Bilateral vestibulopathy: Diagnostic criteria

Consensus document of the Classification Committee of the Bárány Society

Michael Strupp1, Ji-Soo Kim2, Toshihisa Murofushi3, Dominik Straumann4, Joanna C. Jen5,
Sally M. Rosengren6, Charles C. Della Santina7, Herman Kingma8
1
Dept. of Neurology and German Center for Vertigo, University Hospital Munich, Germany
2
Dept. of Neurology, Seoul National University College of Medicine, Seoul National
University Bundang Hospital, Seoul, South Korea
3
Dept. of Otolaryngology, Teikyo University School of Medicine, Mizonokuchi Hospital
Kawasaki, Japan
4
Dept. of Neurology, University Hospital Zurich, University of Zurich, Switzerland
5
Depts. of Neurology and Neurobiology, University of California, Los Angeles, USA
6
Dept. of Neurology, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia
7
Dept. of Otolaryngology-Head and Neck Surgery, Johns-Hopkins University, Baltimore, USA
8
Dept. of Otolaryngology, Maastricht, The Netherlands/Department of Medical Physics, Tomsk
Research State University, Russian Federation

Corresponding author
Michael Strupp, MD, FANA, FEAN,  Dept. of Neurology and German Center for Vertigo,
Munich, Germany, University Hospital Munich, Campus Grosshadern, Marchioninistrasse 15,
81377 Munich, Germany
Phone: ++49 89 44007 3678
Fax: ++49 89 44007 6673
E-mail: [email protected]
Keywords: bilateral vestibulopathy, vertigo, dizziness, disequilibrium, vestibular, diagnostic
criteria, Bárány Society
Abstract
This paper describes the diagnostic criteria for bilateral vestibulopathy (BVP) by the
Classification Committee of the Bárány Society. The diagnosis of BVP is based on the patient
history, bedside examination and laboratory evaluation. Bilateral vestibulopathy is a chronic
vestibular syndrome which is characterized by postural imbalance and/or unsteadiness of gait,
which worsen in darkness and/or on uneven ground, as well as, in a minority of patients, by
head or body movement-induced blurred vision or oscillopsia. There are typically no symptoms
while sitting or lying down under static conditions.
The diagnosis of BVP requires bilaterally significantly impaired or absent function of
the vestibulo-ocular reflex (VOR). This can be diagnosed for the high frequency range of the
angular VOR by the head impulse test (HIT), the video-HIT (vHIT) and the scleral coil
technique and for the low frequency range by caloric testing.
For the diagnosis of BVP, the horizontal angular VOR gain on both sides should be <
0.6 (angular velocity 150-300°/s) and/or the sum of the maximal peak velocities of the slow
phase caloric-induced nystagmus for stimulation with warm and cold water on each side < 6°/s
and/or the horizontal angular VOR gain < 0.1 upon sinusoidal stimulation on a rotatory chair
(0.1 Hz, Vmax = 50°/sec). For the diagnosis of probable BVP the above mentioned symptoms
and a bilaterally pathological bedside HIT are required
Complementary tests that may be used but are currently not included in the definition
are: a) dynamic visual acuity (a decrease of ≥ 0.2 logMAR is pathological); b) Romberg
(indicating a sensory deficit of the vestibular or somatosensory system and therefore not
specific); and c) cervical and ocular vestibular-evoked myogenic potentials (c/oVEMP) for
otolith function.
At present the scientific basis for further subdivisions into subtypes of BVP is not
sufficient to put forward reliable or clinically meaningful definitions. Depending on the affected
anatomical structure and frequency range, different subtypes may be better identified in the
future: impaired canal function in the low- or high-frequency VOR range only and/or impaired
otolith function only; the latter is evidently very rare.
Bilateral vestibulopathy is a clinical syndrome and, if known, the etiology (e.g., due to
ototoxicity, bilateral Menière’s disease, bilateral vestibular schwannoma) should be added to
the diagnosis. Synonyms include bilateral vestibular failure, deficiency, areflexia, hypofunction
and loss.
Introduction
The Bárány Society representing the international community of basic scientists,
otolaryngologists and neurologists committed to vestibular research mandated a Classification
Committee for an International Classification of Vestibular Disorders (ICVD). Individual
disorders are defined by classification panels, which include otolaryngologists and neurologists
from at least three continents. The ICVD has already published a consensus on the definitions
of vestibular symptoms (1), vestibular migraine (2), Menière’s disease (3), benign paroxysmal
positional vertigo (4) and vestibular paroxysmia (5).
In 1882 W. James reported on the “sense of dizziness in deaf-mutes” (6). In 1907 R.
Bárány described a bilaterally reduced caloric response also in deaf-mutes (7). In 1941, Dandy
described oscillopsia and postural instability exacerbated by visual deprivation in subjects on
whom he had performed bilateral vestibular neurectomy in an effort to treat Menière’s disease
(8). Movement-induced oscillopsia was identified as a frequent additional symptom in 1965
(9); for additional references related to the history of bilateral vestibulopathy (BVP) see (10).
In 1989 this syndrome was more precisely defined in patients presenting with imbalance and
oscillopsia, worsening in darkness, without hearing loss or other neurological symptoms and
was called “idiopathic bilateral vestibulopathy” (11). In 2005 it was demonstrated that BVP
also leads to impaired spatial memory and hippocampal atrophy (12), later confirmed by other
MRI studies (13;14). In 2009 a subtype with bilateral absence of vestibular evoked myogenic
potentials (VEMP) in the presence of normal caloric response was described (15). An
association between BVP and impaired cerebellar dysfunction has been described in many
publications (16-20) with a particular syndrome “Cerebellar Ataxia, Neuropathy and Vestibular
Areflexia” (CANVAS), a gangliopathy with cerebellar atrophy, described in 2011 (21).

Based on the literature on this topic there is evident agreement on

a. the leading symptoms: postural imbalance and unsteadiness of gait, which both worsen in
darkness and on uneven ground; head or body movement induced oscillopsia in some
patients, in particular during walking, which engenders head movements with high
frequency spectral content, particularly during each heel strike (15;17;19;22-26);
b. the bedside diagnosis of a bilaterally deficient angular vestibulo-ocular reflex (aVOR) by
the head impulse test (HIT) (27). It has its limitations (28): only VOR deficits with a gain
<0.4 can be reliably detected by the bedside HIT (29) and in cerebellar disorders its
interpretation is often difficult (30);
c. the use of caloric irrigation and/or the video-HIT to diagnose a peripheral vestibular deficit
(31-35). Rotational chair testing is nowadays less often applied;
d. dynamic visual acuity as a complementary test (36);
e. the etiology of BVP: often it remains unclear. Frequent known causes are ototoxic drugs,
bilateral Menière’s disease, meningitis, genetic mutations and there is an association with
cerebellar disorders (17;19).

