Hindawi Publishing Corporation

Advances in Otolaryngology
Volume 2014, Article ID 792635, 17 pages
http://dx.doi.org/10.1155/2014/792635

Review Article
Benign Paroxysmal Positional Vertigo:
An Integrated Perspective
Kourosh Parham
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Connecticut Health Center,
Farmington, CT 06030-6228, USA
Correspondence should be addressed to Kourosh Parham; [email protected]
Received 9 February 2014; Accepted 31 May 2014; Published 17 July 2014
Academic Editor: Ryosei Minoda
Copyright 2014 Kourosh Parham. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Benign paroxysmal positional vertigo (BPPV), the most common cause of dizziness, occurs in all age groups. It presents with
vertigo on head movement, but in older patients presentation may be typical and thus accounting for a low recognition rate in the
primary care setting. It may be recurrent in up to 50% of cases. BPPV is associated with displacement of fragments of utricular
otoconia into the semicircular canals, most commonly the posterior semicircular canal. Otoconia are composed of otoconin and
otolin forming the organic matrix on which calcium carbonate mineralizes. Otoconia may fragment with trauma, age, or changes
in the physiology of endolymph (e.g., pH and calcium concentration). Presentation varied because otoconia fragments can be
displaced into any of the semicircular canals on either (or both) side and may be free floating (canalolithiasis) or attached to the
cupula (cupulolithiasis). Most cases of BPPV are idiopathic, but head trauma, otologic disorders, and systemic disease appear to be
contributory in a subset. Positional maneuvers are used to diagnose and treat the majority of cases. In rare intractable cases surgical
management may be considered. A strong association with osteoporosis suggests that idiopathic BPPV may have diagnostic and
management implications beyond that of a purely otologic condition.

1. Epidemiology and Impact

Dizziness arising from vertigo is a common morbidity that
adversely affects balance and quality of life. A study of a
nationally representative sample of 4,869 adults living in
Germany who were screened for moderate or severe dizziness
found a prevalence of 22.9% for dizziness/vertigo in the prior
12 months [1]. In that study, the prevalence and incidence of
vestibular vertigo were 4.9% and 1.4%, respectively. They also
found that, compared to nonvestibular dizziness, vestibular
vertigo was more frequently followed by medical consultation, sick leave, interruption of daily activities, and avoidance
of leaving the house.
Population studies such as the above consistently show
that benign paroxysmal positional vertigo (BPPV) is the
most common cause of dizziness [2]. In a large registry
that included data collected from 4,294 patients with vertigo
in 13 countries generated over a 28-month period (the
Registry to Evaluate the Burden of Disease in Vertigo, the
so-called REVERT registry) nearly 1/3 were diagnosed to

have BPPV [3]. BPPV can occur throughout the lifespan,

from childhood [4] into old age. While presentation with
complaints consistent with BPPV is very common, the prevalence of undiagnosed BPPV is also high. In a prospective
study in a community-based hospital located in a small
Midwestern US city, 198 young adults (99 men and 99
women), aged 1834 years, who were not being treated for
dizziness or balance problems, were recruited [5]. Besides
obtaining history and completing questionnaires, subjects
underwent vestibular positional assessment for BPPV with
infrared camera-equipped goggles recorded on digital media.
The prevalence of BPPV in this young adult population was
a surprising 9%. The rate of undiagnosed BPPV remains
high throughout lifespan. Similar to the rate observed in the
young adults, consecutive examinations of 100 older patients
in an urban geriatric clinic revealed a 9% rate of undiagnosed BPPV [6]. The one-year prevalence of individuals
with BPPV attacks (new-onset and recurrent) is believed to
rise steeply with age: from 0.5% in 18- to 39-year olds to
3.4% in individuals over 60 years of age and the cumulative

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(lifetime) incidence of BPPV reaches almost 10% by the age
of 80 [2]. These statistics are very reproducible, for example,
11% of a large population of 75-year-olds manifested BPPV
symptoms [7]. Women are two times more likely to suffer
from BPPV [2]. Patients with BPPV are 5 times more likely
to have relatives with BPPV compared to other dizzy patients
suggesting a familial tendency [8].
Subjectively, the primary complaint at presentation is
dizziness triggered by movement, such as looking up or
on head turn. The intense sensation of vertigo triggered
typically is short; however, patients feel off balance even when
avoiding sudden head movements. Common characteristics
of BPPV include rotational vertigo (in 86%), oscillopsia
(31%), nausea (33%), vomiting (14%), imbalance (49%), fear
of falling (36%), and falls (1%) [2]. As such, BPPV has adverse
psychosocial consequences including reduced health-related
quality of life [9], severe subjective impairment, and avoidance behavior in 70% of sufferers [10]. Patients with BPPV
are more likely to have depression and reduced activities
of daily living scores and sustained a fall in the previous 3
months [6]. High incidence in the geriatric population is of
particular concern because they are already at risk (e.g., due
to existing balance problems, osteoporosis, etc.) for morbidity
(e.g., bone fractures) and mortality (e.g., skull fracture and/or
intracranial hemorrhage, fat emboli form hip fractures) from
falls. BPPV increases the risk of falls, especially in the geriatric
patients [11]. Older patients (older than 70 years of age)
with BPPV take longer to seek help and may present with
complaints of unsteadiness or imbalance without vertigo
sensation [12]. This was also found in a group of older patients
referred to a Falls and Syncope Unit for evaluation who were
eventually diagnosed with BPPV [13]. The reason for referral
for evaluation of falls and syncope in this group of older,
undiagnosed BPPV patients may be their less obvious and less
characteristic presentation [13].
The economic burden of vertigo was evaluated using, in
the 4,294 patients, multinational REVERT database which
includes data from 618 centers [14]. Among those still
employed, 69.8% had reduced their workload, 63.3% had lost
working days, and 4.6% had changed their jobs. 5.7% had quit
their jobs. In the 3 months preceding a visit, patients used
emergency services 0.4 0.9 times, primary care consultations 1.6 1.8 times, and specialist consultations 1.4 2.0
times (all mean SD). A mean of 2.0 5.4 days/patient was
also spent in hospital due to vertigo. Therefore, in addition
to the negative impact on the patient from a humanistic
perspective, vertigo, including BPPV, has considerable impact
on work productivity and healthcare resource use. The costs
of caring for BPPV are estimated to be more than $2,000
per individual, much of that arising from expenses associated
with unnecessary diagnostic measures and ineffective therapy
[15].
Reflecting the natural course of the disease, BPPV
episodes are typically self-limited. Episodes of BPPV are
mostly short with a median duration of 2 weeks, possibly
accounting for why only 8% of all participants with BPPV
received effective therapy [2]. In more than half of the
patients, BPPV is a recurrent disease with a recurrence risk of
approximately 15% per year [2]. The probability of recurrence

Advances in Otolaryngology
Superior
Posterior

Anterior

Superior semicircular canal

Inferior
Posterior semicircular canal

Utricle
Saccule

Horizontal semicircular canal

Cochlea

Figure 1: Schematic illustration of the inner ear composed of

the cochlear and vestibular end organs. Structural relationship of
the semicircular canals relative to one another and the utricle is
demonstrated.

is not different between the three semicircular canals [16]. In

about 25% of recurrences, contralateral ear has been reported
to be involved, leading to the suggestion that some systemic
factors might facilitate otoconia detachment [16].
Despite the fact that BPPV is a relatively common condition, because the severity and nature of presenting complaints
can vary, BPPV has a low recognition rate in the primary
care setting [17]. The failure to correctly diagnose BPPV likely
accounts for the poor referral patterns and low proportion
of patients who receive appropriate symptom relief from the
available treatments.

