Edited by: Dominik Straumann, University Hospital Zurich, Switzerland
Reviewed by: Maurizio Versino, Pavia University, Italy; Maurizio Barbara, University La Sapienza, Italy
*Correspondence: Raymond van de Berg, Department of Otolaryngology and Head and Neck Surgery, Maastricht University Medical Centre, Postbus 5800, 6202 AZ Maastricht, Netherlands. e-mail:
This article was submitted to Frontiers in Neuro-otology, a specialty of Frontiers in Neurology.
This is an open-access article distributed under the terms of the
For more than a decade, research has been conducted into development of an invasive vestibular prosthesis (vestibular implant) (Gong and Merfeld,
Firstly, motion is detected by gyroscopes which send their signals to a processor. Secondly, the signals are processed to create an adequate stimulus with the right pulse characteristics (frequency, current, shape). Thirdly, the stimulus is delivered by electrodes to the vestibular nerve (Gong and Merfeld,
Studies have shown that it is possible to induce a nystagmus which corresponds to the plane of the canal innervated by the electrically stimulated nerve branch (Gong and Merfeld,
To be close to the vestibular nerve, in order to give selective stimulation and have as little crosstalk as possible (the spread of the current to other than the targeted anatomical structures which leads to unintended activation of them) to the facial nerve, cochlear nerve, and other ampullary nerves (Wall et al.,
To be reached with as few surgical risks as possible. Damage to the facial nerve and deafening the patient are the main risks involved in the surgical approach of some specific locations (Gacek,
To stimulate a vital part of the vestibular nerve. Studies show that, depending on pathology and elapsed time since onset of disease, different parts of the vestibular sensory system are affected to a different extent. This results in varying amounts of neurons available for the electrodes. Therefore, it is believed that different stimulus locations should be considered. Proposed locations are the ampullae, along the course of the vestibular branches, or Scarpa’s ganglion (Gacek,
Previously, two types of approach have been developed for implantation of a vestibular implant:
An approach to the lateral ampullary nerve (LAN), superior ampullary nerve (SAN), and posterior ampullary nerve (PAN), for extralabyrinthine stimulation.
An approach to the ampullae of the semicircular canals (ampullar approach), for intralabyrinthine stimulation.
In Geneva an approach to the PAN, LAN, and SAN has been developed and tested in humans (Wall et al.,
This surgery involves two different approaches, one for the PAN, the other one for the LAN and SAN. The PAN is reached by a transmeatal approach in which the floor of the round window niche is drilled in its most rostral part. Then, the nerve is “blue-lined” and an electrode is inserted. This technique is extracted from that described by Gacek to treat benign paroxysmal positional vertigo (Gacek,
It is shown that electric stimulation from these locations induces a nystagmus which corresponds to the plane of the canal innervated by the stimulated nerve branch, and that it is possible to elicit smooth oscillatory eye movement by modulating the amplitude or frequency of the stimulation (Wall et al.,
There are a number of possible drawbacks to this type of approach. Firstly, there is a risk of sensorineural hearing loss, especially when drilling out the osseous ampulla which could result in accidental damage to the membranous labyrinth. For the approach to the PAN, the risk of sensorineural hearing loss varies from 3.6 to 38% (Epley,
The main advantage, however, is the very close proximity of the electrodes to the nerves, which could allow for highly selective stimulation with little current, leading to little current spread and crosstalk (Merfeld et al.,
In other studies, an approach to the ampullae of the semicircular canals is used (Gong and Merfeld,
In animals, it is shown that it is possible to induce an electrically evoked nystagmus which corresponds to the plane of the stimulated canal. However, there are still some drawbacks that have to be investigated. For example: deafening the patient, and creating a sufficient response (Gong and Merfeld,
The main advantages of this type of approach are that the facial nerve remains relatively safe from damage and that the middle ear structures are preserved (Wall et al.,
The ampullar approach appears to be relatively safe, with few drawbacks, and easier to use than the LAN/SAN/PAN-approach. However, the drawbacks and possible risks of the ampullar approach, namely more current spread, sensorineural hearing loss (Tang et al.,
Performing the ampullar approach in a human, and specifying/modifying the technique in order to minimize surgical drilling and damage to the otic capsule;
Showing and discussing the preliminary results of ampullar stimulation under general anesthesia.
The ampullar approach has previously been performed by using a cortical mastoidectomy, exposition of the semicircular canals, extensive bluelining of the semicircular canals, and fenestrating them at the thin segment or adjacent to the ampullary ends (Gong and Merfeld,
Intra-operative facial nerve monitoring was used.
