Introduction
Persistent postural-perceptual dizziness (PPPD) is characterized by chronic dizziness
as the chief complaint and has been newly listed in the 2018 revision of the 11th
version of the International Classification of Diseases (ICD-11) provided by the World
Health organization (WHO).[1] The diagnostic criteria listed by the Barany Society include lightheadedness as
the chief complaint and unsteadiness or nonspinning vertigo persisting for at least
3 months. Furthermore, the patient must view moving objects and complex visual patterns,
and symptoms must be aggravated by standing or walking as well as during active or
passive body movements. Typically, PPPD is secondary to balance disorders, such as
vestibular diseases. Although organic vestibular disorders or psychiatric diseases
may be present as comorbidities or complications, they do not account for the symptoms[2]
[3]
[4]
[5] ([Table 1]). To date, although cases of transition from peripheral vertigo disorders, such
as Meniere's disease (MD) or benign paroxysmal positional vertigo (BPPV), to PPPD
have been reported in Japan,[6]
[7] there is a paucity of data on the rate of and tendency to such transitions.
Table 1
Criteria for the diagnosis of persistent postural-perceptual dizziness (PPPD)
|
PPPD is a chronic vestibular disorder defined by criteria A–E below. All five criteria
must be fulfilled to make the diagnosis:
|
|
A. One or more symptoms of dizziness, unsteadiness, or non-spinning vertigo are present
on most days for 3 months or more
|
|
1. Symptoms last for prolonged (hours-long) periods of time, but may wax and wane
in severity
|
|
2. Symptoms need not be present continuously throughout the entire day
|
|
B. Persistent symptoms occur without specific provocation; but are exacerbated by
three factors:
|
|
1. Upright posture
|
|
2. Active or passive motion without regard to direction or position, and
|
|
3. Exposure to moving visual stimuli or complex visual patterns
|
|
C. The disorder is precipitated by conditions that cause vertigo, unsteadiness, dizziness,
or problems with balance including acute, episodic, or chronic vestibular syndromes,
other neurologic or medical illnesses, or psychological distress
|
|
1. When the precipitant is an acute or episodic condition, symptoms settle into the
pattern of criterion A as the precipitant resolves, but they may occur intermittently
at first, and then consolidate into a persistent course
|
|
2. When the precipitant is a chronic syndrome, symptoms may develop slowly at first
and worsen gradually
|
|
D. Symptoms cause significant distress or functional impairment
|
|
E. Symptoms are not better accounted for by another disease or disorder
|
Source: Staab JP, Eckhardt-Henn A, Horii A, et al. Diagnostic criteria for persistent
postural-perceptual dizziness (PPPD): consensus document of the committee for the
Classification of Vestibular Disorders of the Bárány Society. J Vestib Res 2017;27(04):191–208.[2]
In this study, I describe the identification of first-onset cases of definite BPPV
among patients with vertigo and then retrieve and retrospectively review the data
for such cases, including age at the initial visit, sex, affected side, complications,
type of BPPV, time to transition to PPPD, and the rate of transition to PPPD.
Materials and Methods
Among the patients who visited my clinic between June 1, 2020, and May 31, 2021, only
those who had been newly diagnosed with BPPV as per criteria for definite diagnosis
established by the Japan Society for Equilibrium Research were included in the study
and their medical records were reviewed. The following data were retrieved for analysis:
age at initial visit, sex, affected side, interval between the first vertigo episode
and the initial visit, time to remission, hypertension, hyperlipidemia, diabetes mellitus,
heart diseases such as arrhythmia, insomnia, migraine, complications such as psychiatric
diseases, type of BPPV, rate of transition to PPPD, and time to transition to PPPD.
