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Subgroup characteristics of myasthenia gravis-related autoantibodies.
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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 detectab...
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Citations
... This group of patients does not include neonatal MG affecting newborns and caused by the transfer of antibodies from a mother with MG to her baby during pregnancy. In most cases, neonatal MG is temporary, as the mother's antibodies are gradually cleared from the baby's system 13 . There is a wide range of variability in the presentation and severity of symptoms in juveniles, as in adult MG patients. ...
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR⁺ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.
... Symptom onset is often delayed by 6 to 72 h [31]. Even with delayed onset, 80% present within 24 h postpartum [32]. In a few cases, the initial symptom-free period lasts up to 4 days [28,33]. ...
... Complete resolution is observed in less than 2 months in 90% of children. The remaining 10% recover spontaneously within 4 months [32]. The empirically observed time course of TNMG matches the theoretically calculated time for IgG clearance, 15 weeks, which is equal to five times the normal half-life of IgG [34]. ...
... TPE should be reserved for the most severe cases [71]. MuSK-TNMG responds less efficiently to acetylcholine-esterase inhibitors [32,39]. Thus, the requirement for IVIG/TPE is often more pronounced in MuSK-TNMG. ...
Myasthenia gravis (MG) is a rare autoimmune disease. Transient neonatal myasthenia gravis (TNMG) is caused by pathogenic maternal autoantibodies that cross the placenta and disrupt signaling at the neuromuscular junction. This is a systematic review of this transient immunoglobulin G (IgG)-mediated disease. TNMG affects 10–20% of children born to mothers with MG. The severity of symptoms ranges from minor feeding difficulties to life-threatening respiratory weakness. Minor symptoms might go unnoticed but can still interfere with breastfeeding. Acetylcholine-esterase inhibitors and antibody-clearing therapies such as immunoglobulins can be used to treat TNMG, but most children do well with observation only. TNMG is self-limiting within weeks as circulating antibodies are naturally cleared from the blood. In rare cases, TNMG is associated with permanent skeletal malformations or permanent myopathy. The mother’s antibodies can also lead to spontaneous abortions. All healthcare professionals meeting pregnant or birthing women with MG or their neonates should be aware of TNMG. TNMG is hard to predict. Reoccurrence is common among siblings. Pre-pregnancy thymectomy and intravenous immunoglobulins during pregnancy reduce the risk. Neonatal fragment crystallizable receptor (FcRn) blocking drugs for MG might reduce TNMG risk.
... A similar congenital genetic defect affecting the NMJ is congenital myasthenia or congenital myasthenic syndrome, which is not an autoimmune disorder [3]. In addition, transient neonatal myasthenia results from trans-placental transport of IgG from the mother with MG to the affected neonates [4]. The term myasthenia gravis pseudo-paralytic was proposed in 1895, and the first treatment of MG is recorded in 1934, using the anticholinesterase inhibitor physostigmine. ...
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG.Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like.
... Myasthenia gravis is an autoimmune disorder where autoantibodies target the postsynaptic membrane of the neuromuscular junction, causing skeletal muscle weakness and fatigue. In more than 90% of patients, the antibodies are against the muscle acetychoin receptor (AChR), and a small proportion of patients have antibodies against the muscle-specific tyrosine kinase (MuSK) or liporptein receptor-related protein 4 (LPR4) [3]. MG is a relatively rare disorder with an incidence of 1.7-30 cases per million people per year and a prevalence of 77.7 cases per million people [4.5], with a female predominance of 18-25 years of age [6]. ...
... Antibodies provoke the disease by acting on the receptors by: accelerating the degradation of the receptors, blocking the access of acetylcholine to the AChR, and activating and amplifying the complement system, promoting the destruction of the postsynaptic membrane [3]. The presented case of TNMG is mediated by anti-AChR antibodies, which was demonstrated by the high titer of anti-AChR antibodies in a newborn from a mother with MG. ...
... In TNMG, exsanguinous transfusion instead of plasmapheresis could be useful, but there are still divided views about the use of this treatment in newborns. Neonatal Fc receptor antagonists (FcRn inhibitor) are under research as a new treatment for this condition, which improves IgG catabolism leading to a reduction in the concentrations of pathogenic autoantibodies [3]. ...
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.
... is an acquired disease which occurs in 10 to 20% of infants born to a mother with myasthenia gravis. [1][2][3] Transient neonatal myasthenia gravis occurs as a result of the passive transfer of maternal antibodies affecting the fetus' synaptic transmission at the motor end plate. It is characterized by abnormal muscle fatigability. ...
... The prevalence of MG occurring in the general population is 77.7 cases per million persons. 4 The infant born to a mother with MG is at risk of having TNMG with an incidence of 10 to 20%. [1][2][3] However, the risk of TNMG in a sibling, is significantly higher in subsequent pregnancies, as described in our cases. 2 Infants born to women with MG may have a transient neonatal myasthenic syndrome because of placentally transferred maternal anti-AChR or anti-muscle-specific receptor tyrosine kinase (MuSKR) antibodies. ...
