Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA).
To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function.
This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022.
Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values.
The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points.
Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment.
In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials.
ClinicalTrials.gov Identifier: NCT03359096.

The topographical relationships among the lower cranial nerves, internal carotid artery (ICA), and internal jugular vein (IJV) in the upper parapharyngeal neurovascular bundle remain obscure. Thus, details of the anatomy were examined in human fetus histology. We observed the horizontal histological sections from 20 midterm (9-18 weeks) and 12 near-term (28-40 weeks) fetuses. At the external skull base, the glossopharyngeal nerve crosses the anterior aspect of the IJV to reach the medially located Hyrtl\'s fissure in the petrous temporal bone. The nerve crossed the anterior aspect of the ICA medially near or below the first cervical nerve root. Below the hypoglossal nerve canal, the accessory nerve crosses the anterior or posterior aspects of the IJV and moves laterally. During the half-spiral course, the hypoglossal nerve was tightly attached to the posterolateral-anterior aspects of the vagus nerve and surrounded by a common nerve sheath. The glossopharyngeal ganglia sometimes extended inferiorly to the level of the hypoglossal nerve canal but were absent along the inferior course. The inferior vagal ganglion rarely extends above the occipital condyle. The superior cervical sympathetic ganglion occasionally extends above the first cervical nerve root. The IJV (or ICA) descends to the lateral (or medial) margins of the parapharyngeal neurovascular bundle. The glossopharyngeal (or accessory) nerve crosses the ICA (or IJV) to exit the bundle at the base of the skull (or below the hypoglossal nerve canal). The glossopharyngeal and vagus inferior ganglia differ at each site.

BACKGROUND: The hypoglossal canal is a dual bone canal at the cranial base near the occipital condyles. The filaments of the hypoglossal nerve pass through the canal. It also transmits the meningeal branch of the ascending pharyngeal artery, the venous plexus and meningeal branches of the hypoglossal nerve. The hypoglossal nerve innervates all the intrinsic and extrinsic muscles of the tongue except the palatoglossal and is fundamental in physiological functions as phonation and deglutition. A surgical approach to the canal requires knowledge of the main morphometric data by neurosurgeons.
METHODS: The present study was carried out on 50 adult dried skulls: 31 males: age range 18-85 years; 19 females: age range 26-79 years. The skulls came from the \'\'Leonetto Comparini\'\' Anatomical Museum. The skulls belonged to people from Siena (Italy) and its surroundings (1882-1932) and, therefore, of European ethnicity. The present study reports (a) the osteological variations in hypoglossal canal (b) the morphometry of hypoglossal canal and its relationship with occipital condyles. One skull had both the right and left hypoglossal canals occluded and, therefore, could not be evaluated. None of the skulls had undergone surgery.
RESULTS: We found a double canal in 16% of cases, unilaterally and bilaterally in 2% of cases. The mean length of the right and left hypoglossal canals was 8.46 mm. The mean diameter of the intracranial orifice and extracranial orifice of the right and left hypoglossal canals was 6.12 ± 1426 mm, and 6.39 ± 1495 mm. The mean distance from the intracranial end of the hypoglossal canal to the anterior and posterior ends of occipital condyles was 10,76 mm and 10,81 mm. The mean distance from the intracranial end of the hypoglossal canal to the inferior end of the occipital condyles was 7,65 mm.
CONCLUSIONS: The study on the hypoglossal canal adds new osteological and morphometric data to the previous literature, mostly based on studies conducted on different ethnic groups.The data presented is compatible with neuroradiological studies and it can be useful for radiologists and neurosurgeons in planning procedures such as transcondilar surgery. The last purpose of the study is to build an Italian anatomical data base of the dimensions of the hypoglossal canal in dried skulls..

