4. Discussion
In our patient cohorts we observed no significant differences between
the clinically non-affected side and the clinically affected side of
unilaterally affected patients with MD independently of the used MRI
sequence when using the Bonferroni correction for multiple testing.
4.1. Different models of ethiopathogenesis
The pathogenesis of MD is still incompletely understood and the disease
can be difficult to diagnose in early stages
(2, 13,
16). Autoimmune processes
(17) and viral infections, such as latent
herpes simplex virus type-1 that may cause vestibular neuritis
(18), may play a role in the induction of
MD. The involved immunological mechanisms are still not clear, but
approximately one-third of the MD cases may have an autoimmune origin
(19-21). Further pathophysiological
aspects have been discussed, such as genetic predisposition
(22), excitotoxicity, chronic otitis
media (20), cellular apoptosis and
oxidative stress. Reactive oxygen species, specifically nitric oxide
generated by nitric oxide synthase, regulate the cochlear blood flow and
lead to the release of mitochondrial cytochrome c, which is an important
mediator of the intrinsic pathway of apoptosis
(23, 24).
The presence of hydrops may thus cause neuronal damage in the inner ear
via a process of excitotoxicity (1,
25). This neuronal damage could possibly
affect the VIIIth and potentially also the
VIIth cranial nerve.
Our data, however, demonstrated no differences in nerve diameters when
comparing the clinically non-affected to the clinically affected side of
unilaterally affected MD patients, possibly pointing toward a more
systemic process that leads to subclinical reaction of the contralateral
ear in clinically unilaterally affected MD patients. Kariya et al found
equal results when comparing the mean number of spiral ganglion cells,
the mean loss of inner and outer hair cells in patients and the damage
of the stria vascularis with unilateral MD
(3). This may support autoimmune processes
or genetic predispositions, whereas local processes such as
excitotoxicity and reactive oxygen species seem less likely. Moreover,
our data did not show a correlation to clinical symptom duration, which
again may point toward a very longstanding underlying process prior to
the onset of clinical symptoms. On the other hand, it could also
indicate that there is no change in the 7th and 8th cranial nerves in
MD. However, this contradicts our previous study, which showed thicker
nerves in patients with MD compared to a healthy control group
(8).
4.2. MRI difficulties
Moreover our data showed different means for the same patients at the
same measuring levels in dependence of the employed MRI sequence. These
differences occur due to different variable sequence parameters such as
slice thickness, different partial volume effects and the relatively
small sample size. Where measurements varied largely between
VIIth and VIIIth cranial nerve,
differences between the 4 employed sequences were small. However, due to
the limited sample size, a significant positive correlation could only
be shown for the IR-0.3 and IR-0.5 for VIIth and
VIIIth cranial nerve. This reflects the difficulty of
comparing absolute morphometric parameters in different MRI-studies
performed with different sequences on different scanners.
In an explorative approach, without catering for multiple testing,
scattered single parameters were found to be significant, these findings
showed no specific pattern. Therefore Bonferroni correction was applied.
4.3. Study Limitations
Our study has several limitations that need to be taken into account
when interpreting the data. First, our sample size was limited,
especially when performing the subgroup analyses. Larger studies are
warranted to confirm our results. Second, we did not compare our
measurements to an age- and sex-matched healthy control cohort to
analyze differences to a clinically unaffected control population. As
shown in our previous study (8) only few
surveys (5-7,
10) with measurements of the
VIIth and VIIIth cranial nerves had
been published, mostly in normal hearing patients. The comparison of
these published data also showed differences of nerve diameters
according to the measuring point and the used MRI sequence.