Transient Neonatal Myasthenia Research Articles

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

PurposeMyasthenia 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.MethodsRetrospective analysis of maternal and neonatal outcome in a cohort of pregnant MG patients treated at a tertiary care centre in Germany.ResultsOverall, 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).ConclusionsMaternal 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 as a Common Complication of a Rare Disease: A Systematic Review.

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.

Newborn from the third deed with severe Transient Neonatal Myasthenia Gravis: Case report

Newborn from the third deed with severe Transient Neonatal Myasthenia Gravis: Case report

Transient Neonatal Myasthenia Gravis: Case Report

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.

New diagnosis of myasthenia gravis in the third trimester – A case report

Myasthenia gravis (MG) is an acquired autoimmune disorder of the neuromuscular junction with an annual incidence rate of 2 to 21 per million. A 25-year-old primiparous woman with no significant medical history presented for a routine antenatal appointment at 37weeks of gestation. She reported a two-week history of transient diplopia and a five-month history of fluctuating weakness in her proximal limbs. Pertinent neurological exam findings included right upper limb flaccidity, and bilateral upper and lower limb weakness more pronounced in the upper limbs and in proximal muscle groups. Cranial nerves III, IV and VI showed mild restriction in all directions, with diplopia in horizontal and downwards gaze. Following one week of investigations, including spirometry, magnetic resonance imaging of brain and spine, and needle electromyography, she was diagnosed with MuSK (anti-muscle-specific tyrosine kinase antibodies) associated myasthenia gravis. Potential complications in this context included myasthenic crisis, delivery complications, and transient neonatal myasthenia gravis. She was initially treated with 5days of plasmapheresis and prednisone. She proceeded to have an elective caesarean section for unstable lie at 39weeks of gestation under combined spinal/epidural anaesthesia without complications. The baby boy was born in good health, was monitored over four days and did not display signs of myasthenia gravis. This case outlines the rare occurrence of newly diagnosed myasthenia gravis in pregnancy, the complexities of management, and need for early multidisciplinary care.

The impact of Myasthenia Gravis antibody status on pregnancy and neonatal outcomes (P1-8.007)

<h3>Objective:</h3> The objective of this study to assess the impact of Myasthenia Gravis (MG) serological status on pregnancy-related and neonatal outcomes. <h3>Background:</h3> Pregnancy has a variable effect on the course of MG. Current knowledge describes an increased likelihood of flares in the first trimester and the postpartum period, an increased risk of caesarean section and ICU admission, transient neonatal MG and arthrogryposis. It’s unknown if serological status impacts pregnancy and neonatal outcomes. <h3>Design/Methods:</h3> An online survey was developed in conjunction with patient representatives from the Myasthenia Gravis Foundation of America. Respondents who have (or had) ovaries, uterus, and/or cervix with a diagnosis of MG. For the current analysis, those with at least one pregnancy in prior 10 years were included. Information on disease course, pregnancy complications, antibody status, fetal and neonatal outcomes was collected. <h3>Results:</h3> 157 opened the survey, and 142 met entry criteria for a response rate of 90%. 96 pregnancies were analyzed. MG symptoms appeared to worsen regardless of antibody status in the first trimester and postpartum. Antibody negative vs AchRAB and MUSK participants respectively, reported a greater risk of ICU admission (23% vs 16% and 12%, P =0.058 ) intubation ( 50% vs 4% and 17% P value 0.007) C-section ( 92% vs 23% and 42%, put p-0.001), neonatal MG rates (67% vs 8% and 0%, P value 0.001), and unplanned pregnancy (75% vs 21% and 50%, put p-value 0.004). <h3>Conclusions:</h3> This is the first know study of the association between negative serological status and poor pregnancy outcomes and although limited in size, may influence future preconception counselling and pregnancy monitoring. Highlighting the importance of interdisciplinary preconception and antenatal care including Neurology, Maternal-Fetal-Medicine and Neonatology. Findings of transient neonatal myasthenia gravis and arthrogryposis in seronegative individuals suggests that another, currently unknown antibody or biological process may be present in the seronegative group. Future, larger studies are warranted. <b>Disclosure:</b> Dr. Al Hussona has nothing to disclose. Dr. Izenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Izenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Izenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Izenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aaron Izenberg. Dr. Barnett Tapia has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Barnett Tapia has received personal compensation in the range of $0-$499 for serving as a Consultant for Sanofi. Dr. Barnett Tapia has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Barnett Tapia has received research support from Department of defense. The institution of Dr. Barnett Tapia has received research support from Muscular dystrophy canada. The institution of Dr. Barnett Tapia has received research support from MgNet. The institution of Dr. Barnett Tapia has received research support from NIH. Dr. Barnett Tapia has received intellectual property interests from a discovery or technology relating to health care. Dr. Berndl has nothing to disclose.

