Study design considerations for sleep-disordered breathing devices.

None: In recent years, sleep-disordered breathing (SDB) has been recognized as a prevalent but under-diagnosed condition in adults and has prompted the need for new and better diagnostic and therapeutic options. To facilitate the development and availability of innovative, safe and effective SDB medical device technologies for patients in the United States, the US Food and Drug Administration collaborated with six SDB-related professional societies and a consumer advocacy organization to convene a public workshop focused on clinical investigations of SDB devices. Sleep medicine experts discussed appropriate definitions of terms used in the diagnosis and treatment of SDB, the use of home sleep testing versus polysomnography, clinical trial design issues in studying SDB devices, and current and future trends in digital health technologies for diagnosis and monitoring SDB. The panel's breadth of clinical expertise and experience across medical specialties provided useful and important insights regarding clinical trial designs for SDB devices.

Bacterial meningitis among children with cochlear implants beyond 24 months after implantation.

BACKGROUND: More than 11000 children in the United States with severe-to-profound hearing loss have cochlear implants. A 2002 investigation involving pediatric cochlear implant recipients identified meningitis episodes from January 1, 1997, through September 15, 2002. The incidence of pneumococcal meningitis in the cohort was 138.2 cases per 100000 person-years, >30 times higher than that for children in the general US population. Children with implants with positioners were at higher risk than children with other implant models. This higher risk of bacterial meningitis continued for up to 24 months after implantation. OBJECTIVE: To evaluate additional reported cases to determine whether the increased rate of bacterial meningitis among children with cochlear implants extended beyond 24 months after implantation. METHODS: Our study population consisted of the cohort of children identified through the 2002 investigation; it included 4265 children who received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were <6 years of age at the time of implantation. We calculated updated incidence rates and incidence according to time since implantation. RESULTS: We identified 12 new episodes of meningitis for 12 children. Eleven of the children had implants with positioners; 2 children died. Six episodes occurred >24 months after implantation. When cases identified in the 2002 and 2004 investigations were combined, the incidence rate of > or =24-months postimplantation bacterial meningitis among children with positioners was 450 cases per 100000 person-years, compared with no cases among children without positioners. CONCLUSIONS: Our updated findings support continued monitoring and prompt treatment of bacterial infections by health care providers and parents of children with cochlear implants. This vigilance remains important beyond 2 years after implantation, particularly among children with positioners. The vaccination recommendations for all children with implants, with and without positioners, and all potential recipients of implants continue to apply.

Self-triggered functional electrical stimulation during swallowing.

Hyolaryngeal elevation is essential for airway protection during swallowing and is mainly a reflexive response to oropharyngeal sensory stimulation. Targeted intramuscular electrical stimulation can elevate the resting larynx and, if applied during swallowing, may improve airway protection in dysphagic patients with inadequate hyolaryngeal motion. To be beneficial, patients must synchronize functional electrical stimulation (FES) with their reflexive swallowing and not adapt to FES by reducing the amplitude or duration of their own muscle activity. We evaluated the ability of nine healthy adults to manually synchronize FES with hyolaryngeal muscle activity during discrete swallows, and tested for motor adaptation. Hooked-wire electrodes were placed into the mylo- and thyrohyoid muscles to record electromyographic activity from one side of the neck and deliver monopolar FES for hyolaryngeal elevation to the other side. After performing baseline swallows, volunteers were instructed to trigger FES with a thumb switch in synchrony with their swallows for a series of trials. An experimenter surreptitiously disabled the thumb switch during the final attempt, creating a foil. From the outset, volunteers synchronized FES with the onset of swallow-related thyrohyoid activity (approximately 225 ms after mylohyoid activity onset), preserving the normal sequence of muscle activation. A comparison between average baseline and foil swallows failed to show significant adaptive changes in the amplitude, duration, or relative timing of activity for either muscle, indicating that the central pattern generator for hyolaryngeal elevation is immutable with short term stimulation that augments laryngeal elevation during the reflexive, pharyngeal phase of swallowing.

Suppression of thyroarytenoid muscle responses during repeated air pressure stimulation of the laryngeal mucosa in awake humans.

Repeated stimulation of the laryngeal mucosa occurs during speech. Single stimuli, however, can elicit the laryngeal adductor response (LAR). Our hypothesis was that the LAR to repeated rapid air pressure stimuli is centrally suppressed in humans. Hooked-wire electrodes were inserted into the thyroarytenoid and cricothyroid muscles on both sides and into the posterior cricoarytenoid muscle on one side. Pairs of air puff stimuli were presented to the mucosa over the arytenoids at pressure levels three times threshold with interstimulus intervals from 250 to 5,000 ms. Bilateral thyroarytenoid responses occurred at around 150 ms to more than 70% of the initial stimuli. With repeated presentation at intervals of 2 seconds or less, the percent occurrence decreased to less than 40% and response amplitudes were reduced by 50%. Central suppression of adductor responses to repeated air puff stimuli may allow speakers to produce voice without eliciting reflexive spasms that could disrupt speech.

Distal spinal and bulbar muscular atrophy caused by dynactin mutation.

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions.

Practice parameter: laryngeal electromyography (an evidence-based review).

This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. The review yielded 584 articles of which 33 met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the 2 techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications.

Practice parameter: laryngeal electromyography (an evidence-based review).