2. Applied Anatomy
The inner ear contributes to two senses: balance and hearing.
It is the exclusive end organ for hearing which is served by
the cochlea. The vestibular component of the inner ear is
an important end organ for balance which in coordination
with other inputs (i.e., proprioceptive and visual) to the brain
subserves the sense of balance. The peripheral vestibular
system consists of five distinct elements on each side: three
semicircular canals and two otolithic organs, the saccule and
the utricle (Figure 1). There are excellent reviews of peripheral
vestibular anatomy and function available elsewhere [18, 19].
A brief overview is offered here to facilitate an appreciation
of the pathophysiology of BPPV.
The inner ear membranous structures and epithelium are
encased in the otic capsule which is one of the densest bones
in the body. The otic capsule, located in the petrous portion of
the temporal bone, unlike other bones in the body, has very
little turnover, in part because of factors such as osteopontin
in inner ear fluids that suppress bone remodeling [20]. The
bony canal houses a membranous duct with the space in
between being filled by perilymph. The fluid composition
of perilymph is similar to that of cerebrospinal fluid. The
membranous duct is filled with endolymph. Secretion of
endolymph is localized to the stria vascularis in the cochlea
and the dark cells in the vestibule. The ampulla of the semicircular canal secrete a potassium-rich, positively polarized
fluid, the secretion of which is dependent on basolateral Na+,

Advances in Otolaryngology
K(+)-ATPase, and Na-K-Cl cotransporter [21]. The ampulla
rests at one end of the bony/membranous canal and houses
the crista ampullaris. The crista ampullaris includes sensory
transducers (the hair cells) and the supporting structures,
as well as a gelatinous fibrillar matrix, referred to as the
cupula, in which stereocilia of the hair cells are embedded.
The specific gravity of the cupula is similar to that of the
endolymph. With rotation of the head, the endolymph filling
the membranous ducts is displaced resulting in pushing or
pulling of the cupula thus deflecting the stereocilia. Depending on the direction of the deflection and the ear in question
(toward or away from the kinocilium), the hair cells can be
stimulated or suppressed. The resulting signal is carried to the
brain by the vestibular branch of the cranial nerve VIII which
consists of bipolar afferents whose peripheral endings include
large calyxes for faithful sensorineural synaptic transmission
from the hair cells.
The three canals lie nearly perpendicular to each other
and can code three planes (roll, pitch, and yaw) along the -,
-, and -axes [22]. Pitch plane corresponds to laying down,
sitting up from supine position, or looking up- or downward,
while movement along the roll plane corresponds to rotating
the head toward the right or left in supine position [23].
Movement along the yaw plane is rotating head to the left
or right in the sitting position. Therefore, the semicircular
canals are best suited for detecting angular acceleration
during rotational head movements. The kinocilium faces the
utricle in the horizontal semicircular canal and faces away
from the utricle for the posterior and superior semicircular
canals. Deflection toward the kinocilium (utricopedal) results
in excitation and away from the kinocilium (utricofugal)
produces inhibition. The kinocilia of the crista ampullaris
in the posterior and superior (anterior or vertical) semicircular ducts are oriented to depolarize the hair cells when
endolymph moves in the utricofugal direction. Head turn to
one direction in a given plane results in movement of the
endolymph in the opposite direction. Each semicircular canal
works in concert with the corresponding canal located on the
other side of the head. They are both oriented in the same
plane; however, hair cells would be expected to convey the
opposite signal to the brain due to the opposite direction of
endolymph/cupula displacement on head rotation.
The otolithic organs are best suited for detecting linear
acceleration. They consist of the utricle and the saccule.
Because of their orientation, which is orthogonal to one
another, the utricle is more sensitive to linear acceleration
and head movements in the horizontal plane, whereas the
saccule is more sensitive to linear acceleration and head
movements in the vertical plane. The saccule is in continuity
with the cochlea through ductus reunions, thus has some lowfrequency sound sensitivity. The utricle is more proximate
to the semicircular canals which are in continuity with the
vestibule, but appears to have some sound sensitivity as well
[24]. Macula of the utricle and saccule house the sensory
receptors, the hair cells. The sensory epithelium projects hair
cells into an otoconial membrane (a viscous gel layer) on
which the otoconia rest. The crystals get displaced during
linear acceleration, which in turn deflects the ciliary bundles
of the hair cells and thus alters the vestibular signal sent to

3
the brain. Otoconia are calcite crystals composed of calcium
carbonate [25]. They have a specific weight of 2.95 grams
per cubic cm and are typically hexagonal in shape and 3 to
30 m long (see below). Because of their mass, they permit
sensitivity to gravitational forces.
Saccular function can be measured using vestibular
evoked myogenic potentials (VEMP) [26, 27]. VEMP can
help identify lesions along the pathway that connects the
saccule via the inferior vestibular nerve and the descending
vestibulospinal pathways to primarily the ipsilateral sternocleidomastoid muscle. The stimulus is a series of tone
bursts and the evoked potentials are averaged to generate
a waveform. Subjectively, dizziness with sensation of falling
is typically associated with saccular dysfunction and VEMP
abnormalities [28]. A variant of the cervical VEMP is a myogenic response that has been evoked around the eye (ocular
VEMP) [29, 30]. In ocular VEMP, tone bursts delivered to one
ear evoke myogenic potentials in the contralateral inferior
oblique muscles with information being conveyed through
afferent fibers travelling in the superior vestibular nerve.
Clinically, applications of ocular VEMP are limited. However,
in one study, abnormal function of the utricle was implied by
abnormal ocular VEMPs recorded in BPPV patients [28].

3. Formation and Structure of Otoconia

Wang and colleagues were able to identify the principal
organic component of the otoconia and partially sequenced
and cloned the major protein component of murine otoconia,
otoconin 90 [31]. Because of its similarity to secretory
phospholipase A2 (sPLA2), this gene was referred to as
PLA2-like (PLA2L) and enabled the identification of human
otoconin 90. The rigid structure of sPLA2 is conveyed by six
or seven disulfide bonds and is conserved in the otoconia
and is essential for optimal interaction of the molecule with
the mineral phase [32]. The molecular weight of otoconin
90 ranges between 90 and 100 kD, about half of which is
accounted for by posttranslational modifications, consisting predominantly of sulfated glycosaminoglycans. Using a
hyaluronidase-gold labeling technique, the localization of
glucuronic acid-containing glycosaminoglycans in the gerbil
utricle was examined by Tachibana and Morioka [33]. They
observed that otoconia and the gelatinous layer of the otoconial membrane were strongly labeled by hyaluronidase-gold
and secretory granules in supporting cells suggesting that the
organic matrix of otoconia is secreted from these cells. The
hyaluronidase labeling is lost as otoconia degenerate and are
absorbed into dark cells.
Another protein, otolin, was described as the principal
scaffold protein which was initially characterized in the zebra
fish [34, 35]. Otolin is a short chain collagen with a highly
interactive C1q globular domain. Subsequent work in mouse
documented the mammalian ortholog of otolin [32, 36, 37].
Zhao and colleagues used gene targeting and protein analysis
techniques to demonstrate that otoconin 90 is essential for
formation of the organic matrix of otoconia by specifically
recruiting other matrix components, which include otolin
[38]. They demonstrated that this matrix controlled otoconia
growth and morphology by embedding the crystallites during

