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Neonatal myasthenia gravis: Specific advantages of repetitive stimulation over edrophonium testing
Neonatal Myasthenia Gravis: Specific Advantages of Repetitive Stimulation Over Edrophonium Testing Ross M. Hays, MD and Linda J. Michaud, MD
A premature infant with neonatal myasthenia gravis is presented to illustrate the utility of electrodiagnosis. The patient, born to a mother with myasthenia gravis, suffered additional problems, including hypoxia and subependymal hemorrhage which potentially contributed to hypotonia and poor respiratory effort, thus complicating the diagnosis. Standard testing with edrophonium originally was negative which cast doubt on the diagnosis; however, a repetitive motor nerve stimulation test demonstrated a significant decremental response which was consistent with neonatal myasthenia gravis. This decremental response was corrected following intravenous infusion of edrophonium. In the newborn with suspected myasthenia gravis, repetitive motor nerve stimulation may be a more reliable diagnostic procedure than the more frequently recommended pharmacologic tests. Use of this electrodiagnostic procedure in combination with pharmacologic testing may improve diagnostic accuracy in the premature infant and lead to earlier treatment.
Hays RM, Michaud LJ. Neonatal myasthenia gravis: Specific advantages of repetitive stimulation over edrophonium testing. Pediatr Neurol 1988;4:245-7.
Introduction
Transient neonatal myasthenia gravis is a potentially life-threatening, but self-limited, disorder [1-3]. Accurate diagnosis will dictate appropriate supportive management From the Department of Rehabilitation Medicine; Children's Hospital and Medical Center; University of Washington School of Medicine; Seattle, Washington.
[1,4,5]. Diagnostic measures used in adults may not be applicable to newborns. Selection of the most appropriate diagnostic study may improve the accuracy of the diagnosis in patients for whom transient neonatal myasthenia may be only one of many problems. Case Report This 2,616 gm male infant was 10ore at 34 weeks gestation to a 33year-old primigravida mother with known myasthenia gravis. The mother had been diagnosed as having generalized myasthenia gravis at approximately 4 weeks gestation. She had presented with a 6 month history of gradual loss of facial muscle strength, intermittent diplopia, dysphagia with occasional choking episodes, and a 6 kg weight loss. She had a marked increase in strength in neck musculature and in chewing following the injection of edrophonium intravenously (0.2 mg). Electrodiagnostic evaluation included a repetitive stimulation test at slow and fast stimulation rates which was negative at the ulnar motor nerve but positive at the accessory nerve. The decremental response between the first and fifth evoked potentials was 45% with slow stimulation; it increased to 52% with post-tetanic exhaustion. Acetylcholine receptor antibody titers, as well as anti-thyroid antibodies, were normal. During the sixth month of gestation, acetylcholine receptor (AChR) blocking and modulating antibody titers were obtained which also were normal. Treatment was initiated with pyridostigmine bromide, 150 mg daily in 3 divided doses. After pulmonary function testing revealed impaired pulmonary mechanics, prednisone was administered; the dose was gradually increased to 50 mg/day. Pregnancy was diagnosed at 7 weeks gestation, 3 weeks after initiation of treatment. An attempt was made to decrease pyridostigmine to 15 mg 3-4 times daily, with an intent to decrease the dosage to the lowest effective level during pregnancy. Prednisone was decreased to an everyother-day schedule. The mother experienced good control of symptoms with pyridostigmine bromide (50-60 mg daily) throughout most of the pregnancy; the medication dosage was gradually reduced and discontinued by 16 days prior to delivery. Fetal movements were reported to be normal throughout the pregnancy. Spontaneous vaginal delivery with low forceps under epidural anesthesia was complicated by a double nuchal cord. Apgar scores were 2 at 1 min and 4 at 5 min. No respiratory effort was observed during the first minute of life; the infant was intubated and ventilated with subsequent improvement in color and the onset of spontaneous respiration. Initial examination otherwise was remarkable for marked