Anatomic-Based Technique for Sensing Lead Placement in Hypoglossal Stimulator Implantation.

Placement of the sensing lead can be challenging in obese and Down syndrome patients. This article presents an alteration in technique for its placement for these patient populations. Laryngoscope, 2024.

Implementing a Streamlined Hypoglossal Nerve Stimulator Pathway: Cost, Time to Surgery, and Outcomes.

Objective: To evaluate the costs, time to surgery, and clinical outcomes associated with implementing a streamlined hypoglossal nerve stimulator (HGNS) implantation pathway. Study Design: Retrospective cohort study. Setting: Single tertiary care center in the United States from 2016 to 2023. Methods: Patients with a lack of complete concentric collapse of the velum during volitional snore on in-office laryngoscopy qualified for the streamlined HGNS pathway. This pathway consisted of confirmatory drug-induced sleep endoscopy (DISE) followed immediately by HGNS implantation during the same surgical encounter. Outcomes were compared to patients in the traditional pathway (standalone DISE followed by HGNS implantation on a later date). Results: A total of 68 patients (13 streamlined, 55 traditional) with obstructive sleep apnea who underwent HGNS implantation were included. Patients were predominately male (70.6%) and White (95.6%) and had a mean (SD) age of 63.5 (10.0) years. The streamlined pathway was associated with a significant reduction in both hospital costs (mean difference $9258, 95% confidence interval [CI]: 3690-14,825; P = .002) and time to surgery (mean decrease of 3.82 months, 95% CI: 0.83-6.80 months; P = .013) compared to the traditional pathway. Patients in both groups had reduction in apnea-hypopnea index and Epworth Sleepiness Scale score, with no significant differences in comparisons between groups. Conclusion: In select patients, the streamlined HGNS pathway may expedite time to surgery and reduce hospital costs with comparable clinical outcomes to a traditional 2-stage pathway. Further research is warranted to validate patient selection and better understand longitudinal outcomes.

Cost-Effectiveness of Hypoglossal Nerve Stimulation for Pediatric Severe Obstructive Sleep Apnea in Down Syndrome Patients.

OBJECTIVE: To examine the cost-effectiveness of hypoglossal nerve stimulation (HGNS) implantation at an early age in simulated pediatric cohorts with Down Syndrome (DS) and severe obstructive sleep apnea (OSA). STUDY DESIGN: Cost-utility analysis. SETTING: Hypothetical cohort. METHODS: A Markov model simulated 3 pediatric cohorts with DS and OSA beginning at age 4 years until 21 years. Cohorts received HGNS implants in early childhood, late childhood, or adulthood at age 4, 13 (current FDA-approved age), or 18 years, respectively. Input model parameters were obtained from the literature and our institution. Outcomes were measured with an incremental cost-effectiveness ratio (ICER), measured in dollars per quality-adjusted life-year (QALY). Deterministic 1-way sensitivity analyses were conducted to evaluate the effects of parameter uncertainty. RESULTS: Results (total costs; total QALYs) across the time horizon were determined for each cohort: early implantation ($83,300.35; 15.79), late ($48,319.09; 14.98), and adult ($38,721.07; 14.55). ICERs were $48,892.47 per QALY for early vs late implantation, $43,471.15 per QALY for early vs adult implantation, and $30,959.58 per QALY for late vs adult implantation. All ICERs were below a willingness-to-pay threshold of $50,000 per QALY. Varying the discount rate and utility expectedly varied the ICERs and cost-effectiveness. Threshold analysis showed early implantation to be cost-effective for a HGNS implantation cost up to $62,230 compared to late implantation. CONCLUSION: The current study suggests HGNS is a cost-effective treatment strategy for pediatric patients with DS and severe OSA. Our findings also suggest cost-effectiveness at ages younger than 13, the current age of FDA approval.

Upper Airway Stimulation for Children and Adolescents with Down Syndrome: Long-Term Follow-Up.

