Nontraumatic atlantoaxial rotary subluxation in the pediatric otolaryngology patient. A report of four cases.

Nontraumatic atlantoaxial rotary subluxation (NAARS) is a relatively uncommon entity, with inconsistent presentations. It most commonly follows infectious processes or operative procedures. We present our experience with 4 pediatric otolaryngology patients with NAARS who were treated at the University of Iowa Hospitals and Clinics during a 2-year period beginning in 1997. A review of the symptoms, physical findings, and radiographic abnormalities is presented. Treatment options, varying from muscle relaxants to surgical fusion, are discussed. A high index of suspicion in evaluating children with a stiff neck or pain on attempted motion is essential in order to facilitate prompt diagnosis and appropriate intervention.

Response of the cricothyroid and thyroarytenoid muscles to stereotactic injection of substance P into the region of the nucleus tractus solitarius in developing dogs.

Substance P (SP), a putative sensory neurotransmitter, mediates reflex laryngeal adductor activity in developing dogs. Such reflex activity includes life-threatening laryngospasm induced by stimulation of distal esophageal afferent nerves. The site of SP's activity is unknown. This research was undertaken to determine whether injection of SP into the nucleus tractus solitarius (NTS) of developing beagles alters laryngeal adductor motor activity. Six animals, 57 to 78 days of age, underwent stereotactic injection of 5 to 10 microL of SP into the region of the NTS, identified by electrical stimulation of the ipsilateral superior laryngeal nerve. In 8 additional studies, SP was injected into the cerebellum (2) or brain stem (6) distant from the NTS. Cardiovascular and electromyographic (EMG) responses of the diaphragm and the cricothyroid (CT) and/or thyroarytenoid (TA) muscles were recorded in all 6 animals. Injection of SP into the region of the NTS induced a decrease in blood pressure in all animals and an increase in either ipsilateral CT or TA activity. Three of these animals experienced mixed apnea characterized by sustained EMG activity (spasm) of the ipsilateral CT or TA muscles and an absence of diaphragm EMG activity. The apnea event was fatal in 1 of these animals. In the 6 animals who underwent injections in the brain stem but outside the region of the NTS, diaphragm and laryngeal EMG activity generally did not change after injection of SP, with the exception of 1 animal who experienced a mild, short-lived increase in ipsilateral CT activity. A brief phasic increase in ipsilateral CT activity was seen in both animals who underwent injection of SP into the cerebellum. A putative sensory neurotransmitter, SP evokes ipsilateral CT and/or TA EMG activity when injected into the region of the NTS in developing beagle dogs. This research suggests that SP in the NTS may play a role in mediating life-threatening laryngeal adductor reflexes in developing mammals and may provide important information regarding therapeutic intervention.

Value of pH probe testing in pediatric patients with extraesophageal manifestations of gastroesophageal reflux disease: a retrospective review.

Extended pH probe testing is often performed in patients believed to have extraesophageal symptoms of gastroesophageal reflux disease (GERD), although for this indication its diagnostic value is not well established. A retrospective review of all patients who underwent pH probe testing between 1994 and 1998 was conducted to determine the outcome of antireflux therapy in the subgroup with probable extraesophageal symptoms of GERD. Sixty-eight patients underwent antireflux therapy and had adequate follow-up after pH probe testing to be included in the study. Fifty-eight patients (85%) responded to antireflux therapy (improved, 44%; cured, 41%). The positive predictive value of distal pH probe testing was greater than 90%, but the negative predictive value was less than 50%. The reproducibility of pH probe testing on different study days was poor, but pH probe testing was helpful in assessing the adequacy of antireflux therapy. The presence of gastrointestinal symptoms did not correlate with the response of extraesophageal symptoms to antireflux therapy. Thirteen patients underwent double-probe pH studies. The mean percent time the pH was less than 4 in the upper esophagus was 2.6% (range, 1% to 9.6%). Twelve of these patients were improved or cured with antireflux therapy. Distal pH probe testing is of limited benefit in predicting whether patients with extraesophageal symptoms of GERD will respond to antireflux therapy. If extraesophageal symptoms of GERD are suspected, patients should undergo an empiric trial of antireflux therapy. Distal pH probe testing should be reserved for assessing the adequacy of antireflux therapy if symptoms persist. A prospective, randomized, controlled study will aid in determining the predictive value of double-probe pH studies in pediatric patients with probable extraesophageal symptoms of GERD.

