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Experimental design. (A) Surface reconstruction of an adult human bony labyrinth based on CT images illustrating the oval window (OW) where sound enters the inner ear, round window (RW), lateral canal (LC), posterior canal (PC), superior canal (SC) and location of dehiscence (D)⁵⁹. (i) Navier-Stokes simulation with simplified toroidal canal geometry where sinusoidal pressure Po is applied at the outer tube (black arrows) and pressure is relieved at the dehiscence (D). The bony labyrinth was modeled as a perilymph-filled rigid tube (black outlines), and the membranous labyrinth was modeled as an endolymph-filled elastic tube. Color bar indicates the displacement magnitude of the membranous duct (white is zero, black is maximum). The maximum displacement occurs at the location of the dehiscence (D) and waves propagate away from the dehiscence towards the oval window stimulus site. (B) Membranous labyrinth of the experimental animal model (oyster toadfish), showing the location of the simulated dehiscence (SD) in the lateral canal (LC) and location of single-unit afferent neuron recordings in the LC nerve branch (E) (Adapted in part from Iversen et al.¹⁴ with the permission of the Acoustical Society of America). (ii) The inverse of the inter-spike-interval, Spk-s⁻¹, was recorded. (iii) Close-up of the lateral canal ampulla at the location where velocity fields were measured using PIV.
Source publication
Individuals suffering from Tullio phenomena experience dizziness, vertigo, and reflexive eye movements (nystagmus) when exposed to seemingly benign acoustic stimuli. The most common cause is a defect in the bone enclosing the vestibular semicircular canals of the inner ear. Surgical repair often corrects the problem, but the precise mechanisms unde...
Citations
... The different clinical data in the most recent publications are in accordance with predictions in recent physiological works [25][26][27][28] SVIN when interpreted in the light of these recent works shows a new insight and confirms its value in the armamentarium of first-line vestibular tests in SCD diagnosis. However, third mobile window syndrome most often described in SCD is not specific to this pathology [29] and SVIN is not specific to SCD diagnosis; it may be observed in other third mobile window syndromes, as reported by White [30]. ...
... The variable vertical direction (upor down-beating nystagmus) and horizontal component could not be explained by a single stimulation of the superior SCC. The vertical nystagmus component direction variability could be explained by the current concept of the Tullio phenomenon related to the flow of the endolymph and nonlinear fluid pumping [26][27][28], which will be detailed below. For the horizontal component, stimulation of structures other than the superior SCC was suggested accordingly to what is known from physiology [35,36]. ...
... These clinical results cannot be explained by only the third window mechanism associated with bone conduction facilitation toward the lesion side; they need to be interpreted in light of recent data explaining the Tullio phenomenon reported by Iversen et al. (2018) [26] and Rabbitt et al. [27]. ...
The third window syndrome, often associated with the Tullio phenomenon, is currently most often observed in patients with a superior semicircular-canal dehiscence (SCD) but is not specific to this pathology. Clinical and vestibular tests suggestive of this pathology are not always concomitantly observed and have been recently complemented by the skull-vibration-induced nystagmus test, which constitutes a bone-conducted Tullio phenomenon (BCTP). The aim of this work was to collect from the literature the insights given by this bedside test performed with bone-conducted stimulations in SCD. The PRISMA guidelines were used, and 10 publications were included and analyzed. Skull vibration-induced nystagmus (SVIN), as observed in 55 to 100% of SCD patients, usually signals SCD with greater sensitivity than the air-conducted Tullio phenomenon (ACTP) or the Hennebert sign. The SVIN direction when the test is performed on the vertex location at 100 Hz is most often ipsilaterally beating in 82% of cases for the horizontal and torsional components and down-beating for the vertical component. Vertex stimulations are more efficient than mastoid stimulations at 100 Hz but are equivalent at higher frequencies. SVIN efficiency may depend on stimulus location, order, and duration. In SCD, SVIN frequency sensitivity is extended toward high frequencies, with around 400 Hz being optimal. SVIN direction may depend in 25% on stimulus frequency and in 50% on stimulus location. Mastoid stimulations show frequently diverging results following the side of stimulation. An after-nystagmus observed in 25% of cases can be interpreted in light of recent physiological data showing two modes of activation: (1) cycle-by-cycle phase-locked activation of action potentials in SCC afferents with irregular resting discharge; (2) cupula deflection by fluid streaming caused by the travelling waves of fluid displacement initiated by sound or vibration at the point of the dehiscence. The SVIN direction and intensity may result from these two mechanisms’ competition. This instability explains the SVIN variability following stimulus location and frequency observed in some patients but also discrepancies between investigators. SVIN is a recent useful insight among other bedside examination tests for the diagnosis of SCD in clinical practice.
