The Effect of Lateral Pharyngeal Collapse Patterns on Therapy Response in Upper Airway Stimulation Surgery.

OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated upper airway collapse while sleeping which leads to intermittent hypoxemia. Upper airway stimulation (UAS) is a commonly practiced modality for treating OSA in patients who cannot tolerate, or do not benefit from, positive airway pressure (PAP). The purpose of this study is to identify the effect of lateral pharyngeal collapse patterns on therapy response in UAS. METHODS: A retrospective cohort study from a single, tertiary-care academic center was performed. Patients who underwent UAS between October 2016 and July 2019 were identified and analyzed. Drug-induced Sleep Endoscopy (DISE) outcomes between Apnea-Hypopnea Index (AHI) responders and AHI non-responders were compared. Those with complete concentric collapse at the velopharynx were not candidates for UAS. RESULTS: About 95 patients that underwent UAS were included in this study. Pre- to Post-UAS demonstrated significant improvements in Epworth Sleepiness Scale (12.0 vs 4.0, P = .001), AHI (29.8 vs 5.4, P < .001) and minimum oxygen saturation (79% vs 83%, P < .001). No DISE findings significantly predicted AHI response after UAS. Specifically, multiple types of lateral pharyngeal collapse patterns did not adversely effect change in AHI or AHI response rate. CONCLUSION: Demonstration of lateral pharyngeal collapse on DISE, in the absence of complete concentric velopharyngeal obstruction, does not appear to adversely affect AHI outcomes in UAS patients. LEVEL OF EVIDENCE: VI.

Ansa Cervicalis Stimulation: A New Direction in Neurostimulation for OSA.

BACKGROUND: Hypoglossal nerve stimulation (HNS) is an alternative treatment option for patients with OSA unable to tolerate positive airway pressure but implant criteria limit treatment candidacy. Previous research indicates that caudal tracheal traction plays an important role in stabilizing upper airway patency. RESEARCH QUESTION: Does contraction of the sternothyroid muscle with ansa cervicalis stimulation (ACS), which pulls the pharynx caudally via thyroid cartilage insertions, increase maximum inspiratory airflow (VImax)? STUDY DESIGN AND METHODS: Hook-wire percutaneous electrodes were used to stimulate the medial branch of the right hypoglossal nerve and right branch of the ansa cervicalis innervating the sternothyroid muscle during propofol sedation. VImax was assessed during flow-limited inspiration with a pneumotachometer. RESULTS: Eight participants with OSA were studied using ACS with and without HNS. Compared with baseline, the mean VImax increase with isolated ACS was 298%, or 473 mL/s (95% CI, 407-539). Isolated HNS increased mean VImax from baseline by 285%, or 260 mL/s (95% CI, 216-303). Adding ACS to HNS during flow-limited inspiration increased mean VImax by 151%, or 205 mL/s (95% CI, 174-236) over isolated HNS. Stimulation was significantly associated with increase in VImax in both experiments (P < .001). INTERPRETATION: ACS independently increased VImax during propofol sedation and drove further increases in VImax when combined with HNS. The branch of the ansa cervicalis innervating the sternothyroid muscle is easily accessed. Confirmation of the ansa cervicalis as a viable neurostimulation target may enable caudal pharyngeal traction as a novel respiratory neurostimulation strategy for treating OSA.

A randomized clinical trial on the acute therapeutic effect of TRPA1 and TRPM8 agonists in patients with oropharyngeal dysphagia.

BACKGROUND: Oropharyngeal dysphagia (OD) treatment is moving away from compensatory strategies toward active treatments that improve swallowing function. The aim of this study was to assess the acute therapeutic effect of TRPA1/M8 agonists in improving swallowing function in OD patients. METHODS: Fifty-eight patients with OD caused by aging, stroke, or neurodegenerative disease were included in a three-arm, quadruple-blind, randomized clinical trial (NCT02193438). Swallowing safety and efficacy and the kinematics of the swallow response were assessed by videofluoroscopy (VFS) during the swallow of 182 ± 2 mPa·s viscosity (nectar) boluses of a xanthan gum thickener supplemented with (a) 756.6 µmol/L cinnamaldehyde and 70 µmol/L zinc (CIN-Zn) (TRPA1 agonists), (b) 1.6 mmol/L citral (CIT) (TRPA1 agonist), or (c) 1.6 mmol/L citral and 1.3 mmol/L isopulegol (CIT-ISO) (TRPA1 and TRPM8 agonists). The effects on pharyngeal event-related potentials (ERP) were assessed by electroencephalography. KEY RESULTS: TRPA1 stimulation with either CIN-Zn or CIT reduced time to laryngeal vestibule closure (CIN-Zn P = .002, CIT P = .023) and upper esophageal sphincter opening (CIN-Zn P = .007, CIT P = .035). In addition, CIN-Zn reduced the penetration-aspiration scale score (P = .009), increased the prevalence of safe swallows (P = .041), and reduced the latency of the P2 peak of the ERP. CIT-ISO had no positive effect on biomechanics or neurophysiology. No significant adverse events were observed. CONCLUSIONS AND INFERENCES: TRPA1 stimulation with CIN-Zn or CIT improves the swallow response which, in the case of CIN-Zn, is associated with a significant improvement in cortical activation and safety of swallow. These results provide the basis for the development of new active treatments for OD using TRPA1 agonists.

