Nils Guinand

Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis

The vestibular system plays a crucial role in the multisensory control of balance. When vestibular function is lost, essential tasks such as postural control, gaze stabilization, and spatial orientation are limited and the quality of life of patients is significantly impaired. Currently, there is no effective treatment for bilateral vestibular deficits. Research efforts both in animals and humans during the last decade set a solid background to the concept of using electrical stimulation to restore vestibular function. Still, the potential clinical benefit of a vestibular neuroprosthesis has to be demonstrated to pave the way for a translation into clinical trials. An important parameter for the assessment of vestibular function is the vestibulo-ocular reflex (VOR), the primary mechanism responsible for maintaining the perception of a stable visual environment while moving. Here we show that the VOR can be artificially restored in humans using motion-controlled, amplitude modulated electrical stimulation of the ampullary branches of the vestibular nerve. Three patients received a vestibular neuroprosthesis prototype, consisting of a modified cochlear implant providing vestibular electrodes. Significantly higher VOR responses were observed when the prototype was turned ON. Furthermore, VOR responses increased significantly as the intensity of the stimulation increased, reaching on average 79% of those measured in healthy volunteers in the same experimental conditions. These results constitute a fundamental milestone and allow us to envision for the first time clinically useful rehabilitation of patients with bilateral vestibular loss.

The Modified Ampullar Approach for Vestibular Implant Surgery: Feasibility and Its First Application in a Human with a Long-Term Vestibular Loss

Objective: To assess, for the first time in a human with a long-term vestibular loss, a modified approach to the ampullae and the feasibility of evoking a VOR by ampullar stimulation. Materials and methods: Peroperative stimulation of the ampullae, using the ampullar approach, was performed under full anesthesia during cochlear implantation in a 21-year-old female patient, who had experienced bilateral vestibular areflexia and sensorineural hearing loss for almost 20 years. Results: The modified ampullar approach was performed successfully with as minimally invasive surgery as possible. Ampullar stimulation evoked eye movements containing vectors congruent with the stimulated canal. As expected, the preliminary electrophysiological data were influenced by the general anesthesia, which resulted in current spread and reduced maximum amplitudes of eye movement. Nevertheless, they confirm the feasibility of ampullar stimulation. Conclusion: 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 is 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, as it provides safe access to one of the most favorable stimulus locations for development of a vestibular implant.

The vestibular implant: frequency-dependency of the electrically evoked vestibulo-ocular reflex in humans.

The vestibulo-ocular reflex (VOR) shows frequency-dependent behavior. This study investigated whether the characteristics of the electrically evoked VOR (eVOR) elicited by a vestibular implant, showed the same frequency-dependency. Twelve vestibular electrodes implanted in seven patients with bilateral vestibular hypofunction (BVH) were tested. Stimuli consisted of amplitude-modulated electrical stimulation with a sinusoidal profile at frequencies of 0.5, 1, and 2 Hz. The main characteristics of the eVOR were evaluated and compared to the “natural” VOR characteristics measured in a group of age-matched healthy volunteers who were subjected to horizontal whole body rotations with equivalent sinusoidal velocity profiles at the same frequencies. A strong and significant effect of frequency was observed in the total peak eye velocity of the eVOR. This effect was similar to that observed in the “natural” VOR. Other characteristics of the (e)VOR (angle, habituation-index, and asymmetry) showed no significant frequency-dependent effect. In conclusion, this study demonstrates that, at least at the specific (limited) frequency range tested, responses elicited by a vestibular implant closely mimic the frequency-dependency of the “normal” vestibular system.

Vestibular Implants: 8 Years of Experience with Electrical Stimulation of the Vestibular Nerve in 11 Patients with Bilateral Vestibular Loss

Background: The concept of the vestibular implant is primarily to artificially restore the vestibular function in patients with a bilateral vestibular loss (BVL) by providing the central nervous system with motion information using electrical stimulation of the vestibular nerve. Our group initiated human trials about 10 years ago. Methods: Between 2007 and 2013, 11 patients with a BVL received a vestibular implant prototype providing electrodes to stimulate the ampullary branches of the vestibular nerve. Eye movements were recorded and analyzed to assess the effects of the electrical stimulation. Perception induced by electrical stimulation was documented. Results: Smooth, controlled eye movements were obtained in all patients showing that electrical stimulation successfully activated the vestibulo-ocular pathway. However, both the electrical dynamic range and the amplitude of the eye movements were variable from patient to patient. The axis of the response was consistent with the stimulated nerve branch in 17 out of the 24 tested electrodes. Furthermore, in at least 1 case, the elicited eye movements showed characteristics similar to those of compensatory eye movements observed during natural activities such as walking. Finally, diverse percepts were reported upon electrical stimulation (i.e., rotatory sensations, sound, tickling or pressure) with intensity increasing as the stimulation current increased. Conclusions: These results demonstrate that electrical stimulation is a safe and effective means to activate the vestibular system, even in a heterogeneous patient population with very different etiologies and disease durations. Successful tuning of this information could turn this vestibular implant prototype into a successful artificial balance organ.

