Introduction

Vertigo and dizziness: very high prevalence

Vertigo and dizziness are a frequent reason for medical consultation. In France, there are 300,000 consultations per week, which is more than 15 million per year [1]. Among patients with vertigo and dizziness, the prevalence of vestibular disorders remains difficult to assess, as there is great variability between studies. The study by Bosner et al. (literature review) found a consultation prevalence for vertigo ranging from 1 to 15.5%. The etiologies identified were vestibular vertigo (5.4–42.1%), BPPV (benign paroxysmal positional vertigo) (4.3–39.5%), vestibular neuritis (0.6–24%), and Meniere’s disease (1.4–2.7%) as well as cardiovascular, neurological, and psychogenic pathologies [2]. The study by Hüsle et al. published in 2018 evaluated the epidemiology of peripheral vestibular disorders based on the demographic data of 70 million patients (during 2015) and noted a general prevalence of 6.5% for dizziness. In all ages combined, they found a prevalence of 4.8% for vertigo and dizziness of non-specific origin and 1.6% for peripheral vestibular disorders, with a 0.46% prevalence for BPPV, 0.2% for Meniere’s disease, and 0.16% for vestibular neuritis [3]. The study by Seidel el al., also published in 2018, identified 107,000 patients with vertigo managed by ENT specialists in Germany between 2012 and 2015. This corresponded with 6% of the reasons for consultation, while the most frequent cause was poorly defined. In fact, 67.7% corresponded to “vertigo and dizziness”, followed by 32.3% for "vestibular function disorders" [4]. These two recent publications confirm that there is a high prevalence of peripheral vestibular disorders that represents a major burden on our healthcare systems [5].

Vestibular disorders: a high priority medical need

Despite this high medical need, the management of patients with vertigo and dizziness still suffers from a lack of diagnostic tools to guide therapeutic management in a targeted manner from the early stages of syndrome expression. Of course, structured history taking by an experienced care provider is crucial for making the diagnosis. However, clinicians see patients with extremely diverse clinical presentations depending on the type or stage of the disease responsible for the vestibular disorders. Due to the lack of reliable diagnostic tools to accurately identify the etiology and time course of the vestibular disorder, the management of patients with vertigo and dizziness is in most instances empirical with a broad spectrum of therapeutic approaches, rather than a consensual approach based on clear verified scientific and clinical data.

Peripheral vestibular disorders originate at different levels of the onset, encoding and transmission of vestibular sensory information [6]. In the absence of precise data on the type of vestibular damage that caused vertigo, it is extremely difficult to implement appropriate targeted solutions. Similarly, the lack of information on the vestibular disorder time course is particularly detrimental to any therapeutic approach aimed at slowing the progression of the damage or at promoting neuronal regeneration for functional restoration of vestibular primary synapses [7, 8].

Since the first part of the twentieth century, when Barany demonstrated that pharmacological approaches can significantly reduce the symptoms of inner ear pathologies [9], neuropharmacology has been considered one of the potential solutions to alleviate vestibular disorders. However, this type of approach remains underdeveloped, mainly due to the lack of knowledge on the pharmacological targets available throughout the vestibular sensory network, the modulation of which may provide therapeutic benefit. Current treatments for vertigo and dizziness lack specificity and often also efficacy. In addition, in most instances, the molecular basis for their actions remains unknown. At present, in addition to corticosteroids, for which the clinical benefits for vestibular disorders are still debated [10], there is no treatment to protect or repair the inner ear.

The lack of information on the pathophysiological mechanisms that cause vestibular disorders is also because few research centers are involved in studying their etiology. Various initiatives to unite the different components of the neuro-otology community and share patient data have been launched in Europe [11,12,13]. However, a major effort to combine the resources and know-how of the personnel involved in the care of patients with vestibular disorders is still needed. Too few animal models attempting to reproduce human pathology are currently available to allow understanding of the correlation between etiology and symptomatology of vestibular disorders or to test therapeutic strategies to alleviate vertigo episodes, effectively protect the vestibule in pathological conditions, or promote functional restoration following vestibular insult.

A survey of the need for technological innovation in vestibular disorders

In the first instance, the development of knowledge for better management of patients with vertigo and dizziness requires a definition of unmet needs. Due to their proximity with the patient, the physician has a key role in recommending healthcare innovation. In this study, we conducted a survey in French-speaking ENT centers to assess the technological barriers to improving both the diagnosis and treatment of vestibular disorders. To answer this question, we used a questionnaire. The strength of the questionnaire evaluation method is that the people involved contribute a wide range of expertise or opinion in a relatively short time. One of the challenges is choosing the panel. Particular attention to the inclusion criteria, as well as participant qualifications, credibility and willingness to participate, are required so that the panel represents a range of relevant experiences. The other issue is defining the level of consensus. Studies to establish treatment protocols and medical procedures lean towards high predefined levels of agreement, generally > 80% agreement. Studies where the outcome is less critical for health, such as defining research priorities, may allow for less stringent levels of consensus [14, 15].

