Neurologic Evaluation in Children With Laryngeal Cleft

Key Points

Questions  When and why should patients with laryngeal cleft undergo neurologic evaluation and what imaging should be performed?

Findings  In this medical record review of 242 patients with laryngeal cleft, 36% were referred to a neurologist; of these, 38% had examination findings indicative of neuromuscular dysfunction or dyscoordination. Abnormalities were found in 32 of 50 patients who underwent brain imaging.

Meaning  Referral to a neurologist and magnetic resonance imaging of the brain are recommended when (1) the degree of aspiration noted on a modified barium swallow study cannot be explained by the anatomical defect, (2) significant oral and/or oropharyngeal dysphagia is present, (3) a patient fails to improve, or (4) any neurologic symptoms or signs are present.

Importance  Referral to a neurologist and imaging play important roles in the management of laryngeal cleft. Swallowing involves a complex series of neuromuscular interactions, and aspiration can result from anatomical causes (eg, laryngeal cleft), neuromuscular disorders, or some combination thereof. To date, no protocols or guidelines exist to identify which patients with laryngeal cleft should undergo neuroimaging studies and/or consultation with a neurologist.

Objective  To establish guidelines for neurologic evaluation and imaging techniques to identify or rule out neuromuscular dysfunction in children with laryngeal cleft.

Design  Retrospective review of the medical records of 242 patients who were diagnosed with laryngeal cleft at a tertiary children’s hospital between March 1, 1998, and July 6, 2015. Based on this review, an algorithm to guide management of laryngeal cleft is proposed.

Main Outcomes and Measures  Data extracted from patient medical records included the type of laryngeal cleft, details of neurologic referral, results of neuroimaging studies, and objective swallow study outcomes.

Results  Of the 242 patients, 142 were male and 100 were female. Mean age at the time of data analysis was 8.7 years (range, 10 months to 25 years), and there were 164 type I clefts, 64 type II, 13 type III, and 1 type IV. In all, 86 patients (35.5%) were referred to a neurologist; among these, 33 (38.4%) had examination findings indicative of neuromuscular dysfunction or dyscoordination (eg, hypotonia, spasticity, or weakness). Abnormal findings were identified in 32 of 50 patients (64.0%) who underwent brain imaging. Neurosurgical intervention was necessary in 3 patients diagnosed with Chiari malformation and in 1 patient with an intraventricular tumor detected on neuroimaging.

Conclusions and Relevance  A substantial proportion of patients with laryngeal cleft have coexistent neuromuscular dysfunction as a likely contributing factor to dysphagia and aspiration. Collaboration with a neurologist and appropriate neuroimaging may provide diagnostic and prognostic information in this subset of patients. At times, imaging will identify critical congenital malformations that require surgical treatment.

Laryngeal cleft is a congenital condition in which an opening in the posterior laryngotracheal wall allows food and liquids to pass from the esophageal lumen to the airway and causes aspiration.¹ This anatomical abnormality is exceptionally rare, occurring in approximately 0.01% of the population.² Symptoms include dysphagia with aspiration, chronic cough, gagging, hoarseness, and respiratory infections. Not all patients are symptomatic, however, especially those with less severe clefts. Diagnosis requires a high index of suspicion as well as direct visualization through laryngoscopy.

The severity of a laryngeal cleft is measured using the Benjamin-Inglis system, which consists of 4 categories based on the depth of the cleft.³ Although less severe clefts—type I and some type II clefts—can often be managed conservatively, type III and type IV clefts typically require endoscopic or open surgical repair.⁴ With treatment, aspiration is often either completely resolved or significantly improved. However, many patients with laryngeal cleft continue to aspirate despite complete surgical closure.¹ This finding suggests that laryngeal incompetence and aspiration in these patients is a result of several contributing factors. Indeed, one factor typically associated with postoperative swallowing function appears to be the presence of neurologic comorbidities, which have the potential to markedly disrupt the complex neuromuscular activity required for deglutition.¹

Patients with laryngeal cleft who have neurologic comorbidities are less likely to achieve normal swallowing function by means of surgical repair.⁵ In these patients, the anatomical deficiency is only one of multiple factors contributing to dysphagia and aspiration. If underlying neurologic issues go unrecognized, these patients may continue to aspirate and could develop life-threatening complications, such as pulmonary compromise. It is therefore important to identify and refer the subset of patients with laryngeal cleft who are at greatest risk for undiagnosed neurologic or neuromuscular disorders. We performed a retrospective review of 242 pediatric patients with laryngeal cleft at a tertiary children’s hospital—with a focus on those referred to a neurologist—to learn more about the etiology of their aspiration. The purpose of our investigation was to provide recommendations outlining when to consider neurologic evaluation in patients with laryngeal cleft.