Issues that have to be addressed and if possible defined in future updates are: First, what are
pathological values for the caloric response and the gain of the angular VOR (aVOR) to qualify
for the diagnosis of BVP with a reasonable specificity and sensitivity? Second, what is the role
of testing the vertical canals with the HIT (37) and testing the otolith organs with cervical and
ocular VEMPs (cVEMP/oVEMP) for BVP? Third, are there different subtypes of BVP in terms
of reduced function of the low and high frequency aVOR (35), different canals (37) and/or of
otolith function?
Methods
The present work forms part of an ongoing multi-year project to develop an ICVD, which uses
a structured process for developing international consensus definitions for vestibular symptoms,
syndromes, disorders, and diseases. This process, overseen by the Classification Committee of
the Bárány Society (CCBS), is based on expert, multi-disciplinary committees with
international representation developing diagnostic criteria for subsequent comment and
refinement prior to publication. These criteria are built on a critical appraisal of current best
scientific evidence. All definitions are supported by notes, comments, and written discussion
according to a template established by the CCBS for ICVD. The criteria for BVP were
developed iteratively over a three-year period (2014-2017) through discussion, presentation,
and refinement. Special care was taken to ensure that the criteria are specific and practical and
can be applied in every country all over the world. This is particularly true for the use of certain
laboratory examinations not available everywhere.
Diagnostic criteria for bilateral vestibulopathy
A. Chronic vestibular syndrome with at least three of the following symptoms
1. Postural imbalance1
2. Unsteadiness of gait1
3. Movement-induced blurred vision or oscillopsia during walking or quick head/body
movements2
4. Worsening of postural imbalance or unsteadiness of gait in darkness and/or on uneven
ground3
B. No symptoms while sitting or lying down under static conditions4
C. Bilaterally reduced or absent angular VOR function documented by
- bilaterally pathological horizontal angular VOR gain < 0.6, measured by the video-HIT5
or scleral-coil technique and/or
- reduced caloric response6 (sum of bithermal max. peak SPV on each side < 6°/sec7)
and/or
- reduced horizontal angular VOR gain < 0.1 upon sinusoidal stimulation on a rotatory
chair (0.1 Hz, Vmax = 50°/sec).
D. Not better accounted for by another disease

Diagnostic criteria for probable bilateral vestibulopathy

A. Chronic vestibular syndrome with at least two of the following symptoms
1. Postural imbalance1
2. Unsteadiness of gait1
3. Movement-induced blurred vision or oscillopsia during walking or quick head/body
movements2
4. Worsening of postural imbalance or unsteadiness of gait in darkness and/or on uneven
ground3
B. No symptoms while sitting or lying down under static conditions4
C. Bilaterally pathological horizontal bedside head impulse test8
D. Not better accounted for by another disease
Notes:
1. These symptoms in BVP are caused by the sensory vestibular deficit leading to impaired
vestibulo-spinal reflexes leading to higher body sway and broad-based gait.
2. About 30 to 40% of the patients report oscillopsia during active body movements such as
walking and/or passive head movements (e.g., travelling in a vehicle) (19;23;38); in rare
cases oscillopsia can even occur in time with the heartbeat. Oscillopsia is caused by head
movement induced retinal slip due to the VOR deficit for which other systems cannot fully
compensate (26). It leads to a reduction of dynamic visual acuity (see below). In contrast,
for slow and low frequency head movements the smooth pursuit system can stabilize
fixation when a visible target is present.
3. When explicitly asked, many patients with BVP report a worsening of postural imbalance
and unsteadiness of gait in darkness and on uneven ground (19;23) because they depend
more on visual and somatosensory control. This is also associated with a higher risk of falls
in darkness (39). Imbalance is even worse if there is an additional sensory polyneuropathy
(40).
4. Typically there are no symptoms when sitting or lying down under static conditions because
subjects do not rely very much on the vestibular system under these circumstances. Some
patients may report on oscillopsia while sitting induced, for instance, by heart beats or
chewing.
5. Video-HIT: It is possible to quantify the aVOR function by a video-oculography system
(video-HIT) that measures head and eye velocity during passive head rotation (150°/s –
300°/s), similar to the scleral-coil technique which can, of course, also be used. Thereby,
the gain of the aVOR can be determined and catch-up saccades can be detected even if they
are of short latency and already occur during the head impulses (covert catch-up saccades)
(31;32;41). Horizontal VOR velocity gain is the ratio of angular eye velocity to angular
head velocity. It can also be measured as the ratio of the area under curve (AUC) of the
angular eye velocity divided by the AUC of angular head velocity. According to a study on
60 healthy subjects (42), the lower limit of the normal horizontal VOR velocity gain (2SD
below mean) is 0.79 at 80 ms and 0.75 at 60 ms. The lowest and highest values of the normal
horizontal VOR velocity gain are 0.76 and 1.18 at 80 ms and 0.65 and 1.17 at 60 ms. There
is a decline of normal horizontal VOR velocity gain at 80 ms with aging by 0.012 per decade
with increasing age (95% CI 0.001 to 0.022; p = 0.028). Normal horizontal VOR velocity
gain at 60 ms also declines with aging. Horizontal VOR velocity gain was found to decline
by 0.017 per decade with increasing age (95% CI 0.006 – 0.029; p = 0.005). Taking this into
account, the authors agreed on a pathological gain of the video-HIT < 0.6. The specific role
of testing the VOR gain of the vertical canals for the diagnosis of BVP has to be further
evaluated. According to a video-HIT study of all three semicircular canals in patients with
BVP, the anterior canals seem less often impaired in aminoglycoside vestibulotoxicity,
Menière’s disease and BVP of unknown etiology (37).
6. Caloric testing: the low frequency aVOR can be tested by bithermal caloric stimulation
during 30 seconds with a minimum of 200 ml warm (44°C) and cold (30°C) water and
measurement of the peak SPV of caloric induced nystagmus at the culmination phase. The
lower threshold applied for the mean SPV is generally lower for the cold than for the warm
irrigation. As the response to the cold and warm irrigation can be affected by a spontaneous
nystagmus, most laboratories use the sum of absolute values of nystagmus peak SPV to
both responses of each ear as a criterion for excitability. In our experience, the lower limit
of the normative data applied for the sum of the mean SPV upon cold (30°C) and warm
(44°C) irrigation per ear varies among laboratories from 20-25 O/sec (personal
communication/discussions during conferences and courses of HK). A sum of both
responses per ear < 6 O/sec can therefore be considered a safe criterion to point to BVP. The
absence of a VOR to caloric irrigation with ice water also points to BVP. To test for
 convection-dependent responses to ice water independent of the direct inhibitory effect ice
water cooling has on vestibular nerve activity, the subject initially undergoes ice water
irrigation while supine with the head of the bed elevated 20 deg. Once the nystagmus starts,
the examiner assists the subject in quickly flexing at the hips, pitching the torso and head
forward and down so that the nose points toward the floor. If the nystagmus initially
observed was due to convection of endolymph, then its direction should reverse; if it does,
then at least some vestibular hair cell function is present. If the nystagmus does not reserve,
then the initial response can be attributed mainly to direct inhibition of the vestibular nerve,
and one can conclude that there is little or no vestibular hair cell function (if central causes
of failed vestibular reflexes, including sedating medications, have been excluded).
7. Rotational tests: the low to middle frequency aVOR can be tested using a rotatory chair.
The rotatory chair tests are especially useful when the video-HIT or caloric tests cannot be
executed or are not tolerated, or appropriate instruction is difficult (e.g. cervical limitations,
anxiety, young infants). Although many stimulus profiles are used (e.g., sinusoidal
stimulation or velocity steps), a significant disadvantage of rotatory chairs is that rotation
tests performed at accelerations less than ~1000°/s2 are less sensitive than the video HIT
(with high acceleration) and caloric irrigation (stimulating each ear independently) for
detection of unilateral reduced vestibular function when the opposite labyrinth is normal.
Therefore, strict criteria are required for diagnosis of unilateral vestibulopathy with rotary
chair stimuli to avoid inclusion of false positives. In contrast, rotatory chairs are useful for
diagnosis of BVP because they enable delivery of en bloc, passive, whole-body rotations in
darkness, which can identify BVP in subjects for whom bedside HIT or vHIT responses are
augmented by cervico-ocular reflexes, anticipatory saccades, and other non-labyrinthine
visual stabilizing systems. A gain of the aVOR of less than 0.15 upon sinusoidal stimulation
in the range from 0.05 to 0.1 Hz at a maximum angular velocity of 60°/sec suggests BVP,
as does a short time constant of VOR responses during constant-velocity step rotations.
8. Bedside HIT: The patient is asked to look at the tip of the examiner’s nose. The examiner,
in turn, holds the head of the patient firmly and delivers impulses with high acceleration,
but limited amplitudes (< 15O), in the horizontal plane to each side in pseudo-random order.
After each impulse, the head is held in the eccentric position and the eyes are carefully
observed for catch-up saccades that bring the eyes back on the visual target, i.e. the tip of
the examiner’s nose, which indicates a deficient VOR (27). In patients with BVP with
complete or almost complete loss of VOR, catch-up saccades are elicited by head impulses
to both sides (29). Sometimes the catch-up saccades have a very short latency and therefore
occur already during the head impulse. Such covert catch-up saccades cannot be seen
clinically, which results in a false-negative bedside HIT (33). Finally, using the bedside HIT
only severe deficits of the angular VOR below 0.4 can be reliably detected (29).
Comments