Our objective was to identify a consensus of clinician opinions on the priority needs for innovation in the field of vestibular disorders to improve the management of dizzy patients. The long-term effort required in this study highlighted several priority areas for development, aimed at researchers and industrialists, to improve the care of patients with vertigo and dizziness.

Materials and methods

Study design

The study design was validated with the hospital methods department. The protocol consisted of five steps.

Step 1: Problem definition

Vestibular disorders are common. A lack of diagnostic tools frequently leads to non-specific diagnoses, as evidenced by the 67.7% of “dizziness and light-headedness” diagnoses without a precise nosological diagnosis in the Seidel study [4]. There is also an obvious lack of therapeutic tools. Therefore, we considered it essential to identify the needs for innovation in this field so that they could be prioritized and then to present the different players, researchers and industrialists with the clinician’s needs. The immediate objective of this study was to reach a consensus on these needs.

Step 2: Choosing the expert panel

We selected teams from French-speaking ENT centers (mainly French but also Belgian and Swiss) where neuro-otology is practiced. They were committed clinicians with updated knowledge of vestibular pathologies. These clinicians were considered experts in vestibular disease pathology, management and exploration. They were also internationally recognized for their participation in congresses and publications in this field. Therefore, the panel chosen was appropriate to address the issue. Nineteen centers were contacted. No financial compensation was offered.

Step 3: Establishing and describing the questionnaire

The questionnaire consisted of 56 close-ended questions to which practitioners were asked to give a score of importance ranging from 0 to 10 (0: no importance, 10: maximum importance). A comment area was provided at the end of the questionnaire, which allowed clinicians to give a more precise opinion on the questions (we thought this would ensure that the proposals were more comprehensive). The questions were based on two main themes. The first theme addressed the knowledge required to ensure targeted effective management of the various vestibular pathologies (“Required knowledge” theme). The questions concerned the main vestibular pathologies: Meniere’s disease, BPPV, vestibular neuritis, vestibular migraine and otolithic disorder. For these 5 pathologies, the questions were mainly related to pathophysiological mechanisms and diagnostic and therapeutic approaches. For example, for Meniere's disease, the questions concerned "Pathophysiology and the relationship between symptoms and hydrops", "relationship with inflammation", "relationship with anxiety and stress", "relationship with hormonal variations and ischemia", "relationship with endolymph pressure variations", "identification of predictive factors of progression", "identification of predictive factors of bilateral occurrence", "development of new systemic treatments", and "development of new topical treatments". The second theme addressed the question of the technological barriers to overcome in order to improve the diagnosis and treatment of vestibular disorders ("Barriers to overcome" theme). The different proposals were classified into 4 subthemes: "View", "Record", "Measure", and "Evaluate". The subtheme "View" referred to the different modalities of viewing/imaging the vestibular organ and vestibular pathways (vestibular cells, vascularization, endo/peri-lymphatic fluids and their exchanges, the cortex, and diffusion modalities between the middle and inner ear, in particular). The subtheme "Record" referred to the modalities of collecting peripheral and central vestibular activity information (electrophysiological or imaging). The subtheme "Measure" was related to the different blood, urinary or other sampling methods (e.g., the CSF) that could reflect the functionality of the vestibular system and possible relationships with hormones, homeostasis of calcium or other components of body fluids as well as determine the levels of the different treatments administered systemically or topically in the different inner ear compartments. The subtheme "Evaluate" was a group of more general questions related to the modalities of evaluating the functionality and dysfunctions of the vestibular system, as well as the epidemiology, quality of life and medical practices.

Step 4: Distribution and collection of questionnaires

The questionnaires were sent by e-mail to all teams, accompanied by a note explaining the survey process. The practitioners then returned the questionnaires either by e-mail, mail or personal delivery. During the collection period, some practitioners were contacted by telephone to make them aware of the process if a completed questionnaire was not returned within 1 month.

Step 5: Data analysis

We opted for a purely descriptive analysis of the results and analyzed the frequency distribution of scores, medians, standard deviations, and distributions. We predefined the consensus as an agreement of at least 75% of the participants (and a score ≥ 8/10). This figure was determined based on data available in the literature that indicated a score ≥ 70% as appropriate to interpret the data [16]. The results were all expressed on a graph using box-and-whisker plots or box plots.