OBJECTIVE(S): Hypoglossal nerve stimulation (HGNS) is safe and effective for patients with Down syndrome (DS) and severe persistent obstructive sleep apnea (OSA). Long-term outcomes for this patient population have not been evaluated. METHODS: A prospective single-group multicenter cohort study with 1-year follow-up was conducted between 2015 and 2021 among 42 adolescent patients with DS and severe persistent OSA. Here, we evaluate long-term outcomes in this patient cohort. Patients were evaluated with polysomnogram (PSG) at three timepoints: pre-implantation (timepoint 1), 1-year post-implantation (timepoint 2), and long-term follow-up (timepoint 3). RESULTS: Long-term follow-up data were available for 33 of 42 patients. Mean (SD) of timepoint 3 was 4.0 (1.9) years after implantation. Using a therapy response definition of a 50% decrease in Apnea Hypopnea INdez (AHI) from timepoint 1, the response rate was 69.7% (23/33) at timepoint 2 and 87.9% (29/33) at timepoint 3. From timepoint 1, there was a mean (SD) decrease in AHI of 12.7 (13.4) events/h at timepoint 2 and 15.7 (13.1) events/h at timepoint 3. The mean percentage change in AHI between timepoints 1 and 2 was -51.1% (95% CI: -32.8% to -69.3%) and between timepoints 1 and 3 was -59.6% (95% CI: -42.0% to -77.3%). CONCLUSION: Patients with DS and severe persistent OSA who undergo HGNS implantation may continue to experience improvement in PSG parameters at long-term follow-up. Future studies are needed to assess additional long-term outcomes in this patient population, including neurocognition and quality of life. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Persistent Hypoglossal Artery as a Rare Anatomical Variation Mimicking Carotid Artery Aneurysm: A Case Report.

We present a case of a rare vascular variation of the persistent hypoglossal artery (PHA) in a 57-year-old Caucasian female patient with a medical history of poorly controlled hypertension, headaches, diabetes mellitus, and depression. This anatomical variation was initially misdiagnosed as an internal carotid artery (ICA) aneurysm during the extracranial carotid Doppler imaging conducted due to nonspecific symptoms of cerebrovascular insufficiency, manifesting as coordination disturbances. PHA is one of the four vertebrobasilar anastomoses, originating from the cervical segment of the ICA. Together with the hypoglossal nerve, the meningeal branch of the ascending pharyngeal artery, and an emissary vein from the basilar plexus, it traverses the hypoglossal canal and enters the posterior cranial fossa, where it joins the basilar artery. This artery typically involutes during embryonic development but can persist into adulthood. If present, PHA is most often asymptomatic; however, it can be associated with pathological conditions such as atherosclerosis, cerebral ischemia, aneurysms, and arteriovenous malformations. This case highlights the diagnostic challenges posed by this anatomical variation and underscores the importance of further investigations in confirming accurate vascular anatomy. Here, we discuss the diagnostic criteria for PHA, its clinical significance, and therapeutic modalities.

Respiratory pathology in the TDP-43 transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in death within 2-5 years of diagnosis. Respiratory failure is the most common cause of death in ALS. Mutations in the transactive response DNA binding protein 43 (TDP-43) encoded by the TARDBP gene are associated with abnormal cellular aggregates in neurons of patients with both familial and sporadic ALS. The role of these abnormal aggregates on breathing is unclear. Since respiratory failure is a major cause of death in ALS, we sought to determine the role of TDP-43 mutations on the respiratory motor unit in the Prp-hTDP-43A315T mouse model - a model that expresses human TDP-43 containing the A315T mutation. We assessed breathing using whole-body plethysmography, and investigated neuropathology in hypoglossal and phrenic respiratory motor units. Postmortem studies included quantification of hypoglossal and putative phrenic motor neurons, activated microglia and astrocytes in respiratory control centers, and assessment of hypoglossal and phrenic nerves of TDP43A315T mice. The male TDP43A315T mice display an early onset of rapid progression of disease, and premature death (less than 15 weeks) compared to control mice and compared to female TDP43A315T mice who die between 20 and 35 weeks of age. The TDP43A315T mice have progressive and profound breathing deficits at baseline and during a respiratory challenge. Histologically, hypoglossal and putative phrenic motor neurons of TDP43A315T mice are decreased and have increased microglial and astrocyte activation, indicating pronounced neurodegeneration and neuroinflammation. Further, there is axonopathy and demyelination in the hypoglossal and phrenic nerve of TDP43A315T mice. Thus, the TDP-43A315T mice have significant respiratory pathology and neuropathology, which makes them a useful translatable model for the study of novel therapies on breathing in ALS.

