Evaluation of Cognitive Functioning Before and After Cochlear Implantation in Adults Aged 55 Years and Older at Risk for Mild Cognitive Impairment.

Importance: Given the rapidly rising dementia incidence, management of modifiable risk factors, such as hearing loss, is vital. Multiple studies have demonstrated an improvement of cognitive functioning in older adults with severe hearing loss after cochlear implantation; however, few of these studies, to the authors' knowledge, specifically analyzed participants achieving poor cognitive results preoperatively. Objective: To evaluate the cognitive functioning of older adults with severe hearing loss at risk for mild cognitive impairment (MCI) before and after cochlear implantation. Design, Setting, and Participants: This prospective, longitudinal cohort study performed at a single center reports data obtained over a 6-year period (April 2015 to September 2021) of an ongoing prospective, longitudinal cohort study on cochlear implant outcomes in older adults. A consecutive sample of older adults with severe hearing loss eligible for cochlear implantation was included. All participants obtained a Repeatable Battery for the Assessment of Neuropsychological Status for hearing-impaired patients (RBANS-H) total score indicative of MCI preoperatively. Participants were assessed before cochlear implant activation and 12 months after cochlear implant activation. Intervention: The intervention consisted of cochlear implantation. Main Outcome and Measure: The primary outcome measure was cognition, measured by the RBANS-H. Results: A total of 21 older adult cochlear implant candidates were included in the analysis (mean [SD] age, 72 [9] years; 13 [62%] men). Cochlear implantation was associated with an improvement of overall cognitive functioning 12 months after activation (median [IQR] percentile, 5 [2-8] vs 12 [7-19]; difference, 7 [95% CI, 2-12]). Eight participants (38%) surpassed the MCI cutoff (16th percentile) postoperatively, while the overall median cognitive score remained under this cutoff. In addition, participants' speech recognition in noise improved, with a lower score indicating improvement (mean [SD] score, +17.16 [5.45] vs +5.67 [6.3]; difference, -11.49 [95% CI, -14.26 to -8.72]), after cochlear implant activation. Improvement of speech recognition in noise was positively associated with improvement in cognitive functioning (rs, -0.48 [95% CI, -0.69 to -0.19]). Years of education, sex, RBANS-H version, and symptoms of depression and anxiety were not related to the evolution in RBANS-H scores. Conclusions and Relevance: In this prospective, longitudinal cohort study, cognitive functioning and speech perception in noise showed a clinically meaningful improvement 12 months after cochlear implant activation in older adults with severe hearing loss at risk for MCI, suggesting that cochlear implantation is not contraindicated in cochlear implant candidates with cognitive decline and should be considered after multidisciplinary evaluation.

The Core Rehabilitation Outcome Set for Single-Sided Deafness (CROSSSD) study: International consensus on outcome measures for trials of interventions for adults with single-sided deafness.

BACKGROUND: Single-sided deafness (SSD) has functional, psychological, and social consequences. Interventions for adults with SSD include hearing aids and auditory implants. Benefits and harms (outcome domains) of these interventions are until now reported inconsistently in clinical trials. Inconsistency in reporting outcome measures prevents meaningful comparisons or syntheses of trial results. The Core Rehabilitation Outcome Set for Single-Sided Deafness (CROSSSD) international initiative used structured communication techniques to achieve consensus among healthcare users and professionals working in the field of SSD. The novel contribution is a set of core outcome domains that experts agree are critically important to assess in all clinical trials of SSD interventions. METHODS: A long list of candidate outcome domains compiled from a systematic review and published qualitative data, informed the content of a two-round online Delphi survey. Overall, 308 participants from 29 countries were enrolled. Of those, 233 participants completed both rounds of the survey and scored each outcome domain on a 9-point scale. The set of core outcome domains was finalised via a web-based consensus meeting with 12 participants. Votes involved all stakeholder groups, with an approximate 2:1 ratio of professionals to healthcare users participating in the Delphi survey, and a 1:1 ratio participating in the consensus meeting. RESULTS: The first round of the survey listed 44 potential outcome domains, organised thematically. A further five outcome domains were included in Round 2 based on participant feedback. The structured voting at round 2 identified 17 candidate outcome domains which were voted on at the consensus meeting. Consensus was reached for a core outcome domain set including three outcome domains: spatial orientation, group conversations in noisy social situations, and impact on social situations. Seventy-seven percent of the remaining Delphi participants agreed with this core outcome domain set. CONCLUSIONS: Adoption of the internationally agreed core outcome domain set would promote consistent assessment and reporting of outcomes that are meaningful and important to all relevant stakeholders. This consistency will in turn enable comparison of outcomes reported across clinical trials comparing SSD interventions in adults and reduce research waste. Further research will determine how those outcome domains should best be measured.