The additional data obtained from the comment section were qualitative and intended to assess the innovation needs in detail. We carried out a syntactic and semantic analysis and summarized the main ideas expressed by as many people as possible.

Results

Response rate

Thirteen centers replied to the questionnaire, corresponding to a participation rate of 68.4%.

Answers to the questionnaire

The results related to the theme "Required knowledge" are presented in Fig. 1. Those related to the theme "Barriers to overcome" are presented in Fig. 2. Thirteen questions were selected as having a consensus among the experts, according to the predefined criteria.

Fig. 1
figure 1

Data obtained for the “Required knowledge” questions. Each point corresponds to the score obtained, out of 10. The median is represented by the line in the box. The interquartile range box represents the central half (50%) of the data and indicates the distance between the first and third quartiles (Q1–Q3). The whiskers extend on both sides of the box and represent the lower 25% and upper 25% ranges of the given values. The questions that met the predefined criteria are in green, and the questions that did not meet the predefined criteria are in red

Full size image
Fig. 2
figure 2

Data obtained for the “Barriers to overcome” questions. Each “point” corresponds to the score obtained, out of 10. The median is represented by the line in the box. The interquartile range box represents the central half (50%) of the data and indicates the distance between the first and third quartiles (Q1–Q3). The whiskers extend on both sides of the box and represent the lower 25% and upper 25% ranges of the given values. The questions that met the predefined criteria are in green, and the questions that did not meet the predefined criteria are in red

Full size image

For the "Required knowledge" theme, 8 questions met the criteria (Fig. 1).

In the results from the analysis regarding the "Required knowledge" theme in Fig. 1, it can be noted that 8 (questions 29, 36, 37, 38, 46, 49, 53 and 56) of the 28 questions met the predefined criteria, i.e., they obtained a score of more than 8 from at least 75% of the centers surveyed and had a median score of more than 8. These eight questions are detailed below, classified under their subtheme. In the Meniere subtheme, three questions were considered to be priorities: (29) pathophysiology and the relationship between symptoms and hydrops (med = 9; Qmin = 5, Qmax = 10); (36) development of new systemic treatments (med = 9, Qmin = 5, Qmax = 10); and (37) development of new topical treatments (med = 10; Qmin = 6, Qmax = 10). Although the other questions did not meet the priority criteria, the scores for all Meniere’s disease questions were high (med ≥ 7). The Meniere theme had the highest scores of the entire questionnaire. For the BPPV subtheme, only one question was considered a priority: (38) pathophysiology (med = 9; Qmin = 0, Qmax = 10). The other questions, except for the one related to risk factors for recurrence, obtained the lowest scores of the questionnaire. This was the theme with the two lowest rated questions [(40) related to stress, (44) related to provocation material]. In the vestibular neuritis subtheme, two questions were priorities: (46) differentiating between vascular and viral affections (med = 9; Qmin = 7, Qmax = 10) and (49) receiving acute phase treatments to limit the duration and disability related to vertigo (med = 9; Qmin = 3, Qmax = 10). In the migraine subtheme, no issue was considered a priority. The distribution of scores in this theme varied significantly depending on the teams interviewed. In the otolithic disorder subtheme, two questions were considered priorities: (53) being able to better understand and measure the intricacy of the otolithic system and the vertical canal system (med = 9, Qmin = 3, Qmax = 10) and (56) using imaging or another technique to view functional modifications or alterations, if any, in the vestibular pathways from the periphery to the cortex (med = 9; Qmin = 3, Qmax = 10).

In their comments, clinicians expressed the need for innovation in Meniere's disease, which is a disabling condition. They expressed the difficulties related to management encountered by practitioners in some cases as a result of little or no specific targeted therapeutic approach. Imaging was highlighted, especially hydrops imaging. Clinicians reported a current lack of available treatment (both topical and systemic) and the lack of targeted therapy. They clearly expressed the importance of topical treatment but also mentioned the lack of knowledge regarding distribution mechanisms and mechanisms of action. As far as BPPV, the experts expressed the need to be able to confirm or rule out the theory of otoliths and mobile amalgams. For vestibular neuritis, clinicians expressed the need for additional tests to differentiate the types of pathogenic substrates underlying a particular syndrome. How can vascular and viral causes be differentiated? How can we view the effects of acute peripheral vestibular syndrome? Clinicians suggested using "inflammation" imaging methods as in neurology or imaging of cell or nerve damage as in ophthalmology. They noted the need to improve or develop imaging techniques to provide solid arguments for a vascular, viral or other cause. Clinicians also complained about the fact that there is only symptomatic treatment for this condition. For otolithic pathology (whose in which otolithic maculae are suspected to be involved), clinicians want to see the development of more reliable electrophysiological examinations to help clarify the correlation between the observed symptoms and macula/otolithic system deficits. They suggested that techniques for "peripheral vestibular" evoked potential recording should be further developed.

