Pediatric Annals

URGENT AND EMERGENT CASES WITH A TWIST 

Why So Sleepy?

Richard J Scarfone, MD; Amy L Puchalski, MD

Abstract

CASE PRESENTATION

A 5-month-old white female infant was brought to the emergency department with the chief complaints of decreased activity and poor feeding for 2 days. Five days prior to presentation, she had had clear rhinorrhea and a nonproductive, nonparoxysmal cough that had resolved after 4 days. On the morning of presentation, she had a single episode of nonbloody, nonbilious emesis. There was no diarrhea or fever noted at home. For 2 days, she had been increasingly sleepy and intermittently fussy, had not been rolling over or reaching for objects, and had shown little interest in breastfeeding. She had taken in only 6 ounces of formula and little breast milk in the past 24 hours and had decreased output of urine. There had been no known trauma and she had no known ill contacts. The only medication in the home was chlorpropamide, but it was kept out of reach of the infant and her 3-year-old brother.

The infant had had a normal spontaneous vaginal delivery. Her mother had been healthy throughout the pregnancy and had tested negative for group B streptococci. The infant's perinatal course was uncomplicated and she was discharged home on the second day of life. She had frequent episodes of regurgitating after feeding and had been diagnosed as having gastroesophageal reflux. She had not been treated with any medications and was thriving. Her development was normal and she had never been hospitalized. Her immunizations were up-to-date and she had no known allergies. The family and social histories were unremarkable. The infant's mother, who did not work outside of the home, was the principal caretaker.

On presentation, the infant's vital signs included a temperature of 37.7°C, a heart rate of 114 beats per minute, a respiratory rate of 32 breaths per minute, and a blood pressure of 90/60 mm Hg. She weighed 13 pounds, 14 ounces (40th percentile). An examination of the head revealed a flat anterior fontanelle without swelling or bruising of the scalp. Her pupils were 4 mm and reactive and her optic discs were not visualized. The tympanic membranes were erythematous and mobile and she had clear nares and oropharynx with moist mucous membranes. Her neck was supple without adenopathy.

An examination of the chest and lungs was unremarkable. A cardiovascular examination revealed strong pulses, normal perfusion, and a regular heart rhythm without murmurs. Her abdomen was soft and nondistended, and she cried during the abdominal examination. There were no abdominal masses or organomegaly. No stool was obtained on rectal examination and results of the genitourinary examination were within normal limits. Her skin was without bruising.

Her neurologic examination was notable for somnolence. She responded to voices by opening her eyes partially. She had an intact gag reflex and exhibited generalized floppiness with little spontaneous movement. Reflexes and cranial nerves were intact.

UfITIAL DIAGNOSIS

Given this infant's age, sleepiness, poor feeding, and episode of emesis, her pediatrician had sent her to the emergency department with a suspicion of intussusception.

DIFFERENTIAL DIAGNOSIS

The table includes a partial list of potential causes for somnolence and floppiness in an infant. High on the list of considerations are infectious processes, such as sepsis, meningitis, or encephalitis. The lack of fever and irritability in this patient made these diagnoses unlikely. Additionally, this patient had a subacute onset of illness during several days, whereas patients with serious infections would tend to have signs and symptoms more rapidly. Other symptoms that may characterize sepsis or meningitis include vomiting, seizures, respiratory distress, poor feeding, and inconsolability. Although it is prudent to have a low threshold to screen for infection in the infant presenting…

CASE PRESENTATION

A 5-month-old white female infant was brought to the emergency department with the chief complaints of decreased activity and poor feeding for 2 days. Five days prior to presentation, she had had clear rhinorrhea and a nonproductive, nonparoxysmal cough that had resolved after 4 days. On the morning of presentation, she had a single episode of nonbloody, nonbilious emesis. There was no diarrhea or fever noted at home. For 2 days, she had been increasingly sleepy and intermittently fussy, had not been rolling over or reaching for objects, and had shown little interest in breastfeeding. She had taken in only 6 ounces of formula and little breast milk in the past 24 hours and had decreased output of urine. There had been no known trauma and she had no known ill contacts. The only medication in the home was chlorpropamide, but it was kept out of reach of the infant and her 3-year-old brother.

The infant had had a normal spontaneous vaginal delivery. Her mother had been healthy throughout the pregnancy and had tested negative for group B streptococci. The infant's perinatal course was uncomplicated and she was discharged home on the second day of life. She had frequent episodes of regurgitating after feeding and had been diagnosed as having gastroesophageal reflux. She had not been treated with any medications and was thriving. Her development was normal and she had never been hospitalized. Her immunizations were up-to-date and she had no known allergies. The family and social histories were unremarkable. The infant's mother, who did not work outside of the home, was the principal caretaker.