This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders, including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. Thirty-three of the 584 articles met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications.

Laryngeal electromyography: an evidence-based review.

This article reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. Thirty-three of the 584 articles met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing the use of laryngeal EMG for other applications.

Risk of bacterial meningitis in children with cochlear implants.

BACKGROUND: In June 2002, the Food and Drug Administration received reports of bacterial meningitis in patients with cochlear implants for treatment of hearing loss. Implants that included a positioner (a wedge inserted next to the implanted electrode to facilitate transmission of the electrical signal by pushing the electrode against the medial wall of the cochlea) were voluntarily recalled in the United States in July 2002. METHODS: We identified patients with meningitis and conducted a cohort study and a nested case-control investigation involving 4264 children who had received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were less than six years of age when they received the implants. We calculated the incidence of meningitis in the cohort and assessed risk factors for meningitis among patients and among 199 controls, using data from interviews with parents and abstracted from medical records. RESULTS: We identified 26 children with bacterial meningitis. The incidence of meningitis caused by Streptococcus pneumoniae was 138.2 cases per 100,000 person-years--more than 30 times the incidence in a cohort of the same age in the general U.S. population. Postimplantation bacterial meningitis was strongly associated with the use of an implant with a positioner (odds ratio, 4.5 [95 percent confidence interval, 1.3 to 17.9], with adjustment for medical, surgical, and environmental factors) and with the joint presence of radiographic evidence of a malformation of the inner ear and a cerebrospinal fluid leak (adjusted odds ratio, 9.3 [95 percent confidence interval, 1.2 to 94.5]). The incidence of meningitis among patients who had received an implant with a positioner remained higher than the incidence among those whose implants did not have a positioner for the duration of follow-up (24 months from the time of implantation). CONCLUSIONS: Parents and health care providers should ensure that all children who receive cochlear implants are appropriately vaccinated and are then monitored and treated promptly for any bacterial infections after receiving the implant.

Laryngeal elevation achieved by neuromuscular stimulation at rest.

During swallowing, airway protection is achieved in part by laryngeal elevation. Although multiple muscles are normally active during laryngeal elevation, neuromuscular stimulation of select muscles was evaluated to determine which single muscle or muscle pair best elevates the larynx and should be considered during future studies of neuromuscular stimulation in dysphagic patients. Hooked-wire monopolar electrodes were inserted into mylohyoid, thyrohyoid, and geniohyoid muscle regions in 15 healthy men selected for having a highly visible thyroid prominence for videotaping. During trials of single, bilateral, and combined muscle stimulations, thyroid prominence movements were video recorded, digitized, and normalized relative to elevation during a 2-ml water swallow. Individual muscle stimulation induced approximately 30% of the elevation observed during a swallow and approximately 50% of swallow velocity, whereas paired muscle stimulation resulted in approximately 50% of the elevation and approximately 80% of the velocity produced during a swallow. Paired muscle stimulation produced significantly greater elevation than single muscle stimulation and could assist with laryngeal elevation in dysphagic patients with reduced or delayed laryngeal elevation.

Mucosal afferents mediate laryngeal adductor responses in the cat.

Laryngeal adductor responses (LAR) close the airway in response to stimulation of peripheral afferents in the superior laryngeal nerve. Although both mucosal afferents and proprioceptive receptors are present in the larynx, their relative contribution for reflex elicitation is unknown. Our purpose was to determine which receptor types are of importance in eliciting the LAR. A servomotor with displacement feedback was used to deliver punctate displacements to the body of the arytenoid cartilage and overlying mucosa on each side of the larynx in eight anesthetized cats. The same displacements were delivered both before and after surgical excision of the overlying mucosa. With the mucosa intact, early short-latency component R1 LAR responses recorded from the thyroarytenoid muscles were frequent (ipsilateral > 92%, contralateral > 95%). After the mucosa was removed, the LAR became infrequent (<3%) and was reduced in amplitude in both the ipsilateral and contralateral thyroarytenoid muscle recording sites (P < 0.0005). These findings demonstrate that mucosal mechanoreceptors and not proprioceptive afferents contribute to the elicitation of LAR responses in the cat.

The effect of neuromuscular stimulation of the genioglossus on the hypopharyngeal airway.

OBJECTIVES: To determine the effects of neuromuscular stimulation (NS) of the genioglossus muscle on hypopharyngeal airway size. STUDY DESIGN: Fourteen consecutively recruited healthy volunteers underwent percutaneous electrical NS of the genioglossus muscle. METHODS: Bipolar hooked wires were inserted percutaneously into the genioglossus muscle and used for NS. The anterior--posterior diameter of the hypopharynx was measured at the level of the superior edge of the epiglottis at baseline and during NS from recorded video endoscopic examinations. RESULTS: NS of the genioglossus muscle resulted in a significant increase in the diameter of the hypopharyngeal airway (P =.002) compared with baseline, ranging from a 33% to 284% increase in airway diameter. Three of the 14 patients demonstrated modest decreases in airway diameter, likely the result of faulty electrode placement in surrounding tongue retrusive muscles. CONCLUSIONS: NS of the genioglossus muscle was effective in increasing the hypopharyngeal airway and may provide a useful alternative to direct stimulation of the hypoglossal nerve with a nerve cuff electrode in the development of neuroprosthetic treatments for obstructive sleep apnea.