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.