Long-term stimulation by implanted pacemaker enables non-atrophic treatment of bilateral vocal fold paresis in a human-like animal model.

A wide variety of treatments have been developed to improve respiratory function and quality of life in patients with bilateral vocal fold paresis (BVFP). One experimental method is the electrical activation of the posterior cricoarytenoid (PCA) muscle with a laryngeal pacemaker (LP) to open the vocal folds. We used an ovine (sheep) model of unilateral VFP to study the long-term effects of functional electrical stimulation on the PCA muscles. The left recurrent laryngeal nerve was cryo-damaged in all animals and an LP was implanted except for the controls. After a reinnervation phase of six months, animals were pooled into groups that received either no treatment, implantation of an LP only, or implantation of an LP and six months of stimulation with different duty cycles. Automated image analysis of fluorescently stained PCA cross-sections was performed to assess relevant muscle characteristics. We observed a fast-to-slow fibre type shift in response to nerve damage and stimulation, but no complete conversion to a slow-twitch-muscle. Fibre size, proportion of hybrid fibres, and intramuscular collagen content were not substantially altered by the stimulation. These results demonstrate that 30 Hz burst stimulation with duty cycles of 40% and 70% did not induce PCA atrophy or fibrosis. Thus, long-term stimulation with an LP is a promising approach for treating BVFP in humans without compromising muscle conditions.

Impact of Human Papillomavirus-Negative Dominance in Oropharyngeal Cancer on Overall Survival: A Population-Based Analysis in Germany from 2018 to 2020.

The impact of the relation of human papillomavirus (HPV) and smoking status of oropharyngeal squamous cell carcinoma (OPSCC) on overall survival (OS) was investigated in a retrospective population-based study in Thuringia, Germany. A total of 498 patients with OPSCC (76.9% men; mean age 62.5 years) from 2018 to 2020 were included. OPSCC cases were 37.3% HPV-positive (+) (31.2% smokers; mean incidence: 2.91/100,000 population) and 57.8% HPV-negative (63.5% smokers; mean incidence: 4.50/100,000 population). Median follow-up was 20 months. HPV+ patients had significantly better OS than HPV-negative (-) patients (HPV+: 2-year OS: 90.9%; HPV-: 2-year OS: 73.6%; p < 0.001). In multivariable analysis, HPV- patients (hazard ratio (HR) = 4.5; 95% confidence interval (CI): 2.4-8.6), patients with higher N classification (N2: HR = 3.3; 95% CI: 1.71-6.20; N3: HR = 3.6; 95% CI: 1.75-7.31) and with a higher cancer staging (III: HR = 5.7; 95% CI: 1.8-17.6; IV: HR = 19.3; 95% CI: 6.3-57.3) had an increased hazard of death. HPV- smokers formed the majority in Thuringia. Nicotine and alcohol habits had no impact on OS. Optimizing OPSCC therapeutic strategies due to the dominance of HPV- is more important than discussing de-escalation strategies for HPV+ patients.

[Management of blunt and penetrating laryngeal trauma]. / Management von stumpfen und scharfen Kehlkopfverletzungen.

Patients presenting with laryngotracheal trauma can be in a life-threatening situation. Early recognition of the severity of the injury and, if necessary, surgical intervention within the first 24-48 h increases the chance of achieving a good functional late result. Preservation or restoration of voice and swallowing function is the long-term therapeutic goal. Precise assessment of the extent of the injury can be achieved using a combination of computed tomography and flexible laryngotracheoscopy. Symptoms often do not reflect the extent of the injury, which can vary from endolaryngeal hemorrhage to complete laryngotracheal separation. Conservative treatment consists of observation with symptomatic therapy. On the other hand, surgery may include endolaryngeal repair and/or transcervical reconstruction; securing the airways is of utmost importance.

[Neurolaryngology]. / Neurolaryngologie.

