Transverse sinus stenosis in a patient with IIH. Left: narrowing of transverse sinuses bilaterally (arrows). Right: Resolution of stenosis , Fuente de la Imagen: http://pedclerk.bsd.uchicago.edu/page/pseudotumor-cerebri
Bilateral transverse sinus stenosis in patients with tinnitus
Fuente de la imagen: http://pedclerk.bsd.uchicago.edu/page/pseudotumor-cerebri
SUMMARY
Tinnitus
is a frequent complaint in patients affected by intracranial
hypertension (IH). Recently, some studies have reported an association
between idiopathic intracranial hypertension (IIH) and bilateral
transverse sinus stenosis (BTSS). We investigated the relationship
between BTSS and monosymptomatic tinnitus, regardless of its clinical
characteristics, in subjects without clinical evidence of IH. We
selected 78 subjects (all women, mean age 49.5 ± 10.36) affected by
tinnitus, without clinical history of audiological and otological
pathologies, enrolled among outpatients of the Institute of Audiology
and Phoniatrics in Catanzaro, Italy, over a 2 year period. All subjects
underwent psychometric evaluation, psychoacoustic assessment,
neurological and ophthalmological examination, cerebral magnetic
resonance venography (MRV) and brain magnetic resonance imaging (MRI).
MRV identified BTSS in 17.9% (14 patients). In the BTSS group, tinnitus
was bilateral/central in 21%, and monolateral in the remaining patients
(50% left; 29% right ear). It was more frequently pulsating in the BTSS
group, but 64.9% of BTSS subjects described their tinnitus as stable. No
features of tinnitus showed statistical significance in association
with BTSS. In BTSS subjects, we found values suggesting IH by lumbar
puncture (LP) in 40% of cases. In these patients, LP gave immediate
improvement of tinnitus. The association between BTSS and tinnitus,
regardless of its features, must be considered when other causes of
tinnitus are excluded.
KEY WORDS: Idiopathic intracranial hypertension (IIH), Magnetic resonance venography (MRV), Bilateral transverse sinus stenosis
(BTSS), Tinnitus
Introduction
Tinnitus
is a common condition that affects a broad range of patients, with some
uncertainties about its prevalence and incidence, and a great variety
of aetiopathogenetic and diagnostic issues. Prevalence data range from 3
to 30%, without consistent findings with regard to relationship between
prevalence and age or gender
Idiopathic
intracranial hypertension (IIH) is a condition characterized by raised
intracranial pressure without any identifiable pathology in the brain
and with normal cerebrospinal fluid (CSF) composition. IIH may occur
with and without papilloedema
It predominantly affects overweight women, and while headache is the
most common symptom, disturbance of vision and tinnitus are also very
frequent complaints
. In particular, tinnitus is reported in 55%-60% of patients
Recently, a connection between bilateral transverse sinus stenosis (BTSS) and IIH with or without papilloedema
Considering this and the well-known relationship between intracranial and cochlear fluids
hypothesizing that an alteration of venous cerebral circulation,
especially BTSS, could be the basis of onset and maintenance of
monosymptomatic tinnitus in subjects without clinical evidence of
elevated intracranial pressure, we investigated the frequency of
association between tinnitus and BTSS and the possibility to define some
specific features of tinnitus that allow us to suspect BTSS.Material and methods
The
study population consisted of 78 patients affected by tinnitus (ages 27
to 69, mean age 49.5 ± 10.36), enrolled according to selection
criteria, among those admitted to Institute of Audiology and Phoniatrics
in Catanzaro, Italy, over a 2 year period, starting from February 2008.
We selected only females as IH affects predominantly women
Tinnitus was diagnosed and assessed according to criteria described later.
All
patients underwent otolaryngological and neurological examination,
standardized clinical general examination and, as IH affects
predominantly overweight women, we also included evaluation of body mass
index (BMI: weight in kilograms divided by the square of height in
meters)
Examination and interviews were conducted by the same physicians.
Given
the availability in literature of data about the prevalence of BTSS in
normal subjects and, in this particular case, personal data already
published in a previous paper
the authors decided to make utilize these previous data without
violating of ethical and economic precepts by carrying out expensive
imaging exams in normal subjects.Inclusion criteria
Female
sex, tinnitus for at least two months, monosymptomatic, regardless of
its characteristics, and an age between 25 and 70 years.
