Neonatal Myasthenia Gravis Research Articles

Transient Neonatal Myasthenia Gravis in a Baby Born to a Mother With New-Onset Anti-MuSK-Mediated Myasthenia Gravis

We describe a 30-year-old pregnant woman with undiagnosed weakness who delivered a severely weak neonate. Subsequent workup of the mother revealed myasthenia gravis with muscle-specific kinase antibodies. The infant responded to intravenous immunoglobulin and symptoms normalized. He was presumed to have an anti-muscle-specific kinase-mediated transient neonatal myasthenia gravis.

Transient Neonatal Myasthenia Gravis Revealing a Myasthenia Gravis and a Systemic Lupus Erythematosus in the Mother: Case Report and Review of the Literature

Transient neonatal myasthenia gravis (TNMG) and neonatal lupus are rare conditions due to the transplacental passage of antibodies. We describe a unique case of TNMG, revealing a myasthenia gravis (MG) associated with systemic lupus erythematosus (SLE) in the mother. J. M., 8 days of age, was admitted for jaundice. Examination revealed poor sucking, facial weakness, and hypotonicity. TNMG was confirmed with a high level of antiacetylcholine receptor antibodies in the infant and his mother. No sign of neonatal lupus was observed. Clinical recovery was obtained. The elder brother had autism. In case of previous maternal MG, a low percentage of infants develop TNMG (10 to 20%), but monitoring is required at birth. Improvement is usually obtained within 3 weeks. No correlation has been found between maternal symptoms, antibodies titer, and signs of TNMG. Most cases of neonatal lupus are associated with positive anti-SSA/SSB antibodies in the mother. Both conditions, MG and SLE, are reported, but pregnancies are very few. Autism in the brother focuses on its relationship with immune diseases.

FETAL ACETYLCHOLINE RECEPTOR INACTIVATION SYNDROME AND MATERNAL MYASTHENIA GRAVIS

The fetal acetylcholine receptor (AChR) is present until 33 weeks gestation, when the fetal (γ) subunit is replaced by the adult (e) subunit. Most infants of myasthenic mothers are asymptomatic despite intrauterine exposure to AChR antibodies (AChR Ab). A higher fetal to adult AChR Ab ratio can lead to transient neonatal myasthenia gravis (TNMG) in 10–15% of infants or rarely to arthrogryposis multiplex congenita (AMC). Here we report three brothers with facial diplegia, highly arched palate, velopharyngeal incompetence, conductive hearing loss, and cryptorchidism. The maternal fetal AChR Ab were elevated. We propose the term fetal acetylcholine receptor inactivation syndrome and suggest this phenotype results from inactivation of the fetal subunit during a critical period of fetal muscle development. ### Case report. A 33-year-old woman developed ptosis, facial weakness, generalized fatigue, and elevated AChR Ab (>1,000, normal <0.4). Thymectomy, pyridostigmine, prednisone, and plasmapheresis improved her symptoms. Subsequently, she had three successive pregnancies with polyhydramnios and normal fetal movements while continuing prednisone. Each son was born at term by C-section with no respiratory distress. During her first pregnancy, the mother received no plasmapheresis. At birth, the infant (figure, A) had hypotonia, poor suck, and inability to swallow. He remained in the neonatal intensive care unit (NICU) with TNMG for 5 weeks and improved with IV immunoglobulin (IVIg) and nasogastric (NG) tube feedings. At 5 years he has microcephaly, facial diplegia with inability to close mouth …

Neonatal myasthenia gravis: antigenic specificities of antibodies in sera from mothers and their infants

Transient neonatal myasthenia gravis (MG) is a human model of passively transferred MG. In an effort to understand the characteristics of the most pathogenic antibodies in MG, we studied the fine antigenic specificities of anti-AChR antibodies in sera from 21 MG mothers (nine of which had transiently transferred the disease) and 17 of their infants. Although in a few cases significant differences in antibody specificities were observed between mothers and infants, whether myasthenic or not, generally the antigenic specificities of the antibodies in sera from infants were very similar to those of their mothers. Furthermore, no characteristic differences were detected between the antibody repertoires of mothers who transferred the disease and those who did not.

