Evolution of Vestibular Function in Patients with Sensorineural Hearing Loss and Cochlear Implant

UNIVERSITY OF MEDICINE AND PHARMACY ”GRIGORE T. POPA” IAȘI

PhD THESIS ABSTRACT

EVOLUTION OF VESTIBULAR FUNCTION IN PATIENTS WITH SENSORINEURAL HEARING LOSS AND COCHLEAR IMPLANT

SCIENTIFIC COORDINATOR Prof. Dr. COBZEANU Mihail Dan

PhD STUDENT HERA Maria Cristina

2020

TABLE OF CONTENTS

THE GENERAL PART...... 1 I INTRODUCTION. CURRENT STAGE OF KNOWLEDGE ...... 1 II ELEMENTS OF ANATOMY AND PHYSIOLOGY OF THE HUMAN AUDITORY AND VESTIBULAR SYSTEM ...... 3 II.1. Anatomy of the auditory system...... 3 II.2. Physiology of the auditory system...... 6 II.3. Anatomy of the auditory system...... 8 II.4. Physiology of the vestibular system...... 12 III THE COCHLEAR IMPLANTATION...... 17 III.1. The cochlear implant system ...... 17 III.2. Indication of cochlear implant hearing rehabilitation...... 18 III.3. Cochlear implantation techniques...... 20 IV EVOLUTION OF THE VESTIBULAR SYSTEM UNDER THE INFLUENCE OF THE COHLEAR IMPLANTATION...... 24 IV.1. Development of balance in the child and the peculiarities of the hearing-impaired child ...... 24 IV.2. The role of the cochlear implant in compensating for vestibular deficit and the risk of iatrogenic vestibular deficit ...... 26 V CURRENT METHODS OF EVALUATION AND DIAGNOSIS OF THE VESTIBULAR SYSTEM ………………………………………………………………………………………………………...... 28 V.1. Initial clinical examination: ENT clinical examination, static and dynamic balance tests, Head Impulse Test (HIT), Subjective Visual Vertical Testing (SVT)...... 28 V.2. Videonystagmography (VNG) and electronystagmography (ENG)...... 29 V.3. The caloric test...... 36 V.4. Cervical vestibular-evoked myogenic potential (cervical VEMP)...... 39 V.5. Ocular vestibular-evoked myogenic potential ( ocular VEMP)...... 41 V.6. Computerized dynamic posturography...... 41 V.7. Video Head Impuse Test (HIT) ...... 44 THE PERSONAL PART...... 46 VI REASONS FOR CHOOSING THE RESEARCH TOPIC AND THE DEFINED DIRECTIONS OF STUDY ...... 46 VII VESTIBULAR STATUS AND EVOLUTION OF THE BALANCE SYSTEM IN ADULT PATIENTS WITH COCHLEAR IMPLANTS...... 47 VII.1. Introduction...... 47 VII.2. Materials and methods...... 47 VII.3. Results...... 49 VII.4. Discussions...... 86 VII.5. Conclusions...... 97 VIII PREOPERATIVE AND POSTOPERATIVE VESTIBULARY STATUS IN CHILDREN WITH COCHLEAR IMPLANTS………………………………………………………………………………………...... 99 VIII.1. Introduction...... 99 VIII.2. Materials and methods...... 100 VIII.3. Results...... 101 VIII.4. Discussions...... 111 VIII.5. Conclusions...... 121 IX THE EFFECTS OF INSERTING ELECTRODE HOLDER BY COCHLEOSTOMY VERSUS ROUND WINDOW ON THE VESTIBULAR FUNCTION...... 123

IX.1. Introduction...... 123 IX.2. Materials and methods...... 124 IX.3. Results...... 124 IX.4. Discussions...... 131 IX.5. Conclusions...... 136 X GENERAL CONCLUSIONS...... 138 XI ELEMENTS OF ORIGINALITY OF THE THESIS...... 140 XII PERSPECTIVES OPENED UP BY THE PHD STUDY...... 141 XIII DIFFICULTIES AND LIMITS OF THE RESEARCH...... 142 REFERENCES...... 143

