Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: 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. Intervention: 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. Main Outcomes and Measures: 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). Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.

Association of Hypoglossal Nerve Stimulation With Improvements in Long-term, Patient-Reported Outcomes and Comparison With Positive Airway Pressure for Patients With Obstructive Sleep Apnea.

Importance: Hypoglossal nerve stimulation (HNS) and positive airway pressure (PAP) have been shown to improve patient-reported outcomes (PROs) in obstructive sleep apnea (OSA). However, to our knowledge, there are no data that compare change in PROs between HNS and PAP or that indicate whether HNS improves comorbid insomnia or depression in the long term. Objectives: To determine whether HNS is associated with improvements in patient-reported sleepiness, insomnia, and depression in the long term and to compare the respective associations of HNS and PAP with improved PROs. Design, Setting, and Participants: This retrospective cohort study used data from patients treated at the Cleveland Clinic for OSA. Participants received either HNS (referred sample) from November 1, 2015, to September 31, 2018, or PAP (previous cohort) from January 1, 2010, to December 31, 2014, for OSA. Patients were matched 3:1 for PAP:HNS based on age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), sex, and apnea hypopnea index (AHI). Data were collected at baseline and at prespecified follow-up points. Data were analyzed from March 26, 2020, to September 9, 2021. Exposures: Treatment with HNS vs PAP. Main Outcomes and Measures: Data collected included AHI and Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI), and Patient Health Questionnaire-9 (PHQ-9; depression) scores. Results: Among 85 patients receiving HNS (mean [SD] age, 62.8 [9.5] years; 59 men [69.4%]; 77 White patients [90.6%]; mean [SD] BMI, 28.8 [3.1]), compared with 217 matched patients receiving PAP (mean [SD] age, 62.1 [9.9] years; 157 men [72.4%]; 173 White patients [81.2%]; mean [SD] BMI, 29.5 [3.1]) included in the analysis, significant improvements were seen in PHQ-9 scores for HNS vs PAP (least square means, -4.06 [95% CI, -5.34 to -2.79] vs -2.58 [95% CI, -3.35 to -1.82]; mean difference, -1.48 [95% CI, -2.78 to -0.19]) with comparable improvements in ESS, FOSQ, and ISI scores. Clinically meaningful differences were observed in 42 of 65 HNS group patients (64.6%) vs 118 PAP group patients (54.5%) for ESS scores, 29 of 49 HNS group patients (59.2%) vs 67 of 217 PAP group patients (30.9%) for FOSQ scores, 14 of 48 HNS group patients (29.2%) vs 53 of 217 PAP group patients (24.4%) for PHQ-9 scores, and 23 of 49 HNS group patients (46.9%) vs 79 of 217 PAP group patients (36.4%) for ISI scores. At the 1-year post-HNS assessment, meaningful improvements were seen in 17 of 28 patients (60.7%) for ESS scores, 11 of 20 patients (55.0%) for FOSQ scores, 7 of 23 patients (30.4%) for PHQ-9 scores, and 11 of 25 patients (44.0%) for ISI scores. Conclusions and Relevance: In this cohort study of patients with OSA, sustained improvements in PROs were observed 1 year after HNS and were comparable to those for PAP at 3 months. These findings suggest that HNS is a viable treatment for improving insomnia and depression in patients with OSA.

Association between anxiety, depression, and emotional distress and hypoglossal nerve stimulator adherence.

