Stridor Related to Vagus Nerve Stimulator: A Case Report.

Implantation of a vagus nerve stimulator (VNS) can be an effective treatment for medically refractory seizures. Laryngeal side effects from a VNS can include hoarseness, cough, and shortness of breath. This report highlights a 5-year-old female who presented with stridor in the setting of acquired laryngomalacia, global developmental delay, and a VNS device. The case demonstrates that a VNS can exacerbate the symptoms of acquired laryngomalacia and that close monitoring of laryngeal side effects is crucial to optimizing care in this population. Laryngoscope, 131:E1733-E1734, 2021.

Human laryngeal sensory receptor mapping illuminates the mechanisms of laryngeal adductor reflex control.

OBJECTIVE: The laryngeal adductor reflex (LAR) is an airway protective response triggered by sensory laryngeal receptors. It is unknown whether different glottic and supraglottic subsites vary in their reflex elicitation abilities. The recent discovery that a bilateral LAR is present in humans under general anesthesia upon laryngeal mucosal stimulation has enabled us to map the sensory receptor density for LAR elicitation at different laryngeal subsites. Our findings expose the likely mechanisms of LAR control. METHODS: Prospective series of 10 patients undergoing laryngoscopy. Laryngeal subsites (epiglottic tip, membranous vocal fold, midventricular vocal fold, posterior supraglottis, epiglottic petiole) were stimulated via direct laryngoscopy with a bipolar probe. Vocal fold responses were recorded by endotracheal tube and hook wire electrodes, and visual observation. RESULTS: Posterior supraglottic stimulation elicited bilateral LARs in all patients at all intensities. Membranous vocal folds, epiglottic petiole, and subglottis elicited no LAR. Ventricular fold and epiglottic tip responses converted from ipsi- to bilateral at high intensities. CONCLUSION: There are likely three checkpoints for control of the LAR in humans. These checkpoints protect against inappropriate LAR activation during volitional tasks without compromising airway protection: 1) topographical differences in receptor density with the highest density in subsites most likely to contact foreign substances; 2) absence of receptors in membranous vocal folds; and 3) central summation threshold for crossed interneuron activation at brainstem level where only strong intensity stimuli will elicit bilateral responses. Checkpoint dysfunction provides a novel framework to diagnose and treat disease processes, including aspiration, laryngospasm, and sudden infant death. LEVEL OF EVIDENCE: 4. Laryngoscope, E365-E370, 2018.

Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

OBJECTIVES/HYPOTHESIS: Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. STUDY DESIGN: In vivo canine model. METHODS: In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. RESULTS: The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. CONCLUSIONS: Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. LEVEL OF EVIDENCE: NA Laryngoscope, 127:1633-1638, 2017.

Three-dimensional posture changes of the vocal fold from paired intrinsic laryngeal muscles.

OBJECTIVES/HYPOTHESIS: Although the geometry of the vocal fold medial surface affects voice quality and is critical in the treatment of glottic insufficiency, the prephonatory shape of the vocal fold medial surface is not well understood. In this study, we activated intrinsic laryngeal muscles individually and in combinations, and recorded the temporal sequence and precise three-dimensional configurational changes of the vocal fold medial surface. STUDY DESIGN: In vivo canine hemilarynx model. METHODS: A hemilaryngectomy was performed in an in vivo canine model and ink was used to mark the medial surface of the in situ vocal fold in a grid-like fashion. The thyroarytenoid (TA), lateral cricoarytenoid (LCA), cricothyroid (CT), and posterior cricoarytenoid (PCA) muscles were stimulated individually and in combinations. A right-angle prism whose hypotenuse formed the glottal midline provided two distinct views of the medial surface for a high-speed digital camera. Image-processing package DaVis (LaVision Inc., Goettingen, Germany) allowed time series cross-correlation analysis for three-dimensional deformation calculations of the vocal fold medial surface. RESULTS: Combined TA and LCA activation yields an evenly adducted rectangular glottal surface. Addition of thyroarytenoid to cricoarytenoid adducts the vocal fold from inferior to superior in a graded fashion allowing formation of a divergent glottis. Posterior cricoarytenoid has a bimodal relationship with thyroarytenoid favoring abduction. Cricothyroid and lateral cricoarytenoid yield unique glottal postures necessary but likely not conducive for efficient phonation. CONCLUSIONS: Understanding the three-dimensional geometry of the vocal fold medial surface will help us better understand the cause-effect relationship between laryngeal physiology and phonation. LEVEL OF EVIDENCE: NA Laryngoscope, 127:656-664, 2017.

