Boris A. Stuck

Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US

Tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction for treatment of obstructive sleep apnea syndrome.

2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age <or=40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care.

Multilevel Surgery for Obstructive Sleep Apnea: Short-Term Results

In recent years a considerable effort has been made to establish the use of different surgical techniques for the treatment of obstructive sleep apnea syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to tongue base hypertrophy remains in many ways an unsolved problem. The aim of this study was to evaluate the safety and efficacy of tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction in the treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were treated with radiofrequency tissue ablation. An intensified treatment protocol was used, delivering 2,800 J per treatment session under local anesthesia. Two nights of polysomnography testing were performed before and after treatment. Daytime sleepiness, snoring and postoperative morbidity were assessed using questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to 24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured after the procedure (reduction in RDI of S 50% and a postoperative RDI of <15/h) and ten (55%) showed an improvement of >20% in their RDI. Daytime sleepiness and snoring improved significantly. Peri- and postoperative morbidity was low; one severe complication occurred (tongue base abscess). We were able to achieve similar cure and responder rates to those reported in a recently published pilot study but with a reduced number of treatment sessions. We believe that this technique may improve patient acceptance and have beneficial cost implications.

Long-Term Results of Palatal Implants for Primary Snoring

OBJECTIVE: To determine the efficacy of a new multilevel surgical protocol for obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Sixty patients with moderate to severe OSA because of multilevel pharyngeal obstruction were enrolled into this prospective, controlled clinical trial after clinical examination, endoscopy, and polysomnography. Surgery included uvulaflap, tonsillectomy, hyoid suspension, and radiofrequency treatment of the tongue base (group A). A second group did not receive hyoid suspension (group B). In both groups, nasal surgery was performed if necessary. Polysomnography and Epworth Sleepines Scale (ESS) were recorded at baseline and 2 to 15 months after surgery. RESULTS: In group A, the mean apnea-hypopnea index (AHI) decreased significantly after surgery (38.9 ± 20.0 vs 20.7 ± 20.6, P < 0.0001), whereas in group B the AHI did not. All secondary variables (minimal oxygen saturation, mean oxygen saturation, arousal index), and the ESS significantly improved in group A with only changes in arousal index and ESS reaching levels of significance in group B. CONCLUSION: The presented protocol including the hyoid suspension proved to be effective in the treatment of OSA, whereas surgery without hyoid suspension was less successful.

Information processing during sleep: the effect of olfactory stimuli on dream content and dream emotions

OBJECTIVE: To determine the safety and efficacy of the Pillar Palatal Implant System over a 1-year follow-up period. STUDY DESIGN AND SETTING: In this prospective study, 40 healthy adult patients with primary snoring due to palatal flutter were treated after clinical, polysomnographic, and endoscopic examination. Under local anesthesia 3 implants were placed into the soft palate. Postoperative morbidity and functional parameters were assessed. Snoring and daytime sleepiness were assessed before and 90, 180, and 360 days after surgery. Objective data were obtained by polysomnography and SNAP-recording before and 90 days after treatment. RESULTS: All implants were placed without complications. A total of 13 implants partially extruded uneventfully in 10 patients. Functional parameters remained unchanged. After 1 year, snoring was reduced from 7.1 ± 1.9 to 4.8 ± 2.5 (Visual-Analogue-Scale, P < 0.05) and daytime sleepiness from 6.1 ± 3.2 to 4.9 ± 3.1 (Epworth-Sleepiness-Scale, P < 0.05). SNAP data and polysomnography parameters showed clinically irrelevant changes. CONCLUSION: Our data demonstrate a significant decrease in snoring and daytime sleepiness over a period of one year.

