Myasthenia gravis.

Myasthenia gravis (MG) is a rare neuromuscular junction disorder that is characterized by fatigable weakness of muscles. People with MG experience various clinical manifestations based on the muscles involved. MG can be autoimmune, paraneoplastic, congenital, medication-related, or transient in the neonatal period due to the passive placental transfer of antibodies from mothers with MG. Acetylcholine receptor antibodies are seen in the majority of patients with MG. However, other antibodies have been discovered in the last 20 years, including muscle-specific tyrosine kinase (MuSK) and lipoprotein-related peptide 4 (LRP4), and are now available through commercial testing. More recently, a handful of other antibodies have been associated with MG; however, they are not presently available for routine testing. A disease classification system has been developed by the Myasthenia Gravis Foundation of America (MGFA) and is commonly used worldwide. A number of objective and subjective outcome measures have been developed and validated over the years and have been proven useful for both clinical and research purposes, serving as primary and secondary outcome measures in most clinical trials. A growing number of therapies are available for both acute and chronic management of MG, with several new mechanistic approaches under investigation. An international consensus guidance for the management of MG was first published in 2016 and updated in 2020.

Myasthenia gravis and pregnancy: Lessons learned from a complex a case report.

Myasthenia gravis primarily affects young adults, with a higher incidence in women, particularly between the ages of 20 and 30. When a young woman with myasthenia gravis contemplates pregnancy, healthcare providers must consider the potential implications. The interplay between hormonal factors and changes in the immune system establishes a complex relationship between myasthenia gravis and pregnancy. On one hand, pregnancy can alter the course of the disease, while on the other hand, the disease can impact the progression of the pregnancy and the well-being of the fetus. In this case report, we present the case of a 28-year-old woman suffering from myasthenia gravis who had undergone a thymectomy 5 years ago and was being treated with an acetylcholinesterase inhibitor. After a planned conception, the patient presented a relapse of her disease during the third trimester of pregnancy, with the onset of severe hydramnios. This observation highlights a specific case of decompensation of myasthenia gravis during pregnancy, associated with the presence of severe hydramnios. Subsequently, we delve into the existing literature to examine the reciprocal influence between myasthenia gravis and pregnancy, as well as the effects of anti-myasthenic treatments on pregnancy outcomes.

Pregnancy in myasthenia gravis: a retrospective analysis of maternal and neonatal outcome from a large tertiary care centre in Germany.

PURPOSE: Myasthenia gravis (MG) is a rare, potentially life-threatening autoimmune disease with fluctuating muscle weakness frequently affecting women of childbearing age. MG can affect maternal as well as neonatal outcome with risk of worsening of myasthenic symptoms in the mothers and risk of transient neonatal myasthenia gravis (TNMG) and arthrogryposis multiplex congenita (AMC) or foetal acetylcholine receptor antibody-associated disorders (FARAD) in the neonates. METHODS: Retrospective analysis of maternal and neonatal outcome in a cohort of pregnant MG patients treated at a tertiary care centre in Germany. RESULTS: Overall, 66 pregnancies were analysed. During 40 (63%) pregnancies, women experienced a worsening of myasthenic symptoms, of whom 10 patients (15.7%) needed acute therapy with IVIg or plasma exchange. There was no case of myasthenic crisis. Rate of caesarean section was comparable to the overall C-section rate at our centre (38% vs. 40%). However, there was a slightly higher rate for operative vaginal delivery (15% vs. 10%) as potential indicator for fatiguing striated musculature in MG patients during the expulsion stage. Rate of TNMG as well as AMC was 3% (two cases each). CONCLUSIONS: Maternal and neonatal outcome in our cohort was favourable with a low rate of myasthenic exacerbations requiring acute therapies and a low rate of TNMG and AMC/FARAD. Our data might help neurologists and obstetricians to advice MG patients with desire to have children.

Transient Neonatal Myasthenia Gravis Born to a Mother with Asymptomatic MG: A Case Report.

Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.

[Myasthenia gravis-Gender aspects and family planning]. / Myasthenia gravis ­ Genderaspekte und Familienplanung.

BACKGROUND: There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age. OBJECTIVE: Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived. MATERIAL AND METHODS: Narrative literature review. RESULTS: In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies. CONCLUSION: Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.