Systematic Literature Review of Hearing Preservation Rates in Cochlear Implantation Associated With Medium- and Longer-Length Flexible Lateral Wall Electrode Arrays.

Background: The last two decades have demonstrated that preoperative functional acoustic hearing (residual hearing) can be preserved during cochlear implant (CI) surgery. However, the relationship between the electrode array length and postoperative hearing preservation (HP) with lateral wall flexible electrode variants is still under debate. Aims/Objectives: This is a systematic literature review that aims to analyze the HP rates of patients with residual hearing for medium-length and longer-length lateral wall electrodes. Method: A systematic literature review methodology was applied following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations to evaluate the HP rates of medium-length and longer-length lateral wall electrodes from one CI manufacturer (medium length FLEX 24, longer length FLEX 28 and FLEX SOFT, MED-EL, Innsbruck, Austria). A search using search engine PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) was performed using the search terms "hearing preservation" or "residual hearing" and "cochlear implant" in "All fields." Articles published only in English between January 01, 2009 and December 31, 2020 were included in the search. Results: The HP rate was similar between medium-length (93.4%-93.5%) and longer (92.1%-86.8%) electrodes at 4 months (p = 0.689) and 12 months (p = 0.219). In the medium-length electrode group, patients under the age of 45 years had better HP than patients above the age of 45 years. Conclusions: Both medium-length and longer electrode arrays showed high hearing preservation rates. Considering the hearing deterioration over time, implanting a longer electrode at primary surgery should be considered, thus preventing the need for future reimplantation.

Multimodal phenotypic labelling using drug-induced sleep endoscopy, awake nasendoscopy and computational fluid dynamics for the prediction of mandibular advancement device treatment outcome: a prospective study.

Mandibular advancement device (MAD) treatment outcome for obstructive sleep apnea (OSA) is variable and patient dependent. A global, clinically applicable predictive model is lacking. Our aim was to combine characteristics obtained during drug-induced sleep endoscopy (DISE), awake nasendoscopy, and computed tomography scan-based computational fluid dynamic (CFD) measurements in one multifactorial model, to explain MAD treatment outcome. A total of 100 patients with OSA were prospectively recruited and treated with a MAD at fixed 75% protrusion. In all, 72 underwent CFD analysis, DISE, and awake nasendoscopy at baseline in a blinded fashion and completed a 3-month follow-up polysomnography with a MAD. Treatment response was defined as a reduction in the apnea-hypopnea index (AHI) of ≥50% and deterioration as an increase of ≥10% during MAD treatment. To cope with missing data, multiple imputation with predictive mean matching was used. Multivariate logistic regression, adjusting for body mass index and baseline AHI, was used to combine all potential predictor variables. The strongest impact concerning odds ratios (ORs) was present for complete concentric palatal collapse (CCCp) during DISE on deterioration (OR 28.88, 95% confidence interval [CI] 1.18-704.35; p = 0.0391), followed by a C-shape versus an oval shape of the soft palate during wakefulness (OR 8.54, 95% CI 1.09-67.23; p = 0.0416) and tongue base collapse during DISE on response (OR 3.29, 95% CI 1.02-10.64; p = 0.0464). Both logistic regression models exhibited excellent and fair predictive accuracy. Our findings suggest DISE to be the most robust examination associated with MAD treatment outcome, with tongue base collapse as a predictor for successful MAD treatment and CCCp as an adverse DISE phenotype.

Functional imaging improves patient selection for mandibular advancement device treatment outcome in sleep-disordered breathing: a prospective study.

