What is Menière's disease? A contemporary re-evaluation of endolymphatic hydrops.

Menière's disease is a chronic condition with a prevalence of 200-500 per 100,000 and characterized by episodic attacks of vertigo, fluctuating hearing loss, tinnitus, aural pressure and a progressive loss of audiovestibular functions. Over 150 years ago, Prosper Menière was the first to recognize the inner ear as the site of lesion for this clinical syndrome. Over 75 years ago, endolymphatic hydrops was discovered as the pathologic correlate of Menière's disease. However, this pathologic finding could be ascertained only in post-mortem histologic studies. Due to this diagnostic dilemma and the variable manifestation of the various audiovestibular symptoms, diagnostic classification systems based on clinical findings have been repeatedly modified and have not been uniformly used in scientific publications on Menière's disease. Furthermore, the higher level measures of impact on quality of life such as vitality and social participation have been neglected hitherto. Recent developments of high-resolution MR imaging of the inner ear have now enabled us to visualize in vivo endolymphatic hydrops in patients with suspected Menière's disease. In this review, we summarize the existing knowledge from temporal bone histologic studies and from the emerging evidence on imaging-based evaluation of patients with suspected Menière's disease. These indicate that endolymphatic hydrops is responsible not only for the full-blown clinical triad of simultaneous attacks of auditory and vestibular dysfunction, but also for other clinical presentations such as "vestibular" and "cochlear Menière's disease". As a consequence, we propose a new terminology which is based on symptomatic and imaging characteristics of these clinical entities to clarify and simplify their diagnostic classification.

Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients.

BACKGROUND: Dexmedetomidine is a highly selective and potent α(2)-adrenoceptor agonist registered for sedation of patients in intensive care units. There is little information on factors possibly affecting its pharmacokinetics during long drug infusions in critically ill patients. We characterized the pharmacokinetics of dexmedetomidine in critically ill patients during long-term sedation using a population pharmacokinetic approach. METHODS: Twenty-one intensive care patients requiring sedation and mechanical ventilation received dexmedetomidine with a loading dose of 3-6 µg kg(-1) h(-1) in 10 min and a maintenance dose of 0.1-2.5 µg kg(-1) h(-1) for a median duration of 96 h (range, 20-571 h). Cardiac output (CO), laboratory and respiratory parameters, and dexmedetomidine concentrations in arterial plasma were measured. The pharmacokinetics was determined by population analysis using linear multicompartment models. RESULTS: The pharmacokinetics of dexmedetomidine was best described by a two-compartment model. The population values (95% confidence interval) for elimination clearance, inter-compartmental clearance, central volume of distribution, and volume of distribution at steady state were 57.0 (42.1, 65.6), 183 (157, 212) litre h(-1), 12.3 (7.6, 17.0), and 132 (96, 189) litre. Dexmedetomidine clearance decreased with decreasing CO and with increasing age, whereas its volume of distribution at steady state was increased in patients with low plasma albumin concentration. CONCLUSIONS: The population pharmacokinetics of dexmedetomidine was generally in line with results from previous studies. In elderly patients and in patients with hypoalbuminaemia, the elimination half-life and the context-sensitive half-time of dexmedetomidine were prolonged.

Tinnitus complaint behaviour in long-standing Menière's disorder: its association with the other cardinal symptoms.

OBJECTIVE: To explore factors that determines tinnitus complaint behaviour in patients with chronic long-standing Menière's disorder. DESIGN AND SETTING: A questionnaire-based cross-sectional investigation. This included the Oto-neurological questionnaire, the Hearing Disability and Handicap Scale (HDHS), Hearing Measurement Scale (HMS) on sound localisation and the Dizziness Handicap Questionnaire (DHQ). PARTICIPANTS: Randomly selected 183 members of the Finnish Menière's Federation. INTERVENTION: Postal questionnaire. MAIN OUTCOME MEASURE: International Tinnitus Inventory and impact of tinnitus. RESULTS: The 183 patients,[36 men and 147 women; mean age, 63 years] had their Meniere's disorder-like symptoms, with a mean of 18 years [range, 1-43], 19% of patients ranked tinnitus as their most severe symptom, and 10% experienced tinnitus as causing a severe or very severe impact. Regression analysis indicated that 41% of International Tinnitus Inventory variance and 28% of tinnitus impact variance were explained by the cardinal symptoms of Menière's disorder. Furthermore, 40% of International Tinnitus Inventory and 25% of tinnitus impact variance were explained by symptom-related disabilities (HDHS, HMS and DHQ). Aural pressure, hearing loss and gait problems were the most important predictors of tinnitus complaint. Understanding what people say and limitation of activities because of vertigo were the most important related disabilities. CONCLUSION: Tinnitus shares a significant variance with the other cardinal symptoms in patients with long-standing Menière's disorder. As the impact is significantly related to activity limitations based on hearing disability and vertigo, the results suggest that therapeutic efforts to reduce tinnitus in Menière's disorder should include the alleviation of balance and hearing problems.