Hypoglossal nerve stimulation for obstructive sleep apnea in adults: An updated systematic review and meta-analysis.

OBJECTIVES: This study aims to evaluate the efficacy of Apnex, Inspire, and ImThera hypoglossal nerve stimulation (HGNS) devices in changing the severity of obstructive sleep apnea (OSA). METHOD: ology: A systematic search was conducted across the databases to collect baseline and postoperative outcome measures. Articles were then filtered and data from post-filtration was extracted. The efficacy of each device was assessed individually, and the reported outcomes were analyzed at short-term (≤1 year) and long-term (>1 year) intervals. RESULTS: A total of 30 papers were included; 26 were single-arm studies encompassing 549 middle-aged overweight patients. Four RCTs included 273 participants. Results show that HGNS is an effective and safe treatment option. The Inspire device significantly improved, reducing the apnea-hypopnea index (AHI) by -20.14 events/h in the short term and -15.91 events/h in the long term. It also decreased the oxygen desaturation index (ODI) by -14.16 events/h (short term) and -12.95 events/h (long term). Patient-reported outcomes showed decreased Epworth Sleepiness Scale (ESS) scores by -5.02 (short term) and -4.90 (long term) and improved Functional Outcomes of Sleep Questionnaire (FOSQ) scores by 3.58 (short term) and 3.28 (long term). The Apnex and the ImThera devices featured similar improvements but to a lesser extent. CONCLUSION: Hypoglossal nerve stimulation is a safe and effective treatment for patients with OSA, exhibiting high adherence and satisfaction rates. However, it is important to note the potential for refining selection criteria to include a wider spectrum of patients with OSA.

Relationship of Modified Sleep Apnea Severity Index and HGNS Efficacy and Adherence in OSA Patients.

OBJECTIVES: Hypoglossal nerve stimulation (HGNS) is a treatment option for patients with CPAP-intolerant (CPAPi) obstructive sleep apnea (OSA). The modified sleep apnea severity index (mSASI) combines patient anatomy, weight, sleep study metrics, and symptoms into a composite index ranging from 1 (least severe) to 3 (most severe). Prior studies have associated mSASI with quality of life, CPAP adherence, and hypertension, but its utility in CPAPi patients is unknown. We evaluate the relationship between mSASI, HGNS efficacy, and adherence. METHODS: Retrospective cohort study of consecutive CPAPi OSA patients who underwent HGNS from 2014 to 2023. Patients were included if data were available to calculate preoperative mSASI and postoperative HGNS adherence/efficacy. Kruskal-Wallis rank-sum, Fisher's exact, and Chi-squared tests were performed. RESULTS: 264 patients were included (mean age = 61.3 years, 95% White, 66% Male). Preoperatively, 168 (64%) patients had mSASI of 1, 81 (31%) mSASI = 2, and 15 (5.7%) mSASI = 3. At 3 months post-op, patients with baseline mSASI of 1, 2, and 3 showed 6.72, 6.39, and 5.88 hours/night of device usage (p = 0.4). This pattern persisted, although showing no significance, at 6 months, 12 months, and most recent follow-up. There were similar reductions in Epworth Sleepiness Scale (ESS) across cohorts, with the mSASI3 group having the highest ESS postoperatively (p < 0.01). Sher15 response was similar between cohorts (mSASI1 = 52%, mSASI2 = 40%, mSASI3 = 25%, p = 0.2). CONCLUSION: Preoperative mSASI was not significantly correlated with HGNS adherence. Higher baseline mSASI was associated with greater postoperative daytime sleepiness. Further study is needed to evaluate mSASI as a tool within this population. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Reestablishment of the Smile after Hypoglossal-Facial Nerve Transfer: What Can We Learn?

