A Newly Discovered Tendon Between the Genioglossus Muscle and Epiglottic Cartilage Identified by Histological Observation of the Pre-Epiglottic Space.

Epiglottic retroversion is difficult to explain anatomically. One reason is inadequate structural identification of the ligaments in the submucosal tissue anterior to the epiglottis (pre-epiglottic space, PES). Although studies have shown that tongue root movement plays a role in epiglottic retroversion, few morphological reports have investigated the attachment of the lingual muscles to the epiglottis. This study reconstructed the fiber structure of the PES by comprehensively analyzing fiber alignment in the PES focusing on the hyoepiglottic ligament, which runs between the lingual muscles and the epiglottis. Gross and microscopic observations of the submucosal structures from the tongue to the larynx of 20 cadavers (10 men, 10 women; mean age 79 years) were performed. A tendon continuing from the posterior part of the genioglossus muscle and attaching to the center of the epiglottic cartilage was identified in the midline area of the epiglottis. We named this tendon the glossoepiglottic tendon. In contrast, the hyoepiglottic ligament is found between the hyoid bone and the epiglottis and is attached from the lateral margin of the epiglottic cartilage to its base. Furthermore, the glossoepiglottic tendon consists of a high-density fiber bundle that is thicker than the hyoepiglottic ligament. These results show that the conventional hyoepiglottic ligament has a two-layer structure consisting of an upper fiber bundle connected to the genioglossus muscle and a lower fiber bundle connected to the hyoid bone. Sustained contraction of the posterior part of the genioglossus muscle therefore places the epiglottis under persistent traction, suggesting that its relaxation may cause epiglottic retroversion.

Task-Specific Lingual Dystonia During Japanese Religious Services.

INTRODUCTION: Lingual dystonia is a subtype of oromandibular dystonia characterized by involuntary contractions of the tongue muscles, often provoked by speaking or eating. METHODS: This study reports six Japanese cases (four female and two male, mean age at onset of 49.5 years) with task-specific lingual dystonia during praying. In the early phase, all patients experienced lingual protrusion exclusively during Japanese religious services. When the patients start speaking, the tongues protrude forward, making it difficult to pronounce words. The patients were treated with multimodal treatment, including muscle afferent block (MAB) therapy comprising local anesthetic injection, botulinum toxin (onabotulinumtoxinA) injection, and a sensory trick splint. RESULTS: MAB therapy was conducted in five patients (mean time: 5.8), and botulinum toxin injection was administered in four patients (mean time: 8). The injected muscles were the genioglossal muscles and, in one case, the lateral pterygoid muscle. Sensory trick splints were inserted in three patients. After the multimodal therapy, the patients were able to pronounce words smoothly and clearly. Oromandibular Dystonia Rating Scale scores improved significantly (P<0.005) from baseline (187 points) to endpoint (47 points) with a mean follow-up of 4.7 years. CONCLUSION: Although this entity is rare, medical and dental professionals should be aware of this peculiar symptom. Multimodal therapy is required to ensure effective treatment of praying-induced lingual dystonia.

A Pilot Randomized Controlled Trial of Effect of Genioglossus Muscle Strengthening on Obstructive Sleep Apnea Outcomes.

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 > 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 > 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 > 0.05). The effectiveness of upper airway muscle training exercise as an adjunct treatment requires further study.

Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress.

Chronic intermittent hypoxia (CIH) has been shown to induce cell apoptosis in multiple organs of the human body. The present study aimed to assess the effects of exogenous klotho on CIH-induced genioglossus muscle injury, as well as the involvement of endoplasmic reticulum stress (ERS) in this process. A total of 36 adult C57BL/6 male mice were assigned to normoxia control (NC), CIH and CIH + klotho groups (n=12 mice/group). ELISA was performed to detect the level of klotho protein in the serum and in the genioglossus muscle tissue samples. Apoptosis was evaluated using the TUNEL assay. Reactive oxygen species (ROS) levels were quantified using a dihydroethidium assay kit, and the protein and mRNA levels of ERS-associated proteins (namely, glucoseregulated protein 78, C/EBP homologous protein, cleaved caspase-12 and cleaved caspase-3) in genioglossus samples were assessed using immunoblot assay and reverse transcription-quantitative PCR, respectively. Compared with the NC group, the quantities of klotho protein in the serum and genioglossus muscle tissue samples in the CIH group were significantly decreased, whereas the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were significantly increased. Following supplementation with exogenous klotho protein, the klotho protein levels in the serum and genioglossus muscle tissue of mice were found to be markedly increased, and the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were decreased compared with those in the CIH group. Taken together, the results of the present study have demonstrated that exogenous klotho may inhibit apoptosis of genioglossus myocytes in mice by inhibiting ROS-associated ERS.

