A 21Zi-InOnLh-OId African American male infant was reported by his parents to have had 2 days of increasing irritability and decreasing oral intake. They had taken him to the emergency department the previous evening for evaluation of a runny nose and crankiness. He had been diagnosed as having a viral upper respiratory tract infection after he demonstrated the abilities to be fed and consoled. Overnight he was described as "restless and whiny." He continued to have rhinorrhea, but no fever, vomiting, or diarrhea was reported. His parents had not noticed any difficulties with breathing. Although taking less formula than usual, he was faring well with a commercial rehydration solution and had normal output of urine.
The infant had been born via an uncomplicated cesarean section after a full-term pregnancy, and had previously been thriving. He was receiving no medications, and had no hospitalizations or surgeries except for a peripartum circumcision.
In the emergency department, he was found to have a temperature of 37.8°C, a heart rate of 187 beats per minute, a respiratory rate of 42 breaths per minute, and a blood pressure of 87/65 mm Hg. The infant appeared tired but nontoxic, and he was easily consoled in his mother' s arms. An examination of his head was notable for clear nasal discharge and copious saliva. Mild intercostal retractions were evident, but there was no grunting or flaring. Auscultation revealed inspiratory stridor without crackles or expiratory wheezes. The heartbeat was regular and no murmur was heard. The abdomen was soft without any palpable masses. The extremities were warm, were well perfused, and had equal pulses. The infant moved all extremities symmetrically and had good tone. The hemoglobin oxygen saturation as measured by pulse oximetry was 100%. Chest and lateral neck radiographs were interpreted as displaying subglottic narrowing (the "steeple" sign), but there was no evidence of foreign body, lung consolidation, or abnormalities of the great arteries.
The most notable findings during this patient's physical examination were inspiratory stridor and intercostal retractions. The Latin word stridulus, from which stridor has been derived, refers to a whistling sound. As a physical sign, stridor is indicative of turbulent airflow through a partially obstructed extrathoracic airway.
One of the first determinations in the differential diagnosis of neonatal stridor is whether the respiratory ailment is congenital or acquired. The lack of previous symptoms of respiratory distress and normal results on examination of the lungs the preceding evening, combined with a seemingly viral respiratory tract prodrome, suggested that the infant suffered from croup. Historically, croup was a cattarhal syndrome of hoarse voice, barking cough, inspiratory stridor, and respiratory distress with several etiologies. During the early 20th century in the United States, diphtheria was the most common cause of this syndrome.1 The diagnosis of croup is now reserved almost exclusively for viral laryngotracheitis.2
Differential Diagnosis of Stridor\
Viral laryngotracheitis most commonly produces a croup syndrome in children between 1 and 6 years old, with a peak incidence of 5 cases per 100 children between 1 and 2 years old.3 Parainfluenza viruses account for most cases of croup, but adenovirus, respiratory syncytial virus, and influenza are also common etiologies.
Although most cases of viral croup are selflimited, corticosteroids and alpha-adrenergic agonists have been demonstrated to be beneficial therapies.2 This patient received two nebulized racemic epinephrine treatments by inhalation, and methylprednisolone was given intravenously without subsequent clinical improvement. The persistence of the airway obstruction and the young age of the patient necessitated a consideration of other diagnoses. It was presumed that the patient had a congenital, anatomic laryngotracheal obstruction worsened by concomitant upper respiratory tract infection. He was admitted to the pediatric intensive care unit.
As described previously, croup is the most common cause of acute stridor in children. Croup is rare in children younger than 6 months, and it is usually accompanied by upper respiratory tract symptoms, a barking cough, and low-grade fever. It is often most severe at night. Laryngomalacia is the most common cause of chronic stridor, and overall is the leading cause of stridor in neonates.4 A helpful diagnostic clue in the evaluation of stridor from laryngomalacia is that it generally worsens when the child is in the supine position. It may be underappreciated that vocal cord paralysis is the second most common cause of stridor in the neonatal period.5 Several anatomic, inflammatory, and other acquired causes of infantile stridor are presented in Table 1. It is comforting to note that active Haemophilus influenzae type b immunization has led to a major decline in the incidence of bacterial epiglottitis among children within the United States.6
The patient's clinical status deteriorated shortly after he was transferred to the intensive care unit. His respiratory distress worsened with severe inspiratory stridor and marked supraclavicular and intercostal retractions. He responded to strong tactile stimulation with facial grimacing and movement of his extremities. He remained afebrile, but became hypertensive with a blood pressure of 153/73 mm Hg. His anterior fontanelle was noted to be bulging.