Severe neonatal myasthenia due to maternal anti-MuSK antibodies

Anti-MuSK antibodies have been reported in about 40–50% of patients with seronegative myasthenia gravis. Curiously, this condition has never been reported in association with fetal or transient neonatal myasthenia gravis, despite a known female predominance. We report the case of a 22-year-old woman who developed seronegative, mild steroid-responsive myasthenia gravis. When aged 26, she gave birth to a baby boy with neonatal myasthenia gravis characterized by hypotonia, stridor and sucking difficulties. Intubation was required for a few weeks. Anti-MuSK antibodies were assessed and found positive in both patients. Progressive hydramnios during the last trimester, with a decrease in spontaneous fetal mobility in the last weeks, long-lasting stridor, ptosis and occasional difficulties in swallowing liquids till two years of age, despite anti-MuSK antibodies becoming negative, suggest a fetal onset. The possible pathophysiology of this disorder, based on recent findings on the expression and function of MuSK protein, is reviewed.

ISOLATED FACIAL AND BULBAR PARESIS: A PERSISTENT MANIFESTATION OF NEONATAL MYASTHENIA GRAVIS

The differential diagnosis of congenital facial and bulbar paresis in toddlers includes myotonic dystrophy, congenital myopathies, congenital myasthenic syndromes, Moebius syndrome, and 22q11 deletion syndrome. We report on a 6-year-old boy with a history of neonatal hypotonia and severe feeding difficulties followed by persistent isolated facial and bulbar paresis of unknown etiology. When he was 3 years old, his mother was diagnosed with myasthenia gravis (MG) and we concluded that his condition was a rare and persistent manifestation of neonatal MG. ### Case reports. The boy presented with neonatal hypotonia and poor spontaneous movements without respiratory distress or arthrogryposis. Sucking was absent; he was tube fed for 2 weeks. His tone progressively improved; he walked at 13 months but prominent facial weakness and feeding difficulties persisted. He was referred to us at 30 months with severe dysarthria. There was no complaint of fatigue or weakness. At age 5 his weight was 10 kg (<p3), his height was 86 cm (p3), and he had no ptosis or ophthalmoplegia. He had facial weakness, a constantly open mouth, and a high arched palate (figure). The soft palate was immobile and speech was extremely nasal and dysarthric. The tongue was normal. He could not whistle or blow his cheeks. Limb muscle strength and …

Can neonatal myasthenia gravis be predicted?

To determine any association between history of mothers with myasthenia gravis (MG) and the occurrence of neonatal myasthenia gravis (NMG). The prospective study involved pregnant women with MG and their newborns delivered in our center throughout the nine-year period. The study included 16 newborns with NMG and 33 healthy newborns without symptoms of NMG. Their outcome was evaluated in relation to the duration of the illness (<5, 5-10, >10 years) and maternal therapy (no therapy, mestinon, corticosteroid, or combination of the two). The duration of maternal illness and type of therapy were not predictive of neonatal outcomes (P=0.159, and P=0.578, respectively). The duration of illness and therapy of women with MG do not correlate with manifestation of NMG and do not predict which pregnancies would result in an affected child. Because of possible severe, unpredictable, and life threatening NMG, these births should be carried out in a tertiary birth center.

Juvenile form of myasthenia gravis presenting as recurrent pulmonary infection with atelectasis

Myasthenia gravis (MG), a chronic disease characterized by unusual fatigability of voluntary muscles, was first described by Willis. Three forms of MG are seen in childhood: juvenile MG, congenital MG and transient neonatal MG. Aside from age of onset, there is no difference in terms of pathology and pathogenesis between juvenile MG and adult-onset MG. Juvenile MG, like adult MG, appears to result from T-cell-initiated antibodies directed against end-plate Ach receptor protein. The onset of juvenile myasthenia can be insidious, although at times it is rapid, often a sequel to an acute febrile illness. Generally, muscles innervated by the cranial nerves are affected first, with bilateral ptosis being the most common presenting sign. Generalized weakness and dysphagia are less common presenting symptoms, while the clinical course is highly variable.

Outcome of myasthenia gravis mothers and their infants.

The aim of this retrospective study was to assess neonatal outcomes of pregnant women with myasthenia gravis (MG). Pregnant women with MG who were treated in our hospital over an 8-year period were enrolled. Data relating to the course of the mother's MG (including the anti-acetylcholine receptor antibody (anti-AchR) titer and drug dosage), delivery mode, delivery course, puerperium period, and neonatal outcomes were obtained from the medical records. Twelve women with MG had 13 pregnancies in our hospital from January 1997 to December 2005. None of the mothers needed intensive care. Two patients delivered vaginally, and ten delivered by cesarean section. Fourteen infants were born at an average gestational age of 37.2 +/- 2.0 weeks; their average birth weight was 2838.6 +/- 724.2 g. Two neonates (14.2%) had a congenital anomaly. Transitory neonatal myasthenia gravis (NMG) was diagnosed in one infant (7.1%). In our study, MG exacerbations occurred in 38.5% of the patients. Postpartum, all MG patients experienced deterioration except one patient who deteriorated in the first trimester with a concomitant upper airway tract infection. Only 1 of the 14 neonates developed transient NMG; the incidence of transient NMG was lower than that previously reported. There was no correlation between the occurrence of NMG and the maternal anti-AChR titer. The cesarean section rate was approximately 33%; this high rate of elective cesarean sections in these MG patients could have prevented the occurrence of some of the complications related to vaginal delivery.