4
seeding and growth. During otoconia development, the
organic matrix forms prior to calcium carbonate (CaCO3 )
deposition and provides optimal calcification efficiency. Yang
and colleagues showed that matrix components are recruited
to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia [36]. Specifically, they
demonstrated that otoconin 90 binds otolin. In wild type
mice otoconin 90 leads to an enrichment of Ca(2+) in the
luminal matrices of the utricle and saccule, whereas absence
of otoconin 90 in the null mice leads to significantly reduced
matrix-Ca(2+). Both otoconin 90 and otolin were noted to
increase the propensity of extracellular matrix to calcify in
cell culture, but together they had a synergistic effect on
calcification.
Andrade and colleagues used immunogold TEM to localize matrix proteins in mice [39]. They made several key observations. First, they demonstrated a high density of otoconin
90 in the inner core of otoconia, where they are arranged
in oval patterns implying that otoconin 90 is attached to
a scaffold consisting of the hexagonal fibrillar meshwork,
characteristic of otolin. Second, the level of mineralization
was much higher in the outer cortex where mineralized fiber
bundles are arranged parallel to the surface. Based on this
finding and observation from decalcification experiments,
they concluded that otolin matrix fibrils serve as scaffold to
guide mineralization mediated by otoconin 90. Third, they
showed that individual crystallites assemble into iso-oriented
columns and that the columns are arranged in parallel lamellae which convert into mineralized blocks for hierarchical
assembly into the complex otoconial mosaic. Fourth, they
demonstrated that in young mice the fibrils interconnecting
otoconia consisted of the short chain collagen otolin. Fifth,
they also observed that in old mice the superficial layer of
mouse otoconia demineralized thus producing weakening
or loss of anchoring of the organic fibrils interconnecting
otoconia.
Using energy dispersive X-ray microanalysis and powder
X-ray diffraction, otoconia have been described as calcitebased nanocomposites consisting of a relatively uniform
outer shape with a cylindrical bulbous body (belly) and three
rhombohedral, terminal planes at both ends which are part of
its branches [40]. Degenerative changes can range from mild
structural alteration such as fissures and surface roughening
of the less dense belly area to fractures and disintegration
leading to loss of otoconia [40]. The final component of
the disintegrating otoconia that leads to fragment formation
occurs in the belly [40]. These degenerative changes tended
to increase with age. With age, the superficial layer of mouse
otoconia becomes demineralized resulting in weakening or
loss of anchoring of the fibrils interconnecting otoconia [39].
Consequently, otoconia can detach from each other and be
released into the endolymphatic space by minor mechanical
disturbances. The mechanisms leading to degeneration and
eventual fragmentation of otoconia remain unknown.
Other mechanisms that could contribute to otoconia
fragmentation include a change in endolymph such as change
in pH, specifically acidic range, or calcium concentration.
For example, EDTA exposure causes an anisotropic solubility of human otoconia, affecting the belly region [41].

Advances in Otolaryngology
Aminoglycosides such as gentamicin can also induce morphological changes in the structure of otoconia leading to
eventual fragmentation and dissolution [41].
In summary, these results demonstrate that otoconia are
composed of organic and inorganic components. The organic
matrix is primarily composed of otoconin 90, around an
otolin scaffold. The combination of these two components
attracts and facilitates mineralization of calcium carbonate
around the inorganic matrix to form calcite crystals. The
otoconia are held anchored together with otolin-based fibrils.
The structure of otoconia and the fibrils that hold them
together is affected by the aging process and other disease
processes, thus creating conditions under which otoconia can
fragment and separate from the otoconial membrane.

4. Mechanisms of Disease
BPPV is believed to arise from displacement of particulate
matter, likely fragments of otoconia from the utricle, into
the semicircular canals. This idea was initially put forth by
Schuknecht [42, 43] based on intricate insight in vestibular
structure and function and histopathologic observations
of basophilic staining masses of granular or homogeneous
material found attached to the cupula of the posterior semicircular canal on the affected side. In a subsequent report,
Schuknecht and Ruby reported finding copular deposits in
37% of temporal bone specimens and that 58% of these were
located in the posterior canal [44]. Although the mechanisms
leading to BPPV symptoms were a matter of long-standing
debate [45], today, there is little doubt about the role of
particulate matter. The involvement of particulate matter
within the posterior semicircular canal has been established
intraoperatively in patients with BPPV [46, 47]. Welling and
colleagues prospectively examined the posterior semicircular
canal of patients with and without a clinical history of
BPPV for the presence of particulate matter. No particles
were observed intraoperatively in any of the 73 patients
undergoing labyrinthine surgery (vestibular schwannoma
excision or labyrinthectomy) without a history of BPPV [48].
Particulate matter was observed in only 8 of 26 patients with
intractable BPPV at the time of the posterior semicircular
canal occlusion procedure. Similarly, Beyea and colleagues
reported 20% incidence of free floating particles in the posterior semicircular canal of patients undergoing transmastoid
posterior canal plugging for intractable BPPV [49]. However,
particulate matter has also been reported in non-BPPV
patients who underwent posterior canal fenestration carried
out in patients undergoing acoustic tumor removal via a
translabyrinthine approach [50]. Particles were identified
in the membranous labyrinth in nine out of ten patients.
However, only one of these patients described positional
vertigo preoperatively. These observations suggest that mere
presence of particulate matter is not sufficient and that there
are other conditions that can influence the expression of
disease symptoms.
Suzuki and colleagues created an in vitro experimental
model by placing the posterior semicircular canal isolated
from the frog in Ringers solution. Saccular otoconia were
used to stimulate the cupula [51]. Posterior semicircular canal

Advances in Otolaryngology
ampullary nerve action potentials instantaneously changed
according to the direction of the gravity produced by otoconia. When the otoconia were dropped into the canal
to mimic the condition of moving otoconia in the canal,
the action potentials changed together with the otoconial
flow after a latent period. They interpreted the findings as
moving otoconia (i.e., canalolithiasis) with a latent period
that better explain clinical features of BPPV. Using a similar
approach Otsuka and colleagues used a whole membranous
labyrinth of bullfrogs to replicate the human vestibule [52].
They exposed the posterior semicircular canals but left the
remaining membranous labyrinth encapsulated in the otic
capsule. They demonstrated that a vibratory stimulus (a
surgical drill applied to the surface of the bony capsule) was
able to detach the otoconia from the utricle, consistent with
the view that mechanical insult could be a possible etiology
of BPPV. They adjusted the position of the preparation so that
the dislodged otoconia were attached to the cupular surface
to model cupulolithiasis. Alternatively, when the otoconia
were dislodged and held within the posterior semicircular
canal lumen and the position of the whole preparation was
changed so that the otoconia moved back and forth within the
canal lumen, canalolithiasis was modeled. In the cupulolithiasis model, the vestibular nerve action potentials changed
instantaneously according to the gravitational force on the
cupula. In the canalolithiasis model, the action potentials
changed in combination with the otoconial movement after
a latent period. This experimental preparation has been used
to model canalolithiasis and cupulolithiasis and recorded
ampullary nerve discharges in the bullfrog [53]. In the
canalolithiasis model, the acceleration of the otoconia was
greater for the quick positional change. This resulted in a
greater discharge with a longer duration. With the slow
positional change, the discharges were smaller and shorter. In
the cupulolithiasis model, the discharges were sustained and
their magnitude did not differ between the quick and slow
positional changes. The canalolithiasis model influenced the
magnitude of discharge of the posterior semicircular canal
depending on the speed of the positional change.
Rajguru and Rabbitt induced canalolithiasis in an animal
model (oyster toadfish, Opsanus tau) by introducing heavy
glass microbeads into the lumen of the lateral semicircular
canal [54]. Bead movement under the action of gravity
and canal afferent nerve discharge near the ampulla were
recorded extracellularly in vivo. The magnitude and time
course of the afferent responses explained the symptoms of
BPPV. A single glass bead with a diameter of about 20 m
moving at nearly 80 m/s within the lumen of the canal
elicited pathological afferent inputs to the brain equivalent
to an angular head velocity stimulus of about 100 /s. When
the head was oriented nose-down, beads moved toward the
nose and the lateral canal afferent discharge rate increased.
Afferents that normally encoded angular velocity during
oscillatory head rotations responded with tonic increases in
the discharge rate during gravity-dependent bead movement.
Other afferents, such as the units that rapidly adapt to a step
increase in angular head velocity, responded with an initial
increase in discharge rate followed by a period of adaptation.
Afferent responses occurred in the complete absence of head