LIST OF ABBREVIATIONS

VOR- vestibulo-ocular reflex RS- receptor-stimulator HIT-Head Impulse test videoHIT-video Head Impulse Test HS-Head Shaking Test cVEMP- Cervical vestibular-evoked myogenic potential (cervical VEMP) oVEMP- Ocular vestibular-evoked myogenic potential (cervical VEMP) SOT- postural sensory organization test MCT- motor reaction test AVSP- angular velocity of the slow phase DP- directional prevalence LP- labyrinth prevalence

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THE PERSONAL PART

VI. REASONS FOR CHOOSING THE RESEARCH TOPIC AND THE DEFINED DIRECTIONS OF STUDY The choice of the topic for this PhD was made considering the activity and concerns related to the field of audiovestibulogy. The cochlear implant represented a “revolution” in the rehabilitative treatment of deafness, and its use with more and more extensive indications confers study subjects in various directions: clinical-functional, surgical or ethical. Research in the field of vestibulogy is more recent, but the two fields, audiology and vestibulogy, are closely linked by embryological, anatomical and functional relationships. In this respect, the researchers wanted to be able to study all five vestibular sensors present in each inner ear and to present their activity, as an audiogram shows the auditory function. The association between sensorineural hearing loss and vestibular deficit is a reality proved by various studies, as will be presented in the chapters of the paper. The possibility that the cochlear implantation intervention may cause lesions in the vestibular sensor is also described. These elements were a starting point of this study which aims to investigate the aspects of interdependence between vestibular pathology and cochlear implant intervention. The interest in developing these arguments is supported by the fact that there is not much research done on this topic. As explained during the thesis, there are still many aspects to be clarified. The difficulty of being able to centralize and evaluate the existing data lies in the inhomogeneity of the groups, the lack of a complete description of the investigation methods, the variability of the test protocols, the ambiguous nomenclature used. Therefore, an overview to expose as comprehensively as possible different elements was desired. Two samples, adults and children, were analyzed. If in the group of children cVEMP was used as the only test method, the group of adults was subjected to analysis with a complete set of tests: caloric test, Cervical vestibular-evoked myogenic potential, oVEMP, computerized dynamic posturography. Although in the adult group we did not have the results of preoperative tests, the control group consisted of patients diagnosed with bilateral cofosis (deaf or hearing impaired), also including the unoperated ears of unilaterally implanted patients. In the group of children, however, the preoperative and postoperative results reported in both ears and patients are presented as a guide. All our data are compared with the results available in the literature trying to find explanations for the observed phenomena and practical conclusions that could be applied in clinical practice. One concern of this study is related to the prevention of iatrogenic vestibular deficit during implantation intervention. It is reported that the method of inserting the electrode holder can be more or less traumatic. Surgical access is usually done by the two established methods (cochleostomy or round window). Thus, another objective was to compare the two methods in terms of postoperative vestibular deficits relative to each type of surgical approach.

VII. VESTIBULAR STATUS AND EVOLUTION OF THE BALANCE SYSTEM IN ADULT PATIENTS WITH COCHLEAR IMPLANT

VII.1 Introduction The cochlear implant is the indicated procedure for auditory rehabilitation in adults and children with sensorineural hearing loss for which traditional prosthesis is ineffective, being widely used throughout the world with optimal results. In recent years, bilateral cochlear implantation has become the standard treatment, especially in children with severe and profound bilateral congenital hearing loss. Symptoms of vestibular deficit caused by surgical maneuver have been reported in patients with cochlear implant immediately in the postoperative period or later in time. The anatomical relationship between the cochlear and vestibular spaces explains the vestibular dysfunction due to the insertion of the electrode holder. Despite the growing interest in this topic in recent years, there are still a limited number of studies on the possible vestibular consequences after cochlear implant surgery. The introduction of the electrode holder can damage the vestibular receptor cells, as demonstrated by some histopathological studies. Handzel (1) et al. shows that in 59% of the implanted temporal cliffs, the cochlea was hydropic and in most cases the sac collapsed. The mechanism could be the insertion of the electrode holder that induces a direct trauma to the cochleo-vestibular organ, as well as other phenomena: perilymphatic fistula, endolymphatic hydrops, intraoperative Gusher phenomenon, autoimmune reaction of the inner ear caused by the presence of the electrode, contamination with germs involved in local infections, vascular lesions (ischemic or hemorrhagic) or direct electrical stimulation (2). As more and more patients receive cochlear implants each year, the number of patients at risk of vestibular damage is increasing (3). So as to limit the possible structural and functional damage of the inner ear, medical research works in two directions: to create smaller and less traumatic devices and to establish the minimally invasive 1 surgical technique. The aim of our study was to evaluate the condition of the vestibular peripheral sensors in the cochlear implanted ears compared to the non-implanted hearing-impaired ears in adults.

