[Personal experience in the diagnosis of vestibular patients: transition from empirism to scientific vestibular medicine].
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Education, Medical↗
Biomedical subjects
V Honrubia
Publications and source records attributed to V Honrubia.
Mechanism of posterior semicircular canal stimulation in patients with benign paroxysmal positional vertigo.
A quantitative study of the stimuli and vestibulo-ocular response associated with benign paroxysmal positional vertigo (BPPV) was made to test and further develop the canalithiasis theory of BPPV. The angular velocities of the head in the planes of the semicircular canals during the Dix-Hallpike test were measured in four healthy subjects using electromagnetic sensors to record the position of the head in a six degrees of freedom paradigm. Next, the nystagmus reactions in seven patients diagnosed with idiopathic BPPV were recorded with video-oculography. The characteristics of the vestibulo-ocular reflex (VOR) response were analyzed using three-dimensional vector techniques. The angular velocity of the head was primarily, but not exclusively, in the plane of the posterior semicircular canal (PSC) in question. Both the anterior and horizontal canals were also stimulated by a lesser degree. The duration of the motion stimulus in the PSC was < 1.3 s with peak angular velocities of 150 deg/s. The eye response in BPPV patients began 4 s after the test and had a duration of 15-20 s. Peak slow-component eye velocities of about 42 deg/s were reached 3-5 s after onset of nystagmus. The motion of the eye, as predicted by the cupulolithiasis theory, is disconjugated and has torsional, vertical, and horizontal components. In the eye ipsilateral to the tested ear it is primarily torsional (0.80, 0.54, 0.16) and in the contralateral eye it is mainly vertical (0.57, 0.73, 0.08). These results suggest that particles, initially resting on the floor of the cupula dome in the PSC, are perturbed by the Dix-Hallpike test and disperse freely into the endolymph where they are propelled by gravity into the canal lumen. This creates abnormal pressure on the cupula and the specific VOR activation of the ipsilateral superior oblique and the contralateral inferior rectus muscles, whose force vectors are indistinguishable from the measured eye motion vectors. The estimated pressure exerted on the crista is approximately 10(-2) dyn/cm2.
Adult↗
Mechanism of posterior semicircular canal stimulation in patients with benign paroxysmal positional vertigo.
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Eye Movements↗
Interlaboratory variability of rotational chair test results II: analysis of simulated data.
Standardization of rotational chair testing across laboratories has not been achieved because of differences in test protocol and analysis algorithms. The Interlaboratory Rotational Chair Study Group was formed to investigate these differences. Its first study demonstrated significant variability in calculated results using actual patient data files. No estimation of accuracy could be made, however, because the "true" values of response parameters were unknown. In this study we used simulated "patient" data files to further explore the differences among analysis algorithms. We found a high degree of agreement and accuracy across laboratories using automated analysis of high signal-to-noise/low-artifact data for gain, phase, and asymmetry. Variability increased significantly for the lower signal-to-noise ratio/higher artifact files. Operator intervention generally improved accuracy and decreased variability, but there were cases in which operator intervention reduced accuracy.
Computer Simulation↗
Expression of BDNF and TrkB mRNAs in the crista neurosensory epithelium and vestibular ganglia following ototoxic damage.
Following ototoxic lesion with the aminoglycoside gentamicin, the vestibular neurosensory epithelia undergo degeneration and then limited spontaneous regeneration. The spatio-temporal expression of brain-derived neurotrophic factor (BDNF) and of its high affinity receptor (trkB) mRNA was investigated in the vestibular end organs and ganglia of chinchillas following gentamicin ototoxicity. In the vestibular ganglia of untreated chinchillas, the level of expression of BDNF mRNA is low. At 1 and 2 weeks after intraotic treatment with gentamicin, BDNF mRNA levels in the vestibular ganglia were elevated significantly compared to untreated chinchillas and chinchillas 4 weeks after treatment. At 4 weeks after gentamicin treatment, BDNF mRNA levels were at intact levels of expression. In the crista ampullaris, high levels of BDNF transcripts were found in the untreated chinchillas. At 1 and 2 weeks after treatment, when only supporting cells are present in the crista, BDNF mRNA was undetectable. Four weeks after aminoglycoside treatment BDNF mRNA was present in the epithelium but at lower levels than in the intact epithelium. In contrast to its ligand, high levels of trkB mRNA hybridization were present in the vestibular ganglia of untreated chinchillas and trkB mRNA levels did not change following gentamicin treatment. In the vestibular epithelia, trkB mRNA was not detected either in the intact epithelium or after gentamicin ototoxicity. These data suggest that BDNF may be involved in the maintenance of the vestibular ganglia and contribute to neurite outgrowth to new and repaired hair cells following ototoxic damage.