PURPOSE: To evaluate relationships between hypoglossal nerve stimulator (HNS) adherence and the presence of anxiety, depression, and emotional distress. METHODS: This is a cross-sectional study of subjects with moderate to severe obstructive sleep apnea (OSA), who had HNS implanted and activated at The Ohio State University Medical Center (OSUMC). Patient usage data from the previous 6 months was obtained from 33 patients. Adherence was defined as ≥28 h of use per week. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were administered, and the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) score was calculated for all subjects. RESULTS: Sixty-five percent were adherent with average usage of 46.5±11.7 h per week vs 7.7±7.5 h per week in the non-adherent group. The average GAD-7 were 3.90±3.98 in the adherent group vs. 8.27±6.69 in the non-adherent group (p=0.049). PHQ-9 score was 6.15±4.31 vs. 10.09±7.53 (p=0.118), and PHQ-ADS was 10.05±7.49 vs. 19.20±9.80 (p=0.035). There were no statistically significant differences in age, gender, pre-treatment AHI, and post-treatment AHI between the two groups, though there was a trend to higher age in the adherent group. CONCLUSIONS: This study demonstrated higher GAD-7 and PHQ-ADS scores in the non-adherent group compared to those who were adherent to HNS supporting that anxiety and emotional distress may contribute to HNS therapy adherence. To our knowledge, this is the first study evaluating the relationship between anxiety, depression, emotional distress, and HNS adherence. Screening patients with the GAD-7 and PHQ-9 prior to implantation may be helpful when evaluating patient adherence to therapy.

Chronic inflammatory demyelinating polyneuropathy with hypoglossal nerve involvement and inverted Beevor's sign: case report.

BACKGROUND: Cranial nerve involvement is not commonly encountered in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); this is especially true for involvement of the hypoglossal nerve. Neither Beevor's sign nor its inverted form has previously been described in CIDP. CASE PRESENTATION: A 28-year-old man presented with distal-predominant limb weakness and numbness at the age of 18. A diagnosis of CIDP was made, which was confirmed by electrodiagnostic evidence of demyelination. He responded well to intravenous immunoglobulin and glucocorticoid treatment and achieved remission for 5 years. However, the same symptoms relapsed at the age of 28 and lasted for 10 months. On examination, in addition to limb sensory impairment and muscle weakness, mild bilateral facial paresis, tongue atrophy and fasciculations, and inverted Beevor's sign were also observed. A brief literature review of cranial nerve involvements in CIDP and Beevor's sign or its inverted form were also performed. CONCLUSIONS: Cranial nerves may be affected in patients with CIDP. Facial palsy is most frequently present, while hypoglossal nerve involvement is rare. Inverted Beevor's sign can appear in CIDP patients.

Effect of Electrode Configuration and Impulse Strength on Airway Patency in Neurostimulation for Obstructive Sleep Apnea.

OBJECTIVES/HYPOTHESIS: Hypoglossal nerve stimulation (HNS) has gained increasing interest for the treatment of patients with obstructive sleep apnea (OSA). Drug-induced sleep endoscopy (DISE) can both exclude improper airway collapse patterns and visualize airway changes under stimulation. Stimulation outcome effects depend on the impulse voltage and electric field resulting from the electrode configuration of the implanted device. The effects of various combinations of voltage and electric field on DISE airway patterns in contrast to awake endoscopy are unknown. STUDY DESIGN: Cohort study. METHODS: During therapy adjustment about 6 months after implantation, patients underwent a DISE and awake endoscopy with 100% and 125% of functional voltage in three typical electrode configurations (+ - +, o - o, - - -). All videos were analyzed by two separate persons for the opening of the airway at velum, tongue base, and epiglottis level. RESULTS: Thirty patients showed typical demographic data. The opening effects were visible in all patients, but there were changes between different electrode configurations. Several demographic or therapeutic aspects such as obesity, OSA severity, or prior soft palate surgery were associated with changes arising from different electrode configurations, but none resulted in a consistently better airway opening. CONCLUSIONS: In patients with poor results during the therapy adjustment, electric configuration changes can improve airway patency-an independent variable from increasing voltage. As these effects can only be seen in awake endoscopy or DISE, both endoscopies with live stimulation may be considered in cases with insufficient improvement in apnea-hypopnea index after initiation of HNS therapy. LEVEL OF EVIDENCE: Prospective case series; level 4. Laryngoscope, 131:2148-2153, 2021.