A prospective database was maintained of all patients diagnosed with laryngeal cleft at our institution beginning in March 1998. Institutional review board approval was obtained for a retrospective review of this database for the period from March 1, 1998, to July 6, 2015. Each patient’s medical record was individually reviewed. Data extracted from the patient records included the type of laryngeal cleft, whether a visit to a neurologist occurred within the specified time frame, the reason for referral, the imaging performed, and the results of any neuroimaging studies and a modified barium swallow (MBS) study. Diagnosis of laryngeal cleft was made by direct laryngoscopy with palpation of the interarytenoid space. Clefts were classified as previously described by Benjamin and Inglis.³ Surgical repair, when indicated, was performed by suspension laryngoscopy with carbon dioxide laser ablation of interarytenoid mucosa and approximation of the cleft with an absorbable suture, with the exception of 1 type IV cleft that was repaired via an open approach with the patient undergoing cardiopulmonary bypass. Referrals to a neurologist were made at the discretion of the treating physician. Based on our review and clinical experience, we propose an algorithm to guide management of laryngeal clefts.

During the period of review, 242 patients were diagnosed with a laryngeal cleft: 142 patients (58.7%) were male and 100 (41.3%) were female. Mean age at the time of data analysis was 8.7 years (range, 10 months to 25 years), and there were 164 type I clefts (67.8%), 64 type II (26.4%), 13 type III (5.4%), and 1 type IV (0.4%).

Of the 242 patients with laryngeal cleft, 86 (35.5%) were seen by a neurologist within our institution. Among these patients, 33 (38.4%) had examination findings indicative of neuromuscular dysfunction or dyscoordination (eg, hypotonia, spasticity, or weakness). Referral to a neurologist was made specifically to investigate symptoms of aspiration in 42 patients (48.8%). Fourteen referred patients (16.3%) were syndromic or had been born prematurely.

Besides evaluation of aspiration, the most common reasons for referral were muscle weakness and/or persistent falling followed by suspected seizure activity, developmental delays, and behavioral issues. Gastrostomy tubes were placed in 62 of the 242 patients (25.6%). Of these, 4 patients were evaluated by a neurologist, had gastrostomy tubes placed, and did not undergo laryngeal cleft repair.

In our cohort of 242 patients with laryngeal cleft, 50 (20.7%) underwent brain magnetic resonance imaging (MRI). These patients were indicated for MRI because their clinical neurologic examination results suggested abnormalities in the central nervous system. Twelve (5.0%) of these patients also underwent brain ultrasonography in addition to MRI. Abnormal findings were identified in 32 of 50 patients (64.0%) who underwent brain imaging. White matter changes (eg, delayed myelination, demyelination, or leukomalacia) were the most common finding and present in 15 patients (30.0%). Ventricular irregularities were identified in 3 patients (6.0%). Neuroimaging findings led to neurosurgical interventions in 4 patients (8.0%); surgical indications were Chiari malformation in 3 patients and an intraventricular tumor in 1 patient.

Of the 42 patients referred to a neurologist for aspiration, 16 (38.1%) had an abnormal MRI finding. A neurologist confirmed that dysphagia was likely to be caused primarily by neurologic issues in 4 (9.5%) of the patients referred for aspiration.

Swallowing is a multifaceted sensorimotor activity that involves both the somatic and autonomic nervous systems. It is divided into 3 phases, beginning with the oral phase, in which voluntary movement of the bolus into the pharyngeal cavity triggers the swallow reflex.⁶ This leads to the pharyngeal phase, which moves the bolus down into the esophagus, where the involuntary esophageal phase begins.^7,8 Although simple in theory, the process requires the involvement of muscles of the lips, submental group, tongue, palate, larynx, pharynx, and esophagus that undergo subsequent excitation and inhibition by cranial nerves V, VII, IX, X, and XII.⁹ Thus, disorders affecting the cerebral or peripheral nervous system have the potential to cause neurogenic dysphagia that may misdirect food and liquids into the airway.¹⁰

