Novel THAP1 sequence variants in primary dystonia.

BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.

Postintubation phonatory insufficiency: an elusive diagnosis.

OBJECTIVE: To describe postintubation phonatory insufficiency, a routinely overlooked complication of prolonged intubation. This entity results from an erosive injury with permanent divots of the medial surfaces of the arytenoid cartilages and/or scarring of the anterior cricoarytenoid joint capsule so that during phonation there is incomplete adduction and a glottic gap remains. SETTING: Tertiary care center. STUDY DESIGN/RESULTS: We present a retrospective review of the findings of 138 patients evaluated for chronic intubation injuries in our voice laboratory using a diagnostic model composed of pertinent history, elicited vocal capabilities and limitations, and an intense fiberoptic laryngeal examination directed at revealing the suspected injuries. CONCLUSION/SIGNIFICANCE: In many patients, the diagnosis of postintubation phonatory insufficiency was made years after the intubation injury occurred and after numerous nondiagnostic examinations elsewhere. Mechanisms of intubation injury are reviewed, and prevention and treatment of the condition are discussed.

Endoscopic laser cricopharyngeal myotomy to salvage tracheoesophageal voice after total laryngectomy.

Development of voice after tracheoesophageal puncture, following laryngectomy, is sometimes hampered by spasm of the cricopharyngeal muscle. This problem has been addressed by various means, including bougienage, botulinum toxin injection, and open surgical division of the muscle. We believe that endoscopic carbon dioxide laser cricopharyngeal myotomy represents a direct, simple, and effective solution.

Role of sensation in swallowing function.

OBJECTIVES: Sensation in the oral cavity and laryngopharynx has long been believed to be crucial for normal swallowing. One illustration of this belief has been intense interest in reconstruction after cancer resection using sensate tissue transfer as a means of improving swallowing function. A contrarian view is that mucosal sensation, by itself, is, in fact, relatively unimportant to swallowing function. STUDY DESIGN: A prospective study was designed to test the hypothesis that normal swallow function can occur with anesthesia of the upper aerodigestive tract mucosa. METHODS: Baseline (sensate) swallowing function of 13 healthy adults was assessed via video endoscopic swallow studies (VESS). Each subject was then topically anesthetized with lidocaine applied to the oral cavity, oropharynx, hypopharynx, and larynx. Swallowing was then reassessed via VESS and compared to the baseline examination to look for differences in function. RESULTS: There was little difference in swallowing ability between sensate and anesthetized states, even though all the subjects felt that their swallowing had been profoundly disrupted after lidocaine was applied. The main difference was a small increase in the time from food administration to swallowing. A few experienced trace aspiration, which was instantly eliminated on subsequent swallows with simple coaching. CONCLUSION: Normal swallowing can occur spontaneously or with simple coaching even with complete anesthesia of the upper aerodigestive tract mucosa. Current beliefs about the value of sensate free flaps and the importance of sensation in swallowing in general may need refinement.

Voice quality after narrow-margin laser cordectomy compared with laryngeal irradiation.

Voice quality remains the issue often used to support preference for radiotherapy in treatment of early glottic cancer. We therefore conducted a perceptual voice study in 2 groups, one treated with radiotherapy for malignant disease and the other with narrow-margin laser cordectomy for either malignant or extensive benign lesions. Sequential patients, 12 treated with radiotherapy and 30 with CO(2) laser excision, were included. Voice samples were recorded before and at intervals after surgery. Ratings of validated judges were used for statistical analysis of various voice characteristics at each time point. Voice deteriorated temporarily after surgery as compared with the radiated group; however, at 6 and 24 months no significant differences were found between the groups. Preferential use of narrow-margin laser cordectomy for appropriate early glottic tumors can be supported not only for oncologic reasons but also on the basis of voice results, cost, and efficiency considerations.

Current evaluation and treatment of patients with swallowing disorders.

To determine the varied causes of oropharyngeal dysphagia and their respective pathophysiology, a working understanding of the normal anatomy and function of the highly integrated mechanism of swallowing is outlined. This information is presented as the basis for a reasoned and detailed approach to the history, physical examination, and endoscopic evaluation of normal and altered oropharyngeal swallowing. The management of swallowing disorders depends on the nature and magnitude of the responsible clinical condition. Conservative and surgical approaches are discussed. These modalities and their indications are described in detail.

Contemporary diagnosis of the dysphagic patient.

A variety of tests are available to aid in the diagnosis and management of dysphagia. In this article the advantages and disadvantages of many of these tests are described. Special attention is given to the videoendoscopic swallowing study (VESS). An overall treatment plan is described.

Videoendoscopic swallowing study for diagnosis of Zenker's diverticuli.

The videoendoscopic swallowing study (VESS) provides an efficient, cost-effective method for swallowing evaluation in the clinic. Previously thought to be of little value for disorders of the proximal esophagus, this retrospective study (n = 33) demonstrates a high level of sensitivity (85%) and specificity (86%) of VESS for detecting Zenker's diverticuli in patients with symptoms of swallowing dysfunction. Furthermore, the key finding of postswallow reflux into the hypopharynx reliably distinguishes cricopharyngeus dysfunction from diverticuli in this population. This study shows that VESS can provide useful information about the proximal esophagus.