Hypoglossal Nerve Stimulation Therapy for the Treatment of Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) therapy was approved in 2014 for the treatment of obstructive sleep apnea in patients who are intolerant to continuous positive airway pressure (CPAP) therapy, which is reported in up to 40-60% of patients. This therapy works via direct neurostimulation of the hypoglossal nerve in synchrony with respiration, to open the airway via tongue stiffening and protrusion. Studies have demonstrated significant reductions in both respiratory parameters such as disordered breathing indices, as well as subjective sleep complaints, such as daytime sleepiness, with the use of this therapy. This has increased the repertoire of treatment options for sleep providers to recommend to those patients that are intolerant to CPAP therapy.

Adverse Events in Hypoglossal Nerve Stimulator Implantation: 5-Year Analysis of the FDA MAUDE Database.

OBJECTIVE: Use of hypoglossal nerve stimulator implantation has dramatically improved the surgical treatment of multilevel airway collapse during obstructive sleep apnea (OSA). Understanding causes of adverse events and their impact on patients undergoing stimulator implantation will help improve patient preparation and surgical practices to avoid future complications. STUDY DESIGN: This study is a retrospective review of the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, a publicly available voluntary reporting system. SETTING: National patient event database. METHODS: The MAUDE database was searched for reports associated with the terms "hypoglossal nerve stimulator" and "Inspire," being the only currently FDA-approved system for upper airway stimulation for OSA. All records were searched with the events limited in dates between May 2014 and September 2019. RESULTS: A total of 132 patient reports were identified over the 5-year inclusion period, containing 134 adverse events. The reported adverse events resulted in 32 device revision procedures as well as 17 explantations. Device migration and infection were 2 of the most commonly reported adverse events. Complications not witnessed in previous large-scale clinical trials included pneumothorax, pleural effusion, and lead migration into the pleural space. CONCLUSION: Previous data have demonstrated hypoglossal nerve stimulator implantation results in reliable OSA improvement. However, a number of technical difficulties and complications still exist during the perioperative period, which should be communicated to patients during the surgical consent process.

Ultrasound Localization and Percutaneous Electrical Stimulation of the Hypoglossal Nerve and Ansa Cervicalis.

OBJECTIVE: Hypoglossal nerve stimulation for obstructive sleep apnea (OSA) can be effective for appropriately selected patients, but current patient selection criteria are complex and still result in a proportion of nonresponders. Ansa cervicalis stimulation of the infrahyoid cervical strap muscles has recently been proposed as a new form of respiratory neurostimulation (RNS) therapy for OSA treatment. We hypothesized that percutaneous stimulation of both nerves in humans with temporary electrodes would make testing of the physiologic response to different RNS strategies possible. STUDY DESIGN: Nonrandomized acute physiology study. SETTING: Tertiary care hospital. METHODS: Fifteen participants with OSA underwent ultrasonography and placement of percutaneous electrodes proximal to the medial division of the hypoglossal nerve and the branch of the ansa cervicalis innervating the sternothyroid muscle (ACST). Procedural success was documented in each participant, as were any failures or procedural complication. RESULTS: The hypoglossal nerve was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 13 of 15 (86.7%). The ACST was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 14 of 15 (93.3%). Stimulation failure of the hypoglossal nerve was due to suboptimal electrode placement in 1 participant and electrode displacement in the other 2 cases. No complications occurred. CONCLUSIONS: The hypoglossal nerve and ACST can be safely stimulated via percutaneous electrode placement. Larger trials of percutaneous stimulation may help to identify responders to different RNS therapies for OSA with temporary or permanent percutaneous electrodes. Techniques for electrode design, nerve localization, and electrode placement are described.

Home Sleep Testing to Direct Upper Airway Stimulation Therapy Optimization for Sleep Apnea.

OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) is a well-established treatment option for obstructive sleep apnea (OSA). This study aimed to determine if there are benefits in performing a home sleep test (HST) to evaluate postoperative sUAS effectiveness after patient acclimatization compared to the generally used polysomnography (PSG) titration, as measured by long-term follow-up outcomes. STUDY DESIGN: Retrospective comparative cohort analysis. METHODS: We conducted an analysis of consecutive patients at our center who had completed a 6-month follow-up (month 6 [M6]) and recorded data from M6, month 12 (M12), and month 24 (M24). After device activation, we performed an HST with the patient's stimulation settings, and measured the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and device usage. These values were compared to patients who had undergone PSG-based device titration. RESULTS: Baseline values of the initial 131 patients show high ESS and moderate OSA. At the 2-month time point of the HST, nearly half of the patients (46.2%) reached an AHI ≤15/hr, and approximately a fifth (19.2%) reached <5/hr. The PSG and HST groups differed in median ESS at M24, but no other differences were observed for ESS at M6 and M12. Both groups showed similar AHI, oxygen desaturation, and usage hours per week. CONCLUSIONS: Adjusting therapy by using the HST technique after device activation and acclimatization has clinical and economic advantages. These advantages are contingent on several conditions being met when deviating from the standard device protocol, including precise communication with the referring sleep medicine physicians, especially their role in helping with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1375-E1379, 2021.

Motor axonopathies in a mouse model of Duchenne muscular dystrophy.

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.

Evaluation of Therapeutic Positive Airway Pressure as a Hypoglossal Nerve Stimulation Predictor in Patients With Obstructive Sleep Apnea.

Importance: Recent retrospective hypoglossal nerve stimulation (HGNS) outcomes data suggest that patients with low therapeutic positive airway pressure (PAP) levels achieve greater success than patients with high therapeutic PAP levels. Objective: To examine the use of therapeutic nasal PAP levels at the soft palate in predicting the outcomes of HGNS for patients with obstructive sleep apnea. Design, Setting, and Participants: This prospective cohort study used drug-induced sleep endoscopy (DISE) to evaluate the predictive capacity of therapeutic PAP levels in HGNS outcomes. In an academic sleep surgery center, 27 consecutive patients with obstructive sleep apnea who underwent DISE before implantation of an HGNS device were evaluated. The study was conducted from May 1, 2018, to June 26, 2019. Exposures: Positive airway pressure delivered through a nasal mask during DISE. Main Outcomes and Measures: Improvement in apnea-hypopnea index as measured from full-night preoperative and postoperative efficacy studies. Results: Twenty-seven patients met all inclusion criteria. The mean (SD) age was 62.0 (14.4) years, 14 participants were men (51.9%), and mean body mass index was 28.1 (4.0). Responders to HGNS therapy (n = 18) had significantly lower mean (SD) palatal opening pressure compared with nonresponders (n = 9) (5.0 [2.8] vs 9.2 [3.7] cm H2O, respectively; mean difference, -4.2; 95% CI, -6.8 to -1.6 cm H2O). After adjusting for age, sex, and body mass index, the mean palatal opening pressure value for the responders remained 3.5 cm H2O lower (95% CI, -6.7 to -0.4 cm H2O) than that of nonresponders. A palatal opening pressure cutoff level less than 8 cm H2O demonstrated a positive predictive value of 82.4%; sensitivity, 77.8%; and specificity, 66.7%. Conclusions and Relevance: In this small prospective cohort study, therapeutic nasal PAP levels during DISE differed significantly between responder and nonresponders to HGNS. Because DISE represents a mandatory, relatively standardized diagnostic tool for HGNS candidacy, the use of therapeutic nasal PAP through DISE can be broadly implemented and studied across multiple centers to possibly improve patient selection for HGNS.

Contralateral Tongue Muscle Activation during Hypoglossal Nerve Stimulation.

