RESULTADOS: Se encontraron 12 reportes de caso, dos con eclampsia y MG; el caso aquí reportado es el número 13. Ocho pacientes no recibieron medicamentos profilácticos de eclampsia y tres de ellas convulsionaron. En las que se usó sulfato de magnesio, todas cursaron con crisis miasténica. CONCLUSIONES: La evidencia actual en cuanto a la profilaxis y el tratamiento de la eclampsia y la MG corresponde a reportes de casos. El uso de sulfato de magnesio está contraindicado en pacientes con MG, por lo que se han utilizado fenitoína y levetiracetam.

OBJECTIVE: To report a case of pregnant women with myasthenia gravis (MG), plus preeclampsia-eclampsia and myasthenic crisis in the mediate puerperium; to conduct a literature review regarding its pharmacological management. METHOD: 26-year-old primigravida with 36 weeks of gestation and previous history of MG, who developed eclampsia and was treated with phenytoin for 24 hours, with later spontaneous delivery without any complications nor new seizures; and myasthenic crisis on day 11 of the puerperium associated with urinary tract infection and sepsis. A literature review was conducted in PubMed, Cochrane, Embase, LILACS and Scopus, using the controlled vocabulary "Hypertension, Pregnancy-Induced", "Preeclampsia" and "Eclampsia", combined with "Myasthenia Gravis", between 1960 and June 2020, in English and Spanish. RESULTS: 12 case reports were found, two of these with eclampsia and MG, the case reported here was number 13. In eight cases patients did not receive any prophylactic drugs for eclampsia and three of them had convulsions. In the cases where magnesium sulfate was used, all developed myasthenic crisis. CONCLUSIONS: The current evidence regarding prophylactic management and treatment corresponds to case reports. The use of magnesium sulfate is contraindicated in patients with MG, therefore phenytoin and levetiracetam have been used.

Timectomía transesternal extendida en pacientes con miastenia grave / Extended Transsternal Thymectomy in Patients with Myasthenia Gravis

Introducción: La miastenia grave adquirida es un trastorno de la transmisión neuromuscular, causado por la unión de autoanticuerpos con los componentes de la placa neuromuscular, más frecuentemente con el receptor de acetilcolina. Objetivo: Evaluar los resultados quirúrgicos inmediatos, obtenidos con la timectomía extendida en pacientes con miastenia grave timomatosa y no timomatosa. Métodos: Se realizó un estudio observacional, prospectivo y descriptivo para evaluar los resultados postoperatorios inmediatos de 21 pacientes intervenidos por miastenia grave entre junio de 2015 y mayo de 2020. Las variables estudiadas fueron edad, sexo, lesiones tímicas asociadas y resultados inmediatos: complicaciones y mortalidad ocurridas hasta 30 días de la intervención. Los datos fueron obtenidos de una base en Microsoft Access. Resultados: Dieciséis (76,2 por ciento) pertenecían al sexo femenino y 5 (23, 8 por ciento) al masculino. El mayor número correspondió a la MG con timoma, seguido por la MG e hiperplasia tímica (8) y uno con MG y restos tímicos. Se complicaron tres pacientes (14,3 por ciento). Uno presentó dos complicaciones: enfisema subcutáneo y septicemia, el siguiente, fiebre sin causa aparente y, el último, infección superficial de la herida. No hubo fallecidos. Conclusiones: La timectomía transesternal extendida permite extirpar el timo y la mayor parte de los tejidos adiposo y tímico aberrante, en el cuello y el mediastino. En pacientes tratados por equipos multidisciplinarios, con experiencia en esta cirugía, las complicaciones y la mortalidad tempranas usualmente son favorables(AU)

Introduction: Acquired myasthenia gravis (MG) is a neuromuscular transmission disorder caused by the union of autoantibodies and the components of the neuromuscular plaque, most frequently with the acetylcholine receptor. Objective: To assess the immediate surgical outcomes of extended thymectomy in patients with thymomatous and nonthymomatous myasthenia gravis. Methods: An observational, prospective and descriptive study was carried out to assess the immediate postoperative outcomes of 21 patients operated on for myasthenia gravis between June 2015 and May 2020. The variables studied were age, sex, associated thymic lesions, and immediate outcomes: complications and mortality that occurred up to thirty days after the intervention. The data were obtained from a Microsoft Access database. Results: Sixteen (76.2 percent) belonged to the female sex and five (23.8 percent) to the male sex. The highest number corresponded to MG with thymoma, followed by MG and thymic hyperplasia (8) and one with MG and thymic remains. Three patients (14.3 percent) were complicated. One had two complications: subcutaneous emphysema and septicemia; the next had unexplained fever; and the last one had superficial wound infection. There were no deaths. Conclusions: Extended transsternal thymectomy allows removal of the thymus and most of the adipose and aberrant thymic tissues in the neck and mediastinum. In patients treated by multidisciplinary teams, with experience in this surgery, outcomes regarding early complications and mortality are usually favorable(AU)

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Perfil de salud oral de pacientes diagnosticados con miastenia gravis / Oral health profile of patients diagnosed with miastenia gravis

Objetivo: Determinar el perfil de salud oral de los pacientes diagnosticados con miastenia gravis de la Asociación Miastenia Gravis Perú (Lima). Material y métodos: Se realizó un muestreo no aleatorio con la participación de 75 pacientes con diagnóstico de miastenia gravis, a los cuales se les evaluó la prevalencia y el promedio de caries según el índice CPOd, índice de higiene oral IHO, tipo de maloclusión dentaria y simetría facial. Resultados: Se encontró una prevalencia de caries dental del 100%, con un promedio de 17,26 piezas dentales con experiencia de caries, y el 42,7% de los pacientes presentó un nivel deficiente de higiene oral. Asimismo, se encontró un 38,7% y un 24,0% con maloclusión clase II y III, respectivamente, y el 74,7% presentó asimetría facial, siendo estas las características principales de su perfil de salud oral. Conclusiones: Los pacientes diagnosticados con miastenia gravis de la Asociación Miastenia Gravis Perú (Lima) presentan un alto promedio de caries dental y la mayoría muestra maloclusiones II o III, un nivel de higiene dental deficiente y asimetría facial. (AU)

