The effectiveness of endolymphatic duct blockage versus endolymphatic sac decompression in patients with intractable Ménière*s disease

- Ménière*s disease
Ménière*s disease (MD) is an incapacitating disease of recurrent vertigo
attacks, accompanied by hearing loss, tinnitus and/or aural fullness. Between
the attacks of vertigo intervals of days, weeks or even months may occur (Lopez
2015, Pullens 2013). The natural course of MD has been studied and it has been
found that the attacks of vertigo become less severe and disappear after two
years in 60% and after eight years in 80% of patients (Portmann 1980;
Silverstein 1989, Perez 2008, Van Esch 2016). In the end phase of the disease
patients without vertigo attacks may still suffer from lasting hearing loss and
tinnitus and chronic instability caused by hypofunction of the labyrinth.
Significant comorbidity is seen in patients with Ménière*s disease. The most
important comorbidities that may also cause dizziness are anxiety disorders and
BPPV (van Esch, 2016).

MD is an idiopathic disease associated with endolymphatic hydrops in the inner
ear (Merchant, 2005). Visualization of the hydrops became possible with the
introduction of delayed post-contrast high resolution MR imaging (Nakashima
2007; Naganawana, 2014; Baráth, 2014). Moreover, recent publications underline
the relevance of the signal intensity of the perilymphatic fluid (Bernaerts
2019, Shi 2018, Steekelenburg 2020). This signal intensity is a surrogate
marker for the permeability of the blood-perilymph barrier, and may therefore
reflect acute inflammation or recent activity related to a vertigo attack.

Few articles have been published on the epidemiology of MD. Great variation
exists in the published reports of the prevalence of MD, ranging from 34.5
cases per 100,000 population in Japan (Shojaku 2005) to 46 cases per 100,000
population in Sweden (Stahle 1978). In the United States of America, reported
prevalence is much higher: Alexander (Alexander 2010) reports 190 patients per
100,000, Waldislavosky-Waserman (Wladislavosky-Waserman 1984) reports a
prevalence of 218 per 100.000. The difference in prevalence might be due to the
wide variations in definitions of MD.
In the Netherlands, a population of 60-100 per 100,000 patients is severely
impaired (defined as low quality of live) by the disease (Mateijsen, 2001).
There seems to be a slight female preponderance, with up to 1.3 times more
women affected than men. The disease is more common in adults in their fourth
and fifth decade of life (Kotimaki 1999, Perez 2008, Van Esch 2016).


Currently, there is not specific guideline for the treatment of MD in the
Netherlands. The guideline *Dizziness in Elderly* of the Dutch ENT Society
(*Duizeligheid bij ouderen*, NVNKO, 2015) advises to refer the patients to a
specialized ENT surgeon. The guidelines *Dizziness* of the Dutch General
Practitioner Society (Bouma 2017) for general practitioners also advises to
refer the patient to an ENT surgeon, but only in case of rapid progressive
hearing loss or additional complaints such as instability, head ache of
persisting tinnitus.
The treatment of MD both in primary and secondary care setting is focused on
the reduction of the frequency and intensity of vertigo attacks. Current
treatments have either proven to be ineffective (Betahistin;Adrion 2016), only
have a temporary effect (intratympanic dexamethasone injections; McRackan 2014,
or methylprednisolone; Patel 2016), or destroy the labyrinth function
(intratympanic gentamicin, labyrinthectomy, selective neurectomy;Pullens 2013;
Harner 2001, Sennaroglu 2001). Surgical destruction of the labyrinth reduces
the episodes of attacks but causes loss of balance as well, due to one
dysfunctional labyrinth. Moreover, permanent hearing loss is reported after
this treatment.

- Endolymphatic sac surgery
Other surgical treatment techniques target the endolymphatic sac (ES). The
advantage of these procedures is that they are non-destructive and do therefore
not affect the cochlear and vestibular function, thereby preserving hearing and
balance. These procedure involve decompression, shunting or drainage of the ES.

Endolymphatic sac decompression (ESD) consists of a mastoidectomy and, after
identification of the endolymphatic sac, wide decompression of this structure
(Sennaroglu, 2001). ESD has few surgical complications in comparison with the
ablative surgery mentioned above. There is no consensus on the effect of
decompression. Convert et al (Convert 2006) report improved quality of life
after decompression in a case study of 90 subjects after a follow up period of
57.5 months on average.


Drainage or shunting of the endolymphatic sac (ESS) involves identification of
the ES, followed by incision of the sac. A shunt is then placed, enabling
drainage of the endolymph.
There are several studies that were directed to investigate the effectiveness
of ESS (Bretlau 1989, Thomsen 1998, Brinson 2007). Bretlau and Thomsen compared
ESS to a sham operation; no differences between the groups was observed.
Brinson compared ESS to ESD performed on 88 and 108 patients, respectively. He
concluded that both procedures are effective

Multiple histological studies refute the rationale of endolymphatic sac
surgery. Firstly, Chung et al (2011), performed a histopathological study 15
patients who had undergone ESS. If the endolymphatic sac does indeed have a
function in resorption of the endolymph but does so inadequately, ESS and
especially ESD would allow expansion of these structures and would therefore
diminish hydrops. However, diffuse hydrops on temporal bone was seen in the
cochlea, the saccule, the utricle, and the ampulla after ESD. The authors
conclude that ESD does not relieve hydrops in patients with Ménière*s disease.
In addition, if the ES was responsible for endolymph resorption, an increase of
hydrops can be expected after amputation of the ES. However, Linthicum et al.
(2011) reported a case in which removal of the ES did not lead to an increase
of hydrops, as seen on temporal bone histopathology. In the assessed samples,
Reissner*s membrane was attached to the spiral ligament in a normal way,
without any evidence of hydrops in the cochlea. In conclusion, the role of the
ES is not merely absorption of the endolymph and therefore, providing more
space to allow dilatation is not the solution for the observed hydrops.