VII.2 Materials and methods In this retrospective cohort study, we included 45 adult patients (aged 16 to 73 years, with a mean age of 43.89 years) with profound bilateral hearing loss, no personal history of meningitis, posto-traumatic hearing loss or otospongiosis and without any known vestibular pathology. The study group thus included 97 ears, 47 operated ears and 50 unoperated ears. Of these, 14 patients were implanted on both ears, 19 patients were implanted unilaterally and the rest (12 patients) were not implanted at all. The implanted patient group contains the sub-group of implanted ears 47 ears (14x2 + 19) and the group of unimplanted ears (19 ears). In order to establish a control group (unoperated ears) numerically comparable to that of the operated ears, 12 patients (24 ears) were enrolled, with bilateral deep sensorineural hearing loss, without any otological surgery in the past and without a personal history of vestibular pathology. We mention that in 7 of the operated patients (7 ears) there were results of vestibular tests performed both before implantation and after implantation, on the implanted ear. Thus, the subgroup of unoperated ears that will constitute the final control group amounts to 50 (19 + 24 + 7) unoperated ears. The statistics performed on the ears will include the 90 tested ears (47 implanted ears, 43 unimplanted ears), but also the preoperative results from the 7 implanted ears that we managed to test before surgery and which will be assimilated to unimplanted ears ( 43 + 7 = 50). Cochlear implants were performed by the same surgeon and cochlear implant systems were provided by Cochlear (CI 24R and CI 522 models), MedEl (Concerto and Synchrony models) and Oticon/ Neurelec (Digisonic SP and Digisonic SP Binaural models). The surgical approach was classic, with retroauricular incision, mastoidectomy and posterior tympanotomy. The type of insertion was chosen by the intraoperative surgeon, depending on the local anatomy for the best placement of the electrode: through the round window in seven cases (in some cases it was necessary to remove part of the bone "frame" of the round window for a better view) or by cochleostomy (25 cases). For each implanted ear, a temporal bone X-ray (modified Stenvers projection) was performed to verify the correct positioning of the intracochlear electrodes and the postoperative position of the receptor-stimulator. The time between cochlear implant surgery and vestibular examinations ranged from 3 to 22 months. The status of peripheral vestibular sensors was assessed in each patient using the same examination protocol, including the following tests: clinical examination of the ear, tympanometry, bi-thermal caloric test, cervical vestibular-evoked myogenic potential (cVEMP) and ocular vestibular-evoked myogenic potential (oVEMP), computerized dynamic posturography.

