Dear Sirs,
It was an incidental observation in our tertiary outpatient dizziness center that
patients with acquired bilateral vestibulopathy (BVP) rarely complain about being
anxious about falling. This is surprising, since a bilateral vestibular deficit impairs
postural stability and thus causes frequent falls [1], in particular during locomotion
on uneven ground and in darkness when vision cannot substitute. In a controlled cross-sectional
study, the rate of recurrent fallers was increased in BVP patients despite a low-to-normal
fear of falling as determined by the Falls Efficiency Score International [2]. Two
epidemiological studies had shown that patients with vestibular disorders with episodic
vertigo, such as vestibular migraine and Menière’s disease, suffer from increased
psychiatric comorbidity with anxiety and affective disorders, which was not the case
in patients with BVP [3–5]. Furthermore, a recent study on the susceptibility to fear
of heights in BVP patients did not demonstrate an increase in susceptibility (29%
in BVP vs 28% of the general population) despite an objective higher risk of falling
from height [6]. In contrast, patients with other vestibular syndromes showed an increased
susceptibility to fear of heights.
This raised the question of whether intact vestibular function is relevant for distressing
anxiety related to the particular type of vertigo or—in other words—whether loss of
vestibular function reduces the liability to anxious behavior. This might be possible
since Balaban and co-workers showed that there are neurological bases of links between
balance control and anxiety. They described pathways that mediate autonomic control,
vestibulo-autonomic interactions, and anxiety within a circuitry including a parabrachial
nucleus network and its reciprocal connections with the central amygdaloid nucleus,
the infralimbic and insular cortex, and the hypothalamus [7–10].
We carried out a survey on a total of 7083 outpatients with the key symptoms of vertigo,
dizziness, and balance disorders all diagnosed in the German Center for Vertigo and
Balance Disorders (DSGZ), Munich, Germany, in the years from 2010 to 2012 (group 1,
N = 687) and 2015 to 2017 (group 2, N = 6396). All patients completed the Vertigo
Handicap Questionnaire (VHQ [11]) to measure physical and psychosocial handicap due
to vertigo and dizziness using 25 items. In addition to a sum-score, the VHQ allows
two subscale scores, handicapped activity, and anxiety, to be generated. The latter
was relevant for the current investigation. Moreover, all patients completed the Beck
Anxiety Inventory (BAI; [12]) and the subscale Trait Anxiety of the State-Trait Anxiety
Inventory (STAI; [13]) as further measures to assess anxiety in general. A total of
547 patients of group 1 were additionally examined with the Structured Clinical Interview
for DSM-IV (SCID-I; [14]) to assess patients’ mental disorders and psychiatric comorbidity
independently of their diagnoses given by the senior physician of the DSGZ (for details,
see [15]). All subjects gave their written informed consent and signed a form confirming
that they agree to further anonymous data analysis.
Linking diagnoses to VHQ forms was done with custom Java®9-based software combined
with a MySQL® Database by automatically analyzing medical documents. These documents
were the result of outpatient routines at the DSGZ, including clinical neurological
and neurootological examination, comprehensive neurophysiological diagnostics (including
the video head impulse test, caloric testing, neuroorthoptic examination with cover
test, adjustments of the subjective visual vertical, measurements of ocular torsion
by fundus photographs, and posturography). All patients were finally seen by an experienced
consultant supervisor from the center. Keywords for the common vestibular disorders,
such as bilateral vestibulopathy (BVP), benign paroxysmal positional vertigo (BPPV),
vestibular neuritis or unilateral vestibulopathy (UVP), vestibular paroxysmia (VP),
Menière’s disease (MD), vestibular migraine (VM), and functional vertigo and dizziness
(FD), were used for automatic filtering of the VHQ-linked forms. Statistical analysis
was performed using R Core Team (2017), R-Statistics 3.4.3 [16]. Groups 1 and 2 were
compared with a sensitivity analysis regarding demographic variables (age and gender)
and vestibular diagnoses. The groups did not differ significantly in these variables
(group 1: age 53.71 ± 15.78 years, female/male ratio 1.49; group 2: age 56.02 ± 24.41 years,
female/male ratio 1.26).
This resulted in n = 575 patients with BVP, n = 672 with BPPV, n = 453 with UVP, n = 314
with VP, n = 514 with MD, n = 886 with VM, and n = 416 patients with FD for the total
number of 3830 patients (groups 1 and 2) with consolidated data sets. The VHQ anxiety
scores of the 687 patients of group 1 were lowest for patients with chronic BVP and
UVP and highest for patients with FD (Fig. 1a). Significantly higher VHQ anxiety scores,
as compared to BVP, were found for BPPV, VP, MD, VM, and FD; the disorders were listed
according to the significance level. The low anxiety scores in BVP patients of group
1 were confirmed for the consolidated data sets of the pooled data of groups 1 and
2 (Fig. 1c). Regarding the scores on the BAI and the STAI-trait, patterns for the
diagnostic groups showed no significant group differences (Fig. 1b), which means that
the VHQ anxiety scores cannot simply be explained by psychiatric comorbidity of anxiety
disorders. In terms of psychiatric diagnoses, 48.8% (n = 267) patients fulfilled a
diagnosis according to SCID-I criteria. Of those, 28.9% (n = 158) were diagnosed with
an anxiety disorder, 24.9% (n = 136) with a somatoform disorder, 19.0% (n = 104) with
an affective disorder, 2.9% (n = 16) with a substance abuse disorder, and 0.7% (n = 4)
with an eating disorder. These numbers were also reported by Lahmann and co-workers
[5] who have analysed the prevalence of psychiatric disorders in the same sample (group
1).