Noninvasive electrical stimulation of oropharyngeal muscles in obstructive sleep apnea.

Introduction: Continuous positive airway pressure (CPAP) therapy remains the standard treatment for obstructive sleep apnea. However, its proven effect is useless if the patient does not tolerate the treatment. The electrical stimulation approach has been investigated for several decades now and it seems that the implantable devices for invasive electrical stimulation of hypoglossal nerve are viewed as effective with some of them already approved for human use.Areas covered: in this review, we intent to summarize the existing records of noninvasive stimulation in sleep apnea to make the scientific community aware of the details before deciding on its future. We believe that this is a battle still to fight and more could be done bearing in mind the safety of this method.Expertopinion: noninvasive electrical stimulation has been left behind based on few, small and inconsistent studies using different stimulation parameters. These studies are difficult to compare and to draw conclusions.Electrical stimulation is a field for research in the treatment of obstructive sleep apnea, with many aspects still to be discovered, and which may become a therapeutic alternative to the use of CPAP in certain patients.

Randomized Trial on the Effects of High-Dose Zopiclone on OSA Severity, Upper Airway Physiology, and Alertness.

BACKGROUND: Studies indicate that standard doses of hypnotics reduce or do not change the apnea-hypopnea index (AHI) or pharyngeal muscle activity. A 1-month trial of nightly zopiclone (7.5 mg) modestly reduced the AHI vs baseline without changing other sleep parameters or next-day sleepiness. RESEARCH QUESTION: This study aimed to determine the effects of high-dose zopiclone (15 mg) on AHI, arousal threshold, genioglossus muscle responsiveness, and next-day alertness in selected people with OSA (low to moderate arousal thresholds without major overnight hypoxemia). We hypothesized that high-dose zopiclone would yield greater increases in arousal threshold and therefore larger reductions in AHI but may come at the expense of increased hypoxemia and next-day impairment. STUDY DESIGN AND METHODS: Twenty-eight participants (AHI = 29 ± 20 events/h) suspected to have low to moderate arousal thresholds were studied during two in-laboratory polysomnographies, separated by 1 week, with an epiglottic pressure catheter and genioglossus intramuscular electrodes. Participants received 15 mg of zopiclone or placebo at each visit according to a double-blind, randomized, crossover design. Each morning, subjective sleepiness and alertness via a driving simulator task were assessed. RESULTS: The AHI did not change from placebo to zopiclone (-1.5 events/h; 95% CI, -6.6 to 3.5 events/h; P = .54). Arousal threshold, genioglossus muscle responsiveness, and most other sleep parameters and measures of next-day sleepiness and alertness also did not change with zopiclone. INTERPRETATION: A single night of treatment with high-dose zopiclone does not systematically reduce the AHI or increase the arousal threshold in selected people with OSA. The mechanisms for these unexpected findings require further investigation. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: ACTRN12617000988358; URL: https://www.anzctr.org.au.

Obstructive Sleep Apnea: Emerging Treatments Targeting the Genioglossus Muscle.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway obstruction caused by a loss of upper airway dilator muscle tone during sleep and an inadequate compensatory response by these muscles in the context of an anatomically compromised airway. The genioglossus (GG) is the main upper airway dilator muscle. Currently, continuous positive airway pressure is the first-line treatment for OSA. Nevertheless, problems related to poor adherence have been described in some groups of patients. In recent years, new OSA treatment strategies have been developed to improve GG function. (A) Hypoglossal nerve electrical stimulation leads to significant improvements in objective (apnea-hypopnea index, or AHI) and subjective measurements of OSA severity, but its invasive nature limits its application. (B) A recently introduced combination of drugs administered orally before bedtime reduces AHI and improves the responsiveness of the GG. (C) Finally, myofunctional therapy also decreases AHI, and it might be considered in combination with other treatments. Our objective is to review these therapies in order to advance current understanding of the prospects for alternative OSA treatments.

Genial tubercle position and genioglossus advancement in obstructive sleep apnea (OSA) treatment: a systematic review.