Transient neonatal myasthenia gravis: case report

Transient neonatal myasthenia gravis (TNMG) is a distinct type of myasthenia gravis (MG), a temporary autoimmune condition due to the mother’s antibodies crossing over the placenta and affecting the baby. Studies suggest that 10 to 15% of infants born to mothers suffering from MG will develop TNMG. Undoubtedly, if not diagnosed and treated in time, TNMG can be a serious condition, even life-threatening. Almost 80% of newborns will present symptoms in the first 24 hours of life that will last up to 4 weeks and a complete recovery is expected by 2 months of age. Only 10% of the affected infants may still be symptomatic at 4 months.

Myasthenia gravis in pregnancy: Systematic review and case series.

BackgroundMyasthenia gravis is an autoimmune disease which can impact pregnancy.MethodsSix databases were systematically searched for studies with at least five subjects reporting pregnancy outcomes for women with myasthenia gravis in pregnancy. Assessment of bias was performed for all included studies. Forty-eight cases from our own centre were also included in the analysis.ResultsIn total, 32 publications met inclusion criteria for systematic review, for a total of 33 unique data sets including 48 cases from our institution. Outcome data was available for 824 pregnancies. Spontaneous vaginal delivery occurred in 56.3% of pregnancies. Overall risk of myasthenia gravis exacerbation was 33.8% with a 6.4% risk of myasthenic crisis in pregnancy and 8.2% postpartum. The incidence risk of transient neonatal myasthenia gravis was 13.0%.ConclusionsThe current systematic review provides the best estimates of risk currently available to aid in counselling women with myasthenia gravis in pregnancy.

Myasthenia gravis during pregnancy: what care should be taken?

Myasthenia gravis (MG) is an autoimmune disease in which the peak incidence is among women of childbearing age. For this reason, there is an overlap between the occurrence of this disease and pregnancy. It is known that MG symptoms can worsen during pregnancy and postpartum, and that pregnancy has special characteristics in MG patients. Children born to myasthenic mothers are at risk of having transient neonatal myasthenia. We briefly review the main relationships between MG and pregnancy, and we make recommendations for MG therapy, pregnancy, delivery, breastfeeding and newborns.

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

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. We reviewed our own experience of infants who underwent routine inpatient monitoring for TNMG and combined our local data with observations from previous studies. 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. TNMG signs were mostly not life-threatening. We suggest only 4 days of routine postnatal observation for infants born to women with MG.

Neuromuscular Junction Disorders and Floppy Infant Syndrome: A Comprehensive Review.

Floppy infant syndrome, also sometimes referred to as rag-doll syndrome, is characterized by hypotonia that could present as either peripheral hypotonia or central. Depending on the origin of hypotonia, the infant will present with different symptoms that ultimately have the characteristic feature of hypotonia. The clinical examination is crucial in diagnosing floppy infant syndrome in the neonate period, but the most critical factor is investigating and diagnosing the underlying cause of hypotonia. Regardless of whether the underlying cause of hypotonia is peripheral or central in origin, the presentation of floppy infant syndrome focuses on observing for the presence or absence of specific signs such as ‘frog-leg’ posture, significant head lag on traction or pull-to-sit maneuver, or the feeling of ‘slipping through the hands’ when the infant is held under the arms. Infantile botulism, transient neonatal myasthenia gravis, congenital myasthenia gravis, hypermagnesemia, and aminoglycoside toxicity are all neuromuscular junction disorders that are considered to be a differential diagnosis of floppy infant syndrome. These neuromuscular junction disorders ultimately impact the presence of acetylcholine within the neuromuscular junction. While some of these disorders may impact the acetylcholine receptors, others may cause a depletion within the end-plate anticholinesterase enzyme. A deficiency within the anticholinesterase deficiency may cause desensitization to acetylcholine, which could also cause present with floppy infant syndrome as well. Depending on the underlying causative disorder leading to the presence of floppy infant syndrome, the treatment will vary considerably. Treatment of the underlying causative syndrome resulting in the presentation of floppy infant syndrome deals with the symptoms of hypotonia, and as a result, the decreased muscle tone, diminished tendon reflexes, any feeding or respiratory difficulties diminish.

Transient neonatal myasthenia gravis following maternal myasthenia gravis presenting in pregnancy after treatment with Alemtuzumab

Abstract Ojectives Transient neonatal Myasthenia gravis is a postsynaptic neuromuscular junction disorder seen in 10–21% of infants born to mothers with myasthenia gravis. Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of multiple sclerosis. The possibility of developing Myasthenia gravis in a pregnant mother treated with Alemtuzumab is rare. Case presentation We report a case of transient neonatal myasthenia gravis following treatment with Alemtuzumab for multiple sclerosis in the mother. Conclusions Therapy with Alemtuzumab increases the risk of secondary autoimmune diseases including Myasthenia gravis.