Objective The aim of this study was to assess the ability to smile following a hypoglossal-facial nerve transfer (N12-N7). Design This is a retrospective chart review. Setting National tertiary referral center for skull base pathology. Participants Seventeen patients. Main Outcome Measures The ability to smile following an N12-N7 transfer was assessed by five medical doctors on photographs of the whole face and frontal, orbital, and oral segments. The (segmented) photographs were scored for the symmetry, asymmetry, and correct or incorrect assessment of the affected side. Results Seventeen patients were analyzed by 5 assessors providing 85 assessments. The whole face at rest was judged symmetrical in 26% of the cases and mildly asymmetrical in 56%. Frontal, orbital, and oral segments were symmetrical in 63, 20, and 35%, respectively. The affected side was correctly identified in 76%. When smiling, the whole face was symmetrical in 6% and mildly asymmetric in 59%. The affected side was correctly identified in 94%. The frontal, orbital, and oral segments during smiling were symmetrical in 67, 15, and 6%, respectively. The affected side of the frontal, orbital, and buccal facial segments during smiling was correctly identified in 89, 89, and 96%, respectively. Interobserver variability with Fleiss' kappa analysis showed that the strength of the agreement during smile of the total face was good (0.771) Conclusion Following an N12-N7 transfer, a good facial symmetry at rest can be achieved. During smiling, almost all patients showed asymmetry of the face, which was predominantly determined by the orbital and oral segments. To improve the ability to smile after an N12-N7 transfer, additional procedures are needed.

Successful treatment of recurrent extracranial hypoglossal schwannoma using the neuroendoscopic transnasal far-medial approach.

Background: Extracranial hypoglossal schwannomas are rare, and transcranial skull base surgery can be challenging due to their proximity to the lower cranial nerves, jugular vein, vertebral artery, and carotid artery. The application of neuroendoscopic surgery for extracranial hypoglossal schwannomas has rarely been reported. Case Description: A 53-year-old woman previously underwent lateral suboccipital surgery for a hypoglossal schwannoma when she was 25 years old. The patient had experienced aggravated dysphagia over the past month. Radiological examination revealed a recurrent extracranial hypoglossal schwannoma invading the left side of the clivus. The neuroendoscopic transnasal far-medial approach was performed, and the recurrent schwannoma was completely removed without any significant perioperative complications or recurrence for 3 years. Conclusion: Our report highlights the usefulness of the neuroendoscopic transnasal far-medial approach for the removal of recurrent extracranial hypoglossal schwannomas. The neuroendoscopic approach offers a viable and less invasive alternative to traditional transcranial skull-base surgery, especially in complex cases involving critical anatomical structures. The reported case study underscores the potential of neuroendoscopic surgery as a valuable tool in managing challenging skull-base tumors.

An Unusual and Discrepant Presentation of a Skull Base Paraganglioma.

Paragangliomas are rare tumors of neuroendocrine origin. Within the head and neck, these tumors are slow-growing and locally destructive, with a small malignant potential. Vagal paragangliomas (VPs) originate from paraganglia around the vagus nerve, typically at the level of the skull base. Cranial nerve deficits are common at presentation, with the vagus nerve and hypoglossal nerves being most affected. Similarly, hypoglossal paragangliomas (HPs) originate from around the hypoglossal nerve but are extremely rare and less documented. We describe the case of a patient presenting with an isolated hypoglossal nerve palsy in the setting of a tumor that radiologically represents a VP. A descriptive literature review was conducted to highlight presentation, management, and outcomes related to this pathology. A 65-year-old male presented to the clinic with tongue fasciculations and several years of dysarthria. Physical examination showed intermittent right tongue fasciculations in addition to ipsilateral hemi-atrophy. A computed tomography scan with contrast revealed an enhancing skull base mass inferior to the right carotid space. Subsequently, magnetic resonance imaging with contrast further delineated its anatomic involvement and site of origin, allowing for the diagnosis of a VP. After further discussion with the patient about his clinical findings, the decision was made to proceed with observation and serial imaging. Skull base paragangliomas are a rare pathologic entity that may pose a challenging multidisciplinary approach to optimize management strategies. Treatment may vary on a case-by-case basis and is dependent on patient and tumor characteristics.