STUDY OBJECTIVES: Mandibular advancement devices (MADs) are a noninvasive treatment option for patients with obstructive sleep apnea (OSA) and act by increasing the upper airway volume. However, the exact therapeutic mechanism of action remains unclear. The aim of this study was to assess MAD mechanisms using functional imaging that combines imaging techniques and computational fluid dynamics and assess associations with treatment outcome. METHODS: One hundred patients with OSA were prospectively included and treated with a custom-made MAD at a fixed 75% protrusion. A low-dose computed tomography scan was made with and without MADs for computational fluid dynamics analysis. Patients underwent a baseline and 3-month follow-up polysomnography to evaluate treatment efficacy. A reduction in apnea-hypopnea index ≥ 50% defined treatment response. RESULTS: Overall, 71 patients completed both 3-month follow-up polysomnography and low-dose computed tomography scan with computational fluid dynamics analysis. MAD treatment significantly reduced the apnea-hypopnea index (16.5 [10.4-23.6] events/h to 9.1 [3.9-16.4] events/h; P < .001, median [quartile 1-quartile 3]) and significantly increased the total upper airway volume (8.6 [5.4-12.8] cm3 vs 10.7 [6.4-15.4] cm3; P = .003), especially the velopharyngeal volume (2.1 [0.5-4.1] cm3 vs 3.3 [1.8-6.0] cm3; P < .001). However, subanalyses in responders and nonresponders only showed a significant increase in the total upper airway volume in responders, not in nonresponders. CONCLUSIONS: MAD acts by increasing the total upper airway volume, predominantly due to an increase in the velopharyngeal volume. Responders showed a significant increase in the total upper airway volume with MAD treatment, while there was no significant increase in nonresponders. Findings add evidence to implement functional imaging using computational fluid dynamics in routine MAD outcome prediction. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT01532050; Identifier: NCT01532050. CITATION: Van Gaver H, Op de Beeck S, Dieltjens M, et al. Functional imaging improves patient selection for mandibular advancement device treatment outcome in sleep-disordered breathing: a prospective study. J Clin Sleep Med. 2022;18(3):739-750.

Natural sleep endoscopy in obstructive sleep apnea: A systematic review.

This study's objective is to systematically review the literature on natural sleep endoscopy (NSE), including the set-up, different scoring systems, visualized collapse patterns during natural sleep, additional measurements, and comparison of upper airway collapse between NSE and drug-induced sleep endoscopy (DISE). A computerized search on Medline, Web of Science and the Cochrane library was conducted, obtaining 39 hits. Ten prospective studies were included in which NSE was performed in adults with obstructive sleep apnea (OSA). This study's findings suggest the soft palate to be the most frequent site of obstruction (58.8 %), followed by the tongue base (43.2 %), lateral walls (29.9 %), and epiglottis (22.4 %), which is in line with previous findings during DISE. Based on this literature review, the authors conclude that at this stage high quality, comparative research between DISE and NSE is missing. To adequately compare findings between OSA patients, endoscopic classification of upper airway collapse should be standardized. Non-invasive predictive tools to determine pharyngeal collapse are currently under investigation and may obviate the need for invasive endoscopy. This review highlights the contribution of NSE in validating such novel diagnostic methods and in studying upper airway mechanics in a research setting, yet larger and adequately powered studies are needed.

Endotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy.Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy.Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. Raw baseline polysomnographic data from 91/126 patients were available for analysis. Traits-loop gain, arousal threshold, collapsibility, and muscle compensation-were calculated from the baseline polysomnography data according to Sands and colleagues (AJRCCM 2018, SLEEP 2018). Logistic regression assessed apnea-hypopnea index (AHI)-adjusted associations between HGNS response (>50% reduction in AHI to <10/h at 1 yr) and OSA traits.Measurements and Main Results: Overall, HGNS treatment reduced AHI from 30.7 (24.9-39.9) to 8.5 (4.0-19.5) events/h (P < 0.0001; median [quartiles 1-3]); N = 53/91 were responders. In adjusted analysis, a favorable response to therapy was independently associated with higher arousal threshold (odds ratio [95% confidence interval]: 6.76 [2.44-23.3], P = 0.001), greater compensation (odds ratio: 4.22 [1.70-12.55] per SD, P = 0.004), and lower loop gain (in milder collapsibility, per significant interaction, P = 0.003). The higher arousal threshold was evident in responders before adjusted analysis. Predicted responders had an approximately fourfold lower treatment AHI versus predicted nonresponders (4.9 [2.7-8.5] vs. 20.7 [10.9-29.7], P < 0.0001; median [quartiles 1-3]); differences remained significant after cross-validation.Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy.This analysis was a secondary analysis of the STAR trial registered with clinicaltrials.gov (NCT01161420).

