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Superior Canal Dehiscence
Mechanisms of Pressure Sensitivity in a Chinchilla Model
Timo P. Hirvonen, MD;
John P. Carey, MD;
Cindy J. Liang;
Lloyd B. Minor, MD
Arch Otolaryngol Head Neck Surg. 2001;127:1331-1336.
ABSTRACT
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Background Patients with superior canal dehiscence syndrome may experience vertigo
and nystagmus when pressure changes occur in the external auditory canal,
the middle ear, or the intracranial space. The cause is a defect in the bone
of the superior canal.
Objective To study the mechanisms of pressure sensitivity of the labyrinth in
superior canal dehiscence syndrome and its surgical repair in a chinchilla
model.
Methods We investigated the changes in firing rates of vestibular nerve afferents
in the chinchilla in response to changes in external auditory canal pressure
before and after fenestration of the superior canal, and after repair of the
fenestra.
Results Before superior canal fenestration, external auditory canal pressure
changes caused no responses in horizontal canal or otolith afferents, and
only 1 of 9 superior canal afferents responded to pressure. After fenestration,
all superior canal afferents were excited by positive pressure and inhibited
by negative pressure. Half of 18 otolith and most (21 of 33) horizontal canal
afferents were unaffected by pressure. The superior canal afferents had higher
pressure gain than the horizontal canal afferents (P
= .03). Pressure responses could be abolished only by applying a rigid seal
to the fenestra.
Conclusions Fenestration of the superior canal rendered all superior canal afferents
sensitive to pressure, whereas less than half of the other afferents became
pressure sensitive. The direction of the superior canal afferent responses
agreed with the predictions of our model of endolymph flow within the superior
canal. A rigid seal applied to the fenestra abolished pressure sensitivity
while maintaining physiologic rotational sensitivity.
INTRODUCTION
THE VESTIBULAR labyrinth can become sound (Tullio phenomenon) or pressure
(Hennebert sign) sensitive in pathological states affecting the integrity
of the labyrinthine bone.1-2 Recently,
Minor and colleagues3 identified the superior
canal dehiscence syndrome, in which the bone overlying the superior semicircular
canal is deficient. Carey and colleagues4 described
histological correlates of the syndrome in a temporal bone survey. The dehiscence
creates an additional third mobile window in the labyrinth, which may cause
episodic vertigo and nystagmus in response to intense sound or changes in
external ear canal, intracranial, or middle ear pressure.5
The axis of evoked nystagmus in the superior canal dehiscence syndrome
aligns with the plane of the affected superior canal, indicating that the
response originates mainly from that canal.6-7
Accordingly, Yagi et al8 found that patients
with a labyrinthine fistula in a single semicircular canal showed compensatory
eye movements within the plane of that canal. Cremer et al9
studied a patient with a postoperative fistula in the posterior semicircular
canal, and found that pressure changes in the external ear canal induced nystagmus
in the plane of the affected posterior canal.
The proposed mechanism for the nystagmus evoked by pressure changes
in the external auditory canal in patients with superior canal dehiscence
syndrome is motion of the ampulla of the superior canal related to the increased
compliance of the endolymphatic system created by the dehiscence. In this
hypothesis (Figure 1), positive
pressure in the external ear canal would move the tympanic membrane and stapes
inward. Normally, outward movement of the round window membrane would relieve
the resulting pressure gradient. The presence of a third mobile window allows
the membranous canal to bulge upward through the overlying defect in the bone.
The flow of endolymph would deflect the superior canal cupula away from the
utricle, which would excite hair cells and afferents of the superior canal
crista. Conversely, negative pressure in the external ear canal would lead
to outward movement of the tympanic membrane and the stapes. This would cause
utriculopetal endolymph movement in the superior canal, and subsequently decrease
the firing rate of superior canal afferents. According to the first law of
Ewald,10 stimulation of each canal produces
eye rotation in the plane of the stimulated canal. Correspondingly, we have
observed a nystagmus that is characteristic for excitation of the affected
superior canal during the Valsalva maneuver against pinched nostrils: mixed
vertical-torsional nystagmus, with the slow phase components directed upward
and away from the affected ear.6 During the
Valsalva maneuver against a closed glottis, the flow is reversed. The maneuver
increases intracranial pressure, distending the dura mater into the dehiscence
and displacing the canal fluids and the cupula toward the utricle. This is
an inhibitory stimulus, and we have observed a nystagmus in the same plane
but in a direction opposite to that previously described. Thus, the clinical
data support the hypothesis that these pressure changes mediate vertigo and
nystagmus through superior canal afferents.