VII.3 Results The data were collected using Microsoft Excel. They were subsequently exported to the SPSS 24.0 program for statistical processing. Initially, the statistical analysis was performed on the entire group of 45 patients. Thus, the descriptive analysis of the group, Romberg, Unterberger tests, position manoeuvres, Head Shaking and Head Impulse test and computerized posturography results were reported to the patient, so to the total group of 45 units (12 unoperated, 19 with unilateral cochlear implants and 14 bilateral cochlear implants). Subsequently, calculations were performed on the group of 97 ears studied (operated and unoperated) to report the vestibular deficits highlighted. The group of ears with pre- and post-operative evaluations was also analyzed separately. The analyzed group consisting of 45 patients was made up of 25 women (55.6%) and 20 men (44.4%). Of the 45 patients, 10 come from rural areas (22.2%) and 35 from urban areas (77.8%). The following analyzes relate to patients, generally at the level of the whole group and comparatively between the three subgroups. The Romberg test result was normal in 41 of the cases (91.1%) and pathological in 4 cases (8.9%), representing unsystematic deviations. The results of the Unterberger test reveal a proportion of 80% (36 patients) normal results and 20% (9 patients) pathological results. The Roll test for the right ear presented the following results: 42 patients (93.3%) presented physiological results, and 3 patients (6.7%) presented nystagmus. The Roll test for the left ear is also presented with a clear 2 majority of normal results (42 patients) 93.3%, just like the Test roll on the right. The Dix Hallpicke test on the right shows, like the other tests, normal results in a majority of 91.1% (41 patients), while only 8.9% (4 patients) show a pathological nystagmus in this diagnostic maneuver. The Dix Hallpike maneuver for the left ear is in line with the other diagnostic tests with 42 normal results (93.3%) and 3 (6.7%) pathological results. Head Shaking reveals 3 cases of nystagmic response (6.7%), the rest of the patients (93.3%) presenting physiological responses, and pathological cases are located exclusively in the groups of operated patients. The Diagnostic maneuver Head Impulse Test presents, unlike all other diagnostic tests, a higher percentage of pathological responses (28.9%), representing 13 patients out of a total of 45. Cochlear implantation devices were provided by the manufacturers Cohlear, Medel, Oticon. The following statistics will take into account the 90 ears (operated ears tested only postoperatively and unoperated ears), but also the preoperative results from the 7 operated ears that we managed to test before surgery.

Figure 7.27 Study of the three vestibular sensors according to the operator status

The analysis of the vestibular status by sensors according to the operator status facilitates the following observations: -the function of the lateral canal was preserved in 70.2% of the implanted cases versus 74% of the unoperated cases; hyporeflexia is better represented in the case of implanted ears 21.3% versus 12% in non-implanted cases; areflexia represents 8.5% of implanted cases compared to 14% in non-implanted cases. -the saccular function was preserved in 51.1% of implanted cases versus 54% of unoperated cases; hyporeflexia is represented in the case of implanted ears in a proportion of 8.5% versus 10% in non-implanted cases; areflexia represents 40.4% of implanted cases compared to 36% in non-implanted cases. - the utricular function was preserved in 42.6% of implanted cases versus 48% of unoperated cases; hyporeflexia is represented in the case of implanted ears in a proportion of 2.1% versus 2% in non-implanted cases; areflexia represents 55.3% of implanted cases compared to 50% in non-implanted cases. The tests performed in this study aim to evaluate three (lateral canal, sac and utricle) of the five sensors present in the inner ear. Thus, the vestibular involvement was studied according to the number of dysfunctional sensors (one/ two/ three) reporting the data to the operative status (implanted ear/ unimplanted ear). It was observed that the percentage of ears without any vestibular deficit is higher in unimplanted ears (42%) than in implanted ears (34%). The lesion of only one of the three sensors is represented without major differences: in unimplanted ears 3

12%, and in implanted ears 14%. Impairment of two sensors is also more present in operated ears (31.9%) than in unimplanted ears (26%). The percentage of dysfunction of all three sensors tested is equally represented in the two subgroups: 19.1% for implanted ears and 20% for non-implanted ears.