Pathogenesis and treatment of juvenile onset recurrent respiratory papillomatosis.

Juvenile onset recurrent respiratory papillomatosis is the most common cause of laryngeal tumors in children. This disease is caused by infection of the human papillomavirus, a virus whose complete genetic structure is now known. New, more directed agents show promise for improved control of papillomatosis in preliminary studies. Concurrently, there is an increasing awareness of methods to reduce surgical morbidity. At present, the role of preventive efforts including elective caesarian section remains uncertain.

Laryngomalacia and its treatment.

OBJECTIVE: To determine 1) airway outcome of infants with laryngomalacia who do not undergo routine direct laryngoscopy (DL) and bronchoscopy (B), 2) the age at resolution of laryngomalacia, and, 3) outcome of supraglottoplasty as a function of the type of laryngomalacia and the presence of concomitant disease. STUDY DESIGN: Retrospective chart review. METHODS: The records of all infants diagnosed with laryngomalacia by flexible fiberoptic laryngoscopy (FFL) between 1990 and 1998 in the Department of Otolaryngology--Head and Neck Surgery, University of Iowa (Iowa City, IA) were reviewed. The type of laryngomalacia was designated by a new classification scheme (types 1-3) based on the site of supraglottic obstruction and the type of supraglottoplasty indicated, should the patient later require surgical intervention. The log rank test was used to compare age at resolution and outcome between types of laryngomalacia and between infants with isolated laryngomalacia versus those with additional congenital abnormalities and/or severe neurological compromise. RESULTS: The type of laryngomalacia was evident in 48 of the 58 charts reviewed and included type 1 (57%), type 2 (15%), type 3 (13%), or combined types (15%). Twenty percent had severe neurological compromise and/or multiple congenital anomalies. The median time to resolution of stridor in these patients was not significantly delayed when compared with infants who had isolated airway anomalies (36 and 72 wk, respectively, vs. 36 wk for isolated laryngomalacia; P<.4). Time to resolution did not correlate with the type of laryngomalacia. In 22 infants, clinical symptoms or findings suggested a synchronous airway lesion, and direct laryngoscopy and bronchoscopy were performed. In 11 infants, a second airway lesion was diagnosed (in four cases by FFL and in 7 cases by direct laryngoscopy and bronchoscopy). Complications did not arise in infants who did not undergo direct laryngoscopy and bronchoscopy. Eleven infants with severe laryngomalacia required surgical intervention. The success of supraglottoplasty did not correlate with the type of laryngomalacia or the presence of other congenital anomalies. CONCLUSIONS: Routine direct laryngoscopy and bronchoscopy as part of the evaluation of laryngomalacia are not warranted. Performing these procedures should be based on clinical and physical evidence of a concomitant airway lesion. In general, laryngomalacia will resolve within the first year of life, even in children with multiple congenital anomalies and/or severe neurological compromise. The proposed classification scheme is advantageous in that it is simple and correlates the site of obstruction with the surgical procedure most likely to effect a cure, should the patient require a supraglottoplasty. Surgical management is necessary in approximately 15% to 20% of affected infants.

Cervical vertebral anomalies in patients with anomalies of the head and neck.

Congenital head and neck anomalies can occur in association with vertebral anomalies, particularly of the cervical vertebrae. While the former are easily recognized, especially when part of a syndrome, the latter are often occult, thereby delaying their diagnosis. The presence of vertebral anomalies must be considered in pediatric patients with head and neck abnormalities to expedite management of select cases and to prevent neurologic injury. We present our experience with 5 pediatric patients who were referred to the Department of Otolaryngology-Head and Neck Surgery at the University of Iowa with a variety of syndromic anomalies of the head and neck. Each patient was subsequently also found to have a vertebral anomaly. The relevant embryogenesis of the anomalous structures is discussed, with highlighting of potential causes such as teratogenic agents and events and germ-line mutations. A review of syndromes having both head and neck and vertebral anomalies is presented to heighten awareness of otolaryngologists evaluating children with syndromic disorders. Finally, the findings on radiographic imaging studies, particularly computed tomography, are discussed to facilitate the prompt diagnosis of vertebral anomalies.