On presentation, the infant's vital signs included a temperature of 37.7°C, a heart rate of 114 beats per minute, a respiratory rate of 32 breaths per minute, and a blood pressure of 90/60 mm Hg. She weighed 13 pounds, 14 ounces (40th percentile). An examination of the head revealed a flat anterior fontanelle without swelling or bruising of the scalp. Her pupils were 4 mm and reactive and her optic discs were not visualized. The tympanic membranes were erythematous and mobile and she had clear nares and oropharynx with moist mucous membranes. Her neck was supple without adenopathy.

An examination of the chest and lungs was unremarkable. A cardiovascular examination revealed strong pulses, normal perfusion, and a regular heart rhythm without murmurs. Her abdomen was soft and nondistended, and she cried during the abdominal examination. There were no abdominal masses or organomegaly. No stool was obtained on rectal examination and results of the genitourinary examination were within normal limits. Her skin was without bruising.

Her neurologic examination was notable for somnolence. She responded to voices by opening her eyes partially. She had an intact gag reflex and exhibited generalized floppiness with little spontaneous movement. Reflexes and cranial nerves were intact.

UfITIAL DIAGNOSIS

Given this infant's age, sleepiness, poor feeding, and episode of emesis, her pediatrician had sent her to the emergency department with a suspicion of intussusception.

DIFFERENTIAL DIAGNOSIS

The table includes a partial list of potential causes for somnolence and floppiness in an infant. High on the list of considerations are infectious processes, such as sepsis, meningitis, or encephalitis. The lack of fever and irritability in this patient made these diagnoses unlikely. Additionally, this patient had a subacute onset of illness during several days, whereas patients with serious infections would tend to have signs and symptoms more rapidly. Other symptoms that may characterize sepsis or meningitis include vomiting, seizures, respiratory distress, poor feeding, and inconsolability. Although it is prudent to have a low threshold to screen for infection in the infant presenting with changes in mental status, the likelihood in this patient was so low that such screening was not pursued.

Ingestions are a frequent explanation for changes in mental status in the pediatric population. Most ingestions occur in children 1 to 4 years old as unintentional overdoses and among adolescents intent on committing suicide.1 Ingestions are less common in young infants, but may be seen in the setting of child abuse or administration by an older sibling. Somnolence is a common sign of ingestion of barbiturates, benzodiazepines, opiates, anticholinergics, oral hypoglycemics, and ethanol. An evaluation of vital signs, pupillary size and reactivity, and bowel sounds are invaluable in establishing the presence of a specific "toxidrome." Barbiturates, benzodiazepines, and opiates usually cause respiratory depression or bradycardia and changes in mental status. Ingestions of opiates are also characterized by miosis. Conversely, anticholinergics cause tachycardia, hypertension, mydriasis, dry and warm skin, and coma. The lack of a history of ingestion or vital sign or pupillary abnormalities in this patient made ingestion an unlikely explanation.

Another consideration when assessing an infant with altered or depressed mental status is accidental head injury or inflicted trauma, such as shaken baby syndrome. Physicians must have a high index of suspicion for inflicted injury and should consider the diagnosis in infants who present with unexplained seizures, lethargy and vomiting, or difficulty breathing. The infant who appears "septic" and is afebrile may be a victim of physical abuse. Other than retinal hemorrhages, physical findings are nonspecific and may include apnea or bradycardia, a bulging fontanelle, contusions of the extremities, active seizing, or a focal neurologic examination. The absence of external evidence of abuse such as bruising or a scalp hematoma does not rule out this possibility. After initial stabilization, the diagnostic workup should include an examination of the retina for hemorrhages, a survey of the skeleton for fractures, and a computed tomography scan of the head for intracranial hemorrhages. Shaken baby syndrome was a definite consideration in this patient and plans were made to obtain a computed tomography scan of the head.

Table

TABLEDifferential Diagnosis of Somnolence

TABLE

Differential Diagnosis of Somnolence

Seizures can result in altered mental status and floppiness, both during and soon after the event. Infants with seizures are more likely to have an underlying anatomic or metabolic abnormality compared with older children or adults. Breathholding spells, which may be confused with seizures, typically occur in children 9 months or older. This infant did not have any risk factors for seizures, such as birth asphyxia, and had not had any witnessed clonic jerking of the arms or legs.