Animals↗
Current status of electronystagmography testing.
ENG testing, whether computerized or not, remains the most useful means of assessing the vestibular system. The caloric test provides invaluable site-of-lesion information that objectively documents a peripheral vestibular lesion. Double (bithermal) caloric irrigation of each ear provides a more thorough and wider range test of inner ear function than a single caloric irrigation because the vestibular system is both excited and inhibited, causing responses in opposite directions, which are important in evaluating patients with underlying spontaneous nystagmus. In an age in which economically efficient and clinically effective diagnostic methods are in high demand, ENG testing remains the gold standard of vestibular function tests.
Calorimetry↗
Glutamate-like immunoreactivity during hair cell recovery after gentamicin exposure in the chinchilla vestibular sensory periphery.
OBJECTIVE: Determine the expression of glutamate by immunohistochemistry in normal and recovering vestibular hair cells in the chinchilla crista ampullaris after gentamicin ototoxicity. STUDY DESIGN: In five groups of three animals each, ototoxicity was produced by placing gentamicin (50 microg)-impregnated Gelfoam pellets within the perilymphatic space of the superior semicircular canal. Animals were sacrificed at 1, 2, 4, 8, and 16 weeks after treatment. A group of normal (n=3) animals was also processed. METHODS: For the detection of glutamate the inner ears of these animals were dissected, and the horizontal cristae ampullaris embedded in plastic. Two-micron-thick tissue sections were obtained and incubated with monoclonal antibodies against glutamate. The immunoreaction was detected using the avidinbiotinylated-complex technique and diaminobenzidine was the chromogen. RESULTS: Normal sensory epithelia demonstrated type I and type II hair cells with moderate glutamate-like immunoreactivity. Supporting cells demonstrated no glutamate-like immunoreactivity. Afferent nerve fibers and calyxes surrounding type I hair cells demonstrated strong glutamate-like immunoreactivity. At 1 and 2 weeks after treatment the few type II hair cells surviving ototoxic treatment (15%-18%) contained moderate glutamate-like immunoreactivity, supporting cells showed no immunoreactivity, and nerve terminals and fibers displayed strong immunoreactivity. At 4 and 8 weeks after treatment, recovered hair cells (80%) had greater glutamate-like immunoreactivity when compared with normal hair cells, supporting cells displayed no glutamate-like immunoreactivity, and afferent fibers contained strong glutamate-like immunoreactivity. At 16 weeks, glutamate-like immunoreactivity in hair cells returned to normal level. CONCLUSION: Glutamate may be used as an indicator of hair cell differentiation and as an index of the molecular recovery of hair cells after ototoxicity.
Animals↗
Origins of the short latency vestibular evoked potentials (VsEPs) to linear acceleration impulses.