When the superior and lateral semicircular canals fuse at the vestibule, they make a “V-shape.” Therefore, after the mastoidectomy and posterior tympanotomy, minimally invasive bluelining of the anterior ends of the canals (adjacent to each ampullary end) was obtained by drilling cranially at the dome of the lateral canal and following it, until the “V” appeared. A small diamond burr (2 mm) was used. As the anterior end of the superior canal was located by following the lateral canal, no more drilling of the superior canal was necessary. Eventually, approximately only 3 mm of the anterior ends of both canals were blue-lined. After that, a small fenestration adjacent to each of the ampullary ends was made. In this case, a manually positioned temporary electrode was inserted (see below). Permanent electrodes would be inserted in the case of a vestibular implant (Figures
The ampulla of the posterior canal is located nearby the oval window and stapes. Therefore, it is located medial to the facial nerve, at an imaginary almost horizontal line through the stapes footplate, between the sigmoid sinus and the facial nerve (Figure
The subject of this experiment was a 21-year-old woman undergoing surgery for cochlear implantation, performed by the last-named author in Maastricht University Medical Centre. Due to meningitis in her childhood, she became bilaterally deaf with bilateral vestibular areflexia. She reported no vestibular complaints.
Three inclusion criteria were fulfilled:
mean peak slow phase velocity of ≤5°/s in bilateral bithermal caloric irrigations;
pathological Head-Impulse-Test (HIT) for horizontal and vertical canals;
low or no gain on rotatory chair tests.
Electro-nystagmography (ENG) was used for vestibular testing. Bilateral bithermal (30° and 44°) caloric irrigations were performed by experienced technicians in standard conditions. Rotatory chair tests consisted of horizontal and vertical torsion swing (0.11 Hz, ωmax = 100°/s) and bilateral velocity steps (ω = 250°/s). Manual HITs were recorded with a high speed camera [CASIO Exilim, Pro EX-F1, 12× optical zoom, high speed camera, 300 frames per second (fps)] in the three semicircular canal planes. The presence of correction saccades was considered as pathological. She showed no response to bilateral vestibular galvanic stimulation. These vestibular tests were only performed pre-operatively.
Informed consent, and approval from the Medical Ethical Committee, in accordance with the Helsinki Declaration, were obtained (protocol name and number: “Electric stimulation of the ampullary nerves in patients with bilateral vestibular loss” – NL31405.068.10; World Medical Association General Assembly,
To check the locations of the fenestrations, and to show the feasibility of evoking a VOR by stimulating the ampullary nerves via the ampullae, a monopolar electrode was used to electrically stimulate the ampullae. It was manually positioned on the cristae of the ampullae for intralabyrinthine stimulation. The return electrode was placed on the patient’s back. When measurements were completed, the canals were closed with bone wax and Tissucol® (Baxter, aprotinin, trombin).
Matlab© software was used to drive a real-time processor (RP2.1 Real-Time Processor, Tucker-Davis Technologies© which was connected to a galvanic stimulator (Maastricht Instruments bv©) where the stimulus was converted to a current. A monopolar stimulator (Standard Prass Flush-Tip Stimulator Probe, Medtronic©) of 500 μm was used to deliver the current to the nerves.
Biphasic pulses of 200 μs phase duration with a repetition rate of 200 Hz were used. Amperage was modulated step by step from 0 to a maximum of 1 mA. Pulse train duration was 10 s with on/off periods of 0.5 s.
The horizontal, vertical, and torsional eye movements were recorded using video oculography (Clinical Video Eye Tracker, Maastricht Instruments bv©) at 50 samples/s. Recordings were analyzed off-line with algorithms written in Matlab© software. Horizontal, vertical, and torsional components were estimated at suprathreshold stimulation parameters.
The whole procedure was performed under general anesthesia. Propofol 6 mg/kg/h and Remifentanil 0.35 mcg/kg/min were administered during the surgical approach. When electric stimulation and measurements commenced, Propofol was stopped, and Remifentanil was continued at the same dosage. After electric stimulation, the cochlear implantation procedure was resumed with Propofol only (8 mg/kg/h).
The modified ampullar approach was performed successfully: the ampullae from the anterior, lateral, and posterior canal were reached, with minimal bluelining of the anterior ends of the canals. No damage to the facial nerve, ossicular chain, or inner ear structures was observed.