Epidemiology
The prevalence of BVP in the US adult population was estimated to be 28 per 100,000 in 2008
(43). The relative incidence of BVP was estimated to be 4 to 7% in various reports (17;19;23).
The age distribution of patients with BVP ranges from youth to old age depending on the
etiology. The mean age at which the diagnosis is established is given as around 50-60 years
(11;17;19;23;35).

Natural course of the disease

In about 60% of patients the disease develops slowly and progressively. Forty percent of the
patients have a course of events marked by episodes of dizziness leading incrementally to
bilateral loss of function, again depending on the etiology (19). Some patients could have a
progressive course after recurrent attacks with spinning vertigo (19;44;45) (in these cases an
autoimmune or vascular or rarely infectious process has to be considered). Bilateral
vestibulopathy causes an impairment of the health-related quality of life in 90% of the patients
(46;47). In follow-up studies on patients with BVP the clinical findings, especially in terms of
caloric responses showed a slight worsening over time (47;48).

Pathophysiology
Bilateral impairment or loss of peripheral vestibular input causes deficits of vestibulo-ocular
and vestibulo-spinal reflexes, orientation, navigation, and spatial memory: (1) As a result of a
reduced gain of the aVOR, the visual world cannot be stabilized on the retina during high-
acceleration head movements, which leads to head-movement induced oscillopsia (9) and
reduced dynamic visual acuity (49). (2) Balance during standing and locomotion is impeded
due to insufficient vestibulo-spinal reflexes (50), especially if postural control cannot
appropriately rely on proprioceptive (e.g. on soft or uneven ground) or visual input (e.g. in
darkness). (3) In the absence of visual and proprioceptive cues, patients with BVP lose their
sense of earth-verticality and become disoriented (e.g. when trying to dive). (4) Spatial learning
performance is delayed as a consequence of anatomical and functional changes in the
hippocampal formation (12;13).

Bedside examination:
a) Bedside HIT: HIT is a simple bedside test for high-frequency VOR function (27). The
examiner gives a subject high-acceleration head rotation with small amplitudes. The subject
is asked to fixate the examiner’s nose. Corrective saccades after head rotation (catch-up
saccades) imply impaired angular VOR. Although it is applicable for diagnosis of BVP,
bedside HIT could overlook patients with covert catch-up saccade (33;51). It is evidently
only reliable in patients with a severe aVOR deficit with a gain < 0.4 (29)
b) Dynamic visual acuity test: The examiner shakes the head of a subject rapidly (displacement
of 10-15O at approx. 2 Hz) in the horizontal plane. Impaired aVOR results in a drop of visual
acuity. A decrease of ≥ 0.2 LogMAR units is pathological.
c) Romberg test: This is a test of static balance. A subject is asked to stand on a firm, earth-
horizontal surface with the feet together with eyes open and then closed. When the subject
shows obvious sway or fall with eyes closed despite no sway or fall with eyes open, the
Romberg test is regarded as pathological. A pathological Romberg test implies vision-
dependency for maintenance of body balance. While patients with BVP show a positive
Romberg test (preferably tandem Romberg with the eyes open and closed), patients with
severe proprioceptive loss could also show a positive Romberg test.
Laboratory examinations

During head movements, efficient stabilization of the image on the retina is necessary to
preserve visual acuity. In patients with BVP, gaze stabilization fails and can lead to significant
deterioration in visual acuity during head movements. Visual acuity in dynamic conditions can
be assessed by testing for dynamic visual acuity (DVA). Dynamic visual acuity testing can be
performed in many ways: the patient has to read letters from a visual acuity chart or a computer
screen during active or passive, vertical or horizontal head movements, or while walking on a
treadmill at different velocities (52). Passive high-angular-velocity movements (150°/s) have
been shown to be most useful for discrimination between healthy subjects and patients with a
unilateral or bilateral vestibular loss. However, that study did not include DVA testing by
walking on a treadmill (49). A decline of more than 2 lines on the optotype chart is considered
abnormal (53), although a loss of 2 lines (0.2 logMAR) is not unusual for healthy subjects. In
order to trade sensitivity for specificity, 4 lines may be required (54). Moreover, DVA may
show false negative results due to mechanisms that at least partially compensate for the retinal
instability during head movements (49). However, in subjects with unilateral and bilateral
vestibular loss, computerized DVA testing reached a sensitivity of 94.5% and a specificity of
95.2% (55). In another group of BVP patients, DVA was impaired in 96% of the cases (23).
To conclude, DVA can help to establish the diagnosis of BVP, but a normal DVA does not
definitely rule out BVP, and an impaired DVA does not imply vestibular hypofunction per se.
It is still not understood by which specific vestibular deficits (which semicircular canal, which
otolith organs and which frequencies) DVA decreases.