OBJECTIVE: The effectiveness of upper airway stimulation via hypoglossal nerve stimulation for obstructive sleep apnea depends upon the pattern of tongue muscle activation produced. This study investigated the nature of contralateral tongue muscle activation by unilateral hypoglossal nerve stimulation using intraoperative nerve integrity monitoring in conjunction with electromyography and explored the relationship between contralateral tongue muscle activation and polysomnographic measures of obstructive sleep apnea severity. STUDY DESIGN: Prospective case series. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Fifty-one patients underwent unilateral (right) hypoglossal nerve stimulator implantation for obstructive sleep apnea. Neurophysiological data included electromyographic responses in ipsilateral (right) and contralateral (left) genioglossus muscles in response to intraoperative bipolar probe stimulation (0.3 mA) of medial hypoglossal nerve branches. Clinical data included pre- and postoperative apnea-hypopnea indices and oxygen desaturation levels. RESULTS: A subset of patients (20/51, 39%) exhibited electromyographic responses in both the ipsilateral and contralateral genioglossus (bilateral), whereas the remaining patients (31/51, 61%) exhibited electromyographic responses only in the ipsilateral genioglossus (unilateral). The baseline characteristics of bilateral and unilateral responders were similar. Both groups exhibited significant and comparable improvements in apnea-hypopnea index and oxygen desaturations after hypoglossal nerve stimulation. Neither the amplitude nor the latency of contralateral genioglossus responses was predictive of clinical outcomes. CONCLUSION: A subset of patients undergoing unilateral hypoglossal nerve stimulation exhibits activation of contralateral genioglossus muscles. Patients with unilateral and bilateral genioglossus responses exhibit comparable, robust improvements in apnea-hypopnea index and oxygen desaturation levels.

Respiratory pattern and phrenic and hypoglossal nerve activity during normoxia and hypoxia in 6-OHDA-induced bilateral model of Parkinson's disease.

Respiratory disturbances present in Parkinson's disease (PD) are not well understood. Thus, studies in animal models aimed to link brain dopamine (DA) deficits with respiratory impairment are needed. Adult Wistar rats were lesioned with injection of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle. Two weeks after hypoxic test was performed in whole-body plethysmography chamber, phrenic (PHR) and hypoglossal (HG) nerve activities were recorded in normoxic and hypoxic conditions in anesthetized, vagotomized, paralyzed and mechanically ventilated rats. The effects of activation and blockade of dopaminergic carotid body receptors were investigated during normoxia in anesthetized spontaneously breathing rats. 6-OHDA injection affected resting respiratory pattern in awake animals: an increase in tidal volume and a decrease in respiratory rate had no effect on minute ventilation. Hypoxia magnified the amplitude and minute activity of the PHR and HG nerve of 6-OHDA rats. The ratio of pre-inspiratory to inspiratory HG burst amplitude was reduced in normoxic breathing. Yet, the ratio of pre-inspiratory time to total time of the respiratory cycle was increased during normoxia. 6-OHDA lesion had no impact on DA and domperidone effects on the respiratory pattern, which indicate that peripheral DA receptors are not affected in this model. Analysis of monoamines confirmed substantial striatal depletion of dopamine, serotonin and noradrenaline (NA) and reduction of NA content in the brainstem. In bilateral 6-OHDA model changes in activity of both nerves: HG (linked with increased apnea episodes) and PHR are present. Demonstrated respiratory effects could be related to specific depletion of DA and NA.

Electromyographic evaluation of the facial and motor donor nerves before facial reanimation surgery in Moebius syndrome.

BACKGROUND: Moebius syndrome is a clinical entity characterized by bilateral facial and abducens nerve palsies; other cranial nerver might be affected as well. So far, no studies have reported the electromyographic responses of the facial musculature in this group of patients. OBJECTIVE: The objective of our study is to describe the electromyographic responses of the facial muscle and the main donor nerves for facial reanimation in patients with Moebius syndrome. METHOD: We analyzed electromyographies from the facial, hypoglossal, masseterine (trigeminal) and accessory nerves from patients with Moebius syndrome treated between 2010 and 2016. Results are presented as percentages and central tendency measures. RESULTS: 24 patients were included, mean age 11.79 ± 9.39 years. The facial nerve showed complete unilateral recruitment in 4 patients, partial bilaterally in 11, 7 showed no activity bilaterally and two had unilateral inactivity. The masseterine was normal in 14 patients, had partial recruitment bilaterally in 4 and unilaterally in 4 cases. The accessory nerve was normal in 20 patients, showed partial recruitment bilaterally in 3 and unilaterally in 1 patients. The hypoglossal was normal in 22 patients, and altered in 2 cases. CONCLUSION: Patients with Moebius syndrome show several degrees of alteration in electromyographic evaluation of the facial nerve. Electromyography is a useful tool in evaluating potential motor donor nerves for facial reanimation surgery.