5
movement and quantified the pathological inputs to the brain
that arise from canalolithiasis.
Others have adopted a mathematical modeling approach
to BPPV. Squires and colleagues utilized known hydrodynamic calculations and make reasonable geometric and
physical approximations to derive an expression for the
transcupular pressure exerted by a settling solid particle
in canalolithiasis [55]. Based on this model, the authors came
to several conclusions: (1) a pressure amplification occurs as
otoconia enter a narrowing duct; (2) an average-sized otoconium requires approximately 5 seconds to settle through the
wide ampulla, where is not amplified, which suggests a
mechanism for the observed latency of BPPV; (3) an averagesized otoconium beginning below the center of the cupula
can cause a volumetric cupular displacement on the order of
30 pL, with nystagmus of order 2 /s, which is approximately
the threshold for sensation; and (4) larger cupular volume
displacement and nystagmus could result from larger and/or
multiple otoconia. This group also utilized their model to
estimate dynamic cupular and endolymph displacements
elicited during horizontal canal BPPV provocative diagnostic
maneuvers and canalith repositioning procedures [56]. The
activation latencies in response to a horizontal canal BPPV
provocative diagnostic test were predicted to vary depending
upon the initial location of the canalith debris (e.g., within
the horizontal canal lumen versus in the ampulla). Results
explained why the onset latency of ocular nystagmus evoked
by the Dix-Hallpike provocative maneuver for posterior canal
BPPV are typically longer than the latencies evoked by
analogous tests for horizontal canal BPPV.
Obrist and colleagues used an in vitro model to test
the canalolithiasis hypothesis [57]. They carefully scaled the
physical and geometrical parameters to study the mechanics
of BPPV on an enlarged model of a single semicircular
canal with laser vibrometry and video particle tracking. Early
results support the prevalent theories on the mechanisms of
BPPV.
Zucca and colleagues hypothesized that spontaneous
recovery in untreated BPPV patient (usually in 26 weeks) is
mainly due to the fact that endolymph, owing to its low calcium content (20 microM), is able to dissolve otoconia [58].
They immersed frog saccular otoconia in normal endolymph
(Ca2+ content 20 microM) and in Ca2+-rich endolymphatic
fluids (up to 500 microM) over a 3-week period. They
demonstrated that normal endolymph can dissolve otoconia
very rapidly (in about 20 hours). When the endolymphatic
Ca2+ content was increased (50 to 200 microM), otoconia
dissolution time was slowed down (about 100 to 130 hours,
resp.) and it completely stopped when the endolymphatic
Ca2+ content was of 500 microM.
To summarize, based on clinical and experimental evidence, displaced fragments of otoconia into the semicircular
canals are now widely accepted as the cause of BPPV symptoms. However, a critical mass appears to be needed to evoke
clinical symptoms, as mere presence of fragments within
the semicircular canal is not always sufficient to induce a
change in vestibular nerve activity. Experimental models
effectively simulate canalolithiasis and cupulolithiasis providing empirical evidence in support of prevalent hypothesis on

6
pathophysiology of BPPV. Concentration of calcium in the
endolymph plays an important role in the rate of resorption of
otoconia and may influence the duration of a BPPV episode.

5. Diagnosis of Cupulolithiasis and

Canalolithiasis and Identifying the
Affected Canal
Historical recognition of BPPV and use of provocative
positioning techniques in its diagnosis had been a point of
discussion. Lanska and Remler [45], based on an excellent
review of the extant medical literature, noted that Barany
in 1921 was the first to describe BPPV in detail. They also
credited Dix and Hallpike [59] as being the first to clearly
describe both the currently used provocative positioning
technique and the essential clinical manifestations of BPPV
elicited by that technique. The Dix-Hallpike maneuver is now
a standard component of the evaluation of the dizzy patient.
When performing this procedure, the examiner stands to one
side of the patient and rotates the patients head 45 degrees
to that side to align the ipsilateral posterior semicircular
canal with the sagittal plane of the body. Next, the examiner
moves the patient, whose eyes are open, from the seated
to the supine test-ear-down position and then extends the
patients neck slightly so that the chin is pointed slightly
upward. The latency, duration, and direction of nystagmus,
if present, and the latency and duration of vertigo, if present,
are noted. Each position should be maintained at least 30
45 seconds or until nystagmus resolves. If positive, rotary
nystagmus toward the test ear is commonly observed, which
is induced by the movement of free-floating debris within
the affected canal (away from the cupula, inducing deflection
of the cupula away from the vestibule). If no nystagmus is
observed, or if observed once it resolves, the patient is seated
upright and once again eyes are monitored for nystagmus
which is once again documented as above. The procedure is
repeated for the opposite ear. More recently, head shaking
during the exam has been proposed to increase the diagnostic
yield of the Dix-Hallpike exam [60]. Specifically, patients
suspected of having posterior canal BPPV, but with negative
Dix-Hallpike, are recommended to undergo head shaking
Dix-Hallpike. This subgroup of patients is suspected of having
a milder form of posterior canal BPPV (also see below for
subjective BPPV). The side-lying test which also stimulates
the posterior semicircular canal may be more suitable for
older patients because the head and neck are fully supported
by the examination table [7]. In this test, after seating the
patient on the examination table, the head is turned 45 away
from the involved ear then the patient lies on the side of the
involved ear [61].
Lansk and Remler point out that despite their important contributions, neither Barany nor Dix and Hallpike
understood the pathophysiology of BPPV nor did they
appreciate that the positioning techniques they used actually demonstrated pathology in the semicircular canals
rather than the utricle. They go on to attribute the modern understanding of the pathophysiology of BPPV to
Schuknechts proposal that the dysfunction resulted from

Advances in Otolaryngology
the gravity-dependent movement of loose or fixed dense
material within the posterior semicircular canal (cupulolithiasis) [42]. They add that although Schuknechts formulations were not consistent with all clinical features of the
disease, they led to the modern canalolithiasis theory and
highly effective canalith repositioning or liberatory maneuvers for BPPV. Hall and colleagues brought clarity to understanding the mechanisms underlying posterior canal BPPV
by emphasizing the importance of fatigability of symptoms
[62]. Hall and colleagues noted that, under the influence of
gravity, a density differential between the endolymph and the
cupula will cause displacement of the cupula when changes
in head position occur. They explained that BPPV can be
divided into two types based on the presence or absence
of fatigability. Specifically, nonfatigable nystagmus was the
result of particles being fixed on the cupula (cupulolithiasis),
whereas fatigable nystagmus was due to free floating particles
within the body of posterior semicircular canal. This latter
condition was subsequently referred to as canalolithiasis
[63].
Theoretically, if particulate matter can be located in the
long arm of the semicircular canals or attached to the cupula,
distally, it could also be present in the short arm or attached
to the cupula, proximally. Indeed a histopathologic study
reported that canaliths have been found to be located in the
short arm of the semicircular canals (proximate to the utricle)
[64]. Clinical correlate of this entity has yet to be defined.
Posterior canal BPPV is the most common. In a study
of 614 BPPV patients over an 11-year period, the posterior
semicircular canal was affected in 543 cases (88.4%), the
horizontal in 39 (6.4%), and the superior canal in 32 (5.2%)
[16].
BPPV of the posterior canal, the most inferior canal,
is believed to be much more frequent because gravitational
forces settle the particles in this canal, particularly when
the patient is in the lateral supine position [65]. In contrast,
the superior semicircular canal is the highest point of the
labyrinth, thus it is rarely involved in BPPV. To settle particles
into the superior canal, very marked hyperextension of the
head is required [65].
Several authors have characterized horizontal BPPV [66,
67]. Horizontal BPPV is triggered when the head of the
supine patient is turned from side to side and is characterized
by a bidirectional horizontal nystagmus. As with posterior
BPPV there are also two subtypes of horizontal BPPV
depending on the location of the otoconia fragments. In
canalolithiasis, fragments of otoconia move freely in the
horizontal semicircular canal inducing stimulatory utriculopetal endolymph flow, whereas in cupulolithiasisotoconia
are attached to the cupula or are trapped in the proximal
segment of the canal near to the cupula. In canalolithiasis,
vertigo is triggered by circular acceleration in the plane of
the horizontal semicircular canal while, in cupulolithiasis,
vertigo is triggered when the head changes position, but
not by circular acceleration. In canalolithiasis, nystagmus is
geotropic (toward the undermost ear) and more intense after
rotation of the head toward the affected side. In cupulolithiasis, the nystagmus during cupulolithiasis of the horizontal
semicircular canal is apogeotropic (away from the undermost