Neurological and neurophysiological knowledge of neuromuscular diseases is combined in neurolaryngology with experience from laryngology. Laryngeal electromyography (LEMG) is the most important diagnostic and prognostic tool in neurolaryngology. It can be combined with diagnostic electrostimulation. Interest in LEMG today extends beyond the thyroarytenoid muscle to all accessible laryngeal muscles. LEMG should be performed and interpreted according to a standardized protocol. Main applications of LEMG are confirmation, topodiagnostic and prognostic assessment of vocal fold paralysis. It is possible to differentiate fresh from old recurrent laryngeal nerve lesions as well as mechanical vocal fold fixations from paralysis. Needle guidance for botulinum toxin injections in spasmodic dysphonia and for augmentation laryngoplasty can be supported by LEMG, but also by laryngeal ultrasound. The timing of therapy for temporary and permanent augmentations, thyroplasty and reinnervation surgery may be better defined with experience from neurolaryngology. The use of diagnostic neurostimulation can reveal any remaining active movement potential of a vocal fold and thus help identify candidates for future laryngeal pacemaker treatments. Other topics in neurolaryngology include spasmodic dysphonia and underlying neurological diseases such as stroke, central vocal fold paralysis, essential tremor and Parkinson's disease. Laryngoscopic, clinical and LEMG characteristics of these diseases are presented.

Laryngeal Synkinesis: A Viable Condition for Laryngeal Pacing.

Laryngeal synkinesis as a form of defective healing is the rule rather than the exception in persistent vocal fold paralysis. It typically occurs 4-6 months after the onset of the recurrent laryngeal nerve paralysis. The incidence is up to 85%. Not all laryngeal muscles need to be equally affected. Reliable evidence can only be provided by a laryngeal electromyography. Physiological co-activation of the laryngeal muscles during antagonistic maneuvers must be considered. Although synkinesis undeniably worsens the prognosis for a motion recovery, it protects the muscle fibers from degeneration. A differentiation is required between favorable synkinesis (type I according to Crumley), which does not always require further therapy in the case of unilateral paralysis, and unfavorable forms of synkinesis (type II-IV) according to Crumley, which are associated with a functionally relevant malposition of the vocal fold(s) or with vocal fold jerks. Particularly when bilateral vocal fold motion does not return, type I synkinesis can be a good prerequisite for new dynamic therapy approaches, such as laryngeal pacing. The rarely occurring type II-IV synkinesis should, whenever possible, be transformed into a more favorable type I synkinesis by selective or non-selective reinnervation at an early stage of the disease. The latter applies to expected muscle atrophy with insufficient regrowth of nerve fibers.

Vocal fold paresis: Medical specialists' opinions on standard diagnostics and laryngeal findings.

PURPOSE: There is still no clear consensus on the diagnostic value of specific laryngeal findings in patients with suspected vocal fold paresis (VFP). The aim of the study was to establish expert opinion on criteria for the diagnosis of VFP in Europe. METHODS: A cross-sectional survey using the questionnaire introduced by Wu and Sulica for US American experts was addressed to laryngeal experts in Germany, Austria, and Switzerland and in a second survey wave to members of the European Laryngological Society. RESULTS: 100 respondents returned survey 1 (response rate 47.2%). 26% worked at a university department. 28% regularly used laryngeal electromyography (LEMG). A pathologic test results in LEMG was considered to have the strongest positive predictive value for VFP (79 ± 23%), followed by a decreased vocal fold abduction (70 ± 29%), decreased vocal fold adduction (61 ± 34%), and atrophy of the hemilarynx (61 ± 31%). The multivariate analysis showed the predictive value of LEMG was estimated lower by respondents from non-university hospital (ß = - 16.33; confidence interval (CI) = - 25.63 to - 7.02; p = 0.001) and higher in hospitals with higher frequency of VFP patients per months (ß = 1.57; CI = - 0.98 to 2.16; p < 0.0001). 30 ELS members returned survey 2 (response rate, 8.4%). Their answers were not significantly different to survey 1. CONCLUSIONS: The laryngology experts in Europe rely on LEMG for diagnosis of VFP like the US American experts, but paradoxically only a minority uses LEMG frequently. Next to LEMG, motion abnormities were considered to have the best predictive value for the diagnosis of VFP.