Upper-Airway Stimulation Before, After, or Without Uvulopalatopharyngoplasty: A Two-Year Perspective.

OBJECTIVE: Upper airway stimulation (UAS) is an effective second-line treatment for obstructive sleep apnea (OSA). In certain patients, there is a considerable need for advanced programming, notably with inadequate palatal response to therapy. The aim of the study was to investigate the impact of uvulopalatopharyngoplasty and tonsillectomy (UPPP-TE) on UAS therapy outcomes from a 2-year perspective after implantation. METHODS: This study included all consecutive patients implanted with UAS in which a full set of 1- and 2-year follow-up assessments (M12 and M24) were obtained. Cases were analyzed in three groups: patients with UPPP-TE after (group 1) and before (group 2) UAS, and those without UPPP-TE (group 3). RESULTS: Therapy success could be achieved in about 80% of the entire cohort. Groups 2 and 3 did not differ significantly with regard to obesity, Apnea-Hypopnea Index, or Oxygen Desaturation Index. With regard to initial sleep endoscopy, there were fewer patients without any obstruction at the palatal and oropharyngeal levels and higher prevalence of lateral obstruction patterns at oropharynx in group 1 in contrast to groups 2 and 3. Groups 2 and 3 showed similar results, although group 2 patients underwent UPPP-TE before UAS implantation. CONCLUSION: UPPP-TE should be considered in patients with persistent OSA after UAS implantation if the obstruction is identified at the level of velum and oropharynx. Although this approach has higher response rates and better outcomes can be achieved in patients with UAS, there is no indication for patients to routinely undergo UPPP-TE prior to UAS implantation. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:514-518, 2019.

The BDNF polymorphism Val66Met may be predictive of swallowing improvement post pharyngeal electrical stimulation in dysphagic stroke patients.

BACKGROUND: The aim of this study was to explore the effect of brain-derived neurotrophic factor (BDNF) polymorphism rs6265 (Val66Met) in both "natural" and treatment induced recovery of swallowing after dysphagic stroke. METHODS: Sixteen dysphagic stroke patients that completed a single-blind randomized sham controlled trial of pharyngeal electrical stimulation (PES) within 6 weeks of their stroke (N=38), were genotyped for the BDNF SNP Val66Met (rs6265) from saliva samples. These patients received active or sham PES according to randomized allocation. PES was delivered at a set frequency (5 Hz), intensity (75% of maximal tolerated), and duration (10 minutes) once a day for three consecutive days. Clinical measurements were taken from patients at baseline, 2 weeks and 3 months post entering the study. Changes in swallowing ability based on the dysphagia severity rating scale (DSRS) were compared between active and sham groups and associated with BDNF SNP status. KEY RESULTS: In the active stimulation group, patients with the Met BDNF allele demonstrated significantly greater improvements in DSRS at 3 months compared to patients homozygous for the Val allele (P=.009). By comparison, there were no significant associations at the 2 week stage in either the active or sham group, or at 3 month in the sham group. Functional scores including the Barthel Index and modified Rankin scale were also unaffected by BDNF status. CONCLUSIONS & INFERENCES: Our findings suggest an association between BDNF and stimulation induced swallowing recovery. Further work will be required to validate these observations and demonstrate clinical utility in patients.

Upper Airway Collapsibility Assessed by Negative Expiratory Pressure while Awake is Associated with Upper Airway Anatomy.