Effect of displacement, velocity, and combined vibrotactile tilt feedback on postural control of vestibulopathic subjects.

Vibrotactile tilt feedback was used to help vestibulopathic subjects control their anterioposterior (AP) sway during sensory organization tests 5 and 6 of Equitest computerized dynamic posturography. We used four kinds of signals to activate the feedback. The first signal was proportional (P) to the measured tilt of the subject, while the second used the first derivative (D) of the tilt. The third signal was the sum of the proportional and one half of the first derivative signals (PD). The final signal used a prediction of the subject's sway projected 100 msec in advance. The signals were used to activate vibrators mounted on the front of the torso to signal forward motion, and on the back of the torso for backward motion. Subject responses varied significantly with the kind of feedback signal. Proportional and derivative feedback resulted in similar root mean squared tilt, but the PD signal significantly reduced the tilt compared to either P or D feedback. The predicted motion signal also reduced the response compared to the PD signal. These preliminary results are somewhat consistent with an inverted pendulum model of postural control, but need to be confirmed with a larger study that also considers mediolateral tilt and feedback. The improvement by using a predictor is consistent with compensating for a neural processing delay.

Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers.

BACKGROUND: This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. METHODS: Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. RESULTS: L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50)

I.V. ropivacaine compared with lidocaine for the treatment of tinnitus.

BACKGROUND: I.V. lidocaine has been used to ameliorate tinnitus, but in general its effect has been limited. The longer acting local anaesthetic ropivacaine may be more effective. METHODS: A total of 19 randomized, double-blind, cross-over study patients suffering from chronic tinnitus were given a 30 min i.v. infusion of ropivacaine or lidocaine 1.5 mg kg(-1) at an interval of 2-3 months. The intensity of tinnitus was evaluated on tinnitus handicap inventory (THI) scale and on the visual analogue scale (VAS). Plasma ropivacaine and lidocaine concentrations were determined. RESULTS: In both treatments, the infusion decreased the VAS score significantly. At the end of infusion, a > or =50% reduction in VAS score was observed in five patients by ropivacaine and in one patient by lidocaine, but this effect was sustained for 1 h only in three patients. However, the THI scores did not differ significantly within or between treatments. On the post-infusion day, three patients after ropivacaine and five after lidocaine treatment had > or =30% improvement in the THI score. Four weeks later, one patient after ropivacaine and two after lidocaine had a > or =30% reduction in the THI score. One patient developed seizures soon after ropivacaine infusion from which he recovered uneventfully. His plasma concentration of ropivacaine was 1817 ng ml(-1). The highest individual ropivacaine and lidocaine concentrations were 3483 and 1680 ng ml(-1), respectively. CONCLUSIONS: Temporary clinically significant alleviation of tinnitus was observed only in a few individuals after both i.v. ropivacaine and lidocaine. The toxicity of ropivacaine limits its usefulness.

Assessing the depth of dexmedetomidine-induced sedation with electroencephalogram (EEG)-based spectral entropy.

BACKGROUND: Adequate sedation of critically ill patients improves the outcome of intensive care. Maintaining an optimal level of sedation in the intensive care unit (ICU) is difficult because of a lack of appropriate monitoring methods to guide drug dosing. Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, has recently been introduced for the sedation of ICU patients. This study investigated the utility of electroencephalogram (EEG)-based spectral entropy monitoring (with M-ENTROPY, GE Healthcare, Helsinki, Finland) for the assessment of dexmedetomidine-induced sedation. METHODS: Eleven healthy, non-smoking men, aged 23.9 +/- 2.5 years (mean +/- standard deviation), were recruited. Spectral entropy was recorded before and during low (0.5 ng/ml) and high (5 ng/ml) plasma concentrations of dexmedetomidine. At the end of the infusion, subjects were awakened by verbal command and light shaking. RESULTS: Spectral entropy decreased from 84 +/- 5 to 66 +/- 16 (P= 0.029) during low dexmedetomidine levels and from 84 +/- 5 to 20 +/- 12 (P < 0.001) during high dexmedetomidine levels. Transitions during loss and regaining of consciousness were analysed separately. Entropy decreased from 76 +/- 8 before to 43 +/- 10 (P < 0.001) after loss of consciousness, and increased from 14 +/- 4 to 63 +/- 13 (P < 0.001) on regaining of consciousness. These changes were consistent across all subjects. Prediction probability and sensitivity values indicated a high predictive performance of the method. CONCLUSION: The depth of dexmedetomidine-induced sedation can be monitored with EEG-based spectral entropy. These results should be confirmed in a clinical setting.