hypotonicity and a paucity of movement. Muscle bulk was normal. No fasciculations were observed. Deep tendon reflexes were diminished. Weak suck, absent gag reflex, and increased oropharyngeal secretions were evident. The chest was somewhat bell-shaped. After a brief period in which good respiratory effort was sustained, the infant was extubated. He quickly became cyanotic, was reintubated, and mechanical ventilation was reinstituted. This acute decompensation warranted full resuscitation, evaluation of possible sepsis, and presumptive antibiotic treatment. Initial cranial ultrasound revealed a small left subependymal hemorrhage. The infant continued to demonstrate poor tone with limited spontaneous movement, increased oropharyngeal secretions, weak gag with suctioning, and shallow respiratory efforts. Antibiotics were discontinued after 72 hours when cultures proved sterile. In view of the maternal history, the infant underwent edrophonium testing on the second day of life. Respiratory parameters were chosen to monitor the response to anticholinesterase medication. Edrophonium was injected intramuscularly (0.1 mg/kg) during transcutaneous moni-
Communications should be addressed to: Dr. Hays; Department of Rehabilitation Medicine; Children's Hospital and Medical Center; 4800 Sand Point Way NE; EO. Box C-5371; Seattle, WA 98105. Received March 25, 1988; accepted Jane 30, 1988.
Hays and Michaud: Neonatal Myasthenia Gravis
245
1;
I
t
,
|
~
.
~
;
!
A
B
Figure 1. (A) Repetitive stimulation of the median motor nerve with supramaximal stimulus intensity at a rate of 3 Hz demonstrated a decremental response of 23% between the first and fifth responses. (B ) A 10 rain rest period followed to eliminate any possibility of post-exercise facilitation. Edrophonium was infused intravenously (0.15 mg/kg). Repetitive stimulation within 120 sec of infusion revealed complete repair of the decremental response.
toring of CO2; no change from baseline values was detected in response to anticholinesterase administration. A second trial on the same day with a second dose of edrophonium administered intravenously (0.1 mg/kg) also demonstrated no clinical improvement. With the negative response to this trial of anticholinesterase medication, neonatal myasthenia gravis was believed to be unlikely. Other conditions were considered: asphyxia, primary central nervous system abnormality, or other peripheral neuromuscular disorders, including congenital myopathy, myotonic dystrophy, or anterior horn cell disease. Electrodiagnosis was performed on the tenth day of life. Repetitive stimulation of the peroneal motor nerve at supramaximal stimulus intensities and a rate of 3 Hz demonstrated a decremental response of 20% between the first and fifth responses. Monopolar needle examination of multiple muscles at rest was normal with no evidence of spontaneous activity or abnormal repetitive discharges; assessment of recruitment could not be obtained. These results were believed to be highly suggestive of neonatal myasthenia gravis. Pyridostigmine was administered (6.7 mg/kg/day). There was no clinical improvement in either respiratory status or muscular activity. At 20 days of age, repeat electrodiagnostic testing was performed becausme of poor response to pyridostigmine which was discontinued 48 hours prior to the examination. Repetitive stimulation of the median motor nerve with supramaximal stimulus intensity at a rate of 3 Hz demonstrated a decremental response of 23% between the first and fifth responses (Fig 1A). A 10 min rest period followed to eliminate the possibility of post-exercise facilitation. Edrophonium was infused intravenously (0.15 mg/kg). Repetitive stimulation within 120 sec of infusion revealed complete repair of the decremental response (Fig 1B). The in,rant was once again administered pyridostigmine with an increase in the dose to 8 mg/kg/day. Three days later, at 27 days of age, the infant was successfully weaned from assisted ventilation with subsequent acceptable transcutaneous CO2 levels and capillary blood gases. He began to nipple feed on the following day. A marked increase in spontaneous activity was observed in the first 24-48 hours following the increase in pyridostigmine. The infant, weighing 3,405 gm, was discharged at 41 days of age on pyridostigmine therapy; respiratory effort, suck, tone, and activity level all were virtually normal.