Awake endoscopic assessment of the upper airway during tidal breathing: Definition of anatomical features and comparison with drug-induced sleep endoscopy.

OBJECTIVES: Awake nasopharyngoscopy is routinely performed in the assessment of patients who require treatment for sleep-disordered breathing (SDB). However, the applicability and accuracy of Müller's manoeuvre, the main evaluation method for this purpose, are disputable. The current study aimed to introduce an alternative method for awake nasopharyngoscopy in patients with SDB. DESIGN: We defined qualitative anatomical features during tidal breathing at the levels of the soft palate, oropharynx, tongue base, epiglottis and hypopharynx, and compared these awake features to the sites and patterns of collapse as observed during drug-induced sleep endoscopy (DISE). SETTING: Tertiary care academic centre. PARTICIPANTS: Seventy-three patients diagnosed with SDB. MAIN OUTCOME MEASURES: The primary outcome measure was the Kendall's tau correlation coefficient (τ) between observations during awake nasopharyngoscopy and DISE. Kappa-statistics (κ) were calculated to assess the agreement on awake endoscopic features with a second observer. RESULTS: In contrast to epiglottis shape, the modified Cormack-Lehane scale was significantly associated with epiglottis collapse during DISE (P < .0001; τ = .45). Other upper airway features that were correlated with DISE collapse were the position of the soft palate (P = .007; τ = .29), crowding of the oropharynx (P = .026; τ = .32) and a posteriorly located tongue base (P = .046; τ = .32). Interobserver agreement of endoscopic features during tidal breathing was moderate (0.60 ≤ κ < 0.80). CONCLUSION: The current study introduces a comprehensive and reliable assessment method for awake nasopharyngoscopy based on anatomical features that are compatible with DISE collapse patterns.

Unilateral Cochlear Implants for Severe, Profound, or Moderate Sloping to Profound Bilateral Sensorineural Hearing Loss: A Systematic Review and Consensus Statements.

Importance: Cochlear implants are a treatment option for individuals with severe, profound, or moderate sloping to profound bilateral sensorineural hearing loss (SNHL) who receive little or no benefit from hearing aids; however, cochlear implantation in adults is still not routine. Objective: To develop consensus statements regarding the use of unilateral cochlear implants in adults with severe, profound, or moderate sloping to profound bilateral SNHL. Design, Setting, and Participants: This study was a modified Delphi consensus process that was informed by a systematic review of the literature and clinical expertise. Searches were conducted in the following databases: (1) MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE, (2) Embase, and (3) the Cochrane Library. Consensus statements on cochlear implantation were developed using the evidence identified. This consensus process was relevant for the use of unilateral cochlear implantation in adults with severe, profound, or moderate sloping to profound bilateral SNHL. The literature searches were conducted on July 18, 2018, and the 3-step Delphi consensus method took place over the subsequent 9-month period up to March 30, 2019. Main Outcomes and Measures: A Delphi consensus panel of 30 international specialists voted on consensus statements about cochlear implantation, informed by an SR of the literature and clinical expertise. This vote resulted in 20 evidence-based consensus statements that are in line with clinical experience. A modified 3-step Delphi consensus method was used to vote on and refine the consensus statements. This method consisted of 2 rounds of email questionnaires and a face-to-face meeting of panel members at the final round. All consensus statements were reviewed, discussed, and finalized at the face-to-face meeting. Results: In total, 6492 articles were identified in the searches of the electronic databases. After removal of duplicate articles, 74 articles fulfilled all of the inclusion criteria and were used to create the 20 evidence-based consensus statements. These 20 consensus statements on the use of unilateral cochlear implantation in adults with SNHL were relevant to the following 7 key areas of interest: level of awareness of cochlear implantation (1 consensus statement); best practice clinical pathway from diagnosis to surgery (3 consensus statements); best practice guidelines for surgery (2 consensus statements); clinical effectiveness of cochlear implantation (4 consensus statements); factors associated with postimplantation outcomes (4 consensus statements); association between hearing loss and depression, cognition, and dementia (5 consensus statements); and cost implications of cochlear implantation (1 consensus statement). Conclusions and Relevance: These consensus statements represent the first step toward the development of international guidelines on best practices for cochlear implantation in adults with SNHL. Further research to develop consensus statements for unilateral cochlear implantation in children, bilateral cochlear implantation, combined electric-acoustic stimulation, unilateral cochlear implantation for single-sided deafness, and asymmetrical hearing loss in children and adults may be beneficial for optimizing hearing and quality of life for these patients.

