10.14639/0392-100X-N0776
Objective. The purpose of this study was to assess vestibular findings and clinical history in a large cohort of patients affected by Ménière’s disease. Methods. We retrospectively analysed 511 adult patients fulfilling criteria for definite unilateral Ménière’s disease according to Barany Society. Thorough clinical history, audiometric exam, central nervous system MRI, quantification of serum autoantibodies and complete vestibular function test were performed. Results. Mean age at clinical record was 55.4 years, while age at onset of the first vertigo attack was 47.4 ± 14.3 years. Ménière’s disease overlapped with migraine in 43.4% of patients. In 31.7% of cases, positivity was found for at least one autoantibody. Forty-nine patients (9.6%) had family history for Ménière’s disease. Bedside examination resulted in 14.7% positivity for video head impulse test, 58.9% for skull vibration-induced nystagmus, 38.7% for the positional test and 23.1% for the post head shaking test. Complete negative examination was reported in 115 cases. Conclusions. Ménière’s disease was seen to present a characteristic phenotypic pattern in our cohort, confirming the crucial role of thorough anamnesis and bedside examination in diagnosis.
application/xml
1827-675X
776
6
en
Mario Bussi
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
vestibular function tests
Evaluation of a large cohort of adult patients with Ménière’s disease: bedside and clinical history
Text.Serial.Journal
https://www.actaitalica.it/
40
Vestibology
2021-01-21
2020-04-01
2021-01-21
2021-01-21
1
Mario Bussi
2020
10.14639/0392-100X-N0776
Department of Otolaryngology Head & Neck Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
1827-675X
6
vestibular function tests
Evaluation of a large cohort of adult patients with Ménière’s disease: bedside and clinical history
https://www.actaitalica.it/article/download/776/497
40
ACTA OTORHINOLARYNGOLOGICA ITALICA 2020;40:444-449; doi: 10.14639/0392-100X-N0776




Vestibology


Evaluation of a large cohort of adult patients
with Ménière’s disease: bedside and clinical history
Sindrome di Ménière: valutazione dell’esame vestibolare e della storia clinica
in un’ampia popolazione
Roberto Teggi1,2, Rosa Alessia Battista1,2, Federica Di Berardino3, Marco Familiari1,2, Iacopo Cangiano2, Omar Gatti1,
Mario Bussi1,2
1
 Department of Otolaryngology Head & Neck Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; 2 Vita-Salute San
Raffaele University, Milan, Italy; 3 Audiology Unit, Dept of Clinical Sciences and Community Health and Dept. of Specialistic Surgical
Sciences, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, University of Milan, Italy