Discussion Transient neonatal myasthenia gravis was first described by Stricknoot et al. in 1942 [6]. Approximately 10-15% of infants bom to mothers with autoimmune-acquired myasthenia gravis are affected. Antibody titers directed against AChR were reported to be the best indicator of neonatal
246
PEDIATRIC NEUROLOGY
Vol. 4 No. 4
myasthenia gravis onset in 1 study of 30 children with myasthenic mothers [7]. Anti-AChR antibodies are detected in 80-90% of patients with myasthenia gravis; the transient form of neonatal myasthenia gravis in infants born to women with this disease is believed due to transplacental transfer of these antibodies [8]. It has been suggested that AChR-antibody-negative myasthen~a gravis is distinct physiologically and immunologically and may be caused by antibodies to neuromuscular junction determinants other than AChR [9]. Transient neonatal myasthenia gravis in our patient was associated with transplacental transfer of AChR-antibody-negative serum [10]. Muscular weakness often is present within the fn'st 72 hours of birth. The average duration of symptoms is 18 days [2], although much longer courses have been reported [ 11]. Poor feeding is the most common presentation; 70% have generalized weakness and hypotonia which may progress to life-threatening respiratory compromise. With adequate supportive treatment and anticholinesterase medication, the prognosis is excellent [2]. Diagnosis of myasthenia gravis in adults may be determined with a variety of studies: electrophysiologic testing, repetitive motor nerve stimulation, and single fiber electromyography. Pharmacologic evaluations include the edro® phonium (Tensilon) and curare sensitivity tests. Sensory examinations include audiometric testing and oculography [1,4]. In infants, only edrophonium and repetitive nerve stimulation tests are practical. Neonatology texts often recommend edrophonium as the test of choice [12]; at least one author reports edrophonium testing to be "uniformly accurate for diagnosis" [2]. In the newborn with multiple problems, edrophonium alone may not be as sensitive as repetitive nerve stimulation. The usual measures used to monitor improved neuromuscular transmission in the edrophonium test (e.g., muscle strength, eye opening, ventilatory effort)are difficult to evaluate, especially quantitatively, in the newborn. These observations are further complicated when there are other causes of hypotonia and hypoventilation, such as neonatal asphyxia, prematurity, and subependymal hemor-
rhage demonstrated in our patient. Repetitive stimulation of motor nerves by an electrodiagnostician familiar with infants is a more objective measurement. The relative instability of the myoneural junction in newborn and premature infants may diminish the accuracy of post-exercise facilitation and exhaustion but will have no effect on the classic finding of decremental responses at low stimulation rates [3,13]. In our patient, repetitive motor nerve stimulation was positive when carefully performed and monitored edrophonium tests were not. The combination of edrophonium and repetitive stimulation provided further confirmation of the diagnosis. Repetitive motor nerve stimulation is a simple bedside examination with little risk and essentially no long-term side effects. In certain circumstances, such as the sick newbom with suspected myasthenia gravis, it may be a more accurate diagnostic procedure than frequently recommended pharmacologic tests. The combination of electrodiagnostic examination and pharmacologic testing possibly will improve the accuracy of the diagnosis even further. The small size of the patient and immaturity of the nervous system need not preclude the use of this electrodiagnostic evaluation. Although the specific defect at the neuromuscular junction in AChR-antibody-negative neonatal myasthenia gravis is unknown, repetitive stimulation proved reliable in both the mother and neonate in our report. In view of recent reports of successful treatment of affected neonates with exchange transfusion [14], improved accuracy of the diagnosis may lead to provision of earlier treatment.
