TRANSIENT NEONATAL MYASTHENIA GRAVIS (TNMG)
Mothers with autoimmune MG have a 15% incidence of having babies with TNMG despite the finding that all infants born to seropositive mothers have circulating acetylcholine receptor (AChR) antibodies. These normally cross the placenta, entering the fetal circulation to bind at fetal NMJs. Once an affected mother has one TNMG infant, her subsequent babies are likely to be affected.
TNMG infants sometimes have weak fetal movements, display fetal distress during delivery, or severe hypotonia shortly after birth. Other manifestations include facial diplegia, poor suck/feeding, a weak cry, intermittent cyanosis (especially during feeding), and respiratory weakness and/or failure. Muscle stretch reflexes, sphincter function, and sensation are preserved. Ptosis and external ophthalmoplegia are paradoxically less frequent than in juvenile MG. Typically, symptoms are transient, lasting 3 to 12 weeks.
Transient improvement after injection of 0.1 mg/kg of edrophonium supports this diagnosis; however, this is often difficult to assess with a ventilated neonate; not all affected infants respond, and a response does not distinguish TNMG from some forms of CMS. The presence of AChR antibodies provides the definitive diagnostic study when the clinical setting fits. Once delivered, the maternal AChR antibodies are no longer pathogenic even within breast milk. Supportive treatment is the primary therapeutic modality and is necessary until symptoms clear. Acetylcholinesterase inhibitors such as pyridostigmine or neostigmine methylsulfate may be helpful. Both intervenous immune globulin (IVIG) and exchange transfusion provide other therapeutic alternatives.
INFANTILE BOTULISM (IB)
This rare disorder typically occurs in previously healthy infants between the third and sixth months of life, particularly in the Mid-Atlantic states, Utah, and California, although it is occasionally seen in other regions. Clostridium botulinum is an obligatory anaerobic gram-positive spore-forming rod-shaped bacterium that is ubiquitous within the immature gut. It releases a toxin affecting presynaptic ACh release from the NMJ. In economically developed settings, this is the most common form of human botulism. The normal intestinal microflora changes when formula, sometimes honey, and/or solid foods are introduced into the diet. Sometimes this may enhance the ability of C. botulinum to colonize the infant’s colon. This is not a contagious disease.
Infantile botulism usually has a fairly stereotyped clinical presentation. Typically, a previously healthy infant, between ages 10 days and 6 months develops acute hypotonia, generalized weakness, poor feeding secondary to bulbar dysphagia, and poor suck that impairs nursing; also, there sometimes is a potentially life-threatening respiratory crisis. Aspiration often leads to hospitalization of an alert, afebrile, nonirritable infant with poorly reactive pupillary light reflexes, ophthalmoparesis, symmetric facial bulbar weakness, and generalized hypotonia. The mother often notes in retrospect that her baby is constipated—has not “stooled” with normal frequency. The face is typically expressionless, drooling, and there may be a high-pitched, mewing cry. Infantile botulism needs consideration in the differential diagnosis of unexplained respiratory distress in any baby up to 6 months old.
Electromyography is the diagnostic study of choice; rapid repetitive motor nerve stimulation (20 or 50 Hz) of infants with IB demonstrates significant incremental responses (23%-313%). This is in keeping with a presynaptic defect in neuromuscular transmission, with the area that the toxin specifically affects essentially blocking the release of acetylcholine. The botulinum toxin and the Clostridium organism are recoverable from stool.
Treatment primarily is supportive, often with acute intubation. Human-derived botulinum immune globulin (BIG) is beneficial when administered within the first 3 days. Antitoxin per se is not used for infantile botulism because of the possible risk of anaphylaxis. Early aggressive supportive care will ensure that these children all have an excellent outcome.
CONGENITAL MYASTHENIA SYNDROMES (CMS)
CMSs are a group of widely differing, rare familial NMTDs, each characterized by compromised NMT safety margins leading to fatigable weakness.
These genetically determined “myasthenic” disorders usually manifest during the first years of life. Clinically, ptosis and extraocular weakness are often more subtle than in juvenile myasthenia gravis (JMG). In addition, bulbar, neck, and extremity weakness occur sometimes with a restricted distribution.
Respiratory distress leading to sudden death occurs rarely in one CMS, namely end-plate choline acetyltransferase deficiency. These infants develop unexpected episodic attacks of apnea associated with bulbar paralysis occurring precipitously during excitement, exertion, febrile events, or without a known precipitating factor. Some babies have fluctuating ptosis, poor suck and cry, feeding difficulty, and secondary respiratory infections.
EMGs demonstrate a decremental response similar to JMG; this may be restricted to certain muscles and present intermittently.
Cholinesterase inhibitors provide a primary treatment option and may be lifesaving.
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