... For instance, in conditions such as Meniere's disease, characterized by endolymphatic hydrops, the abnormal fluid dynamics may lead to alterations in frequency tuning and cVEMP responses (Maheu et al., 2017;Murofushi et al., 2017;Angeli and Goncalves, 2019). Semicircular canal dehiscence may also induce a similar shift in frequency sensitivity (Songer and Rosowski, 2005;Curthoys and Grant, 2015;Iversen et al., 2018). As seen in our companion study investigating noise-induced vestibular deficits in firefighters, as well as studies from preclinical models of noise exposure, cVEMPs can be particularly useful in detecting early and long-term changes and potentially identifying the neural basis for the observed deficits. ...
Introduction
Cervical vestibular evoked myogenic potentials (cVEMPs) provide an objective measure of the integrity of the sacculo-collic pathway leading to their widespread use as a clinical tool in the diagnostic vestibular test battery. Though the application of cVEMPs in preclinical models to assess vestibular function, as performed in relevant clinical populations, remains limited. The present study aimed to establish a rodent model of cVEMP with standardized methods and protocols, examine the neural basis of the responses, and characterize and validate important features for interpretation and assessment of vestibular function.
Methods
We compared air-conducted sound (ACS)-evoked VEMPs from the sternocleidomastoid muscles in naïve Brown Norway rats. A custom setup facilitated repeatable and reliable measurements which were carried out at multiple intensities with ACS between 1 and 16 kHz and over 7 days. The myogenic potentials were identified by the presence of a positive (P1)-negative (N1) waveform at 3–5 ms from the stimulus onset. Threshold, amplitude, and latency were compared with intensity- and frequency-matched responses within and between animals.
Results
cVEMP responses were repeatedly evoked with stimulus intensities between 50–100 dB SPL with excellent test-retest reliability and across multiple measurements over 7 days for all frequencies tested. Suprathreshold, cVEMP responses at 90 dB SPL for 6–10 kHz stimuli demonstrated significantly larger amplitudes ( p < 0.01) and shorter latencies ( p < 0.001) compared to cVEMP responses for 1–4 kHz stimuli. Latency of cVEMP showed sex-dependent variability, but no significant differences in threshold or amplitude between males and females was observed.
Discussion
The results provide a replicable and reliable setup, test protocol, and comprehensive characterization of cVEMP responses in a preclinical model which can be used in future studies to elucidate pathophysiological characteristics of vestibular dysfunctions or test efficacy of therapeutics.
... Electrocochleography (ECoG) is an additional test used to confirm the diagnosis of SSCD. ECoG measures electrical potentials generated by the inner ear in response to auditory stimulation [14]. Among the measurements recorded by ECoG, the ratio of summating potential (SP) to action potential (AP), SP/AP, is of special interest for SSCD evaluation. ...
... Among the measurements recorded by ECoG, the ratio of summating potential (SP) to action potential (AP), SP/AP, is of special interest for SSCD evaluation. SP represents short latency stimulus evoked response, which is partially generated by otolith organs [14]. In contrast, AP reflects long latency response, which is primarily produced by the cochlea [14]. ...
... SP represents short latency stimulus evoked response, which is partially generated by otolith organs [14]. In contrast, AP reflects long latency response, which is primarily produced by the cochlea [14]. In cases of SSCD, energy gradient shifts cause enhanced vestibular system activation, which leads to increased SP output, while simultaneously diminished cochlear stimulation from energy loss results in decreased AP. ...