Caloric testing
The caloric test, first described by Bárány, is believed to evaluate the low-frequency part (~0.01
Hz) of the horizontal semicircular canal function, which is much lower than the frequency
spectrum of most natural head movements relevant to normal function of the vestibular
labyrinths. This, together with the fact that the caloric stimulus is monaural, is why the caloric
test is considered a non-physiological vestibular test (7;56). On the other hand, the caloric test
is the only widely used clinical test that exclusively stimulates only one side, in contrast to HIT
and all other head rotation tests. Based on extensive research in the twentieth century, the caloric
response is believed to be predominantly induced by convection (57), non-specific thermic
stimulation of hair cells (56) and endolymph expansion (58). Many challenges are met when
using the caloric test for diagnosing BVP. Further, putting Reid’s horizontal plane 20° off
vertical, not 30°, is the optimum pitch for orienting the horizontal canals in an earth-vertical
plane (59). A 5-minute stimulus interval should be maintained between successive irrigations
to reduce the residual effects of the previous irrigation. During each caloric irrigation of 30
seconds duration the stimulus must have the same characteristics: the same total volume of at
least 200 ml water and the same temperatures for cold and warm irrigations (30 and 44 °C,
respectively) (60;61). A 1-degree variation in temperature from the intended 30 or 44 °C can
already result in a 14% difference in stimulation magnitude (62). The required thermic stimulus
is best achieved by the use of water and not by air (61). Statistically higher slow-component
values of the VOR are obtained for water than for air, and evidence shows that air has poorer
test-retest reliability and greater inter-subject variability (for reference see (61)). Based on our
extensive clinical experience in comparing air calorics to water calorics in many hundreds of
patients, we advise using water calorics. However, responses to water calorics also show
considerable test-retest variation and variability between healthy subjects (61). In the past,
responses were quantified by SPV (in the culmination phase) of the caloric nystagmus, the
maximum nystagmus frequency and the total number of nystagmus beats. The maximum SPV
at the time of maximum response (culmination phase) occurs generally about 50–60 s after the
start of irrigation and is the preferred parameter to be determined. Ice water calorics are not
preferred, since they can induce a pseudo-caloric nystagmus by activating a latent spontaneous
nystagmus (23), and the absence of an ice water response does not prove a complete vestibular
areflexia, as was thought in the past. The average maximum SPV varies between laboratories
from 14.9 to 29.7°/s for cold irrigations and from 12.1 to 30.9°/s for warm irrigations
(60;63;64). These normative data will probably reveal a high variability among values. For
example, in one vestibular laboratory, the 95% prediction interval of the average maximum
SPV may vary from 3.4 to 32.9°/s for cold irrigations and from 6.9 to 55.0°/s for warm
irrigations. There is as yet no consensus among investigators about correcting values for age
(64-66). Also, the asymmetry between labyrinths may be up to 19%, and still be within the
normal range (60). This variability may partly be due to uncontrollable factors such as
differences in anatomy of the temporal bone (differences in temperature conduction), blood
flow and middle ear fluids – all the more reason to have controllable factors such as stimulus
parameters and technical skills optimized and to absolutely avoid any visual suppression (60).
A criterion often suggested for diagnosing BVP is to have a sum of 4 irrigations that is less than
20°/s (23;24;60;61;67). While this is sensitive, it could still lead to false-positive results (partly
due to the anatomical variations mentioned above) and also to false-negative results. Other parts
of the vestibular system, such as the remaining semicircular canals and the otolith organs, are
not tested.
To summarize, using the caloric test for diagnosing BVP is challenging, due to the high
standards necessary for testing and difficult interpretation as a result of inter- and intra-subject
variation for which the present diagnostic criteria for BVP are not always sufficient. When the
high testing standards are not adhered to, and inter- and intra-subject variability is not taken
into account, this leads to unnecessary false-positive and false-negative diagnoses of BVP.

Rotatory chair tests

Rotatory chair tests can demonstrate residual vestibular function in patients with severe BVP,
when (almost) no vestibular response is measured with the caloric test (68-70). They can also
provide additional data about central processing of vestibular input from both labyrinths (60).
Two frequently used algorithms are the sinusoidal harmonic acceleration test and the velocity
step test (VST) (71). The sinusoidal harmonic acceleration test is often promoted as a real multi-
frequency rotation test. However, compared to the optimum frequency sensitivity of the
semicircular canals (ranging from about 0.1 to 10 Hz), the sinusoidal harmonic acceleration test
uses only low-frequency stimuli ranging from 0.005 to a maximum of 0.64 Hz. Another
complicating factor is that the total sinusoidal harmonic acceleration test takes considerable
time. Therefore, the frequency response might be affected by changes in alertness of the patient
during the test. The VST involves more high-frequency components compared to the sinusoidal
harmonic acceleration test (step function) and comes closer to HIT. The first challenge when
performing rotatory chair testing is to conduct it in a standardized way. The patient must be
alert, since alertness during rotation increases the gain of the measured VOR (60). Many
vestibular laboratories prefer to have the eyes of the patient open during testing in complete
darkness, since closing the eyes decreases gain of the VOR (72). For the VST, it is preferred
to use the first rotation for familiarization with the test to get responses that are as accurate as
possible (71). The second challenge is to have the right frame of reference for the rotatory tests.
Regarding gain of the VOR, its values differ considerably between vestibular laboratories for
the sinusoidal harmonic acceleration test as well as for the VST. It is therefore common sense
for many vestibular laboratories to have their own normative data wall (73). Furthermore, in
the sinusoidal harmonic acceleration test and the VST, gain is considered to be the most variable
parameter between and within subjects, probably as a consequence of factors such as fatigue,
alertness, stress and habituation (71;74;75). Gain is also reduced by the test itself; rotating in
the dark is an artificial condition that reduces VOR gain (76). Moreover, gain is frequency
dependent: it increases to a certain extent with an increasing modulation frequency (74). Taking
all these facts into account, normative data for a vestibular laboratory can vary widely: for the
sinusoidal harmonic acceleration test, a mean gain of 58.77% with a standard deviation of
13.98% (0.1 Hz, 50°/s peak velocity), and for the VST, a mean gain of 67.66% with a standard
deviation of 18.14% (200°/s deceleration after a continuous velocity of 100°/s rotating to the
right). However, it has been indicated that the sinusoidal harmonic acceleration test and VST
gain parameters can be highly consistent, despite the fact that they are influenced by many other
factors (71). Regarding other parameters, directional preponderance can vary widely within one
vestibular laboratory, up to a 95% prediction interval of 26% (0.05 Hz, 50°/s peak velocity)
(60). Parameters believed to be more consistent and reproducible are the phase in the sinusoidal
harmonic acceleration test and the time constant in the VST (71;75;77). All these facts show
that interpreting the results correctly is the last challenge when using the rotatory chair for
diagnosing BVP. Some authors suggest that rotatory chair tests should be the gold standard
(34;54). If any abnormalities are found in BVP patients, the strongest effects are often found
at low frequencies, with a decrease in gain and an increase in phase (54). However, depending
on the criteria, only 53% of BVP patients show abnormal responses on the rotatory chair. This
emphasizes the need for establishing a standardized protocol for the diagnosis of BVP patients.
So far, the modulation frequencies to be tested and the cut-off criteria have not been established
(23;78). To summarize, use of the rotatory chair is challenging. In order to get reproducible and
consistent results, a high standard for testing is necessary.
Due to inter- and intra-subject variations in some parameters, interpretation of the results
often remains difficult. Despite all these critical considerations, the sinusoidal rotatory test is a
potentially useful tool to augment the diagnosis of BVP in patients where video-HIT or caloric
test are impossible to perform. This holds, for example, in individual cases of anxiety or
anatomical restrictions or infants (calorics) or patients who fail to follow the instructions for
the video-HIT.

Vestibular evoked myogenic potential

Vestibular evoked myogenic potential (VEMP) testing provides useful information about the
otolith organs. The air-conducted sound-evoked cVEMP tests predominantly saccular function
and the bone-conducted vibration-evoked oVEMP tests predominantly utricular
function. There have been several small case series and two larger studies of cVEMP in patients
with BVP showing that cVEMPs are smaller than normal on average and are often absent,
suggesting saccular damage (15;67;79;80). Likewise, oVEMP are also often abnormal in BVP,
indicating utricular damage (15;79;81). Utricular function is correlated with horizontal canal
function in BVP (15). However, as VEMP remain intact in a significant number of patients, the
degree of otolith dysfunction appears to be less than that of canal dysfunction, though this may
differ depending upon the underlying cause of BVP. VEMP therefore provide only supporting
information and are not used in the diagnosis of BVP.
Vestibular evoked myogenic potentials can provide information about the extent of
disease and involvement of the otolith organs in BVP. They can also be used to monitor disease
progression or track the response to any treatment. However, abnormal VEMP should be
interpreted carefully in light of other test results because of the following limitations. The range
of normal VEMP amplitudes is large, positively skewed and, in older people (above about 60
yrs), extends down to an absent response. The range is large because factors other than otolith
function contribute to reflex amplitude: including the intensity of sound or vibration reaching
the otoliths (which is never known), placement of recording electrodes, strength of underlying
muscle contraction (cVEMP) or angle of vertical gaze (oVEMP). The large normal range makes
it difficult to define a meaningful lower limit of normal VEMP amplitude, especially in older
populations. Bilaterally small (or even absent) cVEMP or oVEMP responses are therefore often
a normal finding in older patients. This is in contrast to a VEMP asymmetry, which can be more
confidently interpreted as unilateral otolith dysfunction. Isolated bilateral otolith abnormalities
have been reported ((15); for references (82)), and examination of canal function without otolith
function may overlook these rare cases of BVP. But isolated VEMP abnormalities need to be
carefully distinguished from false positive (abnormal) responses.