Complications of Temperature-controlled Radiofrequency Volumetric Tissue Reduction for Sleep-disordered Breathing

Research has shown that external stimuli presented during sleep can affect dream content, thus reflecting information processing of the sleeping brain. Olfactory stimuli should have a stronger effect on dream emotions because their processing is linked directly to the limbic system. Because selective olfactory stimulation does not increase arousal activity, intense olfactory stimulation is therefore a prime paradigm for studying information processing during sleep. Fifteen healthy, normosmic volunteers were studied by intranasal chemosensory stimulation during rapid eye movement sleep based on air‐dilution olfactometry. For olfactory stimulation, hydrogen sulphide (smell of rotten eggs) and phenyl ethyl alcohol (smell of roses) was used and compared with a control condition without stimulation. The olfactory stimuli affected significantly the emotional content of dreams: the positively toned stimulus yielded more positively toned dreams, whereas the negative stimulus was followed by more negatively toned dreams. Direct incorporations, i.e. the dreamer is smelling something, were not found. The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used. It would be interesting to conduct learning experiments (associating specific odours with declarative material) to study whether this declarative material is incorporated into subsequent dreams if the corresponding odour cue is presented during sleep. It would also be interesting to study the effect of positively toned olfactory stimuli on nightmares.

Anatomic Changes After Hyoid Suspension for Obstructive Sleep Apnea: An MRI Study

Objective--Temperature-controlled radiofrequency volumetric tissue reduction (RFVTR) is a minimally invasive technique used in the treatment of the tongue base, soft palate and turbinates. Complications seem to be rare, but the scope of previous studies was often limited by the small number of patients included. The aim of this study was to evaluate postoperative complications in a large series of patients. Material and Methods--In this retrospective study, temperature-controlled radiofrequency procedures (Somnoplasty®) performed between May 1998 and March 2002 were considered. The charts of the patients were analyzed with regard to intra- or postoperative complications. Results--In total, 322 patients received 497 treatment sessions; 239 of these treatments were isolated and the remaining 258 were combined procedures. Mean follow-up was 122.8±145.5 days. Concerning radiofrequency surgery, nine postoperative complications were observed (2.0%) as follows: ulcerations of the tongue base or soft palate; dysphagia necessitating hospital admission; temporary palsy of the hypoglossal nerve; and an abscess of the base of the tongue. Conclusions--Complications occurring after RFVTR are infrequent and mostly mild. Overall, temperature-controlled RFVTR is a safe procedure when used both in isolation and as part of a combined approach.

Mometasone furoate nasal spray improves olfactory performance in seasonal allergic rhinitis

OBJECTIVE: To assess the effects of isolated hyoid suspension on subjective and objective parameters of obstructive sleep apnea and to evaluate changes in upper airway anatomy with the help of standardized magnetic resonance imaging. STUDY DESIGN AND SETTING: Fifteen patients received isolated hyoid suspension. Changes in respiratory disturbance index were assessed with polysomnography, and anatomical changes with standardized magnetic resonance imaging. Snoring, daytime sleepiness, and functional parameters were assessed with questionnaires. Lateral x-ray cephalometry was performed preoperatively. RESULTS: Mean respiratory disturbance index was reduced from 35.2 ± 19.1 to 27.4 ± 26.2. Forty percent of the patients were classified as responders. Daytime sleepiness improved significantly. Relevant changes in upper airway anatomy could not be detected. There were no remarkable differences between responders and nonresponders in regard to imaging. CONCLUSIONS: Hyoid suspension is effective only in a subgroup of patients and does not lead to relevant changes in airway diameters in the awake patient. Magnetic resonance imaging and x-ray cephalometry do not add additional information for patient selection. SIGNIFICANCE: The reported clinical effects of hyoid suspension are more likely due to functional changes in airway collapsibility than to an enlargement of the upper airway.

Volumetric tissue reduction in radiofrequency surgery of the tongue base.

