Transient Neonatal Myasthenia Gravis: A Case Report.

Transient neonatal myasthenia gravis (TNMG) is a neuromuscular disorder that occurs in infants born from mothers with myasthenia gravis (MG) due to transplacental transfer of antibodies against the acetylcholine receptor. TNMG is a rare form occurring in 10-15% of infants born from mothers with MG. We present a case of a newborn with TNMG with generalized hypotonia and respiratory distress. The newborn shows symptoms of hypotonia, weakened reflexes, poor crying, difficult sucking and potentiated tachydyspnea after 24 hours of birth and needs of assisted mechanical ventilation. Based on the mother's positive history of MG and the high titer of mother's (8.43nmol/l) and newborn's (9.088nmol/l) anti-AChR antibodies, TNMG was diagnosed. The baby was treated with assisted mechanical ventilation and neostig-mine until the anti-AChR antibody titer was negative. Adequate management of the newborn resulted in a positive outcome and evident withdrawal of the symptoms. Although TNMG is one of the rare neuromuscular disorders in newborns that can be treated, a multidisciplinary approach in the management of pregnant women with MG and newborns through timely diagnosis and early appropriate treatment, results in successful resolution of this condition.

The expectant management of a rare neonatal disease: transient neonatal myasthenia gravis.

BACKGROUND: Transient neonatal myasthenia gravis (TNMG) is an acquired disease which occurs in 10 to 20% of infants born to a mother with myasthenia gravis. Even though it is a self-limiting disorder, it may potentially be life-threatening if prompt diagnosis is not made, and expedient supportive respiratory management is not initiated when required. CASE: Here we describe three infants with TNMG. Two of them developed symptoms of TNMG within 24 hours of life, but one developed symptoms at 43 hours of life. One of the patients had an atypical form of TNMG with contracture and hypotonia. The other two infants survived a typical form of TNMG with hypotonia and poor sucking. All cases resolved spontaneously by one to two weeks of life with conservative management. CONCLUSIONS: Infants born to mothers with myasthenia gravis need to be monitored closely for symptoms of TNMG for the first 48 to 72 hours of life. However, the majority of infants with TNMG traverse a benign course and resolve spontaneously with expectant care.

Clinical and pathophysiologic relevance of autoantibodies in neonatal myasthenia gravis.

Between 10% and 20% of neonates born to mothers with myasthenia gravis (MG) develop neonatal MG due to the transfer of maternal autoantibodies across the placenta. Neonatal MG can occur in infants born not only from mothers with acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies but also from mothers without detectable muscle antibodies. The low incidence rate may be due to specific autoantibody characteristics that differ among individuals, but a genetic predisposition in some infants is possible. The majority of reported neonatal MG cases are anti-AChR antibody-positive (AChR-MG), and a high anti-fetal/anti-adult AChR titer ratio in the mother is predictive of its occurrence. However, patients with anti-MuSK antibody-positive MG (MuSK-MG) are more likely to experience exacerbations during pregnancy and have a higher probability of developing neonatal MG than AChR-MG patients. Moreover, maternal MuSK-MG may be associated with early-onset and more severe manifestations of neonatal MG. Although cholinesterase inhibitors have been effectively used for treating neonatal AChR-MG, neonatal MuSK-MG may be more difficult to treat with this type of medication. Maternal MuSK-MG usually greatly benefits from intravenous immunoglobulin (IVIG) and plasma exchange. In neonatal MG, IVIG is considered for severely affected infants with MuSK-MG, but the efficacy of IVIG remains unclear. Although exchange transfusion may be a management adjunct, its clinical benefits are controversial. As the therapy-induced reduction of autoantibodies may be advantageous for fetal outcomes, maternal MG should be effectively treated during pregnancy. However, caution of drug contraindication during pregnancy and lactation must be exercised to avoid unwanted effects for the fetus and neonate. In the future, MG caused by anti-lipoprotein receptor-related protein 4 or other antibodies might be also identified in pregnant women and neonates. Therefore, the determination of autoantibody specificity is essential for successful management.

Transient neonatal myasthenia gravis: refining risk estimate for infants born to women with myasthenia gravis.