Obstructive sleep apnea is associated with high morbidity. Hypoglossal nerve stimulation (HNS) has become a novel (neuro-) surgical treatment strategy for obstructive sleep apnea, demonstrating good success rates. Beyond predefined inclusion and exclusion criteria, no precise data are available, enabling individual preoperative risk assessment. To improve preoperative risk stratification, this study analyzed individual patient factors that affect outcomes of HNS.
Fourteen patients treated with unilateral HNS were analyzed retrospectively. Assessed risk factors included: hypertension, diabetes mellitus, depression, smoking, alcohol consumption, body mass index (BMI), and disease duration. Treatment success was defined as a reduction in the postoperative apnea-hypopnea index (AHI) to ≤20 events/hour, with a relative reduction of at least 50% compared to baseline.
A significant reduction in the postoperative apnea-hypopnea index was observed in all patients (P < 0.0001). BMI correlated significantly with postoperative AHI scores (95% confidence interval, 0.1519-0.8974; P = 0.018). Significant treatment success was observed in 50% of patients. Compared with the \"Excellent Responder group,\" the \"Responder group\" demonstrated a significantly higher BMI (95% confidence interval, 1.174-6.226; P = 0.0078). Diabetes, hypertension, disease duration, smoking, depression, and alcohol consumption were not significantly associated with AHI reduction.
Our findings suggest that BMI may be an independent risk factor for the response to HNS, with patients who had less benefit from therapy having significantly higher BMI than \"Excellent Responders.\" Therefore, carefully selecting patients is crucial in obtaining optimal outcomes with HNS therapy, especially those with a high BMI.

To provide a precise description of the morphology and morphometry of the hypoglossal canal (HC) and its relationship with surrounding structures by using the epoxy sheet plastination technique.
Thirty human cadaveric heads were plastinated into 5 sets of gross transparent plastination slices and 43 sets of ultrathin plastination sections. The HC were examined at both macro- and micro levels in these plastination sections and the reconstructed 3-dimensional visualization model.
The HC was an upward arched bony canal with a dumbbell-shaped lumen. According to the arched trajectory of its bottom wall, the HC could be divided into a medial ascending segment and a lateral descending segment. The thickness of the compact bone in the middle part of the HC was thinner than that at the intracranial and extracranial orifices. In 14 of 43 sides (32.6%), the posterior wall or the roof of the HC were disturbed by passing venous channels which communicated the posterior condylar emissary vein and the inferior petroclival vein. The trajectory of hypoglossal nerve in HC is mainly from anterosuperior to posteroinferior. The meningeal dura and the arachnoid extended into the HC along the hypoglossal nerve to form the dural and arachnoid sleeves and then fused with the nerve near the extracranial orifice of the HC.
Knowledge of the detailed anatomy of the HC can be helpful in avoiding surgical complications when performing surgery for lesions and the occipital condylar screw placement in this complex area.

Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).
To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.
This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023.
Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively.
Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale).
Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol.
This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI.
ClinicalTrials.gov Identifier: NCT02263859.

To establish a new method for fast exposure of the facial nerve and hypoglossal nerve during facial nerve anastomosis surgery.
Dissection of 12 formalin-fixed cadaveric specimens was performed to explore the positional relationship between the posterior belly of digastric muscle (PBD) and the facial nerve and hypoglossal nerve. We retrospectively reviewed patients who underwent facial nerve reconstruction surgery between 2015 and 2020 at Xuanwu Hospital, Capital Medical University, and the optimized surgical strategy based on the PBD was proposed.
The trunk of the hypoglossal nerve runs across the external carotid artery after giving off the descendens hypoglossi located within the 1-cm scope deep to the junction of the tendon and belly of the PBD. The mean depth difference between the hypoglossal nerve and the junction of the tendon and belly of the PBD was 5.48 ± 2.24 mm (range, 1.88-9.27 mm). The stylomastoid foramen segment of the facial nerve was revealed after the parotid gland was dissected within the angle between the anterior margin of the mastoid tip and the inferior margin of the cartilage of the external acoustic meatus.
The facial nerve and hypoglossal nerve can be rapidly identified using the PBD as an anatomical landmark. The end-to-end facial-descendens hypoglossi anastomosis is a reliable facial nerve reconstruction method for patients whose facial nerve was damaged during operation.