Etiology

A broad spectrum of etiologies has been shown to be important causes of BVP. In a case series
of 255 patients reported in 2007, the etiology of BVP was ascertained in approximately 30% of
the patients, with the remainder thought to be idiopathic and degenerative in nature (19). The
three most frequently identifiable causes of BVP include: ototoxic drugs (13%; gentamicin and
other ototoxic antibiotics, anticancer chemotherapy, loop diuretics, aspirin in very high dosages
(83) or styrenes (84)), bilateral Menière’s disease (7%), and meningitis (5%). Other causes are
a) tumors: bilateral vestibular schwannoma in neurofibromatosis type 2, meningeal
carcinomatosis, infiltration of the skull base or due to tumor irradiation; b) autoimmune diseases
(85) like Cogan syndrome (86), neurosarcoidosis, Behçet’s disease, cerebral vasculitis,
systemic lupus erythematosus, granulomatous polyangiitis (Wegener’s granulomatosis); c)
rarer causes such as bilateral labyrinth concussion or superficial siderosis (87;88). In another
case series of 154 patients with BVP, Menière’s disease and ototoxic exposure were the most
common definite etiologies, followed by infectious and genetic causes (89). Indeed, recent
advances in human genetics have led to the identification of firm genetic causes in 15% of the
BVP cohort, with another 10% suspected to have a probable genetic cause (89). The proportion
of patients with a definite etiology was 47% in this study. Some patients with BVP could have
a cerebellar syndrome with downbeat nystagmus (18-20;90). Such cases probably involve a
neurodegenerative illness that affects the vestibular ganglia cells and the cerebellum; it often
occurs with an additional neuropathy: cerebellar ataxia with neuropathy and vestibular areflexia
syndrome (CANVAS). This combination of symptoms occurs in up to 10%-20% of patients
with BVP in some case series (21;91;92).
Predisposing genetic factors are suspected but poorly understood for patients with
idiopathic vestibular loss of function. Genetic factors for susceptibility of toxic damage have
been proposed on the basis of familial cases with BVP with exquisite sensitivity to
aminoglycosides, yet no mitochondrial abnormality or mutations have been demonstrated (90).
Similar to Menière’s disease, familial BVP is commonly found in the setting of migraine,
raising the possibility of selective vulnerability of the inner ear to migraine-related damage (89).
Linkage analysis in a handful of families with BVP suggested a locus on chromosome 6q (93).
Thus far, no mutations have been identified in BVP with normal hearing,  in contrast with an
ever increasing number of genetic loci for hearing loss (94;95). In conclusion, BVP has been
proposed to be a monogenic disorder with different modes of inheritance including autosomal
dominant, autosomal recessive, sex-linked or mitochondrial (96;97). BVP related to migraine
could be a complex trait, as migraine itself is complex. There is continuing effort to characterize
the genetic basis of BVP.

Differential diagnosis

Clinically relevant differential diagnoses are summarized in table 1.

Limitations, areas of uncertainties and deficits in current knowledge

There are several areas of uncertainty in the classification:

1) There has been much discussion about the terminology of the entity. Terms suggested by
the authors in addition to BVP were bilateral vestibular hypofunction, bilateral peripheral
vestibular hypofunction, bilateral vestibular hyopreflexia/areflexia, and bilateral vestibular
deficiency. To come to an agreement on this important issue, a transparent democratic
approach was used with two rounds of voting: firstly, every author could list three terms in
order of preference. Secondly, there was a vote with points for the three favourite terms
with the following results: 21 points for BVP, 11 points for a combined term BVP/bilateral
vestibular hypofunction, 9 points for bilateral vestibular hypofunction only.
2) A major challenge in the classification is that no single test can fully characterize the
functional integrity of the vestibular apparatus.
3) The panel discussed the clinical utility of distinguishing BVP from “probable BVP” as well
as “complete” or “incomplete” BVP based on quantitative measurement from caloric
testing, video-HIT of horizontal and vertical canals, cVEMP and oVEMP and rotational
testing, keeping in mind that the latter is used less and less often. “Probable BVP” is a
working diagnosis for clinical practice in primary care and quantitative measurement of the
vestibular function is required for BVP.
4) A corollary to the definition of BVP is whether there is clinical utility for the sub-
classification of reduced/absent low- vs. high-frequency canal function, horizontal and/or
vertical canal function vs. otolith function. This means partial or complete loss of sensory
function in any subset of the 10 vestibular endorgans on both sides.
5) It has to be kept in mind that VOR responses in some or all tests commonly used to examine
labyrinthine function are used under the assumption that all downstream aspects of the
reflex pathways are normal.
6) The proposed pathological values of reduced peripheral vestibular function as measured by
video-HIT and peak SPV in response to caloric irrigation are a conservative consensus by
the panel to enhance the stringency of the diagnostic criteria. They can therefore be
considered criteria for “profound” BVP, whereas “severe” BVP could be diagnosed in the
setting of less dramatically reduced function on video-HIT and caloric testing.
Acknowledgements. This work was supported by a grant from the Federal Ministry of
Education and Research to the German Center for Vertigo and Balance Disorders (Grant No.
01EO0901 and 01EO1401).
 Reference List 

  (1)   Bisdorff  A,  von  Brevern  M,  Lempert  T,  Newman‐Toker  DE.  Classification  of  vestibular 
symptoms:  towards  an  international  classification  of  vestibular  disorders.  J  Vestib  Res 
2009;19(1‐2):1‐13. 

  (2)   Lempert T, Olesen J, Furman J, Waterston J, Seemungal B, Carey J, et al. Vestibular migraine: 
diagnostic criteria. J Vestib Res 2012;22(4):167‐72. 

  (3)   Lopez‐Escamez  JA,  Carey  J,  Chung  WH,  Goebel  JA,  Magnusson  M,  Mandala  M,  et  al. 
Diagnostic criteria for Meniere's disease. J Vestib Res 2015 Jan 1;25(1):1‐7. 

  (4)   von BM, Bertholon P, Brandt T, Fife T, Imai T, Nuti D, et al. Benign paroxysmal positional 
vertigo: Diagnostic criteria. J Vestib Res 2015;25(3‐4):105‐17. 

  (5)   Strupp  M,  Lopez‐Escamez  JA,  Kim  JS,  Straumann  D,  Jen  JC,  Carey  J,  et  al.  Vestibular 
paroxysmia: diagnostic criteria. J Vestib Res. In press 2017. 

  (6)   James W. The sense of dizziness in deaf‐mutes. Am J Otol 1882;4:239‐54. 

  (7)   Barany  R.  Physiologie  und  Pathologie  des  Bogengangsapparates  beim  Menschen.  Vienna: 
Franz Deuticke; 1907. 

  (8)   Dandy WE. The surgical treatment of Menière disease.  Surg Gynecol Obstet 1941;72:421‐5. 

  (9)   Bender MB. Oscillopsia. Arch Neurol 1965;13:204‐13. 