Pregnancy planning may impact maternal and neonatal outcomes in people with myasthenia gravis.

INTRODUCTION: Myasthenia Gravis (MG) is an acquired autoimmune condition commonly diagnosed in young people of reproductive age resulting in neuromuscular junction dysfunction. The course of MG during pregnancy and its impact on maternal and neonatal outcomes is vary in the literature. Pregnancy planning is a known strategy and modifiable risk factor in obstetric practice to decrease maternal and neonatal morbidity. We aim to assess if planning a pregnancy impacts maternal and neonatal outcomes, MG exacerbation, and pregnancy-related complications. METHODS: This study utilized data from an online, North American survey entitled "A Patient Centered study on Pregnancy in People with Myasthenia Gravis", distributed with the assistance of MG advocacy groups in the United States and Canada. It included individuals with MG who had at least one pregnancy in the last 10-years. Key maternal and neonatal outcomes were compared between planned and unplanned pregnancies. RESULTS: Out of 156 survey participants, 58 had a pregnancy following MG diagnosis, totaling 90 reported pregnancies. Of these, 56 (62.2%) were planned and 34 (37.8%) were unplanned pregnancies. The unplanned pregnancies were associated with more MG exacerbations, hospitalizations, and intensive care unit admission (37.7% vs. 13.7%, 26.5% vs. 11%, and 17.6% vs. 8.9%, respectively, p ≤ .05). The neonatal outcomes did not significantly differ between the groups. DISCUSSION: Planned pregnancies in people with MG may be associated with a reduced gestational and post-partum risk of MG exacerbation, hospitalizations, and ICU admissions. Larger studies are required to confirm this association and account for potential contributing variables.

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 emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

Myasthenia gravis, respiratory function, and respiratory tract disease.

Myasthenia gravis (MG) is characterized by muscle weakness caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction and impair acetylcholine receptor function. Weakness of respiratory muscles represents the most severe MG manifestation, and 10-15% of all patients experience an MG crisis with the need of mechanical ventilatory support at least once in their life. MG patients with respiratory muscle weakness need active immunosuppressive drug treatment long term, and they need regular specialist follow-up. Comorbidities affecting respiratory function need attention and optimal treatment. Respiratory tract infections can lead to MG exacerbations and precipitate an MG crisis. Intravenous immunoglobulin and plasma exchange are the core treatments for severe MG exacerbations. High-dose corticosteroids, complement inhibitors, and FcRn blockers represent fast-acting treatments that are effective in most MG patients. Neonatal myasthenia is a transient condition with muscle weakness in the newborn caused by mother's muscle antibodies. In rare cases, treatment of respiratory muscle weakness in the baby is required.

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.

Treatment considerations in myasthenia gravis for the pregnant patient.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease where muscle antibodies form against the acetylcholine receptor (AChR), MuSK, or LRP4 at the neuromuscular junction leading to weakness. Patients worry about consequences for pregnancy, giving birth, nursing, and child outcome. AREAS COVERED: This review lists the pharmacological treatments for MG in the reproductive age and gives recommendations. Consequences for pregnancy, giving birth, breastfeeding, and child outcome are discussed. EXPERT OPINION: Pyridostigmine, corticosteroids in low doses, and azathioprine are regarded as safe during pregnancy and should be continued. Mycophenolate mofetil, methotrexate, and cyclophosphamide should not be used in reproductive age. Rituximab should not be given during pregnancy. Other monoclonal IgG antibodies such as eculizumab and efgartigimod should be given only when regarded strictly necessary to avoid long-term and severe incapacity. Intravenous and subcutaneous immunoglobulin and plasma exchange are safe treatments during pregnancy and are recommended for exacerbations with moderate or severe generalized weakness. Most MG women have spontaneous vaginal deliveries. Indications for Cesarean section are obstetrical and similar to non-MG women. Neonatal myasthenia manifests as a transient weakness caused by the mother's IgG muscle antibodies and affects 10% of the babies. MG women should be supported in their wish to have children.