OBJECTIVE: To verify the vestibular origin of the short latency (t < 12.5 msec) vestibular evoked potentials (VsEPs) in response to linear acceleration impulses (L-VsEPs) and to differentiate between the contributions of the otolith organs and the semi-circular canals (SCCs) to their initiation. DESIGN AND METHODS: L-VsEPs (stimulus intensity, 3 g; rise time, 1.0 to 1.5 msec) were recorded in fat sand rats (Psammomys obesus) before and after unilateral labyrinthectomy, plugging of the SCCs in the remaining ear, and bilateral labyrinthectomy. Auditory nerve brainstem evoked responses (ABRs) and VsEPs to angular acceleration impulses (A-VsEPs) were also recorded. Wave amplitudes and latencies were statistically analyzed (MANOVA, repeated t-tests). RESULTS: In the intact animal, the linear VsEPs consisted of 5 to 6 waves, several mV in amplitude, with short latencies. The latency of the first wave was 2.0 msec. These waves were abolished after bilateral labyrinthectomy. Before and after plugging of the SCCs, linear acceleration VsEP wave latencies did not change, although amplitudes were slightly reduced. Similar results were obtained with respect to ABRs recorded from the same ear. Angular acceleration VsEPs were abolished after SCC plugging. CONCLUSIONS: These and other results confirm that the linear VsEPs are compound action potentials of the vestibular pathway, the first wave is the response of the vestibular nerve, and they are initiated mainly in the otolith organs.
Animals↗
The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity.
HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) influences the process of hair cell recovery in the vestibular sensory epithelium of the chinchilla after local application of gentamicin (GM). BACKGROUND: Hair cell regeneration in the inner ear after GM ototoxicity has been demonstrated. However, the mechanisms responsible for this recovery have yet to be completely elucidated. This report examines the protective and proliferative effects that BDNF exerts on vestibular hair cells in experiments designed to further elucidate the mechanisms of hair cell regeneration. METHODS: The inner ears of three separate groups of chinchillas were treated with GM only, GM and BDNF simultaneously, and GM followed by BDNF 1 week later. The numbers of hair and supporting cells in the horizontal cristae of each group were then estimated at 1, 2, 4, and 8 weeks, and the data were compared. RESULTS: Type I hair cells after GM treatment completely disappeared. After simultaneous BDNF and GM treatment, their numbers decreased to 23% at 1 week and progressively disappeared by week 8. When BDNF was applied 1 week after GM administration, type I hair cells recovered to 12% at week 4 and 28% at week 8. Type II hair cells after GM treatment decreased to 15%, but recovered to 83% 4 weeks later. Simultaneous administration of BDNF and GM prevented the ototoxic effects of GM alone. When BDNF was administered 1 week after GM, type II hair cell recovery was accelerated and was greater than after GM alone (81% versus 18%). Supporting cells after GM treatment decreased to 74% at 1 week after treatment, recovered to 91% at 2 weeks, and remained at 86% at 4 weeks and 85% at 8 weeks. With the simultaneous administration of BDNF and GM, supporting cells significantly decreased at 2 weeks after treatment (63%), but recovered to normal by week 8. CONCLUSIONS: These results suggest that BDNF provided simultaneously with GM minimizes the ototoxic effect of GM on type II hair cells. The increase in the number of new hair cells when BDNF is provided after ototoxic damage is evidence of the proliferative capacity of this neurotrophic factor.
Animals↗
Paroxysmal positional vertigo syndrome.
INTRODUCTION: This study was initiated to investigate the differential diagnosis of patients with benign paroxysmal positional vertigo (BPPV) of different canals' origin. METHODS: The eye movements of 292 patients were evaluated with the use of Frenzel glasses and infrared video cameras after positional tests. Epley's canal repositioning procedure (CRP) was conducted, with appropriate modifications for individual cases, on every patient. RESULTS: Two different types of positional nystagmus were observed corresponding to the presence of otoliths in the lumen of each of the semicircular canals and on the cupola of the horizontal semicircular canal. The posterior canal was involved in 250 patients unilaterally and 23 patients bilaterally. The anterior canal variety was observed in four patients. In the horizontal canal, nine were of the cupulolithiasis and six of the canalithiasis variety. In seven patients. the affected canal converted to a different location. The canal repositioning procedure eliminated vertigo and abnormal eye movements in 88% of the unilateral posterior canal variety. The success rate of the procedure in the other varieties was 50%. CONCLUSION: Positional vertigo can have characteristics corresponding to the presence of otolith particles in each of the semicircular canals. The treatment requires different strategies to move the otoliths, depending on their location in the vestibule.