In healthy patients with normal swallowing function, the airway is protected by mechanoreceptors and chemoreceptors that activate a series of reflexes in the pharynx, larynx, and esophagus. These reflexes not only physically protect the airway from food entry but also stimulate coughing to facilitate expectoration in the event of laryngeal or tracheal penetration. However, neuromuscular conditions can block these reflexes or interfere with their timing such that ingested material enters the larynx and fails to trigger a strong cough response.^11,12 Some illnesses that predispose children to aspirate include perinatal asphyxia with resultant white matter or deep gray matter injury, nerve injury, congenital hydrocephalus, neonatal intraventricular hemorrhage, familial dysautonomia, Möbius syndrome, myotonic dystrophy, spinal muscular atrophy, de Lange syndrome, X-linked muscular dystrophy, myasthenia gravis, acute or chronic inflammatory demyelinating polyradiculoneuropathy (also known as Landry-Guillian-Barré-Strohl syndrome), cerebral palsy, vocal cord paralysis, and Chiari malformation.¹³ Of note, several neurologic disorders have already been discovered to elicit distinctive patterns of dysphagia. For example, patients with cerebral palsy have oral motor problems and tend to silently aspirate on thin liquids.¹⁴ Patients with spinal muscular atrophy type II, on the other hand, have trouble swallowing semisolid food, with piecemeal deglutition and residue in the valleculae or above the upper esophageal sphincter.¹⁵ In addition, patients with Duchenne muscular dystrophy are known to have more trouble swallowing semisolid and solid food than liquids, which is different from the usual clinical presentation of aspiration.

Anatomical abnormalities in the airway can also play a prominent role in aspiration. Incompetence or deficiency of the tongue base, supraglottis, or glottic larynx can contribute to aspiration. Patients with laryngeal cleft experience a deficiency of the interarytenoid region of the larynx and/or tracheoesophageal wall that provides a direct passageway for food and liquids to enter the airway from the esophageal inlet.

Symptoms that may indicate a problem with aspiration include recurrent pneumonias, malnutrition, impaired lung function, and coughing during or after feeding. Examination may reveal crackles, wheezing, and “wet” upper airway noises or voice quality.¹³ Definitive diagnosis is achieved by visualizing the airway during feeding with an objective swallowing study, either by MBS study—also known as the videofluoroscopic swallow study—or fiberoptic endoscopic evaluation of swallowing.¹³

Initial treatment of children with aspiration involves dietary modification, with thickening of liquids dictated by the results of their MBS or fiberoptic endoscopic evaluation of swallowing study. For children who fail to improve with dietary modifications and feeding therapy, laryngoscopy should be considered to evaluate for anatomical anomalies. Flexible fiberoptic laryngoscopy while the patient is awake can be useful to diagnose vocal fold paresis or paralysis, but it is inadequate for detecting laryngeal cleft, which requires direct laryngoscopy with the patient under anesthesia.

If a patient is diagnosed with laryngeal cleft and aspiration, multiple treatment options can be considered based on cleft severity, feeding ability, neurologic status, and other comorbidities. Surgical repair holds great promise for patients with type II, type III, and type IV clefts.¹³ For most of these patients, the cleft requires repair before they can eat a normal diet without aspirating.¹⁶ After surgery, they receive feeding therapy, which typically involves a thickened liquid diet to prevent aspiration. For the patient who is not a candidate for surgery, a gastrostomy tube might be necessary to ensure that the patient stays well nourished without harming his or her respiratory system.

Only about 50% of our patients with type I cleft required surgical repair, while the other half fared well with conservative management. This nonsurgical treatment involves monitoring swallowing function with serial MBS studies while using compensatory strategies to facilitate feeding. Strategies include learning proper body positioning, using special utensils, administering antireflux medications, and drinking thickened fluids.^17-21 Patients in whom conservative management fails will often proceed to surgical repair.

The treatment algorithm becomes less straightforward when the cause of aspiration is unclear or likely multifactorial. Even in patients with a diagnosed laryngeal cleft, other potential contributing factors should be investigated to maximize the chances of successful treatment and to appropriately counsel patients and their families regarding prognosis. Evaluation by a neurologist is one component of the workup that we have found useful for a subset of patients.

