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RATIONALE: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. OBJECTIVES: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). METHODS: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory “drive” (calibrated intraesophageal diaphragm EMG), ventilation (oronasal “ventilation”), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation–drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. MEASUREMENTS AND MAIN RESULTS: REM sleep (⩾10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], −21.8% [−31.2% to −12.4%] of eupnea; P

The pharyngeal airway behaves like an artificial collapsible tube within a rigid box. Any combinations of (1) increase of the tissue pressure surrounding the pharyngeal airway, (2) decrease of the intraluminal airway pressure, and (3) reduction of the longitudinal pharyngeal wall tension can collapse the pharyngeal airway and induce inspiratory flow limitation. Surface forces may contribute to the development of pharyngeal airway narrowing. Pharyngeal muscle contraction dilates and stiffens the pharyngeal airway by changing its mechanical properties. Wakefulness is the strongest stimulus to maintain the pharyngeal muscle activity.

Currently, there is no established technique to directly measure extrinsic tongue muscle activation during selective hypoglossal stimulation therapy (sHNS) in patients with obstructive sleep apnea syndrome (OSAS) in a simple, non-invasive clinical setting. Ultrasound shear-wave elastography (US-SWE) enables quantitative measurement of tissue stiffness. We investigated whether US-SWE is able to detect changes in muscle stiffness of the tongue during sHNS. Patients with OSAS treated with sHNS were prospectively enrolled. A standardized US-SWE protocol was used to selectively measure tissue stiffness of the geniohyoid muscle (GH) and genioglossus (GG) muscles on the side of stimulator implantation (sGH, sGG) and on the contralateral side (nGH, nGG) without and with sHNS. Eighteen patients were included (median age = 62 years, interquartile range: 56-65, 83.3% male). Median shear-wave velocity (SWV) increased during contraction with each patient's clinically prescribed therapeutic regimen in the sGH (+19%, p = 0.020) and sGG (+81%, p0.001) and decreased during contraction in the nGH (-8%, p = 0.107) and nGG (-8%, p = 0.396). Differences in SWV during contraction were significant only on the side of stimulation (sGG +81%, sGH +19%). SWE measurements had excellent reliability as reflected by a Cronbach α value ≥0.9 for all target muscles pre- and post-contraction and an item-total correlation ≥0.5. US-SWE allows reliable measurement of SWV as an indicator of muscle stiffness of extrinsic tongue muscles. This non-invasive method provides new possibilities to distinguish and characterize responders from non-responders in hypoglossal stimulation therapy. Compared with the regular visual assessment of tongue movement, US-SWE of individual muscle groups provides a new non-invasive imaging tool in patients with OSAS.

Hong Huang, Wenyang Li, Hongyu Jin, Lei Zhang, Zhijing Wei, Wei Wang Institute of Respiratory and Critical Care, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Wei WangInstitute of Respiratory and Critical Care, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People’s Republic of ChinaTel +86 24 83282529Fax +86 2483282002Email wwbycmu@126.comPurpose: Tongue strength training (TST) has been shown to decrease the apnea-hypopnea index in some patients with obstructive sleep apnea (OSA). However, whether TST modulates the central regulation of genioglossus and influences the stability of the upper airway remains unknown. The purpose of this study was to dynamically assess the effect of TST on the upper airway.Methods: Sixteen adult male Sprague–Dawley rats were studied to explore the mechanism of TST improving the upper airway function. The rats were randomly assigned to the normal control (NC) and TST groups. The TST group underwent 8-week progressive resistance tongue exercise training. Transcranial magnetic stimulation (TMS) responses and EMG activities were consistently recorded for 2 h on days 0, 14, 28, and 56 of the experiments in both groups. Theoretical critical pressure (Pcrit) value was measured on days 0, 14, 28, and 56.Results: The TST group showed shorter TMS latency and higher genioglossus EMG activity, which lasted from 5 min to 80 min after training on day 56 of training, than the NC group. The TST group showed significantly lower theoretical Pcrit values on days 28 and 56 of training than the NC group (-4.07± 0.92 vs -3.12± 0.77 cmH2O, P< 0.05, -4.66± 0.74 vs -3.07± 0.38 cmH2O, P< 0.01).Conclusion: This study revealed that an 8-week TST could gradually and transiently increase corticomotor excitability of genioglossus, elevate the genioglossus EMG activity, and ultimately enhance the stability of the upper airway during daytime. Moreover, improved neuromuscular excitability occurred prior to the enhanced upper airway stability. These findings provide a theoretical foundation for TST as a promising treatment for OSA patients.Keywords: tongue strength training, genioglossus, upper airway critical pressure, transcranial magnetic stimulation, corticomotor excitability

This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

Background and objective Animal studies indicate that alpha-1 adrenergic receptor agonists and antimuscarinic agents improve genioglossus muscle activity during sleep and may be candidates for the pharmacological treatment of OSA. On the other hand, noradrenergic stimulants may be wake-promoting or cause insomnia symptoms if taken before bedtime, and the addition of a medication with sedative properties, such as an antihistaminic, may reduce these side effects. In this study, we aimed to determine the effects of the combination of an alpha-1 adrenergic agonist (pseudoephedrine) and an antihistaminic-antimuscarinic (diphenhydramine) on OSA severity (AHI), genioglossus responsiveness and other endotypic traits (Vpassive , muscle compensation, LG and arousal threshold). Methods Ten OSA patients performed a randomized, placebo-controlled, double-blind, crossover trial comparing one night of pseudoephedrine 120 mg plus diphenhydramine 50 mg (DAW1033D) to placebo administered prior to sleep. The AHI, genioglossus muscle responsiveness to negative oesophageal pressure and the endotypic traits were measured via PSG. Results The participants' median (interquartile range) age was 50 (46-53) years and body mass index (BMI) was 34.3 (30.6-39.2) kg/m2 . The drug combination had no effect on AHI (21.6 (9.1-49.8) on placebo vs 37.9 (5.1-55.4) events/h on DAW1033D, P > 0.5) or genioglossus responsiveness (6.0 (2.6-9.2) on placebo vs 4.0 (3.5-7.3) %/cm H2 O). Amongst the phenotypic traits, only Vpassive was improved by 29 (3-55) % eupnoea, P = 0.03 (mean (95% CI)). Conclusion The combination of pseudoephedrine and diphenhydramine did not improve OSA severity or genioglossus responsiveness but induced a small improvement in upper airway collapsibility, possibly due to the decongestant effect of the medications. The results of this study do not support the use of these medications for OSA treatment.

