Cricopharyngeal sphincter muscle responses to transcranial magnetic stimulation in normal subjects and in patients with dysphagia.

OBJECTIVE: Cricopharyngeal (CP) muscle of the upper oesophageal sphincter (UES) has a significant role in the pharyngo-esophageal phase of deglutition. The linkage between the CP muscle of UES and the motor cortex has not been previously studied electrophysiologically in healthy humans and in patients with neurogenic dysphagia. METHODS: Needle recordings of EMG responses were carried out from the CP sphincter muscle following transcranial magnetic stimulation (TMS) over the vertex around the Cz electrode position (cortical MEP), and on the parieto-occipital skull and the occiput ipsilaterally (peripheral MEP) in 14 healthy control subjects and in 26 patients with and without neurogenic dysphagia. Needle recordings obtained from the cricothyroid muscle of the larynx were also evaluated in six healthy subjects. RESULTS: The cortical motor latency of CP sphincter muscle was 10.7+/-0.5 ms with an amplitude of 0.8+/-0.2 mV in healthy subjects. Both the latency and amplitude of CP-MEP were facilitated during swallowing. The peripheral MEP of the CP muscle was very stable in all normal subjects (5.1+/-0.3 ms; 1.3+/-0.3 mV) and swallowing did not influence these parameters. The cortically elicited CP-MEP was significantly longer than the cortical MEPs obtained from the cricothyroid muscle of the larynx. In 10 dysphagic patients with corticobulbar tract involvement (6 ALS and 4 pseudobulbar palsy) and with pathologic and hyperreflexic EMG of the CP-sphincter muscle, the cortical MEP of CP muscle of the upper esophageal sphincter could not be elicited, although the peripheral CP-MEPs were obtained. TMS never produced a swallowing movement in neither healthy subjects nor patients. CONCLUSION: The CP muscle of the upper esophageal sphincter can produce MEPs by cortical TMS and by stimulation at the root/nerve levels of vagus nerve. The MEP latency values and central motor delay suggest that there is an oligosynaptic corticobulbar pathway to the motoneurons of CP muscles. When the pathway is affected by a pathology (i.e. ALS or pseudobulbar palsy) the CP sphincter becomes hyperreflexic due to disinhibition and the cortical MEP of the CP muscle disappears due to degeneration of the corticobulbar pathway. These mechanisms appear to be responsible for the pathogenesis of dysphagia.     

Development of pharyngo‐esophageal physiology during swallowing in the preterm infant

Background Poor feeding is a common cause of prolonged hospitalization of preterm infants. Pharyngeal and upper esophageal sphincter (UES) function of preterm infants has been technically difficult to assess and is therefore poorly characterized. The aim of this study was to assess the development of pharyngeal motility, UES function, and their coordination during nutritive swallowing in preterm infants. Methods Development of swallowing was assessed in 18 preterm infants. High resolution manometry was performed at first oral feeding attempt (31–32 week) and then weekly for 4 weeks. Pharyngeal and UES pressure changes were characterized in 980 swallows. Key Results During swallowing, we observed an age‐related increase in peak pharyngeal pressure at the laryngeal inlet (1 cm above UES) but an age‐related decrease in the time required for the UES to fully relax to nadir. Analysis of the timing of proximal pharyngeal contractile peak and UES nadir showed that the UES was not fully relaxed when bolus propulsive forces were at their peak in the youngest infants. Conclusions & Inferences Results show developmental changes in infant swallow physiology that can be clearly linked to the effectiveness of nutritive swallowing. Most preterm infants demonstrated poor pharyngeal pressures at the laryngeal inlet coupled with poor coordination of pharyngeal propulsion with UES relaxation. These pressure patterns were less efficient than those demonstrated by older infants who were more adept at feeding. These observations may explain why infants under 34 weeks are physiologically unable to feed effectively and experience frequent choking and fatigue during feeding.     