The most common metabolic derangement that afflicts infants is hypoglycemia, defined as a serum glucose level of less than 50 mg /L.1 The maintenance of serum glucose relies on homeostasis among the liver, the muscles, the brain, and the pancreas. Many illnesses can interfere with glucose metabolism, including sepsis, malignancy, inborn metabolic disorders, and liver failure, as can ingestion of salicylates, ethanol, or oral hypoglycemic agents. Urine ketones are usually present in infants with hypoglycemia, and their absence warrants investigation for hyperinsulinism or fatty acid oxidation defects. Infants with hypoglycemia may present with irritability, lethargy, poor feeding, tachycardia, and seizures. The physician should always perform a rapid bedside glucose assessment in an infant presenting with these symptoms and quickly provide dextrose intravenously if hypoglycemia exists.

A rare cause of neuromuscular weakness in infants is myasthenia gravis. Infants can acquire transient neonatal myasthenia gravis in which maternal antibodies to the acetylcholine receptor are transmitted across the placenta and interfere with neuromuscular junction transmission. On the other hand, congenital myasthenia gravis is either an autosomal dominant or a recessive disease that causes interruption of acetylcholine transfer across the neuromuscular junction by a variety of mechanisms.2,3

Myasthenia gravis classically presents with easy fatigability of muscles, manifesting as progressive weakness through the day. The cranial nerves are affected early on, leading to ptosis, ophthalmoplegia, swallowing dysfunction, and facial weakness. The sensory examination and deep tendon reflexes are unaffected. The diagnosis is made by observing the transient resolution of symptoms with the administration of an anticholinesterase, and also by electromyographic demonstration of fatigue with repetitive nerve stimuli. This patient did not have worsening symptoms during the day or abnormal cranial nerve findings.

Spinal muscular atrophy type I, also known as Werdnig-Hoffmann disease, is another infrequent cause of generalized weakness in infants, which may be perceived as an alteration in the level of consciousness. This autosomal recessive disease of the anterior horn cells initially presents with feeding difficulties,1,3'4 which was a symptom noted in our patient. The disease gradually progresses to flaccid paralysis, absent deep tendon reflexes, and lower cranial nerve dysfunction. Tongue fasciculations are a common finding on physical examination, whereas papillary and oculomotor functions are spared. WerdnigHoffmann disease is usually fatal by the age of 2 years.4 Normal reflexes and a lack of fasciculations in our patient made this diagnosis unlikely.

FINAL DIAGNOSIS

Further evaluation revealed that this patient had not had a bowel movement in 6 days. During the evaluation in the emergency department, it was noted that the infant had a weak cry. In this breastfed infant presenting with sleepiness and weakness, these findings raised the concern for infant botulism. Infant botulism is caused by Clostridium botulinum, a gram-positive, sporeforming anaerobic bacteria found in soil, honey, and home-canned foods. It produces one of seven serotypes of neurotoxin, with types A and B being responsible for clinical disease.5 The toxin irreversibly binds to the presynaptic neuron membrane and prevents exocytosis of acetylcholine, thus halting nerve conduction. It affects neurotransmission across ganglionic and postganglionic parasympathetic synapses and neuromuscular junctions. The bacteria can transiently colonize the gastrointestinal tract of susceptible infants and produce toxin that is absorbed systemically. It is the most potent toxin by weight but, fortunately, cannot cross the blood-brain barrier.23

Several epidemiologic factors help identify infants at risk for infant botulism. Geographically, 90% of the cases worldwide occur in North America and are seen almost exclusively in southeastern Pennsylvania, California, and Utah.1'5'6 Infants are generally younger than 6 months and the peak incidence is at 2 to 3 months of age.5"8 Infant botulism is most common in white infants from middle-class families, and there is often a history of increased exposure to soil through parental occupation or nearby construction.1'6'8 These findings implicate spores in soil as the mode of transmission to the patient's gastrointestinal tract. Interestingly, mere is a tendency for victims of infant botulism to be breastfed.1'6'7'9 One hypothesis is that the introduction of new foods to a breastfed infant alters the gastrointestinal flora in a way that favors growth of C. botulinum.6 Also, honey may contain C. botulinum spores and should be avoided for children younger than 12 months.