Definite BPPV was diagnosed according to the diagnostic criteria for dizziness and
vertigo established by the Japan Society for Equilibrium Research. These diagnostic
criteria are based on reference diagnostic criteria that were last revised in 2017.[8] Atypical cases and probable cases were excluded. All cases of PPPD met the diagnostic
criteria established by the Barany Society in 2017.[2]
[3]
[4] Migraine was diagnosed based on International Headache Society (IHS) criteria.[9]
[10] Patients meeting both the Barany Society criteria and the IHS criteria were considered
to have vestibular migraine (VM).[9]
[10]
[11] Patients whose medical interview results indicated a history of peripheral vertigo,
such as vestibular neuritis or MD, and those suffering from recurrent peripheral vertigo
were excluded. An infrared charge-coupled device (CCD) camera was used to check for
nystagmus. Medical evaluation was conducted for hypertension, insomnia, hyperlipidemia,
migraine, heart diseases such as arrhythmia, diabetes mellitus, and psychiatric diseases
(e.g., any previous mental health clinic visits).
Time to remission (duration of clinic visits) was determined based on patient complaints
during a follow-up period of up to 12 months after the initial visit. Remission was
defined as improvement in both nystagmus and subjective symptoms, such as the entire
spectrum of subjective dizziness, namely, lightheadedness and unsteadiness, as well
as vertigo at the time of nystagmus provocation. Cases wherein follow-up visits were
not completed because the patient relocated or the visits were cancelled at the patient's
discretion were recorded as having unknown outcome.
Results
Data from 311 cases (120 men and 191 women) were included, with a mean age (±standard
deviation) of 60.7 ± 17.8 years. Men were aged 14 to 88 (mean age, 64.2 ± 16.3) years,
whereas women were aged 11 to 90 (mean age, 58.5 ± 18.5) years; the mean age of men
was higher ([Fig. 1]).
Fig. 1 Age and sex distribution patterns in patients with benign paroxysmal positional vertigo.
▪ Men; □ Women. Patients aged 60 to 70 years accounted for the greatest proportion
of both men and women and for ∼50% of all patients included in this study.
[Fig. 2] indicates the time elapsed between the first episode and the initial visit: within
3 days in 137 cases, within 7 days in 63 cases, within 14 days in 46 cases, within
21 days in 7 cases, within 28 days in 15 cases, and ≥29 days in 43 cases. These data
indicate that 64.3% of the patients had their initial visit within 7 days of the first
episode. BPPV type was posterior semicircular canal in 172 cases, lateral semicircular
canal in 79 cases, and lateral semicircular canal in 60 cases. Thus, posterior semicircular
canal BPPV was the most common form observed in this cohort. Furthermore, 164 and
147 cases were affected on the right and left sides, respectively, making the right
side the most frequently affected side in this cohort.
Fig. 2 Time interval (days) between the first episode and the initial visit. Of all the
included patients, 64.3% had their initial visit within 7 days after onset.
[Fig. 3] indicates that the time to remission from the initial visit was <0.5 months in 86
cases, <1 month in 69 cases, <2 months in 50 cases, <3 months in 22 cases, and ≥3
months in 57 cases. Treatment outcome was unknown in 27 cases as follow-up could not
be completed. Moreover, 57 patients required ≥3 months to achieve remission; they
represent patients who may be diagnosed with PPPD. Next, 11 (19.3%) patients were
diagnosed with refractory disease due to nystagmus or persistent symptoms, 27 (47.4%)
required long-term follow-up because of repeated symptom relapse despite improvement,
12 (21.1%) met the diagnostic criteria for VM and were diagnosed with VM/BPPV overlapping
syndrome (VBOS, characterized by coexistence of episodic vertigo and VM),[12] and 5 (8.8%) were suspected of having VM or were refractory to BPPV treatment but
showed improvement with concomitant migraine treatment; that is, it is unclear if
they had VBOS or if symptoms were unrelated to episodic vertigo. Thus, there were
only two cases (3.5%) of transition from BPPV to PPPD, yielding in a transition rate
of 0.6% overall or 0.7% when the 27 cases with unknown outcomes are excluded. The
two cases of transition were that of a 75-year-old man and a 70-year-old woman, and
both patients had left-sided posterior semicircular canal-type BPPV.