Fetal Surveillance in Pregnancies with Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune condition, that commonly impacts adult women of reproductive age. Myasthenia gravis in pregnancy is rare, but the incidence is higher in different geographical areas. Pregnancies in mothers with MG can have an unfortunate outcome. Acetylcholine receptor antibodies may pass into the fetal circulation and can affect the fetal neuromuscular junction, generating transient MG or even fetal arthrogryposis. The 2016 and 2021 International Consensus Guidance for Management of Myasthenia Gravis issued by Myasthenia Gravis Foundation of America is lacking in recommendation for fetal surveillance for pregnancies in women with MG. The aim of this paper is to highlight fetal and neonatal complications in mothers with MG and to offer antenatal care insights. Close maternal and pregnancy monitoring can improve pregnancy outcome. Patients with MG should be encouraged to conceive, to avoid triggers for exacerbations of the disease during pregnancy and a multidisciplinary team should be established to ensure the optimal support and therapy.

Transient Neonatal Myasthenia Gravis: A Case Report.

Myasthenia gravis (MG) in the neonate is usually due to placentally transferred antibodies to the acetylcholine receptor (AChR), resulting in impaired neuromuscular transmission. It occurs in 10%-15% of newborns born to women with MG. We present a male newborn admitted to the neonatal intensive care unit (NICU) 38 hours after birth due to feeding difficulties and choking episodes. He was born to a mother with MG after an uneventful, well-followed pregnancy. Physical examination revealed a weak cry, persistent inability to fully close his eyelids, weak facial mimic, and a mouth that was always held open with swallowing and sucking difficulties. He assumed a frog leg position and showed generalized hypotonia with marked head lag. No respiratory distress was present. Laboratory evaluation showed an elevated anti-acetylcholine receptor antibody concentration (36.30 nmol/L; normal: <0.25 nmol/L). Transient neonatal myasthenia gravis (TNMG) was admitted, and an anticholinesterase agent was initiated. Given that he showed only a mild clinical improvement, two doses of immunoglobulin were administered on the eighth and ninth days of life. Anticholinesterase agents were progressively reduced and suspended on day 31 of life with clinical improvement. He was discharged home at one month of life clinically asymptomatic. He was evaluated one month later and was doing well. A positive history of MG in the mother associated with a suggestive physical examination may be sufficient to make the diagnosis of transient neonatal MG, emphasizing the importance of good medical history. With prompt diagnosis and appropriate management, most newborns experience spontaneous remission after a period of weeks to months.

Myasthenia Gravis Can Have Consequences for Pregnancy and the Developing Child.

Myasthenia gravis (MG) with onset below 50 years, thymic hyperplasia and acetylcholine receptor (AChR) antibodies is more common in females than in males. For a relatively large group of MG patients, pregnancy represents therefore an important question. The muscle weakness, the circulating autoantibodies, the hyperplastic thymus, the MG drug treatment, and any autoimmune comorbidity may all influence both mother and child health during pregnancy and also during breastfeeding in the postpartum period. Mother's MG remains stable in most patients during pregnancy. Pyridostigmine, prednisolone, and azathioprine are regarded as safe during pregnancy. Mycophenolate, methotrexate and cyclophosphamide are teratogenic and should not be used by women with the potential to become pregnant. Rituximab should not be given during the last few months before conception and not during pregnancy. Intravenous immunoglobulin and plasma exchange can be used for exacerbations or when need for intensified therapy. Pregnancies in MG women are usually without complications. Their fertility is near normal. Vaginal delivery is recommended. MG patients have an increased rate of Cesarean section, partly due to their muscle weakness and to avoid exhaustion, partly as a precaution that is often unnecessary. Around 10% of the newborn develop neonatal myasthenia during the first few days after birth. This is transient and usually mild with some sucking and swallowing difficulties. In rare cases, transplacental transfer of AChR antibodies leads to permanent muscle weakness in the child, and arthrogryposis with joint contractures. Repeated spontaneous abortions have been described due to AChR antibodies. MG women should always give birth at hospitals with experience in newborn intensive care. MG does not represent a reason for not having children, and the patients should be supported in their wish of becoming pregnant.

Myasthenia Gravis with Anti-Muscle-Specific Tyrosine Kinase Antibody during Pregnancy and Risk of Neonatal Myasthenia Gravis: A Case Report and Review of the Literature.