Value of imaging studies in vertiginous children.

OBJECTIVE: Imaging of the head is expensive and can be stressful for children, some of whom need anesthesia for the procedure. The aim of this study was to determine which vertiginous children benefit most from head imaging. METHODS: We conducted a retrospective chart review of all children aged under 18 years who were referred to the Helsinki University Children's Hospital Radiology Department (tertiary referral center) for head computerized tomography (CT) or magnetic resonance imaging (MRI) over a 1-year period. We analyzed and reviewed the medical records of 87 children who had undergone imaging of the head due to vertigo. RESULTS: Altogether 978 children underwent imaging of the head for various indications. Of these, 87 aged 0-16 years (mean age 8 years) were imaged because of vertigo. Abnormalities were seen in the images of 37 children; 23 were new findings and 14 showed no change in comparison to earlier deviant images. The most common abnormalities in head imaging were brain tumors, infections, multiple sclerosis lesions, and other lesions in T2-weighted images. Of the 23 vertiginous children with a new finding, 19 also had neurological deficits. While four children had no neurological symptoms, three had intense headaches. CONCLUSIONS: Head imaging is necessary for vertiginous children with neurological deficits or persistent headaches or who have sustained a head trauma. If vertigo is the only symptom without trauma, imaging studies will not aid diagnostic work-up.

Effect of age and repeated hyperbaric oxygen treatments on vagal tone.

OBJECTIVES: To evaluate the influence of repeated hyperbaric oxygen (HBO2) exposures and age on vagal response to hyperbaric oxygenation, and to evaluate the timing of changes in vagal activity during the treatments. STUDY DESIGN: Open, controlled, non-randomized study. METHODS: Heart rate variability of 23 patients with chronic osteomyelitis or radionecrosis of the jaw or reconstructive surgery of the facial region was studied during repeated treatments. During each treatment, the patients were exposed to HBO2 at 2.5 ATA and heart rate variability was measured using power spectral analysis before compression, three times at 2.5 ATA and during and after decompression. The patients were grouped according to age (Cut-off point 50 years). Statistical analysis was carried out using analysis of variance for repeated measurements. RESULTS: Repeated exposures did not change vagal response to hyperbaric oxygenation. Vagal activity measured by HF power increased significantly in both age groups during the HBO2 exposures but there were no significant difference between the groups in the response. However, the level of HF power was significantly higher in the subjects under 50 years old. Significant differences between consecutive measurements were related to pressure changes. CONCLUSIONS: Repeated therapeutic HBO2exposures are not causing permanent changes in vagal control of the heart. Vagal responsiveness to hyperbaric hyperoxia is preserved in advanced age.

Control of sway using vibrotactile feedback of body tilt in patients with moderate and severe postural control deficits.

We evaluated the effect of the vibrotactile display of body tilt upon the postural stability of vestibulopathic subjects during standing. Two groups were studied: those with moderate and with severe deficits as defined by postural stability test scores. They were studied under conditions of distorted sensory input, and during anterior-posterior perturbations. Seventeen subjects, with uni- or bilateral vestibular deficits, as determined by electronystagmography and vertical axis rotation, were tested using Equitest computerized dynamic posturography (CDP). Based on their performance on the CDP they were divided into two groups having either moderate (nine subjects) or severe (eight subjects) postural control deficits. Their anterior-posterior (A/P) body motion at the waist was measured with a micromechanical rate gyroscope and a linear accelerometer. The resulting tilt estimate was displayed by a vibrotactile array attached to the torso. The vibration served as a tilt feedback to the subject. The subject's performance was evaluated using the root-mean-square (RMS) of both the A/P body motion and center-of-pressure (CoP) estimates. Sensory distortions were introduced using the Equitest Sensory Organization Tests (SOT). These tests are designed to distort A/P sensory inputs while standing. The SOT 5 distorts proprioceptive information about ankle joint movement, while the subject stands eyes-closed on a moving support platform that measures foot pressure. The SOT 6 adds distorted visual information about body movement instead of testing with eyes closed. Perturbations were introduced using the Equitest Motor Control Tests (MCT). These move the support platform forward or backward with small, medium and large displacements in the horizontal plane while measuring subjects' foot pressure responses. We used the medium and large backward tests. Vibrotactile display of body tilt reduced the subjects' A/P sway and improved their balance. The finding was more evident for those subjects with severe deficits than those moderate ones. This trend was found for both SOT 5 and 6, as well as the medium and large MCT. Additionally, during the MCT, the peak deflection and mean recovery time also decreased significantly.