The vestibular implant: quo vadis?

Objective: To assess the progress of the development of the vestibular implant (VI) and its feasibility short-term. Data sources: A search was performed in Pubmed, Medline, and Embase. Key words used were “vestibular prosth*” and “VI.” The only search limit was language: English or Dutch. Additional sources were medical books, conference lectures and our personal experience with per-operative vestibular stimulation in patients selected for cochlear implantation. Study selection: All studies about the VI and related topics were included and evaluated by two reviewers. No study was excluded since every study investigated different aspects of the VI. Data extraction and synthesis: Data was extracted by the first author from selected reports, supplemented by additional information, medical books conference lectures. Since each study had its own point of interest with its own outcomes, it was not possible to compare data of different studies. Conclusion: To use a basic VI in humans seems feasible in the very near future. Investigations show that electric stimulation of the canal nerves induces a nystagmus which corresponds to the plane of the canal which is innervated by the stimulated nerve branch. The brain is able to adapt to a higher baseline stimulation, while still reacting on a dynamic component. The best response will be achieved by a combination of the optimal stimulus (stimulus profile, stimulus location, precompensation), complemented by central vestibular adaptation. The degree of response will probably vary between individuals, depending on pathology and their ability to adapt.

Bilateral Vestibular hypofunction: insights in etiologies, clinical subtypes, and Diagnostics

Objective To evaluate the different etiologies and clinical subtypes of bilateral vestibular hypofunction (BVH) and the value of diagnostic tools in the diagnostic process of BVH. Materials and methods A retrospective case review was performed on 154 patients diagnosed with BVH in a tertiary referral center, between 2013 and 2015. Inclusion criteria comprised (1) imbalance and/or oscillopsia during locomotion and (2) summated slow phase velocity of nystagmus of less than 20°/s during bithermal caloric tests. Results The definite etiology of BVH was determined in 47% of the cases and the probable etiology in 22%. In 31%, the etiology of BVH remained idiopathic. BVH resulted from more than 20 different etiologies. In the idiopathic group, the percentage of migraine was significantly higher compared to the non-idiopathic group (50 versus 11%, p < 0.001). Among all patients, 23.4% were known with autoimmune disorders in their medical history. All four clinical subtypes (recurrent vertigo with BVH, rapidly progressive BVH, slowly progressive BVH, and slowly progressive BVH with ataxia) were found in this population. Slowly progressive BVH with ataxia comprised only 4.5% of the cases. The head impulse test was abnormal in 94% of the cases. The torsion swing test was abnormal in 66%. Bilateral normal hearing to moderate hearing loss was found in 49%. Blood tests did not often contribute to the determination of the etiology of the disease. Abnormal cerebral imaging was found in 21 patients. Conclusion BVH is a heterogeneous condition with various etiologies and clinical characteristics. Migraine seems to play a significant role in idiopathic BVH and autoimmunity could be a modulating factor in the development of BVH. The distribution of etiologies of BVH probably depends on the clinical setting. In the diagnostic process of BVH, the routine use of some blood tests can be reconsidered and a low-threshold use of audiometry and cerebral imaging is advised. The torsion swing test is not the “gold standard” for diagnosing BVH due to its lack of sensitivity. Future diagnostic criteria of BVH should consist of standardized vestibular tests combined with a history that is congruent with the vestibular findings.

Taste disturbance following tonsillectomy–a prospective study†

Persistent taste disturbance is a rare complication after tonsillectomy and mainly documented by case reports or a few retrospective and prospective trials with a limited number of patients. None could clarify frequency, time course, or prognosis of long‐lasting dysgeusia after tonsillectomy. The aim of the study was to provide a symptom‐based follow‐up after tonsillectomy to assess postoperative taste disorders.