For the "Barriers to overcome" theme, five questions met the criteria (Fig. 2).

The results for the "Barriers to overcome" theme in Fig. 2 show that 5 (questions 7, 9, 12, 13 and 20) out of 28 questions met the predefined criteria. These five questions are classified under the subthemes and detailed below. In the visualization (“View”) subtheme, the questions selected were (7) visualization of fluid flows in the inner ear (med = 9; Qmin = 5, Qmax = 10) and (9) visualization of inflammation in the middle ear windows and the different inner ear compartments (med = 9, Qmin = 0, Qmax = 10). In the record subtheme, two questions were considered priorities: (12) recording central electrical activity during vestibular stimulation (med = 9; Qmin = 1, Q max = 10) and (13) recording macula and ampulla vestibular-evoked potentials (med = 9; Qmin = 5, Qmax = 10). In the measure subtheme, the pharmacological question was the only one that interested the majority: (20) measure of the inner concentration and half-life of a pharmacological agent (med = 9; Qmin = 3, Qmax = 10). In the evaluate subtheme, none of the questions met the criteria for priority.

In their comments, the clinicians expressed their wishes for imaging techniques allowing visualization of the endo/perilymphatic fluids under normal and altered conditions, especially upon hydrops, as well as signs of inner ear inflammation with diffusion MRI techniques. They also complained about the current unavailability of a method for vestibular-evoked potentials, equivalent to AEP (auditory evoked potentials), and the need for a "vestibulogram" at their disposal. They suggested more natural stimuli than the caloric test, such as movements and surface collections, and expressed a preference for noninvasiveness.

Discussion

Validity of the survey

The objective of our study was to identify the need for innovations regarding vestibular disorders. To our knowledge, there is no similar work in the literature to date. We selected a panel of hospital centers with expert practitioners involved in the management of the dizzy patient. It can be assumed that the needs reported by the “experts” in this questionnaire and identified as priorities reflect the current need for innovation in this specific field. The response rate to our questionnaire was 68.4%. An average response score of 60.6% was found for other evaluations by questionnaires, and our higher rate reflects the practitioners’ interest in the process [17].

The results

Several priority areas to be developed were highlighted through this analysis. The first area relates to the knowledge of the pathophysiological mechanisms that support the main encountered pathologies. This need is particularly relevant to Meniere's disease (question 29), BPPV (question 38), vestibular neuritis (question 46), and otolithic disorders (questions 53 and 56). The second area relates to the need to develop new therapeutic modalities or new routes of administration for pharmacological compounds. This need mainly relates to Meniere's disease (questions 36 and 37) and vestibular neuritis (question 49). In general, the possibility of measuring the impact of treatments administered to the tissues of the inner ear is desired (question 20). Another priority for development relates to imaging techniques. Clinicians would like to see the development of inner ear-specific imaging methods to allow clinicians to decipher the neurophysiological basis of the observed symptoms. This wish was expressed throughout the responses and in questions 7, 9, and 56. Clinicians require the development of new electrophysiological techniques allowing the identification of vestibular pathways from the vestibular organ to cortical or subcortical areas (questions 12–13). The aim is to obtain a “vestibulogram” that corresponds to a summary graph of the various vestibular explorations and test all frequencies of the five vestibular organs (saccular and utricular maculae and ampullas of the three semicircular canals) and the different peripheral and central vestibular pathways.

Understanding the pathophysiological mechanisms that cause vestibular disorders is mandatory for clinicians, as evidenced by the results obtained in this study. This understanding determines how the disorders are managed, whether with drugs, surgery, rehabilitation or a combination of all three. Let us use Meniere's disease as an example. It is well established that endolymphatic hydrops play a role, although the precise mechanism is not fully understood. The presence of hydrops does not always leads to the expression of symptoms of the disease [18, 19]. Observations in animal models in which endolymphatic hydrops have been induced have provided valuable information on the relationships between hydrops and electrophysiological changes and on how these changes influence inner ear function. The role of the endolymphatic sac in regulating the endolymph and the cascade of histopathological changes associated with chronic hydrops are currently well established. An increasing number of models are now available that allow specific examination of these inter-relationships [20]. Studying these inter-relationships further provides hope that treatments will be developed to rescue the inner ear, possibly through controlling endolymphatic hydrops, and thereby avoiding progressive and chronic alterations supporting the maintenance of symptoms.