Postural instability in Meniere's disease.

In order to characterize the postural instability by duration of Meniere's disease (MD) we present the results of 180 MD patients tested on posturography. The duration of the disease varied from 4 weeks to 36 years. The patients were clinically examined and they had filled a questionnaire concerning their symptoms. Postural instability was examined by a force platform posturography and the results are expressed as sway velocities (SV). There was no statistically significant difference in the mean SV between groups of different duration of MD. The number of the patients with normal eyes open SV declined by duration of the illness from 73% to 38% but the decline was not statistically significant. The mean age in the different duration groups of MD varied from 47 to 61 years. In general 58% of the patients had their eyes open SV in normal range and 55% when measured eyes closed. When examining the SV between the 4 different hearing stages of MD we found that those belonging into the group III (pure tone average [PTA] 41-70 dB) had significantly higher eyes open and eyes closed SV's than the patients in the group I (PTA under 25 dB).

Vestibular dysfunction in adult patients with osteogenesis imperfecta.

Progressive hearing loss is a major symptom in osteogenesis imperfecta (OI), a genetic brittle bone disease. Vertigo is frequently associated with otosclerosis in which the hearing loss clinically resembles that in OI. Vertigo is also common in basilar impression (BI) found in up to 25% of adult OI patients. In order to evaluate the cause, frequency, and characteristics of vertigo in OI, 42 patients were studied by interview, clinical examination, and audiological examination supplemented with electronystagmography (ENG) and lateral skull radiography. Audiometry showed hearing loss in 25 patients (59.5%). Nine patients (21%) displayed abnormal skull base anatomy in the forms of basilar impression, basilar invagination, or both, all designated here as BI. Twenty-two patients (52.4%) reported vertigo, mostly of floating or rotational sensation of short duration. Patients with hearing loss tended to have more vertigo than patients with normal hearing. Vertigo was not correlated with type of hearing loss or auditory brain-stem response (ABR) pathology. ENG was abnormal in 14 patients (33.3%). No dependency was found between vertigo and deviant ENG results. Patients with BI tended to have more vertigo than patients with normal skull base but the difference was not statistically significant. Neither ENG pathology, nor the presence or type of hearing loss showed correlation with BI. In conclusion, vertigo is common in patients with OI. In most cases, it may be secondary to inner ear pathology, and in only some patients does BI explain it. Since some OI patients without BI or hearing loss also suffer from vertigo, further clinical and neurological studies are needed to define the pathogenesis of vertigo in OI.

Instantaneous beat-to-beat variability reflects vagal tone during hyperbaric hyperoxia.

Hyperbaric hyperoxia affects heart rate variability (HRV) by increasing parasympathetic activity. The purpose of this study was to evaluate the applicability of instantaneous beat-to-beat variability (SD1 of Poincaré plot analysis) in detecting changes in vagal tone and to evaluate possible changes in the fractality of heart rate dynamics (alpha1 of detrended fluctuation analysis) during hyperbaric hyperoxia. Continuous three-lead ECG recordings were taken in ten divers who were treated at 2.5 ATA with air (PO2 47 kPa) and oxygen (PO2 235 kPa) for 60 min. Power spectral analysis, Poincaré plot analysis and alpha1 were analyzed before compression, after 30 min and after 55 min at 2.5 ATA. Correlations between the variables were calculated after 55 min exposure. SD1 and high frequency (HF) power increased significantly but alpha1 decreased during hyperbaric hyperoxia (PO2 235 kPa). HF power and SD1 also correlated significantly. However, HF power and SD1 correlated inversely with alpha1. During hyperbaric hyperoxia, SD1 reflects vagal activity and can be used instead of HF power, if stationary conditions cannot be achieved. The decreasing alpha1 indicates more random heart rate dynamics during hyperbaric hyperoxia.

Hearing loss and tinnitus in Meniere's disease.