Figure 7.29 Study of vestibular impairment according to the operator status

Looking at the same aspect of vestibular damage in general and referring to the two categories of ears (implanted/ unimplanted) we notice that the vestibular deficit is present in the group of implanted ears in a higher proportion 66% compared to 58% in unoperated ears. The combined study between the results of the Head Shaking test (0-normal, 1-pathological) and the functional impairment of the lateral canal depending on the operator status does not show statistically significant correlations. Unlike the Head Shaking test, the same combined analysis of the Head Impulse Test results (0-normal/ 1- positive right/ 2 positive left/ 3-positive bilateral) depending on the canal vestibular impairment and operator status shows a correlation statistics between these data. The results obtained when performing computerized posturography in all patients denote the lack of acute vestibular deficits or their compensation in the examined patients. We will analyze the 7 patients (14 ears) for whom vestibular test data are available both pre-operatively and postoperatively

Figure 7.49 Variation of the vestibular receptor status

The analysis of the function variation of all the three vestibular sensors in the 14 ears after the implantation 4 intervention highlights the following: -for the lateral canal the percentage of areflexia (28.6%) remains constant after implantation, there being no variation even for the proportion of ears with normal function (71.4%) -saccule and utricle present at the preoperative moment 57.1% cases of normal function, and 42.9% are areflexia. After implantation, only 14.3% of cases preserve the saccular function, 14.3% are hyporeflexia, and 71.4% of cases are areflexia.

Figure 7.50 Global impairment variation (at least one sensor affected) (0- all functional sensors, 1- impairing one sensor, 2- impairing two sensors, 3- impairing 3 sensors)

Considering the group of 14 ears, we defined vestibular damage as impairing one sensor, two sensors or three sensors on each ear and we studied its variation depending on the surgery. This is how it is observed: -normal function is present before surgery in 42.9% of the ears, and after implantation in only 14.3%. -impairment of a single sensor exists only before implantation in 14.3% of the sensors - impairment of two sensors is present in 26.8% of cases in the preoperative period and in 57.1% of cases in the postoperative period. - impairment of three sensors is present in 14.3% of patients at the preoperative time and in 28.6% of cases after implantation