Collateral reinnervation by the superior laryngeal nerve after recurrent laryngeal nerve injury

This study investigates the role of the intact superior laryngeal nerve (SLN) in the reinnervation process of one of the laryngeal muscles, the posterior cricoarytenoid muscle (PCA), following recurrent laryngeal nerve (RLN) injury. Using a chronic RLN injury model in the adult rat, PCA reinnervation was assessed by retrograde double-tracing techniques in combination with electrophysiology and immunohistochemistry of muscle sections. The results demonstrate that the PCA receives dual innervation from both laryngeal nerves even in the uninjured system. Functionally significant collateral reinnervation originates from intact SLN fibers following RLN injury, mainly due to intramuscular sprouting rather than by recruitment of more motor neurons. This may be important when choosing surgical and/or medical treatment for patients with RLN injury.     

Analysis of the respiratory role of pharyngeal constrictor motoneurons of cat

The electromyogram of the middle pharyngeal constrictor muscle and the electroneurogram of the phrenic nerve was recorded in parallel with measurements of tidal inspiration and tracheal airflow in chloralose-urethane anesthetized cats. In eupnea, pharyngeal constrictor exhibited tonic and expiratory phasic activity. Lung inflation inhibited phasic pharyngeal constrictor activity to reveal its tonic component; lung deflation eliminated both phasic and tonic components. Vagotomy eliminated these static lung volume effects and increased spontaneous cyclic activity. Hypocapnia abolished phasic activity and unmasked its tonic component in vagotomized cats. Hypercapnia increased cyclic pharyngeal constrictor activity (vagi intact or cut). Weak superior laryngeal or glossopharyngeal nerve stimulation had little or no effect during inspiration; during expiration, superior laryngeal nerve stimulation evoked a short lasting attenuating effect, and glossopharyngeal nerve stimulation exerted a long lasting blocking effect. (vagi intact or cut). Pharyngeal constrictor, like laryngeal adductors, is classified as an expiratory resisting type muscle. Pharyngeal constrictor reduces dead space during hypercapnia thereby promoting the exodus of CO₂. Comparison of vagal and other respitatory motoneurons reveals some special features of neural control of respiration heretofore overlooked.     

Intraoperative monitoring of the recurrent laryngeal nerve using acoustic, free-run, and evoked electromyography.

The purpose of this study was to explore advantages and disadvantages of electrodes used for monitoring of the recurrent laryngeal nerve (RLN) and to determine the postoperative outcome in 135 patients. A pilot study examined 11 patients to compare the clinical performance of two commercially available recording electrodes and three stimulation electrodes for RLN neuromonitoring. After determining the most reliable and consistent stimulating/recording electrode combination, 124 patients were then monitored. In a total of 135 patients there was no permanent iatrogenic nerve damage to the RLN, although 2 patients developed transient vocal hoarseness that resolved shortly postoperatively. An initial "searching" current for evoked electromyography (EMG) was delivered at 0.7 mA and then decreased to a value of 0.35 mA, which reliably elicited RLN stimulation with a minimal incidence of false-positive results. The combination of auditory feedback from the mechanically elicited EMG and a control channel involving EMG monitoring of an additional peripheral muscle improved the detection of artifact and improved the clinical efficacy of intraoperative electromyography. A video camera showed the surgical manipulation on the EMG screen, allowing the neurophysiologist to correlate dissection with RLN status and location. Auditory responses from the nerve helped to determine the type of distress the RLN was encountering.     

Effect of Stimulating Peripheral and Central Neural Pathways on Pharyngeal Muscle Contraction Timing During Swallowing in Dogs

The effect of stimulating peripheral and central neural pathways on the electromyographic activity in the hyopharyngeal, thyropharyngeal, and cricopharyngeal muscles was studied in eight dogs during 1) eating, 2) unilateral electrical stimulation of the superior laryngeal nerve, and 3) unilateral electrical stimulation of the solitary nucleus. The duration of pharyngeal swallowing was significantly shorter during eating than during stimulation of the solitary nucleus in the anesthetized dog (mean difference 127 ms, SEM 9, n = 15). The duration of pharyngeal swallowing was significantly shorter during eating than during stimulation of the superior laryngeal nerve in the awake dog (mean difference 84 ms, SEM 13, n = 9). The duration of pharyngeal swallowing during stimulation of the superior laryngeal nerve under anesthesia was significantly shorter than during stimulation of the solitary nucleus under anesthesia (mean difference 58 ms, SEM 18, n = 9). The difference in duration of pharyngeal swallowing during stimulation of the superior laryngeal nerve between the awake state and during anesthesia was not significant (mean 19 ms, SEM 14, n = 9). It was concluded that stimulation of peripheral and central neural pathways resulted in different pharyngeal muscle contraction timing during swallowing in dogs.     