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Figure 1. Hypothesis for the mechanism of
the superior canal dehiscence syndrome. A dehiscent bone in the superior canal
acts as a third mobile window in the labyrinth. Positive pressure (arrows)
moves the tympanic membrane and ossicular chain inward and causes utriculofugal
endolymph flow in the superior canal. This causes excitation of the superior
canal afferents.
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To our knowledge, these hypothesized changes in the physiologic mechanisms
created by the dehiscence have not been previously tested in an animal model.
Moreover, the extent to which vestibular end-organs other than the superior
canal are stimulated by pressure changes in patients with superior canal dehiscence
syndrome is also unknown. Finally, surgical repair techniques have not been
studied in an experimental model. We recorded responses of vestibular nerve
afferents in chinchillas in response to changes in external ear canal pressure
before and after fenestration of the superior canal, and again after repair
of the fenestra. We found that afferent responses to pressure followed the
predictions of the endolymph flow model. Superior canal afferents always responded
to external ear canal pressure changes after fenestration, and so did 36%
of horizontal canal afferents and half of otolith afferents. Afferent responses
to pressure could be abolished by rigidly sealing the bony defect, but the
canal did not need to be plugged in such a way as to preclude physiologic
sensitivity to head movements.
SUBJECTS AND METHODS
SUBJECTS AND AFFERENT RECORDINGS
Institutional guidelines of The Johns Hopkins University School of Medicine,
Baltimore, Md, regarding animal experimentation were followed. Nine adult
chinchillas of either sex were anesthetized with intraperitoneal 5,5-diallylbarbituric
acid (Dial; Sigma Chemical Co, St Louis, Mo), 40 mg/kg. A tracheotomy was
performed to maintain a patent airway, and animals were kept at a core body
temperature with a servocontrolled heating pad (model 40-90-8B; Frederick
Haer & Company, Bowdoinham, Me). After placement in a stereotactic holder,
the superior bulla was opened. The extracranial facial and superior vestibular
nerves were identified, and the bone overlying the eighth nerve was removed.
Extracellular afferent potentials were recorded with glass microelectrodes
(model M1B100F-4; World Precision Instruments, Inc, Sarasota, Fla) filled
with 3N sodium chloride and with impedances of 10 to 30 M . Microelectrodes
were mounted on a 3-dimensional microdrive (model MO-22; Narishige Scientific
Instrument Lab, Tokyo, Japan) and directed into the eighth nerve. Extra-axonal
activity was amplified 500 to 5000 times (model 2400A; Dagan Corporation,
Minneapolis, Minn), bandpass filtered from 100 Hz to 3 kHz, digitized at 5
kHz, and stored. The stereotactic apparatus was mounted on a gimballed structure
that allowed any of the semicircular canals to be tilted into the earth-horizontal
plane for rotational testing. The structure was mounted on a servocontrolled
rate table (model 130-80/ACT2000; Acutronic USA, Inc, Pittsburgh, Pa) programmed
to provide various earth-horizontal rotations.
Once an afferent was isolated, each unit was sampled for 10 to 20 seconds
at rest before stimulation. Then the structure was tilted to determine if
the afferent was tilt sensitive, ie, an otolith afferent, and rotated in the
various canal planes to determine if it was a canal afferent, and, if so,
which canal it innervated.11 Normalized coefficients
of variation (CVs) were computed to classify afferents as regular (CV<0.1),
intermediate (0.1 CV0.2), or irregular (CV>0.2). The pressure sensitivity
was calculated from neuronal responses measured in spikes per second (sp ·
s-1) with regard to pressure change, measured in millimeters
of mercury (mm Hg). The rotational sensitivity was measured as change in firing
rate in spikes per second per rotational velocity in degrees per second (deg ·
s-1).
FENESTRATION OF THE SUPERIOR CANAL
A 0.3-mm fenestra was made with a footplate perforator at the uppermost
portion of the superior canal, where it protruded into the mastoid bulla.
After recording afferent responses with the fenestra open, it was covered
with muscle alone or in combination with a rigid layer of cyanoacrylate, and
the stimuli were repeated.