Treatment of lymphangiomas in children: an update of Picibanil (OK-432) sclerotherapy.

Picibanil (OK-432) is a sclerosing agent derived from a low-virulence strain of Streptococcus pyogenes that induces regression of macrocystic lymphangiomas. This report describes a prospective, nonrandomized trial to evaluate the efficacy of Picibanil in the treatment of 13 affected children ranging in age from 1 to 94 months. On average, 4.1 fluoroscopically guided intracystic injections were performed per child, with an average total dose of 0.56 mg of Picibanil. As judged by physical examination and radiographic studies, 5 children (42%) showed a complete or substantial response, and 2 children (16%) showed an intermediate response. No response was seen in 5 children (42%), 2 of whom had massive craniofacial lymphangioma. Factors that contribute to failure with Picibanil sclerotherapy are the presence of a significant microcystic component to the lesion, massive craniofacial involvement, and previous surgical resection. Macrocystic lymphangiomas of the infratemporal fossa or cervical area have the best response to therapy.

Malignant triton tumor of the head and neck: A case report and review of the literature.

BACKGROUND: Malignant triton tumor (MTT) is a relatively rare, aggressive tumor comprised of both malignant schwannoma cells and malignant rhabdomyoblasts. Because MTT frequently arises in the head and neck, the otolaryngologist must be aware of the nature of the tumor and its response to various treatment modalities. METHOD: This article reviews the treatment and outcome of all reported cases of MTT arising in the head and neck. CONCLUSIONS: Although statistical analysis is limited by the short duration of follow-up of many patients, complete tumor resection appears to carry an improved chance of survival. Adjuvant radiation and chemotherapy may also improve survival, although a benefit of these therapies was not well demonstrated in this small series.

Effect of intravenous calcitonin gene-related peptide antagonist on the laryngeal chemoreflex in piglets.

The laryngeal chemoreflex (LCR) is characterized by mixed apnea and cardiovascular instability and is elicited by applying water to the laryngeal mucosa of developing animals. The LCR may be fatal in very young animals, and the reflex has been postulated as a possible mechanism of sudden infant death syndrome. Several antagonists have been found to alter the severity of the LCR, but the primary neurotransmitters involved in mediating the reflex response are not yet well understood. This study investigates the effect, on the LCR, of the pharmacologic antagonism of calcitonin gene-related peptide (alphaCGRP), a neurochemical found in abundance in the mammalian laryngeal mucosa and its innervating system. The LCR was elicited in 10 mixed breed piglets, 17.7 days of age (12 to 22 days), before and during infusion of alphaCGRP 8-37, a pharmacologic inhibitor of alphaCGRP, and cardiorespiratory and laryngeal responses were compared. The duration of obstructive apnea decreased from 17.9 to 9. 8 seconds (P < 0.03) in the presence of alphaCGRP 8-37. Mean central apnea did not change for the group (P > 0.05), although it was completely inhibited in 2 animals. Cardiovascular changes were not significantly altered by the alphaCGRP inhibitor. alphaCGRP appears to play a regulatory role in the apneic response of the LCR, particularly its obstructive component, but not the cardiovascular response.

An update on the treatment of hemangiomas in children with interferon alfa-2a.