Purpose of Review
Symptomatic superior semicircular canal dehiscence (SSCD) consists of a wide array of auditory and vestibular symptoms that result from a “third window,” or bony opening, into the superior semicircular canal. This article is aimed at reviewing the pathophysiology, assessment methods, etiologies, treatment options, and correlation with head trauma for this unique entity.
Recent Findings
Common SSCD symptoms include chronic disequilibrium, abnormal eye movements, and auditory disturbances. The pathologic opening into the bony labyrinth by SSCD can lead to irregular fluid flow and pressure gradients, disrupting inner ear function. Most patients with incidentally discovered SSCD on imaging are asymptomatic; a secondary injury event is believed to trigger onset of symptoms via acute intravestibular and/or intracranial pressure changes. Multiple treatment options exist for SSCD, ranging from conservative measures to invasive surgeries.
Summary
Abnormal vestibular and auditory functions are common symptoms of SSCD, which may be precipitated by head trauma. SSCD management should match the severity of symptoms to maximize benefits while minimizing morbidity.
... However, in a few cases, apparent discrepancies concerning the nystagmus direction following the stimulus location (10,13,23) and frequency (direction changing nystagmus) (8, 10) have been described, and rare cases of prolonged after-nystagmus mimicking a "spontaneous nystagmus" after the stimulus offset have been reported (8,10). We suggest that these last results need to be interpreted in light of the flow and pumping mechanism of the Tullio phenomenon discussed below (25). ...
Nystagmus produced in response to air-conducted sound (ACS) stimulation—the Tullio phenomenon—is well known in patients with a semicircular canal (SCC) dehiscence (SCD). Here we consider the evidence that bone-conducted vibration (BCV) is also an effective stimulus for generating the Tullio phenomenon. We relate the clinical evidence based on clinical data extracted from literature to the recent evidence about the physical mechanism by which BCV may cause this nystagmus and the neural evidence confirming the likely mechanism. The hypothetical physical mechanism by which BCV activates SCC afferent neurons in SCD patients is that traveling waves are generated in the endolymph, initiated at the site of the dehiscence. We contend that the nystagmus and symptoms observed after cranial BCV in SCD patients is a variant of Skull Vibration Induced Nystagmus (SVIN) used to identify unilateral vestibular loss (uVL) with the major difference being that in uVL the nystagmus beats away from the affected ear whereas in Tullio to BCV the nystagmus beats usually toward the affected ear with the SCD. We suggest that the cause of this difference is a cycle-by-cycle activation of SCC afferents from the remaining ear, which are not canceled centrally by simultaneous afferent input from the opposite ear, because of its reduced or absent function in uVL. In the Tullio phenomenon, this cycle-by-cycle neural activation is complemented by fluid streaming and thus cupula deflection caused by the repeated compression of each cycle of the stimuli. In this way, the Tullio phenomenon to BCV is a version of skull vibration-induced nystagmus.
... Not all patients with a CT-verified SCD show all these results, and the variability, even within a patient, has been puzzling. In this paper, we show that some of the puzzles can now be resolved thanks to recent modeling, neural recordings, and direct measurement of fluid movement in a semicircular canal after an SCD [14]. Angular acceleration stimulation of a canal causes an increased firing rate in primary vestibular afferents that result in nystagmus in healthy adult animals. ...
... Grieser et al. demonstrated that their model could explain many aspects of the data of Carey et al. and so of the Tullio phenomenon [19]. However, as later noted by Iversen et al., the Grieser model could not explain the frequency-dependent reversal of the neural response to ACS or the spread of activation to other canals without an SCD [14]. ...
... The present paper reviews the available neural data and shows that the apparently inconsistent data are consistent with the Iversen and Rabbitt model and results explained below. These guinea pig results were reported at the 2016 meeting of the Association for Research in Otolaryngology [26], and the following year Rabbitt and Iversen presented a new explanation of the effect of vibration on canal responses after an SCD [27], which was later formalized in detail [14]. They confirmed their model by recording single primary neurons in toadfish after SCD and by direct optical measures of fluid flow in response to BCV. ...