Allergic reaction to hypoglossal nerve stimulator: a case report.

Little is documented about the frequency and management of allergic reactions to hypoglossal nerve stimulator implants. This case describes a 69-year-old female with obstructive sleep apnea who received the hypoglossal nerve stimulator device and had an adverse reaction concerning for an allergic reaction to the medical device. The complication was managed via topical steroids, and while the patient's symptoms initially resolved, she experiences continued intermittent maculopapular pruritic rashes approximately once per week. This case details the patient's presentation, including progression and management, while also highlighting the diagnostic challenges in identifying allergic reactions to medical implants and offering considerations for future management.

Baseline Characteristics Associated with Hypoglossal Nerve Stimulation Treatment Outcomes in Patients with Obstructive Sleep Apnea: A Systematic Review.

Hypoglossal nerve stimulation (HGNS) has emerged as an effective treatment for obstructive sleep apnea (OSA). Identifying baseline characteristics that prospectively could predict treatment outcomes even better is crucial for optimizing patient selection and improving therapeutic success in the future. A systematic review was conducted following PRISMA guidelines. Literature searches in Medline, Web of Science, and Cochrane databases identified studies assessing baseline characteristics associated with HGNS treatment outcomes. Inclusion criteria focused on studies with adult patients diagnosed with OSA, treated with HGNS, and assessed using full-night efficacy sleep studies. Risk of bias was evaluated using the NICE tool. Twenty-six studies met the inclusion criteria. Commonly reported baseline characteristics with predictive potential included BMI, site of collapse, and various pathophysiological endotypes. Most studies used the original Sher criteria to define treatment response, though variations were noted. Results suggested that lower BMI, absence of complete concentric collapse at the palatal level, and specific pathophysiological traits were associated with better HGNS outcomes. This review identified several baseline characteristics associated with HGNS outcomes, which may guide future patient selection. Importantly, patients were already preselected for HGNS. Standardizing response criteria is recommended to enhance the evaluation and effectiveness of HGNS therapy in OSA patients.

A novel method to reconstruct the complex facial nerve defect after extended parotidectomy with masseteric nerve and descending hypoglossal nerve.

This study aims to present a novel technique for reconstructing complex facial nerve defects using the masseteric nerve and descending hypoglossal nerve. Here, we report a case involving a patient with locally advanced parotid malignancy who underwent extended parotidectomy with resection of the invaded facial nerve. Following tumor resection, the proximal end of the facial nerve was inaccessible, leading to the formation of multiple distal branch defects. Subsequently, we performed reconstruction of the complex facial nerve defect using the masseteric nerve for the zygomatic and upper buccal branches and the descending hypoglossal nerve for the lower buccal and submandibular branches. There were no significant operative or post-operative complications observed. Upon 18 months of follow-up, the facial function of the patient had been restored to House-Brackmann-III grade. In conclusion, this dual nerve transposition approach proves to be an effective method for reconstructing complex facial nerve defects subsequent to extended parotidectomy.

Giant pituitary macroadenoma with apoplexy presenting with isolated bilateral hypoglossal nerve palsy: illustrative case.

