Thousands of rescued harbor seals (Phoca vitulina) require rehabilitation worldwide. Many require resource intensive gavage feeding due to abandonment soon after birth. Little is known about seal swallowing, therefore, our primary objective was to determine the feasibility of conducting videofluoroscopic swallowing studies (VFS) on seal pups prior to their release. Secondarily, we propose swallowing phase descriptions. We adapted a VFS approach used in humans and our feasibility parameters included: bolus detection and consumption, and number of analyzable swallowing events. Unrestrained seals were imaged in a dry environment using a Siemens mobile c-arm fluoroscopy unit. Oral boluses were thawed herring injected with liquid barium suspension (105% w/v). Two independent raters described swallows using a standardized approach with results summarized descriptively. We successfully completed freely-behaving VFS with two infant seals (1 male: 8 wks, 3 d; 1 female: 5 wks, 3 d). Both consumed five boluses with six fully analyzable swallowing events. We describe four swallow phases: preparatory, prehension, oropharyngeal and esophageal. Airway protection likely occurs in two ways: (1) during the preparatory phase through modified corniculate cartilage contact with the glottis and (2) with soft palate contact to the base of tongue prior to swallow initiation. We have conducted a unique VFS approach on rehabilitated seals, prior to their release. We have described airway protection and suggest that swallowing is initiated earlier in the feeding process than described previously. This protocol success will afford: (1) collection of normative swallowing data, and (2) future knowledge translation from humans to seals.

Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurological and systemic comorbidities, including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently, we showed the postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests that glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.

OBJECTIVE: The laryngeal adductor reflex (LAR) is vital for airway protection and can be electrophysiologically obtained under intravenous general anesthesia (IGA). This makes the electrophysiologic LAR (eLAR) an important tool for monitoring of the vagus nerves and relevant brainstem circuitry during high-risk surgeries. We investigated the intra-class variability of normal and expected abnormal eLAR.
METHODS: Repeated measures of contralateral R1 (cR1) were performed under IGA in 58 patients. Data on presence/absence of cR2 and potential confounders were also collected. Review of neuroimaging, pathology and clinical exam, allowed classification into normal and expected abnormal eLAR groups. Using univariate and multivariate analysis we studied the variability of cR1 parameters and their differences between the two groups.
RESULTS: In both groups, cR1 latencies had coefficients of variation of <2%. In the abnormal group, cR1 had longer latencies, required higher activation currents and was more frequently desynchronized and unsustained; cR2 was more frequently absent.
CONCLUSIONS: cR1 latencies show high analytical precision for measurements. Delayed onset, difficult to elicit, desynchronized and unsustained cR1, and absence of cR2 signal an abnormal eLAR.
CONCLUSIONS: Understanding the variability and behavior of normal and abnormal eLAR under IGA can aid in the interpretation of its changes during monitoring.

BACKGROUND: Swallow and cough impairments lead to aspiration and reduced clearance of aspirate material. Both behaviors are impaired in Parkinson\'s disease, but it is unknown whether a similar relationship of dysfunction exists in forms of atypical Parkinsonism (APD). Elucidating this association in APD may lead to early, comprehensive airway protection treatment.
OBJECTIVE: We tested the hypotheses that swallow deficits in APD are associated with impaired cough and that airway protective dysfunction is associated with longer disease duration.
METHODS: Swallowing difficulty was described by 11 participants with APD. Penetration-Aspiration Scale (PAS) and DIGEST scores for thin liquid trials were extracted from medical records of videofluoroscopic swallow study reports. Voluntary and capsaicin induced-reflex cough measures of flow, volume, and timing were analyzed.
RESULTS: While most participants did not have post-swallow residue, ~80% received abnormal PAS scores and reported swallowing difficulty. Those with abnormal PAS scores had lower voluntary cough expired volume (P = 0.037; mean rank difference = 5.0); lower reflex inspiratory flow rate (P = 0.034; mean rank difference = 5.5); and longer reflex expiratory flow rise time (P = 0.034; mean rank difference = 5.5). Higher PAS scores and reduced reflex cough volume acceleration were significantly correlated (r = -0.63; P = 0.04) and longer disease duration predicted larger voluntary cough expired volume (R2  = 0.72) and longer flow rise times (R2  = 0.47).
CONCLUSIONS: As swallow safety worsens, so might the ability to clear the airways with effective cough in in APD; particularly with longer disease duration. Assessing cough in conjunction with swallowing is important for informing airway protection treatment plans in APD.

