We report a patient with paradoxical vocal fold motion (PVFM) due to pantothenate kinase-associated neurodegeneration, a rare neurodegenerative disease and a subclass of neurodegeneration with brain iron accumulation disorders. PVFM is marked by normal vocal fold anatomy and physiology with intermittent adduction during the respiratory cycle. Many etiologies have been reported and include laryngeal hypersensitivity such as asthma and gastroesophageal reflux, functional disorders, and neurologic disorders such as focal respiratory dystonia. This case highlights the occasional association of PVFM with underlying neurologic disorders, especially those that disrupt autonomic functioning.

Objectives

The objective of this study was to measure the elastic modulus (Young's modulus) of canine vocal fold cover layers.

Study design

Basic science study.

Methods

Cover layers from vocal folds of eight canine larynges were dissected. Cover layer samples from the mid-membranous, medial vocal fold surface area were used to measure material stiffness using a previously validated indentation method. Cover layers from two human larynges were also measured as control references. Superior and inferior medial cover layers were measured separately. A total of 15 superior medial surface and 17 inferior medial surface specimens from the canine and two and four specimens, respectively, from the human were tested.

Results

In the canine larynges, the mean Young's modulus of the superior medial surface was 4.2 kPa (range, 3.0-5.4 kPa; standard deviation [SD], 0.6 kPa) and of the inferior medial surface was 6.8 kPa (range, 5.4-8.5 kPa; SD, 0.8 kPa). Measurements on human cover samples were 5.0 kPa (range, 4.7-5.4 kPa; SD, 0.5 kPa) and 7.0 kPa (range, 6.7-7.3 kPa; SD, 0.3 kPa) for the superior medial and inferior medial surface, respectively. Human measurements were similar to the previously validated measurements. There was no difference between the stiffness measurements in the human and canine cover layer samples (P>0.05).

Conclusions

The elastic stiffness (Young's modulus) of the canine and human vocal fold cover layers is similar. Findings support the use of canine larynx as an externally valid model to study voice production.

We report a patient with tracheopathia osteoplastica (TPO), a rare or perhaps underrecognized disorder, detected in approximately 1 in every 2000 to 5000 patients who undergo bronchoscopy. TPO is marked by proliferation of bony and cartilaginous spurs leading to airway stenosis. Multiple submucosal cartilaginous and osseous nodules can develop in the respiratory tract and may involve the entire trachea and mainstem bronchi. Symptoms may range from a completely silent condition to life-threatening respiratory failure and diagnosis is made based on radiological and bronchoscopic findings. Although the etiology has not been established, TPO can be familial and is sometimes associated with chronic inflammation, such as seen with rheumatic diseases. This case highlights the need for understanding TPO so that it can be differentiated from potentially serious conditions such as necrotizing granulomatous diseases, invasive infections, and cancer.

Syncope is common, affecting approximately 1 million Americans every year. Although multiple pathophysiological mechanisms regarding its etiology have been documented, neurocardiogenic or vasovagal syncope is the most common cause of these episodes. Other less appreciated etiologies include various cardiac abnormalities in which a structural, electrical, or obstructive disturbance leads to a temporary reduction in blood flow to the brain, resulting in transient loss of consciousness. Cardiac malignancies, while rare, can present with syncope by either disrupting the cardiac conduction apparatus or simply obstructing blood flow through the cardiac chambers. Electrocardiograms and echocardiography are often very helpful in identifying these abnormalities. Here, we report a rare case of late-stage invasive squamous cell carcinoma of the lung presenting with recurrent syncopal events. The cancer invaded the cardiac right atrium causing various dysrhythmias, leading to a very rare cause of cardiogenic syncope. We also discuss how lung cancer can present in a subclinical manner and at times without obvious respiratory symptoms, dramatic physical examination abnormalities, and/or thoracic imaging abnormalities on chest radiograph.

We report a patient with tracheopathia osteoplastica (TPO), a rare or perhaps underrecognized disorder, detected in approximately 1 in every 2000 to 5000 patients who undergo bronchoscopy. TPO is marked by proliferation of bony and cartilaginous spurs leading to airway stenosis. Multiple submucosal cartilaginous and osseous nodules can develop in the respiratory tract and may involve the entire trachea and mainstem bronchi. Symptoms may range from a completely silent condition to life-threatening respiratory failure and diagnosis is made based on radiological and bronchoscopic findings. Although the etiology has not been established, TPO can be familial and is sometimes associated with chronic inflammation, such as seen with rheumatic diseases. This case highlights the need for understanding TPO so that it can be differentiated from potentially serious conditions such as necrotizing granulomatous diseases, invasive infections, and cancer.

Objectives/hypothesis

An animal vocal fold replacement model is needed to investigate treatments for vocal fold scarring. We developed a rabbit surgical model, hypothesizing that orthotopic vocal fold cover implants would attach and survive. We further hypothesized that superficial scarring would be limited, allowing unimpeded vibration.

Study design

Translational research: animal surgical study.

Methods

Rabbit vocal fold covers were excised and immediately reimplanted. After 4 weeks, rabbits were phonated and vibration was recorded with high-speed videography. Larynges were then excised, elastic moduli measured by indentation, and covers sectioned for histology.

Results

Five of six rabbits survived. Phonation was achieved in all, with mucosal waves evident. Elastic modulus did not differ significantly from contralateral uninjured control vocal folds. Histology demonstrated epithelial integrity, partial preservation of elastic fibers, and variable degrees of collagen deposition.

Conclusions

Vocal fold cover implantation in rabbits is feasible, and grafts survived. Attachment onto the thyroarytenoid muscle prevented excessive scarring, maintained tissue mechanics, and preserved mucosal vibration.

Level of evidence

NA.

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca(2+)-activated K(+) channels (KCa2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca(2+)-dependent. Further, the Ca(2+) dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca(2+)-activated K(+) channels (KCa2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca(2+)-dependent. Further, the Ca(2+) dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.