SUMMARY
Objective. The purpose of this study was to assess vestibular findings and clinical history in
a large cohort of patients affected by Ménière’s disease.
Methods. We retrospectively analysed 511 adult patients fulfilling criteria for definite uni-
lateral Ménière’s disease according to Barany Society. Thorough clinical history, audiomet-
ric exam, central nervous system MRI, quantification of serum autoantibodies and complete
vestibular function test were performed.
Results. Mean age at clinical record was 55.4 years, while age at onset of the first vertigo
attack was 47.4 ± 14.3 years. Ménière’s disease overlapped with migraine in 43.4% of
patients. In 31.7% of cases, positivity was found for at least one autoantibody. Forty-nine
patients (9.6%) had family history for Ménière’s disease. Bedside examination resulted in        Received: April 2, 2020
14.7% positivity for video head impulse test, 58.9% for skull vibration-induced nystagmus,       Accepted: July 16, 2020
38.7% for the positional test and 23.1% for the post head shaking test. Complete negative
examination was reported in 115 cases.                                                           Correspondence
Conclusions. Ménière’s disease was seen to present a characteristic phenotypic pattern in        Roberto Teggi
                                                                                                 San Raffaele Hospital, via Olgettina 60, 20132
our cohort, confirming the crucial role of thorough anamnesis and bedside examination in
                                                                                                 Milan, Italy
diagnosis.                                                                                       Tel. +39 02 26433522. Fax +39 02 26433508
KEY WORDS: Ménière’s disease, migraine, autoimmunity, family history, vestibular                 E-mail: teggi.roberto@hsr.it
function tests
                                                                                                 Funding
                                                                                                 None.
RIASSUNTO
Obiettivo. Analizzare un’ampia casistica di pazienti affetti da sindrome di Ménière con          Conflict of interest
particolare attenzione al dato anamnestico ed ai test di funzione vestibolare.                   The Authors declare no conflict of interest.
Metodi. Sono stati raccolti retrospettivamente i dati di 511 pazienti affetti da sindrome di
Ménière monolaterale definita, che soddisfacevano i criteri della Barany Society. Ogni pa-
                                                                                                   How to cite this article: Teggi R, Battista RA,
ziente è stato sottoposto a raccolta anamnestica, esame audiometrico tonale, RM encefalo,          Di Berardino F, et al. Evaluation of a large co-
test di autoimmunità ed esame otovestibolare.                                                      hort of adult patients with Ménière’s disease:
Risultati. L’età media alla presentazione clinica è stata di 55,4 anni mentre l’età del primo      bedside and clinical history. Acta Otorhi-
episodio di vertigine è risultata essere 47,4 ± 14,3. Il 43,4% della popolazione soffre con-       nolaryngol Ital 2020;40:444-449. https://doi.
testualmente di emicrania. Nel 31,7% dei casi è stata quantificata una positività di almeno        org/10.14639/0392-100X-N0776
un autoanticorpo. Quarantanove pazienti hanno riferito un familiare affetto da possibile
sindrome di Ménière. La video head impulse è risultata positiva nel 14,7%, il test vibratorio    © Società Italiana di Otorinolaringoiatria
nel 58,9%, 38,6% il test posizionale nel 38,7% e la HST nel 23,1%; una completa negatività       e Chirurgia Cervico-Facciale

ai test vestibolari è stata rilevata in 115 casi.
Conclusioni. La sindrome di Ménière è spesso associata ad un fenotipo clinico e stru-                           OPEN ACCESS
mentale suggestivo che conferma il ruolo cruciale di una attentata raccolta anamnestica e        This is an open access article distributed in accordance with
dell’esame vestibolare nella diagnosi.                                                           the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                                 Commercial-NoDerivatives 4.0 International) license. The
PAROLE CHIAVE: sindrome di Ménière, emicrania, autoimmunità, familiarità, esame                  article can be used by giving appropriate credit and mentio-
                                                                                                 ning the license, but only for non-commercial purposes and
vestibolare                                                                                      only in the original version. For further information: https://
                                                                                                 creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                               Ménière’s disease: bedside examination and clinical history