Advances in Otolaryngology
ear) and more intense after rotation of the head toward
the unaffected ear. It is recommended that, for patients
presenting with symptoms of BPPV, if the Dix-Hallpike test
is negative, a supine roll test be performed to assess for lateral
canal BPPV [68].
Clinically identifying the affected side in horizontal canal
BPPV can be challenging. The problem is that during diagnostic maneuver (e.g., the supine head roll test, also known
as the Pagnini-McClure maneuver), one horizontal canal
cannot be isolated from the other, as both head positions
stimulate the horizontal canals resulting in nystagmus with
either ear down. In addition, horizontal canal BPPV causes
direction-changing nystagmus. As noted above, horizontal
BPPV-related nystagmus can be geotropic or apogeotropic,
but the direction of the nystagmus relative to the ground is
the same in both positions of the supine head roll test. Ewalds
second law provides guidance on determining the affected
side. Ewalds three laws were generated after experiments
in pigeons whose semicircular canals were stimulated using
pneumatic devices [69]. They state that a stimulation of the
semicircular canal causes a movement of the eyes in the
plane of the stimulated canal. In the horizontal semicircular
canals, an ampullopetal endolymph movement causes a
greater stimulation than an ampullofugal one. In the vertical
semicircular canals, the reverse is true. Ewalds second law has
profound clinical implications. The directional asymmetry
implies that, in persons who have lost inner ear function
on one side, the remaining side should produce higher
velocity nystagmus when the head is being rotated towards
the remaining intact ear (ampullopetal), but less when the
head is being rotated towards the side of vestibular loss. Aron
and Bance provided validation of Ewalds second law in a rare
case combining horizontal canal BPPV with a dead ear on
the contralateral side, therefore arising from a known side
[70]. They presented the case of an 87-year-old male with
history of invasive left ear cholesteatoma which had fistulized
into the horizontal canal. He underwent successful resection
of disease with postoperative caloric testing showing absent
responses on the left side and a dead ear. Ten years later,
the patient presented with chronic dysequilibrium aggravated
by head movements. Dix-Hallpike test was negative, but a
supine head roll test demonstrated bilateral apogeotropic,
horizontal nystagmus, which was more pronounced with the
head turned to the left. Videonystagmography demonstrated
the increased slow phase velocity of the nystagmus when
the head was turned to the left (i.e., away from the affected
ear). This case corroborates Ewalds law for lateralization of
apogeotropic horizontal canal BPPV.
Patients with lateral canal BPPV may also exhibit a
mild spontaneous horizontal nystagmus while in the sitting
position but because presentation of nystagmus is strongly
influenced by head position and movements, this type of
nystagmus may be more accurately referred to as pseudospontaneous nystagmus [71]. It beats toward the healthy
side when the lateral canal BPPV is geotropic and toward
the affected side when it is apogeotropic and when absent
[71, 72]; it is sometimes possible to evoke it with a mild
shaking of the head [71]. Patients with apogeotropic show predominantly contralesional head-shaking nystagmus, whereas

7
patients with geotropic type do not show any directional
preponderance [72].
The bow and lean test has been promoted as a useful
method to identify the affected side in horizontal canal BPPV
[73]. In a prospective study, for diagnostic purposes, subjects
were divided into two groups: standard head roll test versus
the bow and lean test. The latter group had better remission
rates for both canalolithiasis and cupulolithiasis of the lateral
canal.
Initial presenting history can be an important aid in
identification of the involved canal. There is a relationship
between the position that initially provoked vertigo and the
affected semicircular canal in patients with BPPV. History
taking regarding the side of provoking position at the
onset of vertigo helps predict the side affected by BPPV in
both posterior canal BPPV and geotropic horizontal canal
BPPV [23]. Although the type of BPPV cannot be predicted
by the initial position provoking vertigo, the side of the
BPPV is strongly correlated to the head-turning side in the
supine position that initially provide vertigo in this group of
patients.
When apogeotropic horizontal canal BPPV is suspected,
further detailed examinations using additional localization
methods, including supine head roll test and pitch-plane
test, are typically needed. The waking-up position was the
most common situation that initially provoked vertigo in
all subtypes of BPPV, including geotropic and apogeotropic
horizontal canal BPPV [23].
Until recently diagnosing of superior (anterior) semicircular canal BPPV was controversial. Because of its anatomical
location, the superior semicircular canal is rarely affected
in BPPV. In a retrospective study where over a 1-year
period 4,320 patients consulting for otoneurological disease
were investigated by otological, videonystagmography, and
neurological examination, BPPV was diagnosed in 1,430
patients (33%) [65]. Among these the posterior semicircular
canal was involved in 1,325 patients (92.6%), the horizontal
semicircular canal in 85 patients (5.9%), the posterior semicircular canal and ipsilateral superior semicircular canal in
19 patients (0.01%), and the superior semicircular canal only
in one patient (0.0007%). In the 20 patients with superior
semicircular canal BPPV, the Dix-Hallpike test induced apogeotropic horizontal torsional nystagmus beating towards the
uppermost ear in the lateral supine position with reversal on
standing. That is nystagmus beating towards the uppermost
ear on the Dix-Hallpike test is consistent with BPPV involving
the superior semicircular canal of the uppermost ear. The
author suggests that the torsional component of nystagmus
and not just the vertical component must be taken into
account to facilitate the diagnosis.
Multiple canals can be involved at presentation, not
uncommonly after head trauma [74]. Involvement of multiple
canals can give rise to atypical presentation and challenging
management with repositioning maneuvers [74, 75]. It has
been argued that the most significant factor in diagnosis
of the type of BPPV is observation of the characteristics
of the provoked nystagmus during the diagnostic positional
maneuvers, although the combination of posterior-anterior
canal involvement remains particularly challenging [76].

Special considerations are warranted in the geriatric population, because geriatric patients with BPPV usually report
dizziness or imbalance and do not always describe a rotatory
crisis. Batuecas-Caletrio and colleagues have argued that the
Dix-Hallpike and supine roll tests should be performed in
older patients with dizziness, despite the fact that they do not
complain of spinning sensation with positional changes [12].
Finally, a number of studies have reported that the right
ear is predominantly affected [10, 12, 16]. It has been suggested
that prolonged lying may facilitate the deposition of otoconia
on the cupula or contribute to their loosening from the utricle
(see below) and that this mechanism might also explain why
the laterality of BPPV often corresponds to the preferred side
of lying during sleep [77].

Advances in Otolaryngology

Posterior semicircular canal

canaliths

6. Treatment
Mechanical repositioning: historically, as the proposed mechanism involving cupulolithiasis and canalolithiasis became
more widely accepted, the idea of using head positioning
maneuvers to relieve symptoms of BPPV evolved as an
alternative to conservative management (i.e., avoidance of
provocative head positions and changes) and surgical procedures. Brandt and Daroff used a physical therapy approach
involving repeated maneuvers to loosen and disperse the
degenerated otolithic material from the cupula [78]. These
efforts were followed by liberatory maneuver of Semont [79]
and subsequently canalith repositioning procedure of Eply
(Figure 2) [80, 81]. Given that the dominant view at that
time was that BPPV arose from the involvement of the
posterior semicircular canal, these repositioning procedures
were mainly directed at providing relief of posterior canal
BPPV. However, several varieties of BPPV can be experienced
depending on the semicircular canal involved, whether or not
cupula is involved, single or multiple canal involvement, and
sidedness of the affected structures. In fact, the effectiveness
of the repositioning maneuvers varies depending on correct
identification of the affected canal.
To assess the effectiveness of the Epley maneuver in
treatment of posterior semicircular canal BPPV, Hilton and
Pinder, in a Cochrane review, compared Epley maneuver
versus placebo Epley maneuver versus untreated controls
[82]. They evaluated the frequency and severity of attacks of
vertigo, proportion of patients improved by each intervention, and conversion of a positive Dix-Hallpike test to a
negative Dix-Hallpike test. Fifteen randomized trials were
identified but twelve studies were excluded because of a high
risk of bias, leaving three trials in the review. Trials were
mainly excluded because of inadequate concealment during
randomization, or failure to blind outcome assessors. The
studies included in the review addressed the efficacy of the
Epley maneuver against a sham maneuver or control group.
They concluded that the Epley maneuver is a safe effective
treatment for posterior canal BPPV. A more recent review
83 arrived at the same conclusion, noting that based on a
systematic review of all relevant randomized controlled trials
(Level I evidence) there is strong evidence of efficacy of the
Epley maneuver in treatment of posterior canal BPPV, with
no serious adverse effects.