Fig. 1
a Vertigo Handicap Questionnaire (VHQ) anxiety score boxplots from different vestibular
syndromes of consolidated data sets from patient group 1 (n = 687) for each disease
and a t test significance level compared to the reference group of bilateral vestibulopathy
(BVP) (*p ≤ 0.05; **p ≤ 0.01, ***p ≤ 0.001; ****p ≤ 0.0001, ns p > 0.05). Vestibular
syndromes were bilateral vestibulopathy (BVP), unilateral vestibulopathy/vestibular
neuritis (UVP), benign paroxysmal positional vertigo (BPPV), vestibular paroxysmia
(VP), Menière’s disease (MD), vestibular migraine (VM), and functional vertigo/dizziness
(FD). Note that the scores were lowest for BVP and UVP and highest for MD, VM, and
especially for FD. Median (horizontal solid line), mean (diamond square), boxplot
rectangle (lower 25% quantile and higher 75% quantile). A quantification of the effect
size magnitude was performed using the thresholds defined in Cohen [20], i.e., Cohen’s
d. The magnitude was assessed using the thresholds provided in Cohen [20], i.e., |d| < 0.2
negligible, |d| < 0.5 small, |d| < 0.8 medium, otherwise large. Cohen’s d is given
with 95% lower and upper limits for each disease. b For data set 1 (n = 687), in which
the Structured Clinical Interview for DSM-IV (SCID-I) was performed, BAI (Beck Anxiety
Inventory; white) and STAI (State-Trait Anxiety Inventory; grey) score value boxplots
and outliers (black dots) are given for each disease to show that the low VHQ anxiety
scores are not associated with psychiatric comorbidity (anxiety disorders). Cut-off
ranges for the BAI have been suggested as follows: 0–7 (no or minimal anxiety), 8–15
(mild anxiety), 16–25 (moderate anxiety), and above 25 (severe anxiety). The STAI
cut-off values proposed in the literature for clinically relevant anxiety effect are
39–40 for the original English version. c VHQ anxiety score boxplots from different
vestibular syndromes of consolidated data sets from patient groups 1 and 2 (n = 3830)
for each disease and a t test significance level compared to the reference group of
BVP (**p ≤ 0.01; ****p ≤ 0.0001; ns p > 0.05). A quantification of the effect size
magnitude was performed using the thresholds defined in Cohen [20], i.e., Cohen’s
d. Cohen’s d is given with 95% lower and upper limits for each disease
The present data strongly support the view that a functioning peripheral vestibular
system is the prerequisite for the development of anxiety related to vertigo and explains
why anxiety scores were low in BVP patients. In contrast, all episodic vestibular
syndromes as well as chronic functional dizziness revealed increased VHQ anxiety scores
with the highest for MD, VM, and FD. One cannot simply compare our current data with
the former epidemiological studies on psychiatric comorbidity in dizzy patients based
on SCID-I diagnoses [5]. In the latter, a higher comorbidity incidence of anxiety/phobic,
affective, and somatoform disorders was found especially in episodic vertigo syndromes
but not in BVP. The low incidence of comorbidities in BVP patients was also seen in
the current study.
It is well acknowledged in affective neuroscience that the vestibular and also the
cerebellar systems are reciprocally connected to various anxiety and fear brain structures
(for review: [17]). Such a network which probably involves the thalamus and hypothalamus
provides the structure for coordination of sensorimotor behavior, emotional, higher
vestibular cognitive, and visceral functions [17, 18]. Beside the basic circuitry
connecting the emotional and vestibular systems (by a parabrachial nucleus network
and its connections [7, 8]) an attempt has also been made at the cortical level—by
use of transcranial direct current stimulation over the posterior parietal cortex—to
reveal a link between anxiety and the vestibular system, i.e., the vestibulo-cortical
dominance [19]. Thus, a close interaction between the vestibular and the emotional
systems seems to exist at several lower as well as higher brain levels. However, our
study does not allow interpretations as to specific structural and functional links
between anxiety and the vestibular system. The major point we want to make here is
the separation between psychiatric comorbidity in dizzy patients and anxiety triggered
by particular vestibular disorders in patients who do not fulfill the diagnostic criteria
of an associated psychiatric disorder. Nevertheless, in patients with a bilateral
loss of peripheral vestibular function, both anxiety related to vertigo and psychiatric
comorbidity are low.