Seizures induce obstructive apnea in DBA/2J audiogenic seizure-prone mice: Lifesaving impact of tracheal implants.

The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure-induced laryngospasm and obstructive apnea lasting until respiratory arrest. We hypothesized that DBA/2J mice, which display lethal audiogenic seizures, would be protected from death by implanting a tracheal T-tube as a surrogate airway. In a 2 × 2 design, mice were implanted with either open or closed tracheal T-tubes and treated with either low-dose ketamine/xylazine to moderate thoracic spasm during the tonic seizure phase or no drug. Animals receiving both treatments had the highest survival rate, followed by animals receiving the open tube without ketamine/xylazine. The odds ratio for survival was >20 higher with an open T-tube (odds ratio = 24.14). The impact of open tracheal tubes indicates that the mechanism of death in DBA/2J mice involves seizure-induced upper airway obstruction until respiratory arrest. These results, our rat work, and our demonstration of inspiratory effort-based electromyographic signals and electrocardiographic abnormalities in rats and humans suggest that seizure-induced laryngospasm and obstructive apnea directly link seizure activity to respiratory arrest in these sudden death examples.

Obstructive apnea due to laryngospasm links ictal to postictal events in SUDEP cases and offers practical biomarkers for review of past cases and prevention of new ones.

Seizure spread into autonomic and respiratory brainstem regions is thought to play an important role in sudden unexpected death in epilepsy (SUDEP). As the clinical dataset of cases of definite SUDEP available for study grows, evidence points to a sequence of events that includes postictal apnea, bradycardia, and asystole as critical events that can lead to death. One possible link between the precipitating seizure and the critical postictal sequence is seizure-driven laryngospasm sufficient to completely obstruct the airway for an extended period, but ictal laryngospasm is difficult to fully assess. Herein, we demonstrate in a rat model how the electrical artifacts of attempts to inspire during airway obstruction and features of the cardiac rhythm establish this link between ictal and postictal activity and can be used as practical biomarkers of obstructive apnea due to laryngospasm or other causes of airway obstruction.

Systematic Review and Meta-Analysis of Post-Treatment PET/CT in HPV-Associated Oropharyngeal Cancer.

OBJECTIVE: To perform a systematic review with meta-analysis to investigate the utility of post-treatment PET/CT specifically in HPV-associated oropharyngeal squamous cell carcinoma following curative intent treatment. METHODS: Random-effects meta-analysis was used to pool data from 7 observational studies (2013-2019) obtained from a database search of PubMed, Web of Science, and EMBASE using an a priori protocol with dual independent evaluation for inclusion, risk of bias assessment for acceptable methodology, and extraction of data for analysis. PET/CT results, treatment failure, imaging and interventions subsequent to PET/CT findings, and efficacy of salvage therapy were extracted. RESULTS: Of the 907 post-treatment scans, PET/CT results were largely negative (76.2%; 95% CI, 63.4-85.6) and least often positive (11.3%; 95% CI, 8.8-14.4). PET/CT results were equivocal for 22.5% (95% CI, 12.5-36.9) and equivocal/positive for 34.2% of patients (95% CI, 25.1-44.5). Patients with an initial positive scan had the highest treatment failure rates (43.1%; 95% CI, 21.4-67.7) and those with an initial negative scan had the lowest rates (7.4%; 95% CI, 5.7-9.7). The equivocal and equivocal/positive scans had intermediate prevalence of 16.5% (95% CI, 9.4-27.6) and 16.7% (95% CI, 9.1-28.7), respectively. CONCLUSION: The low treatment failure rate following a negative PET/CT scan is reassuring, but the data are consistent with treatment failure rates up to 9.7% suggesting follow-up of these patients is prudent. Additionally, the low positive predictive value for treatment failure observed alludes to use of post-treatment PET/CT in HPV-associated disease frequently leading to unnecessary subsequent imaging and intervention.

Causes and Effects Contributing to Sudden Death in Epilepsy and the Rationale for Prevention and Intervention.

Sudden unexpected death in epilepsy (SUDEP) claims the lives of one in every thousand epileptic patients each year. Autonomic, cardiac, and respiratory pieces to a mechanistic puzzle have not yet been completely assembled. We propose a single sequence of causes and effects that unifies disparate and competitive concepts into a single algorithm centered on ictal obstructive apnea. Based on detailed animal studies that are sometimes impossible in humans, and striking parallels with a growing body of clinical examples, this framework (1) accounts for the autonomic, cardiac, and respiratory data to date by showing the causal relationships between specific elements, and (2) highlights specific kinds of data that can be used to precisely classify various patient outcomes. The framework also justifies a "near miss" designation to be applied to any cases with evidence of obstructive apnea even, and perhaps especially, in individuals that do not require resuscitation. Lastly, the rationale for preventative oxygen therapy is demonstrated. With better mechanistic understanding of SUDEP, we suggest changes for detection and classification to increase survival rates and improve risk stratification.