BACKGROUND: To systematically review the literature for methods to localize the genial tubercle as a means for performing an advancement of the genioglossus muscle. METHODS: PubMed, Google Scholar, CRISP, EMBASE, CINAHL, and Scopus were searched from inception through June 16, 2015. RESULTS: One hundred fifty-two articles were screened, and the full text versions of 12 articles were reviewed in their entirety and 7 publications reporting their methodology for localizing the genial tubercle. Based upon these measurements and the results published from radiographic imaging and cadaveric dissections of all the papers included in this study, we identified the genial tubercle as being positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandibular border. CONCLUSION: Based upon the results of this review, the genial tubercles were positioned within the mandible at a point 10 mm from the incisor apex and 10 mm from the lower mandible border. It may serve as an additional reference for localizing the genial tubercle and the attachment of the genioglossus muscle to the mandible, although the preoperative radiological evaluation and the palpation of the GT are recommended to accurately isolate.

Anatomical analysis to establish the optimal positioning of an osteotomy for genioglossal advancement: a trial in cadavers.

Genioglossal advancement, which is one of the treatments for obstructive sleep apnoea, can be effective only if it contains enough genial tubercle for an osteotomy. The aim of this study was to establish the position of the genial tubercle and of the optimal osteotomy during genioglossal advancement. Twenty-four adult cadavers with intact bony mandibular structures were included. Five variables were measured: the width and height of the genial tubercle (GTW); the distance from its inferior border to the inferior border of the mandible (IGT-IBM); the distance from the superior border of the genial tubercle to the inferior border of the mandible (SGT-IBM); and the width of the intermental foramen (IMFW). The following mean (SD) (range) measurements were obtained: GTW 7.38 (1.43) (4.5-10.0); GTH 7.94 (1.45) (5.0-10.0); IGT-IBM 7.96 (2.29) (4.0-12.0); SGT-IBM 15.90 (2.29) (12.0-20.0); and IMFW 56.65 (6.44) (43.0-67.0) mm. Of the 24 cadavers, 22 showed evidence of optimal positioning when the osteotomy was placed 2mm higher than the SGT-IBM measured on the inner table. This suggests that an optimal osteotomy, which includes the genial tubercle, may be possible in most patients when the osteotomy is positioned 2mm higher at the SGT-IBM.

Effect of bite openings and mandibular protrusion on genioglossus muscle activity in healthy adults with oral appliance.

Oral appliance (OA) can effectively treat obstructive sleep apnea; however, numerous types of oral appliances and designs are variable and the precise mechanisms behind differences in treatment outcomes are uncertain. The objective of this study was to evaluate the effects of different degrees of mandibular position [4° of bite openings (BO): 2, 4, 8 and 12 mm; and protrusion (P): 0, 50%, MAX], for both the upright and supine positions: BO2 mm_P0%, BO4 mm_P0%, BO4 mm_P50%, BO4 mm_PMAX, BO8 mm_P0%, BO12 mm_P0%; with an OA on the: (1) activity of the genioglossus (GG) muscle by electromyogram, (2) inspiration by airflow sensor, and (3) recording mandibular movements (incisor and mandibular condyle point) in each position. Nine healthy male adults (age 27.5 ± 1.30 years) were recruited. The results show that GG muscle activity increased significantly from BO 4 mm_P0% to BO12 mm_P0% during the supine position, and the strongest signal was found in BO4 mm_PMAX, compared to all of the other positions, and GG muscle activity in BO4 mm_P0% tended to be lower. From supine to upright position the inspiration increased significantly but GG muscle activity did not. These results might be a stimulus to augment a compensatory mechanism of GG muscle induced by OA, however, mainly in protrusion position. The increase of BO (2-12 mm) and even maximum protrusion might not negatively affect the temporomandibular joint.

Genioglossus muscle advancement and simultaneous sliding genioplasty in the management of sleep apnoea.

Genioglossus muscle advancement (GMA) was reported in 1993 as an option for the surgical treatment of obstructive sleep apnoea syndrome (OSAS), in the context of phase I of the Stanford University (Powell-Riley) protocol. The rationale for this technique is the placement of tension on the base of the tongue, thus preventing the tongue from falling back into the posterior airway space. However, in retrognathic patients undergoing phase I of the Stanford University protocol, an additional genioplasty will provide a better aesthetic outcome. Furthermore, genioplasty is one of the most common and versatile techniques used for the correction of dentofacial deformities. The aim of this article is to describe a technique that allows a combination of genioglossus muscle advancement (GMA) and a simultaneous sliding genioplasty. This technique can be used in patients undergoing phase I surgery, or in patients in whom a sliding genioplasty could be complemented by GMA. The advantage of this procedure is the aesthetic enhancement obtained in GMA patients. The indications, contraindications, complications, and outcomes of surgery in the first 15 patients treated with this technique are reported herein.

Electrical stimulation for the treatment of obstructive sleep apnoea: a review of the evidence.

