Botulinum toxin in the treatment of cricopharyngeal dysphagia.

Dysphagia is a common symptom in various neurological disorders affecting pharyngeal functions. Cricopharyngeal dysfunction is one of the major findings in these patients. The most effective treatment for restoring normal swallowing function in persistent cricopharyngeal dysfunction is cricopharyngeal myotomy, especially when mechanical obstruction or a well-localized neuromuscular dysfunction, such as a cricopharyngeal muscle spasm, is present. However, when there is a more diffuse neurological disorder present the results of surgery are more disappointing. In unclear cases, or in patients with temporary problems, no good method other than swallowing training, bougienage, and tube feeding are available. During the past decade, botulinum toxin has been found to be of therapeutic value in the treatment of a variety of neurological disorders associated with inappropriate muscular contractions such as torticollis and spasmodic dysphonia. Recently, injections of botulinum toxin in patients with cricopharyngeal muscle dysfunction have been reported to result in marked relief of dysphagia. In this article we describe our experiences with botulinum toxin injections to treat four patients suffering from deglutition problems and cricopharyngeal dysphagia of different origins. Botulinum toxin was injected into the cricopharyngeus muscle that was identified by endoscopy under general anesthesia. In this study, no major side effects were observed. Three patients obtained a significant improvement of esophageal symptoms after the first injection. The treatment had limited effect in one patient who had reflux disease and only slight cricopharyngeus dysfunction.

Long-term results of tracheostomy for severe obstructive sleep apnea syndrome.

Severe obstructive sleep apnea (OSAS) is most often accompanied by metabolic syndrome, obesity, diabetes and coronary disease. In its most severe form, it is a life-threatening condition, requiring active and immediate help. Nasal continuous positive airway pressure (CPAP) is the most efficient nonsurgical treatment for patients with OSAS. However, for anatomical, disease-related and subjective reasons, many patients cannot accept this treatment. A permanent tracheostomy may be one alternative in such patients who, in addition, often suffer from extreme obesity and severe heart disease. In this paper, we describe the long-term follow-up results of 7 patients suffering from OSAS and treated with permanent tracheostomy. All the patients (5 men, 2 women) were diagnosed using the static charge sensitive bed method and night-time oximetry for sleep analysis. The mean body mass index (BMI) of the patients ranged from 34 to 60 and the age from 41 to 64 years. All the patients had severe OSAS and long periods of low oxygen saturation (SaO2) levels. Six patients had a CPAP trial before tracheostomy. Only 2 patients tolerated the trial but, despite the continuous use of CPAP, they were nonresponders. Permanent tracheostomy was done according to normal routine in each patient. After primary healing of 2 days, they used silver cannulae, which also allowed them to speak. The patients were evaluated every year after the tracheostomy. After some practical difficulties including proper maintenance of the cannula, all the patients quickly learned the correct management. In postoperative sleep studies, nadir SaO2 levels had improved significantly, obstructive apneas had disappeared and the subjective quality of life had improved. No marked changes in BMI were found.

The tonic sympathetic input to the cochlear vasculature in guinea pig.

Vascular tones is an essential component in maintaining steady regional blood flow and dynamic responsiveness of a vascular bed. Sympathetic innervation can contribute to vascular tone. Although certain studies have reported evoked changes in cochlear blood flow (CBF) with activation of the sympathetic fibers to the cochlear vasculature, other studies have failed to show evidence of sympathetic contribution to CBF regulation when the cervical sympathetic fibers were unilaterally sectioned. We hypothesized that the bilateral 'sympathectomy of the stellate ganglia' would remove sufficient sympathetic input to the cochlea to yield a change in CBF resting level. To test this hypothesis a new technique was used to expose the stellate ganglia (SG) bilaterally and induce a chemical sympathectomy. We observed that unilateral SG blockade with 2 microliters of 4 mM lidocaine hydrochloride on either side produced a 5-10% increase in CBF, which recovered to baseline during the following 2 min. A subsequent blockade of the contralateral SG produced a rapid 25-35% increase, which then recovered partially during the following 3-4 min, remaining 5-15% above the baseline over a 20 min measurement period. Superior cervical ganglion transection did not affect CBF. Our results provide evidence for the existence of a tonic sympathetic component in the control of vascular tone in guinea pig cochlea. This neural effect is derived bilaterally from SG. This result is consistent with previous anatomical studies showing the bilateral innervation of the cochlea by the SG sympathetic fibers and with previous physiological studies on the bilaterality of evoked changes in CBF due to electric stimulation of SG.

Transtympanic electrocochleography in evaluation of cochleovestibular disorders.