Exclusion criteria
Clinical
history of audiological and otological pathologies (other clear causes
for tinnitus, Ménière's disease, acoustic neuroma, noise-induced hearing
loss, assumption of drugs inducing tinnitus
,
etc.), otological surgery, were excluded. In order to exclude
presbycusis, individuals with a pure-tone average over 30 dB HL for
2-4-8 kHz were not included in the study. Presence of papilloedema and
abnormalities in neurological examination. Assessment of tinnitus
We carried out careful evaluation of tinnitus that included both evaluation by questionnaires for psychometric assessment
and hyperacusisas well as psychoacoustic assessment.
Our protocol included: i) A thorough history with detailed interview; ii) questionnaire for hyperacusis
The
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and tinnitus handicap inventory iii) physical examination; iv) pure-tone thresholds with air and bone
conduction and speech audiometry; v) tinnitus test battery: tinnitus
loudness and pitch matching, minimal masking levels (MML s), loudness discomfort levels (LDL s)
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vi) acoustic-immittance measurements with tympanometry and
acoustic-reflex thresholds (only if tolerated comfortably by patient and
always after the results of the hyperacusis questionnaire). We did not
perform the residual inhibition test because of its controversial
clinical and scientific valueNeuroimaging studies
All
patients included in this study underwent brain gadolinium- enhanced
magnetic resonance imaging (MRI) to exclude acoustic neuroma or other
neoformative causes for tinnitus. Patients with normal MRI underwent MRV
of the brain with a 1.5 T scanner (GE Medical systems, Milwaukee, WI),
using three dimensional phase-contrast (PC) techniques
All brain MRV were analyzed by the same neuroradiologists who were
blinded to patient history. We classified the transverse sinus stenosis
(TSS) as absent or present. BTSS was considered when the signal flow was
lacking (flow gap) in the midlateral portion of both transverse
sinuses.CSF measurements
10 patients with BTSS underwent lumbar puncture to evaluate CSF opening pressure
The test was not performed in the remaining 4 patients because they denied consent.Statistical analysis
Statistical analyses were performed using Primer®
software. The statistical assessment of differences between classes was
performed using Fisher's exact test and the chi-square test. A p-value
< 0.05 was considered statistically significant. We also evaluated
the Mantel-Haenzel odds ratio and performed multivariate logistic
analysis using a multiple logistic regression model.
Results
We
studied 78 subjects, all females, affected by tinnitus, regardless of
its clinical characteristics, carefully ruling out specific causes.
Imaging studies
MR
V identified the presence of BTSS in 14 subjects (17.9%); this was
significantly different from that in subjects with normal CSF pressure
(1.8%; p = 0.000734; odds ratio [OR ] = 0.0996)
In 17 patients (21.7%), the test did not highlight any specific
alteration, while in the remaining 47 (60.2%) MR V detected various
degrees of transverse sinus (TS) alterations (hypoplasia or asymmetry)
that did not reach the level of stenosis or bilateral extension (Table I).
MR
venography results. MRV identified the presence of BTSS in 17.9% of
subjects (p = 0.000734 vs. no-BTSS subjects; OR = 0.0996).
Next, we investigated the site (Table II), type (Table III), pitch (Table IV) and loudness (Table V) of tinnitus.
Tinnitus
site. Compared with the BTSS group, there was a higher frequency of
bilateral/central localization of tinnitus in the no-BTTS group, as well
as in normal subjects (p = 0.008717, OR = 2.4052).
Tinnitus
type. Pulsatile was more frequent for tinnitus in the BTSS group
compared to the no-BTSS group (p = 0.000244, OR = 0.2532).
Tinnitus
type. Pulsatile was more frequent for tinnitus in the BTSS group
compared to the no-BTSS group (p = 0.000244, OR = 0.2532).
Tinnitus site
In
the BTSS group, tinnitus was bilateral/central in only 21% of cases,
while it was monolateral in the remaining patients (50% left ear; 29%
right ear). In the no-BTSS group, tinnitus was localized
bilaterally/centrally in 39%, on the left ear in 48.4% and on the right
side in 12.5% of cases. Compared to the BTSS group there was a higher
frequency of bilateral/central localization of tinnitus in the global
no-BTTS group, as well as in normal subjects (p = 0.008717, OR = 2.4052)
(Table II).