OBJECTIVE: To report the benefits and complications of subcutaneous interferon alfa-2a therapy for hemangiomas in children. DESIGN: Prospective nonrandomized trial. SETTING: Tertiary care pediatric referral center. PATIENTS: Twenty-four pediatric patients diagnosed with massive or life-threatening hemangiomas. INTERVENTIONS: Each patient received daily subcutaneous injections of interferon alfa-2a to a target dose of 3 million U/m2 of body surface area for a minimum of 4 months. Nineteen patients completed therapy and have received adequate follow-up. MAIN OUTCOME MEASURES: Clinical and radiographic comparisons before, during, and after therapy. Reduction in hemangioma size was graded as complete (>90%), substantial (50%-80%), intermediate (20%-40%), or no response (<10%). RESULTS: Mean age at institution of therapy was 9.6 months, and mean duration of treatment was 10.2 months. Most patients (70%) had not received prior therapy. Responses were as follows: complete, 8 patients (42%); substantial, 3 patients (16%), intermediate, 5 patients (26%); and no response, 3 patients (16%) (n = 19). During therapy, 5 patients (26%) developed neurological abnormalities: 3 had an unsteady gait, and 2 had fine motor deficits. Only 1 of these 5 patients required premature termination from the study, and the neurological abnormalities in all 5 patients resolved after treatment was discontinued. Two of the 4 patients with neurological findings who completed therapy demonstrated complete resolution of their hemangiomas. Patients who developed neurological abnormalities began interferon alfa-2a therapy at an earlier age (4.7 months) than patients without neurological difficulties (aged 11.1 months). The mean time from initiation of therapy to the appearance of neurological complications was 4.8 months. CONCLUSIONS: In pediatric patients with massive or life-threatening hemangiomas, interferon alfa-2a therapy is an effective treatment option. However, neurological evaluation before and during therapy with interferon alfa-2a should be performed owing to a significant incidence of neurological abnormalities (28%). Although all children with neurological findings demonstrated neurological recovery after discontinuation of therapy, we have changed our protocol and now more gradually increase the dosage of interferon alfa-2a up to 3 million U/m2 per day. The effect of this modification on the development of neurological abnormalities has not yet been determined.

Effect of intravenous substance P on laryngeal adductor activity in young dogs.

Reflex laryngeal adduction is a component of both the laryngeal chemoreflex and the esophagolaryngeal adductor reflex, two life-threatening reflexes that occur in immature animals. These two reflex responses are also thought to exist in infants and may play a role in causing life-threatening laryngospastic events and perhaps sudden infant death syndrome. Identifying neurotransmitters that mediate laryngeal adduction is important to understanding the mechanism of reflex laryngeal responses and to identifying potential means of pharmacologic prevention. Substance P (SP), a tachykinin, putatively functions as a sensory neurotransmitter and may play a role in mediating laryngeal reflexes. Substance P-immunoreactive-like fibers and receptors are present in the subepithelial tissues of the larynx, the vagus nerves, the nodose and jugular ganglia, and the vagal brain stem nuclei. In this investigation, the effect of SP infusion on laryngeal motor activity in an in vivo model is reported. Substance P was infused intravenously into 8 puppies (20 to 133 days of age, mean 81.2), on a mean of 3.0 occasions (range 1 to 6). Cardiovascular, respiratory, arterial blood gas, and cricothyroid (CT), thyroarytenoid (TA), and genioglossus electromyographic (EMG) responses to infusion of the tachykinin were recorded and subsequently analyzed. The SP infusion induced a marked increase in CT or TA EMG activity in 23 of 24 studies, and the increase was typically apparent within 60 seconds of the infusion. An increase in genioglossus EMG activity did not occur. An immediate, profound decrease in mean arterial pressure and an increase in respiratory rate and depth of chest wall excursion accompanied the laryngeal response. Arterial blood gas values remained unchanged (p > .05). The laryngeal adductor response to SP infusion was blocked when animals were pretreated with a systemic SP antagonist (Pfizer CP-96,345). This study demonstrates that peripheral infusion of the tachykinin SP induces a marked increase in laryngeal adductor activity. The response may be blocked by pretreatment of animals with a systemic SP antagonist. Because SP is thought to act primarily as a sensory neurotransmitter, these findings may be important in understanding the mechanism of reflex laryngeal adductor responses.

Role of substance P in the laryngeal chemoreflex.