Aged↗
Static and dynamic posturography in patients with vestibular and cerebellar lesions.
OBJECTIVE: To assess the diagnostic usefulness of posturography in 2 well-defined patient groups with impaired balance. PATIENTS: Ten control subjects, 10 patients with bilateral vestibular loss, and 10 patients with cerebellar atrophy. OUTCOME MEASURES: Amplitude, velocity, and frequency of sway in the anteroposterior and medial-lateral directions on a static platform, on foam, and on a moving platform. RESULTS: Both patient groups consistently had increased sway compared with controls, particularly when standing on foam or on a moving platform with eyes closed. Sway amplitude and velocity were increased about the same amount. The Romberg ratio (sway with eyes closed/sway with eyes open) did not reliably differentiate patients from controls or the 2 patient groups from each other. Some patients with cerebellar atrophy exhibited a characteristic body tremor at about 3 Hz in the anteroposterior direction. CONCLUSIONS: Although sway amplitude and velocity were consistently increased in patients with bilateral vestibular loss and patients with cerebellar atrophy, none of the posturography measurements reliably distinguished the 2 patient groups. The finding of increased frequency of sway in the anteroposterior direction in patients with cerebellar atrophy was of limited value since the tremor was visible at the bedside.
Adult↗
Vestibular nerve regeneration in the bullfrog, Rana catesbeiana: peripheral dendrites.
Three experiments were conducted on healthy adult bullfrogs (Rana catesbeiana) for the purpose of investigating three characteristics of centrifugal vestibular afferent regeneration after complete transection of the anterior division of the vestibular nerve (AVN). In experiment 1 total fiber count and axon diameter measurements were obtained from the anterior canal nerve at three different time periods and compared with normal. The normal group (n = 3) demonstrated a total fiber count of 1001 +/- 76 (SEM). The early time period (1 to 2 weeks, n = 3) did not completely regenerate as demonstrated by a total fiber count of 282 +/- 23. The intermediate (4 to 6 weeks, n = 3) and late (8 to 16 weeks, n = 3) groups exhibited total fiber counts of 907 +/- 29 and 946 +/- 50, respectively, which were not different from normal (Mann-Whitney U, p > 0.2). Evaluation of fiber diameter distribution of the intermediate and late regenerated nerves revealed a reduction in axon diameter caliber compared with normal (analysis of variance, p < 0.0001). Thus transection of the AVN results in regeneration of all afferents that exhibit a reduction in axon diameter. In experiment 2 fibers innervating the anterior canal crista (ACC) were prelabeled before nerve transection. After the labeling procedure the AVN (n = 3) was sectioned at a location that resulted in denervation of three vestibular receptors: the ACC, horizontal canal cristae (HCC), and utricular macula. After 4 weeks of regeneration the ACC fibers that were prelabeled were observed innervating all three denervated vestibular receptors. This result demonstrated that reinnervation of the peripheral vestibular end organs after AVN transection is a nonspecific process. In experiment 3, 167 regenerated canal afferents were evaluated for functional recovery 16 weeks after transection. Both spontaneous and rotation-induced discharge characteristics were obtained and compared with those obtained from a sample of 254 normal afferents in a previous study (Hoffman LF. Factors affecting the response dynamics of canalicular primary afferent neurons in the bullfrog. St. Petersburg (FL): Association for Research in Otolaryngology; 1989). The mean spontaneous discharge coefficient of variation (CV) +/- standard deviation was 0.60 +/- 0.32 and 0.49 +/- 0.33 for ACC and HCC regenerated afferents, respectively, which did not differ from the normal means of 0.63 +/- 0.33 and 0.54 +/- 0.36 (Mann-Whitney, p > 0.2). Response gains and phases obtained during 0.05 Hz sinusoid rotations at 15 degrees/second maximum horizontal table velocity also demonstrated normal discharge characteristics. The mean phases were -28.2 +/- 25.2 degrees and -55.9 +/- 21.5 degrees for regenerated ACC and HCC afferents, respectively, which were not different from the normal means of -33.77 +/- 24.31 degrees and -58.0 +/- 23.3 degrees (Mann-Whitney U). Furthermore, regenerated afferents exhibited a positive association between phase and CV, which was also true for normal afferents (correlation analysis, p > 0.001). Although the mean gains for regenerated ACC and HCC (7.13 +/- 5.5 and 3.3 +/- 2.4 spikes x sec(-1)/degrees x sec(-2), respectively) afferents were reduced from normal ACC and HCC (14.8 +/- 12.52 and 7.76 +/- 6.58 spikes x sec(-1)/degrees x sec(-2), respectively) afferents (Mann-Whitney U, p > 0.0001), a positive association between gain and CV was also demonstrated by regenerated afferents, as was the case for normal afferents (correlation analysis, p < 0.001). Thus the overall response discharges of regenerated afferents were comparable with normal afferents. Normally, large fibers innervate central regions of the receptor, and smaller fibers innervate the peripheral regions. However, the data from experiments 1 and 2 demonstrate that vestibular nerve regeneration results in a dissociation between the normal topographic organization of fiber size and regional innervation of the receptor epithelium. (ABSTRACT TRUNCATED)