In our cohort of 242 patients with laryngeal cleft, 86 (35.5%) were seen by a neurologist at our institution, with 42 of these patients (48.8%) referred specifically for aspiration. Based on our experience, referral to a neurologist is indicated when (1) the degree of aspiration on MBS cannot be explained by the anatomical defect (eg, aspiration of all consistencies in a patient with a type I cleft), (2) significant oral and/or oropharyngeal dysphagia is present because this is less likely to be related to the laryngeal cleft, (3) a patient fails to show any substantial improvement with time and proper medical management, or (4) any neurologic symptoms or signs are identified on the patient’s history and physical examination results (eg, history of seizures, cranial neuropathy, significant developmental delay, hypotonia, or spasticity).

Our data indicate that neuromuscular disorders are common among patients with laryngeal cleft and are found in 38.4% of those evaluated by a neurologist or in 13.6% overall. The higher figure likely overestimates the true incidence as these patients presumably had a high prereferral suspicion for a neurologic comorbidity, while the lower figure may underestimate the incidence given that 156 of our 242 patients (64.5%) were never formally evaluated for neurologic conditions.

We recommend imaging when findings on the neurologic examination suggest central nervous system abnormalities. These findings include cranial neuropathies; a history of oromotor dysfunction, such as excessive drooling or poorly organized chewing; and marked developmental delay. Any child who presents with hypotonia or spasticity should be considered for imaging. The hypotonic child with preserved deep tendon reflexes (thus arguing against a primary neuromuscular disorder) should undergo imaging since the source of the hypotonia is likely central and not peripheral. The presence of any dysmorphic craniofacial features also increases the likelihood of brain malformations and should also lead to imaging.

Our preferred imaging method is MRI of the brain because many of the abnormalities we seek to address are infratentorial; in children, these abnormalities are far better visualized with MRI. Given the interest in brainstem and cerebellum abnormalities, the MRI should include sagittal FIESTA (fast imaging employing steady state acquistion) sequencing because this method is particularly advantageous for identifying brainstem and Chiari malformations. A set of standard sequences, including fluid-attenuated inversion recovery and T1- and T2-weighted images, is also indicated.

Imaging abnormalities were common among the patients we studied and were found in 32 of 50 patients (64.0%) who underwent imaging. Thus, the yield of this procedure in this population is clearly high enough to justify its use according to the above-noted differential diagnosis. In 4 patients, findings were noteworthy enough to necessitate neurosurgery. Three of these patients were identified as having a Chiari malformation, which is known to cause vocal fold paresis and/or paralysis and can have a marked effect on swallowing. A fourth patient had an intraventricular tumor diagnosed in the course of the workup that may have otherwise gone undiagnosed for some time.

This investigation is limited by its retrospective study design. All data collection was limited to review of our departmental database and electronic medical records, which may not include all patient details. For example, this medical record review does not capture neurologic evaluations that occurred outside our institution. In addition, referrals to a neurologist were made at the discretion of the treating physician, and the majority of our patient sample was never formally evaluated for neurologic abnormalities. Therefore, our findings may underestimate the true incidence of neurologic conditions in children with laryngeal cleft.

Comorbid neuromuscular disorders are common in patients with laryngeal cleft. We recommend referral to a neurologist when (1) the degree of aspiration on an MBS study cannot be explained by the anatomical defect, (2) significant oral and/or oropharyngeal dysphagia is present, (3) a patient fails to improve, or (4) any neurologic symptoms or signs are present. Magnetic resonance imaging should be considered in the presence of dysmorphic craniofacial features, cranial neuropathies, marked hypotonia with preserved deep tendon reflexes, spasticity, or any history of anterior oromotor dysfunction.

Corresponding Author: Reza Rahbar, DMD, MD, Department of Otolaryngology and Communication Enhancement, Boston Children’s Hospital, 300 Longwood Ave, LO-367, Boston, MA 02115 (reza.rahbar@childrens.harvard.edu).

Accepted for Publication: December 11, 2016.

Published Online: April 6, 2017. doi:10.1001/jamaoto.2016.4735

Author Contributions: Drs Walker and Rahbar had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Walker, Kenna, Rahbar.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Walker, Irace, Rahbar.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Irace, Kenna, Rahbar.

Administrative, technical, or material support: Irace, Kenna, Rahbar.

Study supervision: Kenna, Rahbar.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Meeting Presentation: This paper was presented as a poster at the Annual Meeting of the American Society of Pediatric Otolaryngology; May 18-22, 2016; Chicago, Illinois.