Proposed Mechanism-Based Risk Stratification and Algorithm to Prevent Sudden Death in Epilepsy.

Sudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of death in young adults with uncontrolled seizures. First aid guidance to prevent SUDEP, though, has not been previously published because the rarity of monitored cases has made the underlying mechanism difficult to define. This starkly contrasts with the first aid guidelines for sudden cardiac arrest that have been developed based on retrospective studies and expert consensus and the discussion of resuscitation challenges in various American Heart Association certificate courses. However, an increasing amount of evidence from documented SUDEP cases and near misses and from animal models points to a consistent sequence of events that starts with sudden airway occlusion and suggests a mechanistic basis for enhancing seizure first aid. In monitored cases, this sudden airway occlusion associated with seizure activity can be accurately inferred from inductance plethysmography or (depending on recording bandwidth) from electromyographic (EMG) bursts that are associated with inspiratory attempts appearing on the electroencephalogram (EEG) or the electrocardiogram (ECG). In an emergency setting or outside a hospital, seizure first aid can be improved by (1) keeping a lookout for sudden changes in airway status during a seizure, (2) distinguishing thoracic and abdominal movements during attempts to inspire from effective breathing, (3) applying a simple maneuver, the laryngospasm notch maneuver, that may help with airway management when aggressive airway management is unavailable, (4) providing oxygen early as a preventative step to reduce the risk of death, and (5) performing cardiopulmonary resuscitation before the limited post-ictal window of opportunity closes. We propose that these additions to first aid protocols can limit progression of any potential SUDEP case and prevent death. Risk stratification can be improved by recognition of airway occlusion, attendant hypoxia, and need for resuscitation.

A Resuscitation Option for Upper Airway Occlusion Based on Bolus Transtracheal Lung Inflation.

BACKGROUND: Acute laryngospasm sufficient to cause obstructive apnea is a medical emergency that can be difficult to manage within the very short time available for establishing an airway. We have presented substantial evidence that laryngospasm-based obstructive apnea is the cause of sudden death in epilepsy, and airway management is particularly challenging during seizure activity. OBJECTIVE: We sought to determine if the transtracheal delivery of a bolus of oxygen or room air below the level of an obstruction to inflate the lungs could be an effective method to prolong the time available for responders seeking to establish a stable airway, and, if so, what could be learned about optimization of delivery parameters from a rat model. METHODS: Rats were fitted with a t-shaped tracheal tube for controlling access to air and for measuring airway pressures. After respiratory arrest from simulated laryngospasm, bolus transtracheal lung inflation with a volume of gas equivalent to half the vital capacity was delivered to the closed respiratory system as the only resuscitation step. RESULTS: Bolus lung inflation was sufficient for resuscitation, improving cardiac function and re-establishing adequate oxygen status to support life. Inflation steps could be repeated and survival times were approximately 3 times that of non-inflated lungs. CONCLUSION: The properties and consequences of bolus lung inflation are described as a foundation for procedures or devices that can be useful in cases of severe laryngospasm and other cases of upper airway obstruction. LEVEL OF EVIDENCE: 3.

American Thyroid Association Scientific Statement on the Use of Potassium Iodide Ingestion in a Nuclear Emergency.

This document serves to summarize the issues and the American Thyroid Association (ATA) position regarding the use of potassium iodide as a thyroid blocking agent in the event of a nuclear accident. The purpose is to provide a review and updated position statement regarding the advanced distribution, stockpiling, and availability of potassium iodide in the event of nuclear radiation emergencies in the United States.

Carcinoma of the oropharynx: factors affecting outcome.

OBJECTIVES/HYPOTHESIS: To assess the value of both patient- and tumor-related factors of oropharyngeal squamous cell carcinoma in predicting patient outcome, with respect to the three primary subsites of the disease. It was hypothesized that the subsite has a significant impact on outcome. STUDY DESIGN: Historical cohort study. METHODS: A chart review was conducted of 126 patients diagnosed with squamous cell carcinoma of the oropharynx over a 10-year period. The oropharynx was divided into the following subsites: 1) base of tongue, 2) tonsil and pillars, and 3) uvula, soft palate, and posterior pharyngeal wall. Patient-related factors included age and gender. Tumor-related factors included American Joint Committee on Cancer stage, T stage, N stage, and grade. These factors were compared using the end points of disease-free survival and treatment response (complete response or partial response/no response). RESULTS: Tumor-related factors such as American Joint Committee on Cancer stage (P = .016) and T stage (P = .008) had a significant impact on treatment response. The American Joint Committee on Cancer stage (P = .030) and the T stage (P = .005) were also significant predictors of disease-free survival. Base-of-tongue lesions responded significantly worse to treatment than did tonsil and pillar or uvula, soft palate, and posterior pharyngeal wall lesions (P = .014). The disease-free survival for base-of-tongue cancer was significantly worse than for tonsil and pillar or for uvula, soft palate, and posterior pharyngeal wall cancer (P = .010). CONCLUSION: Patient-related factors such as age and gender were not significant in predicting disease-specific outcome. Important tumor-related factors were the American Joint Committee on Cancer stage and the T stage. Among the oropharyngeal subsites, squamous cell carcinoma of the base of tongue was associated with the worst outcome.