Figure 2: Illustration of the Epley maneuver for the treatment of

left posterior canal BPPV. From a seated position (top), the patients
head is turned 45 to the left (2nd from top). The patient is laid down
with the head rotated to the left and neck is extended (3rd from top).
Next, the head is turned 90 to the right (4th from top) followed
by rolling the body to the right such that patient is lying on the
right shoulder looking toward the floor (2nd from bottom). Finally,
the patient is returned to the seated position with head remaining
rotated to the right (bottom). Each position is held for at least 3060
seconds or until nystagmus or vertigo has resolved. Frenzel lenses
can facilitate visualization of nystagmus. Adapted from Mitka [151].

There are currently two practice guidelines that are

available for diagnosis and management of BPPV, one by
the American Academy of Neurology [83] and another by
American Academy of Otolaryngology-Head & Neck Surgery
[68]. They both offer thorough reviews of the available
evidence and validate the effectiveness of the Epley maneuver
in management of posterior semicircular canal BPPV.
A more recent Cochrane review compared a modification
of Epley maneuver to the standard Epley maneuver [84].
Nine studies included post-Epley postural restrictions. Such
restrictions could include using a neck brace, head movement
restrictions (avoiding bending the head up and down or
bending over), and instructions to sleeping upright. The
review concluded that there was a statistically significant
advantage of post-Epley postural restrictions. Specifically, it
was found that in the experimental group 88.7% versus 78.2%
in the control group converted from a positive to negative
Dix-Hallpike test.
The same Cochrane review found that there is insufficient
evidence to support the routine application of mastoid
oscillation during the Epley maneuver. Mastoid oscillation
involves applying vibration to the mastoid bone behind the
ear during the maneuver (an augmented Epley).
In a prospective study in geriatric BPPV patients, both
clinical and functional aspects of body balance, including

Advances in Otolaryngology
postural instability, improved after treatment with the modified Epley maneuver [85]. However, in the older patients,
the effectiveness of therapeutic repositioning maneuver (see
below) is lower than those under 70 and the recurrences are
more frequent [5].
At present, the best available treatment of the horizontal
canal BPPV is the roll (Barbecue or Lempert) maneuver [67,
8689]. The procedure is effective in managing lateral canal
BPPV in a lower proportion of patients than Epley maneuver
is in control of posterior canal BPPV (<75% versus 88%,
resp.). The Gufoni maneuver is another technique that has
been reported as effective in treating horizontal canal BPPV.
In a double-blind randomized controlled trial, this maneuver
proved effective for both geotropic and apogeotropic forms
with 84% relief of vertigo after 24 hrs [90].
Options in management of the cupulolithiasis of the horizontal semicircular canal are very limited where the challenge
is to detach the otoconia fragments from the cupula. It has
been suggested that repetitive somersaults may be beneficial.
In somersaults, acceleration in the forward-facing direction
may induce an intracanalicular force strong enough to detach
otoconia debris from the cupula and the ongoing rolling
may move loose otoconia debris back into the utricle [91].
Yamanaka and colleagues described the head-tilt hopping
exercise in treatment of cupulolithiasis associated with BPPV
of the horizontal semicircular canal, which is characterized
by apogeotropic direction-changing nystagmus [92]. This
treatment is designed to release otoconial debris adherent to
the cupula as the patients hopped while tilting their heads
laterally. The treatment required several sessions daily over a
4-week period. Nystagmus of 33.3% patients with intractable
lateral canal BPPV disappeared immediately after the first
training session and after 1 and 4 weeks of the training, 56%
and 70% of patients that had experienced improvements,
respectively. It is important to note, however, given the
natural history of BPPV, that absence of untreated control
group significantly weakened the potential for generalization
of this study.
In a recent study of 965 BPPV patients, canalith repositioning procedures (Epley and Barbeque maneuvers) provided long-lasting noninvasive treatment for BPPV with 85%
effectiveness after the first procedure [89]. Fourteen percent
of patients had recurrences, with this group of patients
having characteristics of being older or having history of head
trauma or vestibular neuropathy. The authors suggested that
geriatric patients, because of a significantly higher recurrence
rate, should have additional education to minimize potential
morbidity of their falls.
In general, The Epley maneuver is effective in treatment
of superior semicircular canal in 94.1% of cases after one
treatment and 97.5% after multiple treatments [65]. However,
in another report, therapeutic maneuvers were found to be
more effective in resolving posterior canal or horizontal canal
BPPV than superior canal BPPV [16]. Specific maneuvers for
relief of superior canal BPPV have been described [93, 94].
For example, a sequence of maneuvers consisting of head
positioning beginning supine with head hanging 30 degrees
dependent with respect to the body, then supine with head
inclined 30 degrees forward, and ending sitting with head 30

9
Nerve to superior semicircular canal
Nerve to utricle
Facial nerve

Nerve to horizontal
semicircular canal
Nerve to posterior
semicircular canal
(singular nerve)

Nerve to saccule
Cochlear nerve

Figure 3: Schematic illustration of the nerves travelling through the

internal auditory canal, including branches of the eighth cranial to
the vestibular end organs. Singular nerve innervates the ampulla of
the posterior semicircular canal.

degrees forward are reported to relieve 100% of vertigo and

nystagmus in one retrospective series [93].
Canalith repositioning, in an appropriately selected
patient, is a generally safe procedure. Minor adverse events
of canalith repositioning include severe nausea and vertigo
during the procedure and instability or light-headedness
for approximately 48 hours after the procedure [89]. Other
complications have also been reported. The most common
complication is canal switching, where otoliths from one
semicircular canal are unintentionally displaced into another.
Canal switching has been reported in 6% of the patients with
posterior canal BPPV [95]. Canal switching appears to more
likely during Epley than Semont maneuver because of the
higher number of maneuver steps during which the head
is in the dependent position [96]. A very rare and unusual
complication is internal carotid artery dissection, with only
one reported case [97].
Despite the effectiveness of the Epley maneuver to treat
BPPV, it remains underutilized in many settings to which
sufferers initially present, such as the emergency room [98].
Surgical management: surgical options are pursued when
debilitating posterior canal BPPV is unresponsive to bedside repositioning. Posterior ampullary (singular) nerve
transaction was the first proposed surgical treatment for
intractable posterior canal BPPV [99]. Gacek was motivated
by Schuknechts observations of otoconial mass embedded
in the cupula of the posterior canal crista (see above) which
is innervated by the posterior ampullary branch of the
inferior vestibular nerve (Figure 3). Gacek proposed singular
neurectomy through a tympanotomy approach under local
anesthesia for treatment of disabling chronic (greater than 1
year) BPPV [100].
Posterior semicircular canal occlusion (canal plugging)
was first described by Parnes and McClure [47]. This operation can be effectively performed using a transmastoid
approach [49]. Plugging is performed with bone dust mixed
with fibrinogen sealant (bone pate) which is gently packed
into a fenestration drilled into the posterior semicircular
canal. In one series, all but one of 44 patients who underwent
this procedure were relieved of BPPV on follow-up between
6 months and 12 years [101]. This treatment produces temporary postoperative imbalance and motion sensitivity for
several weeks, but spares hearing.