Camphor is a highly toxic ingredient that can be found in commonly used rubs and preparations such as Tiger balm and Vicks. There is a wide range of symptoms resulting from camphor oil toxicity, manifesting in sweating and agitation and can progress to more serious symptoms of seizures, cardiac arrhythmias, and cardiopulmonary arrest. We present a 61-year-old male, who is a known case of major depressive disorder, was brought to the emergency department on 10/09/2022, two hours after ingesting approximately 500 mL of camphor oil in its liquid form. He developed two episodes of tonic-clonic seizures at home and then later had another episode in the emergency department. As he presented to the emergency room, he was confused, agitated, restless, and diaphoretic. The management in the Emergency Department started with assessing his airway and administration of intravenous (IV) benzodiazepines and IV fluids. The ECG revealed sinus rhythm with borderline QT and QRS. During his stay in the emergency room, his mental status worsened and he became more confused and restless, and he developed another tonic-conic seizure. Therefore, he was intubated. The patient was shifted and managed in the intensive care unit, and 48 hours later the patient was extubated. This case report illustrates the importance of addressing the potential risks of home remedies as they are increasingly being used by the population considering them as safe. Camphor, being the most cultivated essential oil, is a highly toxic compound that, even in very small concentrations, can be lethal to infants and children. It is a component of numerous over-the-counter remedies and has the potential for accidental consumption. Generalized tonic-clonic seizure being the most prominent manifestation which can occur as early as five minutes after exposure needs to be anticipated and treated accordingly. Treatment for symptomatic patients is primarily supportive with special attention paid to QRS complex widening in the ECG.

Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger Complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.

Timely and complete laryngeal closure is critical for a successful swallow. Researchers have studied laryngeal closure, including true vocal cords (TVC) closure, closure of the arytenoids to the epiglottis base (laryngeal vestibule closure), and epiglottic inversion, but the most commonly available imaging tools have limitations that do not allow the study of these components individually. Swallowing computerized tomography (CT) has enabled three-dimensional dynamic visualization and quantitative evaluation of swallowing events providing a unique view of swallowing-related structures and their motion. Using CT, TVC closure can be visualized and evaluated on any plane or cross-section without being obscured by of laryngeal vestibule closure or epiglottis inversion. The current review summarizes the results of five papers evaluating the effects of bolus consistency and volume, posture, and age on TVC closure. The combined results of these studies suggest that TVC closure is responsive to oral sensory input based on bolus consistency and size and can be modulated in response to conditions perceived to increase the risk of airway invasion. These results are meaningful for dysphagia rehabilitation as it suggests that interventions to improve TVC closure are likely to enhance airway protection.

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function.

BACKGROUND: Improvement and maintenance of bulbar function are goals of disease-modifying treatments for spinal muscular atrophy (SMA). Lack of standardized measures and a widely accepted definition of bulbar function represents a gap in SMA care.
OBJECTIVE: A multidisciplinary team conducted post-hoc analyses of pooled data from one phase 1 (START) and two phase 3 (STR1VE-US, STR1VE-EU) studies to define and evaluate bulbar function of infants with SMA type 1 after receiving one-time gene replacement therapy, onasemnogene abeparvovec.
METHODS: We defined bulbar function as the ability to meet nutritional needs while maintaining airway protection and the ability to communicate verbally. Four endpoints represented adequate bulbar function: (1) absence of clinician-identified physiologic swallowing impairment, (2) receiving full oral nutrition, (3) absence of adverse events indicating pulmonary instability, and (4) the ability to vocalize at least two different, distinct vowel sounds. We descriptively assessed numbers/percentages of patients who achieved each endpoint and all four collectively. Patients were followed until 18 months old (STR1VE-US and STR1VE-EU) or 24 months (START) post-infusion.
RESULTS: Overall, 65 patients were analyzed for swallowing, nutrition intake, and adverse events, and 20 were analyzed for communication. At study end, 92% (60/65) of patients had a normal swallow, 75% (49/65) achieved full oral nutrition, 92% (60/65) had no evidence of pulmonary instability, 95% (19/20) met the communication endpoint, and 75% (15/20) achieved all four bulbar function components in the composite endpoint.
CONCLUSIONS: In these three clinical trials, patients with SMA type 1 who received onasemnogene abeparvovec achieved and maintained the bulbar function criteria utilized within this investigation.

Effective cough requires a significant increase in lung volume used to produce the shear forces on the airway to clear aspirated material. This increase in tidal volume during cough, along with an increase in tidal frequency during bouts of paroxysmal cough produces profound hyperventilation and thus reduces arterial CO2. While there are several reports in the literature regarding the effects of hypercapnia, hyperoxia, and hypoxia on cough, there is little research quantifying the effects of hypocapnia on the cough reflex. We hypothesized that decreased CO2 would enhance coughing. In 12 spontaneously breathing adult male cats, we compared bouts of prolonged mechanically stimulated cough, in which cough induced hyperventilation (CHV) was allowed to occur, with isocapnic cough trials where we maintained eupneic end-tidal CO2 by adding CO2 to the inspired gas. Isocapnia slightly increased cough number and decreased esophageal pressures with no change in EMG magnitudes or phase durations. The cough-to-eupnea transition was also analyzed between CHV, isocapnia, and a third group of animals that were mechanically hyperventilated to apnea. The transition to eupnea was highly sensitive to added CO2, and CHV apneas were much shorter than those produced by mechanical hyperventilation. We suggest that the cough pattern generator is relatively insensitive to CHV. In the immediate post-cough period, the appearance of breathing while CO2 is very low suggests a transient reduction in apneic threshold following a paroxysmal cough bout.