Rationale: Obstructive sleep apnea is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. The main goal of our study was to determine if designer receptors exclusively activated by designer drugs (DREADD) could be used to activate the genioglossus muscle as a potential novel treatment strategy for sleep apnea. We have previously shown that the prototypical DREADD ligand clozapine-N-oxide increased pharyngeal diameter in mice expressing DREADD in the hypoglossal nucleus. However, the need for direct brainstem viral injections and clozapine-N-oxide toxicity diminished translational potential of this approach, and breathing during sleep was not examined.Objectives: Here, we took advantage of our model of sleep-disordered breathing in diet-induced obese mice, retrograde properties of the adeno-associated virus serotype 9 (AAV9) viral vector, and the novel DREADD ligand J60.Methods: We administered AAV9-hSyn-hM3(Gq)-mCherry or control AAV9 into the genioglossus muscle of diet-induced obese mice and examined the effect of J60 on genioglossus activity, pharyngeal patency, and breathing during sleep.Measurements and Main Results: Compared with control, J60 increased genioglossus tonic activity by greater than sixfold and tongue uptake of 2-deoxy-2-[18F]fluoro-d-glucose by 1.5-fold. J60 increased pharyngeal patency and relieved upper airway obstruction during non-REM sleep.Conclusions: We conclude that following intralingual administration of AAV9-DREADD, J60 can activate the genioglossus muscle and improve pharyngeal patency and breathing during sleep.

Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad). One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points. (1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study. Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy.

Background Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway collapse during sleep. The contraction of upper airway dilator muscles plays a crucial role in maintaining UA patency. Chronic intermittent hypoxia (CIH) is the most important pathophysiological process of OSA. Exposure to CIH induced not only the damage of dilator muscles but also the plasticity of the muscles. This study aimed to dynamically assess the influence of CIH on the upper airway. Methods The experiments were performed on 44 rats. They were randomly divided into a normoxia (NO) group (n=22) and CIH group (n=22). In each group (n=6, respectively), EMG, transcranial magnetic stimulation (TMS) response, and critical pressure (Pcrit) value were recorded on day 0 (the day before exposure), and the 7th, 14th, 21st, and 28th day of air/CIH exposure. For each group, 16 rats were used for transmission electron microscopy observations on day 0, and the 7th, 14th and 28th day of air/CIH exposure (n=4 for every time point). Results Compared to the NO group at the same point, the CIH group showed a damaged ultrastructure of genioglossus, increased activity of genioglossus corticomotor area, and increased Pcrit of the upper airway from the 7th to the 28th day of CIH. Increased EMG activity occurred at the 14th day of CIH and lasted for 2 weeks. Conclusion The elevated genioglossus corticomotor excitability in response to the CIH could not counterbalance the damage effect of CIH on upper airway dilator muscles, which ultimately increased the collapsibility of the upper airway.

Lingual frenotomy has become an increasingly common surgical procedure, performed for a broad range of indications from birth through adulthood. This study utilizes histology to define the structure and tissue composition of the lingual frenulum and floor of mouth (FOM) fascia. En bloc specimens of anterior tongue, lingual frenulum, and FOM tissues were harvested from ten embalmed adult cadavers. An additional three fresh tissue cadaveric specimens were frozen with the tongue supported in an elevated position, to enable harvesting and paraffin embedding of the elevated lingual frenulum as a discrete specimen. All 13 specimens were prepared as ten-micron coronal sections using stains to determine the general morphology of the lingual frenulum, its relationship to neighbouring structures (Mason’s Trichrome), presence of elastin fibers (Verhoeff-van Gieson), and collagen typing (Picrosirius Red). Our results have shown a submucosal layer of fascia spanning horizontally across the FOM was present in all specimens, with variability in fascial thickness and histologic composition. This FOM fascia suspends the sublingual glands, vessels, and genioglossus from its deep surface. The elevated lingual frenulum is formed by a central fold of this FOM fascia together with the overlying oral mucosa with variability in fascial thickness and composition. With tongue elevation, the fascia mobilizes to a variable extent into the fold forming the frenulum, providing a structural explanation for the individual variability in lingual frenulum morphology seen in clinical practice.

Background Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. Methods Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed. Results We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles. Conclusions Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.

Obstructive sleep apnea (OSA) is more common in patients with asthma, and inhaled corticosteroids may contribute to OSA pathogenesis in these patients. This study tested the effects of orally inhaled fluticasone propionate (FP) on extrinsic tongue muscles. Unanesthetized rats were treated with FP or placebo for 28 days. On day 29, tongue retrusive and protrusive functions were tested via hypoglossal nerve stimulation under a state of anesthesia, followed by genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscle extraction, after euthanasia, for histology [myosin heavy chain (MHC) fibers and laminin content reflecting extracellular matrix (ECM)]. On protrusive testing, FP increased percent maximum tetanic force at 40 Hz ( P = 0.03 vs. placebo) and endurance index ( P = 0.029 vs. placebo). On retrusive testing, FP increased maximum twitch ( P = 0.026 vs. placebo) and tetanic forces ( P = 0.02 vs. placebo) with no effect on endurance index. On histology, FP increased GG cross-sectional area of MHC type IIa ( P = 0.036 vs. placebo) and tended to increase type IIb ( P = 0.057 vs. placebo) fibers and HG MHC IIx fibers ( P = 0.065). The FP group had significantly increased laminin-stained areas, of greatest magnitude in the HG muscle. FP affects tongue protrusive and retrusive functions differently, concurrent with a shift in MHC fibers and increased ECM accumulation. These differential alterations may destabilize the tongue’s “muscle hydrostat” during sleep and promote collapse. NEW & NOTEWORTHY The effects of inhaled corticosteroid on upper airway may contribute to OSA pathogenesis in asthma. In this study, we tested the effects of orally inhaled fluticasone propionate on tongue protrusive and retrusive functions and on tongue extrinsic muscle fiber composition and molecular properties. We found that fluticasone treatment: 1) increased protrusive endurance and retrusive maximum twitch and tetanic force; and 2) on histology, increased cross-sectional area of myosin heavy chain (MHC) type IIa fibers and tended to increase cross-sectional area of MHC type IIb fibers in the protrusive muscle and of MHC IIx fibers in the retrusors. It also increased laminin-stained areas, across extrinsic tongue muscles, of greatest magnitude in the retrusors; and 3) reduced protein degradation and activated pathways associated with increased protein synthesis in the protrusor. These differential effects on the protrusors and retrusors may destabilize the tongue’s “muscle hydrostat” properties during sleep and promote collapse.

Objective Sleep apnea research cites that an oral appliance, which places the mandible in a more forward position and the genioglossus (tongue muscle) on the floor of the mouth, improves aspects of the pharyngeal opening. Exercise science research has cited improvements in airway dynamics and physiological variables with oral appliance use during exercise. Thus, the purpose of this study was to design an oral appliance that would act on the genioglossus and determine if there were effects on respiratory parameters while exercising. Materials and methods Seventeen healthy subjects ages 18–43 participated in this study. Prior to the exercise protocol, the order of the oral applicance (OA) or no oral appliance (no OA) condition was randomly assigned to subjects, with subjects completing both conditions. Respiratory parameters (respiratory rate, ventilation, oxygen, and carbon dioxide) were measured between conditions while subjects ran for 10 min at steady state. Results The results demonstrated that both respiratory rate (25.97 BPM, OA and 28.35 BPM, no OA) and ventilation (47.66 l/min, OA and 50.34 l/min, No OA) were significantly lowered (p < .01) in the OA condition. There were no differences in carbon dioxide (1.89 l/min, no OA and 1.88 l/min, OA) or oxygen outcomes (2.17 l/min, no OA and 2.17 l/min OA). Discussion The outcomes from this study suggest that the design of the oral appliance elicits an effect on the genioglossus, thereby resulting in lowered respiratory rate and ventilation with no negative effects on oxygen uptake during exercise.