MYASTHENIA GRAVIS: P.374Surrogacy prevents recurrence of fetal acetylcholine receptor inactivation syndrome

Fetal acetylcholine receptor inactivation syndrome (FARIS) is a recently recognized congenital myopathy due to in utero exposure to maternal acetylcholine receptor (AChR) antibodies directed against the fetal AChR. Unlike transient neonatal myasthenia gravis, FARIS extends well beyond the neonatal period. We review the literature, report the second case of FARIS born to an asymptomatic mother, and describe how surrogacy successfully prevented the development of FARIS. We describe a non-consanguineous couple whose first 3 pregnancies were complicated by FARIS. All 3 fetuses had polyhydramnios and arthrogryposis. Only one child survived the neonatal period, a term female born with weakness, respiratory and bulbar insufficiency. She improved markedly during childhood, but still has significant facial weakness. Extensive investigations in the siblings, including whole exome sequencing, were negative. The mother, who is completely asymptomatic for myasthenia gravis (MG), was then found to have elevated AChR antibodies, clinching the diagnosis of FARIS. This couple then had recourse to a surrogate, using their own ovum and sperm. Ultrasounds were normal. A female child was born at term, without any feature of FARIS. At 3 months, she is healthy and developing normally. We found 12 other FARIS cases from 6 different families. Only one other mother was asymptomatic for MG. Children who survive the neonatal period typically improve, but have persistent myopathic facies. The recurrence risk is extremely high. More aggressive MG treatment during pregnancy appears to lessen the severity, but does not prevent the development of FARIS. FARIS is a myopathy caused by in utero exposure to maternal AChR antibodies directed against the fetal AChR. Diagnosing FARIS is particularly challenging when the mother is not known for MG, but has important clinical implications for future pregnancies. Therefore, FARIS should be included in the differential diagnosis of congenital myopathies.

Frequency and risk factors for transient neonatal myasthenia

Frequency and risk factors for transient neonatal myasthenia

Intravenous immunoglobulin as monotherapy for myasthenia gravis during pregnancy

IntroductionPregnant women with myasthenia gravis (MG) are at increased risk of complications and adverse outcomes, including the teratogenic effects of many drugs used to treat MG women of childbearing age. The effectiveness of intravenous immunoglobulins (IVIg) on other autoimmune mediated diseases has been extensively reported in recent years, although little is known about the role of IVIg in the treatment of MG during pregnancy. We designed this study to determine the effectiveness of IVIg as monotherapy during pregnancy for women with MG. Material and methodsFive pregnant MG patients (mean age at delivery 36.4years, SD 5.8, range 29.4–45.2) were studied in 2013–14. Their treatment was switched to monthly IVIg cycles 2months before the pregnancy. Follow-up included monthly neurological QMG throughout the pregnancy and postpartum, obstetrical monitoring during monthly visits in the first two trimesters of the pregnancy, fortnightly visits between week 32 and week 36, and weekly visits after 36weeks, and neonatal follow-up after delivery. ResultsWe observed no exacerbations during pregnancy, delivery or post-partum. The mean QMG score at baseline (before pregnancy) was 7.4 points in five women with generalized forms of MG. The maximum mean value reached during pregnancy was 8.6 points. The mean pregnancy duration was 38 w+5 d. No infant with transient neonatal myasthenia gravis. ConclusionsThese results suggest that monotherapy with IVIg during pregnancy in MG patients could be promising, although confirmation is required in studies with larger populations.

Pediatric Myasthenia Gravis

Myasthenia gravis is a disorder of neuromuscular transmission that leads to fatigue of skeletal muscles and fluctuating weakness. Myasthenia that affects children can be classified into the following 3 forms: transient neonatal myasthenia, congenital myasthenic syndromes, and juvenile myasthenia gravis (JMG). JMG is an autoimmune disorder that has a tendency to affect the extraocular muscles, but can also affect all skeletal muscles leading to generalized weakness and fatigability. Respiratory muscles may be involved leading to respiratory failure requiring ventilator support. Diagnosis should be suspected clinically, and confirmatory diagnostic testing be performed, including serum acetylcholine receptor antibodies, repetitive nerve stimulation, and electromyography. Treatment for JMG includes acetylcholinesterase inhibitors, immunosuppressive medications, plasma exchange, intravenous immunoglobulins, and thymectomy. Children with myasthenia gravis require monitoring by a pediatric ophthalmologist for the development of amblyopia from ptosis or strabismus.