A comparison of methods of botulinum toxin injection for abductory spasmodic dysphonia.

Treatment of abductory spasmodic dysphonia with botulinum toxin injection into the posterior cricoarytenoid muscles often results in only partial symptom relief. In contrast, excellent results can be achieved after thyroarytenoid injection for the adductory type of spasmodic dysphonia. One reason for disappointing results may be inaccurate placement of the botulinum toxin into the posterior cricoarytenoid muscles. We describe a new approach to posterior cricoarytenoid injection used in 18 patients for treatment of abductory spasmodic dysphonia. Of the 30 patients treated for abductory spasmodic dysphonia at Loyola University-Chicago, 6 underwent both a retrocricoid approach and the newer transcricoid method, thus allowing patient and clinician comparison of techniques. We and all six of our patients preferred the transcricoid approach because of less discomfort, equivalent or better voice results, and fewer side effects.

Endoscopic CO2 laser excision of large or recurrent laryngeal saccular cysts in adults.

Saccular cysts are uncommon disorders that represent cystic dilatation of the laryngeal saccule. They are distinguished from laryngoceles by their lack of lumenal continuity with the endolarynx, and the fact that they are not air filled. Voice change is the most common clinical presentation in adults, whereas airway compromise is more common in infants. Management recommendations range from observation of asymptomatic lesions, to endoscopic marsupialization or excision, to excision through a laryngotomy or the thyrohyoid membrane. The literature states that large or recurrent saccular cysts require the exposure afforded by a transcervical approach. This report describes complete endoscopic laser excision of large, symptomatic saccular cysts in seven adults. Four of the seven patients were referred with recurrent cysts after the failure of endoscopic marsupialization procedures. None required tracheotomy, and only three of seven were observed overnight in the hospital. Surgical technique with emphasis on complete excision, pre- and postoperative radiographic and surgical anatomy, and treatment outcome are discussed.

Vocal fold microsurgery in singers.

Some singers with benign vocal fold mucosal lesions remain unacceptably impaired vocally in spite of compliance with a regimen of medical treatment and voice therapy lasting several months-or even years. I present here my experience with 62 singers who, because of this predicament, chose to undergo vocal fold microsurgery. This series is the second largest reported to date in English literature. Procedures are presented which were used for patient selection, education, and vocal retraining, as well as for surgery itself and postoperative care. Results reported here include (a) comparison of my auditory-perceptual ratings of singing voice impairment before and after surgery, (b) preoperative versus postoperative videostroboscopic findings, (c) postoperative rate of return to public singing, and (d) postoperative patient questionaires which sought to uncover patient/singer perceptions of the results of vocal fold surgery. Excellent results were achieved overall with a very low incidence of untoward results, and no complications were encountered.

Indirect larynx and pharynx surgery: a replacement for direct laryngoscopy.

During a 2-year period, 192 indirect surgeries on the laryngopharynx were performed in an outpatient videoendoscopy laboratory under topical anesthesia with or without intravenous sedation. These procedures included cancer staging and biopsy; vocal fold injections of Teflon, Gelfoam, botulinum toxin, or steroids; glottic web lysis; and granuloma removal. The techniques used to perform these procedures are elucidated. Careful chart review of these patients shows that indirect surgery was performed successfully in 96% of cases. Intravenous conscious sedation was utilized in 39% of patients. No significant complications were encountered. By avoiding the need for an operating room, hospitalization, or general anesthesia, this technique was clearly as safe or safer, more convenient for surgeon and patient, and more cost-effective than the same procedure would have been via the traditional direct laryngoscopy. As the authors have already done in their practices, the indirect method should therefore be reinstated as the preferred approach to the clinical circumstances described here.

Suction drain management of salivary fistulas.

Salivary fistulas remain an unpleasant complication of upper aerodigestive tract surgery. To avoid a disastrous outcome such as carotid rupture, clinicians "medialize" (i.e., incise the skin flap in the anterior aspect of the neck and insert a Penrose drain) to divert fistula fluid from the carotid sheath and then perform laborious wound care. Meanwhile, patients endure the unpleasant odor, discomfort due to the wound dressing, occasional secondary surgical procedures, a lengthened hospital stay, and increased financial costs. In an effort to mitigate these problems, suction drains that had been placed at the time of the original surgical procedure were used as an alternative management technique. Out of a population of 118 reviewable patients who underwent standard or extended variations of supraglottic laryngectomy, partial laryngopharyngectomy, near-total laryngectomy, or total laryngectomy between 1988 and 1992, 16 patients appropriate for inclusion in this study developed postsurgical fistulas. Eight of these patients were treated with traditional medialization procedures, and the other 8 patients were treated with suction drainage. Comparison of the two groups revealed no significant difference with respect to complications or time to fistula closure. The advantages of simplified postsurgical care, less patient discomfort, reduced time demands on the clinician, and cost containment were noted for the group treated with suction drainage.