The laryngeal chemoreflex (LCR) is a potentially life-threatening reflex that is elicited in immature animals by the topical application of water to the laryngeal mucosa. The reflex response is characterized by immediate apnea and laryngeal adduction and delayed cardiovascular instability. The cardiorespiratory changes of the LCR may be life-threatening, particularly in very immature animals such as piglets under 2 weeks of age. The afferent and efferent limbs of the LCR are mediated through the vagus nerve, but the neuromediators responsible for the reflex changes have not yet been clearly elucidated. Previous agonist and antagonist studies in immature dogs demonstrated that substance P, a sensory tachykinin, mediates the life-threatening esophagolaryngeal adductor reflex elicited by distal esophageal sensory nerve stimulation. This study was conducted to determine if substance P also plays a role in mediating the LCR. The LCR response was compared before and after treatment with intravenous substance P antagonist (Pfizer CP-96,345-1) in eight piglets (mean 27.7 days of age). The laryngeal and cardiovascular responses of the animals following intravenous administration of the tachykinins substance P, neurokinin A, and neurokinin B were also assessed. Pretreatment with substance P antagonist did not alter the LCR's duration of apnea (p > .10), laryngeal adductor response, or early change in mean arterial pressure (p > .10), although the early maximal heart rate response was significantly altered (p < .01). Intravenous substance P, neurokinin A, and neurokinin B did not reproduce the laryngeal respiratory response of the LCR. We conclude that substance P, neurokinin A, and neurokinin B are not key neurotransmitters of the LCR.

Ectopic cervical thymic masses in infants: a case report and review of the literature.

Ectopic cervical thymic tissue is a rare cause of neck masses in infants with only nine cases reported in the literature. This entity should be considered in the differential diagnosis of infantile neck masses to prevent inadvertent total thymectomy and its possible deleterious effects on the developing immune system. The case report of a 2-month-old infant with ectopic thymic tissue presenting as a solid cervical mass is reviewed as is the literature of such lesions. The embryology of the thymus, the effect of early total thymectomy in laboratory animals, and the management of neck masses in infants are discussed.

A classification scheme for paradoxical vocal cord motion.

Paradoxical vocal cord motion (PVCM) is characterized by the inappropriate adduction of the true vocal cords during inspiration. Multiple causes have been proposed for this group of disorders, which share the common finding of mobile vocal cords that adduct inappropriately during inspiration and cause stridor by approximation. Management of this group of disorders has been complicated by the lack of a classification scheme to include all types of PVCM. We propose that PVCM be classified according to its underlying etiology and recognize the following causes of the disorder: 1. brainstem compression; 2. cortical or upper motor neuron injury; 3. nuclear or lower motor neuron injury; 4. movement disorder; 5. gastroesophageal reflux; 6. factitious or malingering disorder; 7. somatization/conversion disorder. Case reports are presented to illustrate the characteristic features and diagnostic evaluation used in assessing patients with PVCM. Management varies depending on the cause of PVCM and entails speech therapy, pharmacologic therapy, behavioral modification, and/or surgical intervention. Recognition of the multiple causes of PVCM allows otolaryngologists to formulate well-directed diagnostic evaluation and treatment.

Treatment of massive or life-threatening hemangiomas with recombinant alpha(2a)-interferon.