10

7. Etiology
Soto-Varela and colleagues reported that the origin of BPPV
remained unknown in 61.9%, but in the remainder, BPPV
appeared to be associated with previous trauma (6.7% of
all patients), ipsilateral Meni`eres disease (6.5%), ipsilateral
vestibular neuritis (5.6%), history of BPPV affecting the same
ear (5.2%), a severe systemic disease (4.6%), and history
otologic surgery (1%) [16]. Severe systemic disease included
patients with carcinoma who were receiving treatment with
radiotherapy or chemotherapy, recent myocardial infarction,
leukemias treated with chemotherapy, sarcoidosis, and active
ulcerative colitis.
Head trauma is a long recognized cause of BPPV [102].
Traumatic BPPV is more likely to be bilateral, occurring in
25% compared with only 2% in idiopathic BPPV [103]. A
variant of posttraumatic BPPV is postsurgical BPPV. Among
nearly 1000 cases, the incidence of BPPV after surgical
drilling of the temporal bone was around 1%, and the horizontal semicircular canal of the contralateral ear was predominantly involved (90%) [104]. Maxillofacial (orthognathic)
surgery has been reported to result in BPPV which can be
bilateral and incapacitating occurrence which resolves slowly
[105, 106]. Another example is rhinoplasty, possibly due to
utilization osteotomies [107]. In comparing management of
posttraumatic BPPV with idiopathic vertigo, it appears that
typically more positioning maneuvers are needed to achieve
relief in the former [108, 109].
Physical activity can also influence occurrence of BPPV
independent of any specific trauma. Physical activity such as
swimming [110] and mountain biking [111] have also been
reported to trigger BPPV. On the other hand, prolonged bed
rest has been recognized for a long time as a provoking factor
for BPPV. It was suggested that prolonged lying may facilitate
the deposition of otoconia on the cupula or contribute to their
loosening from the utricle [112]. The above mechanism might
also explain why the laterality of BPPV often corresponds to
the preferred side of lying during sleep [77]. Consequently,
it has been hypothesized that mild to moderate physical
activity might relocate the particles from the canal, thus
preventing the accumulation of an adequate number of
otoconia necessary for forming an agglomerate [113]. Authors
quantified physical activity during leisure, household, and
occupational activities over a 7-day period in a group of 63
BPPV and 63 age- and gender-matched subjects. Physical
activity was significantly lower in patients with idiopathic
BPPV than in controls regardless of gender and occupational
activity. The difference was mainly in individuals older than
60 years. Most of the individuals at this age are retired, which
explains why leisure and household activities may become
more important. While geriatric patients did not differ from
controls in occupational activity, they demonstrated less
daily leisure and household activity than controls. Finally,
trauma can also be without a direct physical component. For
example, radiation therapy for treatment of nasopharyngeal
carcinoma has been reported to induce BPPV [114]. Other
unusual causes include occlusion of the anterior vestibular
artery causing a sudden vertigo crisis (Lindsay-Hemenway
syndrome) that includes otolith disease [115].

Advances in Otolaryngology
Given that BPPV affects a substantial proportion of the
population and that there remain significant limitations in
our ability to fully control its symptoms and recurrences, over
the past decade effort has been directed at identification of
medical factors that may predispose a patient to development
of idiopathic BPPV. Associations have been reported between
BPPV and diabetes [116]. In a case-control histopathologic
human temporal bone study, temporal bones from patients
with type 1 diabetes mellitus and normal temporal bones from
age-matched individuals were histopathologically examined
[117]. It was found that the prevalence of cupular and freefloating deposits in the lateral and posterior semicircular
canals was significantly higher in type 1 diabetes mellitus
patients compared with normal temporal bones. Another
systemic link was described recently where the lipid profiles
and serum uric acid levels were found to be higher in patients
with BPPV than in controls [118]. Curiously, serum uric acid
levels decreased one month after the BPPV attack; however,
the mechanisms behind these observations have not yet
been elucidated. Other conditions that have been associated
with BPPV include chronic thyroiditis [119], hypertension,
hyperlipidemia, and stroke [2].
To find a statistical link between common comorbidities affecting the elderly population (hypertension, diabetes,
osteoarthrosis, osteoporosis, and depression) and recurrent
episodes of BPPV data from over 1,000 BPPV patients in 11
centers across 7 countries were examined [120]. The results
showed the presence of at least one comorbid disorder in 20%
of subjects and 2 or more in 37% of subjects. Furthermore,
it was noted that over 50% of subjects had at least one
recurrence and that the higher the number of comorbidities,
the greater the number of recurrences.
Among the comorbidities, the association with osteoporosis has raised much interest, in part because it implies
that abnormal bone turnover may underlie BPPV. Vibert
and colleagues reported that among thirty-two 5085-yearold Swiss women with idiopathic BPPV, 75% had osteopenia/osteoporosis on dual X-ray absorptiometry (DEXA)
[121]. Jang and Kang reported that Korean women (2069
years of age) with idiopathic BPPV had lower bone mass density (BMD) values compared to normal controls [122]. They
also reported that patients with low BMD measured by DEXA
had increased recurrence rate and required an increased
number of canalith repositioning maneuvers. Jeong and
colleagues evaluated BMD of 209 Korean men and women
with idiopathic BPPV and compared them to control subjects
without history of vertigo. The prevalence of osteopenia and
osteoporosis was higher in both women and men with BPPV
than in controls [123]. Mikulec and colleagues conducted a
retrospective chart review to assess the prevalence of treated
osteoporosis (on antiresorptive therapy) in 260 women with
and without BPPV between 51 and 80 years of age [124].
They observed a statistically significant negative association
between BPPV and treated osteoporosis in women aged
5160 years but not the older group. Among Japanese BPPV
patients with osteoporosis, the incidence of recurrence was
56.3% (compared to 16.1% in those with normal bone mineral
density) and the frequency of BPPV recurrence increased as
BMD decreased [125]. Finally, Korean patients with BPPV

Advances in Otolaryngology
show a higher prevalence of vitamin D deficiency [126]
and a recent pilot study showed that in 4 Austrian patients
with BPPV recurrence, vitamin D levels were lower than
those without recurrence and recurrences were relieved with
vitamin D supplementation [127].
Although these studies have investigated the association
between BPPV and low bone mineral density, the cooccurrence of two morbidities is not by itself supportive of
causation. Low bone mineral density (e.g., in premenopausal
women) might reflect low peak bone mass based on genetic
predisposition, environment, and lifestyle factors [128] and
osteopenia/osteoporosis are prevalent disorders of aging.
Furthermore, a limitation of asserting an association based
on DEXA scan findings is that any physiological alterations
in bone turnover take about one year to be detectable by
DEXA scan [129]. Since osteoporosis is a slowly changing
disease process there is an obvious incongruence between
DEXA scan findings and BPPV episodes, which tend to
present abruptly and typically are self-limited (days to weeks
in duration). An alternative approach is to examine biochemical markers of bone turnover, whose levels change rapidly
(within 13 months) and are more temporally relevant to the
natural history of BPPV. Parham and colleagues used these
markers to demonstrate that idiopathic BPPV patients tend
to have higher levels of biochemical markers of bone turnover
and that these levels are influenced by vitamin D level [130].