  (10)   Hess  K.  Vestibulotoxic  drugs  and  other  causes  of  acquired  bilateral  peripheral 
vestibulopathy.  In:  Baloh  RW,  Halmagyi  GM,  editors.  Disorders  of  the  vestibular 
system.Oxford: Oxford University Press; 1996. p. 360‐73. 

  (11)   Baloh RW, Jacobson K, Honrubia V. Idiopathic bilateral vestibulopathy. Neurology 1989;39(2 
Pt 1):272‐5. 

  (12)   Brandt T, Schautzer F, Hamilton D, Brüning R, Markowitsch HJ, Kalla R, et al. Vestibular loss 
causes  hippocampal  atrophy  and  impaired  spatial  memory  in  humans.  Brain 
2005;(128):2732‐41. 

  (13)   Kremmyda O, Hufner K, Flanagin VL, Hamilton DA, Linn J, Strupp M, et al. Beyond Dizziness: 
Virtual  Navigation,  Spatial  Anxiety  and  Hippocampal  Volume  in  Bilateral  Vestibulopathy. 
Front Hum Neurosci 2016;10:139. 

  (14)   Gottlich M, Jandl NM, Sprenger A, Wojak JF, Munte TF, Kramer UM, et al. Hippocampal gray 
matter volume in bilateral vestibular failure. Hum Brain Mapp 2016 May;37(5):1998‐2006. 

  (15)   Fujimoto  C,  Murofushi  T,  Chihara  Y,  Suzuki  M,  Yamasoba  T,  Iwasaki  S.  Novel  subtype  of 
idiopathic  bilateral  vestibulopathy:  bilateral  absence  of  vestibular  evoked  myogenic 
potentials in the presence of normal caloric responses. J Neurol 2009 Sep;256(9):1488‐92. 

  (16)   Bronstein  AM,  Mossman  S,  Luxon  LM.  The  neck‐eye  reflex  in  patients  with  reduced 
vestibular and optokinetic function. Brain 1991;114:1‐11. 
  (17)   Rinne T, Bronstein AM, Rudge P, Gresty MA, Luxon LM. Bilateral loss of vestibular function: 
Clinical findings in 53 patients. J Neurol 1998;245(6‐7):314‐21. 

  (18)   Migliaccio  AA,  Halmagyi  GM,  McGarvie  LA,  Cremer  PD.  Cerebellar  ataxia  with  bilateral 
vestibulopathy:  description  of  a  syndrome  and  its  characteristic  clinical  sign.  Brain  2004 
Feb;127(Pt 2):280‐93. 

  (19)   Zingler VC, Cnyrim C, Jahn K, Weintz E, Fernbacher J, Frenzel C, et al. Causative factors and 
epidemiology of bilateral vestibulopathy in 255 patients. Ann Neurol 2007 Jun;61(6):524‐32. 

  (20)   Wagner JN, Glaser M, Brandt T, Strupp M. Downbeat nystagmus: aetiology and comorbidity 
in 117 patients. J Neurol Neurosurg Psychiatry 2008 Jun;79(6):672‐7. 

  (21)   Szmulewicz DJ, Waterston JA, Halmagyi GM, Mossman S, Chancellor AM, Mclean CA, et al. 
Sensory  neuropathy  as  part  of  the  cerebellar  ataxia  neuropathy  vestibular  areflexia 
syndrome. Neurology 2011 May 31;76(22):1903‐10. 

  (22)   Rinne T, Bronstein AM, Rudge P, Gresty MA, Luxon LM. Bilateral loss of vestibular function. 
ACTA OTO LARYNGOL SUPPL 1995;Issue 520 II:247‐50. 

  (23)   Kim S, Oh YM, Koo JW, Kim JS. Bilateral vestibulopathy: clinical characteristics and diagnostic 
criteria. Otol Neurotol 2011 Jul;32(5):812‐7. 

  (24)   Agrawal Y, Bremova T, Kremmyda O, Strupp M. Semicircular canal, saccular and utricular 
function in patients with bilateral vestibulopathy: analysis based on etiology. J Neurol 2013 
Mar;260(3):876‐83. 

  (25)   Simmons FB. Patients with bilateral loss of caloric response. Ann Otol Rhinol Laryngol 1973 
Mar;82(2):175‐8. 

  (26)   Leigh RJ, Brandt T. A reevaluation of the vestibulo‐ocular reflex: New ideas of its purpose, 
properties, neural substrate, and disorders. Neurology 1993;43(7):1288‐95. 

  (27)   Halmagyi GM, Curthoys IS. A clinical sign of canal paresis. Arch Neurol 1988;45:737‐9. 

  (28)   Jorns‐Haderli  M,  Straumann  D,  Palla  A.  Accuracy  of  the  bedside  head  impulse  test  in 
detecting vestibular hypofunction. J Neurol Neurosurg Psychiatry 2007 Oct;78(10):1113‐8. 

  (29)   Yip CW, Glaser M, Frenzel C, Bayer O, Strupp M. Comparison of the bedside head impulse test

with the video head impulse test in clinical practice setting: a prospective study of 500
outpatients. Funct Neurol. In press 2016. 

  (30)   Kremmyda O, Kirchner H, Glasauer S, Brandt T, Jahn K, Strupp M. False‐positive head‐impulse 
test in cerebellar ataxia. Front Neurol 2012;3:162. 

  (31)   MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse 
test: diagnostic accuracy in peripheral vestibulopathy. Neurology 2009 Oct 6;73(14):1134‐
41. 

  (32)   Bartl K, Lehnen N, Kohlbecher S, Schneider E. Head impulse testing using video‐oculography. 
Ann N Y Acad Sci 2009 May;1164:331‐3. 
  (33)   Weber KP, Aw ST, Todd MJ, McGarvie LA, Curthoys IS, Halmagyi GM. Head impulse test in 
unilateral vestibular loss: vestibulo‐ocular reflex and catch‐up saccades. Neurology 2008 Feb 
5;70(6):454‐63. 

  (34)   Furman JM, Kamerer DB. Rotational responses in patients with bilateral caloric reduction. 
Acta Otolaryngol 1989 Nov;108(5‐6):355‐61. 

  (35)   Moon  M,  Chang  SO,  Kim  MB.  Diverse  clinical  and  laboratory  manifestations  of  bilateral 
vestibulopathy. Laryngoscope 2016 Mar 12. 

  (36)   Demer JL, Honrubia V, Baloh RW. Dynamic visual acuity: a test for oscillopsia and vestibulo‐
ocular reflex function. Am J Otol 1994 May;15(3):340‐7. 

  (37)   Tarnutzer AA, Bockisch CJ, Buffone E, Weiler S, Bachmann LM, Weber KP. Disease‐specific 
sparing of the anterior semicircular canals in bilateral vestibulopathy. Clin Neurophysiol 2016 
Aug;127(8):2791‐801. 

  (38)   McGath JH, Barber HO, Stoyanoff S. Bilateral vestibular  loss and oscillopsia. J Otolaryngol 

1989 Aug;18(5):218‐21. 

  (39)   Fujimoto C, Murofushi T, Chihara Y, Ushio M, Suzuki M, Yamaguchi T, et al. Effect of severity 
of vestibular dysfunction on postural instability in idiopathic bilateral vestibulopathy. Acta 
Otolaryngol 2013 May;133(5):454‐61. 

  (40)   Paulus W, Straube A, Brandt T. Visual postural performance after loss of somatosensory and 
vestibular function. J Neurol Neurosurg Psychiatry 1987;50(11):1542‐5. 