The relationship between specific nasopharyngoscopic features and treatment deterioration with mandibular advancement devices: a prospective study.

STUDY OBJECTIVES: The variable efficacy of mandibular advancement device (MAD) treatment necessitates both accessible and accurate methods for patient selection. However, the role of awake nasopharyngoscopy for this purpose remains dubious. We introduced an assessment method based on anatomical upper airway features during tidal breathing for nasopharyngoscopy. The current study aimed to relate these features to MAD treatment outcome. METHODS: One hundred patients diagnosed with obstructive sleep apnea were prospectively recruited for MAD treatment in a fixed 75% degree of maximal protrusion. Nasopharyngoscopic observations during Müller's maneuver and tidal breathing were recorded both with and without MAD. Treatment outcome, confirmed by 3-month follow-up polysomnography with MAD, was classified as (1) apnea-hypopnea index reduction ≥ 50%, (2) treatment apnea-hypopnea index < 5 events/h, and (3) ≥ 10% increase in apnea-hypopnea index compared with baseline (treatment deterioration). RESULTS: A complete dataset was obtained in 65 patients. After adjusting for baseline apnea-hypopnea index, body mass index, and supine dependency, the position of the soft palate (odds ratio, 4.0; 95% confidence interval, 1.3-11.8; P = .013) and crowding of the oropharynx (odds ratio, 7.7; 95% confidence interval, 1.4-41.4; P = .017) were related to treatment deterioration. Addition of both features significantly (P = .031) improved the accuracy of baseline models based on clinical measurements alone. Moreover, with the MAD in situ, a posteriorly located soft palate (odds ratio, 9.8; 95% confidence interval, 1.7-56.3; P = .010) and a posteriorly located tongue base (odds ratio, 7.4; 95% confidence interval, 1.5-35.9; P = .013) were associated with treatment deterioration. CONCLUSIONS: Awake nasopharyngoscopy might be a valuable office-based examination to exclude the risk of treatment deterioration and improve patient selection for MAD treatment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Predicting Therapeutic Outcome of Mandibular Advancement Device Treatment in Obstructive Sleep Apnea (PROMAD); URL: https://clinicaltrials.gov/ct2/show/NCT01532050; Identifier: NCT01532050.

Drug-Induced Sleep Endoscopy Upper Airway Collapse Patterns and Maxillomandibular Advancement.

OBJECTIVES/HYPOTHESIS: To evaluate upper airway (UA) collapse patterns during drug-induced sleep endoscopy (DISE) and maxillomandibular advancement (MMA) surgery outcome, paying particular attention to the DISE phenotype complete concentric collapse at the level of the palate (CCCp). STUDY DESIGN: Prospective case series. METHODS: Nineteen patients diagnosed with obstructive sleep apnea (OSA) prospectively underwent mandibular advancement device (MAD) treatment followed by MMA surgery. UA collapse patterns were evaluated before and after MMA surgery. Baseline apnea-hypopnea index (AHI) was compared with AHI during MAD treatment and after MMA surgery. UA collapse patterns and the presence of baseline CCCp were assessed. AHI differences between patients with and without CCCp after MMA surgery were compared. RESULTS: In 14 patients, a full dataset was obtained: 8/6 (male/female), mean age = 51 ± 7 years, body mass index (BMI) = 25.6 ± 3.7 kg/m2 , and baseline AHI = 40.2 ± 25.6 per hour of sleep. MMA surgery reduced AHI to 9.9 ± 7.2 per hour of sleep (P = .0001). Eight patients benefited from additional AHI reduction compared to MAD treatment (P = .0113). Six out of 14 (43%) patients showed baseline CCCp. Baseline patient characteristics (age, BMI, and AHI) did not significantly differ between patients with and without CCCp. AHI was equally reduced after MMA, whether (P = .0145) or not (P = .0075) CCCp was present at baseline. All patients showed resolution of CCCp (P = .0159) during postoperative DISE. CONCLUSIONS: CCCp seems not to be a negative predictor for MMA surgery outcome measured by AHI reduction. Furthermore, MMA is likely to eliminate CCCp. Therefore, MMA might be a solution for OSA patients showing CCCp and broadens the perspective for personalized medicine and combination therapy. However, a large sample is required for definitive results. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E268-E274, 2020.