OBJECTIVE: Transient neonatal myasthenia gravis (TNMG) can render a neonate vulnerable to catastrophic respiratory depression. Our aim was to describe the clinical manifestations of TNMG, and to determine when the myasthenic signs become apparent in TNMG. METHODS: We reviewed our own experience of infants who underwent routine inpatient monitoring for TNMG and combined our local data with observations from previous studies. RESULTS: Only three case series (n = 110) reported both the type and timing of onset of myasthenic signs. Adding local data (n = 37) yielded 147 infants born to women with MG. Fifteen infants (10%) developed signs of TNMG with onset being 1.5 ± 2.6 days (mean ± 3SD) after birth. Feeding difficulties and low tone were the commonest presenting signs, and only 1 of the 147 infants needed intubation for hypoventilation. CONCLUSIONS: TNMG signs were mostly not life-threatening. We suggest only 4 days of routine postnatal observation for infants born to women with MG.

Myasthenia gravis and pregnancy.

Myasthenia gravis (MG) is an autoimmune disorder with bimodal age of presentation, occurring in young women of reproductive age and at an older age in men. Occasionally, MG is diagnosed during pregnancy. Management of MG includes symptomatic treatment with cholinesterase inhibitors and immunosuppressive therapy for controlling the disease activity. Treatment of MG in women of reproductive age, who may be contemplating pregnancy, requires discussion regarding the choice of medication as well as the understanding of risks/adverse effects involved with various treatments. During the peripartum period, it is essential to ensure careful monitoring of the disease state along with the well-being of the mother and fetus and to coordinate neonatal monitoring overseen by a multidisciplinary team comprising a high-risk maternal fetal medicine specialist, a neurologist familiar with these complex issues, and a neonatologist.

Management of Myasthenia Gravis in Pregnancy.

Myasthenia gravis is an autoimmune disorder characterized by fluctuating weakness of extraocular and proximal limb muscles. It occurs in 1 in 5000 in the overall population and is 2 times more common in women than men. The onset in women is most common in the third decade, and risk of severe exacerbation occurs most frequently in the year after presentation. The disease does not have an impact on fertility and overlap with pregnancy is expected. This article provides a description of the disease process and its impact on the expecting mother, fetus, and newborn. Management options in pregnancy and lactation are discussed.

Miastenia gravis y maternidad / Myasthenia gravis and pregnancy

OBJETIVOS: Conocer el imaginario de las mujeres embarazadas sobre la maternidad. MATERIAL Y MÉTODO: Estudio llevado a cabo con metodología cualitativa. La información se generó mediante entrevistas semiestructuradas y se realizó un análisis sociológico de los discursos. Los sujetos de estudio fueron 10 mujeres embarazadas de 36-37 semanas de gestación. Se atendió a los aspectos éticos y legales. RESULTADOS: La decisión de ser madre es, en ocasiones, poco explícita: la maternidad aparece como destino femenino, enaltecida por ser fuente de nuevas experiencias y satisfacciones, pero también relacionada con un aumento de las obligaciones y las responsabilidades, con las consiguientes repercusiones en la vida personal y laboral. Las mujeres expresan inseguridad e incertidumbre ante el nuevo papel requerido: el de madre. El instinto maternal aparece en el imaginario de las mujeres, pero no el paternal. CONCLUSIONES: La fuerte asociación entre maternidad e identidad femenina en el orden cultural y simbólico hegemónico actúa como motor en la decisión de ser madre. El instinto maternal aparece en el imaginario de las mujeres para dar una explicación naturalista al rol de madre. Surge la preocupación acerca de las estrategias necesarias para conciliar la vida laboral con la familiar: las renuncias laborales están relacionadas con la naturalización del rol de madre. La maternidad es una experiencia individual contextualizada en un entorno social, cultural, histórico, económico y laboral. Estudiar las creencias y los valores de una sociedad androcéntrica nos permitirá conocer las interacciones que se dan en ella, y reconocer a las mujeres como agentes capaces de construir nuevos significados. Una madre no nace, se hace

OBJECTIVES: To know how pregnancy, delivery and postpartum period are affected by myasthenia gravis and to analyze the management of the disease during this period. METHODS: A bibliographic search has been done in CINAHL, PubMed, Science Direct, Scopus, Proquest, Lilacs, Scielo, Cochrane Plus, Cuiden Plus and IME databases. RESULTS: We have chosen 40 articles. Myasthenia in pregnancy is associated to an increased risk of preterm delivery, premature ruptured membranes and neonatal mortality. Instrumental labor is recommended to avoid maternal weakness. Breastfeeding is not contraindicated if maternal disease is well-controlled. CONCLUSIONS: Myasthenia gravis increases the risk of complications during this period. Pregnancy has to be planned in advance. Fetal monitoring is essential

Miastenia gravis y embarazo: caso clínico / Myasthenia gravis and pregnancy: clinical case