Expiration-related neurons in the region of the retrofacial nucleus: Vagal and laryngeal inhibitory influences

The influences of vagal and laryngeal afferent inputs on expiration-related neurons of B?tzinger complex were studied in anesthetized, paralyzed and artificially ventilated cats. Unilateral electrical stimulation (single shocks or short trains of stimuli at 200 Hz) applied to the cervical vagus nerve or to the superior laryngeal nerve induced inhibitory effects on the activity of these neurons. During apnoea due to hyperventilatory hypocapnia, expiration-related units displayed a low level of tonic activity which was rhythmically inhibited by pump-induced lung inflations. The functional significance of these findings is briefly discussed.     

Effect of neurotrophin-3 on reinnervation of the larynx using the phrenic nerve transfer technique

Current techniques for reinnervation of the larynx following recurrent laryngeal nerve (RLN) injury are limited by synkinesis, which prevents functional recovery. Treatment with neurotrophins (NT) may enhance nerve regeneration and encourage more accurate reinnervation. This study presents the results of using the phrenic nerve transfer method, combined with NT-3 treatment, to selectively reinnervate the posterior cricoarytenoid (PCA) abductor muscle in a pig nerve injury model. RLN transection altered the phenotype and morphology of laryngeal muscles. In both the PCA and thyroarytenoid (TA) adductor muscle, fast type myosin heavy chain (MyHC) protein was decreased while slow type MyHC was increased. These changes were accompanied with a significant reduction in muscle fibre diameter. Following nerve repair there was a progressive normalization of MyHC phenotype and increased muscle fibre diameter in the PCA but not the TA muscle. This correlated with enhanced abductor function indicating the phrenic nerve accurately reinnervated the PCA muscle. Treatment with NT-3 significantly enhanced phrenic nerve regeneration but led to only a small increase in the number of reinnervated PCA muscle fibres and minimal effect on abductor muscle phenotype and morphology. Therefore, work exploring other growth factors, either alone or in combination with NT-3, is required.     

Videofluoroscopic assessment of swallowing function in patients with myasthenia gravis

Swallowing function in myasthenia gravis (MG) was investigated by videofluoroscopy (VF). A total of 23 VF examinations were performed on 11 MG patients at various time points over the exacerbation and remission stages of disease. The assessment parameters on VF examination are set as follows: bolus transport from the mouth to the pharynx, bolus holding in the oral cavity, velopharyngeal seal, tongue base movement, pharyngeal constriction, laryngeal elevation, upper esophageal sphincter (UES) opening, and bolus stasis at the pyriform sinus (PS). Aspiration was also assessed on VF examination. Aspiration was seen in 34.8%, and half of these cases involved silent aspiration. Three of four cases that showed silent aspiration went on to experience aspiration pneumonia during the follow-up term. By Spearman's rank correlation, disturbance of laryngeal elevation was significantly correlated with aspiration (p=0.001), and incomplete UES opening was not significantly, but tended to be, correlated with aspiration (p=0.067). Although other parameters in the oral and pharyngeal phase on VF examination, such as bolus transport from the oral cavity to the pharynx, pharyngeal constriction, or stasis at the PS, were remarkably disturbed (in more than 50% of the examinations), those parameters were not good indicators for aspiration. When a disturbance of laryngeal elevation is found at a bedside clinical test, we recommend performing precise swallowing evaluation, such as VF, Fiberoptic Endoscopic Evaluation of Swallowing (FEES), and/or scintigraphic assessment of swallowing, for MG patients, to detect silent aspiration.     