Myasthenia gravis in pregnancy and birth: identifying risk factors, optimising care

Women with myasthenia gravis (MG) have increased risk of pregnancy complications and an adverse pregnancy outcome. This study examined risk factors for such complications in order to improve the care for pregnant MG women. Through the Medical Birth Registry of Norway, 73 MG mothers with 135 births were identified. Their obstetrical and clinical records were examined. Data on pregnancy, delivery and the newborn were combined with information on mother's disease. The risk for neonatal MG was halved if the mother was thymectomized (P = 0.03). Children with neonatal MG were more likely to display signs of foetal distress during delivery (P = 0.05). Only in one-third of the pregnancies did the patient see a neurologist during pregnancy. These patients used MG medication more often during pregnancy (P = 0.001), and were more likely to be thymectomized (P = 0.007). They also had a higher rate of elective sections (P = 0.009). Thymectomy may have a protective effect against neonatal MG. Neonatal MG can cause foetal distress during delivery. Most MG women benefit from being examined by a neurologist during pregnancy, to minimize risks and select the best delivery mode in collaboration with obstetricians.

Artrogryposis multiplex congenita - a rare fetal condition caused by maternal myasthenia gravis

To look at the occurrence of arthrogryposis multiplex congenita in newborn of mothers with myasthenia gravis (MG) and factors connected to this. We retrospectively studied 176 births by 79 MG mothers, recorded in the Medical Birth Registry of Norway (MBRN). Four (2.2%) newborns (including one pair of twins) born with severe skeletal anomalies were identified. All four children died. Three had findings consistent with arthrogryposis multiplexa congenita (AMC), one had a fetal akinesia deformation sequence (FADS). The mother of the child with FADS had previously given birth to a child with neonatal MG. She was now in complete MG remission. The mother of the twins with AMC later gave birth to a child with neonatal MG. Siblings of an affected child -- either with neonatal MG or AMC -- have an increased risk to develop either neonatal MG or AMC. As this appears to be independent of the MG mother's clinical state, it is important to discuss previous pregnancy outcomes with all female MG patients.

Myasthénie auto-immune et grossesse : évolution clinique, accouchement et post-partum

To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital. Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis. During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies. Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.

MIASTENIA GRAVIS: EMBARAZO E IMPACTO PERINATAL

SUMMARY A total of 19 pregnancies in 9 patients with myasthenia gravis are analyzed. Two exacerbations of myasthenia gravis were observed. One associated to the use of aminoglycosides to treat an acute pyelonephritis. A debut of myasthenia gravis occurred during the 24th week of gestation. There were three cases of neonatal myasthenia gravis that appeared in the same patient, two newborn died after 29 and 25 days respectively, in spite of treatment. One case of preterm childbirth was observed and six cases (35%) of intrauterine growth retardation.

Myasthenia gravis and pregnancy: clinical implications and neonatal outcome

BackgroundThe myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients.MethodsTo describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome.ResultsFrom January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11%) had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39%) had clinical worsening of the condition of 9 other patients (50%) remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns.ConclusionsThe clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population.

Pediatric myasthenia gravis and velopharyngeal incompetence

Objective: To determine the clinical course of velopharyngeal incompetence in children with myasthenia gravis (MG). Methods: A 30-year retrospective study was performed using the medical records of 538 children who presented with velopharyngeal inadequacy (VPI) to a tertiary care academic pediatric center. Children with velopharyngeal incompetence due to myasthenia gravis were identified and their clinical courses were reviewed. Results: Four children were identified with velopharyngeal incompetence associated with myasthenia gravis. All four children required intervention for improvement of speech intelligibility. A speech prosthesis was the uniform intervention. Conclusion: Neonatal myasthenia gravis patients should be followed long-term as symptoms may recur as speech impairment. In addition, a high index of suspicion for this entity is required for early diagnosis due to the highly variable presentation and clinical course.