It was also noted that clinicians were willing to question certain dogmas, as evidenced by the interest in the question on pathophysiology in BPPV. Difficulties are rarely encountered in the management of this disorder, yet the question is a high priority, which reflects the expectations of clinicians who want to see developments in pathophysiological knowledge. The theory of otoliths and BPPV is entirely based on three points: the postmortem anatomopathological observation of basophilic compounds on the cupula of a semicircular canal of the petrous bone by Schuknecht [21], the effectiveness of positioning maneuvers, and the perioperative detection of floating particles in the semicircular canals by Dr. Parnes [22].

Beyond a better understanding or identification of the underlying pathophysiological mechanisms, the priority for clinicians is to treat patients and to better understand and quantify the effect of treatments in the inner ear. Drug treatments for vertigo and dizziness have changed little in recent years, sometimes resulting in failure by the practitioner to treat some patients. The pharmacopeia for vertigo is based on treatments to reduce symptoms (anti-vertigo and antiemetic drugs) and on "causal" treatments to counteract the presumed causes of the various vestibular pathologies. Nevertheless, in Meniere's disease, in situ therapies, widely used since the 2000s [23], have changed practices and in most cases allowed improvement of patients' quality of life by reducing or even eliminating vertigo episodes. Transtympanic gentamicin enabled successful treatment of vertigo related to Meniere's disease in 84% of patients [24]. The clinical benefit of chemical labyrinthectomy is currently recognized, but uncertainties remain as to its exact mode of action. Dexamethasone, administered transtympanically, is also a therapeutic alternative for the treatment of vertigo in Meniere's disease and enables control of symptoms, with a reported success rate ranging from 47 to 91% depending on the study [25–27]. However, the mode of action of corticosteroids is still poorly understood. It is assumed that the anti-inflammatory properties of corticosteroids act on the labyrinth and that corticosteroids act by regulating the absorption of Na+ and osmotic flow in the inner ear. However, additional data are needed to better understand their mechanism and mode of action [25, 28]. These two therapeutic drug modalities clearly illustrate the need to improve the specificity and efficacy of vestibular pharmacology.

Suggested modalities

Clinicians have suggested several ways to develop pathophysiological knowledge and new therapies. Imaging is expected to be the most promising way to decipher the substrates of the different vestibular peripheral disorders, as well as a suitable tool for monitoring the effects of treatments. The recent development of MRI associated with gadolinium provides a tool to discriminate between endo- and perilymphatic spaces and, therefore, reveal endolymphatic hydrops in vivo [29]. Recent studies have focused on MRI with gadolinium injection and delayed acquisitions in the differential diagnosis of endolymphatic hydrops [30]. Access to indirect recording of macula and otolithic system activity is already possible. However, no "direct" electrophysiological examination can reliably monitor the different levels of the vestibular pathways, and the recording central activity remains difficult to perform and interpret. Nonetheless, recent years have provided real innovations in the practice of neuro-otology, such as the development of the Video Head Impulse Test (VHIT), which now enables evaluating the function of the different vestibular sensors at high-frequency stimulations. Clinicians prioritize the development of a "vestibulogram" to monitor the whole functionality of the vestibule in the same way that it is possible to obtain an audiogram and to be able to adapt the tools already in use by incorporating the concepts of portability and noninvasiveness.

Limitation of the study

A potential limitation of the survey is that only ENT experts have been included. Maybe neurologists or physical therapists with a neuro-otological expertise would have judged a bit differently. Moreover, some aspects (like cognitive, emotional consequences of disease) may have been neglected. Among the five vestibular pathologies selected in this survey, four have well-defined diagnostic criteria, while the otolithic disorder remains far less defined.

Conclusion

This study is a snapshot of the needs for innovation of medical practitioners in neuro-otology. The information collected outlines future research directions in the field of vestibular disorders. It also encourages optimization of the translational approach between fundamental research and clinical practice. Through this survey, an inventory of needs from the practitioner's point of view has been summarized. It provides a global view of the needs in terms of knowledge and expectations in terms of technological development to improve the care of the dizzy patient. This study demonstrated the interest of clinicians in this type of consultation, as evidenced by the 70% response rate to the questionnaire. The answers delineate a true interest in approaches to optimize diagnostic and treatment methods for unstable and dizzy patients. The clinicians’ main desire was for better identification of the pathophysiological mechanisms responsible for the major syndromes encountered in vestibular pathology. The clinicians’ second wish was for new therapeutic modalities. Clinicians are positioning themselves as actors in this development of knowledge and practices and suggest imaging and electrophysiology as major fields of research to better understand the structural and functional parameters of the vestibule under normal and pathological conditions.