STUDY OBJECTIVES: There is a growing interest to develop a simple method to characterize the mechanisms leading to upper airway collapse in order to guide treatment options in patients with obstructive sleep apnea (OSA). Critical closing pressure (Pcrit) during sleep is able to predict the anatomical component of OSA. However, Pcrit is a laborious method that is only used for research purposes. The application of negative expiratory pressure (NEP) is a simple method to assess upper airway collapsibility that can be easily performed during wakefulness. We hypothesized that NEP will be, similarly to Pcrit, associated with upper airway anatomy assessed by computed tomography (CT) scan. METHODS: Patients under investigation for OSA underwent polysomnography, CT of the upper airway, NEP while awake, and Pcrit during sleep. NEP was performed with -5 cm H2O in supine position using a nasal mask. Pcrit was measured during sleep induced by low doses of midazolam. RESULTS: Twenty-eight male subjects were studied (age 45 ± 13 y, body mass index 29.4 ± 4.9 kg/m2, apnea-hypopnea index (AHI) 30 ± 26, range 2 to 86 events/h). NEP and Pcrit were similarly associated with tongue area (r = 0.646 and r = 0.585), tongue volume (r = 0.565 and r = 0.613) and pharyngeal length (r = 0.580 and r = 0.611), respectively (p < 0.05 for all comparisons). NEP and Pcrit were also significantly correlated with AHI (r = 0.490 and r = 0.531). NEP and Pcrit were significantly higher in patients with severe OSA than the remaining population. CONCLUSIONS: NEP is a simple and promising method that is associated with the anatomical component of upper airway collapsibility. NEP may be valuable to select patients for noncontinuous positive airway pressure alternative therapies for OSA.

Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. METHODS: We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks. RESULTS: In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred. CONCLUSIONS: In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641.

Characterizing the mechanisms of central and peripheral forms of neurostimulation in chronic dysphagic stroke patients.

BACKGROUND: Swallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration. OBJECTIVE/HYPOTHESIS: Our hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response. METHODS: In 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy. RESULTS: Corticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = -2.79) was observed compared to sham. CONCLUSIONS: In this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = -.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.

Parameters affecting pharyngeal response to genioglossus stimulation in sleep apnoea.

Chronic stimulation of the hypoglossus nerve may provide a new treatment modality for obstructive sleep apnoea (OSA). In previous studies we observed large differences in response to stimulation of the genioglossus (GG). We hypothesised that both individual patient characteristics and the area of the GG stimulated are responsible for these differences. In the present study, we compared the response to GG electrical stimulation at the anterior area (GGa-ES), which activates the whole GG and the posterior area (GGp-ES), which activates preferentially the longitudinal fibres. Studies were performed in 14 propofol-sedated OSA patients. The parameters evaluated included cephalometry, pressure-flow relationship and pharyngeal shape and compliance assessed by pharyngoscopy. Compared with GGa-ES, GGp-ES resulted in significantly larger decreases in the critical value of end-expiratory pressure (P(crit)) (from 3.8 ± 2.2 to 2.9 ± 3.3 and -2.0 ± 3.9 cmH(2)O, respectively (p<0.001)). Both tongue size and velopharyngeal shape (anteroposterior to lateral ratio) correlated significantly with the decrease in P(crit) during GGp-ES (R = 0.53 and -0.66, respectively; p<0.05). In the patients with the larger tongue size (n = 7), the decrease in P(crit) reached 8.0 ± 2.2 cmH(2)O during GGp-ES. We conclude that directing stimulation to longitudinal fibres of the GG improves the flow-mechanical effect. In addition, patients with large tongues and narrow pharynx tend to respond better to GGp-ES.

[Effects on function rehabilitation of vocal cord after vocal cord polyps surgery treated with acupuncture at Sheng's four points of throat].

OBJECTIVE: To observe the effects on function rehabilitation of vocal cord after vocal cord polyps surgery treated with acupuncture at Sheng's Four Points of Throat. METHODS: Sixty cases were randomly divided into a combined therapy group of Four Points of Throat and medication (group 1, 30 cases) and a medication group (group 2, 30 cases). In group 1 Four Points of Throat were punctured and routine medication was applied; in group 2, only routine medication was applied. The scores of symptom-sign and status of voice were observed and analyzed before and after treatment in two groups. RESULTS: At 4th day after the surgery, the improvement of the symptom-sign scores in group 1 was more significant than that in group 2 (P < 0.05); and the voice analysis status in group 1 was superior to that in group 2 (all P < 0.05). The total effective rate was 83.3% (25/30) in group 1, which was superior to that of 60.0% (18/30) in group 2 (P < 0.05). CONCLUSION: The effect on function rehabilitation of vocal cord after vocal cord polyps surgery treated with the combined therapy group of Four Points of Throat and routine medication is favorable, superior to that with routine medication therapy.

[Electric stimulation in dysphagia therapy--a review]. / Elektrische Stimulation in der Dysphagietherapie - Eine Ubersicht.

In the last years an increased interest in the electrical stimulation has consisted in the treatment of dysphagia. In the article we introduce the anatomical and physiological premises for the method. In a critical analysis the present state of art is represented, the clinical results are checked and the chances for the future are examined.

Dysphagia and nutrition problems in infants with apert syndrome.