Fig. 3 Time to remission from the initial visit (duration of clinic visits; in months).
Of all the included patients, 72.9% achieved remission within 3 months after the first
visit.
Comorbidities included hypertension in 48 cases, hyperlipidemia in 33, heart disease
in 28, diabetes mellitus in 22, and insomnia in 16 cases. Furthermore, 29 patients
had migraine (multiple answers allowed) and 13 patients had undergone or were undergoing
outpatient treatment for psychiatric disorders. As described earlier, there were 12
cases of probable VBOS, 5 cases of suspected VBOS or refractory BPPV that improved
with concomitant treatment for migraine (remained inconclusive whether they had VBOS
or were unrelated to episodic vertigo), and 12 cases where migraine was merely a complication
with no effects on dizziness. Of the two patients who underwent a transition to PPPD,
the man had hypertension and the woman had both diabetes mellitus and hypertension.
Case 1
Patient: A 75-year-old man.
Chief complaint: Vertigo.
History of present illness: The patient became aware of vertigo associated with head
movements when he rolled over in his sleep. Additionally, he had experienced vertigo
on other occasions during the past 5 days before he first presented to the clinic.
Therefore, he visited a local neurosurgery clinic where he underwent head magnetic
resonance imaging (MRI) and other evaluations, but as the neurosurgeon found no abnormalities,
he was referred to our clinic.
Past medical history: Hypertension was being managed by an internist.
Family history: Unremarkable.
Pure-tone audiometry: High-frequency sensorineural hearing loss attributable to aging
was noted, with no difference between the left and the right ears.
Infrared CCD camera and Frenzel goggles: Gaze nystagmus was not seen. As shown in
[Fig. 4], torsional nystagmus with latent time and damping was noted during positional and
positioning tests.
Fig. 4 Nystagmus findings at the initial visit in Case 1. Nystagmus was not noted during
the gaze test; however, torsional nystagmus with latent time and damping was noted
during the positional and the positioning tests.
Caloric nystagmus test: No difference between left and right ears was noted.
Otorhinolaryngologic findings: Unremarkable.
Neurological assessment: No abnormal findings were noted.
Blood tests: Unremarkable.
Disease course: Based on the results of the positional and the positioning tests conducted
at the initial visit, the patient was diagnosed with definite left-sided posterior
semicircular canal-type BPPV. He was prescribed ryokeijutsukanto and betahistine mesylate
and the Semont maneuver was performed. The patient was further instructed to perform
Brandt-Daroff exercises at home. The Semont maneuver had to be repeated as his subjective
symptoms did not improve and nystagmus persisted even after 2 weeks. However, even
though lightheadedness persisted, nystagmus was no longer detected by the positional
or the positioning test conducted 1 month later. Similarly, 2 months later, nystagmus
remained undetectable but lightheadedness continued. Furthermore, as nystagmus had
resolved with no improvement in lightheadedness even at 3 months, an interview with
the patient revealed that persistent lightheadedness occurred when he moved his body,
walked, or looked at supermarket or convenience store shelves. His Niigata PPPD Questionnaire
(NPQ)[3] score was as high as 54 out of 72 points. Based on the aforementioned, a provisional
diagnosis of PPPD was provided, and he was prescribed a selective serotonin reuptake
inhibitor (paroxetine hydrochloride hydrate) and Yokukansan, which resulted in an
improvement of his NPQ score to 25 points.
Case 2
Patient: A 70-year-old woman.
Chief complaint: Vertigo.
History of present illness: The patient presented to the clinic 7 days after she became
aware of vertigo associated with head movements that occurred when she rolled over
in her sleep and on some other occasions.
Past medical history: Hypertension and diabetes mellitus managed by an internist.
Family history: Unremarkable.
Pure-tone audiometry: High-frequency sensorineural hearing loss attributable to aging
was noted with no difference between the left and the right ears.