Animals↗
Hair cell recovery in the chinchilla crista ampullaris after gentamicin treatment: a quantitative approach.
The mechanisms for hair cell recovery were investigated after intraortic application of 50 microg gentamicin into the perilymphatic space of the superior semicircular canal of the chinchilla. Histologic evaluation of one normal group and four posttreatment groups (7, 14, 28, and 56 days) was made with light and transmission electron microscopic techniques. The numeric changes of hair cells and supporting cells was quantified with the dissector technique. At 7 and 14 days after treatment, no type I hair cells were present, and 85% and 88% of type II hair cells were lost. Supporting cells decreased to 76% at 7 days, but they recovered to 91% at 14 days. Recovery of the epithelia was evident 28 days after treatment; 83% were type II hair cells, and 3% were type I hair cells. The supporting cell number remained close to normal (86%). Between 14 and 28 days after treatment, there was an increase of 1758 of type II hair cells, representing approximately 125 new hair cells per day. At the same time interval the number of supporting cells remained near normal. These results suggest that new hair cells might be the result of supporting cell mitotic division and differentiation.
Animals↗
Balance disorders in older persons: quantification with posturography.
We measured sway velocity using static and dynamic posturography in a group of young normal subjects and two groups of subjects older than 75 years; one older group considered their balance normal for their age, and the other reported imbalance. The latter group consisted of patients with documented peripheral and central vestibular disorders and patients with dizziness and imbalance of unknown cause. The velocity of sway was higher in older subjects than in younger subjects and in older subjects who reported imbalance than in age-matched controls. The difference was greater with dynamic posturography than with static posturography, but the posturography data provided little information about the cause of the imbalance and did not correlate with the frequency of reported falls.
Accidental Falls↗
Childhood onset of benign positional vertigo.
Benign positional vertigo (BPV) rarely occurs in children, but we identified three members of a family who developed BPV before age 13 years. All three had migraine headaches and two had spontaneous episodes of vertigo. Vasospasm associated with migraine possibly resulted in ischemic damage to the utricular macule, leading to the development of BPV in these patients.
Age of Onset↗
A novel psychophysical illusion resulting from interaction between horizontal vestibular and vertical pursuit stimulation.
HYPOTHESIS: The hypothesis was tested that the perception of an object's motion is made in relation to an internal reference center (IRC), which is under the influence of vestibular receptors. Experiments were designed to evaluate whether induced vestibular self-motion will interact linearly with the perception of a visual target (VT). BACKGROUND: The major complaint of vestibular patients is vertigo, an illusion of motion. However, there is as yet no objective method to measure this illusion, which is produced by vestibular stimulation. METHODS: Six subjects were instructed to track a vertically moving VT while sinusoidally rotating (0.2 Hz) in the yaw plane at 14, 28, and 42 degrees/s. Eye movements were monitored by electro-oculographic electrodes. RESULTS: During visual-vestibular interaction, all subjects perceived a VT moving obliquely while the eyes moved in the vertical plane. The subject then tilted the VT trajectory until vertical was perceived. At this time, the eye had an oblique vectorial trajectory. Interactive horizontal eye velocities, both vertical and horizontal components, were compared with those from rotation in the dark, showing a strong positive linear relationship (slope = 0.96, r = 0.84, n = 18). CONCLUSIONS: Results support the hypothesis of an egocentric sense of orientation whereby velocity of external objects is evaluated in relation to an IRC that is dependent on the status of the vestibular system. These methods may lead to new techniques for clinical evaluation of vestibular patients.