Tinnitus temporal characteristics
Concerning
the temporal characteristics of tinnitus, it was more frequently
pulsating in the BTSS group compared to the no-BTSS group (p = 0.000244,
OR = 0.2532) (Table III).
On the other hand, we found that the majority of subjects in the BTSS
group (64.9%) described their tinnitus as stable, rather than pulsatile.
Tinnitus pitch
We
separated all subjects into three classes of tinnitus pitch: over 3
kHz, under 3 kHz and those not able to identify a frequency for their
tinnitus. Tinnitus with pitch over 3 kHz was more frequent in both
groups of patients, but the distribution, reported in Table IV, did not show any significant differences.
Other psycho-acoustic tests (Loudness, MMLs, LDLs)
No
differences in tinnitus were seen in other psychoacoustic tests. In
particular (mean values), tinnitus loudness was 8.1 dB SL in the BTSS
group and 7.6 dB SL in the no-BTSS group; MMLs were 11.7 dB SL for the
former, 12.2 dB SL for the latter. Analysis of LDLs revealed values over
90 dB for all frequencies tested in both groups, according to the
results of the hyperacusis questionnaire which did not show the presence
of loudness sensitivity problems.
Psychometric tests
The results of the tinnitus handicap inventory (THI)
and grading of psychometric evaluation are reported in Table V.
Compared to the no-BTSS group, subjects with BTSS reported more
frequently (57.1%) tinnitus that was easily masked by environmental
sounds and easily forgotten with activities, that may occasionally
interfere with sleep but not with daily activities. In the majority of
no-BTSS subjects (67.2%), tinnitus was heard only in a quiet environment
and very easily masked and had no interference with sleep or daily
activities. Only few of these subjects fall in THI grade 3 (10.9%).
These results did not show any statistically significant differences.
The results of hyperacusis questionnaire did not show the presence of
loudness sensitivity problems, according to LDL s performance.BMI
Because
of their frequent association with IH, and, hereupon, with BTSS, we
also investigated for the presence of overweight and obesity (Table VI) and found no statistical significance when matched between different groups.
CSF measurements
We found values suggesting IH
in 40% of BTSS patients (4/10) (Table VII).
Only one (# 13) of these patients referred tinnitus as pulsatile and
bilateral. In the other patients, tinnitus was localized on the left and
was stable. In all of 4 IH cases, LP led to immediate improvement of
tinnitus.Multivariate analysis
We
also performed multivariate logistic analysis using a multiple logistic
regression model considering tinnitus type and site in order to clarify
the association of these variables with the presence of BTSS. The main
conclusion of this analysis is that the tinnitus site (OR = 2.40) seems
to be associated with the presence of BTSS. Considering the other
variables, the results were inconclusive.
Discussion
Tinnitus
is a common and poorly understood disorder, whose aetiopathogenesis is
still under debate, and represents an enormous challenge for both
otologists and neurotologists. In the present study, we hypothesize that
an alteration of venous cerebral circulation, especially BTSS, might be
one of the pathophysiological bases of the disease, even in absence of
clinical evidence of elevated intracranial pressure. The rationale for
this hypothesis relies on the potential effects of vascular
abnormalities (i.e. BTSS) on the fragile homeostasis that exists between
intracranial and labyrinthine fluids. In fact, several lines of
clinical evidence indicate that pressure variations of intracranial
fluids influence labyrinth hydromechanics causing otologic reversible
symptoms such as hypoacusis, vertigo or tinnitus
.
A connection between intracranial and labyrinthine fluids has been
reported, albeit inconstant; the perilymph is, in fact, in direct
relationship with the intracranial fluids district, throughout the
cochlear aqueduct
conversely, the endolymph communicates indirectly with the intracranial
fluids district throughout the endolymphatic sac; the pressure
homeostasis between endolymph and perilymph is maintained by the
Reissner's and other labyrinthine membranes
Different connections are represented by the perivascular and
perineural spaces, even if this is possible only in the presence of high
intracranial pressure or anatomical lesions.