ANTECEDENTES: El síndrome de Moebius es una entidad clínica caracterizada por parálisis bilateral congénita del nervio facial y el abducens. Adicionalmente se pueden encontrar afectados otros pares craneales. Actualmente no existen estudios que reporten la respuesta electromiográfica de la musculatura facial en esta población. OBJETIVO: Describir la respuesta electromiográfica de la musculatura facial y de los principales nervios donadores para reconstrucción facial dinámica en pacientes con síndrome de Moebius. MÉTODO: Se analizaron electromiografías de los nervios facial, hipogloso, maseterino (trigémino) y accesorio en pacientes con síndrome de Moebius atendidos entre 2010 y 2016. Los resultados se presentan en porcentajes y medidas de tendencia central y de dispersión. RESULTADOS: Se incluyeron 24 pacientes, con una edad promedio de 11.79 ± 9.39 años. El nervio facial presentó reclutamiento unilateral completo en 4 pacientes, parcial bilateral en 11 pacientes, en 7 pacientes ausencia de reclutamiento bilateral e inactividad unilateral en 2 pacientes. El maseterino tuvo reclutamiento completo en 14 pacientes, parcial bilateral en 4 pacientes y parcial unilateral en 4 pacientes. El nervio accesorio mostró reclutamiento completo en 20 pacientes, parcial bilateral en 3 pacientes y parcial unilateral en 1 paciente. El hipogloso mostró actividad normal en 22 pacientes, parcial bilateral en 1 paciente y parcial unilateral en 1 paciente. CONCLUSIÓN: Los pacientes con síndrome de Moebius presentan alteraciones en los registros electromiográficos del nervio facial. La electromiografía permite identificar los nervios donadores para realizar la reconstrucción dinámica.

Electrical stimulation of the whole hypoglossal nerve in patients with obstructive sleep apnea.

PURPOSE: Electrical stimulation of the whole hypoglossal nerve (HGp-ES) has been demonstrated to enlarge the pharynx and improve pharyngeal stability and patency to airflow in all animals studied, but not in humans. The present study was undertaken to better understand the effect of HGp-ES on the human pharynx. METHODS: Eight patients with obstructive sleep apnea who had implanted stimulators with electrodes positioned proximally on the main truck of the hypoglossus were studied under propofol sedation. Pharyngoscopy and air flow measurements at multiple levels of continuous positive airway pressure (CPAP) were performed before and during Hgp-ES. RESULTS: HGp-ES that activates both tongue protrusors and retractors narrowed the pharyngeal lumen at the site of collapse (velopharynx in all subjects) from 1.38 ± 0.79 to 0.75 ± 0.44 cm2, p < 0.05 (measured at mid-range of CPAP levels) and lowered airflow (from 8.88 ± 2.08 to 6.69 ± 3.51 l/min, p < 0.05). Changes in critical pressure (Pcrit) and velopharyngeal compliance were not significant, but oropharyngeal compliance decreased (from 0.43 ± 0.18 to 0.32 ± 0.13 cm2/cmH2O, p < 0.05). No correlation was found between the pattern of change in luminal shape (determined as the ratio of a-p vs. lateral diameter when lowering CPAP) or changes in cross-sectional area and airflow during Hgp-ES. CONCLUSIONS: Our findings indicate that human retractors dominate when stimulated together with the protrusors during HGp-ES. While co-activation of retractors may be beneficial, it should be limited. We speculate that exercises that augment protrusor force may improve the response to hypoglossal stimulation. The exclusion of patients with concentric pharyngeal obstruction should be re-evaluated.

Optimizing the Translational Value of Mouse Models of ALS for Dysphagia Therapeutic Discovery.