Impairment of olfactory function is frequently present in patients with allergic rhinitis (1, 2). This seems to be associated particularly with inflammatory processes (3). The aim of this study was to investigate the effects of mometasone furoate nasal spray on olfactory performance in patients with seasonal allergic rhinitis. Twenty-four patients (age 27.3 4.9 years) took part in this double-blind, placebo-controlled, randomized, prospective study (11 placebo, 13 verum). Allergic rhinitis was diagnosed on the basis of a medical history and skin prick tests. Allergy symptoms were quantitatively assessed before and after treatment. Nasal airflow was measured with anterior rhinomanometry. Psychophysical measures of olfactory function were obtained using the ‘Sniffin’ Sticks’ test kit (Heinrich Burghart Elektround Feinmechanik GmbH, Wedel, Germany; bilateral testing of butanol odor threshold, odor discrimination and identification) (4). Patients received mometasone furoate nasal spray (Nasonex, Essex Pharma GmbH, Munchen, Germany) or placebo for 2 weeks. The results were normalized to baseline values. SPSS software (v. 10) was used for statistical analyses. After testing for normal distribution, investigations were performed with the help of variance analyses for repeated measures; nasal air-flow was used as a co-variate. t-tests were employed for between-group analyses and for posthoc comparisons. For correlational analyses, Pearson statistics were used. Symptom scores were reduced in both groups (placebo: 24.7 12.9 to 20.4 14.8 units, mometasone 18.4 13.1 to 8.8 7.6 units; t 1⁄4 0.85, P 1⁄4 0.41). Nasal flow decreased in the placebo group (731 122 to 688 145 cm/s) and increased in the mometasone group (747 177 to 805 93 cm/s). However differences between groups were not significant (t 1⁄4 1.79, P 1⁄4 0.08). When investigating olfactory function, the main effect for the factor ‘treatment’ narrowly missed statistical significance (F [1,21] 1⁄4 3.75, P 1⁄4 0.066). However, there was a significant interaction between the factors ‘test’ and ‘treatment’ (F [2,42] 1⁄4 3.93, P 1⁄4 0.027) indicating that test results differed between groups. Posthoc comparisons revealed that mometasone subjects became more sensitive to butanol than subjects treated with placebo (t 1⁄4 2.22, P 1⁄4 0.037) while there was no such difference for odor identification (t 1⁄4 1.41, P 1⁄4 0.17) or odor discrimination (t 1⁄4 0.92, P 1⁄4 0.37). There was a nonsignificant correlation between normalized air-flow and normalized results of olfactory tests: r24 0.55. Odor threshold significantly improved after 2 weeks of treatment with mometasone furoate nasal spray. This appeared to be independent of the accompanying improvement in allergic symptoms or nasal airflow. This supports the notion that impairment of olfactory function in allergic rhinitis is mostly because of the allergic inflammation and not because of reduced nasal airflow alone. Following topical treatment with steroids, Meltzer et al. (5) reported significant improvement of odor identification, but not of odor thresholds. As they used the Connecticut Chemosensory Clinical Research Center evaluation, differences may relate to different methods of assessing odor threshold. In conclusion, anti-inflammatory treatment with topical nasal steroids not only reduces ‘classical’ symptoms of allergy but improves olfactory function in patients with seasonal allergic rhinitis.

Lesion Formation in Radiofrequency Surgery of the Tongue Base

OBJECTIVES: Radiofrequency surgery is a minimally invasive technique for the treatment of the tongue base in sleep-disordered breathing. The aim of this study was to evaluate the changes in upper airway anatomy induced by radiofrequency surgery with MRI. STUDY DESIGN AND SETTING: 10 patients with sleep-disordered breathing were treated with radiofrequency surgery at tongue base. MRI measurements were performed before and after surgery with the help of a recently published protocol. RESULTS: The mean total number of energy delivered per patient was 4750 ± 1641 Joule. Relevant changes could be observed neither for tongue volume or dimension nor for retrolingual space. CONCLUSIONS: Changes in upper airway anatomy could not be demonstrated. The effects of radiofrequency surgery of the tongue base may more likely be a result of changes in upper airway collapsibility. SIGNIFICANCE: Functional effects of surgical interventions in sleep-disordered breathing should be considered in addition to mechanistic concepts alone.