External Branch of the Superior Laryngeal Nerve Mediated Glottic Closing Force in the Porcine Model.

OBJECTIVES: Based on our laboratory's newly confirmed motor pathway for glottic closure, we measured the glottic closing force (GCF) during isolated stimulation of the external branch of the superior laryngeal nerve (eSLN) in the porcine model. Glottic closure is 1 of the primary mechanisms for prevention of aspiration during deglutition. METHODS: The recurrent laryngeal nerve (RLN) and eSLN were identified bilaterally in 4 porcine necks. Subsequently, GCF was measured with a pressure transducer as the distal ends of individual nerves were stimulated in 4 animals. The RLN mediated GCF was measured first, followed by isolated eSLN mediated GCF, followed by transection of the RLN and repeat measurement of the eSLN GCF. Ultimately, the cricothyroid (CT) muscle attachment was released and the GCF measured. RESULTS: The GCF during isolated eSLN stimulation before and after RLN transection is approximately 89% of the RLN mediated GCF in each animal. The GCF after CT release is approximately 84% of the RLN perceived GCF. Transection of the RLN did not alter the eSLN observed GCF. CONCLUSIONS: The GCF obtained during isolated eSLN stimulation is adequate for delivery of an appropriate laryngeal protective response and may be considered a target motor nerve for augmenting GCF in selected rehab settings.

Prospective validation study of Cernea classification for predicting EMG alterations of the external branch of the superior laryngeal nerve.

PURPOSES: Cernea classification is applied to describe the external branch of the superior laryngeal nerve (EBSLN). Using intraoperative neural monitoring we evaluated whether or not this classification is useful for predicting which EBSLN subtype has an increased risk of injury. METHODS: An analysis of 400 EBSLN. The identification of EBSLN was achieved with both cricothyroid muscle twitch and the glottis evoked electromyography response. We defined S1 initial EBSLN stimulation at identification and S2 final nerve stimulation achieved in the most cranial aspect of the nerve exposed above the area of surgical dissection after superior artery ligation. RESULTS: The mean S1 amplitude acquired was 259+/67 (180-421), 321 +/79 (192-391), 371 +/38 (200-551) µV, respectively, for type 1, 2A, 2B (p = 0.08). The S1 and S2 amplitudes were similar in type 1 (p = 0.3). The S1 and S2 determinations changed significantly in type 2A and 2B (p = 0.04 and 0.03). EBSLN which demonstrated a >25 % decreased amplitude in S2 increased significantly from Type 1 (4.9 %) to Type 2A (11.2 %) and 2B (18 %) (p = 0.01). None of type 1, 2.8 % type 2A and 3 % type 2B showed a loss of EBSLN conductivity. The latency determinations did not vary significantly for any parameter compared. CONCLUSIONS: The Cernea classification was, therefore, found to predict the risk of EBSLN stress. We identified amplitude differences between S1 and S2 determinations in type 2A and 2B, thus confirming that surgical dissection in these subtypes is, therefore, extremely difficult to perform.

The pharyngeal plexus-mediated glottic closure response and associated neural connections of the plexus.

IMPORTANCE: There continues to be a paucity of data regarding the pharyngeal plexus (PP) and its interconnectivity with the laryngeal nerves and function. OBJECTIVE: To identify the specific neural pathways involved in the glottic closure reflex (GCR)-like pathway of the PP and other pathways to the thyroarytenoid (TA) muscle in the porcine model. DESIGN, SETTING, AND ANIMAL SUBJECTS: Animal experimental study from September 2013 to June 2014 conducted in a tertiary academic medical center on male Yorkshire pigs. INTERVENTIONS: Contraction of the TA was detected with electromyography (EMG) during electrical stimulation of the PP in 7 porcine necks. Subsequently, the external branch of the superior laryngeal nerve (eSLN), communicating nerve of Galen (NG), and the recurrent laryngeal nerve (RLN) were sequentially transected to help elucidate the path of neural conduction. MAIN OUTCOMES AND MEASURES: Confirmation of TA muscle contraction by EMG. RESULTS: Stimulation of the PP evoked a response from the TA muscle in 6 of 7 subject animals. In 3 of 7 subjects, a long latency response (mean, 14.62 milliseconds) was identified, which was eliminated only after transection of the RLN. In 3 of 7 subjects, a short latency response (mean 3.05 milliseconds) was identified, which disappeared in 1 subject each by eSLN, RLN, and NG transection. CONCLUSIONS AND RELEVANCE: We identified the specific neural pathway involved in the PP's GCR-like pathway. We also noted a variable direct pattern of innervation to the TA.