Laryngeal reflex regulation: Peripheral and central neural analyses

Because of the many functions (e.g., glottic closure, gagging, coughing, swallowing, speech) in which the internal laryngeal muscles are active, complex regulatory mechanisms must exist to modify and coordinate these activities. Little information is available, however, on these neural mechanisms, and the present study attempted to provide more information by investigating, in the adult cat, the effects of stimuli to various orofacial and upper respiratory tract sites and nerves on 110 single units recorded in individual laryngeal muscles, in the recurrent laryngeal nerve (RLN), and in the brain stem nucleus ambiguus. A particularly powerful excitatory influence on unitary activity related to laryngeal adduction was produced by laryngeal stimuli; in many instances this influence could not be modified by other sensory inputs (e.g., from vagus or glossopharyngeal nerves). Laryngeal stimulation also produced a profound cessation of respiration and suppression of the inspiratory-related activity of laryngeal abductor units. Excitatory and inhibitory effects as a result of interacting various stimuli were also seen in recordings from motoneurons of the RLN and nucleus ambiguus. The effects described show characteristics similar to those noted in other oral-facial muscles and indicate common integrative and regulatory mechanisms. This study in the adult cat provides a basis of comparison for future studies in the kitten where the effects of laryngeal stimulation are augmented to such an extent that they have been implicated in disorders such as the sudden infant death syndrome (SIDS).     

Localization of brain stem motoneurons innervating the laryngeal muscles in the rufous horseshoe bat,rhinolophus rouxi

The motoneurons innervating the laryngeal muscles were localized in the rufous horseshoe bat,Rhinolophus rouxi, using the HRP method. HRP was applied to the cricothyroid muscle and to the cut end of the recurrent laryngeal nerve. Labeled motoneurons were found in two completely separated regions of the nucleus ambiguus. The motoneurons innervating the cricothyroid muscle via the superior laryngeal nerve (SLN) are located withinn the ventrolateral portion of the nucleus reaching the caudal pole of the motor nucleus of the facial nerve. The motoneurons innervating the other intrinsic laryngeal muscles via the recurrent laryngeal nerve (RLN) are situated in the caudal half of the nucleus ambiguus. The innervation is strictly homolateral.     

An electrophysiological investigation of deglutition in man

This article describes a combined electrophysiological and mechanical method used to measure laryngeal movements and related submental EMG activity during swallowing. The mechanical upward and downward movements of the larynx were detected using a piezoelectric sensor while the submental integrated EMG (SM-EMG) was recorded. Measurements were performed in 29 human subjects. The interval between the onsets of the two sensor signal deflections was used as a measure of the time the larynx remained in its superior position during swallowing. In 10 subjects, the cricopharyngeus muscle (CP) of the upper esophageal spinchter showed a continuous tonic EMG activity except during swallowing. All the parameters measured were influenced by the type and volume of the bolus material. The method presented in this study proved its usefulness in the study of the physiology of deglutition as well as in its objective clinical evaluation in patients with dysphagia.© 1995 John Wiley & Sons, Inc.     

Reinnervation of laryngeal muscles: a study of changes in myosin heavy chain expression

Direct repair of the recurrent laryngeal nerve (RLN) results in synkinesis and compromised laryngeal function. We have therefore developed a pig model to investigate whether anastomosis of the phrenic nerve with the abductor branch of the RLN leads to specific reinnervation of abductor muscles. Expression of myosin heavy chain protein (MyHC), a marker of appropriate reinnervation, was determined in the posterior cricoarytenoid (PCA) abductor and thyroarytenoid (TA) adductor muscles following nerve injury and repair. The denervated PCA muscle exhibited decreased levels of the fast-type MyHC isoforms IIA and IIB, and increased slow-type MyHC expression. Similarly, there was a fall in type IIB levels in the denervated TA muscle but increases in both IIA and slow MyHC. Four months after repair, the MyHC expression in the PCA was near normal, suggesting that our model reduces the risk of synkinesis and ensures the accurate muscle reinnervation required for full functional recovery.     

