In the present study, it was first reported the differences between EDB and EDD in the reversal of endolymphatic hydrops in MD. Inner‑ear Gd‑enhanced MRI revealed that both the EDB and EDD procedures could reduce EH in certain patients with MD. The reversal of EH was detected 2 weeks following surgery in the EDD group; by contrast, no reduction in EH was observed 2 weeks after surgery for the patients in the EDB group, although the reversal of EH was identified several months after surgery in this group.
In vivo visualization of hydrops with Gd‑MRI is no longer limited to only showing evidence of the hydrops for the diagnosis of MD. Changes in EH may be used to objectively evaluate and differentiate the effects of various treatments for patients with MD [13-16]. In the present study, a reduction in EH was found in 3 of 10 patients with EDB, and 4 of 9 patients with EDD, suggesting that both the EDB and EDD procedures had the potential to reduce EH in certain patients with MD. However, 5 of 10 patients in the EDB group, and 4 of 9 patients in the EDD group did not exhibit any change in their EH, indicating that sac surgery does not always result in an improvement of EH in MD. An enhancement of EH was identified with 1 patient who underwent EDB, and 1 patient who underwent EDD, and this may have been due to the natural course of MD with the progression of EH [17, 18].
Physiologically, EDB represents a completely different approach to EDD in terms of the surgery that has been taking place over a large number of years with the aim of improving endolymphatic drainage. However, the mechanistic and pathophysiological basis underlying endolymphatic sac surgery remains poorly understood. An immunohistochemical and ultrastructural investigation of the human endolymphatic sac in MD revealed both the secretion of glycoproteins and the possible existence of hypersecretions of endolymph in the sac [19-21], and an increased expression of aquaporin‑2 in the endolymphatic sac epithelium of patients with MD was proposed to be involved in the pathophysiology of EH [22], which may support the hypothesis that an increased secretion outweighs a decreased absorption, resulting in increased pressure in the inner ear [7]. Therefore, by blocking the endolymphatic duct, EH may be decreased due to a reduction in the volume of endolymph in the inner ear arising from the sac, this hypothesis provides the rationale potentially explaining how EDB may work in the treatment of MD. By contrast, EDD is based on the hypothesis that deficient absorption in the endolymphatic sac is one of the causes of EH, regardless of all other uncertainties surrounding the treatment of MD [23, 24]. Endolymphatic sac drainage is still universally considered by surgeons to be an excellent option for vertigo control and hearing preservation [25]; moreover, a decrease in the volume of EH following sac drainage surgery has recently been confirmed with Gd‑MRI [26-28]. However, the reversal of EH achieved in certain patients with MD via the two opposing surgical approaches on the endolymphatic sac, as investigated in the present study, has demonstrated the inhomogeneity and complexity of the mechanisms underpinning the development of EH. The exact role of the endolymphatic sac in MD remains unknown.
Interestingly, in the EDB group, the EH remained unchanged 2 weeks after surgery, and the reversal of EH could only be detected in some of the patients at >12 months following surgery, suggesting the reduction in the volume of endolymph was likely due to a delayed effect associated with the EDB surgery that progressed over time. By contrast, in the EDD group, the reduction in EH could be detected 2 weeks following surgery, suggesting that EDD resulted in the reversal of EH very soon after surgery, which was likely due to the mechanical effect of the opened endolymph sac with an acute reversal of EH. Since no further patients showed any reduction in the endolymph space at >12 months following surgery‑indeed, a recurrence of vestibular hydrops in one patient was detected in comparison with the results of Gd‑MRI 2 weeks following surgery‑a delayed effect on EH for EDD was not found. Although a precise understanding of the physiological mechanisms underlying MD‑related vertigo has yet to be elucidated, vertiginous attack is considered to result from acute development or exacerbation of EH [29], suggesting that the reduced volume of EH was likely to have been associated with a reduction of spells. This hypothesis seems likely to explain how a complete control of vertigo was achieved in the patients in both the EDB and EDD groups who exhibited a reversal of EH in the present study. In addition, a major body of evidence already exists in support of a direct link between hydrops and disordered auditory physiology, suggesting that low‑tone sensorineural hearing loss in MD is caused by the mechanical impact of high endolymphatic pressure [2]; therefore, a reduction in the volume of the endolymph is expected to result in an improvement in hearing. In the present study, all 3 patients in the EDB group for whom reversal of EH was confirmed were found to have improved hearing, revealing a cause‑effect relationship between EH and hearing function. However, with the 4 patients in the EDD group for whom reversal of EH was confirmed, hearing improved in only one patient, worsened in one, and was stabilized in the other two, suggesting no correlation between the changes in hearing function and the volume of EH after sac drainage surgery, a finding that was consistent with previous reports [26-28]. In the former case (EBD), the reversal of EH was found to be a delayed effect associated with the surgery that progressed over time, which was likely to be linked with physiological recovery in the homeostasis of the endolymph. In the latter case (EDD), the reduction in EH was presented as an acute reversal of EH, which was likely to be due to the mechanical effect of drainage of endolymph from an incised sac, suggesting that a different process was operative in terms of the decrease of endolymph volume and consequences of hearing function compared with the former technique.
In addition, high-quality imaging in vivo visualization of hydrops with Gd-MRI is very important, especially for evaluating the dynamic changes of EH. Although promising results have been reported using IV-Gd, which has the advantage of not being an off-label use of Gd [30-33]. Yet, they were too time-consuming to use for routine diagnostic procedures, moreover, it was difficult to obtain serial MRI scans by this heavily T2-weighted 3D FLAIR sequence for evaluating the dynamic changes of EH of “after treatment” and “before treatment” groups. In the present study, the use of IT-Gd + IV-Gd MRI not only improved the effectiveness of imaging and evaluation techniques for EH [34], but also prevented the failure of IT-Gd imaging for ~10% of cases [36], which would have been caused by an insufficient Gd concentration with anatomic barriers to the round window, such as adhesions, bone dust blockage or thickened round window, when the IT-Gd method alone was used [35]. As presented in Figs. 2-5, the MRI technique used in the present study had an equal or superior resolution to other techniques reported in previous literature[14, 15, 26-28]. The comparison of serial MRI scans, which were obtained from multiple section planes in the same ear between the before and after treatment, could clearly identify the dynamic changes of EH, showing an objective marker for assessing the effects of treatment in MD.
There were some limitations associated with the present study; first, there was a lack of pathological evidence in the endolymphatic sac to explain why the reversal of EH could be achieved via two opposing surgical approaches on the sac. Further investigations are necessary to determine whether there were different pathological changes in the endolymphatic sac, comparing between the patients who presented with a reversal of EH and were treated with EDB or EDD, respectively. Second, the degree of EH in the cochlea was assessed by visual comparison of the relative areas of endolymphatic space versus the perilymph space, categorizing each ear as normal, grade I hydrops or grade II hydrops, which may be insensitive to subtle changes among scans.