Infrared CCD camera and Frenzel glasses: Gaze nystagmus was not seen. As shown in
[Fig. 5], torsional nystagmus with latent time and damping was noted upon positional and
positioning testing.
Fig. 5 Nystagmus findings at the initial visit in Case 2. Nystagmus was not noted during
the gaze test; however, torsional nystagmus with latent time and damping was noted
during the positional and the positioning tests.
Caloric nystagmus test: No differences were noted between the left and the right ears.
Otorhinolaryngologic findings: Unremarkable.
Neurological examinations: No abnormal findings were noted.
Blood tests: Unremarkable.
Imaging examinations: Head MRI and MRA were unremarkable.
Disease course: The patient was diagnosed with definite left-sided posterior semicircular
canal-type BPPV based on the results of the positional and positioning tests at the
initial visit. Nystagmus was seen ([Fig. 5]). Pure-tone audiometry indicated high-frequency sensorineural hearing loss with
no differences between left and right ears; this was presumed to be age-related. Therefore,
Ryokeijutsukanto and betahistine mesylate were prescribed and the Semont maneuver
was performed. The patient was also instructed to perform Brandt-Daroff exercises
at home. The Semont maneuver was repeated 2 weeks later because nystagmus persisted
and subjective symptoms had not improved. Precautionary head MRI and MRA were performed,
but no abnormalities were found. Two months later, although nystagmus had resolved,
lightheadedness persisted, and there was no change at 2.5 months after the initial
visit. As nystagmus had resolved but no improvements in lightheadedness were seen
at 3 months, an interview with the patient about her condition revealed that persistent
lightheadedness occurred when she moved her body, walked, or looked at supermarket
or drug store shelves. Furthermore, as her NPQ score was as high at 56 out of 72 points,
she was diagnosed with PPPD and prescribed a selective serotonin reuptake inhibitor
(paroxetine hydrochloride hydrate) and Yokukansan, which led to an improvement in
her NPQ score to 20 points.
Discussion
Since the publication of diagnostic criteria for PPPD by the Barany Society,[2] there has been a renewed focus on conditions that can transition to PPPD.[2]
[3]
[4] Here, cases of definite BPPV that were diagnosed after the first episode were identified
and case data were retrospectively reviewed to understand the factors associated with
transition to PPPD. BPPV was selected because patients can subjectively perceive disease
onset, which enables the accurate determination of time taken to transition from BPPV
onset to PPPD. Even though this is also applicable to vestibular neuritis, this study
focused on BPPV because of the relative rarity of vestibular neuritis.
There were 311 cases of first-onset BPPV in this study cohort, and women accounted
for a greater proportion of the population. Previous studies have also reported that
BPPV is more common in women.[13]
[14] Peak age of BPPV onset in this study was in 60s and 70s and patients in these age
groups accounted for approximately 50% of all patients. Uno et al also reported that
BPPV was most common in individuals aged 60 to 79 years.[15]
Most of the patients in this study presented to the clinic relatively early after
the first episode, probably because only first-onset cases were included. Additionally,
general otorhinolaryngology clinics are easier to visit than hospitals or dizziness
clinics through appointment only. The short time interval between the first episode
and the first visit may also have contributed to the relatively large sample size
of this study (311 cases). Importantly, the higher detection frequency of nystagmus
and greater accuracy of information from patient interviews helped increase the rate
of definitive diagnosis. Posterior semicircular canal type was the most common type
of BPPV, followed by the lateral semicircular canal type, and the lateral semicircular
canal type. Likewise, Uno et al reported that ≥60% of cases were of the posterior
semicircular canal type.[15]
The right side was more commonly affected than the left side and most patients (72.9%)
showed an improvement in <3 months. As shown in [Table 1], diagnostic criteria for PPPD include symptom persistence for at least 3 months;
thus, <20% of first-onset cases were candidates for diagnosis, and the duration of
time to remission alone could confirm that the rate of transition from BPPV to PPPD
was not high. Specifically, cases where improvement was seen after more than 3 months
included 11 (19.3%) patients with refractory disease, 27 cases (47.4%) that required
long-term follow-up because of repeated symptom relapse despite improvement, 12 cases
(21.1%) of probable VBOS,[12] and 5 cases (8.8%) of suspected VM or conditions that are refractory to BPPV treatment.