The goal of this study was to compare dysphagia phenotypes in low and high copy number (LCN and HCN) transgenic superoxide dismutase 1 (SOD1) mouse models of ALS to accelerate the discovery of novel and effective treatments for dysphagia and early amyotrophic lateral sclerosis (ALS) diagnosis. Clinicopathological features of dysphagia were characterized in individual transgenic mice and age-matched controls utilizing videofluoroscopy in conjunction with postmortem assays of the tongue and hypoglossal nucleus. Quantitative PCR accurately differentiated HCN-SOD1 and LCN-SOD1 mice and nontransgenic controls. All HCN-SOD1 mice developed stereotypical paralysis in both hindlimbs. In contrast, LCN-SOD1 mice displayed wide variability in fore- and hindlimb involvement. Lick rate, swallow rate, inter-swallow interval, and pharyngeal transit time were significantly altered in both HCN-SOD1 and LCN-SOD1 mice compared to controls. Tongue weight, tongue dorsum surface area, total tongue length, and caudal tongue length were significantly reduced only in the LCN-SOD1 mice compared to age-matched controls. LCN-SOD1 mice with lower body weights had smaller/lighter weight tongues, and those with forelimb paralysis and slower lick rates died at a younger age. LCN-SOD1 mice had a 32% loss of hypoglossal neurons, which differed significantly when compared to age-matched control mice. These novel findings for LCN-SOD1 mice are congruent with reported dysphagia and associated tongue atrophy and hypoglossal nucleus pathology in human ALS patients, thus highlighting the translational potential of this mouse model in ALS research.

Inclusion of the first cervical nerve does not influence outcomes in upper airway stimulation for treatment of obstructive sleep apnea.

OBJECTIVES/HYPOTHESIS: Upper airway stimulation (UAS) has demonstrated efficacy in the management of obstructive sleep apnea (OSA). Branches of the hypoglossal nerve that selectively activate tongue protrusor and stiffener muscles are included within the stimulation cuff electrode. The first cervical nerve (C1) is often also included to stimulate additional muscles contributing to tongue protrusion and stabilization. The purpose of this study was to determine whether inclusion of the C1 translates into treatment efficacy, decreased voltage requirement, and improved outcomes in patients utilizing UAS. STUDY DESIGN: Single-center, retrospective cohort study. METHODS: One hundred fourteen patients who received a UAS implant at our institution and underwent posttreatment polysomnography were evaluated. Stimulation cuff electrodes in 87 patients included the C1; those in the remaining 27 patients did not include the C1. Demographic data, voltage data, and pre- and posttreatment apnea-hypopnea index (AHI), O2 nadir, and Epworth Sleepiness Scale (ESS) data were collected for all patients. RESULTS: There was no significant difference in stimulation voltage, or posttreatment AHI, O2 nadir, and ESS between the two cohorts. Treatment success, as measured by posttreatment AHI < 20 with a 50% reduction, was similar regardless of C1 inclusion. The same was seen for the percent of patients with AHI < 15 and AHI < 5 after treatment. The distributions of age and body mass index, as well as pre-treatment AHI, O2 nadir, and ESS were also not significantly different between treatment groups. CONCLUSIONS: The current study has demonstrated that inclusion of the C1 in the stimulation cuff electrode of the upper airway stimulator may not provide any additional benefit in therapy for OSA. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E382-E385, 2020.

Hypoglossal Nerve Palsy due to Compression by a Persistent Primitive Hypoglossal Artery: Case Report.

A 51-year-old Japanese woman was admitted to our hospital because of speech difficulty following severe headache. Neurological examination showed dysarthria and tongue weakness on the right side, indicating right hypoglossal nerve palsy. Needle electromyography of the right side of the tongue showed fibrillation potentials. Magnetic resonance angiography and computed tomography angiography revealed a right, persistent, primitive hypoglossal artery (PPHA) that met Lie's diagnostic criteria. Digital subtraction angiography showed an extended PPHA with irregular caliber in the portion running through the right hypoglossal canal. We diagnosed compression neuropathy of the hypoglossal nerve due to PPHA enlargement based on the findings of ipsilateral hypoglossal nerve palsy, fibrillation that indicated peripheral nerve palsy, and the enlarged diameter of the portion of the PPHA running through the right hypoglossal canal. We prescribed antihypertensive therapy. At 1 year after onset, her tongue weakness was alleviated. Clinicians should consider compression neuropathy due to a PPHA as one of the possibilities in the differential diagnosis of hypoglossal nerve palsy.