PRESSURE STIMULATION
Pressure stimuli were generated by an elastic bulb or an air-filled
syringe attached via inelastic tubing to the sealed external ear canal. Pressure
was monitored in centimeters of water based on fluctuations of the fluid column
in an attached burette in 5 animals or by a digital pressure transducer (model
60-3002; Harvard Apparatus, Inc, Holliston, Mass) in another 4. Couplings
between the tubing and the hollow ear bar and between the ear bar and the
external ear canal were sealed with vacuum grease to maintain pressure gradients.
The stimuli used were sinusoidal or pulsatile negative or positive pressure
changes in the external ear canal (mean absolute change, 13 mm Hg; range, -50
to 60 mm Hg).
RESULTS
Pressure responses were recorded from 20 afferents before the fenestration
and from 60 afferents after the fenestration. During the measurements, physiologic
responses of the afferents to linear or angular acceleration remained intact
despite fenestration or the repair technique.
BEFORE FENESTRATION
Responses to pressure stimuli were rare before superior canal fenestration.
Only 1 of 9 superior canal afferents modified its firing rate in response
to pressure stimuli. Two of 9 superior canal afferents showed delayed responses,
in which the firing rate decreased continuously after a few seconds of delay
during prolonged stimulation, and then recovered slowly to the baseline. The
remaining 6 superior canal, 5 horizontal canal, and 6 otolith afferents did
not respond to pressure stimuli before the fenestration.
AFTER FENESTRATION
Changes in the afferent discharge rate during sinusoidal or pulsatile
pressure stimuli were prominent after fenestration (Figure 2 and Figure 3).
Each of the 9 superior canal afferents responded to pressure changes after
fenestration. Pressure-induced responses were noted in 12 (36%) of the 33
horizontal canal afferents and in 9 (50%) of the 18 otolith afferents following
fenestration. Responses to positive pressure were excitatory, and responses
to negative pressure were inhibitory.
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Figure 2. The external auditory canal (EAC)
pressure, the firing rate, and the nerve potential were recorded for a horizontal
canal afferent during sinusoidal pressure stimuli after the fenestration of
the superior canal.
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Figure 3. Changes in the external auditory
canal (EAC) pressure and the firing rate of a superior canal afferent in response
to negative (A) and positive (B) pressure pulses after fenestration of the
canal.
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Pressure sensitivity, defined as the change in firing rate divided by
the change in pressure, was higher for superior canal than for horizontal
canal afferents (mean ± SD, 2.8 ± 1.9 sp · s-1· mm Hg-1 [n = 8] vs 1.3 ± 1.0 sp ·
s-1· mm Hg-1 [n = 5]; P = .03, 1-tailed t test). The mean response
was larger for negative pressure than for positive pressure in regular and
intermediate afferents (mean ± SD, 1.8 ± 1.3 vs 0.8 ±
0.7 sp · s-1· mm Hg-1; P = .005, 1-tailed t test). For
2 irregular afferents (1 superior canal and 1 otolith afferent), pressure
sensitivities could not be compared because of cutoff of the response during
negative pressure. For only one afferent, an irregularly discharging otolith
afferent, the positive and negative stimuli were excitatory.
Pressure responses varied according to afferent discharge regularity.
After the fenestration, 16 (48%) of the 33 regular, 3 (60%) of the 5 intermediate,
and 11 (61%) of the 18 irregular afferents responded to pressure changes.
The magnitude of the pressure sensitivity correlated (r = 0.55, P = .03, 1-way analysis of variance)
with an increase in the CV.
AFTER THE REPAIR OF THE FENESTRA
A loose seal over the fenestra made with muscle placed over the dehiscence
led to a reduction in the pressure responses in 1 superior canal afferent,
but it did not have a significant effect in 3 other afferents. In contrast,
a rigid seal over the fenestra, established by applying cyanoacrylate to the
muscle and allowing it to cure, abolished the pathological pressure effects
(Figure 4). In 3 of these 4 afferents,
it was possible to extract the rigid seal while still recording from the afferent.
Responses of these afferents to pressure after removal of the seal were similar
to those recorded before the repair of the fenestra. The responses to 1-Hz
rotations were unchanged after application of the seal to the fenestra compared
with before application in the 2 afferents that were tested. For the superior
canal afferent, the rotational sensitivity was 0.16 sp · s-1/deg · s-1 before and after the seal was applied.