We examined the electrocochleography (ECochG) parameters in patients suffering from Meniere's disease (n = 5) or other type of vertiginous disorder (n = 4). Fourteen ears were examined by introducing a needle electrode through the tympanic membrane to the promontorium. The summating potential (SP), action potential (AP) and the SP/AP ratio were measured from the alternating polarity click response, and the latency difference from the condensation and rarefaction click responses. These 2 patient groups differed from each other most clearly as to the audiometry results and the duration of symptoms. We also found differences in electrocochleographic results, especially in latency differences between the condensation and rarefaction click responses. Although the present material is small we conclude that transtympanic electrocochleography is a sensitive method to measure cochlear potentials, and might be a valuable addition in diagnosing patients suffering from various cochleovestibular disorders.

Effects of intratympanically delivered lidocaine on the auditory system in humans.

Since lidocaine is used to relieve the symptoms of Meniere's disease and tinnitus, its effects on the human cochlea is of specific interest. In experimental animals, topically administered lidocaine affects cochlear electrophysiology in a specific, dose-dependent manner. In the current study, lidocaine (40 mg in 1 ml of saline) was delivered intratympanically in six patients with essentially normal hearing in an attempt to alleviate tinnitus. Auditory function was assessed by pure tone audiometry, auditory evoked brain stem responses (ABR), and transiently evoked otoacoustic emissions (TEOAE) to observe possible drug effect in the auditory system. In five patients, saline was injected prior to lidocaine for control purposes. Saline injection did not create significant changes in any of the measures. After a 2 hr follow-up period, intratympanic injection of lidocaine caused a 2 to 10 dB reduction in TEOAE level at 1 to 3 kHz frequencies. This reduction was at its maximum at the 30 min post-injection sampling point, and was followed by a slow recovery. At 2 hr post-injection, TEOAE amplitude was still 2 to 4 dB below baseline level. Pure tone thresholds were slightly affected 30 min after intratympanic lidocaine injection, but were fully recovered 1 hr after the injection. Lidocaine injection did not cause any changes in ABR latencies or amplitudes in any of the patients. These results suggest that the dose of intratympanically administered lidocaine used here has a specific effect on the organ of Corti structures in human subjects, without significantly affecting the auditory nerve or central auditory pathways. The relationship of the drug effect in conjunction with a possible effect on inner ear disorder might help to localize the site of disorder.

Neuronal regulation of cochlear blood flow in the guinea-pig.

1. Previous studies have shown that electrical stimulation (ES) of the guinea-pig cochlea causes a neurally mediated increase in cochlear blood flow (CBF). It is known that the centrifugal neuronal input to the cochlea comes through the perivascular sympathetic plexus from the cervical sympathetic chain and along the vestibular nerve (VN) from the periolivary area of the brainstem. Both of these neuronal systems are distributed topographically in the cochlea. 2. In order to study the neural origins of ES-evoked CBF increase, laser Doppler flowmetry was used to test the following hypotheses. (a) The response is regional, that is, limited to the area of the cochlea stimulated. To test this we performed differential ES of the cochlear turns. CBF was measured from either the third or the first turn. (b) The response is mediated via autonomic receptors within the cochlea. To study this, we applied atropine, succinylcholine and idazoxan locally to the cochlea. (c) The response is influenced by neuronal input via the sympathetic cervical chain (SC) and components of the VN. We stimulated and sectioned the SC, and sectioned the VN, to test this hypothesis. 3. We observed that the CBF response was topographically restricted to the stimulated region. Locally applied muscarinic or nicotinic antagonists (atropine and succinylcholine respectively) did not affect the response. However, local idazoxan (an alpha 2-blocker) eliminated the response. Locally applied adrenaline and SC stimulation modified the dynamic range of the response. SC sectioning enhanced the responsiveness of the cochlear vasculature to ES. The VN section caused a temporary decrease in CBF and elimination of the ES-evoked CBF response. 4. We conclude that the release of dilating agents is topographical with respect to ES current flow, the ES-evoked CBF increase is peripherally mediated via alpha 2-receptors, and the response is influenced by input via the SC. The elimination of the response by VN sectioning proximal to the brainstem indicated that fibres of the VN mediate the CBF increase during direct cochlear ES. The data suggest that these fibres may be the efferent limb of a neural loop involved with the regulation of CBF. Such a system could provide a mechanism for the rapid increase in CBF with organ stress.

Epinephrine-induced changes in human cochlear blood flow.

Cochlear blood flow (CBF) was monitored over the basal turn stria vascularis using laser Doppler flowmetry in five human subjects during middle ear surgery. The effects of systemically administered epinephrine (0.3 microgram/kg) and topically applied epinephrine (1:10,000) on the round window membrane (RWM) were examined. Topical epinephrine caused a mean reduction of 60 percent in CBF (maximum peak reduction 65-85% across subjects), which slowly recovered ( > 10 min) toward baseline following epinephrine removal from the RWM. The changes in CBF are similar to those found in animal studies, but are much larger, indicating a relatively more pronounced role of adrenergic agents in CBF control in humans. Systemic epinephrine caused a 40 percent decrease in skin blood flow, a 90 percent increase in blood pressure (BP), above a resting hypotensive mean level of 65 mmHg, and a 50 percent increase in CBF. The CBF change followed the change in BP, but recovered toward baseline more slowly. The dramatic and somewhat prolonged decreases in CBF with RWM application of epinephrine may compromise sensory function and could account for the occasional unexplained sensorineural hearing loss or tinnitus associated with middle ear procedures that use topical epinephrine. The semipermeability of the RWM may, on the other hand, offer a route for therapeutic increases in CBF with vasodilative agents and provide an appropriate treatment for some cases of sensorineural hearing loss.