First functional rehabilitation via vestibular implants

The vestibular system is part of themultisensory balance sense, which is responsible for postural control, gaze stabilization, and spatial orientation. In particular, the vestibulo-ocular reflex (VOR) is responsible for generating compensatory eyemovements relative to headmovements while moving. In patients with a bilateral loss of vestibular function, the VOR is absent or very weak. As a consequence, such patients complain about oscillopsia, the illusory perception of movement of the visual surroundings in dynamic situations. The direct functional consequence of this is an abnormal decrease of visual acuity when in movement (Lambert et al., 2010; Guinand et al., 2012), which translates into difficulty in reading signs and recognizing faces while walking. This considerably contributes to a significant impairment of the quality of life of affected patients. Currently, there is no evidence of an effective treatment for these patients. The idea of electrically stimulating the vestibular system emerged about a decade ago and is based on a concept very similar to that of cochlear implants. Briefly, such a system would use inertial sensors (i.e. a gyroscope and/or accelerometer) to detect motion information. Such information is translated into a pattern of neural excitation code by an external signal processor. This pattern is wirelessly transmitted to an implanted stimulator which finally delivers the corresponding patterns of electrical stimulation via electrodes implanted near the vestibular structures in the neural system. The translation of the cochlear implant concept into a device suitable for stimulating the vestibular system requires two steps: (1) adaptation of the electrode topology to the neural target to be stimulated, and (2) transformation of the pertinent input signal (in this case motion) into a signal that can be processed by the audio processor of a standard cochlear implant. Today, both steps have been completed. A modified cochlear implant providing 1–3 extracochlear electrodes was developed in collaboration with MED-EL (Innsbruck, Austria). Our research group has developed the necessary interfaces to capture the signal coming from a gyroscope and use it to modulate the stimulation signals delivered by the cochlear implant stimulator (Geneva University Hospitals: Device and method for electrical stimulation of neural or muscular tissue; 2013-01-30; European Patent Application 13153300.2-1652). A number of studies have contributed to establish the feasibility of the idea of restoring semicircular canal function via electrical stimulation in animal models. At the same time, several important steps have been taken towards the development of a system allowing for the chronic stimulation of the vestibular system in human patients. For example, special extralabyrinthine (Kos et al., 2006) and intralabyrinthine (Van de Berg et al., 2012) surgical techniques have been developed and the feasibility of electrical stimulation of vestibular structures has been demonstrated both in acute (Guyot et al., 2011a) and chronic configurations (Guyot et al., 2011b). To date, seven volunteer patients with a profound bilateral vestibular loss have received a custom-modified cochlear implant in which one or three electrodes are in contact with the vestibular structures (see Table 1). In addition, since hearing loss due to the implantation of electrodes near the vestibular system remains an important concern, patients were also profoundly deaf in the implanted ear. Two patients (BVL1 and BVL2) were implanted using the intralabyrinthine approach (Van de Berg et al., 2012) in Maastricht (Ethics committee protocol NL36777.068.11/METC 11-2-031). Five patients (BVL3–BVL7) were implanted using the extralabyrinthine approach (Kos et al., 2006) in Geneva (Ethics Committee protocol NAC 11-080). Correspondence to: Marco Pelizzone, Department of Otorhinolaryngology, Head and Neck Surgery, Geneva University Hospital, Geneva, Switzerland. Email: marco.pelizzone@hcuge.ch

Taste disorders after tonsillectomy: A long-term follow-up†

In a former study, taste disturbances after tonsillectomy seemed to be more frequent than expected. Eight percent of patients reported subjective taste disorders 6 months after tonsillectomy. Fifteen patients from the initial trial, who reported taste disorders after tonsillectomy, were contacted again for this long‐term follow‐up. A telephone interview using the same questionnaire addressing the current self‐estimate of taste function was performed. At 32 ± 10 months following surgery, two (0.9%) patients still reported suffering from taste disturbance. This long‐term follow‐up study shows that dysgeusia following tonsillectomy occurs in approximately 1% of patients. These data should be considered when patients are informed about complications after tonsillectomy.

Vestibular assistance systems: promises and challenges

The handicap resulting from a bilateral vestibular deficit is often underestimated. In most cases the deficit settles gradually. Patients do not understand what is happening to them and have many difficulties to describe their symptoms. They have to consult several doctors with different medical specialties before diagnosis. Once the diagnosis is made there is no biological way to “repair” the deficient vestibular apparatus and vestibular exercises are mildly effective. Attempts have been made to help patients using substitution devices replacing the defective vestibular information by tactile or acoustic cues. Currently, efforts are being made towards the development of a vestibular implant, conceptually similar to the cochlear implant for the rehabilitation of deaf patients. In recent years, several experiments on animal models have demonstrated the feasibility of this project. This paper reports the steps accomplished in human experiments and the main results obtained in our laboratory.