Quantitative video laryngoscopy to monitor recovery from recurrent laryngeal nerve injury in the rat.

Recovery from unilateral vocal-fold paralysis is lengthy, unpredictable, and often incomplete, highlighting the need for better treatments of the injured recurrent laryngeal nerve. To be able to monitor recovery of vocal-fold motion in studies with rats, we developed a procedure for quantitative video laryngoscopy. An asymmetry index was defined as a continuous and robust measure of unequal vocal-fold motion and calculated from spectral-density plots of vocal-fold displacements. In a cohort of 8 animals, unilateral vocal-fold paralysis was observed within seconds after clamping of the right recurrent laryngeal nerve and was accompanied by a markedly negative asymmetry index. Over the next month, the asymmetry index gradually returned to zero, concomitant with a visible recovery of vocal-fold motion. Our results suggest that quantitative video laryngoscopy is a sensitive and discriminating method for monitoring recovery from recurrent laryngeal nerve injury and set the stage for testing novel surgical and pharmacological treatments of unilateral vocal-fold paralysis.

Validation of the Modified Brief Fatigue Inventory in head and neck cancer patients.

OBJECTIVE: The aim of this study is to validate the Modified Brief Fatigue Inventory (MBFI). This is the first instrument designed to measure intensity and frequency of fatigue specifically in head and neck cancer patients, potentially allowing objective measurement in addressing this common symptom in a concise yet thorough fashion. STUDY DESIGN: Survey validation. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: The 9-item MBFI was administered to 52 consecutive cancer patients and 57 consecutive controls. Demographics, comorbidities, cancer site, and cancer stage were recorded. Psychometric properties and predictors of the MBFI were analyzed. RESULTS: The MBFI 1-week test-retest reliability was excellent (r = 0.800, P < .001). Internal consistency was also excellent (Cronbach's α = 0.938). Construct validity of the MBFI compared with the previously validated Multidimensional Fatigue Symptom Inventory-Short Form was excellent (r = 0.814, P < .001). Discriminant validity of cancer patients vs controls was significant (P = .027). Predictors of increased MBFI score included American Society of Anesthesiologists (comorbidity) score (bivariate analysis, r = 0.287, P = .039), cancer stage (analysis of variance, P = .007), and adjuvant radiotherapy (t test, P = .016). Cancer stage and comorbidity were further correlated with a multiple regression linear model. No significant relationship was found with age, sex, marital status, education, ethnicity, feeding tube, tracheostomy, or laryngectomy. CONCLUSION: The MBFI is a reliable and valid tool for measuring fatigue levels in head and neck cancer patients. In the context of initial assessment or posttreatment trending, this brief survey can be rapidly administered, providing valuable objective data on a very common and potentially debilitating symptom.

Laryngeal nerve monitoring: current utilization among head and neck surgeons.

OBJECTIVE: There is continued debate over the value of laryngeal nerve monitoring (LNM) during thyroidectomy. Previous studies have suggested that utilization of electromyographic endotracheal tubes for neuromonitoring is limited. We queried head and neck surgeons regarding their attitudes toward LNM. STUDY DESIGN: Voluntary survey. SETTING: Internet based. SUBJECTS AND METHODS: An anonymous survey of the members of the American Head and Neck Society was performed. Information was collected on participants' training history, practice setting, years of experience, and annual volume of thyroid and parathyroid surgeries. Participants' use of LNM and their beliefs regarding possible benefits were assessed. RESULTS: One hundred seventy surveys were completed (18% response rate). Of respondents, 65% use LNM in at least some thyroid and parathyroid cases, 37% always and 28% sometimes. The most commonly cited reasons for LNM use were "medical-legal protection" and "increased confidence." Comparing otolaryngologists to general surgeons, 43% versus 17% (P = .016) always use LNM, 27% versus 36% sometimes use monitoring, and 30% versus 47% never use monitoring. Younger surgeons were more likely to use LNM. CONCLUSION: Currently, no consensus exists regarding the use of LNM during thyroid and parathyroid surgery. Our results suggest that LNM use has become more widespread. Irrespective of the reasons surgeons are adopting LNM, if this trend continues, LNM may eventually become routine practice among head and neck surgeons.