Clinical follow-up of pregnancy in myasthenia gravis patients

This study aimed to analyze the outcome and impact of pregnancy in women with myasthenia gravis (MG). Obstetric and clinical data were retrospectively analyzed before, during and after pregnancy. Predictors of outcome were studied. We included 35 pregnancies from 21 MG patients. In the course of MG symptoms in 30 pregnancies with live births, 50% deteriorated (mainly during the second trimester, p = 0.028), 30% improved, and 20% remained unchanged. The deterioration group had more frequent abnormal repetitive nerve stimulation (RNS) (p = 0.028) and lower myasthenia gravis composite (MGC) scores (p = 0.045) before pregnancy. The improvement group was associated with higher MGC scores (p = 0.012) before pregnancy. The no-change group was associated with longer duration of MG (p = 0.026) and normal RNS (p = 0.008) before pregnancy. The course of MG in the second pregnancy was different from that in the previous pregnancy in 65.3% of cases. Obstetric complications were reported in 20 pregnancies; the most common was preterm premature rupture of membranes (PPROM) (25.8%), and the most severe were abortion (11.4%) and fetal death (2.9%). Most of the patients delivered via caesarean section (66.7%). Spinal anesthesia was performed in 73.3%. Transient neonatal myasthenia gravis occurred in 12.9% of live-born infants, and no predictors were found. In conclusion, severity and duration of MG, RNS and treatment influence MG and pregnancy. Pregnant MG patients have greater rates of PPROM and caesarean delivery. Our data suggest that duration of MG, MGC and RNS before pregnancy may be useful in helping to predict the course of MG during pregnancy.

Pediatric Myasthenia Gravis: A Review

Myasthenia gravis refers to a group of diseases affecting the neuromuscular junction resulting in muscle weakness. The clinical hallmark of this condition is skeletal muscle weakness that worsens with sustained or repetitive muscle activation, caused via disruption of neuromuscular transmission by antibodies directed most commonly against the nicotinic acetylcholine receptor. Transient neonatal myasthenia gravis is caused by the crossing of antibodies from a myasthenic mother to her developing child, while juvenile myasthenia gravis involves the production of antibodies by the child's own immune system against neuromuscular junction components. Ptosis and extraocular muscle weakness are common presenting symptoms of juvenile myasthenia gravis and may be accompanied by, or progress to, generalized weakness. Diagnosis of myasthenia gravis relies on careful neurological examination, supported by additional diagnostic modalities which may include the patient's response to short-acting cholinesterase inhibitors, serum testing for causative antibodies, or electromyography. Management options include cholinesterase inhibitors for symptomatic treatment, immunosuppression with corticosteroids or steroid-sparing immunosuppressants, and thymectomy when a thymoma is identified on imaging.

Myasthenia gravis in pregnancy: Experience of a portuguese center.

We evaluated the clinical course during pregnancy and neonatal outcomes of a cohort of Portuguese women with myasthenia gravis (MG). Retrospective study. Twenty-five patients with 30 pregnancies were included. Mean maternal age was 32.4 ± 4.1 years. Miscarriage rate was 6.7%, with delivery of 28 newborns. Deterioration in MG during pregnancy occurred in 43.3%, and 46.4% occurred at postpartum. Eighty percent were medicated with pyridostigmine, 43.3% with corticosteroids, and 40% with intravenous immunoglobulin. There were no maternal or neonatal deaths. Mean gestational time at delivery was 38.2 weeks. No cases of fetal growth restriction, preeclampsia, preterm delivery, or fetal demise were observed. Global cesarean rate was 64.3%. Two newborns developed transient neonatal myasthenia. A high rate of clinical worsening of MG in the mother was observed in this retrospective study, which highlights the importance of a multidisciplinary approach for avoiding maternal adverse outcomes. Muscle Nerve 54: 715-720, 2016.

Neonatal Outcome in Pregnancies with Autoimmune Myasthenia Gravis

ABSTRACTIntroduction: Acquired autoimmune myasthenia gravis (MG) is an autoimmune process in which antibodies (AB) directed against the acetylcholine nicotinic receptor (AChR) cause weakness and fatigue of striated muscles. Objectives: The objective of this study was to determine the range of clinical manifestations in newborns with transient neonatal myasthenia (TNM). Methods: 62 newborns with mothers who had autoimmune MG were followed by: anthropometric parameters, gestational age, gender, type of delivery completion, Apgar score (AS) in the first and fifth minute, and the emergence of TNM symptoms. Results: For fourteen consecutive years, from a total of 98,000 infants, 62 (0.06%) were born to mothers with autoimmune MG. Four of them (6.4%) had symptoms of TNM. Conclusion: Newborns of mothers with MG manifest clinical features of TNM relative to stage of mother's illness. These newborns need monitoring until the seventh day of life.