Spontaneous and reflexly evoked laryngeal abductor and adductor muscle activity of cat

A study of spontaneous and reflexly evoked activity of laryngeal abductor (posterior cricoarytenoid) and adductor (thyroarytenoid and lateral cricoarytenoid) muscles was carried out in cats anesthetized with chloraloseurethane or made decerebrate and supplemented with ketamine HCl. The posterior cricoarytenoid muscle was active largely during inspiration but showed tonic activity throughout the respiratory cycle; the thyroarytenoid and lateral cricoarytenoid muscles were rhythmically active during expiration. Anesthetic amounts of pentobarbital abolished adductor rhythmicity and enhanced cyclic inspiratory activity of the abductor muscle. Hyperventilation increased the tonic adductor muscle activity while diminishing abductor muscle activity prior to resolution of apnea. Glossopharyngeal (epipharyngeal branch) and superior laryngeal nerve stimulation evoked chiefly excitatory effects on adductors and largely and attenuating effect on the abductor during inspiration. Stimulation of caudal intercostal nerves caused similar effects but to a lesser degree. Peripheral phrenic nerve stimulation during inspiration facilitated reflex abductor muscle activity whereas such stimulation during expiration facilitated reflex adductor muscle activity. The collective evidence further supports the conclusion that the larynx has a dual function: that of a respiratory organ (widening of the glottis during inspiration and its narrowing during expiration) and of a guardian of the lower respiratory tract from invading foreign matter (reflex sphincter action of contracting adductor muscles with relaxation of the abductor).     

Peripheral course and intramucosal distribution of the laryngeal sensory nerve fibers of cats

In order to demonstrate distribution of the laryngeal peripheral sensory nerve fibers of cats, wheat germ agglutinin-horseradish peroxidase was injected into the nodose ganglion. The results were as follows: The internal branch of the superior laryngeal nerve (SLN) innervated ipsilaterally the epiglottis, the aryepiglottic fold, the arytenoid eminence, the rostral aspect of the vocal fold, the laryngeal vestibulum and the mucosa covering the posterior cricoarytenoid muscle. The posterior branch of the recurrent laryngeal nerve (RLN) was divided into two branches. One branch formed Galen's anastomosis together with fibers of the internal branch of the SLN. The other supplied the caudal aspect of the vocal folds and the subglottis, together with fibers of the internal branch of the SLN, bilaterally with ipsilateral predominance. Some fibers of the internal branch of the SLN united with some fibers of the posterior branch of the RLN and penetrated the cricoid foramen to innervate the posterior wall of the glottis and the medial aspect of the arytenoid cartilage bilaterally with ipsilateral predominance.     

A dysphagia study in patients with sporadic inclusion body myositis (s-IBM)

The nature of the swallowing impairment in patients with sporadic inclusion body myositis (s-IBM) has not been well characterized. In this study, we examined ten consecutive s-IBM patients using videofluoroscopy (VF) and computed pharyngoesophageal manometry (CPM). The patients were divided into two groups: patients with complaint and without complaint of dysphagia. VF results indicated pharyngeal muscle propulsion (PP) at the hypopharyngeal and upper esophagus sphincter (UES) in all s-IBM patients. Patients without complaint of dysphagia showed a mild degree of PP, whereas a severe form of PP was observed in patients with complaint of dysphagia. CPM revealed that negative pressure during UES opening was not observed in the s-IBM patients with complaint of dysphagia. Incomplete opening and PP at the UES were observed in all s-IBM patients. These results indicate that the dysphagic processes occur subclinically in s-IBM patients who may not report swallowing impairments.     

Serotonin-mediated excitation of recurrent laryngeal and phrenic motoneurons evoked by stimulation of the raphe obscurus