La miastenia gravis es una enfermedad autoinmune que afecta a la placa motora produciendo debilidad y fatiga en la musculatura estriada. Durante la gestación el curso de la enfermedad es impredecible. Un 10-20% de los neonatos pueden padecer miastenia gravis neonatal por el paso de autoanticuerpos maternos. Reportamos un caso de una gestante añosa, primigesta, con diagnóstico de miastenia gravis previo, que recibió tratamiento multidisciplinario sin presentar complicaciones maternas ni morbilidad neonatal (AU)

Myasthenia gravis is an autoimmune disease that affects the motor plate producing weakness and fatigue in striated muscle. During gestation, the course of the disease is unpredictable. 10-20% of infants may develop neonatal myasthenia gravis by the passage of maternal autoantibodies. We report a case of a pregnant woman aged primgravida diagnosed with myasthenia gravis prior, who received multidisciplinary treatment, without showing maternal complications and neonatal morbidity (AU)

Estado actual de los síndromes miasténicos congénitos / Current status of congenital myasthenic syndromes

Desde la descripción de Engel del primer caso de miastenia congénita en 1977 y el hallazgo en 1995 del primer gen patógeno, el conocimiento de los síndromes miasténicos congénitos se ha ido desarrollando, y se han descrito la base patógena, sus características clínicas, las correlaciones fenotipo-genotipo establecidas y su abordaje terapéutico. En este grupo de enfermedades se altera el margen de seguridad de la transmisión neuromuscular por distintos mecanismos: en la síntesis o almacenamiento de los quantum de acetilcolina en las vesículas sinápticas, en la liberación de acetilcolina en el nervio terminal mediada por calcio o en la eficiencia de la cuanta liberada para generar una despolarización postsináptica. Su conocimiento ha permitido establecer distintas estrategias terapéuticas. En esta revisión se describen las principales actualizaciones de estos síndromes: los genes descritos que clasifican un 50% de los casos, su clasificación actual basándose en la localización de las proteínas que alteran la transmisión neuromuscular, incluyendo un nuevo grupo de miastenias congénitas, los trastornos de la glicosilación, las principales claves diagnósticas y el abordaje terapéutico de este grupo de pacientes infradiagnosticados (AU)

Since Engel reported the first case of congenital myasthenia in 1977 and the first pathogenic gene was found in 1995, knowledge about congenital myasthenic syndromes has continued to grow. Over the years, the pathogenic basis, its clinical features, the phenotype-genotype correlations that have been established and its therapeutic management have all been described. In this group of diseases the safety margin of neuromuscular transmission is altered by different mechanisms: in the synthesis or storage of acetylcholine quanta in the synaptic vesicles, in the calcium-mediated release of acetylcholine in the nerve terminal or in the efficiency of the quantum released to generate a post-synaptic depolarisation. Increased knowledge about them has enabled a number of different therapeutic strategies to be established. In this review the main updates on these syndromes are reported, including: the genes described as classifying 50% of cases, their current classification based on the localisation of the proteins that alter neuromuscular transmission, including a new group of congenital myasthenias, glycosylation disorders, the main key diagnoses and the therapeutic management of this group of under-diagnosed patients (AU)

The Role of Sugammadex in Symptomatic Transient Neonatal Myasthenia Gravis: A Case Report.

We describe the case of a 3-week-old boy with pyloric stenosis who presented for laparoscopic pyloromyotomy in the setting of symptomatic transient neonatal myasthenia gravis. The patient received muscle relaxation with rocuronium, and neuromuscular blockade was successfully reversed with sugammadex with recovery guided by train-of-four monitoring. He was extubated uneventfully without complications. Because sugammadex binds directly to rocuronium rather than interfering with acetylcholine metabolism, it might provide a good option for reversal of neuromuscular blockade in transient neonatal myasthenia gravis.

[Neonatal hyperthyroidism: A sometimes challenging diagnosis]. / L'hyperthyroïdie néonatale : un diagnostic parfois difficile.

Graves disease complicates two pregnancies out of 1000 and when it is known before pregnancy, it warrants careful monitoring of the fetus and the newborn. We report on a case of neonatal hyperthyroidism, which revealed a previously unknown maternal thyroid disease. In this situation, neonatal signs can be misinterpreted, delaying the diagnosis. Neonatal hyperthyroidism is, however, a therapeutic emergency because of the risk of cardiac and neurological complications. The neonatologist must identify thyroid disease in the absence of a maternal history in order to promptly start therapy.

Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis.

We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis.

Ephedrine for myasthenia gravis, neonatal myasthenia and the congenital myasthenic syndromes.