Phenotypic Labelling Using Drug-Induced Sleep Endoscopy Improves Patient Selection for Mandibular Advancement Device Outcome: A Prospective Study.

STUDY OBJECTIVES: Mandibular advancement device (MAD) outcome varies between patients. We hypothesized that upper airway collapse sites, patterns, and degrees assessed during baseline drug-induced sleep endoscopy (DISE) affect MAD outcome. METHODS: One hundred patients with obstructive sleep apnea (OSA) were included and underwent baseline type 1 polysomnography. MAD was fitted intraorally at fixed 75% maximal protrusion. A total of 72 patients completed 3-month follow-up polysomnography and baseline DISE. Response was defined as apnea-hypopnea index (AHI) reduction ≥ 50%, deterioration as AHI increases during MAD treatment compared to baseline. RESULTS: Adjusting for baseline AHI and body mass index, patients with tongue base collapse showed 3.69 higher odds (1.27-10.73; P = .0128) for response. Complete concentric collapse at the level of the palate (5.32 [1.21-23.28]; P = .0234) and complete laterolateral oropharyngeal collapse (6.62 [1.14-38.34]; P = .0330) related to deterioration. Results for tongue base collapse and complete concentric collapse at the level of the palate were confirmed in the moderate to severe OSA subgroup. Applying these results to this selected subgroup increased response rate with 54% and decreased deterioration rate with 53%. These results were confirmed using other response and deterioration definitions. CONCLUSIONS: Three baseline DISE phenotypes identified during drug-induced sleep were significantly related to MAD treatment outcome: one beneficial, tongue base collapse, and two adverse, complete concentric collapse at the level of the palate and complete laterolateral oropharyngeal collapse. If confirmed in future prospective studies, these results could guide patient selection for MAD outcome. CLINICAL TRIAL REGISTRATION: This prospective clinical trial (PROMAD) was registered on Clinicaltrials.gov with identifier: NCT01532050. CITATION: Op de Beeck S, Dieltjens M, Verbruggen AE, Vroegop AV, Wouters K, Hamans E, Willemen M, Verbraecken J, De Backer WA, Van de Heyning PH, Braem MJ, Vanderveken OM. Phenotypic labelling using drug-induced sleep endoscopy improves patient selection for mandibular advancement device outcome: a prospective study. J Clin Sleep Med. 2019;15(8):1089-1099.

Pilot study on patients with Mal de Debarquement syndrome during pregnancy.

AIM: To evaluate if patients with Mal de Debarquement syndrome (MdDS) demonstrate different symptom levels or symptom type during pregnancy. MATERIALS & METHODS: 18 MdDS patients that were or had been pregnant during their condition were recruited to complete a retrospective online questionnaire. Respondents answered questions regarding their basic clinical data, diagnosis, triggers and differences in symptom level and symptom type during pregnancy and before pregnancy. RESULTS: A total of 81.3% reported that their symptoms were reduced during pregnancy compared with before pregnancy. Respondents also reported a different perception of motion and experienced less dizziness while being pregnant. CONCLUSION: The physiological changes that occur during pregnancy improve the symptoms of patients with MdDS, and this is potentially attributable to the rise in estrogen and progesterone.

Sham-Controlled Study of Optokinetic Stimuli as Treatment for Mal de Debarquement Syndrome.

Introduction: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a perception of self-motion in the absence of a stimulus, with two onset types: Motion-Triggered and Spontaneous. Currently, the pathophysiology is unknown and consequently, the therapeutic options are limited. One proposed treatment protocol, developed by Dai and colleagues is based on optokinetic stimulation, which aims to re-adapt the vestibular ocular reflex. This study aimed to reproduce the treatment protocol developed by Dai and colleagues and to assess if a placebo effect is present in the treatment protocol and lastly, aimed to further investigate the treatment on MdDS patient outcomes. Method: Twenty-five MdDS patients (13 Motion-Triggered and 12 Spontaneous) were exposed to 5 consecutive days of optokinetic treatment (consisting of exposure to optokinetic stimuli with head movements). Eleven of these 25 patients were also exposed to 2 days of a sham treatment prior to the OKN treatment. Posturography measurements and reported symptoms [e.g., using the visual analog scale (VAS)] of patients were assessed throughout the treatment. Posturography data of the patients was compared with the data of 20 healthy controls. Results: No placebo effect was recorded with any changes in postural data and VAS scale. After the optokinetic treatment, a significant improvement in postural control was observed in 48% of patients, of whom 70% were of the Motion-Triggered subtype (p-values: Area under the Curve-Anterior Posterior < 0.001; Area under the Curve-Medio Lateral p < 0.001, Confidence Ellipse Area (CEA) < 0.001, Velocity < 0.001). Conclusion: The protocol was effective in approximately half of the MdDS patients that took part in the study, with no placebo effect recorded. The Motion-Triggered group responded better to treatment than the Spontaneous group. In addition to this, this study indicates that the greatest postural changes occur within the first 3 days of treatment, suggesting that a shorter protocol is possible. Overall, these findings support what was previously observed in Dai's studies, that optokinetic stimulation can reduce and ease self-motion perception in those with MdDS. Thus, validating the reproducibility of this protocol, suggesting that a consistent and uncomplicated implementation across treatment centers is possible.