Angular acceleration stimulation of a semicircular canal causes an increased firing rate in primary canal afferent neurons that result in nystagmus in healthy adult animals. However, increased firing rate in canal afferent neurons can also be caused by sound or vibration in patients after a semicircular canal dehiscence, and so these unusual stimuli will also cause nystagmus. The recent data and model by Iversen and Rabbitt show that sound or vibration may increase firing rate either by neural activation locked to the individual cycles of the stimulus or by slow changes in firing rate due to fluid pumping (“acoustic streaming”), which causes cupula deflection. Both mechanisms will act to increase the primary afferent firing rate and so trigger nystagmus. The primary afferent data in guinea pigs indicate that in some situations, these two mechanisms may oppose each other. This review has shown how these three clinical phenomena—skull vibration-induced nystagmus, enhanced vestibular evoked myogenic potentials, and the Tullio phenomenon—have a common tie: they are caused by the new response of semicircular canal afferent neurons to sound and vibration after a semicircular canal dehiscence.
... No significant association was identified between SCDS symptomatology and CA morphology in SCDS ears in the cluster analysis. As the biomechanical basis of both auditory and vestibular manifestations of SCDS overlap, it is poorly understood why some individuals with SCDS lack either auditory or vestibular symptoms [26,27]. Researchers have postulated that the cochlear aqueduct may be an explanation for this phenomenon of variable symptomatology [28,29]. ...
... The impedance of superior canal dehiscence is likely vastly lower than that of the CA under any circumstances, even if the CA is patent, because of the long and thin nature of the CA compared with the extremely short distance across canal dehiscence and the much larger diameter of the typical dehiscence (several mm) vs. CA midpoint diameter (median 0.35 mm, Table 2). Thus, the disruption in the pressure balance between the endolymph and perilymph contributing to abnormal acoustic energy transmission in SCDS are likely governed by parameters of the dehiscence and not by features of the CA [27]. Other works have also explored the contributions to the variable presentations of SCDS from variations in round window compliance, dehiscence size, dehiscence location, and differential central compensatory mechanisms [30][31][32]. ...
The cochlear aqueduct (CA) connects the scala tympani to the subarachnoid space and is thought to assist in pressure regulation of perilymph in normal ears, however, its role and variation in inner ear pathology, such as in superior canal dehiscence syndrome (SCDS), is unknown. This retrospective radiographic investigation compared CA measurements and classification, as measured on flat-panel computerized tomography, among three groups of ears: controls, n = 64; anatomic superior canal dehiscence without symptoms (SCD), n = 28; and SCDS, n = 64. We found that in a multinomial logistic regression adjusted for age, sex, and BMI, an increase in CA length by 1 mm was associated with a lower odds for being in the SCDS group vs. control (Odds ratio 0.760 p = 0.005). Hierarchical clustering of continuous CA measures revealed a cluster with small CAs and a cluster with large CAs. Another multinomial logistic regression adjusted for the aforementioned clinical covariates showed an odds ratio of 2.97 for SCDS in the small CA cluster as compared to the large (p = 0.004). Further, no significant association was observed between SCDS symptomatology—vestibular and/or auditory symptoms—and CA structure in SCDS ears. The findings of this study lend support to the hypothesis that SCDS has a congenital etiology.
... A defect, such as thinning or absence of the bony casing of the semicircular canal, is referred to as a semicircular canal dehiscence (SCD) ( [1,2] see Wackym et al. [3] for a recent extensive review). SCD results in changes in the mechanical operation of the labyrinth [4,5], which causes characteristic symptoms (such as dizziness, autophony, etc.). However, the symptoms are idiosyncratic, and thus, an objective indicator of the SCD is required for diagnosis. ...