Short-latency averaged responses in the recurrent laryngeal nerve (RLN) and C₅ phrenic nerve to electrical stimulation (2.5–80 μA; 2.5–160 Hz; 150 μs pulse duration) of the medullary nucleus raphe obscurus (RO) were investigated in anaesthetized, paralyzed and artificially ventilated cats. The response evoked in RLN by stimulation within RO was excitatory and consisted of a single peak. Characteristics of this response in RLN were compared with those of the delayed excitatory response in C₅ phrenic nerve, which we previously showed to be elicited by stimulation within RO. Mean latency to onset for the excitatory response in RLN was5.7 ± 0.3ms, while the delayed excitatory response in C₅ phrenic nerve occurred at7.0 ± 0.3ms. The excitatory response in both could be evoked when stimulation was applied during inspiration as well as during expiration. The stimulus threshold varied between 2.5 and 5 μA for evoked the inspiratory-phase response in each nerve. The magnitude of this response in RLN and in C₅ phrenic nerve was directly related to current intensity and was dependent upon stimulus frequency. Intravenous administration of the serotonin receptor antagonist, methysergide (0.1–2.4 mg/kg) caused significant dose-related reductions in the response in each nerve. In summary, characteristics of the evoked response in RLN and phrenic nerve are similar in several ways. Both responses are: (1) excitatory in nature, (2) elicited at small stimulus currents, (3) affected similarly by increasing stimulus current and frequency, (4) elicited by stimulation during inspiration and expiration, and (5) mediated at least in part by activation of pathways using serotonin as a neurotransmitter.     

The declining electrical response of muscle to repetitive nerve stimulation in myotonia

The electrical response of muscle to repetitive nerve stimulation was studied in patients with various myotonic disorders. A decrementing response was common but not invariable finding, and was unrelated to the severity or diagnosis. The decrement either continued throughout the period of stimulation or "leveled off", sometimes being followed by an increment. If it occurred at low rates of stimulation, a greater decrement occurred at higher rates, usually after a shorter latent period. It was not related consistently to the presence of weakness, but in patients with myotonia congenita it was more conspicuous and elicited by lower rates of stimulation when transient weakness was a feature of the history.     

Activity of extrinsic tongue muscles during swallowing in sheep

The participation of extrinsic muscles of the tongue in swallowing reflexly induced by stimulation of the superior laryngeal nerve was studied in 7 anesthetized sheep. The tongue retractor muscles (styloglossus and hyoglossus) always discharged in synergy with the suprahyoid (geniohyoid) and jaw (anterior digastric and medial pterygoid) muscles. The main protrusor muscle of the tongue, the genioglossus, was inactive in 5 animals and active in 2. The significance of this muscular synergy is discussed.     

Effect of catecholamines on the swallowing reflex after pressure microinjections into the lateral solitary complex of the medulla oblongata

The present study was carried out to elucidate the influence of catecholamines on swallowing, a polysynaptic reflex organized by an interneuronal network localized mainly within the lateral solitary complex (LSC) of the medulla oblongata. The effects of catecholaminergic agents were investigated in the rat, on rhythmic swallowing elicited by repetitive stimulation of the superior laryngeal nerve (SLN). Catecholaminergic agents were microinjected by pressure application, through multibarrelled glass micropipettes, into the LSC including the tractus solitarius, the swallowing region of the nucleus of the solitary tract and the adjacent reticular formation. Microinjections of noradrenaline (NA, 0.1–5 nmol, 50 nl) induced a significant decrease of the number and the amplitude of the rhythmic swallows elicited by stimulation of the ipsilateral SLN. This inhibitory effect was dose-related. Microinjections of clonidine (2.5 nmol, 50 nl), dopamine (0.25–2.5 nmol, 50 nl) and apomorphine (0.5 nmol, 50 nl), also inhibited swallowing. No significant modification of swallowing was induced by control injections of the vehicle (50 nl) within the active sites. Moreover the NA-induced inhibition of swallowing, was significantly antagonized by pretreatment with the -adrenergic blocker phentolamine applied locally in the LSC. Furthermore neither blood pressure, nor respiratory rhythm were consistently modified by the catecholaminergic microinjections, indicating that the catecholamine-induced inhibition of swallowing was not a secondary side effect originating from alteration of these functions. It can therefore be concluded that the present results demonstrate the existence within the LSC of a catecholaminergic inhibition of the swallowing reflex. This inhibitory effect likely arises from activation of specific catecholaminergic receptors and effects the swallowing structures localized within the LSC, i.e., the laryngeal swallowing afferents running in the solitary tract and/or the swallowing interneurons within the nucleus of the solitary tract.