INTRODUCTION: Obstructive sleep apnoea is an increasingly prevalent clinical condition with significant impact on individuals and public health. Continuous positive airway pressure therapy is the standard treatment, but adherence is limited and alternative treatments are needed. In this context, non-invasive and invasive methods for the electrical stimulation of upper airway dilator muscles have been demonstrated to be effective in selected patients. Areas covered: This review will cover investigations on the clinical effects, safety, and tolerability of non-invasive and invasive electrical stimulation of the upper airway for the management of obstructive sleep apnoea. Following a search of the relevant literature published on PubMed this review is focused mainly on data obtained from randomized clinical trials and clinical studies. Expert commentary: The available evidence provides a rationale to consider upper airway electrical stimulation as treatment for selected patients with obstructive sleep apnoea, who have poor adherence or experience difficulties with continuous positive airway pressure therapy. Non-invasive stimulation using transcutaneous electrodes and implantable hypoglossal nerve stimulator technologies may provide an alternative to continuous positive airway pressure for the treatment of obstructive sleep apnoea via restoration of neuromuscular tone and improved upper airway patency.

Specific branches of hypoglossal nerve to genioglossus muscle as a potential target of selective neurostimulation in obstructive sleep apnea: anatomical and morphometric study.

PURPOSE: To determine the ideal implantation site for selective tongue neurostimulation in obstructive sleep apnea, anatomy of the distal branching of the hypoglossal nerve (HGN) was revisited. METHODS: The HGN distal course and intramuscular distribution to the tongue muscles were studied in 17 embalmed and 5 fresh heads (age 60-98, BMI 20-35). Medial branches supplying selectively the genioglossus (GG) muscle were identified. Then, the distinct bundles entering the oblique (GGo) and horizontal (GGh) parts of the GG were located. Morphometric data were compared to similar measurements made on MRI sections from 12 patients (age 43-71, BMI 18-47). RESULTS: The key facts relevant to optimize stimulation and electrode design are the following: the mean width of both GG muscles in embalmed and fresh cadavers was 20.7 ± 2.9 and 21.4 ± 5 mm, respectively; it is significantly (p < 0.05) superior to the MRI value of 18.26 ± 2.0 mm. Selective nervous branches for GGh and GGo were located at 52 ± 8% of hyoid bone-mandibular symphysis distance and at 5.8 ± 1.1 mm from the inferior border of the GG muscle. The surface of stimulation is a 4.4 ± 1.1 × 6.9 ± 3.8 mm ellipse. CONCLUSIONS: According to our observations, the optimal selective or supra-selective stimulation of the tongue protractor muscles can be performed on the lateral surface of the GG at roughly equal distance between the mandibular symphysis and the hyoid bone, at a depth of about 0.6 cm above the GG lower border.

Efficacy of daytime transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea syndrome: short report.

Obstructive sleep apnea syndrome (OSAS) is characterized by hypotonia of lingual and suprahyoid muscles. Genioglossus muscle is responsible for protrusion and depression of the tongue. Its dysfunction results in occlusion of the upper airways and greater incidence of apnea-hypopnea events during sleep. The aim of this prospective study was to compare the effects of daytime transcutaneous electrical stimulation of the genioglossus muscle and standard continuous positive airway pressure (CPAP) therapy on the quality of sleep, in patients with OSAS. During a 4-week study period, 19 patients with OSAS were subjected to daytime transcutaneous electrical stimulation of the genioglossus muscle before sleep and another 19 subjects underwent standard CPAP therapy. Polysomnography (apnea-hypopnea index, AHI), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to diagnose OSAS and to verify the efficacy of both treatments. Electrical stimulation treatment was reflected by a decrease in PSQI (p = 0.012) but did not influence ESS and AHI values (p > 0.05). In turn, CPAP therapy resulted in a significant decrease in ESS and AHI values (p < 0.001) but exerted no effect on PSQI (p = 0.089). Despite improvement of sleep quality, electrical stimulation does not seem to reduce AHI values in patients with OSAS. Daytime electrical stimulation can be considered as an adjunct treatment in OSAS. Future prospective studies should center on the identification of patients with OSAS who may benefit most from transcutaneous electrical stimulation.

Unilateral Nasal Obstruction during Later Growth Periods Affects Craniofacial Muscles in Rats.