OBJECTIVES: To characterize hearing loss, tinnitus and associative factors in Meniere's disease. METHODS: From our vertigo database consisting of 1356 patients, we retrieved 243 patients with Meniere's disease (MD). RESULTS: Hearing loss was the initial symptom in 13% of cases. Altogether 64% (n=133) of the patients stated that their hearing was reduced during the vertigo attack. The hearing deteriorated more likely during the vertigo attack if the vertigo attack was very intense [r(206)=0.19]. Tinnitus was the initial symptom in 5% of cases. The tinnitus was mild in 38% (n=90), moderate in 32% (n=76) and severe in 30% (n=72) of patients. The intensity of tinnitus correlated with the occurrence of drop attacks [r(237)=0.29], vertigo provoked by head positioning [r(235)=0.25], by physical activity [r(230)=0.33], or by pressure changes [r(239)=0.27]. CONCLUSION: Prolonged disease causes deterioration of hearing. Intense tinnitus is common in MD and is more often seen in late stage of the disease.

Recovery trajectories of vestibulopathic subjects after perturbations during locomotion.

We compared the mediolateral (M/L) responses to perturbations during locomotion of vestibulopathic (VP) subjects to those of controls. Eight subjects with unilateral vestibular loss (100% Reduced Vestibular Response from the caloric test) resulting from surgery for vestibular schwannoma and 11 controls were selected for this study. Despite their known vestibulopathy, all VP subjects scored within the normal range on computerized dynamic posturography Sensory Organization Tests. During gait, subjects were given surface perturbations of the right support-phase foot in two possible directions (forward-right and backward-left) at two possible magnitudes (5 and 10 cm) that were randomly mixed with trials having no perturbations. M/L stability was quantified by estimating the length of the M/L moment arm between the support foot and the trunk, and the M/L accelerations of the sternum and the head. The VP group had greater changes (p < 0.05) in their moment arm responses compared to controls. The number of steps that it took for the moment arm oscillations to return to normal and the variability in the moment arms were greater for the VP group. Differences in the sternum and head accelerations between VP and control groups were not as consistent, but there was a trend toward greater response deviations in the VP group for all 4 perturbation types. Increased response magnitude and variability of the VP group is consistent with an increase in their sensory noise of vestibular inputs due to the surgical lesion. Another possibility is a reduced sensitivity to motion inputs. This perturbation approach may prove useful for characterizing subtle vestibulopathies and similar changes in the human orientation mechanism after exposure to microgravity.

On classification capability of neural networks: a case study with otoneurological data.

We investigated the capability of multilayer perceptron neural networks and Kohonen neural networks to recognize difficult otoneurological diseases from each other. We found that they are efficient methods, but the distribution of a learning set should be rather uniform. Also it is important that the number of learning cases is sufficient. If the two mentioned conditions are satisfied, these neural networks are similarly efficient as some other machine learning methods. The conditions are known in the theory of neural networks [1,2], but not often taken seriously in practice. Both networks functioned as well, excluding the case with several input variables, where the Kohonen neural networks surpassed the perceptron.

Stimulated expression of cyclooxygenase-2 in porcine heart after bypass circulation and cardioplegic arrest.

OBJECTIVES: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes catalyze the initial step in the formation of prostaglandins, which have a role in the regulation of circulation and in inflammatory reactions. As hypoxia is reported to stimulate the expression of COX-2, we have investigated the effects of bypass circulation and cardioplegic arrest on the expression COX-1 and COX-2 in the myocardium of porcine hearts. METHODS: Anaesthetized pigs were connected to cardiopulmonary bypass and the hearts were arrested by cold crystalloid cardioplegia for 30 min and reperfused thereafter for 90 min. Then the mRNA and protein levels of COX-1 and COX-2 were measured from the transmural specimens of the left ventricular myocardium by Northern and Western blot analyses. Reference specimens were from the hearts of unoperated control pigs and from sham-operated pigs, which were connected to cardiopulmonary bypass for 120 min without any aortic clamping. RESULTS: COX-1 mRNA was expressed in unoperated control porcine hearts, whereas the expression of COX-2 mRNA was weak in control hearts. The expression of COX-2 mRNA increased to 170% of the control level in the hearts of sham-operated pigs and to 180% in arrested hearts, while the level of COX-1 mRNA was not changed. Both COX-1 and COX-2 proteins were detected by Western blot analysis in the myocardial specimens of control hearts. After cardioplegic arrest, the level of COX-2 protein increased to 280% of the control level in arrested hearts, whereas the level of COX-1 protein remained unchanged. CONCLUSIONS: These results indicate that the expression of the COX-2 gene is stimulated in the ventricular myocardium of the porcine heart after bypass circulation and cardioplegic arrest.