WOS:000548824300006 Objectives: Among different theories about pathogenesis of obstructive sleep apnea syndrome (OSAS), dysfunction of upper airway muscles still awaits to be delineated. The aim of this study is to examine differences in motor unit potential (MUP) parameters of upper airway muscles between OSAS patients and healthy controls. Methods: Ten male patients diagnosed as OSAS by whole-night polysomnography were analyzed for MUP parameters of genioglossus (GG) muscle, palatoglossus muscle (PG), palatopharyngeus muscle, and uvular (U) muscle. Eight healthy volunteer men matched by age were enrolled as a control group. Results: In PG muscle parameters, the mean MUP area was significantly smaller (P = 0.040) in OSAS patients than those in controls. On the other hand, U muscle parameters showed a significantly larger mean MUP area (P = 0.022) in OUAS patients compared to those in the control group. In OSAS patients, the percentages of polyphasic MUPs of GG and PG muscles were significantly high (P < 0.001 and P = 0.05, respectively). Body mass index was positively correlated with number of phases of GG muscle (rs = 0.63, P < 0.05) and duration of U muscle (rs = 0.71, P < 0.05) in OSAS patients. Other MUP parameters of palatal muscles were similar between the two groups. Conclusion: Our results showed that, although mild in severity, structural neurogenic and myogenic changes characterized as mild and nonuniform MUP changes may co-exist in OSAS patients. These changes in palatal muscles may be attributed to compensatory adaptation of muscle fibers to other precipitating factors in OSAS.

Purpose: Exercise-based treatment approaches for dysphagia may improve swallow function in part by inducing adaptive changes to muscles involved in swallowing and deglutition. We have previously shown that both aging and progressive resistance tongue exercise, in a rat model, can induce biological changes in the genioglossus (GG); a muscle that elevates and protrudes the tongue. However, the impacts of progressive resistance tongue exercise on the retrusive muscles (styloglossus, SG; hyoglossus, HG) of the tongue are unknown. The purpose of this study was to examine the impact of a progressive resistance tongue exercise regimen on the retrusive tongue musculature in the context of aging. Given that aging alters retrusive tongue muscles to more slowly contracting fiber types, we hypothesized that these biological changes may be mitigated by tongue exercise.Methods: Hyoglossus (HG) and styloglossus (SG) muscles of male Fischer 344/Brown Norway rats were assayed in age groups of young (9 months old, n = 24), middle-aged (24 months old, n = 23), and old (32 months old, n = 26), after receiving an 8-week period of either progressive resistance protrusive tongue exercise, or sham exercise conditions. Following exercise, HG and SG tongue muscle contractile properties were assessed in vivo. HG and SG muscles were then isolated and assayed to determine myosin heavy chain isoform (MyHC) composition.Results: Both retrusive tongue muscle contractile properties and MyHC profiles of the HG and SG muscles were significantly impacted by age, but were not significantly impacted by tongue exercise. Old rats had significantly longer retrusive tongue contraction times and longer decay times than young rats. Additionally, HG and SG muscles showed significant MyHC profile changes with age, in that old groups had slower MyHC profiles as compared to young groups. However, the exercise condition did not induce significant effects in any of the biological outcome measures.Conclusion: In a rat model of protrusive tongue exercise, aging induced significant changes in retrusive tongue muscles, and these age-induced changes were unaffected by the tongue exercise regimen. Collectively, results are compatible with the interpretation that protrusive tongue exercise does not induce changes to retrusive tongue muscle function.

Oropharyngeal dysphagia can cause chronic aspiration leading to significant respiratory symptoms. When dysphagia is diagnosed, an underlying cause is sought. We present a case series of 15 children diagnosed aged 6 months to 5 years (mean 2y 5mo; 11 males, four females) over a 6-year period, who were found to have an isolated bulbar palsy on genioglossus electromyography, with no accompanying neurological or neurodevelopmental disorder. Eight children had dysphagia but a normal EMG. In those with isolated bulbar palsy, management included thickened fluids (n=13), cooled boiled water (n=1), and nasogastric tube feeding (n=1). Follow-up over 1 to 8 years (mean 5y) showed complete resolution in six children, improvement in four children, and no improvement in five children (including two requiring fluids via a gastrostomy). Eight children no longer had any respiratory symptoms. Isolated bulbar palsy is under-recognized and has not been reported previously as a cause of significant dysphagia in children.

The genioglossus is a major upper airway dilator muscle. Our goal was to assess the efficacy of upper airway muscle training on Obstructive Sleep Apnea (OSA) as an adjunct treatment. Sixty-eight participants with OSA (AHI &gt, 10/h) were recruited from our clinic. They fall into the following categories: (a) Treated with Automatic Positive Airway Pressure (APAP), (n = 21), (b) Previously failed APAP therapy (Untreated), (n = 25), (c) Treated with Mandibular Advancement Splint (MAS), (n = 22). All subjects were given a custom-made tongue strengthening device. We conducted a prospective, randomized, controlled study examining the effect of upper airway muscle training. In each subgroup, subjects were randomized to muscle training (volitional protrusion against resistance) or sham group (negligible resistance), with a 1:1 ratio over 3 months of treatment. In the baseline and the final visit, subjects completed home sleep apnea testing, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), SF-36 (36-Item Short Form Survey), and Psychomotor Vigilance Test (PVT). Intervention (muscle training) did not affect the AHI (Apnea-Hypopnea Index), (p-values &gt, 0.05). Based on PSQI, ESS, SF-36 scores, and PVT parameters, the changes between the intervention and sham groups were not significant, and the changes were not associated with the type of treatment (p-value &gt, 0.05). The effectiveness of upper airway muscle training exercise as an adjunct treatment requires further study.

New finding What is the central question of this study? Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal-dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity? What is the main finding and its importance? The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. Abstract The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg-positive-pressure application. Moving from the sitting position to the supine position reduces respiratory-related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity.