The videoendoscopic swallowing study: an alternative and partner to the videofluoroscopic swallowing study.

A new, physical examination-based videoendoscopic method of evaluation can enhance considerably the understanding and efficiency of clinicians working with patients with swallowing difficulties. Using the fiberoptic nasolaryngoscope, evaluation of structure and function of palate, pharynx, and larynx, along with sensation of the laryngopharynx, is carried out. Next, patients' swallowing capabilities are assessed as they ingest various food consistencies. This method, formerly called videoendoscopic evaluation of dysphagia (VEED), but perhaps more appropriately termed videoendoscopic swallowing study (VESS) has particular value for patients who cannot undergo the videofluoroscopic swallowing study (VFSS)--for example, because they are bedfast--or those whose swallowing function is changing so rapidly (after a stroke or surgery) as to call for frequent reassessments. This technique is often useful during the initial consultation with new patients complaining of dysphagia, as a "stand alone" method of diagnosis and management. Less frequently, VESS findings, along with patient history, will indicate when VFSS should also be obtained. VESS will orient the examiner to the nature and severity of the problem even in this latter circumstance. In follow-up circumstances, VESS is generally more useful than the VFSS. Case presentations are utilized to illustrate the usefulness of VESS as compared to VFSS.

Videoendoscopic evaluation of patients with dysphagia: an adjunct to the modified barium swallow.

The modified barium swallow is currently the most comprehensive, widely available, and easily interpreted technique for the evaluation of patients with dysphagia by the head and neck surgeon. However, it requires the facilities, personnel, and use of a radiology suite, a trained speech pathologist, and exposure of the patient to radiation. It would therefore be helpful to have an adjunctive, physician based, nonradiographic method of examination that could provide information similar to and possibly even more complete than that supplied by the modified barium swallow. Such an adjunctive method could help otolaryngologist-head and neck surgeons confronted by a new patient with swallowing difficulties to orient themselves to the nature and severity of the problem while waiting for the modified barium swallow to be scheduled, performed, and reviewed. It could also be a helpful tool for management of patients with cancer of the head and neck, whose swallowing function may change rapidly in the early postoperative period. In such cases, intervals between modified barium swallow examinations (dictated by concern over radiation exposure) may be too far apart to allow up-to-the-minute decisions on case management. Finally, some patients who may be too ill to travel to the radiology suite might benefit from a bedside procedure that would yield information about swallowing function similar to that provided by the modified barium swallow. Videoendoscopic evaluation of dysphagia (VEED) is a protocol I developed and have used regularly since 1984. Experience with this method of dysphagia evaluation has shown that it answers the needs outlined above. Its usefulness also goes beyond that of the modified barium swallow by providing a more detailed understanding of the component anatomic and functional deficits that comprise a given patient's swallowing problem, information about upper aerodigestive tract sensory deficits, and a means for visual feedback training of pharyngeal and laryngeal musculature. The protocol is reviewed here. Case reports illustrating the clinical usefulness of VEED as an adjunct to the modified barium swallow are also presented, and the relative strengths and weaknesses of VEED and the modified barium swallow are compared.

Acquired airway obstruction from histologically normal, abnormally mobile supraglottic soft tissues.

In patients with nonmalignant upper aerodigestive tract abnormalities such as cysts, neoplasms, and laryngomalacia, airway obstruction has been described as a function of not only size and location of abnormal structures, but also of their mobility. This paper describes three patients who developed upper airway restriction with stridor due to abnormally redundant and mobile, but histologically normal, supraglottic mucosa. The specific mechanism of and structures involved in obstruction were clearly defined by videolaryngopharyngoscopy. Endoscopic microdissection and/or laser excision of the redundant supraglottic mucosa restored airway patency and completely relieved the obstructive respiratory symptoms. The pulsion effects of inspiratory airflow are postulated as the cause of these acquired lesions. Recommended treatment is reviewed.

Indirect videolaryngoscopy versus direct endoscopy for larynx and pharynx cancer staging. Toward elimination of preliminary direct laryngoscopy.

Thirty-nine patients with cancer of the larynx and pharynx (33 untreated and six previously treated patients) underwent tumor mapping by both direct laryngoscopy (DL) and indirect videolaryngoscopy (IVL). The examiner in each case was unaware of the findings of the other evaluation method. After definitive treatment had been carried out so that pathologic and operative information was also available, comparisons of the accuracies of the two methods of staging were made. In 32 cases, IVL provided information equal to or better than that provided by DL, and a tissue sample also could be obtained during IVL. On the basis of these findings, we conclude that aggressive, office-based IVL can guide initial treatment planning (partial or total laryngectomy versus irradiation) and patient counseling. A confirmatory DL can be performed without surprises at the time of definitive surgery, rather than as a separate procedure - a cost-effective modification of standard practice.