For the horizontal canal afferent, the rotational sensitivity was 0.18 sp ·
s-1/deg · s-1 before and 0.19 sp ·
s-1/deg · s-1 after the seal was
applied.
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Figure 4. A superior canal afferent responding
to sinusoidal external auditory canal (EAC) pressure while the superior canal
fenestra is open (A) or sealed with muscle and a rigid layer of cyanoacrylate
(B).
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COMMENT
We studied the responses of vestibular nerve afferents to pressure changes
applied in the external auditory canal of chinchillas before and after fenestration
of the superior canal. The strongest and most frequent responses were found
in superior canal afferents, which all responded to pressure stimulation after
the fenestration. Positive pressure in the external ear canal uniformly caused
excitation in superior canal afferents, which agrees with our model of utriculofugal
endolymph movement in the superior canal. Accordingly, negative pressure caused
inhibition, consistent with utriculopetal flow of endolymph within the superior
canal.
After the fenestration, some horizontal canal afferents also modified
their firing rates in response to pressure stimuli, although the change in
firing rate induced by a comparable pressure stimulus was greater for superior
than for horizontal canal afferents. The direction of the pressure stimulus
and the response of the afferent were the same for horizontal as for superior
canal afferents: positive pressure resulted in excitation, and negative pressure
resulted in inhibition. There are at least 2 possible mechanisms for these
pressure-induced responses in horizontal canal afferents after fenestration.
First, the increased compliance in the membranous labyrinth established by
the dehiscence may have resulted in ampullopetal deflection of the horizontal
canal ampulla in response to positive pressure and in ampullofugal deflection
in response to negative pressure. Alternatively, dilational pressure might
act across the ampulla of the horizontal canal in the presence of the fistula
in the superior canal. Afferent responses due to dilational pressure have
been shown to occur in toadfish for horizontal canal and utricular afferents.12 Rabbitt et al12 suggest
that dilational pressure may be as important as endolymph flow in the macromechanical
function of the semicircular canal. However, dilational pressure sensitivity
presents a problem for terrestrial vertebrates, in whom atmospheric pressure
changes could be rapidly conveyed to the perilymph compartment via the tympanic
membrane and ossicular chain. If gradients in pressure were created between
endolymph and perilymph, the ampulla would dilate or contract, modulating
canal afferent firing. Presumably, the bony semicircular canal functions to
create a closed system in which pressure is equalized between endolymph and
perilymph. The presence of a fenestra, even remote from the horizontal canal,
could, therefore, produce afferent responses to changes in the external auditory
canal pressure.
After fenestration of the superior canal, the inhibitory responses caused
by negative pressure were generally larger than the excitatory responses evoked
by positive pressure. The direction of responses in other types of vestibular
afferents was similar; only 1 of 18 otolith afferents was excited by both
stimuli. Several clinical reports9, 13-15
have also found that negative pressure in the external ear canal stimulates
the labyrinth more than positive pressure. Physiologically, the excitatory
response to acceleration in vestibular afferents is larger than the inhibitory
response.10 There are at least 2 potential
reasons for the difference in the magnitude of the excitatory and inhibitory
responses to pressure and rotational stimuli. First, negative external ear
canal pressure in our experimental preparation could be more reliably maintained
than could positive pressure. Negative pressures tended to coapt the soft
tissues and vacuum grease and maintain the sealed space of the external ear
canal, whereas positive pressures tended to push open these interfaces. Second,
tympanic membrane displacement to equal pressure stimuli has also been shown
to be significantly larger for outward (caused by negative pressure) than
for inward (caused by positive pressure) motion. This asymmetry may be further
reinforced in the level of malleus movement.16
Wall and Casselbrant17 studied perilymphatic
fistulas in a chinchilla model. They found eye movement responses in 9 (69%)
of 13 ears with an experimental fistula in the bony labyrinth, using external
ear canal pressure levels of ±250 mm H2O. They observed
horizontal and vertical eye movements, but they did not emphasize if the site
of the fistula and the eye movements recorded were correlated. The present
study shows that afferents innervating the superior canal are most sensitive
to pressure stimuli after fenestration of that canal. This is consistent with
our clinical finding that the plane of the eye movements of patients with
superior canal dehiscence syndrome aligns with that of the affected canal.6
Before fenestration, only 1 of the 20 afferents that were tested with
pressure stimuli showed a change in firing rate during the application of
pressure. In contrast, 30 of the 60 afferents recorded after fenestration
had a pressure-induced response. Irregularly discharging afferents were more
sensitive to these pressure stimuli than were regularly discharging afferents.