Paranasal sinus involvement in metastatic carcinoma.

Metastatic carcinoma involving the paranasal sinuses is uncommon. One hundred-sixty seven cases have been published in the literature since 1951. Symptoms, signs, and rhinoscopic and imaging findings are often nonspecific, and the diagnosis may be missed for considerable time. Therefore, a high level of suspicion is warranted in patients with known malignancies presenting with persistent or recurrent rhinosinusitis or facial complaints.

Systematic review of laryngeal reinnervation techniques.

OBJECTIVE: To systematically review outcomes of reinnervation techniques for the management of unilateral vocal fold paralysis (UVFP). DATA SOURCES: Medline and Cochrane databases for English-language studies published between 1966 and 2009 on the surgical management of UVFP. REVIEW METHODS: Studies were excluded if they reported on bilateral vocal fold paralysis, used nonhuman subjects, or did not assess clinical outcomes. Outcomes of interest were visual analysis, acoustic analysis, perceptual analysis, and electromyography. RESULTS: Of 686 initial studies, 14 studies encompassing 329 patients were eligible for analysis. All studies had a case-series design. Of reported patients, 60.2 percent were men, with mean age of 51 years (range, 12-79 years). The most common reinnervation technique was ansa cervicalis-to-recurrent laryngeal nerve (RLN), which was most commonly performed after thyroidectomy (43.5%). Other techniques with reportable outcomes included primary RLN anastomosis, ansa-to-RLN combined with cricothyroid muscle-nerve-muscle pedicle, ansa-to-thyroarytenoid neural implantation, ansa-to-thyroarytenoid neuromuscular pedicle, and hypoglossal-to-RLN. Median postsurgical follow-up was 12 months, and mean time to first signs of reinnervation was 4.5 months (SD 2.9 months). Visual analysis of glottic gap showed the greatest mean improvement with ansa-to-RLN, from 2.25 (SD 0.886) to 0.75 (SD 0.886) mm (P < 0.01). Acoustic analysis showed greatest improvement with neural implantation, with a change in mean phonation time from seven (SD 1.22) to 16 (SD 5.52) seconds (P < 0.01). Perceptual analysis and electromyography demonstrated improvement in all studies. CONCLUSION: Reinnervation is effective in the management of UVFP, although the specific method may be dictated by anatomical limitations. Prospective studies utilizing uniform and consistent outcome parameters are necessary.

Determination of the function of the internal branch of the superior laryngeal nerve after thyroidectomy.

BACKGROUND: Several unique complications of thyroidectomy exist because of its regional anatomy; they are well studied and reported. A majority of thyroidectomy patients report vague upper aerodigestive tract complaints. Despite this, no formal assessment of the integrity of the internal branch of the superior laryngeal nerve after thyroidectomy exists in the literature. METHODS: Thirty three patients undergoing thyroidectomy were prospectively evaluated with preoperative and postoperative laryngopharyngeal sensory testing. RESULTS: Preoperatively, 16 patients (49%) reported dysphagia, and 19 (58%) complained of globus sensation. Postoperatively, 24 (73%) patients complained of dysphagia, and 25 (76%) reported globus sensation. Preoperative sensory testing showed a mean sensory threshold of 2.79 +/- 0.51 mm Hg. The mean change in thresholds postoperatively was trivial (0.07 +/- 0.29 mm Hg), and did not differ significantly from zero (p = .19). CONCLUSIONS: Although most patients report significant difficulty swallowing after thyroidectomy, the sensory nerve to the laryngopharynx remains intact and is not at risk during thyroid surgery.

The Wookey flap revisited.

BACKGROUND: Complete circumferential pharyngoesophageal reconstruction has undergone remarkable changes and developments during the last three decades. Gastric transposition and microvascular techniques are the standards of care. However, in cases of failure, or where other factors such as severe comorbidities prevent the use of microvascular techniques, reconstruction with local flaps provide a reliable option. We have used the Wookey flap technique in six patients with complete circumferential loss of the pharynx and upper esophagus. To make the procedure more reliable, we added a "delay" stage. METHODS: Retrospective review of charts of six Wookey-type reconstructions of the pharynx and upper esophagus done in our department at SUNY-HSC, Brooklyn, and The Long Island College Hospital. RESULTS: Five of the six patients had successful reconstruction of complete circumferential pharyngoesophageal resection. All five resumed oral alimentation. The flap failed in one patient. CONCLUSIONS: The Wookey flap may still provide surgeons with a "last resort" reconstructive option after complete, circumferential pharyngoesophageal resection.