BACKGROUND: Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and neonatal myasthenia gravis, NMG) or by defects in genes for neuromuscular junction proteins (congenital myasthenic syndromes, CMSs). Clinically, some individuals seem to benefit from treatment with ephedrine, but its effects and adverse effects have not been systematically evaluated. OBJECTIVES: To assess the effects and adverse effects of ephedrine in people with autoimmune MG, transient neonatal MG, and the congenital myasthenic syndromes. SEARCH METHODS: On 17 November 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We also searched reference lists of articles, conference proceedings of relevant conferences, and prospective trial registers. In addition, we contacted manufacturers and researchers in the field. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and quasi-RCTs comparing ephedrine as a single or add-on treatment with any other active treatment, placebo, or no treatment in adults or children with autoimmune MG, NMG, or CMSs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study design and quality, and extracted data. We contacted study authors for additional information. We collected information on adverse effects from included articles, and contacted authors. MAIN RESULTS: We found no RCTs or quasi-RCTs, and therefore could not establish the effect of ephedrine on MG, NMG and CMSs. We describe the results of 53 non-randomised studies narratively in the Discussion section, including observations of endurance, muscle strength and quality of life. Effects may differ depending on the type of myasthenia. Thirty-seven studies were in participants with CMS, five in participants with MG, and in 11 the precise form of myasthenia was unknown. We found no studies for NMG. Reported adverse effects included tachycardia, sleep disturbances, nervousness, and withdrawal symptoms. AUTHORS' CONCLUSIONS: There was no evidence available from RCTs or quasi-RCTs, but some observations from non-randomised studies are available. There is a need for more evidence from suitable forms of prospective RCTs, such as series of n-of-one RCTs, that use appropriate and validated outcome measures.

Update on juvenile myasthenia gravis.

PURPOSE OF REVIEW: Juvenile myasthenia gravis is a relatively rare autoimmune neuromuscular disorder. The pathophysiology of juvenile myasthenia gravis is similar to that of adult myasthenia gravis, though there remain important differences regarding presentation and therapeutic options. We review the pathophysiology, clinical presentation, and treatment options for juvenile myasthenia gravis. RECENT FINDINGS: Randomized clinical studies of myasthenia gravis have been carried out primarily in adult populations. As juvenile myasthenia gravis is rare, it has been difficult to collect prospective randomized controlled data to evaluate treatment outcomes and efficacy. A recent retrospective series suggests that, as in adult myasthenia gravis, thymectomy is a viable therapeutic option for selected cases of generalized juvenile myasthenia gravis. This is corroborated by the clinical experience of the authors in a referral center with a cohort of patients affected by juvenile myasthenia gravis over a number of years. SUMMARY: Recent studies illustrate that some, but not all, adult research on myasthenia gravis is applicable to children and adolescents with juvenile myasthenia gravis. Adult research can inform pediatric studies, but should not be regarded as a substitute for dedicated research in those populations.

Congenital myasthenic syndromes and transient myasthenia gravis.

Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis.

Prenatal immunomodulation treatment in neonatal myasthenia gravis.

Neonatal mysthenia gravis (NMG) is a rare cause of arthrogryposis multiplex congenita (AMC) due to diaplacental transfer of maternal acetylcholine receptors (AChR) antibodies. 2 cases of severe NMG complicated by chronic lung disease and pulmonary arterial hypertension are reported. With respect to the severe course of the index patient, prenatal diagnosis and immunomodulation treatment were offered during the 2nd pregnancy. The combination of prenatal immunoadsorption (IA) therapy, administration of intravenous immunoglobulin (IVIG) and prednisolone failed. Failure may be partly explained by immaturity of the infant. However, considering the successful treatment of fetal/neonatal alloimmune thrombocytopenia (AIT) reported in literature, a treatment approach with IVIG doses up to 1-2 g/kg per week plus prednisone/prednisolone at a higher dose up to 1 mg/kg/d might be more effective.