Introduction                                                     free period (at least 15 days from the last vertigo attack). At
                                                                 inclusion all patients presented unilateral MD, while during
Ménière’s disease (MD) is an inner ear disorder charac-
                                                                 different follow-up 21 (4.1%) of them developed bilateral
terised by episodic vertigo, usually preceded by cochlear
                                                                 MD.
symptoms: fluctuating hearing loss, tinnitus and aural full-
                                                                 Clinical history was collected with particular attention to
ness 1. Increased endolymphatic volume (hydrops) is the
                                                                 migraine. According to International Headache Society
commonly accepted pathophysiological mechanism, and
                                                                 (HIS) criteria 10, migrainous headaches typically last be-
this finding is also supported by newly developed imag-
                                                                 tween 4 and 72 h and present at least two of the following
ing techniques 2,3. However, the aetiology of the disorder
                                                                 features:
is not fully understood. Recent publications have focused
                                                                 • unilateral;
on the possibility of differentiating subgroups of unilateral
                                                                 • pulsating;
MD subjects characterised by specific clinical features 4.
                                                                 • moderate or severe intensity of pain;
Moreover, since 8-9% of MD patients have positive fam-
                                                                 • aggravated by, or resulting in the avoidance of, routine
ily history 4, this highlights the possibility to develop new
                                                                    physical activity.
biomarkers including genetic ones 5,6.
                                                                 All patients underwent audiometric exam confirming a low
Currently, diagnosis mainly relies on clinical history and
                                                                 to middle frequencies gap between the two thresholds in at
audiometric exam; in 2015, the Barany Society proposed
                                                                 least 2 frequencies, and concomitant vestibular evaluation,
the following diagnostic criteria for definite MD 7.
                                                                 as routinely done in outpatients presenting for vertigo. Data
A. Two or more spontaneous episodes of vertigo each last-
                                                                 were stored in a protected database. Cases were excluded if
    ing 20 minutes to 12 hours.
                                                                 surgically treated before the examination or if they had un-
B. Audiometrically documented low to medium frequency
                                                                 dergone intratympanic therapy with steroids or gentamicin;
    sensorineural hearing loss in one ear, defining the af-
                                                                 delayed hydrops were not included. All subjects underwent
    fected ear, on at least one occasion before, during, or
                                                                 central nervous system MRI with contrast focused on the
    after one of the episodes of vertigo.
C. Fluctuating aural symptoms (hearing, tinnitus or full-        cerebello-pontine angle to rule out 8th nerve schwannoma.
    ness) in the affected ear.                                   All subjects were asked to assess autoimmunity with a pan-
D. Not better accounted for by another vestibular diagno-        el of anti-nucleus (which were considered positive when
    sis.                                                         with a title at least of 1:160), anti-neutrophil cytoplasmic,
MD presents in association with two other conditions: mi-        anti-thyroids and anti-cardiolipin autoantibodies.
graine and autoimmune disorders. In fact, around 50% of          One-hundred and fifty-five patients were also included in
MD patients also suffer from migraine 8, and proteomics          another genetic study on MD 11.
studies support the possibility of autoimmunity as a poten-
tial mechanism predisposing to MD 9.                             Bedside vestibular examination
Audiometric exam is mandatory for diagnosis of MD, while         Nystagmus was studied with video Frenzel goggles (In-
few studies have been published on vestibular findings dur-      teracoustics - Assens - Denmark); spontaneous nystagmus
ing bedside examination. The purpose of the present study        was assessed with the patient seated in a clinical chair, in
was to assess clinical history and vestibular findings in        primary position and eyes rotated 15° on the right and left
MD patients with 4 tests, namely Video Head Impulse Test         side. Positional nystagmus was assessed in the supine posi-
(Video-HIT), Head Shaking Test (HST) and positional and          tion with the head turned 90° on both sides.
Skull Vibration Test, performed outside attacks of vertigo.      Post head shaking test (HST) was performed with the pa-
                                                                 tient sitting in a clinical chair with the head leaning down
                                                                 by 30°; nystagmus was studied with video Frenzel goggles.
Materials and methods                                            The patient’s head was vigorously rotated for 20 times on
Study cohort                                                     the horizontal plane with a maximum amplitude around 30-
In our retrospective study the sample was composed of 511        40°. Post HST nystagmus was recorded for 1 minute and
adult patients; data were obtained from records of patients      was considered positive when nystagmus lasting at least 5
from 2008 to 2019. The study received ethical approval by        seconds was detected.
an internal committee (No. GO/URC/ER/mm prot 762).               Skull vibration test (Skull Vibration Induced Nystagmus –
Patients were included if they fulfilled criteria for definite   SVIN) was performed at 100 Hz with a commercially availa-
unilateral MD according to the Barany Society; in subjects       ble system (VVIB - Synapsis). Stimuli were applied perpen-
enrolled before 2015 a retrospective analysis of data con-       dicularly to the skin over the mastoid process, posteriorly to
firmed Barany criteria 7. Evaluation was made in a vertigo-      the auricle, at the level of the external acoustic meatus with