Objective: To determine the oral health profile of patients from the Association Myasthenia Gravis Peru, Lima diagnosed with myasthenia gravis. Materials and Methods: A total of 75 non-randomized patients diagnosed with myasthenia gravis were included in the study. The prevalence and average number of caries were evaluated according to the decayed/missing/filled teeth (DMFT) index, the simplified oral hygiene index (OHI), type of malocclusion and dental and facial symmetry. Results: The prevalence of dental caries was 100% , with an average of 17.26, and 42.7% of the patients presenting poor oral hygiene. Likewise, 38.7% and 24% of the patients were found to have class II and III malocclusion, respectively, and 74.7% presented facial asymmetry as the main characteristics of their oral health profile. Conclusions: Patients from the Association Myasthenia Gravis Peru - Lima diagnosed with myasthenia gravis present a high average of dental caries, with most presenting grade II and III malocclusion, facial asymmetry and a poor level of dental hygiene. (AU)

[Perioperative challenges and neuromuscular blockade concerns in robotic thymectomy for myasthenia gravis]. / Desafios perioperatórios e pontos de atenção no bloqueio neuromuscular durante timectomia robótica para miastenia gravis.

Myasthenia Gravis (MG) is an autoimmune disease characterized by weakness and fatigability of skeletal muscles, with improvement following rest. It is a disease of great significance to the anesthesiologist because it affects the neuromuscular junction. Robotic thymectomy has come up in recent times due to the minimally invasive nature and its advantages. This presents a new set of challenges for the anesthesia team, and here we present the various anesthesia considerations and perioperative management in a series of 20 patients who underwent robotic thymectomy. As it is a recent upcoming procedure, there is a paucity of literature on this topic, and most of the available literature talks about One-Lung Ventilation (OLV) and thoracic epidurals. To our notice, this is the first literature without the use of OLV and thoracic epidural for the management of robotic thymectomy.

Una mirada actual a la miastenia gravis / A current look at myasthenia gravis

RESUMEN La miastenia gravis es una enfermedad crónica autoinmune, poco común, cuya prevalencia ha aumentado desde la década de los 80 debido a la mejoría en su diagnóstico y al aumento de la longevidad de la población. Este trabajo tiene como objetivo realizar una actualización acerca de los aspectos de mayor importancia sobre la entidad, conocimiento que todo personal de salud y estudiantes deben poseer. Para ello se consultó un total de 32 referencias bibliográficas resultado de búsquedas en bibliotecas virtuales: Scopus, Google Académico y Medline. Se concluyó que, a partir de la mejora en el conocimiento de la fisiopatología de la enfermedad, el diagnóstico y el tratamiento, se ha logrado reducir la mortalidad, mejorar la calidad de vida de los pacientes y su funcionalidad.

ABSTRACT Myasthenia gravis is a rare, autoimmune chronic disease whose prevalence has increased since the 1980s due to improved diagnosis and increased longevity of the population. The objective of this work is to update the most important aspects of the entity, a knowledge that all health personnel and students must have. For this, a total of 32 bibliographic references resulting from searches in virtual libraries were consulted: Scopus, Google Academic and Medline. It was concluded that, from the improvement in the knowledge of the pathophysiology of the disease, the diagnosis and the treatment, it has been possible to reduce mortality, improve the quality of life of patients and their functionality.

Perioperative challenges and neuromuscular blockade concerns in robotic thymectomy for myasthenia gravis / Desafios perioperatórios e pontos de atenção no bloqueio neuromuscular durante timectomia robótica para miastenia gravis

Abstract Myasthenia Gravis (MG) is an autoimmune disease characterized by weakness and fatigability of skeletal muscles, with improvement following rest. It is a disease of great significance to the anesthesiologist because it affects the neuromuscular junction. Robotic thymectomy has come up in recent times due to the minimally invasive nature and its advantages. This presents a new set of challenges for the anesthesia team, and here we present the various anesthesia considerations and perioperative management in a series of 20 patients who underwent robotic thymectomy. As it is a recent upcoming procedure, there is a paucity of literature on this topic, and most of the available literature talks about One-Lung Ventilation (OLV) and thoracic epidurals. To our notice, this is the first literature without the use of OLV and thoracic epidural for the management of robotic thymectomy.

Resumo Miastenia Gravis (MG) é uma doença autoimune que se caracteriza por fraqueza e fadiga da musculatura esquelética, com melhora após o repouso. É uma doença de grande interesse para o anestesiologista, pois compromete a junção neuromuscular. Recentemente, a timectomia robótica tem sido empregada por apresentar as vantagens da abordagem minimamente invasiva. O procedimento introduz uma série de novos desafios para a equipe de anestesia. Relatamos aqui as várias considerações anestésicas e o cuidado perioperatório em uma série de 20 pacientes submetidos a timectomia robótica. Sendo um procedimento recente, há limitada literatura discutindo esse tópico e, além disso, a maior parte da literatura disponível concentra a atenção na Ventilação Monopulmonar (VMP) e na peridural torácica. A nosso ver, este é a primeiro relato na literatura sem o emprego de VMP e peridural torácica para o manejo da timectomia robótica.