References
[1] Drachman DB. Myasthenia gravis. N Engl J Med 1978;298:13642, 186-93. [2] Fenichel GM. Clinical syndromes of myasthenia in infancy and childhood. Arch Neurol 1978;35:97-103. [3] Namba T, Brown SB, Grob D. Neonatal myasthenia gravis: Report of two cases and review of the literature. Pediatrics 1970; 45:488-504. [4] Patten BM. Myasthenia gravis: Review of diagnosis and management. Muscle Nerve 1978; 1:190-205. [5] Snead OC, Benton JW, Dwyer D, et al. Juvenile myasthenia gravis. Neurology 1980;30:732-9. [6] Stricknoot FL, Schaeffer RL, Bergo HL. Myasthenia gravis occurring in an infant born to a myasthenic mother. J Am Med Assoc 1942; 120:1207-11. [7] Morel E, Eymard B, Vernet-der Garabedian B, Pannier C, Dulac O, Bach JF. Neonatal myasthenia gravis: A new clinical and immunologic appraisal on 30 cases. Neurology 1988;38:138-42. [8] Levinson AI, Zweiman B, Lisak RP. Immunopathogenesis and treatment of myasthenia gravis. J Clin Immunol 1987;7:187-97. [9] Mossman S, Vincent A, Newsom-Davis J. Myasthenia gravis without acetylcholine-receptor antibody: A distinct disease entity. Lancet 1986;1:116-9. [10] Melber D. Maternal-fetal transmission of myasthenia gravis with acetylcholine-receptor antibody. N Engl J Med 1988;318:996. [11]- Branch CE, Swift TF, Dyken PR. Prolonged neonatal myasthenia gravis: Electrophysiological studies. Ann Neurol 1978;3:416-8. [12] Levy HL. Miscellaneous inborn errors of metabolism. In: Avery ME, Taeusch HW Jr, eds. Diseases of the newborn, 5th ed. Philadelphia: WB Saunders, 1984;556. [13] Koenigsberger MR, Patten B, Lovelace RE. Studies of neuromuscular function in the newborn: A comparison of myoneural function in the full term and the premature infant. Neuropaediatrie 1973; 4:350-61. [14] Pasternak JF, Hageman J, Adams A, Philip AGS, Gardner TH. Exchange transfusion in neonatal myasthenia. J Pediatr 1981;99:644-6.
Hays and Michaud: Neonatal Myasthenia Gravis 247
A premature infant with neonatal myasthenia gravis is presented to illustrate the utility of electrodiagnosis. The patient, born to a mother with myasthenia gravis, suffered additional problems, including hypoxia and subependymal hemorrhage which potentially contributed to hypotonia and poor respiratory effort, thus complicating the diagnosis. Standard testing with edrophonium originally was negative which cast doubt on the diagnosis; however, a repetitive motor nerve stimulation test demonstrated a significant decremental response which was consistent with neonatal myasthenia gravis. This decremental response was corrected following intravenous infusion of edrophonium. In the newborn with suspected myasthenia gravis, repetitive motor nerve stimulation may be a more reliable diagnostic procedure than the more frequently recommended pharmacologic tests. Use of this electrodiagnostic procedure in combination with pharmacologic testing may improve diagnostic accuracy in the premature infant and lead to earlier treatment.
Hays RM, Michaud LJ. Neonatal myasthenia gravis: Specific advantages of repetitive stimulation over edrophonium testing. Pediatr Neurol 1988;4:245-7.
Introduction
Transient neonatal myasthenia gravis is a potentially life-threatening, but self-limited, disorder [1-3]. Accurate diagnosis will dictate appropriate supportive management From the Department of Rehabilitation Medicine; Children's Hospital and Medical Center; University of Washington School of Medicine; Seattle, Washington.
