Case 1: Apnea and Hypotonia in a 1-month-old Infant.

Abstract

A 33-day-old male twin presents with apnea. He was delivered at 34.3 weeks by a 30-year-old gravida 6 para 4, aborta 1 woman with negative serologic findings. Her prenatal course was complicated by maternal urinary tract infection treated with antibiotics. The neonate was delivered vaginally at 34.3 weeks and required a 12-day stay in the NICU to establish feedings before being sent home. During the week leading up to apnea at home, he was found to have congestion, increased drooling, and decreased stools. He was feeding less and required syringe feedings. On the day of presentation he was found to have apnea requiring cardiopulmonary resuscitation. He was brought to the children’s hospital emergency department. All other review of symptoms was negative.In the emergency department, the infant is noted to have global hypotonia with weak cry, diminished suck, and grasp reflexes. The rest of the examination findings are normal. He has another episode of apnea and bradycardia requiring intubation and admission to the NICU. During his NICU stay, he remains globally hypotonic with no purposeful movements or reflexes.Differential diagnosis for an infant with hypotonia is broad, including congenital myopathies, neuromuscular disease, metabolic disease, central nervous system disorders, connective tissue disease, and infection.During his NICU stay, he remained globally hypotonic with no purposeful movements or reflexes. He received an extensive evaluation for hypotonia. An evaluation for infection, including respiratory viral panel, blood, urine, and cerebrospinal fluid culture, was negative. Antibiotics were discontinued after 48 hours given the negative cultures. Comprehensive metabolic panel and thyroid studies were all within normal range. Cerebrospinal fluid neurotransmitters were remarkable for low free γ-aminobutyric acid. Urine toxicology screen was positive for lidocaine. Imaging including computed tomography of the head and skeletal survey were all within normal limits. Brain and spine magnetic resonance imaging with spectroscopy was remarkable for symmetric increased T2 signal within the cord corresponding to lateral corticospinal tracts. Electroencephalography showed nonspecific encephalopathy with discontinuous immature pattern. Electromyography showed global prolonged onset motor response and severely decreased amplitude and moderately decreased conduction velocity. Repetitive stimulation of nerves was unable to be completed because of minimal motor responses. Given the history of congestion, constipation followed by descending paralysis, and negative findings on evaluation, clinical suspicion for infant botulism became high, and it was arranged for the infant to receive infant botulism immunoglobulin (BabyBIG) before stool toxin test result was obtained. Within a week of receiving BabyBIG, the infant’s tone markedly improved. He underwent extubation 1 week after the administration of BabyBIG and began tolerating full oral feeds. He was discharged from the hospital tolerating full feeds by mouth and with mild hypertonia that later spontaneously resolved in follow-up clinic. Stool toxin tests later had a positive result for botulinum toxin B and small amounts of botulinum toxin F.Infant botulism is a rare but life-threatening condition caused by a neurotoxin released from Clostridium botulinum, which is classified as a spore-forming, obligate anaerobic gram-positive bacillus. The neurotoxin inhibits the cholinergic neuromuscular junctions of striated and smooth muscles as well as tear, salivary, and sweat glands; this leads to symptoms of generalized weakness, constipation, and inability to tolerate secretions, often confused for upper respiratory symptoms in children. There are 8 different known botulism toxins, toxins A through H. Toxins A, B, E, and rarely, F, G, and H cause human disease. Toxin F is known to have a rapid onset, whereas the others have a more insidious onset. The toxins can be found in foods such as honey or canned items and dust or soil worldwide. The toxin can be acquired through eating contaminated foods, breathing contaminated dust, puncture wounds, or injection drugs with contaminated needles. To diagnose the disease, a high clinical suspicion is needed and the California Department of Health can be contacted for dispersion of BabyBIG. A stool sample should be sent for the toxin, but results take time, and treatment with BabyBIG should not be delayed if the clinical history fits with the signs of botulism. BabyBIG acquired from California does not include immunoglobulins against toxin F; therefore, if no improvement is seen with California’s BabyBIG, the Centers for Disease Control and Prevention can be contacted to inquire for botulinum toxin F immunoglobulins with cases with a positive stool sample. A clinical response to the immunoglobulins should be seen within 1 week, with complete recovery seen within 2 to 3 weeks. This is in contrast to spontaneous resolution in a period of 6 weeks to months over the natural history of the disease if patients remain on life-sustaining support, mainly respiratory support. BabyBIG therapy therefore can decrease morbidity, costs, and mortality.