Myasthenia Gravis in Pregnancy: Report on 69 Cases

Obstetrical & Gynecological Survey 58(3):p 156-157, March 2003. | DOI: 10.1097/01.OGX.0000055745.76455.47

Myasthenia gravis in pregnancy: report on 69 cases

Objective: To review our experience with pregnancies in women with myasthenia gravis (MG). Study design: Sixty nine pregnancies among 65 women with MG patients managed by our department over 28 years were included. The course of the disease in pregnancy, mode of delivery and postpartal period were evaluated. Results: One pregnancy miscarried. In 15% of patients the MG deteriorated in pregnancy a further 16% in the puerperium. 17% of pregnancies were delivered by cesarean section, one due to myasthenia exacerbation. All women with puerperal infections developed exacerbations. One neonatal death, not attributable to myasthenia, was recorded. Transitory neonatal myasthenia gravis (TNMG) was diagnosed in 30% infants. Its incidence was inversely associated with maternal disease duration ( P<0.05). Newborns of thymectomized mothers showed lower rate of neonatal myasthenia compared to those of non-thymectomized women ( P<0.05). Conclusions: MG patients can have normal pregnancy and delivery but the course is unpredictable. Shorter disease history and infection predispose to puerperal exacerbation. Maternal thymectomy lessens the likelihood of neonatal myasthenia. An interdisciplinary approach is required for managing the pregnant women with MG.

Myasthénie et grossesse: l'atteinte du nouveau-né peut être révélatrice

Myasthenia gravis, an autoimmune disease of young women, is due to the dysfunction of neuromuscular transmission. The newborn of a myasthenic mother inconstantly presents a transitory neonatal myasthenic syndrome. Maternal aggravation, or even myasthenic crisis with respiratory failure, can occur in the first three months post-partum. Mrs. S., para two without appreciable medical history, delivered normally a boy weighing 4 kg with an Apgar score of 10/10. At 3 h of life the newborn was admitted to the neonatal care unit for grunting and axial hypotonia. Diagnoses of maternal-fetal infection and fetal distress were excluded. The dissociated pattern of neurological disorders (refusal to drink, axial hypotonia, hypomimia, but good contact and normal alertness) led to search for neuromuscular causes or poison. Myasthenia gravis was then considered and confirmed by maternal electromyography, allowing the diagnosis of transient neonatal myasthenia gravis and early diagnosis and treatment of the maternal myasthenic crisis in a specialized care unit. The outcome of both mother and child was favorable under treatment. Lack of maternal myasthenia gravis history should not result in excluding the diagnosis of transitory neonatal myasthenia gravis when evocative neonatal neurological signs are present. The symptomatology in the newborn may indeed reveal maternal myasthenia gravis, allowing an early diagnosis in both the mother and the newborn.

Failure of intravenously administered immunoglobulin in the treatment of neonatal myasthenia gravis

Neonatal myasthenia gravis is uncommon and life threatening. We describe the use of intravenously administered immunoglobulin, in addition to conventional modalities, in a neonate with severe neonatal myasthenia gravis. However, despite this aggressive management, the child had a prolonged period of weakness requiring intensive care. (J Pediatr 1999;134:233-5)

Course and treatment of myasthenia gravis during pregnancy.

To evaluate the influence of myasthenia gravis (MG) on pregnancy and potential treatment risks for infants and mothers. MG frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Knowledge of the potential effects of 1) pregnancy on the course of MG and 2) the use of immunosuppressive drugs during pregnancy is limited, rendering decision-making difficult for both patient and physician. We studied 47 women who became pregnant after the onset of MG. Immunosuppressive drugs were administered when MG symptoms were not controlled with anticholinesterases. Sixty-four pregnancies resulted in 55 children and 10 abortions. During pregnancy, MG relapsed in 4 of 23 (17%) asymptomatic patients who were not on therapy before conception; in patients taking therapy, MG symptoms improved in 12 of 31 pregnancies (39%), remained unchanged in 13 (42%), and deteriorated in 6 (19%). MG symptoms worsened after delivery in 15 of 54 (28%) pregnancies. Anti-acetylcholine receptor antibody (anti-AChR ab) was positive in 40 of 47 mothers and was assayed in 30 of 55 newborns; 13 were positive and 5 of 55 (9%) showed signs of neonatal MG (NMG). All affected babies were seropositive. Pregnancy does not worsen the long-term outcome of MG. The course of the disease is highly variable and unpredictable during gestation and can change in subsequent pregnancies. The occurrence of NMG does not correlate with either maternal disease severity or anti-AChR antibody titer. Immunosuppressive therapy, plasmapheresis, and i.v. human immunoglobulins can be administered safely if needed.