Influence and interactions of laryngeal adductors and cricothyroid muscles on fundamental frequency and glottal posture control.

The interactions of the intrinsic laryngeal muscles (ILMs) in controlling fundamental frequency (F0) and glottal posture remain unclear. In an in vivo canine model, three sets of intrinsic laryngeal muscles-the thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid plus interarytenoid (LCA/IA) muscle complex-were independently and accurately stimulated in a graded manner using distal laryngeal nerve stimulation. Graded neuromuscular stimulation was used to independently activate these paired intrinsic laryngeal muscles over a range from threshold to maximal activation, to produce 320 distinct laryngeal phonatory postures. At phonation onset these activation conditions were evaluated in terms of their vocal fold strain, glottal width at the vocal processes, fundamental frequency (F0), subglottic pressure, and airflow. F0 ranged from 69 to 772 Hz and clustered into chest-like and falsetto-like groups. CT activation was always required to raise F0, but could also lower F0 at low TA and LCA/IA activation levels. Increasing TA activation first increased then decreased F0 in all CT and LCA/IA activation conditions. Increasing TA activation also facilitated production of high F0 at a lower onset pressure. Independent control of membranous (TA) and cartilaginous (LCA/IA) glottal closure enabled multiple pathways for F0 control via changes in glottal posture.

Intraoperative monitoring: normative range associated with normal postoperative glottic function.

OBJECTIVES/HYPOTHESIS: Despite increasing use of intraoperative nerve monitoring (IONM), there is limited information on normative electrophysiologic electromyographic (EMG) parameters. The objective of this study was to define normative parameters of recurrent laryngeal nerve (RLN) intraoperative neuromonitoring during thyroid surgery associated with normal postoperative vocal cord function. STUDY DESIGN: Prospective data collection in a tertiary care center. METHODS: Quantitative analysis of evoked waveform amplitude and threshold was performed on 125 patients with 167 nerves at risk. Values were displayed as a mean with 5th percentile and 95th percentiles (5th-95th). Postoperative vocal cord function in all patients was documented. RESULTS: All patients had normal postoperative laryngeal function (group I-normal) except for two patients who had postoperative transient vocal cord paralysis (group II-abnormal/outlier). The final amplitude between 247 and 3607 µV at the end of dissection/end of surgery was associated in all group I patients with a normal postoperative neural function. Final intraoperative amplitude measures for group II averaged just 97.5 µV, significantly different than our normative ranges obtained for group I, and fell outside of the group I 5% to 95% percentile range (P = .016). Final amplitude adequately predicted postoperative RLN impaired function immediately after surgery. CONCLUSIONS: We propose IONM EMG data criteria that predict normal postoperative vocal cord function monitoring and provide information about nerve functioning at the end of the operation, thereby allowing adaptation of the surgical strategy when a bilateral procedure is indicated to avoid bilateral nerve paralysis.

Otolaryngology head and neck surgery: an integrative view of the larynx.

The glottis is composed of muscular, cartilaginous, and other viscoelastic tissues which perform some of our most important, complex, coordinated, and life-sustaining functions. Dominated by the thyroarytenoid muscles and associated glottic closure muscles, the larynx is involved in respiration, swallowing, voicing, coughing, valsalva, vomiting, laughing, and crying. With respiration continuing in the background, all other "secondary" laryngeal events seamlessly occur. When the delicate balance of coordinating these events is disrupted by disease or disorder, many of these tasks are compromised. Due to the complex innervation of these volitional and reflexive tasks with brainstem central pattern generators, primary sensorimotor areas and importantly, limbic areas, failure can occur due to disease, anatomic compromise, and even emotional state. Understanding the level of sensorimotor control and interaction among systems that share these laryngeal neuromuscular substrates will improve the diagnostic and therapeutic skill of the clinician when treating compromise of laryngeal function.

Protective role of aerodigestive reflexes against aspiration: study on subjects with impaired and preserved reflexes.