                                                                                                                                    445
R. Teggi et al.




a force around 1 kg; three stimulation trials were performed
on each mastoid, lasting 5-10 seconds each. Eye movements
were studied with video Frenzel goggles and visual fixation
of both eyes was inhibited. The test was considered positive
when a horizontal nystagmus, always beating on the same
side, was elicited in all 6 trials; it was considered “paretic”
when directed toward the healthy side, and “irritative” when
beating toward the affected side 12.
Video head impulse test (video-HIT) was performed only
on the horizontal plane with a commercially available sys-
tem (ICS Impulse, Otometrics, Taastrup, Denmark). Sub-
jects were asked to remove spectacles at least 5 minutes           Figure 1. Age of onset of the first vertigo attack.
before examination and calibration was made before tests.
The calibration was also checked in the horizontal canal
plane with slow sinusoidal movement of the head while the          and inclusion) of disease was 8.3 ± 8.1 years. The distri-
patient was asked to fixate the target. In this way, at least at   bution of age of the first vertigo in the sample is summa-
low head velocity, we could confirm that head-eye velocity         rised in Figure 1. All patients reported several vertigo spells
traces were overlapping and minimised the risk linked to           with nausea/vomiting; audiometric exam presented a hear-
the presence of square waves. Trials with blinks and outli-        ing loss on low frequencies without differences between
ers were automatically excluded. Patients in whom record-          thresholds in 104 cases (20.3%), while all other subjects
ings demonstrated that eye movements always preceded               presented a flat threshold in the diseased ear. Twenty-six
head movements, even after attempts to improve goggle fit,         patients (5.1%) had positive history for Tumarkin attacks.
were not included 13. We considered the exam pathological          The age of these subjects was higher than the entire sam-
when VOR gain was lower than 0.80 and/or when correc-              ple (71 ± 5, p < 0.01). A Spearman test showed correlation
tive saccades were demonstrated, while normal values were          with both patient age (rs 0.25, p = 0.0002) and duration of
detected on the contralateral side.                                vertigo attacks (rs 0.18, p = 0.02).
All procedures were performed by a senior neurotologist.
                                                                   Comorbidities
Statistical analysis                                               In this cohort, 222 (43.4%) suffered from migrainous head-
Quantitative variables are presented as mean ± standard            ache; 27 patients (12.1% of migraineurs) referred visual au-
deviation and categorical as rate on the total sample. A P         ra. The onset of the first migrainous headache was 27 ± 6.3
value < 0.05 was considered statistically significant. Spear-      years. In all subjects except 4 the headache preceded the
man’s test was performed to investigate the association be-        onset of vertigo. Micro-ischaemic lesions were detected on
tween different variables. A linear regression model was           central nervous system MRI in 123 patients (24%).
calculated to assess the independent role of migraine, au-         Positivity for at least one autoantibodies was detected in
toimmunity and family history on age of onset of vertigo;          162 subjects (31.7%). The most common autoimmune dis-
a linear regression was also performed to assess the inde-         orders were thyroiditis (n = 65, 12.7%), undifferentiated
pendent role of age and duration of the disorder on different      connective tissue disease (n = 10, 2%) and rheumatoid ar-
clinical signs. Chi-square and odds ratio were calculated to       thritis (n = 6, 1.2%); in the remaining 81 (16%) patients,
establish the different frequencies of clinical signs in sub-      positivity for autoantibodies was an occasional finding and
jects with and without a comorbidity for migraine and au-          patients did not report clinical signs of an autoimmune dis-
toimmune disorders. We used SPSS software version 22.0             order; consultation with a rheumatologist was asked in all
(SPSS, Inc., Chicago, IL, USA) for statistical analyses.           subjects. Positivity for at least one autoantibody was more
                                                                   represented in the sample of migraineurs (χ2 p = 0.001;
                                                                   odds ratio 0.53, 95% CI 0.36-0.77).
Results                                                            Forty-nine patients (9.6%) had family history, and in 20 a
Study population                                                   first-degree relative reported episodic vertigo and hearing
In our cohort of 511 MD patients, 260 (50.8%) were fe-             loss (mother/father or brother/sister).
males. Mean age at presentation was 55.4 ± 14.1 years              A linear model demonstrated that both migraine and family
(range 18-86) and age at first vertigo attack was 47.4 ± 14.3      history were predictive for earlier onset of the vertigo. The
years. Duration (the period between the first vertigo attack       results are reported in Table I.