Nasal obstruction can occur at different life stages. In early stages of life the respiratory system is still under development, maturing during the growth period. Previous studies have shown that nasal obstruction in neonatal rats alters craniofacial function. However, little is known about the effects of nasal obstruction that develops during later growth periods. The aim of this study was to investigate the effects of nasal obstruction during later periods of growth on the functional characteristics of the jaw-opening reflex (JOR) and tongue-protruding muscles. In total, 102 6-day-old male Wistar rats were randomized into either a control or experimental group (both n = 51). In order to determine the appropriate timing of nasal obstruction, the saturation of arterial oxygen (SpO2) was monitored at 8 days, and at 3, 5, 7, 9, and 11 weeks in the control group. Rats in the experimental group underwent unilateral nasal obstruction at the age of 5 weeks. The SpO2 was monitored at 7, 9, and 11 weeks in the experimental group. The electromyographic responses of JOR and the contractile properties of the tongue-protruding muscles were recorded at 7, 9, and 11 weeks. In the control group, SpO2 decreased until 5 weeks of age, and remained relatively stable until 11 weeks of age. The SpO2 was significantly lower in the experimental group than in the control. In the experimental group, JOR changes included a longer latency and smaller peak-to-peak amplitude, while changes in the contractile properties of the tongue-protruding muscles included larger twitch and tetanic forces, and a longer half-decay time. These results suggest that nasal obstruction during later growth periods may affect craniofacial function.

Detection of genioglossus myoelectric activity using ICA of multi-channel mandible sEMG.

BACKGROUND: Genioglossus myoelectric activity is of great significance in evaluating clinical respiratory function. However, there is a tradeoff in genioglossus EMG measurement with respect to accuracy versus convenience. OBJECTIVE: This paper presents a way to separate the characteristics of genioglossus myoelectric activity from multi-channel mandible sEMG through independent component analysis. METHODS: First, intra-oral genioglossus EMGgenioglossus EMG and three-channel mandible sEMG were recorded simultaneously. The FastICA algorithm was applied to three independent components from the sEMG signals. Then the independent components with the intra-oral genioglossus EMG were compared by calculating the Pearson correlation coefficient between them. RESULTS: An examination of 60 EMG samples showed that the FastICA algorithm was effective in separating the characteristics of genioglossus myoelectric activity from multi-channel mandible sEMG. The results of analysis were coincident with clinical diagnosis through intra-oral electrodes. CONCLUSIONS: Genioglossus myoelectric activity can be evaluated accurately by multi-channel mandible sEMG, which is non-invasive and easy to record.

State-dependent and reflex drives to the upper airway: basic physiology with clinical implications.

The root cause of the most common and serious of the sleep disorders is impairment of breathing, and a number of factors predispose a particular individual to hypoventilation during sleep. In turn, obstructive hypopneas and apneas are the most common of the sleep-related respiratory problems and are caused by dysfunction of the upper airway as a conduit for airflow. The overarching principle that underpins the full spectrum of clinical sleep-related breathing disorders is that the sleeping brain modifies respiratory muscle activity and control mechanisms and diminishes the ability to respond to respiratory distress. Depression of upper airway muscle activity and reflex responses, and suppression of arousal (i.e., "waking-up") responses to respiratory disturbance, can also occur with commonly used sedating agents (e.g., hypnotics and anesthetics). Growing evidence indicates that the sometimes critical problems of sleep and sedation-induced depression of breathing and arousal responses may be working through common brain pathways acting on common cellular mechanisms. To identify these state-dependent pathways and reflex mechanisms, as they affect the upper airway, is the focus of this paper. Major emphasis is on the synthesis of established and recent findings. In particular, we specifically focus on 1) the recently defined mechanism of genioglossus muscle inhibition in rapid-eye-movement sleep; 2) convergence of diverse neurotransmitters and signaling pathways onto one root mechanism that may explain pharyngeal motor suppression in sleep and drug-induced brain sedation; 3) the lateral reticular formation as a key hub of respiratory and reflex drives to the upper airway.

Age-related changes in rat genioglossus, geniohyoid and masseter muscles.

OBJECTIVES: The aim of this study was to elucidate age-related changes from adult to middle age in the contractile properties of the masseter, genioglossus and geniohyoid muscles of the rat. MATERIALS AND METHODS: We analysed the expressions of myosin heavy chain (MyHC) mRNAs and proteins as indicators of the contractile properties in these muscles obtained from rats at 6, 12, 18 and 24 months of age using real-time PCR and SDS-PAGE. RESULTS: We found no marked age-related changes in the expressions of MyHC mRNAs and proteins in rat masseter and geniohyoid muscles, suggesting that the biological ageing process does not affect contractile properties in these muscles. However, we found a decrease in the expression of MyHC IIb mRNA with ageing in the rat genioglossus muscle, suggesting that biological ageing process induces at least some fast-to-slow myofibre phenotype transition. CONCLUSION: The biological ageing process from adult to middle age appears to differentially affect different types of craniofacial muscles.