[1,4,5]. Diagnostic measures used in adults may not be applicable to newborns. Selection of the most appropriate diagnostic study may improve the accuracy of the diagnosis in patients for whom transient neonatal myasthenia may be only one of many problems. Case Report This 2,616 gm male infant was 10ore at 34 weeks gestation to a 33year-old primigravida mother with known myasthenia gravis. The mother had been diagnosed as having generalized myasthenia gravis at approximately 4 weeks gestation. She had presented with a 6 month history of gradual loss of facial muscle strength, intermittent diplopia, dysphagia with occasional choking episodes, and a 6 kg weight loss. She had a marked increase in strength in neck musculature and in chewing following the injection of edrophonium intravenously (0.2 mg). Electrodiagnostic evaluation included a repetitive stimulation test at slow and fast stimulation rates which was negative at the ulnar motor nerve but positive at the accessory nerve. The decremental response between the first and fifth evoked potentials was 45% with slow stimulation; it increased to 52% with post-tetanic exhaustion. Acetylcholine receptor antibody titers, as well as anti-thyroid antibodies, were normal. During the sixth month of gestation, acetylcholine receptor (AChR) blocking and modulating antibody titers were obtained which also were normal. Treatment was initiated with pyridostigmine bromide, 150 mg daily in 3 divided doses. After pulmonary function testing revealed impaired pulmonary mechanics, prednisone was administered; the dose was gradually increased to 50 mg/day. Pregnancy was diagnosed at 7 weeks gestation, 3 weeks after initiation of treatment. An attempt was made to decrease pyridostigmine to 15 mg 3-4 times daily, with an intent to decrease the dosage to the lowest effective level during pregnancy. Prednisone was decreased to an everyother-day schedule. The mother experienced good control of symptoms with pyridostigmine bromide (50-60 mg daily) throughout most of the pregnancy; the medication dosage was gradually reduced and discontinued by 16 days prior to delivery. Fetal movements were reported to be normal throughout the pregnancy. Spontaneous vaginal delivery with low forceps under epidural anesthesia was complicated by a double nuchal cord. Apgar scores were 2 at 1 min and 4 at 5 min. No respiratory effort was observed during the first minute of life; the infant was intubated and ventilated with subsequent improvement in color and the onset of spontaneous respiration. Initial examination otherwise was remarkable for marked hypotonicity and a paucity of movement. Muscle bulk was normal. No fasciculations were observed. Deep tendon reflexes were diminished. Weak suck, absent gag reflex, and increased oropharyngeal secretions were evident. The chest was somewhat bell-shaped. After a brief period in which good respiratory effort was sustained, the infant was extubated. He quickly became cyanotic, was reintubated, and mechanical ventilation was reinstituted. This acute decompensation warranted full resuscitation, evaluation of possible sepsis, and presumptive antibiotic treatment. Initial cranial ultrasound revealed a small left subependymal hemorrhage. The infant continued to demonstrate poor tone with limited spontaneous movement, increased oropharyngeal secretions, weak gag with suctioning, and shallow respiratory efforts. Antibiotics were discontinued after 72 hours when cultures proved sterile. In view of the maternal history, the infant underwent edrophonium testing on the second day of life. Respiratory parameters were chosen to monitor the response to anticholinesterase medication. Edrophonium was injected intramuscularly (0.1 mg/kg) during transcutaneous moni-
Communications should be addressed to: Dr. Hays; Department of Rehabilitation Medicine; Children's Hospital and Medical Center; 4800 Sand Point Way NE; EO. Box C-5371; Seattle, WA 98105. Received March 25, 1988; accepted Jane 30, 1988.
Hays and Michaud: Neonatal Myasthenia Gravis
245
1;
I
t
,
|
~
.
~
;
!
A
B
Figure 1. (A) Repetitive stimulation of the median motor nerve with supramaximal stimulus intensity at a rate of 3 Hz demonstrated a decremental response of 23% between the first and fifth responses. (B ) A 10 rain rest period followed to eliminate any possibility of post-exercise facilitation. Edrophonium was infused intravenously (0.15 mg/kg). Repetitive stimulation within 120 sec of infusion revealed complete repair of the decremental response.