446
                                                                                                                 Ménière’s disease: bedside examination and clinical history




Table I. Age of onset of the first vertigo attack according to different variables.
                                                 Coefficient                      95% CI                                    SE                T Statistic                  p
 Migraine                                               -10.36               -12.96               to -7.76                1.323                  -7.83              < 0.0001
 Family history                                         -4.997               -9.022              to -0.971                2.0490                 -2.44               0.0151
 Autoimmunity                                          -0.9883              -3.5718              to 1.5953               1.31501                 -0.75               0.4527
 Sex                                                    -2.142               -4.721               to 0.436                1.3125                 -1.63               0.1032
Data show a linear model considering the age of onset of vertigo as a dependent variable and migraine, family history and positivity for at least one autoantibody as independent
variables. CI: Confidence Interval; SE: Standard Error



Bedside examination                                                                          We found an overlap between migraine and MD, dem-
Positive video HIT was found in 75 patients (14.7%), posi-                                   onstrated in 43.4% of MD subjects, while a recent study
tive SVIN in 301 (58.9%), positive positional test in 198                                    estimated the lifetime prevalence of migraine in general
(38.7%) and post HST in 118 (23.1%); in 115 subjects all                                     population to be around 10% 14. The association of MD and
clinical signs were negative. Only 2 patients with posi-                                     migraine is still under debate; in a previous work, this co-
tive SVIN demonstrated an “irritative” nystagmus beating                                     morbidity was reported in 56% of MD subjects 8. Further
toward the diseased ear. Patients with positive vestibular                                   works revealed a lower rate of migraineurs4 or showed no
tests in the entire sample and in subsamples, according to                                   association between the two disorders, even if the same au-
comorbidities of migraine or autoimmune disorders, are                                       thor reported that symptoms suggestive of migraine may
reported in Table II. Among 198 patients with positive po-                                   co-exist in patients with hydropic ear 15.
sitional test, 169 showed a monopositional apogeotropic                                      In all, 9.6% of all cases referred family history, which is in
nystagmus turning the head on the affected side, while in                                    accordance with previously reported data 16,17; however, we
29 a bipositional apogeotropic nystagmus was detected; all                                   investigated relatives with episodic vertigo and hearing loss
were characterised by few/no latency, low frequency, long                                    and it was impossible to confirm that cases were at least
lasting nystagmus (more than 3 minutes) and no vertigo.                                      probable MD.
When asked, patients did not refer positioning vertigo in the                                Interesting data was also seen considering the autoimmun-
previous days, possibly related to benign paroxysmal posi-                                   ity spectrum. Positivity for at least one autoantibody was
tional vertigo. Statistical analyses demonstrated that posi-                                 detected in 31.7% of the sample, even if an autoimmune
tive positional tests (n = 198, χ2 p = 0.04; odds ratio = 1.43,                              disorder was diagnosed in only 15.9% of these patients,
95% CI 1.00-2.05), as well as a bipositional apogeotropic                                    with thyroiditis being the most frequent. Positivity for a
nystagmus (n = 19, χ2 p = 0.0016; odds ratio = 2.6, 95%                                      single autoantibody was more frequent in migraineurs. The
CI 1.18-5.72,) were more frequent in migraineurs than in                                     observed value (15.9%) of MD subjects with an autoim-
general sample. The duration of vertigo spells had no cor-                                   mune disorder is consistent with other published studies 4,
relation with the clinical findings.                                                         reported to be around 17% in unilateral MD and over 20%
                                                                                             in bilateral MD 18. Interestingly, the number of patients
                                                                                             with positivity for at least one antibody was 31.7%, which
Discussion                                                                                   is lower than the previously reported percentage (38%) by
Herein, we mainly focused on clinical history and comor-                                     other authors for only anti-thyroid autoantibodies 19. The
bidities, specifically family history, migraine and autoim-                                  association between inner ear disorders and vertigo has
munity (as routinely done in our centre), along with bed-                                    been widely studied in the last years and it should be un-
side examination.                                                                            derlined that autoimmunity has been proposed as a predis-