BACKGROUND & AIMS: Direct evidence to support the airway protective function of aerodigestive reflexes triggered by pharyngeal stimulation was previously demonstrated by abolishing these reflexes by topical pharyngeal anesthesia in normal subjects. Studies have also shown that these reflexes deteriorate in cigarette smokers. Aim of this study was to determine the influence of defective pharyngeal aerodigestive reflexes on airway protection in cigarette smokers. METHODS: Pharyngoglottal Closure reflex; PGCR, Pharyngo-UES Contractile reflex; PUCR, and Reflexive Pharyngeal Swallow; RPS were studied in 15 healthy non-smokers (24.2±3.3 SD y, 7 males) and 15 healthy chronic smokers (27.3±8.1, 7 males). To elicit these reflexes and to evaluate aspiration, colored water was perfused into the hypopharynx at the rate of 1 mL/min. Maximum volume of water that can safely dwell in the hypopharynx before spilling into the larynx (Hypopharyngeal Safe Volume; HPSV) and the threshold volume to elicit PGCR, PUCR, and RPS were determined in smokers and results compared with non-smokers. RESULTS: At baseline, RPS was elicited in all non-smokers (100%) and in only 3 of 15 smokers (20%; P<.001). None of the non-smokers showed evidence of laryngeal spillage of water, whereas 12 of 15 smokers with absent RPS had laryngeal spillage. Pharyngeal anesthesia abolished RPS reflex in all non-smokers resulting in laryngeal spillage. The HPSV was 0.61±0.06 mL and 0.76±0.06 mL in non-smokers and smokers respectively (P=.1). CONCLUSIONS: Deteriorated reflexive pharyngeal swallow in chronic cigarette smokers predispose them to risks of aspiration and similarly, abolishing this reflex in non-smokers also results in laryngeal spillage. These observations directly demonstrate the airway protective function of RPS.

[Electric stimulation in dysphagia therapy--a review]. / Elektrische Stimulation in der Dysphagietherapie - Eine Ubersicht.

In the last years an increased interest in the electrical stimulation has consisted in the treatment of dysphagia. In the article we introduce the anatomical and physiological premises for the method. In a critical analysis the present state of art is represented, the clinical results are checked and the chances for the future are examined.

Obstructive sleep apnea syndrome and asthma: what are the links?

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Reflex vocal fold adduction in the porcine model: the effects of stimuli delivered to various sensory nerves.

OBJECTIVES: The aim of this study was to identify a panel of sensory nerves capable of eliciting an evoked glottic closure reflex (GCR) and to quantify the glottic closing force (GCF) of these responses in a porcine model. METHODS: In 5 pigs, the internal branch of the superior laryngeal nerve (iSLN) and the trigeminal, pharyngeal plexus, glossopharyngeal, radial, and intercostal nerves were surgically isolated and electrically stimulated. During stimulation of each nerve, the GCR was detected by laryngeal electromyography and the GCF was measured with a pressure transducer. RESULTS: The only nerve that elicited the GCR in the 5 pigs was the iSLN. The average GCF was 288.9 mm Hg. CONCLUSIONS: This study demonstrates that the only afferent nerve that elicits the GCR in pigs is the iSLN, and that it should remain the focus of research for the rehabilitation of patients with absent or defective reflex vocal fold adduction.

Mechanisms of active laryngeal closure during noninvasive intermittent positive pressure ventilation in nonsedated lambs.

The present study stems from our recent demonstration (Moreau-Bussiere F, Samson N, St-Hilaire M, Reix P, Lafond JR, Nsegbe E, Praud JP. J Appl Physiol 102: 2149-2157, 2007) that a progressive increase in nasal intermittent positive pressure ventilation (nIPPV) leads to active glottal closure in nonsedated, newborn lambs. The aim of the study was to determine whether the mechanisms involved in this glottal narrowing during nIPPV originate from upper airway receptors and/or from bronchopulmonary receptors. Two groups of newborn lambs were chronically instrumented for polysomnographic recording: the first group of five lambs underwent a two-step bilateral thoracic vagotomy using video-assisted thoracoscopic surgery (bilateral vagotomy group), while the second group, composed of six lambs, underwent chronic laryngotracheal separation (isolated upper airway group). A few days later, polysomnographic recordings were performed to assess glottal muscle electromyography during step increases in nIPPV (volume control mode). Results show that active glottal narrowing does not develop when nIPPV is applied on the upper airways only, and that this narrowing is prevented by bilateral vagotomy when nIPPV is applied on intact airways. In conclusion, active glottal narrowing in response to increasing nIPPV originates from bronchopulmonary receptors.