toring of CO2; no change from baseline values was detected in response to anticholinesterase administration. A second trial on the same day with a second dose of edrophonium administered intravenously (0.1 mg/kg) also demonstrated no clinical improvement. With the negative response to this trial of anticholinesterase medication, neonatal myasthenia gravis was believed to be unlikely. Other conditions were considered: asphyxia, primary central nervous system abnormality, or other peripheral neuromuscular disorders, including congenital myopathy, myotonic dystrophy, or anterior horn cell disease. Electrodiagnosis was performed on the tenth day of life. Repetitive stimulation of the peroneal motor nerve at supramaximal stimulus intensities and a rate of 3 Hz demonstrated a decremental response of 20% between the first and fifth responses. Monopolar needle examination of multiple muscles at rest was normal with no evidence of spontaneous activity or abnormal repetitive discharges; assessment of recruitment could not be obtained. These results were believed to be highly suggestive of neonatal myasthenia gravis. Pyridostigmine was administered (6.7 mg/kg/day). There was no clinical improvement in either respiratory status or muscular activity. At 20 days of age, repeat electrodiagnostic testing was performed becausme of poor response to pyridostigmine which was discontinued 48 hours prior to the examination. Repetitive stimulation of the median motor nerve with supramaximal stimulus intensity at a rate of 3 Hz demonstrated a decremental response of 23% between the first and fifth responses (Fig 1A). A 10 min rest period followed to eliminate the possibility of post-exercise facilitation. Edrophonium was infused intravenously (0.15 mg/kg). Repetitive stimulation within 120 sec of infusion revealed complete repair of the decremental response (Fig 1B). The in,rant was once again administered pyridostigmine with an increase in the dose to 8 mg/kg/day. Three days later, at 27 days of age, the infant was successfully weaned from assisted ventilation with subsequent acceptable transcutaneous CO2 levels and capillary blood gases. He began to nipple feed on the following day. A marked increase in spontaneous activity was observed in the first 24-48 hours following the increase in pyridostigmine. The infant, weighing 3,405 gm, was discharged at 41 days of age on pyridostigmine therapy; respiratory effort, suck, tone, and activity level all were virtually normal.
Discussion Transient neonatal myasthenia gravis was first described by Stricknoot et al. in 1942 [6]. Approximately 10-15% of infants bom to mothers with autoimmune-acquired myasthenia gravis are affected. Antibody titers directed against AChR were reported to be the best indicator of neonatal
246
PEDIATRIC NEUROLOGY
Vol. 4 No. 4
myasthenia gravis onset in 1 study of 30 children with myasthenic mothers [7]. Anti-AChR antibodies are detected in 80-90% of patients with myasthenia gravis; the transient form of neonatal myasthenia gravis in infants born to women with this disease is believed due to transplacental transfer of these antibodies [8]. It has been suggested that AChR-antibody-negative myasthen~a gravis is distinct physiologically and immunologically and may be caused by antibodies to neuromuscular junction determinants other than AChR [9]. Transient neonatal myasthenia gravis in our patient was associated with transplacental transfer of AChR-antibody-negative serum [10]. Muscular weakness often is present within the fn'st 72 hours of birth. The average duration of symptoms is 18 days [2], although much longer courses have been reported [ 11]. Poor feeding is the most common presentation; 70% have generalized weakness and hypotonia which may progress to life-threatening respiratory compromise. With adequate supportive treatment and anticholinesterase medication, the prognosis is excellent [2]. Diagnosis of myasthenia gravis in adults may be determined with a variety of studies: electrophysiologic testing, repetitive motor nerve stimulation, and single fiber electromyography. Pharmacologic evaluations include the edro® phonium (Tensilon) and curare sensitivity tests. Sensory examinations include audiometric testing and oculography [1,4]. In infants, only