In many of these cases, patients were diagnosed with BPPV at the initial visit and
later confirmed to have VM through a second medical interview because subjective vestibular
symptoms persisted after 1 month even though nystagmus had resolved. Furthermore,
approximately 30% of patients who required clinic visits for ≥3 months had migraine-related
conditions. Thus, it appears that BPPV cases requiring long-term visits are often
related to VM. For this reason, some patients with VBOS might also suffer from concomitant
PPPD; however, VBOS improved in most cases when physical therapy for BPPV and pharmacotherapy
for migraine were provided concurrently. Notably, no VBOS patients met the diagnostic
criteria for PPPD.
Only two individuals in their 70s with left-sided posterior semicircular canal-type
BPPV were considered to have undergone transition to PPPD. An analysis of variables
such as sex, time taken to transition to PPPD, characteristics in previous illness,
and age were not possible.
Diseases similar to PPPD have been reported since the establishment of the diagnostic
criteria for PPPD by the Barany Society in 2017,[2] and examples include phobic postural vertigo, space motion discomfort, visual vertigo,
and chronic subjective dizziness. Thus, the Barany Society considers these diseases
to represent different aspects of the same pathological condition, that is, the newly
defined PPPD. In Japan, no large-scale epidemiological studies on PPPD have been conducted
to date but overseas studies, such as those by Bittar and Lins[16] and Yan et al,[17] have reported that PPPD is common in women aged 40 to 69 years and that the prevalence
of anxiety disorder or neuroticism was higher in PPPD patients than in healthy individuals.
Horii reported that PPPD accounted for approximately two-thirds of all cases of dizziness
and that it was the most common cause of chronic dizziness.[4] While the pathophysiology of PPPD has not been fully understood, it is considered
to be a functional disorder, similar to irritable bowel syndrome.[17]
Diagnosis of PPPD requires detailed medical interviews about symptoms and past medical
history, and questionnaires such as NPQ are effective tools.[5] Here, NPQ was used to rule out the possibility of PPPD in refractory cases or in
those requiring long-term follow-up visits. Notably, NPQ scores were less than 27
in such patients, and an NPQ cutoff score of 27 has a reported sensitivity of 70%
and a specificity of 68%.[3] Given that NPQ scores were too low and that these cases did not meet diagnostic
criterion A (lightheadedness, unsteadiness, or non-spinning vertigo), PPPD was considered
an unlikely diagnosis. The NPQ scores in two of the VBOS cases were higher than 27;
however, they did not satisfy diagnostic criterion A (“symptoms are present on most
days” because of fluctuation due to weather and stress).
The first necessary step in the treatment of PPPD is to provide the patient with information
to help understand the condition. Other effective therapeutic options include selective
serotonin reuptake inhibitors, vestibular rehabilitation, and cognitive behavioral
therapy.[5]
[17]
[18]
[19] Nevertheless, it is most important to fully explain vertigo/dizziness-causing conditions
that precede PPPD to affected patients because such information will facilitate a
reduction in risk for transition to PPPD. Moreover, some PPPD patients have also stated
that just being provided an explanation about the presumed precipitants of PPPD relieved
their concerns and alleviated their symptoms. Although precipitants are unknown in
some cases, it is essential to explain likely precipitants of PPPD whenever possible.
The results of this study suggest that the rate of transition from definite BPPV to
PPPD is around 1%; thus, the likelihood of transition to PPPD in first-onset cases
is expected to be low. Further studies in patients experiencing repeated BPPV episodes
are needed to understand transition to PPPD.