As previously reported, a single test measuring oVEMP n10 to 4000 Hz stimuli (bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients, with a sensitivity of 1.0 and specificity of 1.0. This single short screening test has great advantages of speed, minimizing testing time, and the exposure of patients to stimulation. However, a few studies of the 4000 Hz test for SCD have reported sensitivity and specificity values which are slightly less than reported previously. We hypothesized that the rise time of the stimulus is important for detecting the oVEMP n10 to 4000 Hz, similarly to what we had shown for 500 and 750 Hz BCV. We measured oVEMP n10 in 15 patients with CT-verified SCD in response to 4000 Hz ACS or BCV stimuli with rise times of 0, 1, and 2 ms. As a result, increasing the rise time of the stimulus reduced the oVEMP n10 amplitude. This outcome is expected from the physiological evidence of guinea pig primary vestibular afferents, which are activated by sound or vibration. Therefore, for clinical VEMP testing, short rise times are optimal (preferably 0 ms).
... A defect such as thinning or absence of the bony casing of the semicircular canal, is referred to as a semicircular canal dehiscence (SCD) ( [1,2] see Wackym [3]for a recent extensive review ). SCD results in changes in the mechanical operation of the labyrinth [4,5] which causes characteristic symptoms (such as dizziness, autophony etc) but the symptoms are idiosyncratic so an objective indicator of the SCD is required for diagnosis. Clinically this has meant the use of vestibular evoked myogenic potentials (VEMPs) to sound or vibration. ...
We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.
... The fremitus nystagmus displayed by this patient with superior SCC dehiscence is a hallmark of change in the biomechanics of the inner ear. It is thought to be due to the "third window" effect where sound waves, upon entering the inner ear, are shunted directly through the SCC dehiscence, thus erroneously stimulating otolithic organs of the vestibulum and the ampulla of the superior semicircular canal (2,(18)(19)(20). ...
Superior canal dehiscence syndrome (SCDS) is a structural bony defect of the roof of the superior semi-circular canal into the middle cranial fossa and is responsible for the creation of a third window, which alters the dynamics of the inner ear. During humming, vibratory waves entering the vestibulum and cochlea are re-routed through the dehiscence, leading to stimulation of the otolithic and ampullary vestibular organs. This is responsible for the torsional-vertical nystagmus known as “fremitus nystagmus”. In this case report, we video-document a rare case of fremitus nystagmus and its resolution after plugging of the superior semi-circular canal.
... Among them, acoustic activation of the vestibular system has been widely adopted in clinics to test otolith function. Acoustic activation of vestibular organs was first observed in pigeons with fenestrated bony canals (Tullio 1929), sensitivity arising from introduction of a compliant window in the bony labyrinth (Minor et al. 1998;Iversen et al. 2018, Greiser et al. 2016. But, sensitivity to acoustic sound and bone conducted vibrations is not restricted to pathological conditions. ...
... Latencies include the propagation delay as the sound reaches the organ "t 1 ," plus the phase-locking delay "t 2 " accounting for the specific time during the stimulus when the neuron fires. The total delay is t d = t 1 + k*t 2 , where k is the number of cycles skipped between phase locked spikes ("k" is also called the winding ratio, Iversen et al. 2017Iversen et al. , 2018. Shorter latencies in SO and HC neurons (Fig. 10F) suggest the propagation delay is shortest for sounds reaching these organs, while the long latency for PC afferents suggests a much longer propagation delay, as perhaps expected if excitation arises from a wave traveling along the membranous labyrinth to the PC ampulla (Rabbitt et al. 1995(Rabbitt et al. , 2016Iversen and Rabbitt 2017). ...
... Biomechanics is also important because it determines how sound causes mechanical vibration of the vestibular organs and displacement of vestibular hair cell bundles. The fact that sound sensitivity of the semicircular canals increases dramatically following fenestration of the bony labyrinth is direct evidence of the important role played by mechanics in auditory frequency sensitivity of vestibular afferent neurons (Tullio 1929;Carey et al. 2004;Curthoys et al. 2019;Iversen et al. 2018). Finite element (FE) modeling of the rat inner ear was used to examine how air conducted sound might have activated the vestibular organs in the present experiments. ...