This study aimed to determine whether there is impairment of genioglossus neuromuscular responses to small negative pressure respiratory stimuli, close to the conscious detection threshold, in obstructive sleep apnea (OSA). We compared genioglossus electromyogram (EMGgg) responses to midinspiratory resistive loads of varying intensity (≈1.2–6.2 cmH2O·L−1·s), delivered via a nasal mask, between 16 severe OSA and 17 control participants while the subjects were awake and in a seated upright position. We examined the relationship between stimulus intensity and peak EMGgg amplitude in a 200-ms poststimulus window and hypothesized that OSA patients would have an increased activation threshold and reduced sensitivity in the relationship between EMGgg activation and stimulus intensity. There was no significant difference between control and OSA participants in the threshold ( P = 0.545) or the sensitivity ( P = 0.482) of the EMGgg amplitude vs. stimulus intensity relationship, where change in epiglottic pressure relative to background epiglottic pressure represented stimulus intensity. These results do not support the hypothesis that deficits in neuromuscular response to negative upper airway pressure exist in OSA during wakefulness; however, the results are likely influenced by a counterintuitive and novel genioglossus muscle suppression response observed in a significant proportion of both OSA and healthy control participants. This suppression response may relate to the inhibition seen in inspiratory muscles such as the diaphragm in response to sudden-onset negative pressure, and its presence provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure. NEW & NOTEWORTHY Our study used a novel midinspiratory resistive load stimulus to study upper airway neuromuscular responses to negative pressure during wakefulness in obstructive sleep apnea (OSA). Although no differences were found between OSA and healthy groups, the study uncovered a novel and unexpected suppression of neuromuscular activity in a large proportion of both OSA and healthy participants. The unusual response provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.

Objectives This report describes the surgical implantation of a novel bilateral hypoglossal nerve stimulator (Genio system®, Nyxoah S.A., Belgium) and the successful treatment of a patient with moderate obstructive sleep apnea (OSA). Study Design Surgical technique description and case study report. Methods The bilateral implantable stimulator (IS) simultaneously stimulates both genioglossus (GG) muscles to reduce airway obstruction. At night, patients wear an activation chip under their chin that wirelessly transmits energy to the implant and enables the nerve stimulation. Surgical implantation of the IS is performed under general anesthesia by making a small incision above the hyoid bone and dissecting through the platysma, mylohyoid, and geniohyoid muscles to the GG muscle. The hypoglossal nerve branches are then identified, followed by suturing the IS in place. The system was evaluated in an otherwise healthy, 60-year-old woman with moderate OSA (apnea hypopnea index (AHI): 25/hr, nadir O2 saturation: 78%). Appropriate stimulation settings were determined at 2-, 3-, and 6-months post implantation during polysomnography (PSG) and changes in apnea and hypopnea events and oxygen desaturation recorded. Results The surgery was well tolerated by the patient with an uneventful recovery. The PSG at 6 months showed that AHI per hour, obstructive apnea events per hour, hypopnea events per hour, and oxygen desaturation index have been reduced by 88%, 92%, 88%, and 97%, respectively, and nadir O2 saturation improved to 91%. Conclusions The absence of complications and considerable reduction of apnea and hypopnea events in this case study help demonstrate the potential safety and efficacy of the bilateral hypoglossal nerve stimulator. Level of Evidence 4.

Background Oral appliances (OAs) are generally designed to displace the mandible anteriorly and downward, to increase the airway patency. The present study aimed to examine the relationship between genioglossus (GG) muscle activity and mandibular position, considering both anterior and vertical displacements during sleep. Methods Seven healthy male adults aged 29.4 ± 1.99 years were evaluated. Maxillary and mandibular OAs were fabricated from 2-mm-thick resin plates with pressure-welding. The activity of the left GG was recorded using two silver ball electrodes attached to the lingual edge of the mandibular OA. Respiratory status and right masseter muscle activity were measured by an airflow sensor and surface electrodes, respectively. Electroencephalography was used to determine the sleep status. Stage 2 (the second stage of sleep) was defined as the state of sleeping. Four test conditions with different mandibular positions (0 and 50% anterior protrusion) and bite openings (4 mm and 12 mm) were examined. Results GG activity in SL4A (4 mm bite opening, 50% protrusion during sleep) and SL12 (12 mm bite opening, 0% protrusion during sleep) were significantly higher than that in SL4 (4 mm bite opening, 0% protrusion during sleep). Respiratory volume did not significantly differ between all test conditions. Conclusion GG activity is influenced not only by anterior protrusion of the mandible but also by vertical displacement during sleep. Thus, when determining the effectiveness of intraoral appliances in the treatment of obstructive sleep apnea, both protrusion and the size of the mandibular opening should be evaluated and taken into account.

Proper function of pharyngeal dilator muscles, including the genioglossus muscle of the tongue, is required to maintain upper airway patency. During sleep, the activity of these muscles is suppressed, and as a result individuals with obstructive sleep apnea experience repeated episodes of upper airway closure when they are asleep, in particular during rapid-eye-movement (REM) sleep. Blocking cholinergic transmission in the hypoglossal motor nucleus (MoXII) restores REM sleep genioglossus activity, highlighting the importance of cholinergic transmission in the inhibition of hypoglossal motor neurons (HMNs) during REM sleep. Glutamatergic afferent input from neurons in the parahypoglossal (PH) region to the HMNs is critical for MoXII respiratory motor output. We hypothesized that state-dependent cholinergic regulation may be mediated by this pathway. Here we studied the effects of cholinergic transmission in HMNs in adult male and female mice using patch-clamp recordings in brain slices. Using channelrhodopsin-2-assisted circuit mapping, we first demonstrated that PH glutamatergic neurons directly and robustly activate HMNs (PHGlut→ HMNs). We then show that carbachol consistently depresses this input and that this effect is presynaptic. Additionally, carbachol directly affects HMNs by a variable combination of muscarinic-mediated excitatory and inhibitory responses. Altogether, our results suggest that cholinergic signaling impairs upper airway dilator muscle activity by suppressing glutamatergic input from PH premotoneurons to HMNs and by directly inhibiting HMNs. Our findings highlight the complexity of cholinergic control of HMNs at both the presynaptic and postsynaptic levels and provide a possible mechanism for REM sleep suppression of upper airway muscle activity.SIGNIFICANCE STATEMENTIndividuals with obstructive sleep apnea can breathe adequately when awake but experience repeated episodes of upper airway closure when asleep, in particular during REM sleep. Similar to skeletal postural muscles, pharyngeal dilator muscles responsible for maintaining an open upper airway become hypotonic during REM sleep. Unlike spinal motoneurons controlling postural muscles that are inhibited by glycinergic transmission during REM sleep, hypoglossal motoneurons that control the upper airway muscles are inhibited in REM sleep by the combination of monoaminergic disfacilitation and cholinergic inhibition. In this study, we demonstrated how cholinergic signaling inhibits hypoglossal motoneurons through presynaptic and postsynaptic muscarinic receptors. Our results provide a potential mechanism for upper airway hypotonia during REM sleep.

Alzheimer's disease (AD) is a progressive neurodegenerative condition disturbing major brain networks, including those pivotal to the motor control of breathing. The aim of this study was to examine respiratory control in the TgF344-AD transgenic rat model of AD. At 8-11 months of age, basal minute ventilation and ventilatory responsiveness to chemostimulation were equivalent in conscious wild-type (WT) and TgF344-AD rats. Under urethane anesthesia, basal diaphragm and genioglossus EMG activities were similar in WT and TgF344-AD rats. The duration of phenylbiguanide-induced apnoea was significantly shorter in TgF344-AD rats compared with WT. Following bilateral cervical vagotomy, diaphragm and genioglossus EMG responsiveness to chemostimulation were intact in TgF344-AD rats. Amyloid precursor protein C-terminal fragments were elevated in the TgF344-AD brainstem, in the absence of amyloid-β accumulation or alterations in tau phosphorylation. Brainstem pro-inflammatory cytokine concentrations were not increased in TgF344-AD rats. We conclude that neural control of breathing is preserved in TgF344-AD rats at this stage of the disease.