A 31-year-old woman presented with a nasal voice, dysarthria, and upper limb weakness during her first pregnancy. Soon after delivery of her first baby, her symptoms disappeared. At the age of 34 years, during her second pregnancy, her nasal voice re-appeared. After delivery of the second baby, her nasal voice worsened, and bilateral eyelid ptosis and easy fatigability were also evident. She was referred to our hospital. Because of her myasthenic symptoms and anti-muscle-specific tyrosine kinase (MuSK) antibody (Ab)-positive status, she was diagnosed as having myasthenia gravis (MG). Her symptoms were worse than those in her first pregnancy. She was treated with oral steroid and double filtration plasmapheresis. After initiation of treatment, her myasthenic symptoms improved completely. In addition, her baby developed transient neonatal MG (TNMG) on the fourth day after birth and then gradually recovered over 30 days. It should be noted that symptoms of patients with anti-MuSK Ab-positive MG (MuSK-MG) can deteriorate during pregnancy, and the babies delivered of patients with MuSK-MG have a high probability of developing TNMG.

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.

Maternal myasthenia gravis represents a risk for the child through autoantibody transfer, immunosuppressive therapy and genetic influence.

Females with myasthenia gravis (MG) worry about their disease having negative consequences for their children. Autoimmune disease mechanisms, treatment and heredity could all have an impact on the child. This is a subject review where Web of Science was searched for relevant keywords and combinations. Controlled and prospective studies were included, and also results from selected and unselected patient cohorts, guidelines, consensus papers and reviews. Neonatal MG with temporary muscle weakness occurs in 10% of newborn babies where the mother has MG, due to transplacental transfer of antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or lipoprotein receptor-related protein 4 (LRP4). Arthrogryposis and fetal AChR inactivation syndrome with contractures and permanent myopathy are rare events caused by mother's antibodies against fetal type AChR. The MG drugs pyridostigmine, prednisolone and azathioprine are regarded as safe during pregnancy and breastfeeding. Methotrexate, mycophenolate mofetil and cyclophosphamide are teratogenic. Mother's MG implies at least a 10-fold increased risk for MG and other autoimmune diseases in the child. MG females should receive specific information about pregnancy and giving birth. First-line MG treatments should usually be continued during pregnancy. Intravenous immunoglobulin and plasma exchange represent safe treatments for exacerbations. Neonatal MG risk means that MG women should give birth at hospitals experienced in neonatal intensive care. Neonatal MG needs supportive care, rarely also acetylcholine esterase inhibition or intravenous immunoglobulin. Women with MG should be supported in their wish to have children.

An Update: Myasthenia Gravis and Pregnancy.

Myasthenia gravis presents a risk factor for pregnancy and delivery, and can affect the newborn. In return, pregnancy can affect the course of myasthenia and worsen the disease during pregnancy requiring treatment modifications. Treatment optimization and drug safety should be addressed before conception. Delivery is complicated by prolonged labor. Newborns can develop neonatal myasthenia gravis, a treatable and transient disease. Patients should not be discouraged to become pregnant, but provided with supportive counseling, planning, and monitoring in a multidisciplinary team involving obstetrician, anesthesiologist, pediatrician, and neurologist. Pregnancy outcome is favorable in women who receive treatment and expert care.

Management of Myasthenia Gravis During Pregnancy: A Report of Eight Cases.

BACKGROUND: The clinical course of myasthenia gravis (MG) during pregnancy is highly variable and unpredictable. The management of MG in pregnancy has not been standardized. METHODS: Eight cases of MG in pregnancy, who were treated and gave birth in our hospital between 2004 and 2012, were retrospectively reviewed. RESULTS: In three patients, MG deteriorated during pregnancy. Three patients discontinued their medication for MG during their pregnancy, and the other five patients continued on corticosteroid or pyridostigmine. None of the infants showed any congenital abnormalities. Interestingly, there was a trend towards lower birth weight in infants born to women who had an exacerbation of MG during pregnancy. One patient who had unstable MG before pregnancy and voluntarily discontinued the medication for MG at the beginning of pregnancy, experienced MG exacerbation at the 30th week of pregnancy and gave birth prematurely to an infant with transient neonatal MG at the 34th week. The other seven patients had uneventful full-term pregnancy. CONCLUSION: Women with unstable MG should postpone pregnancy to avoid potential risk of MG exacerbation and adverse effects on the fetus. Medication for MG should not be stopped abruptly during pregnancy, particularly for women with unstable MG. MG during pregnancy should be closely monitored and properly controlled.