Endotracheal intubation was performed and mechanical ventilatory support was provided. After administration of antibiotics, a lumbar puncture demonstrated grossly bloody cerebrospinal fluid with an opening pressure of 25 cm of water. Laboratory analysis was remarkable for a serum hemoglobin level of 10 g/dL with normal platelet and white blood cell counts. The partial thromboplastin time was remarkably prolonged to 91.4 seconds, but the prothrombin time of 11.7 seconds was within laboratory standards. There was no family history of bleeding disorders, and the patient had tolerated his circumcision without apparent complication.
Although there was no history of head injury, a computed tomography scan of the head demonstrated a large premedullary hematoma with compression of the medulla and cervicomedullary junction (Fig. 1). There was also an intraventricular hemorrhage within the third and the fourth ventricles with associated hydrocephalus. Quantification of factor VLTI found levels of less than 1% of what was expected. Recombinant factor VTJJ was added to the aggressive treatment of the patient's coagulopathy. After stabilization, laryngoscopic evaluation revealed bilateral vocal cord paralysis. Results of an ophthalmologic examination and skeletal radiographic survey were normal. On discharge to a neurorehabilitation center, the stridor was improved, with residual unilateral, left vocal cord paralysis. The infant was prescribed long-term recombinant factor VHI replacement and is now doing well.
The small caliber of the pediatric airway makes it vulnerable to obstruction. Stridor is a common malady in neonates and children, whose compliant airways are more susceptible to collapse than are those of adults. Evaluation of stridor requires careful consideration of the history, findings on physical examination, and perceived level of airway obstruction. Infants with abrupt onset of severe stridor merit emergent hospitalbased evaluation. In contrast/ nondistressed infants with chronic, mild stridor may be appropriate for evaluation in an outpatient setting.
Figure 1 . Computed tomography scan of the head demonstrating a premedullary hematoma, an intraventricular hemorrhage, and hydrocephalus.
Skilled examiners may learn to discern subtle differences in volume, pitch, and phase of stridor that provide clues to the degree and anatomic level of obstruction.7 Quiet stridor with good air movement is indicative of mild airway narrowing, whereas loud stridor with fair to good air movement indicates significant narrowing. Mild stridor, accompanied by poor air movement, may signify impending airway compromise. Highpitched stridor arises from the glottis. Lowpitched stridor typically arises from pharyngeal obstruction. Lesions at or above the glottis might produce inspiratory stridor, whereas biphasic stridor originates at or below the glottis.
Our patient had stridor due to vocal cord paralysis, the second most common cause of neonatal stridor. More than half of all cases of vocal cord paralysis present within the first 12 hours after birth, and most are recognized within the first 2 years.5 When found, vocal cord paralysis should be considered a physical sign rather than a diagnosis. Vocal cord paralysis is most frequently associated with malformations of the central nervous system, but is also often associated with other congenital anomalies (Table 2). The muscles of the larynx receive subcortical neuronal control, originating from the nucleus ambiguus in the medulla, by means of the vagus nerve (Fig. 2). The vagus nerve branches immediately beneath the skull to form the superior laryngeal nerve. The recurrent laryngeal nerve arises from the vagus in the thoracic cavity.
,We hypothesize that the vocal cord paralysis in our patient resulted from direct compression of the brain stem by a hematoma and increased intracranial pressure from obstructive hydrocephalus. The source of the intracranial hemorrhage in our patient was factor VIH deficiency. Therefore, we believe this to be the second reported case of an infant with stridor as the presenting sign of intracranial hemorrhage from hemophilia A. Fah and Tan detailed a similar presentation in an 11-day-old male neonate.8
Differential Diagnosis of Vocal Cord Paralysis
Figure 2. Anatomic innervation of the laryngeal musculature is supplied by the superior and recurrent laryngeal nerves that branch from the vagus nerve.
The incidence of intracranial hemorrhage in newborns with hemophilia is estimated to be 1% to 4%.9 In many cases, the bleeding may either begin or recur after 5 weeks of age.10 The precipitant for intracranial hemorrhage in infants with hemophilia is not certain, and Eyster et al. were unable to provide an etiology for 38% of 2,500 children and adults with hemophilia who had bleeding of the central nervous system.11 However, a proposed mechanism for intracranial hemorrhage in neonates with hemophilia is birth trauma.12 Our patient was delivered by cesarean section after a failure of progression in vaginal delivery. It seems that cesarean section might be a less traumatic method of delivering the head, but perhaps, in many circumstances, traumatic birthing becomes the reason for cesarean delivery.
Vocal cord paralysis is a common cause of stridor in infancy, and rarely occurs without associated abnormalities in anatomy or physiology. Therefore, stridor in infants should be thought of not only as a symptom of abnormalities of the airways or chest, but also as a possible harbinger of an abnormality of the central nervous system. Although the association between stridor and hemophilia is rare, this case illustrates the need for careful consideration of many factors and diseases when evaluating neonatal stridor.
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Differential Diagnosis of Stridor\
Differential Diagnosis of Vocal Cord Paralysis