edrophonium and repetitive nerve stimulation tests are practical. Neonatology texts often recommend edrophonium as the test of choice [12]; at least one author reports edrophonium testing to be "uniformly accurate for diagnosis" [2]. In the newborn with multiple problems, edrophonium alone may not be as sensitive as repetitive nerve stimulation. The usual measures used to monitor improved neuromuscular transmission in the edrophonium test (e.g., muscle strength, eye opening, ventilatory effort)are difficult to evaluate, especially quantitatively, in the newborn. These observations are further complicated when there are other causes of hypotonia and hypoventilation, such as neonatal asphyxia, prematurity, and subependymal hemor-
rhage demonstrated in our patient. Repetitive stimulation of motor nerves by an electrodiagnostician familiar with infants is a more objective measurement. The relative instability of the myoneural junction in newborn and premature infants may diminish the accuracy of post-exercise facilitation and exhaustion but will have no effect on the classic finding of decremental responses at low stimulation rates [3,13]. In our patient, repetitive motor nerve stimulation was positive when carefully performed and monitored edrophonium tests were not. The combination of edrophonium and repetitive stimulation provided further confirmation of the diagnosis. Repetitive motor nerve stimulation is a simple bedside examination with little risk and essentially no long-term side effects. In certain circumstances, such as the sick newbom with suspected myasthenia gravis, it may be a more accurate diagnostic procedure than frequently recommended pharmacologic tests. The combination of electrodiagnostic examination and pharmacologic testing possibly will improve the accuracy of the diagnosis even further. The small size of the patient and immaturity of the nervous system need not preclude the use of this electrodiagnostic evaluation. Although the specific defect at the neuromuscular junction in AChR-antibody-negative neonatal myasthenia gravis is unknown, repetitive stimulation proved reliable in both the mother and neonate in our report. In view of recent reports of successful treatment of affected neonates with exchange transfusion [14], improved accuracy of the diagnosis may lead to provision of earlier treatment.
References
[1] Drachman DB. Myasthenia gravis. N Engl J Med 1978;298:13642, 186-93. [2] Fenichel GM. Clinical syndromes of myasthenia in infancy and childhood. Arch Neurol 1978;35:97-103. [3] Namba T, Brown SB, Grob D. Neonatal myasthenia gravis: Report of two cases and review of the literature. Pediatrics 1970; 45:488-504. [4] Patten BM. Myasthenia gravis: Review of diagnosis and management. Muscle Nerve 1978; 1:190-205. [5] Snead OC, Benton JW, Dwyer D, et al. Juvenile myasthenia gravis. Neurology 1980;30:732-9. [6] Stricknoot FL, Schaeffer RL, Bergo HL. Myasthenia gravis occurring in an infant born to a myasthenic mother. J Am Med Assoc 1942; 120:1207-11. [7] Morel E, Eymard B, Vernet-der Garabedian B, Pannier C, Dulac O, Bach JF. Neonatal myasthenia gravis: A new clinical and immunologic appraisal on 30 cases. Neurology 1988;38:138-42. [8] Levinson AI, Zweiman B, Lisak RP. Immunopathogenesis and treatment of myasthenia gravis. J Clin Immunol 1987;7:187-97. [9] Mossman S, Vincent A, Newsom-Davis J. Myasthenia gravis without acetylcholine-receptor antibody: A distinct disease entity. Lancet 1986;1:116-9. [10] Melber D. Maternal-fetal transmission of myasthenia gravis with acetylcholine-receptor antibody. N Engl J Med 1988;318:996. [11]- Branch CE, Swift TF, Dyken PR. Prolonged neonatal myasthenia gravis: Electrophysiological studies. Ann Neurol 1978;3:416-8. [12] Levy HL. Miscellaneous inborn errors of metabolism. In: Avery ME, Taeusch HW Jr, eds. Diseases of the newborn, 5th ed. Philadelphia: WB Saunders, 1984;556. [13] Koenigsberger MR, Patten B, Lovelace RE. Studies of neuromuscular function in the newborn: A comparison of myoneural function in the full term and the premature infant. Neuropaediatrie 1973; 4:350-61. [14] Pasternak JF, Hageman J, Adams A, Philip AGS, Gardner TH. Exchange transfusion in neonatal myasthenia. J Pediatr 1981;99:644-6.
Hays and Michaud: Neonatal Myasthenia Gravis 247