A new theory on GABA and Calcitonin Gene-Related Peptide involvement in Mal de Debarquement Syndrome predisposition factors and pathophysiology.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a sensation of motion in the absence of a stimulus, which presents with two subtypes depending on the onset: Motion-Triggered, and Spontaneous or Non-Motion Triggered. MdDS predominantly affects women around 40-50 years of age and a high number of patients report associated disorders, such as migraine and depression. The pathophysiology of MdDS is unclear, as is whether there are predisposing factors that make individuals more vulnerable to developing the condition. Hormonal changes in women similarly to what observed in migraineous patients, as well as depression disorder, have been examined as potential key factors for developing MdDS. Studies on migraine and depression have revealed correlations with hormonal fluctuations in females as well as aberrant levels of some key neurotransmitters such as Gamma-Aminobutyric Acid (GABA) and inflammatory neuropeptides like Calcitonin Gene-Related Peptide (CGRP). Consequently, this manuscript aims to propose a new hypothesis on the predisposing factors for MdDS and a new concept that could contribute to the understanding of its pathophysiology. NEW HYPOTHESIS: Recent findings have demonstrated a role for hormonal influences in MdDS patients, similar to previous observations in patients with depression and migraine. We hypothesize the involvement of gonadal hormones and aberrant neurotransmitter levels, including the GABAergic and serotonergic systems, in MdDS pathophysiology. Our theory is that certain individuals are more vulnerable to develop MdDS during specific gonadal hormonal phases. Furthermore, we hypothesize that it may be possible to identify these individuals by measurement of an existing imbalance of these neurotransmitters or inflammatory neuropeptides like CGRP. FURTHER EVALUATION OF THE HYPOTHESIS: According to one theory, MdDS is considered as a maladaptation of the Vestibular Ocular Reflex (VOR) and velocity storage. When considering this theory, it is essential to highlight that the brainstem nuclei involved in the VOR and the velocity storage include GABAb sensitive neurons, which appear to produce inhibitory control of velocity storage. Responses of these GABAb sensitive neurons are also modulated by CGRP. Thus an alteration of the GABAergic network by imbalances of inhibitory neurotransmitters or CGRP could influence signal integration in the velocity storage system and therefore be directly involved in MdDS pathophysiology. CONSEQUENCE OF THE HYPOTHESIS AND FUTURE STUDIES: A hormonal and neurotransmitter imbalance may act to predispose individuals in developing MdDS. Future studies should focus on the hormonal influences on neurotransmitters (e.g. GABA) and on the trial of CGRP antagonist drugs for the treatment of MdDS patients.

Remotely Controlled Mandibular Positioning During Drug-Induced Sleep Endoscopy Toward Mandibular Advancement Device Therapy: Feasibility and Protocol.