  (41)   Weber  KP,  MacDougall  HG,  Halmagyi  GM,  Curthoys  IS.  Impulsive  testing  of  semicircular‐
canal function using video‐oculography. Ann N Y Acad Sci 2009 May;1164:486‐91. 

  (42)   Mossman B, Mossman S, Purdie G, Schneider E. Age dependent normal horizontal VOR gain 
of head  impulse test as measured with video‐oculography.  J Otolaryngol Head Neck Surg 
2015;44:29. 

  (43)   Ward  BK,  Agrawal  Y,  Hoffman  HJ,  Carey  JP,  Della  Santina  CC.  Prevalence  and  impact  of 
bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey. 
JAMA Otolaryngol Head Neck Surg 2013 Aug 1;139(8):803‐10. 

  (44)   Young  AS,  Taylor  RL,  McGarvie  LA,  Halmagyi  GM,  Welgampola  MS.  Bilateral  sequential 
peripheral vestibulopathy. Neurology 2016 Apr 12;86(15):1454‐6. 

  (45)   Fujimoto  C,  Kinoshita  M,  Kamogashira  T,  Egami  N,  Sugasawa  K,  Yamasoba  T,  et  al. 
Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral 
vestibulopathy. Acta Otolaryngol 2016;136(1):43‐7. 

  (46)   Guinand  N,  Boselie  F,  Guyot  JP,  Kingma  H.  Quality  of  life  of  patients  with  bilateral 
vestibulopathy. Ann Otol Rhinol Laryngol 2012 Jul;121(7):471‐7. 

  (47)   Zingler  VC,  Weintz  E,  Jahn  K,  Huppert  D,  Cnyrim  C,  Brandt  T,  et  al.  Causative  factors, 
epidemiology,  and  follow‐up  of  bilateral  vestibulopathy.  Ann  N  Y  Acad  Sci  2009 
May;1164:505‐8. 

  (48)   Zingler VC, Weintz E, Jahn K, Mike A, Huppert D, Rettinger N, et al. Follow‐up of vestibular 
function in bilateral vestibulopathy. J Neurol Neurosurg Psychiatry 2008;79:284‐8. 
  (49)   Vital  D,  Hegemann  SC,  Straumann  D,  Bergamin  O,  Bockisch  CJ,  Angehrn  D,  et  al.  A  new 
dynamic visual acuity test to assess peripheral vestibular function. Arch Otolaryngol Head 
Neck Surg 2010 Jul;136(7):686‐91. 

  (50)   Horak FB, Buchanan J, Creath R, Jeka J. Vestibulospinal control of posture. Adv Exp Med Biol 
2002;508:139‐45. 

  (51)   Tjernstrom F, Nystrom A, Magnusson M. How to uncover the covert saccade during the head 
impulse test. Otol Neurotol 2012 Dec;33(9):1583‐5. 

  (52)   Guinand N, Pijnenburg M, Janssen M, Kingma H. Visual acuity while walking and oscillopsia 
severity in healthy subjects and patients with unilateral and bilateral vestibular function loss. 
Arch Otolaryngol Head Neck Surg 2012 Mar;138(3):301‐6. 

  (53)   Fife TD, Tusa RJ, Furman JM, Zee DS, Frohman E, Baloh RW, et al. Assessment: vestibular 
testing  techniques  in  adults  and  children:  report  of  the  Therapeutics  and  Technology 
Assessment  Subcommittee  of  the  American  Academy  of  Neurology.  Neurology  2000  Nov 
28;55(10):1431‐41. 

  (54)   Hain TC, Cherchi M, Yacovino DA. Bilateral vestibular loss. Semin Neurol 2013 Jul;33(3):195‐
203. 

  (55)   Herdman SJ, Tusa RJ, Blatt P, Suzuki A, Venuto PJ, Roberts D. Computerized dynamic visual 
acuity test in the assessment of vestibular deficits. Am J Otol 1998 Nov;19(6):790‐6. 

  (56)   Wit  HP,  Segenhout  JM.  Caloric  stimulation  of  the  vestibular  system  of  the  pigeon  under 
minimal influence of gravity. Acta Otolaryngol (Stockh ) 1988;105:338‐42. 

  (57)   Minor LB, Goldberg JM. Influence of static head position on the horizontal nystagmus evoked 
by  caloric,  rotational  and  optokinetic  stimulation  in  the  squirrel  monkey.  Exp  Brain  Res 
1990;82(1):1‐13. 

  (58)   Scherer H, Clarke AH. The caloric vestibular reaction in space. Physiological considerations. 
Acta Otolaryngol 1985 Nov;100(5‐6):328‐36. 

  (59)   Della  Santina  CC,  Potyagaylo  V,  Migliaccio  AA,  Minor  LB,  Carey  JP.  Orientation  of  human 
semicircular canals measured by three‐dimensional multiplanar CT reconstruction. J Assoc 
Res Otolaryngol 2005 Sep;6(3):191‐206. 

  (60)   Van Der Stappen A, Wuyts FL, Van de Heyning PH. Computerized electronystagmography: 
normative data revisited. Acta Otolaryngol 2000 Sep;120(6):724‐30. 

  (61)   Maes L, Dhooge I, De VE, D'haenens W, Bockstael A, Vinck BM. Water irrigation versus air 
insufflation: a comparison of two caloric test protocols. INT J AUDIOL 2007 May;46(5):263‐
9. 

  (62)   Goncalves  DU,  Felipe  L,  Lima  TM.  Interpretation  and  use  of  caloric  testing.  Braz  J 
Otorhinolaryngol 2008 May;74(3):440‐6. 

  (63)   Sills AW, Baloh RW, Honrubia V. Caloric testing 2. results in normal subjects. Ann Otol Rhinol 
Laryngol Suppl 1977 Sep;86(5 Pt 3 Suppl 43):7‐23. 

  (64)   Bruner  A,  Norris  TW.  Age‐related  changes  in  caloric  nystagmus.  Acta  Otolaryngol  Suppl 
1971;282:1‐24. 
  (65)   Peterka  RJ,  Black  FO,  Schoenhoff  MB.  Age‐related  changes  in  human  vestibulo‐ocular 
reflexes: sinusoidal rotation and caloric tests. J Vestib Res 1990;1(1):49‐59. 

  (66)   Mallinson  AI,  Longridge  NS.  Caloric  response  does  not  decline  with  age.  J  Vestib  Res 
2004;14(5):393‐6. 

  (67)   Zingler  VC,  Weintz  E,  Jahn  K,  Botzel  K,  Wagner  J,  Huppert  D,  et  al.  Saccular  function  less 
affected than canal function in bilateral vestibulopathy. J Neurol 2008 Sep 26;255:1332‐6. 

  (68)   Eviatar A. The torsion swing as a vestibular test. Arch Otolaryngol 1970 Nov;92(5):437‐44. 

  (69)   Baloh RW, Sills AW, Honrubia V. Impulsive and sinusoidal rotatory testing: a comparison with 
results of caloric testing. Laryngoscope 1979;89(4):646‐54. 

  (70)   van de Berg R, Guinand N, Guyot JP, Kingma H, Stokroos RJ. The modified ampullar approach 
for vestibular implant surgery: feasibility and its first application in a human with a long‐term 
vestibular loss. Front Neurol 2012;3:18. 

  (71)   Maes L, Dhooge I, De VE, D'haenens W, Bockstael A, Keppler H, et al. Normative data and 
test‐retest reliability of the sinusoidal harmonic acceleration test, pseudorandom rotation 
test and velocity step test. J Vestib Res 2008;18(4):197‐208. 