The lingual frenulum is recognized as having the potential to limit tongue mobility, which may lead to difficulties with breastfeeding in some infants. There is extensive variation between individuals in the appearance of the lingual frenulum but an ambiguous relationship between frenulum appearance and functional limitation. An increasing number of infants are being diagnosed with ankyloglossia, with growing uncertainty regarding what can be considered "normal" lingual frenulum anatomy. In this study, microdissection of four fresh tissue premature infant cadavers shows that the lingual frenulum is a dynamic, layered structure formed by oral mucosa and the underlying floor of mouth fascia, which is mobilized into a midline fold with tongue elevation and/or retraction. Genioglossus is suspended from the floor of mouth fascia, and in some individuals can be drawn up into the fold of the frenulum. Branches of the lingual nerve are located superficially on the ventral surface of the tongue, immediately beneath the fascia, making them vulnerable to injury during frenotomy procedures. This research challenges the longstanding belief that the lingual frenulum is a midline structure formed by a submucosal "band" or "string" and confirms that the neonatal lingual frenulum structure replicates that recently described in the adult. This article provides an anatomical construct for understanding and describing variability in lingual frenulum morphology and lays the foundation for future research to assess the impact of specific anatomic variants of lingual frenulum morphology on tongue mobility. Clin. Anat. 32:824-835, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

Surgical release of the lingual frenulum (frenotomy) has become an increasingly common procedure, performed from birth through to adulthood. Surprisingly, detailed anatomy of the in-situ lingual frenulum has never been described, and no anatomical basis has been proposed for the individual variability in frenulum morphology. The lingual frenulum is frequently referred to as a "cord" or "submucosal band" of connective tissue, yet there is no evidence to support this anatomical construct. This paper aims to describe the anatomy of the in-situ lingual frenulum and its relationship to floor of mouth structures. Fresh tissue microdissection of the lingual frenulum and floor of mouth was performed on nine adult cadavers with photo-documentation and description of findings. The lingual frenulum is a dynamic structure, formed by a midline fold in a layer of fascia that inserts around the inner arc of the mandible, forming a diaphragm-like structure across the floor of mouth. This fascia is located immediately beneath the oral mucosa, fusing centrally with the connective tissue on the tongue's ventral surface. The sublingual glands and submandibular ducts are enveloped by the fascial layer and anterior genioglossus fibers are suspended beneath it. Lingual nerve branches are located superficially on the ventral surface of the tongue, immediately deep to the fascia. The lingual frenulum is not a discrete midline structure. It is formed by dynamic elevation of a midline fold in the floor of mouth fascia. With this study, the clinical concept of ankyloglossia and its surgical management warrant revision. Clin. Anat. 32:749-761, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

Objectives/hypothesis Genioglossus advancement is performed in select patients with obstructive sleep apnea. Surgical techniques attempt to capture the genial tubercle of the mandible; however, measurements of the genioglossus, geniohyoid, and digastric muscles are poorly delineated. This investigation is the largest anatomic study exploring the muscles of genial advancement surgery and the first to quantitatively characterize muscular attachments relative to the tubercle, providing new insights from an anatomic perspective on optimizing muscular advancement. Study design Cadaveric study. Methods Fifty-three fresh cadaveric mandibles underwent dissection of the genial tubercle and genioglossus, geniohyoid, and digastric muscles. Results Genial tubercle, geniohyoid, and genioglossus mean height was 7.78 mm, 5.15 mm, and 6.11 mm, respectively. On average, the geniohyoid began 4.88 mm and ended 10.03 mm from the inferior border of the mandible; the genioglossus 11.91 mm and 18.01 mm, similarly. Intermuscular distance, if present, was 2.67 mm; the muscles overlapped in 28% of cadavers. The combined vertical height of the muscles at their mandibular attachment was 13.94 mm, significantly differing from the height of the genial tubercle. The left and right lateral insertion of the digastric muscles was 19.34 mm and 19.31 mm, respectively, from midline. Conclusions The variable range of muscle attachments suggests that genioglossal and geniohyoid attachments extend beyond the genial tubercle and may not originate concentrically from the tubercle, but overlap and lie in very close proximity. Mandibular anterior muscle attachments require anatomic accuracy and an effective operative evaluation of advancement before reproducible, clinically effective osteotomies can be recommended. Level of evidence NA Laryngoscope, 129:2424-2429, 2019.

BACKGROUND AND PURPOSE: When optimising radiotherapy treatments today, the pharyngeal constrictor muscles and the larynx are usually regarded as the swallowing organs at risk (SWOARs). The purpose of this study was to identify and describe additional, previously undefined groups of muscles (functional units) involved in crucial components of swallowing (hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion), and to emphasise their relevance in radiation-induced dysphagia.MATERIAL AND METHODS: Based on available literature on human anatomy and swallowing physiology, the functional units of muscles involved in HLE, TBR and tongue motion have been identified and described.RESULTS AND CONCLUSION: Functional swallowing units (FSUs) were defined as groups of swallowing muscles sharing their function, that are in close proximity to each other. Seven FSUs involved in HLE, TBR and tongue motion were identified: floor of mouth, thyrohyoid muscles, posterior digastric/stylohyoid muscles complex, longitudinal pharyngeal muscles, hyoglossus/styloglossus muscles complex, genioglossus muscles, intrinsic tongue muscles. The swallowing physiology and anatomy of the FSUs described in this paper will lead to a greater understanding of radiation-induced dysphagia mechanisms and, consequently, to an improvement in the development of swallowing sparing strategies. This article (PART 1) serves as the theoretical foundation for a subsequent article (PART 2), which provides detailed delineation guidelines for FSUs.

Introduction Teaching and learning in anatomy are necessarily dependent on cadaveric dissection. Skillful dissection is the tool which helps in proper visualization of structures in a cadaver. Proper understanding about the course of lingual nerve, hypoglossal nerve, nerve to mylohyoid, and relations between structures present in infratemporal and submandibular regions is important for medical students. The aim of this study is to describe a modified technique of dissection and evaluate medical students' and teachers' response to this approach. Methods The comparative observational study was conducted bilaterally on six adult cadavers. We compared the method of dissection given in standard textbooks with the modified method introduced. The validity and reliability of the newer method of dissection for teaching purpose was assessed by first-year undergraduate medical students using a questionnaire-based tool and feedback from postgraduate students and senior residents. Results The modified method was described as less time consuming, easy to perform, and allowed extensive exploration of the structures in the infratemporal and submandibular regions. Conclusions Proper understanding of the course and relations between structures present in infratemporal and submandibular regions is important for medical students.The modified approach to infratemporal and submandibular regions will facilitate better understanding of the human anatomy.