Typically, constipation is the first sign of infant botulism, although this is often elicited in retrospect from the parents. A few days later, symmetric, descending weakness begins to develop, which may manifest as poor feeding, a weak suck or cry, and ptosis or facial weakness. Parents may also describe the infant as either lethargic or irritable. There is rarely a history of fever. On physical examination, the infant may be alert or sleepy with diminished spontaneous movement, a weak cry, poor gag and suck, sluggish pupillary reactivity, ophthalmoplegia, and flaccid weakness with diminished deep tendon reflexes. The patient may also show signs of autonomic instability, respiratory depression, or dehydration. Symptoms are usually present 1 week prior to admission, peak 2 to 3 weeks after onset, and gradually resolve in the next 1 to 3 weeks. The average length of hospitalization is 5 to 6 weeks.1'6'7,9

The management of infant botulism is primarily supportive. Patients frequently need ventilatory support for respiratory failure. Case series document that anywhere from 20% to 85% of patients require intubation.6-8 Nutrition supplementation and nasogastric or nasojejunal tube feedings are necessary in 70% to 90% of patients.6"8 Other potential complications of infant botulism include syndrome of inappropriate secretion of antidiuretic hormone, pneumonia, urinary tract infections, autonomic instability, tachypnea, bradycardia, seizures, and sudden death. Aminoglycosides may potentiate the neuromuscular blockade of the botulism toxin and thus should be avoided in patients with suspected botulism infection. Studies assessing the efficacy of botulism irnmunoglobulin are under way to determine its ability to shorten the length of supportive care and hospitalization required.

The gold standard of diagnosis is the recovery of the organism or toxin from the infant's stool. This process may take days to weeks to complete, so the diagnosis is typically a clinical one, although supporting data can be obtained from an electromyogram. The classic pattern of infant botulism is brief duration, small amplitude motor unit potentials. High-voltage, repetitive stimuli give a "staircase phenomenon" with incremental response.5'6

This infant was hospitalized with a presumptive diagnosis of infant botulism. Within 24 hours, she had stopped feeding, no longer had a gag reflex, and had worsening hypoventilation. One week into the hospitalization, botulinum toxin was identified in her stool, establishing the diagnosis as infant botulism. She required a ventilator for 3 weeks and made a full and complete recovery after discharge from the hospital.

LESSONS LEARNED

This case illustrates the importance of a comprehensive medical history in establishing a diagnosis. In this era of unprecedented advances in medical technology, it is often a meticulous clinical evaluation that uncovers an unsuspected diagnosis. This child was referred to the emergency department by her pediatrician because of decreased activity, poor feeding, and a concern for intussusception. Lethargy is certainly a common presenting complaint among children with intussusception, although its etiology is unclear.10 The initial differential diagnosis was a broad one and may have led to many expensive and painful diagnostic tests such as a computed tomography scan of the head, skeletal survey, lumbar puncture, and toxicology screen, and also to unnecessary therapeutic interventions such as the administration of broad-spectrum antibiotics.

A careful evaluation revealed that this 5month-old breastfed infant was not demonstrating motor skills such as rolling or reaching, had been constipated, was floppy, and had a weak cry. Thus, although it is rare, infant botulism emerged as the most likely diagnosis. Other diagnoses became so unlikely that it was not necessary to pursue them.

REFERENCES

1. Fleisher GR, Ludwig S. Textbook of Pediatric Emergency Medicine, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000.

2. Anlar B, Ozdirim E, Rend Y, et al. Myasthenia gravis in childhood. Acta Paediatr. 1996;85:838-842.

3. Swaiman KF. Pediatric Neurology- Principles and Practice, 2nd ed. St. Louis, MO: Mosby; 1994.

4. Russman BS, Schwartz RC. Neuromuscular diseases of childhood. Curr Opin Pediatr. 1993;5:669-674.

5. Faucheux RC, Shetty AK, Cowan GS. Infant botulism. Clin Pediatr (Philo). 1997,36:591-594.

6. Long SS, Gajewski JL, Brown LW, Gilligan PH. Clinical, laboratory, and environmental features of infant botulism in Southeastern Pennsylvania. Pediatrics. 1985;75:935-941.

7. Schreiner MS, Field E, Ruddy R. Infant botulism: a review of 12 years' experience at the Children's Hospital of Philadelphia. Pediatrics. 1991;87:159-165.

8. Thompson JA, Glasgow LA, Warpinski JR, Olson C. Infant botulism: clinical spectrum and epidemiology. Pediatrics. 1980;66:936-942.

9. Glatman-Freedman A. Infant botulism. Pediatr Rev. 19%; 17:185-186.

10. Heldrich FJ. Lethargy as a presenting symptom in patients with intussusception. Clin Pediatr (Phila). 1986; 25:363-365.

TABLE

Differential Diagnosis of Somnolence

10.3928/0090-4481-20011001-11

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