OBJECTIVE: The purpose of this study was to identify and describe the nature of dysphagia and nutrition difficulties in infants with Apert syndrome. DESIGN: The study comprised a review of the medical, nutrition, and feeding records of 13 consecutive infants still feeding by the bottle who had been referred to the Craniofacial Unit and analyses of swallow function from videofluoroscopic swallow investigations. MAIN OUTCOME MEASURES: Outcome measures included qualitative analyses of bottle-feeding and nutritional status and quantitative functional severity ratings of dysphagia based on videofluoroscopic swallow investigations using the O'Neil et al. (1999) Dysphagia Outcome Severity Scale. RESULTS: The main qualitative descriptors of oral feeding in this cohort included uncoordinated suck-swallow-breathe patterns, inability to maintain sucking bursts, and changes in respiratory patterns as the feed progressed. Videofluoroscopic evaluations (N = 7) showed silent laryngeal penetration or aspiration in more than half of the cohort. Failure to thrive was a frequent occurrence seen in seven infants, and 9 of the 10 required dietetic intervention and enteral supplements. (Nutritional records were not located for three infants.) CONCLUSIONS: In view of the small sample size and retrospective nature of the study, the results need to be interpreted with caution. However, the study adds to current limited knowledge on feeding and nutrition in Apert syndrome. Further prospective multidisciplinary and objective research is clearly warranted.

[Electrical stimulation of the genioglossus to improve pharyngeal patency in obstructive sleep apnea: comparison of results obtained during sleep and anesthesia].

Contraction of the geniogtossus (GG) has been shown to improve upper airway patency in patients with sleep apnea during sleep and anesthesia. However, a large variability in response exists, requiring selection of adequate patients if GG stimulation should be used as a treatment modality. In the present study, we compared responses in upper airway pressure-flow relationships to electrical stimulation of the GG in patients with obstructive sleep apnea during sleep and mild anesthesia. Nine patients studied during sleep were matched with 9 patients evaluated during propofol anesthesia. Stimulation was performed with fine wire electrodes inserted near the mandibular insertion of the GG. Airflow was measured at muLtiple levels of CPAP, and upper airway collapsibility was defined by the pressure below which airflow ceased (the "critical" pressure, Pcrit). ELectrical stimulation shifted the pressure-flow reLationships toward higher flow Levels in all patients over the entire range of CPAP applied. Pcrit decreased significantly during stimulation-induced contraction of the GG, and similarly in the patients evaluated during sleep and during anesthesia (from 1.6 +/- 2.0 to -1.6 +/- 2.5, and from 1.8 +/- 1.8 to -0.2 +/- 1.8 cmH2O, during steep and anesthesia, respectively, p < 0.01, without a significant change in upstream resistance. Our findings imply that responses in Pcrit to electrical stimulation of the main tongue protrusor during propofoL anesthesia may reflect those observed during sleep, and evaluation of the response of sleep apnea patients to GG stimulation can be evaluated during short anesthesia.

Interacting effects of genioglossus stimulation and mandibular advancement in sleep apnea.

Both mandibular advancement (MA) and stimulation of the genioglossus (GG) have been shown to improve upper airway patency, but neither one achieves the effect of continuous positive airway pressure (CPAP) treatment. In the present study we assessed the combined effect of MA and GG stimulation on the relaxed pharynx in patients with obstructive sleep apnea (OSA). We evaluated responses of upper airway pressure-flow relationships and endoscopically determined pharyngeal cross-sectional area to MA and electrical stimulation of the GG in 14 propofol-anesthetized OSA patients. Measurements were undertaken at multiple levels of CPAP, enabling calculation of the critical closing pressure (Pcrit), upstream resistance (Rus), and pharyngeal compliance. GG stimulation, MA, and the combination of both shifted the pressure:flow relationships toward higher flow levels, resulting in progressively lower Pcrit (from baseline of 2.9 +/- 2.2 to 0.9 +/- 2.5, -1.4 +/- 2.9, and -4.2 +/- 3.3 cmH(2)O, respectively), without significant change in Rus. DeltaPcrit during GG stimulation was significantly larger during MA than under baseline conditions (-2.8 +/- 1.4 vs. -2.0 +/- 1.4 cmH(2)O, P = 0.011). Combining the effect of GG stimulation with MA lowered Pcrit below 0 in all patients and restored pharyngeal patency to a level that enabled flow above the hypopnea level in 10/14 of the patients. Velopharyngeal compliance was not affected by either manipulation. We conclude that the combined effect of MA and GG stimulation is additive and may act in synergy, preventing substantial flow limitation of the relaxed pharynx in most OSA patients.

Evaluating oral stimulation as a treatment for dysphagia after stroke.

Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 +/- 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 +/- 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 +/- 0.07 s and pharyngeal transit time was 0.94 +/- 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 +/- 3.01; sham: 24.9 +/- 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.