Adult↗
Hair cell formation in cultures of dissociated cells from the vestibular sensory epithelium of the bullfrog.
HYPOTHESIS: Bullfrog vestibular hair cells are capable of regenerating in vitro. BACKGROUND: Recent studies have established that sensory organs in the inner ear of vertebrates continue to produce hair cells after birth. However, the mechanisms responsible for the regulation of this process are not well understood. The current study reports the development of a novel method for the culture of dispersed cells from the bullfrog inner ear. METHODS: New hair cell formation in this in vitro preparation was shown by sequential photomicroscopy. Studies with the selective marker for mitotic activity 5-bromo-2-deoxyuridine (BrdU) were done to estimate the level of cell proliferation and to quantify postmitotic hair cell formation. Finally, confirmation of cell type was obtained by scanning electron microscopy and by the use of specific markers for hair cells. RESULTS: Once the optimal culture conditions were established in the initial experiments, the formation of new hair cells was directly visualized in all unstained live cultures and fixed preparations without exception. Asymmetric division of progenitor cells, with subsequent differentiation of one of the daughter cells into new hair cells, also was documented by photomicroscopy. Approximately 12% of the cells were labeled with BrdU, of which 6% were hair cells, showing that new hair cell formation was subsequent to mitotic division in vitro. The identity of newly formed hair cells was verified as follows: 1) morphologically by scanning electron microscopy; 2) by positive labeling with phalloidin-rhodamine, a marker for actin; and 3) by positive calmodulin immunocytochemistry. CONCLUSIONS: This study reports the development of an in vitro culture preparation in which undifferentiated epithelial cells proliferate to become new hair cells. Evidence is provided of division of hair cell progenitors and subsequent differentiation of the daughter cells as one of the mechanisms involved in new hair cell formation in the culture preparation. This newly developed cell culture technique provides a powerful tool for further study of the process of hair cell formation in the vestibular end organ.
Animals↗
Expression of the AMPA-selective receptor subunits in the vestibular nuclei of the chinchilla.
The distribution of the AMPA type glutamate receptor has been investigated throughout the central nervous system; however, no detailed description of its distribution is available in the vestibular nuclei. In the present study, in situ hybridization histochemistry and immunohistochemistry were used to localize the messenger RNAs and proteins of the AMPA-selective receptor subunits GluR1, GluR2, GluR3 and GluR4 in the vestibular nuclei of the chinchilla. Immunohistochemistry with subunits specific antisera showed differential distribution of the subunits in the vestibular nuclei. GluR2/3 antiserum labeled the most neurons, suggesting that many if not all vestibular neurons receive glutamatergic input. GluR1-positive neurons were fewer than GluR2/3 immunoreactive neurons and GluR4 immunoreactivity was found in the fewest number of neurons. GluR1 and GluR4 immunoreactivity was also found in astrocyte-like structures. In situ hybridization with 35S-labeled complementary RNA probes confirmed the distribution of the AMPA receptor subunits obtained by immunohistochemistry. Quantitative analysis of the levels of hybridization showed a high degree of diversity in the levels of expression of the GluR2 subunit mRNA, with the highest levels of expression in the giant Deiter's cells of the lateral vestibular nuclei and the lowest levels in the small neurons throughout the vestibular nuclei. The subunit compositions of the AMPA receptors determine their physiological properties. Differential distribution and levels of expression of the receptor subunits in the vestibular nuclei may be related to the characteristics of information processing through the vestibular system.
Animals↗