Percutaneous biphasic electrical stimulation for treatment of obstructive sleep apnea syndrome.

In this paper, we study the effect of stimulation of the genioglossus with percutaneous biphasic electrical pulses on patients with the obstructive sleep apnea syndrome (OSAS). The experiment was conducted in 22 patients clinically diagnosed with OSAS. The patients were monitored with polysomnography (PSG) in the trial. When the sleep apnea was detected, the genioglossus was stimulated with percutaneous biphasic electrical pulses that were automatically regulated by a microcontroller to achieve the optimal effect. The percutaneous biphasic electrical stimulation caused contraction of the genioglossus, forward movement of the tongue, and relieving of the glossopharyngeal airway obstruction. The SaO2, apnea time, hypoxemia time, and change of respiratory disturbance index (RDI) were compared in patients with treatment and without treatment. With percutaneous biphasic electrical stimulation of the genioglossus, the OSAS patients showed apnea time decreased (P < 0.01), RDI decreased (P < 0.01), and SaO2 increased (P < 0.01). No tissue injury or major discomfort was noticed during the trial. The stimulation of genioglossus with percutaneous biphasic electrical current pulse is an effective method for treating OSAS.

The supraglottic nerve supply: an anatomic study with clinical implications.

OBJECTIVES: To describe the course of the superior laryngeal nerve (SLN) and its branches, in particular, with regard to supraglottic motor and sensory functions. METHODS: In 30 normal human hemilarynges, the SLN with its internal (intSLN) and external branch (extSLN) were dissected under microsurgical conditions and marked with acrylic dye. All anatomic structures of the larynges (muscles, cartilages, and ligaments) were dissected in detail. RESULTS: The intSLN subdivides into three branches. The superior branch (I) runs to the lingual (extralaryngeal) part of the epiglottis and sends small fibers through the epiglottic foramina to the laryngeal surface. The middle branch (II) runs through the aryepiglottic fold into the ventricular fold, and the inferior branch (III) to the piriform sinus and to the postcricoid region, forming various anastomoses (e.g., ansa galeni) with the recurrent laryngeal nerve (RLN). The extSLN runs to the cricothyroid muscle (CT) and sends a branch through the CT along the lower rim of the thyroid cartilage into the larynx and up to the ventricular fold. This ventricular branch is a potential candidate for the innervation of the ventricular muscle (VM). CONCLUSIONS: Our results may contribute to a better understanding of supraglottic actions that provide primary functions of the larynx (such as swallowing, coughing, and breathing). An enhanced knowledge of neurolaryngology also provides a basis for interpreting disorders or paralyzes following surgical treatments (e.g., thyroid surgery, partial laryngectomy) and helps to lower the risks.

Breathing and calling: neuronal networks in the Xenopus laevis hindbrain.

Xenopus laevis is an aquatic anuran with a complex vocal repertoire. Unlike terrestrial frogs, vocalizations are independent of respiration, and a single muscle group--the laryngeal dilators--produces underwater calls. We sought to identify the premotor neural network that underlies vocal behaviors. Vocal patterns generated by premotor networks control laryngeal motor neurons in cranial nucleus (n.) IX-X. Glottal motor neurons, active during respiration, are also present in n.IX-X. We used horseradish peroxidase (HRP), Lucifer yellow, and fluorescently conjugated dextrans to characterize the organization of n.IX-X and to trace premotor neuron projections. Premotor nuclei include the inferior reticular formation (Ri) adjacent to n.IX-X and the pretrigeminal nucleus of the dorsal tegmental area of the medulla (DTAM), the primary descending input to n.IX-X. Intramuscular HRP injections revealed a spatially segregated pattern, with glottal motor neurons in anterior n.IX-X and laryngeal motor neurons in the caudal portion of the nucleus. Dextran injections identified commissural n.IX-X neurons that project to the contralateral motor nucleus and DTAM-projecting n.IX-X neurons. Both neuronal types are clustered in anteromedial n.IX-X, closely associated with glottal motor neurons. Ri neurons project to ipsilateral and contralateral DTAM. Projections from DTAM target n.IX-X bilaterally, and all four identified subtypes receive DTAM input. In contrast, Ri neurons receive little input from DTAM. We hypothesize that connectivity between neurons in n.IX-X, Ri and DTAM may provide mechanisms to generate laryngeal and glottal activity patterns and that DTAM may coordinate vocal and respiratory motor pools, perhaps acting to switch between these two mutually exclusive behaviors.