Table II. Bedside examination results in the entire cohort and subgroups.
                                                Total sample                              Migraineurs                       Autoimmune +                             p
                                                  (n = 511)                                (n = 222)                          (n = 162)
 Video - HIT                                           75 (14.7%)                          25 (11.3%)                          23 (14.2%)                           n.s.
 SVIN                                                  301 (58.9%)                         111 (50%)                            94 (58%)                            n.s.
 Positional test                                       198 (38.7%)                         96 (43.2%)                          67 (41.3%)                           n.s.
 Post HST                                              119(23.1%)                          47 (21.2%)                          36 (22.2%)                           n.s.
Total number and percentage of patients with positive vestibular tests (Video HIT: Video Head Impulse Test; SVIN: Skull Vibration Induced Nystagmus; HST; Head Shaking Test) in the
total population and according to Migraineurs and patients with positivity for at least one of the autoantibodies (Autoimmune +).




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R. Teggi et al.




posing factor to develop MD; this hypothesis is supported          nystagmus is the most common finding in vestibular mi-
by the fact that hydrops can be induced experimentally             graine (VM), it could be assumed that a proportion might
by injection of antigens or monoclonal antibodies and the          experience attacks of both hydrops and VM, and the clini-
deposition of circulating immune complexes may produce             cal finding may be related to the latter 27. The increased rate
inflammation and interfere with the filtering capability of        of positional nystagmus in the subsample of migraineurs
the endolymphatic sac 20,21.                                       seems to support this hypothesis.
Interesting results can be obtained by clinical signs col-         Data from our study support the hypothesis that SVIN has
lected outside vertigo spells. We found a positive video-          a higher sensitivity to detect a vestibular deficit in MD out-
HIT in 14.7% of subjects. These results substantially con-         side a vertigo attack, while HIT is more frequently normal;
firm those of previous works, reporting low percentages of         the finding is not inconsistent with the possibility that a
positive video HIT ranging between 54.5% 20 and 0% 22,23           discrepancy between the 2 tests may be useful in the di-
in patients beyond vertigo attack. It can be speculated that       agnostic pathway. Further studies can assess if a dissocia-
video-HIT studies rapid vestibular acceleration, thus focus-       tion between the 2 tests may be a peculiar characteristic of
ing on irregular neurons and phasic type-1 hair cells whose        MD. Moreover, SVIN mainly detect a deficit of the lateral
activity can be spared in hydrops 24.                              canal function; other tests, ocular and cervical VEMPs, are
SVIN was seen to be a more sensitive test, provoking a con-        promising in studying macular function, above all when
sistent nystagmus beating toward the unaffected side in 301        performed with sounds at different frequencies and study-
patients (58.7) except for two cases in which the nystagmus        ing the tuning curve of responses, thus allowing a mapping
direction was toward the hydropic side. SVIN is a newly pro-       of all parts of the inner ear 28,29.
posed test that is able to reveal nystagmus in patients with       Some weak points in our investigation should be under-
asymmetry in vestibulo-oculomotor reflex. The slow phase           lined. For example, we were unable to retrieve data about
velocity of SVIN seemed to be correlated with that of caloric      all comorbidities or about the number of crises in the last 6
tests, suggesting the possibility that skull vibration mainly      months. On the other hand, even though further studies are
concerns the horizontal canal 12. Moreover, other authors          needed, our data are not inconsistent with the hypothesis
demonstrated a correlation between SVIN and caloric tests          that skull vibration can be easy to perform and fast to orient
when caloric hypofunction was higher than 50% 25. Finally,         the clinician towards diagnosis of a hydropic form.
it has been reported that vibration on mastoid or neck mus-
cles induced a shift of the subjective visual vertical, suggest-   Conclusions
ing an induced deficit of the otolithic organs or vertical semi-
circular canals 26. The literature is poor in this area. Hong et   Thorough clinical history and careful bedside vestibular
al. reported a positive SVIN in 71% of MD subjects beating         examination can orientate the clinician’s suspicions to-
toward the lesion side in 27% of cases 26. Dumas et al. de-        wards MD, thus guiding and confirming definite diagnosis.
scribed a SVIN in 71% of MD patients (most observed in a
pre-attack or a period close to a recent attack) with modified     References
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