STUDY OBJECTIVES: The potential of a remotely controlled mandibular positioner (RCMP) during sleep studies in individual patients suffering from obstructive sleep apnea (OSA) for the determination of the effective target protrusive position (ETPP) of the mandible has been demonstrated. The research goal of this study was to assess the feasibility of the application of RCMP during drug-induced sleep endoscopy (DISE) for the determination of ETPP. METHODS: Ten patients in whom OSA was diagnosed (50% male; age 54 ± 9.5 years; body mass index 26.9 ± 2.1 kg/m2; apnea-hypopnea index 28.4 ± 13.2 events/h) were enrolled prospectively. Dental RCMP trays were fitted during wakefulness. Maximal protrusion and edge-to-edge positions were measured. Upper airway collapsibility was scored during DISE, including full-range mandibular RCMP titration within 45 minutes. ETPP was defined as the mandibular threshold protrusion yielding a stable upper airway in the absence of snoring, oxygen desaturation and apneas. RESULTS: RCMP trays were retentive and no adverse reactions occurred. RCMP was fitted intraorally prior to sedation with maxillary and mandibular trays in edge-to-edge position. Upon sedation, progressive protrusion was performed followed by reversed titration until ETPP was noted. In one patient ETPP was not within the mandibular range of motion. In one patient RCMP needed to be removed because of clenching. CONCLUSIONS: The results of this study illustrate that it is feasible to use RCMP during DISE and to determine ETPP within 45 minutes. Comparative research with polysomnography would be useful to further validate the therapy outcome upon use of RCMP during DISE.

Mal de Debarquement Syndrome: A Retrospective Online Questionnaire on the Influences of Gonadal Hormones in Relation to Onset and Symptom Fluctuation.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a persistent perception of self-motion, in most cases triggered from exposure to passive motion (e.g., boat travel, a car ride, flights). Patients whose onset was triggered in this way are categorized as Motion-Triggered (MT) subtype or onset group. However, the same syndrome can occur spontaneously or after non-motion events, such as childbirth, high stress, surgery, etc. Patients who were triggered in this way are categorized as being of the Spontaneous/Other (SO) subtype or onset group. The underlying pathophysiology of MdDS is unknown and there has been some speculation that the two onset groups are separate entities. However, despite the differences in onset between the subtypes, symptoms are parallel and a significant female predominance has been shown. To date, the role of gonadal hormones in MdDS pathophysiology has not been investigated. This study aimed to evaluate the hormonal profile of MdDS patients, the presence of hormonal conditions, the influence of hormones on symptomatology and to assess possible hormonal differences between onset groups. In addition, the prevalence of migraine and motion sickness and their relation to MdDS were assessed. METHOD: Retrospective online surveys were performed in 370 MdDS patients from both onset groups. Data were analyzed using Fisher's exact test or Fisher-Freeman-Hanlon exact test. When possible, data were compared with normative statistical data from the wider literature. RESULTS: From the data collected, it was evident that naturally cycling female respondents from the MT group were significantly more likely to report an aggravation of MdDS symptoms during menses and mid-cycle (p < 0.001). A few preliminary differences between the onset groups were highlighted such as in regular menstrual cycling (p = 0.028), reporting menses during onset (p < 0.016), and migraine susceptibility after onset (p = 0.044). CONCLUSION: These results demonstrate a potential relation between hormone fluctuations and symptom aggravation in the MT group. This study is an important first step to suggest a hormonal involvement in the pathophysiology of MdDS and provides a base for further hormonal investigation. Future prospective studies should expand upon these results and explore the implications for treatment.

Evaluation of a Trial Period With a Sleep Position Trainer in Patients With Positional Sleep Apnea.

STUDY OBJECTIVES: To assess the overall clinical effectiveness of a sleep position trainer (SPT) in patients with positional obstructive sleep apnea (POSA) and to evaluate how many patients were willing to continue treatment after a 1-month trial period. METHODS: Patients in whom POSA was diagnosed underwent a 1-month trial period with the SPT. Home sleep apnea tests were used to measure baseline data and data following the trial period with the SPT. RESULTS: The 79 patients who completed the study protocol were 81% male, had a mean age of 52 ± 12 years, and a median baseline respiratory event index (REI) of 11 (8, 16) events/h. A significant reduction in overall REI to 5 (3, 10) events/h was observed with the SPT as compared to baseline (P < .001). The median percentage of sleep time in the supine position decreased significantly from 27 (20, 48) to 7 (2, 20) with the SPT (P < .001). Adherence was found to be 95 ± 8%. Of the 44 patients who decided to continue treatment, 27 were categorized as responders (having a decrease in REI of at least 50%) and 17 were non-responders. The most important reasons for not purchasing the SPT were poor objective results, intolerance to the vibrations, cost of the device, persistent daytime sleepiness, or patient preference for other treatment options. CONCLUSIONS: Treatment with the SPT came with high adherence rates and was effective in reducing REI and supine sleep position. The trial period is in the patients' best interest, as it may prevent those who will not benefit from positional training from purchasing an SPT.