To explore the effect of lingual artery ligation on tongue vascularity, we performed an analysis of 25 patients who underwent transoral robotic surgery for base of tongue cancers (May 2011 to December 2019). Hounsfield units of the intrinsic muscles (IMs) and genioglossus muscles (GGs) were measured in postoperative imaging (mean 4 months) as a surrogate for vascularity. In ligated patients (n = 15), the values from the ligated/resected side of the tongue were compared with the contralateral side and the nonligated side of resection. Individually, IMs and GGs on the ligated side demonstrated no significant difference to the contralateral side (P = .662 and .618, respectively). Ligation produced a significant decrease in IM measurements but no difference between GG values vs nonligated patients (P = .050 and .818, respectively). No difference was appreciated in mean values for combined IMs and GGs between cohorts (P = .212). No gross tongue atrophy or complications were incurred. Future studies are warranted to delineate long-term effects.

Key points Recent animal and human physiology studies indicate that noradrenergic and muscarinic processes are key mechanisms that mediate pharyngeal muscle control during sleep. The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, whether these findings translate to the clinically relevant patient population of people with obstructive sleep apnoea (OSA), and the effects of the agents on OSA severity, are unknown. We found that reboxetine plus hyoscine butylbromide reduced OSA severity, including overnight hypoxaemia, via increases in pharyngeal muscle responsiveness, improvements in respiratory control and airway collapsibility without changing the respiratory arousal threshold. These findings provide mechanistic insight into the role of noradrenergic and anti-muscarinic agents on upper airway stability and breathing during sleep and are important for pharmacotherapy development for OSA. Abstract The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, the effects of this drug combination on obstructive sleep apnoea (OSA) severity are unknown. Accordingly, this study aimed to determine if reboxetine plus hyoscine butylbromide reduces OSA severity. Secondary aims were to investigate the effects on key upper airway physiology and endotypic traits. Twelve people with OSA aged 52 ± 13 years, BMI = 30 ± 5 kg/m2 , completed a double-blind, randomised, placebo-controlled, crossover trial (ACTRN12617001326381). Two in-laboratory sleep studies with nasal mask, pneumotachograph, epiglottic pressure sensor and bipolar fine-wire electrodes into genioglossus and tensor palatini muscles were performed separated by approximately 1 week. Each participant received either reboxetine (4 mg) plus hyoscine butylbromide (20 mg), or placebo immediately prior to sleep. Polysomnography, upper airway physiology and endotypic estimates of OSA were compared between conditions. Reboxetine plus hyoscine butylbromide reduced the apnoea/hypopnoea index by (mean ± SD) 17 ± 17 events/h from 51 ± 30 to 33 ± 22 events/h (P = 0.005) and nadir oxygen saturation increased by 6 ± 5% from 82 ± 5 to 88 ± 2% (P = 0.002). The drug combination increased tonic genioglossus muscle responsiveness during non-REM sleep (median [25th, 75th centiles]: -0.007 [-0.0004, -0.07] vs. -0.12 [-0.02, -0.40] %maxEMG/cmH2 O, P = 0.02), lowered loop gain (0.43 ± 0.06 vs. 0.39 ± 0.07, P = 0.01), and improved airway collapsibility (90 [69, 95] vs. 93 [88, 96] %eupnoea, P = 0.02), without changing the arousal threshold (P = 0.39). These findings highlight the important role that noradrenergic and muscarinic processes have on upper airway function during sleep and the potential for pharmacotherapy to target these mechanisms to treat OSA.

Objective Exploring whether the genioglossus discharge in chronic intermittent hypoxia(CIH) – pretreated rats could be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH). Methods Rats were pretreated with CIH for 4 weeks and then were randomly divided into 6 groups: time control, intermittent electric stimulation, AIH, intermittent electric stimulation + AIH, continuous electric stimulation and continuous hypoxia exposure. The genioglossus discharges were recorded and compared before and after stimulation. Normoxic-treated rats were grouped and treated with the same stimulation protocols. Results Intermittent electrical stimulation or AIH temporarily increased the activity of the genioglossus discharge, in which the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation, AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats, in which the degree of the increase was significantly higher than in rats induced by a single intermittent electric stimulation. Conclusion Intermittent electrical stimulation combined with AIH strengthens the genioglossus plasticity in CIH-pretreated rats.

Objective To evaluate the prognostic value of needle electromyography (EMG) genioglossus involvement in patients with amyotrophic lateral sclerosis (ALS) at diagnosis. Methods We separately explored the prognostic value of clinical bulbar lower motor neuron (LMN) signs and EMG genioglossus involvement using Cox proportional hazard models adjusted for age, gender, diagnostic delay, presence of bulbar upper motor neuron (UMN) signs, EMG cervical and lumbosacral region involvement, ALSFRS-R score and C9Orf72 gene status. Then, we compared the prognostic value of EMG masseter and genioglossus abnormalities in a subset of patients in whom both muscles were analysed. Results 103 ALS patients were included in the study. Neurophysiological genioglossus involvement was associated with a shorter survival (p = 0.002), a shorter time to moderate dysphagia (p = 0.0001) and to severe dysarthria (p = 0.012). Its prognostic value was still evident in patients without clinical bulbar LMN signs. Bulbar clinical LMN signs were only associated with an earlier onset of moderate dysphagia (p = 0.0001). EMG masseter abnormalities did not reach statistical significance with regard to all the clinical milestones. Conclusions Genioglossus EMG at diagnosis could provide important information about ALS progression rate. The masseter muscle seems to be less involved in ALS. Significance EMG genioglossus involvement is a prognostic factor in ALS.

Highlights • 13 patients with Meige (craniocervical dystonia) syndrome and breathing difficulties were identified, 6 with and 7 without laryngeal involvement. • 77% had a good (>50%) response to Botulinum toxin injection(s). • Among the 13 Meige patients, all patients, except one, had clinical signs of supra-hyoid muscles involvement, we believe this muscle group is the main cause of the dyspnoea in this specific Meige phenotype., Background Dyspnoea is rarely mentioned in the clinical description of adult-onset isolated dystonia. In this study, we present the clinical features of 13 patients with Meige syndrome (cranio-cervical dystonia) with breathing difficulties. Methods A retrospective case note review was performed of patients presenting with Meige syndrome and shortness of breath, to a neuro-laryngology MDT clinic. Results Some patients were severely limited by their breathlessness, but others did not volunteer these symptoms. The majority of patients were referred with the assumption that the larynx was the cause of the problem; however half the patients did not have evidence of laryngeal involvement. Of the patients who had laryngeal involvement, injecting the larynx alone did not always relieve the dyspnoea. The majority of our patients responded to injection of the suprahyoid muscles, including genioglossus, digastric and mylohyoid. Conclusion We recommend routinely establishing if the patient with Meige syndrome has signs or symptoms of breathlessness, and establishing the level of the problem, as this can be treated successfully.

n.a.