Obstructive sleep apnea (OSA) affects nearly 1 billion people worldwide, including approximately 35 million US residents. OSA has detrimental cardiovascular and neurocognitive consequences. Positive airway pressure corrects sleep disordered breathing but is not always tolerated or used sufficiently. Oral appliances and surgery provide alternatives in select populations but are variably effective. Hypoglossal nerve stimulation can effectively treat obstructive sleep apnea. Targeted hypoglossal nerve stimulation (THN) is simpler than incumbent technology with no sensor and an easier, proximal electrode implantation. The third clinical study of THN, THN3, was the first randomized, controlled trial of hypoglossal nerve stimulation to demonstrate significant improvement of sleep disordered breathing in OSA. The present investigation reports the design of a novel trial of targeted stimulation to provide additional Level 1 evidence in moderate to severe obstructive apnea. OSPREY is a randomized, parallel-arm, 13-month trial wherein all subjects are implanted, 2/3 are activated at Month 1 (\"Treatment\") and 1/3 are activated at Month 7 (\"Control\"). The primary endpoint is the difference in apnea-hypopnea index response rates between Treatment and Control groups at Month 7. Secondary endpoints include quality of life and oximetry metrics. OSPREY follows an adaptive \"Goldilocks\" design which optimizes the number of subjects with the need for high-confidence results. A maximum of 150 subjects is allowed, at which study power of >95% is predicted. Interim analyses begin once 50 patients are randomized and recur after each 20 additional randomizations to detect early success or futility. OSPREY is a unique, efficient trial that should provide high-confidence confirmation of the safety and efficacy of targeted hypoglossal nerve stimulation for moderate to severe obstructive sleep apnea.

There is a paucity of data in the literature describing quantitative exposure of the ventral craniocervical junction through the endonasal corridor in a safe manner mindful of locoregional anatomy.
To quantify ventromedial exposure of O-C1 and C1-2 articular structures after turning an inverted U-shaped nasopharyngeal flap (IUNF) and to obtain measurements assessing the distance of flap margins to adjacent neurovascular structures.
In 8 cadaveric specimens, an IUNF was fashioned using a superior incision below the level of the pharyngeal tubercule of the clivus and lateral incisions in the approximate region of Rosenmuller fossae bilaterally. Measurements with calipers and/or neuronavigation software included flap dimensions, exposure of O-C1 and C1-2 articular structures, inferior reach of IUNF, and proximity of the internal carotid artery (ICA) and hypoglossal nerve to IUNF margins.
The IUNF facilitated exposure of an average of 9 mm of the medial surfaces of the right/left O-C1 joints without transgression of the carotid arteries or hypoglossal nerves. The C1-2 articulation could not be routinely accessed. The margins of the IUNF were not in close (<5 mm) proximity to the ICA in any of the 8 specimens. In 6 of 8 specimens, the dimensions of the IUNF were in close (<5 mm) horizontal or vertical proximity to the hypoglossal foramina.
The IUNF provided safe and reliable access to the medial O-C1 articulation. Given the close proximity of the exocranial hypoglossal foramen, neuronavigation assistance and neuromonitoring with attention to the superolateral IUNF margin are recommended.

UNASSIGNED: Descriptive cross-sectional.
UNASSIGNED: The origin of the lingual artery (LA) has been well studied due to its implication in neck dissection, but the course thereafter to the oral cavity is less described. This cadaveric study traced the journey of the LA from the external carotid artery to its terminal branches in the tongue.
UNASSIGNED: Following bilateral neck dissections in 35 black Kenyan cadavers, the incidence of Beclard\'s, Lesser\'s and Pirogoff\'s triangles, the types of LA origin with its length, relationship to the hyoglossus muscle and anastomosis with other vessels were documented.
UNASSIGNED: Beclard\'s triangle was found in 64 dissections (91.42%), Lesser\'s in 46 dissections (65.71%) and Pirogoff\'s in 39 dissections (55.71%). The LA presented either as a solitary branch (67.15%) or as a branch of either the linguofacial (LFT-24.29%), thyrolingual (TLT-2.72%) or thyrolinguofacial (TLFT-2.86%) trunk. The solitary LA was the longest at 6.93 mm, followed by the TLT branch (6.58 mm), LFT branch (6.12 mm) and TLFT branch (5.65 mm). The majority of solitary LA and LA branches of LFT and TLFT passed through the hyoglossus, while all LA branches of the TLT coursed medial to the muscle. All variants of LA have been found to anastomose with the submental artery (SMA) at frequencies that ranged from 11.10% to 100%.
UNASSIGNED: The LA was found in all cadavers and all Beclards\' triangles. There is a significant incidence of LFT and TLFT variants in the Kenyan population. The LA passed either through or medial to the hyoglossus with no lateral relationship being observed.