Permanent transoral surgery of bilateral vocal fold paralysis: a prospective multi-center trial.

OBJECTIVES/HYPOTHESIS: To describe postoperative adverse events (AEs) and outcomes after transoral surgery for bilateral vocal fold paralysis (BVFP). STUDY DESIGN: Prospective observational multicenter study. METHODS: Thirty-six patients with BVFP underwent transoral surgery using standard surgical procedures to unilaterally widen the glottic area. Postoperative adverse events (AEs) including severe adverse events (SAEs) were registered continuously. Pre- and 6-month postoperative evaluations included the 6-Minute Walk Test, the 36-Item Short Form Health Survey (SF-36), the Glasgow Benefit Inventory, the 12-Item Voice Handicap Index (VHI-12), and a Fiberoptic Endoscopic Evaluation of Swallowing graded according to the Penetration-Aspiration-Scale. RESULTS: The patients underwent posterior cordotomy, partial arytenoidectomy, or permanent laterofixation as single procedures or in combination. Forty-seven percent of the patients had postoperative AEs. Dyspnea was the most frequent AE (45%). In 40% of AEs, the events were severe (SAEs), and 72.5% were related to the study intervention. Revision surgery leading to prolonged hospitalization or rehospitalization was necessary in nine cases (25%). Laterofixation was correlated to a decreased risk of AEs (P = 0.042). Six months after surgery, a significant improvement was seen in the SF-domains: Physical component score (P = 0.008), physical functioning (P = 0.001), physical role (P = 0.031), and vitality (P = 0.032). Concerning the voice handicap, only the VHI-12 physical subscore showed a decrease (P = 0.005). The total score and other VHI-12 subscores did not change significantly (all P > 0.05). CONCLUSION: BCVP patients profit from modern transoral surgery for unilateral glottic widening; quality of life is improved; and the voice is preserved. Nevertheless, postoperative complications are frequent. LEVEL OF EVIDENCE: 2b.

Laryngeal pacing in minipigs: in vivo test of a new minimal invasive transcricoidal electrode insertion method for functional electrical stimulation of the PCA.

Functional electrical stimulation (FES) of the posterior cricoarytenoid muscle (PCA) to restore respiratory function of the larynx may become an option for the treatment of bilateral recurrent laryngeal nerve paralysis (RLNP) in the near future. The feasibility of this has been shown in several animal trials and in a human pilot study. The common open surgical inferolateral approach for electrode insertion into the PCA for FES has a risk of damaging the recurrent laryngeal nerve (RLN) and may result in postoperative swelling and scaring of the larynx. Therefore, a minimal invasive electrode insertion technique is needed. A new miniaturized bipolar spiral tip electrode and a new electrical stimulatable insertion needle were tested in a short-term trial for an endoscopically guided and functionally controlled transcricoidal electrode insertion in eight Göttingen minipigs with bilateral normal RLN function. The feasibility of this technique was evaluated and the achieved positions of the electrodes in the PCA were analyzed using intraoperative stimulation threshold data and 3D-CT reconstructions. In seven cases it was possible to place two well-performing electrodes into the PCA. They were positioned one on either side. In one animal no functioning electrode position could be achieved because the PCA was missed. Thresholds of the electrode tips varied between 0.2 and 2.5 mA (mean 0.71 mA). In any case maximal glottal opening could be reached before adductors were co-activated. The majority of electrodes were placed into the central lower part of the PCA with no apparent correlation between threshold and electrode position. Surgical trauma might be further reduced by using endoscopy via a laryngeal mask avoiding the temporary tracheostomy used in this trial. If the implanted electrodes remain stable in long-term tests, we suggest that this method could soon be transferred into human application.