8. Differential Diagnosis
Although BPPV is one of the most common causes of
vertigo, it is not the only disorder associated with recurrent vertigo. Menieres disease, migraines, vertebrobasilar
insufficiency, and panic disorder are also characterized by
recurrent episodes. Caution in diagnosis BPPV is warranted
as other conditions can present with BPPV-like symptoms.
For example, central vestibular disorders can give rise to
positional nystagmus, which can be mistaken for BPPV. Such
lesions can arise from posterior fossa such as from small
cerebellar strokes [131]. In inner ear pathologies which may
cause vestibulopathies, such as perilymph fistulas, nystagmus
may be enhanced by Dix-Hallpike testing. Furthermore, as
spontaneous nystagmus associated with a perilymph fistula
improves, nystagmus toward the affected ear in the downward
position may misdirect the examiner from the initial pathological trigger of the symptoms. Other vestibulopathies that
cause horizontal nystagmus may also be enhanced by DixHallpike testing. Welgampola and colleagues cite another
example where spontaneous horizontal nystagmus from
acute peripheral vestibulopathies may be enhanced by DixHallpike testing [132]. Specifically, spontaneous nystagmus
from a right-sided vestibular neuritis will be left beating in the
left lateral and right lateral positions. In contrast, nystagmus
from left horizontal canal BPPV will be vigorously left beating
in the left lateral position and will beat less vigorously to
the right in the right lateral position. Low-velocity sustained
horizontal, vertical, or torsional nystagmus can be found
in patients with clinically definite vestibular migraine [133].
BPPV occurs more frequently in patients with migraines than
those without [134]. One study reported that migraines were 3

11
times more likely in BPPV patients than in general population
and a family history of migraine is present in nearly 60%
of BPPV patients [135]. Prevalence of migraine in patients
that have been diagnosed with BPPV of childhood is higher
than in the general population, which led to the proposal that
childhood BPPV is a precursor of migraine [136].
BPPV can occur secondary to various other conditions including viral neurolabyrinthitis, Menieres disease,
and vertebrobasilar ischemia [137]. In Menieres disease,
it has been suggested that hydropic distension or rupture
damages the otolithic apparatus, leading to the release of
otoconia debris which migrate to the semicircular canals
where they may result in BPPV [138]. Balatsouras and
colleagues reported that the BPPV associated with Menieres
disease differs from idiopathic BPPV in regard to several
epidemiological and clinical features, may follow a different
course, and responds less effectively to treatment [139]. In
a retrospective/epidemiological study of 345 BPPV patients,
they identified 8.4% incidence of Menieres disease. The
patients with BPPV associated with Menieres disease tended
to be greater than 90% female, have had a longer duration
of symptoms, commonly had involvement of the horizontal
semicircular canal (25%), had a greater incidence of canal
paresis on videonystagmography, needed more therapeutic
sessions to relieve their BPPV, and had a higher rate of
recurrence.
Lee and colleagues reported that BPPV may occur secondary to inner ear diseases, including idiopathic sudden
sensorineural hearing loss (51%), Menieres disease 28.9%)
and unilateral vestibulopathy such as acute vestibular neuronitis and herpes zoster oticus (20.2%) [140]. They further noted that Menieres associated BPPV most commonly
involved the lateral canal. The durations of treatment for
idiopathic BPPV and BPPV secondary to inner ear diseases
were 2.28 and 4.87 days, respectively. The mean duration of
treatment was 6.28 days for idiopathic sudden sensorineural
hearing loss with BPPV, 5.07 days for BPPV with unilateral vestibulopathy, and 2.28 days for BPPV with Menieres
disease. Of note, BPPV in idiopathic sudden sensorineural
hearing loss patients portends a poor prognosis [141].
There appears to be a variant condition where recurrent
vertigo associated with fast head movements and history
consistent with BPPV is associated with absence of nystagmus
on the Dix-Hallpike maneuver [139, 142145]. This variant
is known as subjective BPPV [139] or sitting-up or Type
2 BPPV [145]. It is characterized by vertigo and/or nausea
in the absence of nystagmus during the Dix-Hallpike or roll
test. Alvarenga and colleagues suggested that the patients
could have small amounts of calcium carbonate particles
stuck to the cupula or floating in the affected semicircular
canal which may not be enough to cause nystagmus, but
sufficient enough to induce nausea and/or vertigo [144].
Others suggest that this condition may be related to chronic
canalolithiasis within the short arm of a posterior canal [145].
An alternate explanation was put forward when Johkura and
colleagues noted that nystagmus may be present but may be
too subtle to detect without additional instrumentation [146].
They investigated 200 geriatric patients with dizziness with
an infrared camera and video-oculography and found a faint

12

Advances in Otolaryngology

positional apogeotropic horizontal nystagmus, compatible

with horizontal semicircular canal BPPV in nearly 50% of
the patients. This nystagmus was not detectable with Frenzel
glasses. Gans has offered a fourth explanation based on
a change in the calcium metabolism and the consequent
nonabsorption of free otoliths [147], which would increase
their quantity in the semicircular canals and enable the
triggering of vertigo upon head movement. Alvarenga and
colleagues suggest that the affected labyrinth can be identified
based on which side induced nausea or vertigo on positioning
testing [144].
Regardless of etiology, BPPV arising from other inner
ear diseases [140, 148] and subjective BPPV [149] can be
treated using the same approach as to typical BPPV, although
success rate may be slightly lower. Finally, intracranial tumors
can cause positional vertigo which should be differentiated
from BPPV based on history and neurotological examination
findings [150]. The differentiating features include symptoms
duration >35 days, sensorineural hearing loss, nonfatiguability positional nystagmus, variable duration and latency
of nystagmus on positional changes, nonresponsiveness to
canalith repositioning, and possible rollover phenomenon.
This latter entity has been referred to as malignant paroxysmal positional vertigo [150].

to be effective in management of the superior canal BPPV. The

Lempert or Gufoni maneuvers can effectively manage lateral
canal BPPV, assuming the affected side has been correctly
identified.
The majority of BPPV cases are idiopathic; however, other
inner ear diseases (e.g., labyrinthitis, Menieres disease) and
head trauma (e.g., accidental or intraoperative/iatrogenic)
can lead to BPPV. Idiopathic BPPV may be closely associated
with systemic diseases such as diabetes and osteoporosis.
A predisposition to developing BPPV is supported by the
high rate of idiopathic disease, recurrences months after
resolution, recurrences that can be in contralateral ear, and
a familial tendency for the occurrence of BPPV.
Further investigation of systemic causes of idiopathic
BPPV may introduce a major shift in the clinical management
paradigm for BPPV. Currently, the dominant clinical perception of idiopathic BPPV is that of a purely otologic disorder
and, therefore, management is focused on canalith repositioning only. With identification of the clinical variables that
contribute to idiopathic BPPV or increase vulnerability to
development of BPPV, clinical management of BPPV will
likely evolve beyond treatment of acute episodes with canalith
repositioning to global management aimed at preventing the
disease and its recurrences.

9. Summary and Future Directions

Conflict of Interests

BPPV is believed to be a focal disorder of the inner ear with

manifestations which affect the well-being and functional
capacity of the sufferers. It occurs more frequently in women
than men (2 to 1 ratio) and its prevalence increases with age.
BPPV arises from displacement of otoconia fragments into
the semicircular; however, a critical mass is needed to evoke
clinical symptoms, as mere presence of fragments within the
semicircular canal is not always sufficient to induce a change
in vestibular nerve activity. Because of the anatomy of the
inner ear, the posterior semicircular canal is more commonly
affected, but lateral and superior canals can also be involved.
In the majority ofcases, diagnostic maneuvers, such as the
Dix-Hallpike and head roll test, can effectively lead to identification of the involved canal, although diagnosing the affected
side in lateral canal BPPV can be challenging. Otoconia are
composed of organic and inorganic components. The organic
matrix is primarily composed of otoconin 90, around an
otolin scaffold. The combination of these two components
attracts and facilitates mineralization of calcium carbonate
around the inorganic matrix to form calcite crystals. The
otoconia are held anchored together with otolin-based fibrils.
The structure of otoconia and the fibrils that hold them
together is affected by the aging process and other disease
process.
The natural history of BPPV is one of a self-limited
disease in which symptoms resolve as otoconia fragments
dissolve into endolymph. The rate of dissolution of the
fragments is dependent on calcium concentration within the
endolymph, such that low concentrations lead to faster resolution. Canalith repositioning maneuvers effectively manage
the majority of cases. Evidence supports treatment of the
posterior canal with the Epley maneuver, which also appears

The author declares that there is no conflict of interests

regarding the publication of this paper.

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