Background: Electrical current can be used to stimulate upper airway dilator muscles to treat obstructive sleep apnoea (OSA). Ultrasound devices are widely available and may be used to detect contraction of the upper airway dilator muscles assessing the functionality of electrical stimulation (ES) used for this treatment. Methods: In a physiological sub-study of a randomised controlled trial, patients with OSA underwent ultrasound examination to assess contraction of the upper airway dilator muscles in response to transcutaneous ES. Ultrasound scans were scored according to the picture quality (poor = ‘0’, acceptable = ‘1’ and good = ‘2’). Tongue base thickness was assessed in mid-sagittal and coronal planes with (D2, A2) and without ES (D1, A1), while awake and seated. The primary outcome was to determine the increase in tongue thickness during ES in both views (D2 – D1 = ΔD), as well as any increase in the cross-sectional area (CSA) in the coronal view (A2 – A1 = ΔA). Data were presented as mean and standard deviation (SD). Results: Fourteen patients [eight male, age 57.5 (9.8) years, body mass index (BMI) 29.5 (2.8) kg/m2] with OSA [Apnea-Hypopnea Index (AHI) 19.5 (10.6) × hour-1] were studied. Quality of the ultrasound scans was acceptable or good with 1.5 (0.5) points. In the mid-sagittal plane, ΔD was +0.17 (0.07) cm in midline and +0.21 (0.09) cm in the widest diameter, a percentual change of 12.2% (4%) and 12.8% (5.2%) (P

Background: Hypoglossal motor nucleus (HN) controls the movement of genioglossus (GG) muscle which results in airway occlusion and the occurrence of obstructive sleep apnea (OSA). Histamine produced by tuberomammillary nucleus (TMN) has a potent excitatory action on GG muscle activity. Methods: C57BL/6 mice were exposed to CIH for 3 weeks to resemble OSA. The histamine H3 receptor (H3R) antagonist ciproxifan was applied to increase histamine in brain. Level of histamine and GG activity were measured. Neuronal activity and repair ability of HN and TMN were analyzed. Results: Significant decline of histamine and GG activity and severe damage of neuronal activity and repair ability of HN and TMN induced by CIH could be ameliorated by ciproxifan. Conclusion: This investigation studied the impacts of ciproxifan on HN and TMN in CIH condition and revealed that negative effects on HN and TMN caused by CIH could be partly ameliorated by ciproxifan, which might open new perspectives for the development of pharmacological treatments for OSA.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by deleterious mutations in the DMD gene which encodes the dystrophin protein. Skeletal muscle weakness and eventual muscle degradation due to loss of dystrophin are well-documented pathological hallmarks of DMD. In contrast, the neuropathology of this disease remains understudied despite the emerging evidence of neurological abnormalities induced by dystrophin loss. Using quantitative morphological analysis of nerve sections, we characterize axonopathies in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe dysfunction in these nerves – which innervate the diaphragm and genioglossus respectively – that we propose contributes to respiratory failure, the most common cause of death in DMD. These observations highlight the importance in the further characterization of the neuropathology of DMD. Additionally, these observations underscore the necessity in correcting both the nervous system pathology in addition to skeletal muscle deficits to ameliorate this disease.

Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus but most brain TRH is located elsewhere where it acts as a neuromodulator. TRH-positive neurons project to the hypoglossal motoneuron pool where TRH receptor RNA shows a high degree of differential expression compared with the rest of the brain. Strategies to modulate hypoglossal motor activity are of physiological and clinical interest given the potential for pharmacotherapy for obstructive sleep apnea (OSA), a common and serious respiratory disorder. Here, we identified the effects on tongue motor activity of TRH and a specific analog (taltirelin) applied locally to the hypoglossal motoneuron pool and systemically in vivo. Studies were performed under isoflurane anesthesia and across sleep–wake states in rats. In anesthetized rats, microperfusion of TRH (n = 8) or taltirelin (n = 9) into the hypoglossal motoneuron pool caused dose-dependent increases in tonic and phasic tongue motor activity (both p < 0.001). However, the motor responses to TRH were biphasic, being significantly larger “early” in the response versus at the end of the intervention (p ≤ 0.022). In contrast, responses to taltirelin were similar “early” versus “late” (p ≥ 0.107); i.e. once elicited, the motor responses to taltirelin were sustained and maintained. In freely behaving conscious rats (n = 10), microperfusion of 10 μM taltirelin into the hypoglossal motoneuron pool increased tonic and phasic tongue motor activity in non-rapid-eye-movement (REM) sleep (p ≤ 0.038). Intraperitoneal injection of taltirelin (1 mg/kg, n = 16 rats) also increased tonic tongue motor activity across sleep–wake states (p = 0.010). These findings inform the studies in humans to identify the potential beneficial effects of taltirelin for breathing during sleep and OSA.

AIM The mylohyoid muscle is often believed to exhibit high physiologic fluoro-deoxy-glucose (FDG) uptake. Aim of this study was to use PET/MR for adequately assessing the normal FDG distribution in floor of the mouth (FOM) muscles and neighboring major salivary glands. MATERIALS AND METHODS Patients scanned with a simultaneous PET/MRI system for initial staging or follow-up of head and neck tumors, with no malignant lesions in salivary glands or in FOM, were included. Volumes-of-interest (VOIs) were positioned separately for bilateral mylohyoid, digastric, genioglossus, and geniohyoid muscles, based on T2-weighted and T1-weighted images, and for bilateral parotid, submandibular, and sublingual glands in the same way. SUVmax was measured for each VOI. RESULTS Six hundred and ninety-two VOIs were positioned. FDG uptake in mylohyoid (SUVmax = 1.94 ± 0.37) and digastric muscles (SUVmax = 2.01 ± 0.37) were significantly higher compared to that in geniohyoid (SUVmax = 1.67 ± 0.53) and genioglossus muscles (SUVmax = 1.75 ± 0.54) (Friedman's test; P

Made available in DSpace on 2020-12-12T02:37:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 The genioglossus advancement muscle is a technique used to treat obstructive sleep apnea and depends on the precise location of the muscle insertion into the geniotubercle. The aim of this article was to present a case report about a 38-year-old male patient with obstructive sleep apnea even after undergoing uvulopalatopharyngoplasty and mentoplasty. A maxillo-mandibular advancement and genioglossus was proposed, for this a virtual planning of the surgical guide was done using a specialized software. The great advantage is to reduce the osteotomy by focusing precisely on the insertion of the muscle. The cutting guide facilitated the surgical procedure in all aspects and brought safety. Oral and Maxillofacial Surgery Department of Surgery and Integrated Clinic São Paulo State University (UNESP) School of Dentistry Division of Dentistry-Oral and Maxillofacial Surgery Medical School (USP) Hospital das Clínicas Oral and Maxillofacial Surgery Department of Surgery and Integrated Clinic São Paulo State University (UNESP) School of Dentistry