Stimulation with 700 μA elicited tonic eye deviation in all three ampullae, confirming the positioning of the electrode and feasibility of ampullar stimulation by this approach.
Maximum vertical and horizontal amplitudes of the eye during ampullar nerve stimulation of the canals ranged from 6.6° to 19°. These results are presented for each canal in Figure
Stimulation of the LAN showed a horizontal component which was away from the stimulation side. The vertical component was upward. For the stimulation of the SAN, the vertical component was upward and the horizontal component was away from the stimulation side. Maximum amplitude of torsion was 17°. Stimulation of the PAN elicited tonic eye deviation with a downward vertical component and a horizontal component away from the stimulation side. When the current was increased to obtain maximum amplitudes, facial twitching was observed in most of the cases.
When stimulation was stopped, the eye returned back to its starting position. Examples are presented in Figures
Regarding the anesthetics, it was clearly observed that after the Propofol was stopped, reactions became more profound once the Propofol was cleared from the body.
During post-operative follow-up, the patient did not suffer from any change in vestibular symptoms. Facial nerve function was preserved.
This study shows, for the first time in a human with a long-term vestibular loss, the modified ampullar approach with minimally invasive surgery and the feasibility of ampullar stimulation. There is an important difference between this human subject and subjects in previous research: previous subjects still had some residual function, or bilateral vestibulopathy was induced by canal plugging or ototoxic medication prior to implantation (Gong and Merfeld,
The modified ampullar approach seems to be a safe approach. Firstly, the facial nerve remains relatively safe from damage when intra-operative facial nerve monitoring is employed. Secondly, middle and inner ear structures are preserved. Thirdly, surgery of the vestibular system is already well known by neuro-otologic surgeons compared to the extralabyrinthine approach to the LAN/SAN/PAN. Fourthly, accidental damage to the canals is reduced, by modifying the ampullar approach into a procedure with minimally invasive surgical drilling, using the “V-shape” of the superior and lateral canal, together with the imaginary horizontal line through the stapes footplate as a reference. This facilitates safe bluelining of only the anterior ends of the canals, adjacent to the ampullary ends. Further advantages of the ampullar approach are that multiple electrodes can be inserted into the ampulla, and that fixating them will be less challenging than with the extralabyrinthine approach. For example, if the array of electrodes shifts accidentally during surgery, another electrode with the best response could be selected for stimulation. In addition, using more electrodes could also facilitate current-steering and precompensation (correcting the misalignment of the VOR-axis by vector summation; Fridman et al.,
One potential disadvantage of intralabyrinthine ampullar stimulation is the general belief of deafening the patient. However, more studies show that, with appropriate surgical technique and equipment, opening the canals carries a risk of hearing loss that is neither severe nor permanent (Parnes and McClure,
It should be noted that the ampullar approach does not rule out the extralabyrinthine approach to the LAN/SAN/PAN. They could be used as complementary procedures (a combination of both approaches in one patient) or as alternatives (the appropriate technique is selected for each patient), depending on the results of future research.
These preliminary results show that ampullar stimulation is possible in a person with a long-term vestibular loss. Stimulation leads to a tonic eye deviation with mixed components and variable maximum amplitudes. Although components are mixed, stimulation always evokes a vector which is congruent with the canal: a horizontal component during LAN-stimulation, an upward component during SAN-stimulation, and a downward component during PAN-stimulation. This component is not always the predominant vector. However, in Figure
Crosstalk is an important factor. Figure
We were able to evoke a VOR under full anesthesia by replacing Propofol by Remifentanil. This is a useful finding since, at least in our clinic, both patients and ethical committees are more likely to cooperate when surgical procedures and investigations are performed under general anesthesia. Although anesthesia will influence the reactions to electrical stimuli (Poon and Irwin,
The modified ampullar approach provides safe access to the ampullae using as minimally invasive surgery as possible. For the first time in a human with long-term bilateral vestibular areflexia, it has been shown that the VOR can be evoked by ampullar stimulation, even when there has been no vestibular function for almost 20 years. This approach should be considered in vestibular surgery, since it provides safe access to one of the most favorable stimulus locations for development of a vestibular implant.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors wish to acknowledge Dr. A. E. W. Hamaekers and Dr. J. Jansen for their contributions to the anesthetic protocol, S. M. H. Jansen for his contributions to the data-analysis, and G. S. Townend for her textual criticism. Also, they wish to thank the reviewers for their valuable comments and suggestions.