OBJECTIVE: To assess the response of massive, life-threatening, or function-impairing hemangiomas in pediatric patients receiving daily alpha(2a)-interferon subcutaneously. METHODS: The effect of 3 or more months of subcutaneous alpha(2a)-interferon (3 mU/m2) was prospectively evaluated in 10 patients with hemangiomas necessitating medical intervention. Hemangioma characteristics and extent were initially assessed by radiographic imaging in all but one patient. alpha(2a)-Interferon tolerance was monitored, and reduction in hemangioma size was recorded as marked (>50%), moderate (25% to 50%), or minimal (<25%). RESULTS: Hemangiomas were apparent at birth in 8 of 10 patients, and alpha(2a)-interferon was initiated at a median age of 4.5 months. Symptoms necessitating therapeutic intervention included congestive heart failure, airway obstruction, dysphagia, infection, failure to thrive, external auditory canal occlusion, visual axis impairment, and severe facial deformity. Four patients received treatment before referral that included systemic steroids (n = 2), intralesional steroids (n = 1), or surgical/laser excision (n = 2). alpha(2a)-Interferon therapy was well tolerated. Most patients had a temporary elevation in body temperature during the first month of therapy. One patient with anorexia required nasogastric feedings and a temporary reduction in her alpha(2a)-interferon dose. An additional patient with irritability was withdrawn from the study at his parents' request even though this symptom persisted after drug cessation. Hemangioma response to alpha(2a)-interferon was marked in six patients, moderate in two, and minimal in one whose lesion had features suggestive of a vascular malformation. Early signs of involution were usually evident within 6 weeks and often heralded by cutaneous blanching. alpha(2a)-interferon therapy was concluded in four patients after a mean duration of 20 months. CONCLUSIONS: Daily subcutaneous alpha(2a)-interferon is well tolerated in pediatric patients and appears effective in hastening involution of symptomatic hemangiomas. A significant response is unlikely in lesions with features suggestive of a vascular malformation.

Recurrent respiratory papillomatosis.

Juvenile-onset recurrent respiratory papillomatosis is a vertically transmitted disease caused by members of the human papilloma virus family. Characterized by the relentless growth of papillomatous lesions of the larynx, recurrent respiratory papillomatosis imposes significant morbidity on patients and strain on their families. Surgical excision of the papillomata remains the mainstay of therapy, but human papilloma virus DNA persists in adjacent, normal-appearing mucosa and likely serves as a reservoir for viral reseeding. Despite multiple adjuvant treatment modalities, a cure for recurrent respiratory papillomatosis remains elusive. Most afflicted patients eventually enter spontaneous remission, but some endure several hundred surgical procedures before this welcome respite.

OK-432 therapy for lymphangiomas.

OBJECTIVE: To assess the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. DESIGN: Nonrandomized trial; follow-up, 4 to 29 months. SETTING: Academic tertiary referral medical center. PATIENTS: Six children with presumed lymphangiomas; age range at initial treatment, 1 month to 7 years 10 months. INTERVENTION: Fluoroscopically guided cyst aspiration, cystography, and injection of OK-432. OUTCOME MEASURES: Clinical and radiographic comparisons before and after therapy. RESULTS: Complete response in 2 macrocystic lymphangiomas; no response in 3 microcystic lymphangiomas; and no response in 1 venous malformation. CONCLUSION: OK-432 sclerotherapy may be effective treatment for macrocystic lymphangiomas.

Postoperative care following single-stage laryngotracheoplasty.

Single-stage laryngotracheoplasty (SSLTP) provides a method of correcting mild-to-moderate laryngotracheal stenosis while avoiding the risks of prolonged laryngeal stenting. Pediatric patients are orally intubated for 5 to 7 days postoperatively to ensure an adequate airway while edema resolves and healing begins. During this period, continuous neuromuscular blockade has been advocated in infants and young children to avoid endotracheal tube trauma to the fresh graft and potentially life-threatening accidental decannulation. Pulmonary atelectasis is the most common morbidity associated with prolonged neuromuscular blockade. Neuromuscular weakness also may follow prolonged paralysis and prolong hospitalization. This paper compares the postoperative course of 17 patients who underwent 18 SSLTP procedures by the senior author. The first 8 patients received continuous neuromuscular blockade in the early postoperative period. To reduce perceived morbidity, the last 9 patients were managed with a protocol that incorporated daily 4- to 8-hour "interruptions" of paralysis. Seven patients tolerated this protocol modification. As a group, these patients had less postoperative pulmonary atelectasis prior to extubation (p < .05) and were extubated sooner than patients receiving continuous neuromuscular blockade (p<.05) without compromising the surgical success of the procedure. Intermittent paralysis permitted for more accurate assessment of pain control and protected against accidental drug accumulation. Although self-extubation did not occur, diligent nursing care with adequate sedation and analgesia is necessary to avoid the risk of accidental extubation.