Purpose In the Union for International Cancer Control classification, extrinsic muscle involvement in oropharyngeal cancers is systematically defined as a T4a tumor, although the term extrinsic may incorrectly imply that these muscles are outside the tongue. Our aim was to describe the topography of extrinsic tongue muscles and show that their involvement in oropharyngeal cancers does not always correspond to T4a staging. Methods This cadaveric study was based on dissections of the tongues of ten healthy subjects. Dissections were carried out using sections, and careful macroscopic examination with a 3.5-diopter magnifying glass allowed the identification of muscles from their origin to their termination. Imagery and histology were excluded to stay as close as possible to the clinical evaluation. Results The sample comprised seven men and three women, with a mean age 82 years. In all the ten cases, the extrinsic muscles were located at the periphery of the tongue. The genioglossus was the only deep extrinsic muscle, extending to the periphery and under the mucous membrane of the tongue. As a result, a T1 tumor can invade the mucous membrane and affect the extrinsic muscles without transforming into a T4a tumor. Conclusion As extrinsic tongue muscles are peripheral and submucosal, the use of the term “deep” is erroneous, as is the systematic usage of extrinsic muscles to define T4a oropharyngeal cancers. This study attempts to explain this error, which is recurrent in the different editions of the Union for International Cancer Control and American Joint Committee on Cancer.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HNS) is an effective surgical alternative for patients with obstructive sleep apnea (OSA). HNS therapy relies on the stimulation of the hypoglossal nerve to open the upper airways. This stimulation could lead to alterations in tongue strength and fatigability, which could alter treatment outcome over time. The aim of the study was to investigate whether HNS alters tongue strength and fatigability. METHODS: Tongue protrusion strength (peak pressure in kPa) and fatigability (time to task failure during 50% of peak pressure contraction) were measured with a pressure transducer at least 2 months after HNS implantation (n = 30). These results were compared to a group of patients with OSA (n = 38) and a non-OSA control group (n = 35). RESULTS: Median tongue protrusion strength was lower (54.7 [43.8, 63.0] versus 60.7 [53.7, 66.0] kPa, P = .013) and fatigue occurred more quickly (21.3 [17.4, 26.3] versus 26.0 [19.3, 31.3] seconds, P = .017) in the patients with OSA compared to the non-OSA control group. In multiple regression analysis, age was a significant factor for tongue strength and diagnosis of OSA for tongue fatigability. Tongue strength and fatigability did not differ between patients with OSA with conservative therapy or observation versus after HNS implantation (51.8 [41.3, 63.4] versus 56.3 [45.0, 62.3] kPa, P = .502; 20.8 [16.3, 26.2] versus 21.8 [18.3, 26.8] seconds, P = .418). CONCLUSIONS: Tongue strength decreases with age. Tongue fatigability is more pronounced in people with OSA. However, approximately 1.5 years of HNS therapy on average does not alter tongue strength or fatigability compared to an OSA control group. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Change in Tongue Strength and Fatigue After Upper Airway Stimulation Therapy; Identifier: NCT03980158 CITATION: Wirth M, Unterhuber D, von Meyer F, et al. Hypoglossal nerve stimulation therapy does not alter tongue protrusion strength and fatigability in obstructive sleep apnea. J Clin Sleep Med. 2020;16(2):285–292.

BackgroundBulbar involvement is a hallmark of amyotrophic lateral sclerosis (ALS), but surprisingly very few studies have addressed the frequency, pattern and clinical relevance of laryngeal involvement in the disease.MethodsTwenty-six patients with spinal-onset ALS underwent nasofibroscopy (NF), followed by laryngeal electromyography (LEMG). We also studied resting activity and motor unit potentials of the genioglossus and masseter muscles.ResultsTwenty-four patients presented neurogenic changes in at least one laryngeal muscle. There were fibrillation and/or fasciculation potentials associated with chronic neurogenic changes in the same muscle in 16 patients; of these, 9 had no alteration in the genioglossus. We found no patient with tongue neurogenic changes and normal LEMG. NF was abnormal in 14 patients; in the remaining 12, LEMG identified neurogenic changes in 11 of them.ConclusionLEMG is able to identify laryngeal denervation in patients with ALS, sometimes before clinical manifestations are noticed. This technique may be a useful diagnostic tool for selected patients with suspicion of ALS.

Genioglossus was stimulated intramuscularly to determine the effect of regional activation of the muscle on tongue movement in eight healthy adults. Stimulation at motor threshold was delivered with a needle electrode inserted to different depths in the anterior and posterior regions of genioglossus. The current amplitude that induced muscle contraction was ∼80% higher for anterior than posterior sites. Evoked tongue movements were determined from stimulus-triggered averages (150 pulses) of the outputs from an accelerometer fixed to the posterosuperior surface of the tongue. The median amplitude [95% confidence intervals] for the resultant acceleration was 0.0 m/s2 [0.0, 0.2] for anterior and 0.6 m/s2 [0.1, 2.8] for posterior sites. There was a positive relationship between acceleration amplitude and stimulation depth in the posterior of genioglossus (p < 0.001), but acceleration amplitude did not vary with stimulation depth in the anterior region (p = 0.83). This heterogeneity in acceleration responses between muscle regions may contribute to differences in collapsibility of the upper airway.

New findings What is the central question of this study? Maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures are measured as inspiratory and expiratory muscle strength, respectively. Is the genioglossus muscle activated during short maximal inspiratory and expiratory efforts through the nose? What is the main finding and its importance? Genioglossus muscle activity occurred with inspiratory muscle activity during a maximal sniff and with expiratory muscle activity during a maximal reverse sniff. These results indicate that genioglossus muscle activity is closely related to the generation of maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures. Abstract Maximal sniff nasal inspiratory pressure (SNIPmax ) is widely used to assess inspiratory muscle strength. The sniff nasal inspiratory pressure (SNIP) is lower in patients with neuromuscular disease with bulbar involvement compared with those without, possibly owing to impaired upper airway muscle function. However, the degree to which the genioglossus (GG) muscle, one of the upper airway muscles, is activated during inspiratory and expiratory efforts through the nose remains unclear. Therefore, we examined GG activity during short and sharp inspiratory and expiratory efforts through the nose, i.e. sniff and reverse sniff manoeuvres. In eight normal young subjects, we inserted fine wire electrodes into the GG muscle, parasternal intercostal and scalene (inspiratory) muscles and transversus abdominis (expiratory) muscle. We assessed EMG activity of each muscle and measured SNIP and reverse sniff nasal expiratory pressure (RSNEP) during sniffs and reverse sniffs from low to high intensities in the sitting position. The highest SNIP and RSNEP were analysed as SNIPmax and maximal RSNEP (RSNEPmax ), respectively. In each subject, GG EMG activity increased linearly with increasing SNIP and RSNEP. The SNIPmax and RSNEPmax were -85.1 ± 15.9 and 83.2 ± 24.2 cmH2 O, respectively. Genioglossus EMG activity varied with EMG activity of the parasternal intercostal and scalene muscles during generation of SNIPmax and with EMG activity of the transversus abdominis muscle during RSNEPmax . Genioglossus EMG activity during generation of SNIPmax was higher than during RSNEPmax (62.9 ± 31.1% EMG of SNIPmax , P = 0.012). These results suggested that GG activity was closely related to the generation of both SNIPmax and RSNEPmax .