  (72)   Moller  C,  Odkvist  L,  White  V,  Cyr  D.  The  plasticity  of  compensatory  eye  movements  in 
rotatory tests. I. The effect of alertness and eye closure. Acta Otolaryngol 1990 Jan;109(1‐
2):15‐24. 

  (73)   Wall  C3,  Black  FO,  Hunt  AE.  Effects  of  age,  sex  and  stimulus  parameters  upon  vestibulo‐ 
ocular responses to sinusoidal rotation. Acta Otolaryngol Stockh 1984;98(3‐4):270‐8. 

  (74)   Barnes GR. Visual‐vestibular interaction in the control of head and eye movement: the role 
of visual feedback and predictive mechanisms. Prog Neurobiol 1993 Oct;41(4):435‐72. 

  (75)   Li CW, Hooper RE, Cousins VC. Sinusoidal harmonic acceleration testing in normal humans. 
Laryngoscope 1991 Feb;101(2):192‐6. 

  (76)   Leigh  RJ,  Sawyer  RN,  Grant  MP,  Seidman  SH.  High‐frequency  vestibuloocular  reflex  as  a 
diagnostic tool. Ann N Y Acad Sci 1992 May 22;656:305‐14. 

  (77)   Jenkins HA,  Goldberg  J.  Test‐retest reliability  of the  rotatory  test  in normal  subjects.  Adv 
Otorhinolaryngol 1988;41:190‐5. 

  (78)   Perez FA, Guinand N, van de Berg R, Stokroos R, Micera S, Kingma H, et al. Artificial balance: 
restoration  of  the  vestibulo‐ocular  reflex  in  humans  with  a  prototype  vestibular 
neuroprosthesis. Front Neurol 2014;5:66. 

  (79)   Agrawal Y, Bremova T, Kremmyda O, Strupp M. Semicircular canal, saccular and utricular 
function in patients with bilateral vestibulopathy: analysis based on etiology. J Neurol 2013 
Mar;260(3):876‐83. 

  (80)   Brantberg K, Lofqvist L. Preserved vestibular evoked myogenic potentials (VEMP) in some 
patients  with  walking‐induced  oscillopsia  due  to  bilateral  vestibulopathy.  J  Vestib  Res 
2007;17(1):33‐8. 
  (81)   Chiarovano E, Zamith F, Vidal PP, de WC. Ocular and cervical VEMPs: a study of 74 patients 
suffering from peripheral vestibular disorders. Clin Neurophysiol 2011 Aug;122(8):1650‐9. 

  (82)   Curthoys IS, Manzari L. Otolithic disease: clinical features and the role of vestibular evoked 
myogenic potentials. Semin Neurol 2013 Jul;33(3):231‐7. 

  (83)   Strupp  M,  Jahn  K,  Brandt  T.  Another  adverse  effect  of  aspirin:  bilateral  vestibulopathy.  J 
Neurol Neurosurg Psychiatry 2003 May;74(5):691. 

  (84)   Fischer  CS,  Bayer  O,  Strupp  M.  Transient  bilateral  vestibular  dysfunction  caused  by 
intoxication with low doses of styrene. Eur Arch Otorhinolaryngol 2014 Mar;271(3):619‐23. 

  (85)   Arbusow V, Strupp M, Dieterich M, Stocker W, Naumann A, Schulz P, et al. Serum antibodies 
against membranous labyrinth in patients with "idiopathic" bilateral vestibulopathy. J Neurol 
1998 Mar;245(3):132‐6. 

  (86)   Gluth MB, Baratz KH, Matteson EL, Driscoll CL. Cogan syndrome: a retrospective review of 
60 patients throughout a half century. Mayo Clin Proc 2006 Apr;81(4):483‐8. 

  (87)   Ushio M, Iwasaki S, Sugasawa K, Murofushi T. Superficial siderosis causing retrolabyrinthine 
involvement  in  both  cochlear  and  vestibular  branches  of  the  eighth  cranial  nerve.  Acta 
Otolaryngol 2006 Sep;126(9):997‐1000. 

  (88)   Kang KW, Lee C, Kim SH, Cho HH, Lee SH. Bilateral Vestibulopathy Documented by Video 
Head Impulse Tests in Superficial Siderosis. Otol Neurotol 2015 Dec;36(10):1683‐6. 

  (89)   Lucieer  F,  Vonk  P,  Guinand  N,  Stokroos  R,  Kingma  H,  van  de  Berg  R.  Bilateral  Vestibular 
Hypofunction:  Insights  in  Etiologies,  Clinical  Subtypes,  and  Diagnostics.  Front  Neurol 
2016;7:26. 

  (90)   Kirchner  H,  Kremmyda  O,  Hufner  K,  Stephan  T,  Zingler  V,  Brandt  T,  et  al.  Clinical, 
electrophysiological,  and  MRI  findings  in  patients  with  cerebellar  ataxia  and  a  bilaterally 
pathological head‐impulse test. Ann N Y Acad Sci 2011 Sep;1233:127‐38. 

  (91)   Kirchner  H,  Kremmyda  O,  Hufner  K,  Stephan  T,  Zingler  V,  Brandt  T,  et  al.  Clinical, 
electrophysiological,  and  MRI  findings  in  patients  with  cerebellar  ataxia  and  a  bilaterally 
pathological head‐impulse test. Ann N Y Acad Sci 2011 Sep;1233(1):127‐38. 

  (92)   Pothier DD, Rutka JA, Ranalli PJ. Double Impairment: Clinical Identification of 33 Cases of 
Cerebellar Ataxia with Bilateral Vestibulopathy. Otolaryngol Head Neck Surg 2011 Dec 9. 

  (93)   Jen JC, Wang H, Lee H, Sabatti C, Trent R, Hannigan I, et al. Suggestive linkage to chromosome 
6q in families with bilateral vestibulopathy. Neurology 2004 Dec 28;63(12):2376‐9. 

  (94)   Jen  JC.  Bilateral  vestibulopathy:  clinical,  diagnostic,  and  genetic  considerations.  Semin 
Neurol 2009 Nov;29(5):528‐33. 

  (95)   Frejo L, Giegling I, Teggi R, Lopez‐Escamez JA, Rujescu D. Genetics of vestibular disorders: 
pathophysiological insights. J Neurol 2016 Apr;263 Suppl 1:45‐53. 

  (96)   Jen JC. Genetics of vestibulopathies. Adv Otorhinolaryngol 2011;70:130‐4. 
  (97)   Elstner M, Schmidt C, Zingler VC, Prokisch H, Bettecken T, Elson JL, et al. Mitochondrial 12S 
rRNA  susceptibility  mutations  in  aminoglycoside‐associated  and  idiopathic  bilateral 
vestibulopathy. Biochem Biophys Res Commun 2008 Dec 12;377(2):379‐83. 
 
 Cerebellar ataxias without bilateral vestibulopathy
 Downbeat nystagmus syndrome
 Functional dizziness: perceived persistent postural dizziness, phobic postural dizziness,
visual induced dizziness
 Unilateral vestibular deficit
 Intoxications
 Vestibular suppressant medications
 Orthostatic tremor
 Visual disorders (if oscillopsia is prominent)
 Peripheral neuropathies
 Movement disorders: Parkinson’s disease, atypical Parkinson’s syndromes, multiple system
atrophies
 Central gait disorders due to normal pressure hydrocephalus, frontal gait disorders, lower-
body Parkinson, subcortical vascular encephalopathy or multiple sclerosis

Table 1: Differential diagnosis of bilateral vestibulopathy