Morbilidad materna: hospitalización ante-parto / Maternal morbidity: ante partum hospitalization

Determinar la incidencia de admisiones antenatales en gestantes portadoras de enfermedades severas que implican un tratamiento intrahospitalario, revelando así la morbilidad materna, además de conocer sus repercusiones perinatales. Estudio observacional, descriptivo, analítico realizado durante el trienio 2008-2010. Hubo 5 815 nacimientos, 1 033 admisiones antenatales, 230 neonatos con morbilidad neonatal y 34 muertes feto-neonatales. Las embarazadas debían tener 20 semanas o más de gestación, hospitalizadas 2 días o más, fueron dadas de alta sin parir y luego regresaron para su asistencia obstétrica definitiva. Departamento de Obstetricia y Ginecología, Hospital "Dr. Adolfo Prince Lara", Departamento Clínico Integral de la Costa, Universidad de Carabobo. Puerto Cabello. Hubo una incidencia de 17,76 pacientes hospitalizadas antenatalmente por cada 100 nacimientos o 1 cada 5,6 nacimientos. Las patologías más frecuentes fueron las propias del embarazo (57,41 por ciento): la amenaza de parto prematuro (18,20 por ciento), preeclampsia (9,78 por ciento), hemorragia placentaria (6,68 por ciento), oligohidramnios (6,58 por ciento) y anemia (5,52 por ciento). Las patologías asociadas al embarazo (33,98 por ciento): infección urinaria (14,13 por ciento) y diabetes(9,49 por ciento) La morbilidad neonatal global fue 22,26 por ciento, aportada principalmente por patologías propias del embarazo: amenaza parto pretérmino (20,43 por ciento), preeclampsia (13,04 por ciento), y hemorragia placentaria (10 por ciento); de las asociadas: infección urinaria 14,35 por ciento y diabetes 14,35 por ciento. La mortalidad feto-neonatal fue de 3,3 por ciento, contribuyendo predominante prematurez y malformación fetal (29,41 por ciento), preeclampsia (26,47 por ciento), el desprendimiento prematuro de placenta y la placenta previa (17,65 por ciento). Hubo una incidencia elevada de admisiones antenatales, causadas por entidades que obligan a un diagnóstico precoz...

To determine the incidence of antenatal admissions in pregnant women carrying a severe illness involving hospital management, revealing maternal morbidity, in addition to knowing their impact perinatal outcomes. An observational, descriptive, analytical study, made during the 2008-2010 period. There were 5 815 births, 1 033 antenatal admissions, 230 infants with neonatal morbidity and 34 fetal and neonataldeaths. Pregnant women should take 20 weeks or more gestation, hospitalized 2 days or more, were discharged without giving birth and then returned for final delivery care. Department of Obstetrics and Gynecology, Hospital "Dr. Adolfo Prince Lara". Departamento Clinico de la Costa. University of Carabobo. Puerto Cabello, Estado Carabobo, Venezuela. There was an incidence of patients hospitalized antenatally 17.76 per 100 births or 1 in 5.6 children. The most frequent pathologies were typical of pregnancy (57.41 percent): preterm delivery threatens (18.20 percent), pre-eclampsia (9.78 percent), placental hemorrhage (6.68 percent), oligohydramnios (6.58 percent) and anemia (5.52 percent). Pregnancy-associated pathologies (33.98 percent): urinary tract infection (14.13 percent) and diabetes (9.49 percent). Neonatal morbidity rate was 22.26 percent, contributed mainly by pathologies of pregnancy: preterm delivery threatens (20.43 percent), pre-eclampsia (13.04 percent), and placental hemorrhage (10 percent), associated: urinary tract infection 14.35 percent and diabetes 14.35 percent. Feto-neonatal mortality was 3.3 percent, contributing predominant: prematurity and fetal malformation (29.41 percent), pre-eclampsia (26.47 percent), abruptio placenta and placenta previous (17.65 percent). There was a high incidence of antenatal admissions caused by entities that require early diagnosis and better management in order to lessen the economic impact and the serious repercussions hospital perinatal evidenced

[A pregnant patient with anti-MuSK antibody positive myasthenia gravis and her infant with transient neonatal myasthenia gravis].

A 30-year-old healthy woman experienced speech disturbance and swallowing difficulty at two months of pregnancy. She was diagnosed as myasthenia gravis (MG) with anti-MuSK antibodies. At eight months of pregnancy, bulbar palsy, eye movement disturbance, and muscle weakness worsened unexpectedly. Plasma exchange was performed three times daily starting from the 1st day of the 37th pregnancy week (2 L/day, albumin substitution of 5%) and the patient underwent caesarean section and gave birth to the girl safely. The infant had anti-MuSK antibodies in the serum and umbilical cord blood. The infant's suckling power was weak. The infant was diagnosed as transient neonatal myasthenia gravis. There is no case where management of MG has been performed from the period of pregnancy for anti-MuSK positive patients. For the control of Anti-MuSK positive patients in addition to normal care for Anti-AChR antibodies positive patients, it is important to carefully observe symptoms caused by bulbar palsy, draw attentions on malnutrition and polyhydramnios, and perform simple plasmapheresis on regular basis without any delay.