Moreover,
experimental demonstration of the connections between the intracranial
and labyrinthine fluids has been reported in animal models, showing the
absence of modifications within labyrinthine fluids if the cochlear and
vestibular aqueducts were closed
The
cochlear aqueduct seems to act as a low pass filter, avoiding strong
and dangerous transmission of intracranial pressure variations to the
labyrinthine fluids. On the other hand, it is important to underscore
that the anatomical features of the cochlear aqueduct may per se
lead to potential loss of efficacy, due to the progressive but variable
degree of sealing throughout life. The percentage of this closure among
life is reported to be very different in the literature
Nonetheless,
mechanisms of reabsorption and, therefore, of pressure regulation, of
cerebrospinal fluid (CF) are well known. It occurs mainly at the level
of arachnoid granulations that are located, to a large extent, in
transverse sinuses. The functions of these structures are CF
reabsorption and its transportation in the bloodstream. A transverse
sinus stenosis could influence CF reabsorption with indirect
consequences on labyrinthine hydromechanics.
All these
considerations, together with those on pathophysiological mechanisms of
IIH, already discussed in the introduction, prompted us to consider a
possible association between the BTSS and abnormal homeostasis among
intracranial and cochlear fluids.
The first aim of our
study was to evaluate the frequency of association between BTSS and
tinnitus. For this purpose we selected subjects affected by
monosymptomatic tinnitus, without clinical signs of IH. In this first
step of our study, we choose to reinforce the sample to evaluate if
there is some basis for our hypothesis by enrolling only female patients
due to the higher incidence of IH among women
We planned to extend our evaluation to a cohort with males in a second step.
BTSS is reported in 1.8% of subjects with normal CSF pressure
. As mentioned in the methods section, we decided to utilize personal data already published in a previous paper for ethical and economical reasons.
In
our cohort, we found a significantly higher percentage (17.9%) of
bilaterally abnormal transverse sinuses, therefore hypothesizing that
this condition might be one of the causes of tinnitus. Given the
frequent association between BTSS and IIH, we investigated if IH was
present in our BTSS cases, even if without clinical evidence.
Indeed,
4 of 10 subjects that underwent LP presented values suggesting IH.
Moreover, in these 4 subjects LP determined recovery from tinnitus. This
allowed for two considerations: the first on therapeutic effect on
tinnitus from IH treatment, and the second on need to investigate the
suspect of IH in presence of monosymptomatic tinnitus without evident
causes. Our second aim, consequential to the first, was to characterize
some features of tinnitus linked to BTSS based on the findings of MRV.
Our
results highlighted that the common association between some features
of the tinnitus (e.g. pulsatility, low frequency pitch) and its
"vascular" origin appears to be more unlikely. Pulsatility, in fact, was
reported in only 35.9% of our BTSS group, and in just one of patients
with a diagnosis of IH after LP. Thus, it cannot be considered as a
criterion for the suspect of association with BTSS. This result could be
explain by the subjective nature of information about tinnitus, despite
careful interviews. However, in the literature there are reports that
agree with this finding
No other feature of tinnitus showed statistical significance in association with BTSS.
With
reference to site of tinnitus, there is agreement between our results
and literature data about the prevalence of localization on the left in
both groups, as well as the more frequent bilateral localization in the
no-BTSS group compared to the BTSS one
Therefore, a potential limitation of our study is when to indicate MRV
in the clinical management of patients suffering from tinnitus. MRV, as
described earlier, is a fast non-invasive tool that does not necessitate
the use of contrast agents. Nonetheless, at present, there are no
clinical and/or instrumental features that can be used as a specific
marker to address tinnitus patients to further MRV imaging studies.
On
the basis of the described significant association with BTSS, we
hypothesize that this venous alteration can be considered as one
potential pathophysiological mechanism of tinnitus. Based on our
selection criteria that excluded IH symptoms, this conclusion is also
valid in subjects without clinical evidence of IH . As a consequence,
monosymptomatic tinnitus maybe an important symptom if IIH without
papilloedema is suspected, regardless of its features. The therapeutic
effect of LP on tinnitus in subjects with IH reinforces the hypothesis
of a direct influence between labyrinthine and intracranial fluids,
confirming observations reported in the literature
This allows us to underscore that tinnitus, when linked to venous
stenosis and IIH , may benefit from pharmacological drugs for IH .Acknowledgements
The authors would like to thank Pietro Hiram Guzzi for his precious contribution in statistical analysis.
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fuente:
Acta Otorhinolaryngol Ital. 2012 August; 32(4): 238–243.
Acta Otorhinolaryngol Ital. 2012 August; 32(4): 238–243.
PMCID: PMC3468936
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