... However, specificity of antibodies, in that, a higher ratio of anti-fetal to anti-adult AChR antibodies in the myasthenic mother may predispose to the occurrence of neonatal MG, and more severe or persistent myopathic features such as, arthrogryposis. 3 There are two clinical forms of TNMG: the typical presentation, which is more common, with an incidence rate of approximately 71% and, the atypical form in about a third (29%). 1 The typical form commonly develops symptoms more rapidly, as in Case 2 and 3, that include poor sucking and swallowing, weak cry, facial diplegia and ptosis, ophthalmoparesis, generalized hypotonia and respiratory distress. Some infants develop severe respiratory distress requiring assisted mechanical ventilation. ...
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.
... Generalmente, la MG neonatal transitoria no necesita tratamiento; algunos casos requerirán alimentación por sonda o ventilación mecánica. Se pueden administrar pequeñas dosis de piridostigmina y la inmunoglobulina intravenosa se recomienda para casos graves [24,25]. ...
Introduction:
Myasthenia gravis is characterized by skeletal muscle weakness, the most common initial presentation includes ocular weakness with asymmetric ptosis and binocular diplopia. Around 19-50% of pregnant women with myasthenia gravis will experience a worsening of the disease. The objective of this article was to review the current information regarding the interrelation between MG and pregnancy; as well as its approach.
Development:
Bibliographic search in databases such as PubMed, ScienceDirect, SciELO, Google Scholar and medRxiv. Original articles, reviews, series and case reports between 2013 and 2022 are included.
Conclusions:
Myasthenia gravis would not significantly effects on pregnancy; however, pregnancy can exacerbate the disease, especially during the first trimester or after delivery. The approach to pregnant women with myasthenia gravis must be multidisciplinary and involves the adjustment of pharmacological treatment and constant monitoring.
... Pregnancy, on the other hand, has little effect on the disease's long-term fate [39]. Symptom exacerbations are much more common in the first trimester, although symptom relief is more common in the second and third trimester, possibly due to hormone-mediated immunosuppression that occurs in typically developing pregnancies [40]. Though illness exacerbations typically resolve following spontaneous abortion, pregnancy termination does not affect the relative likelihood or severity of myasthenic aggravation. ...
Background
Fetal acetylcholine receptor antibody-associated disorders (FARAD), caused by in utero exposure to maternal antibodies directed against the fetal acetylcholine receptor (AChR), is a rare condition occurring in newborns of myasthenic mothers. Only two cases of FARAD children born to asymptomatic mothers are published.
Case
We report a completely asymptomatic mother of two FARAD children presenting exclusively with positive AChR antibodies. After birth, the first child needed intensive care therapy due to generalized hypotonia, respiratory problems, dysphagia, necessitating tube feeding and gastrostomy. FARAD was suspected because of ptosis, a hypomimic face, and confirmed by increased AChR antibodies in the mother. The mother became pregnant again 2 years later. Since FARAD is likely to reoccur and it is known that intensity of maternal myasthenia gravis treatment determines postnatal outcome, monthly intravenous immunoglobulin (IVIG) therapy was started at 12 weeks gestational age. The second child needed a short mask ventilation for initial stabilization at birth, but her muscle weakness improved rapidly and tube feeding was not necessary. Similar to her sister a tent-shaped mouth and a somewhat myopathic face persisted, but motor milestones were reached in time.
Conclusions
These observations highlight that FARAD is an important differential diagnosis of genetically determined congenital neuromuscular disorders even in asymptomatic mothers, and that IVIG therapy during the pregnancy has the potential to improve the outcome of the children.
Purpose: Transient neonatal myasthenia gravis (NMG) results from the transplacental transfer of antibodies of mothers with an autoimmune form of myasthenia gravis. The clinical presentation develops in 10%–20% of their children. This study aimed to present a case of a newborn with transient myasthenia gravis (MG) born to a mother diagnosed with MG. Case presentation: The disease manifested itself as generalized hypotonia, weak cry, respiratory distress, poor sucking, and facial diplegia. The symptoms were usually self-limiting, and transient supportive treatment was required. A diagnostic test was a good clinical response of the child to the administration of an acetylcholinesterase inhibitor. After the clearance of antibodies from the child's blood, long-term therapy was not necessary and the disease resolved. Treatment was supportive and included the administration of smaller and more frequent meals via a tube, noninvasive or invasive support of respiratory function, and use of acetylcholinesterase inhibitors (neostigmine and pyridostigmine). Conclusion: Pediatric patients diagnosed with transient NMG are extremely rare in everyday clinical practice, and hence it is important to be familiar with it.
Transient neonatal myasthenia gravis (TNMG) is secondary to transplacental transfer of maternal IgG antibodies against acetylcholine receptor (AChR). This leads to weakness of skeletal muscles with hypotonia and ptosis during neonatal period, often in the first 3–48 hrs of life. This produces Obstructive Sleep Apnea (OSA), worst in REM sleep stage due to increasing hypotonia. Such neonates have associated problem with feeding and are at the risk for aspiration. Most important is the maternal diagnosis of autoimmune myasthenia gravis (MG) with antibodies against AChR. Transplacentally transferred IgG antibodies are degraded over time, usually by 2–4 months, hence the name “Transient Neonatal”. The actual duration depends on the level of these antibodies in the patient. Due to this, usually, treatment is conservative/supportive and long term prognosis is excellent. Polysomnogram is necessary to make sure that the infant is not having severe hypoxemia during sleep requiring treatment.KeywordsTransient Neonatal Myasthenia Gravis (TNMG)Polysomnogram (PSG)Obstructive Sleep Apnea (OSA)acetylcholine receptor (AChR) antibodies