The success rates of these surgical interventions vary between 30-95%
(Sennaroglu 2001; Huang 1991; Silverstein 1989, Durland 2005, Pullens 2013;
Convert 2006). It should be noted that the natural course of MD is also
favourable, and it cannot be determined to what extent this outcome is due to
the surgical intervention. Moreover, the placebo effect may play a major role
in the relief of complaints, as 70% of MD patients in all groups (all surgical
interventions as well as the control groups) experienced some relief of
complaints. This either implicates a beneficial effect of any surgical
intervention or of any intervention, be it surgical or non-surgical. This was
earlier suggested by Thomsen (Thomsen 1981).
Because the beneficial effect of any sort of endolymphatic sac surgery is not
sufficiently proven, these procedures arenot performed in The Netherlands as
standard treatment for MD. However, in many other countries decompression is
performed as part of usual care.

- Endolymphatic duct blockage
Recently, a new surgical intervention has been studied by Saliba et al. (Saliba
2015). A paradigm shift for the pathofysiological model of MD underlies this
new treatment. Until now it is believed that the disease is caused by a surplus
of endolymph originating in the inner ear, caused by a disequilibrium in the
production of endolymph in the inner ear and its resorption in the
endolymphatic sac (Merchant, 2005, Semaan, 2010, Salt, 2010). However, Saliba
et al. state that the organic substrate of the disease - the surplus of
endolymph causing the hydrops - originates in the endolymphatic s

This study assesses whether EDB surgery will result in a significant reduction
in the number of patients without vertigo spells at 12 months follow up,
compared to patients who undergo endolymphatic sac decompression.

This is a prospective, multicentre, randomised, double blinded, parallelgroup
trial. The study will take 4 years: 6 months of start up time, 2 years of
inclusion, 1 year of follow up and 6 months to analyse the results.

Participating centres are: Haaglanden Medisch Centrum (Den Haag),
HagaZiekenhuis (Den Haag), LUMC (Leiden), Apeldoorns Duizeligheidscentrum Gelre
Ziekenhuizen, Beatrix Ziekenhuis (Gorinchem), Erasmus Medisch Centrum
Rotterdam, Gelderse Vallei Wageningen, Isala (Zwolle), Maastricht UMC, Medisch
Centrum Leeuwarden, Radboud UMC (Nijmegen), UMC Utrecht, Wilhelmina Ziekenhuis
Assen

- Surgical procedure in EDB group
First, a canal wall-up mastoidectomy is performed: the mastoid tegmen, sigmoid
sinus, and sinodural angle are identified, and the posterior bony external ear
canal wall is thinned. The posterior semi-circular canal (PSCC) and the dura
mater of the posterior fossa are identified. Using the prominence of the
horizontal semi-circular canal, Donaldson*s line is identified to approximate
the position of the endolymphatic sac. The bone over the sac and the dura are
thinned with diamond burrs. The sac is completely skeletonized. The
infralabyrinthine dura is exposed because the main body of the sac and its
lumen often lie within this area. The bone of the vestibular aqueduct operculum
is dissected. The posterior fossa dura from the retrolabyrinthine bone medial
to the sac around the endolymphatic duct is exposed in order to identify the
duct in its superior and inferior part in continuity from the endolymphatic
sac, and to create a place to insert the tips of the instrument to clip the
duct. At this level, care must be taken not to traumatize the dura, which is
often thin.

Finally, the dissected endolymphatic duct is blocked with an adequate titanium
clip (Weck Horizon, size *micro* to *wide). The size and numbers of clips used
will be determined intraoperatively. The titanium clips are applied by using a
clip applier (Weck Horizon) and a McGee bending forceps (Aesculap). In the case
of tearing of the dura leading to liquor leakage, this will be treated with
tisseel, fascie and novacol. The cortex is not restored. The skin is closed in
a regular way.

- Surgical procedure in sham group
The same surgical procedure is carried out in the sham group. After
identification of the endolymphatic duct, a CT scan is performed to assess if
the endolymphatic duct was identified correctly. After ensuring the structure
is indeed the duct, it is decompressed.

As for every surgery and general anesthesia, this intervention comes with risk.
Firstly the risk of general anesthesia (mortality of 34 per 1 million
patients).
The specific risks of this surgical procedure are:
- Injury to the facial nerve
- Injury to posterior semi-circular canal with loss of vestibular function
- Injury to the sigmoid sinus
- Hearing loss
- Leakage of cerebrospinal fluid (CSF), presenting after the operation
- Meningitis
- BPPV

These risk are related to the region where the intervention takes place.
Because the operation procedure of Saliba was enhanced by Blom, we do expect
lower rates of leaks of CSF and BPPV. Other complications that were mentioned
above have not been seen. Overall, we do think these risks are proportional.

The additional visits and tests are concentrated in 4 visits over a period of a
year. We do think this is not too much of a burden for the patient. Completing
the daily questionnaire demands motivation, but we asked several patients for
their opinion and they think it is feasible. Moreover, the relevant patient
community supports the study.