The findings are consistent with the notion that the dehiscence creates a
third mobile window into the labyrinth, rendering it more sensitive to pressure
stimuli.
Irregularly discharging afferents were more sensitive to pressure than
were regularly discharging afferents. A similar difference in sensitivity
to rotation is noted for high-gain irregularly discharging afferents compared
with regularly discharging afferents.18 The
proportion of units sensitive to pressure was also highest in the group of
irregular afferents.
The fenestra made in the superior canal in our experiments was 0.3 mm
in diameter and was open to air, whereas the diameter of dehiscence in patients
with superior canal dehiscence syndrome is several millimeters and opens into
the middle cranial fossa. Most afferents in our study modulated their firing
rate after fenestration, with external ear canal pressure changes of only
a few millimeters of mercury. These pressure levels correspond to those delivered
through a pneumatic otoscope during the clinical fistula test, but a direct
comparison with pressure levels applied through Valsalva maneuvers is difficult.
Thus, the level of critical pressure producing clinical symptoms and signs
in patients with superior canal dehiscence syndrome remains to be studied.
An ideal repair of a canal dehiscence would close the defect so as to
eliminate these pathologic responses, but maintain the patency of the lumen
of the canal, allowing physiologic endolymph flow and the transduction of
information about head movements. We attempted such a repair by sealing the
fenestra with muscle without obliterating the lumen of the canal. Sealing
with soft tissue alone failed to abolish pressure responses. Instead, rigid
repair of the superior canal fenestra abolished pathologic vestibular afferent
responses to pressure, but still preserved physiologic responses to head rotation.
Thus, a rigid seal appears to be important for immediate elimination of the
pressure sensitivity of the labyrinth in patients with superior canal dehiscence
syndrome. This has important implications for surgeons planning to repair
a dehiscent canal. A rigid closure, as might be achieved with bone or bone
cement, would seem to be required for elimination of symptoms. The availability
of calcium phosphate bone cements to close such defects is appealing, but
the potential ototoxicity of such materials in contact with perilymph has
not been determined. It is also possible that soft tissue repair alone would
eventually lead to scarring and rigidity of the seal. Therefore, a further
evaluation of these 2 techniques will need to consider the long-term effects
of each.
CONCLUSIONS
The findings in our animal model confirm that the pressure responses
in superior canal dehiscence syndrome originate mainly from superior canal
afferents. Fenestration of the superior canal rendered all superior canal
afferents sensitive to pressure, whereas less than half of the other afferents
became pressure sensitive. The direction of the superior canal afferent responses
agrees with our model of endolymph flow within the superior canal. The surgical
repair of superior canal dehiscence syndrome should aim to rigidly seal the
superior canal defect, which immediately abolished the pressure sensitivity
while maintaining the physiologic rotational sensitivity in our experimental
model.
AUTHOR INFORMATION
Accepted for publication July 11, 2001.
This study was supported by research grants from the Finnish Academy
(grant 48029), the Finnish Medical Association, and the Finnish Research Foundation
of Otology, Helsinki, Finland (Dr Hirvonen); grant R01 DC02390 from the National
Institute of Deafness and Other Communication Disorders, Bethesda, Md; and
the American Hearing Research Foundation, Chicago, Ill.
Presented as a poster at the 22nd Midwinter Meeting of the Association
for Research in Otolaryngology, St Petersburg, Fla, February 7, 2001.
We thank Brian Dunham, MD, for preparing Figure 1.
Corresponding author and reprints: John P. Carey, MD, Department
of Otolaryngology–Head & Neck Surgery, The Johns Hopkins Outpatient
Center, 601 N Caroline St, Baltimore, MD 21287-0910 (e-mail: jcarey{at}jhmi.edu).
From the Departments of Otolaryngology–Head & Neck Surgery
(Drs Hirvonen, Carey, and Minor) and Biomedical Engineering (Ms Liang and
Dr Minor), The Johns Hopkins University School of Medicine, Baltimore, Md;
and the Department of Otolaryngology–Head & Neck Surgery, Helsinki
University Central Hospital, Helsinki, Finland (Dr Hirvonen).
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