Influence of calcitonin-gene related peptide on cochlear blood flow and electrophysiology.

Intra-arterially infused calcitonin gene-related peptide (CGRP) induced dose-dependent decreases in both systemic blood pressure and cochlear blood flow (CBF). However, when subjects were pretreated systemically or locally with the specific receptor antagonist CGRP(8-37), CBF increased, despite decreases in systemic blood pressure in response to CGRP infusions. Micro-infusions of CGRP directly into the supplying arterial network of the cochlea induced dose-dependent increases in CBF that were blocked by CGRP(8-37) pretreatment. Cochlear electrophysiology, as assessed by cochlear action potential and cochlear microphonics, remained unchanged following each condition tested. These results indicate that CGRP is involved in systemic regulation of blood pressure and contributes to the regulation of CBF.

Dynamic response of cochlear blood flow to occlusion of anterior inferior cerebellar artery in guinea pigs.

In this study we investigated the autoregulation and hemodynamics of cochlear blood flow (CBF) as measured by laser-Doppler flowmetry. When the anterior inferior cerebellar artery was clamped, CBF decreased approximately 40% (not to "biological zero"), followed by a gradual increase. When the clamp was released, CBF quickly increased to as much as 167% of the baseline level and then slowly returned to baseline. We assume that the dynamic CBF response to anterior inferior cerebellar artery clamping reflects primarily a combination of passive elastic properties of the cochlear vessels and active autoregulatory mechanisms. The decrease portion of the negative phase and the increase portion of the positive phase reflect mainly passive behavior, static compliance, and resistance of vessels, whereas the slow exponential negative and positive changes indicate an active response of vessels: an autoregulatory mechanism based on compensatory vascular dilation and constriction. Our preliminary data show a very strong CBF autoregulatory response to a change in intravascular pressure. Sympathetic stimulation can enhance this autoregulation, and CO2 inhalation promotes compensatory dilation and inhibits compensatory vascular constriction.

Stellate ganglion drives sympathetic regulation of cochlear blood flow.

The functional properties of the sympathetic fibers innervating the cochlea are not well understood. Adrenergic fibers supplying lateral wall structures of the cochlea have been observed terminating on radiating arterioles and collecting venules. Adrenergic fibers also terminate as 'free' endings in the spiral osseous lamina. Stimulation or transection of sympathetic fibers originating from superior cervical chain and supplying the cochlea have yielded mixed results concerning many aspects of cochlea physiology. In order to clarify the origin of sympathetic fibers and their role in control of cochlear blood flow (CBF), we examined the effect of electrical stimulation of the stellate ganglion (ESS) and transection of postganglionic fibers from the stellate on CBF measured by laser Doppler flowmetry and on systemic blood pressure (BP) in the guinea pig. ESS produced a 20-35% increase in BP and 10-15% decrease in CBF. The decrease in CBF presumably reflects the net result of increased perfusion pressure, local autoregulatory mechanisms, and a direct sympathetic-induced vasoconstriction. Section of the immediate postganglionic sympathetic trunk had little or no effect on the ESS-related change in BP; however, it eliminated the CBF reduction. Intravenously infused beta 1-blocker diminished the BP increase due to ESS, while the electrically-evoked reduction in CBF remained. Local application of an alpha-blocker on the round window blocked ESS evoked CBF reductions without altering the BP increase. These data confirm the functional role of sympathetic projections from the stellate ganglion in CBF regulation in guinea pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Betahistine-induced vascular effects in the rat cochlea.

Betahistine (BH) has been used widely to treat cochlear disorders, such as tinnitus and Meniere's disease. The mechanism of action of BH in the cochlea is assumed to be based on its histamine-like effect on H1 receptors in the cochlear vasculature, leading to an increased cochlear blood flow (CBF). Recently it has been shown that BH can strongly affect H3 heteroreceptors (a novel histamine receptor subclass) in the periphery, via an autonomic ligand. This mechanism may also contribute to the BH effects on CBF. This study was to validate BH effects in the cochlear vasculature and to investigate the possible mechanisms of action of this drug in the inner ear vasculature. We assessed the effects of BH on CBF with the laser Doppler flowmeter in 23 rats and concluded that BH affects vascular conductivity in the cochlea in a dose-dependent fashion; betahistine diffuses through the round window, but does not have access to vascular receptors or ligands once in the labyrinthine fluids; and the H1 receptors mediate the systemic and peripheral vascular effects of BH, whereas the cochlear effect involves cholinergic receptors.