BACKGROUND: Giant pituitary prolactinomas are rare entities that can present with pituitary apoplexy and acute neurological decline. Isolated acute hypoglossal nerve palsy is an extremely rare presentation that is not well described in the literature. The authors describe the case of a giant prolactin-secreting adenoma with apoplexy that presented with isolated bilateral hypoglossal palsy, followed by a brief review of the literature and management strategies. OBSERVATIONS: A 62-year-old female with a history of neck pain presented after a syncopal episode with dysarthria and dysphagia attributed to bilateral hypoglossal nerve palsies. Magnetic resonance imaging revealed a giant apoplectic pituitary tumor with extensive suprasellar and clival extension, including clear invasion of bilateral occipital condyles on computed tomography. The patient underwent urgent endoscopic transsphenoidal decompression and debulking of her tumor and was started on medical therapy with immediate, significant improvement in the bilateral hypoglossal nerve palsies. LESSONS: Prolactinomas presenting with acute neurological decline, including bilateral hypoglossal nerve palsy, can benefit from urgent endoscopic transsphenoidal surgical decompression and safe debulking. Bilateral condylar tumor invasion may not always require craniocervical surgical fixation in the acute setting. Patients should be followed up and monitored clinically and radiographically for any signs of craniocervical instability after the initiation of medical therapy. https://thejns.org/doi/10.3171/CASE24326.

Magnetic resonance imaging features of bilateral multiloculated extraneural ganglion cysts of the occipito-atlanto-axial joint causing hypoglossal nerve paralysis in a dog.

A 14-year-old spayed female Miniature Pinscher presented with tongue curling, dysphagia, hypersalivation, and sublingual gland swelling. Comprehensive evaluation, including neurologic and musculoskeletal examinations, blood work, and urinalysis, revealed no abnormalities other than tongue-related signs. Magnetic resonance imaging (MRI) revealed a multilobed cystic structure in the occipito-atlanto-axial joint, compressing the right hypoglossal canal. The lesion appeared cerebrospinal fluid (CSF)-like on T1-weighted and T2-weighted images, and hyperintense compared with CSF on fluid-attenuated inversion recovery T2-weighted images. The scans suggested mucinous content with enhanced peripheral areas on contrast-enhanced images. Surgical removal and drainage of this cyst were performed, and clinical signs improved markedly. The dorsal cyst was tentatively diagnosed as a ganglion cyst based on histopathologic and imaging findings. Ganglion cysts should be considered in the differential diagnosis for dogs with similar MRI findings and neurologic signs.

Radiographic and neurological outcomes of Gamma Knife radiosurgery for lower cranial nerve schwannomas: a single-institution experience.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

Persistent Hypoglossal Artery.

Teaching point: Persistent hypoglossal artery is an extremely rare anatomical variant but has diagnostic and therapeutic relevance.

Timeline of hypoglossal motor neuron death and intrinsic tongue muscle denervation in high-copy number SOD1G93A mice.

In amyotrophic lateral sclerosis (ALS) postmortem tissue and the SOD1 mouse model at mid-disease, death of hypoglossal motor neurons (XII MNs) is evident. These XII MNs innervate the intrinsic and extrinsic tongue muscles, and despite their importance in many oral and lingual motor behaviours that are affected by ALS (e.g., swallowing, speech, and respiratory functions), little is known about the timing and extent of tongue muscle denervation. Here in the well-characterised SOD1G93A (high-copy) mouse model, we evaluated XII MN numbers and intrinsic tongue muscle innervation using standard histopathological approaches, which included stereological evaluation of Nissl-stained brainstem, and the presynaptic and postsynaptic evaluation of neuromuscular junctions (NMJs), using synapsin, neurofilament, and α-bungarotoxin immunolabelling, at presymptomatic, onset, mid-disease, and endstage timepoints. We found that reduction in XII MN size at onset preceded reduced XII MN survival, while the denervation of tongue muscle did not appear until the endstage. Our study suggests that denervation-induced weakness may not be the most pertinent feature of orolingual deficits in ALS. Efforts to preserve oral and respiratory functions of XII MNs are incredibly important if we are to influence patient outcomes.