I.1. Discussions The study we proposed on the influence of cochlear implantation on the sensors of the vestibular system involved a series of features on data collection, reflected in the selection and special organization of the patient group and subgroups of analysis. This specific of the research is detailed in the following comments and discussions. The descriptive statistical analysis shows a homogeneous group in terms of the distribution of patients by gender, which benefits the study, because no significant differences related to gender can be discussed. In any case, the stability of the vestibular functions of the inner ear in the cochlear implantation process has not been the subject of special debates in any specialized publication. As in many other situations of analysis of the addressability and access of patients to modern means of diagnosis and treatment, it is confirmed in our study that most patients treated by cochlear implantation come from urban areas, a phenomenon explained by differences in culture and information between the two categories of population and through socio-economic barriers. The combined analysis of the environment of origin by gender confirms that the group is balanced from this point of view as well. The lower average age of the rural subgroup may indicate a higher level of information and interest in therapy among the young rural population than in the middle-aged population. The data on the analysis of the average age according to the environment of origin are statistically significant (p = .036). We analyzed the vestibular sensory status through objective diagnostic tests that have been developed in recent years for the evaluation of the vestibular system in modern medicine: caloric test for semicircular horizontal canal, cVEMP for the saccular function and oVEMP for the utricular function. All mentioned sensors were evaluated for all patients in the study groups, implanted, non-implanted and cochlear ears. The analysis of all 97 ears in the study led to the following conclusions. The canal function is better preserved in the non-implanted ears (74%), compared to the operated ones (70%) in which the iatrogenic damage also occurs. Hyporeflexia is present in a higher percentage in implanted ears 5 probably as an effect of surgery, and areflexia is more present in the case of unimplanted ears as evidence of vestibular deficit associated with hearing loss. The canal receptor, as shown in our study, is the least affected by surgery. The saccular function presents a more accentuated deterioration compared to the canal function, both at the preoperative moment (46%) but also at the postoperative moment (48.9%), the areflexia becoming more numerous after the surgery. This is in agreement with various publications that support the risk of injury to the saccular sensor, which is the closest anatomically to the cochlea. The utricular function, according to our study, is the most affected, with post-implant flexion exceeding 50% (55%). Cases of hyporeflexia are numerically negligible in both categories of ears (implanted/ unimplanted), the lesion being expressed predominantly by areflexia. The vestibular system of the ear can be impaired by altering the functioning of one of the sensors, two of them or completely, by impairing all three sensors. Both the situations of impairing one sensor and impairing two sensors are more numerous in the subgroup of implanted ears (14.9% and 31.9%, respectively) than those not implanted (12%, respectively 26%), which is intuitive considering the vestibular injury risk that surgery poses. We emphasize that all categories of impairment are, however, also present in the group of unoperated ears, in considerable proportions, the differences from the group of operated ears not being statistically significant. This confirms the data in the literature that support the vestibular damage associated with hearing loss. The percentage of vestibular damage of all three sensors is similar in the case of the two categories of unimplanted / implanted ears (20% versus 19.1%). We approached an analysis of associative sensory vestibular impairment, evaluating the percentage of ear impairment based on impairment to a vestibular sensor, the association of impairment to two sensors or the association of impairment to all three sensors we studied. We compared the measurement results on the non- implanted ears with those of the implanted ears at the same time. On unimplanted ears we have 12% unisensory impairment compared to 14.9% on implanted ears, there is a difference of 2.9% that can be attributed to cochlear implantation. At the same time, the damage to two sensors is found in non-implanted ears at 26%, while on implanted ears it increases to 31.9%, a difference of 5.9% potentially determined by cochlear implantation. Regarding the association of three sensors affected simultaneously, the situation of implanted ears is similar to non- implanted ears, with only a difference of 1% (20% multisensory deficit for implanted ears versus 19.1% in non- implanted ears). The paradoxical difference of 0.9% in the advantage of implanted ears can be due either to a transient vestibular deficit in the group of non-implanted ears, or to an effect resulting from the statistical analysis, being an extremely small variation. In any case, it is obvious that vestibular impairment is more present in the group of implanted ears than in that of non-implanted ears (66% versus 58%). Although the results are not statistically significant, we can say that the difference in our study supports the hypothesis of the potential for significant damage to the vestibular sensor following cochlear implantation. The subgroup of 7 patients for whom there are both preoperative and postoperative data in both ears (14) was analyzed as a stand-alone group. Next we analyze the data obtained on this subgroup. The lateral canal is unaffected by CI intervention, all operated ears retaining the function of the lateral canal at the preoperative status, while the saccule and utricle are considerably impaired. Thus, we considered that the analysis of the concomitant impairment of more than one vestibular sensor, which brings a special degree of functional impairment, is necessary to adequately illustrate our study. We compared this global postoperative deficit with the global preoperative situation. It turned out that postoperatively we have no case in which only one sensor was affected. Impairment of two of the ear sensors increases from 28.6% in the pre- implantation phase to 57.1% after implantation. The cases of ears with impairment of all three sensors increase from 14.3% before implantation to 28.6% after implantation. Cases of normal function (all three sensors integrated) decrease, consequently, from 42.9% before implantation to 14.3% after implantation. Analyzing the available data from the literature, we identified several studies that analyze vestibular symptoms after cochlear implant intervention. The variability of these results can be explained by several considerations. One of these is the time of examination. It is known that there may be manifestations in the immediate postoperative period, but which are temporary, not constituting a permanent vestibular deficit. Another factor is the patient’s age of the, the most elderly may be likely to have such manifestations in the absence of the cochlear implant. Also, the mode of analysis (questionnaires/ anamnesis) is different from one study to another. It should be borne in mind that a patient with a cochlear implant may suffer, like any other patient, from a vestibular pathology independent of the cochlear implant, or caused by the unimplanted ear. A detailed anamnesis to eliminate such pathologies is essential for a correct interpretation of the results. In our study, two patients reported persistent chronic instability. The association of sensorineural hearing loss with vestibular pathology in patients candidates for cochlear implantation, allowed the quantitative assessment of this type of combined deficit of inner ear functions and also the 6 evaluation of vestibular receptors before implantation, results that different authors have published in articles which I analyzed. From the documentation phase, we noticed that studies on this topic are relatively rare in recent years, which supports, moreover, the need for this research. Vestibular deficit in objectively measured cochlear implant patients is reported differently by the authors. In our study of unimplanted ears, the canal deficit was highlighted in 26% of the ears (including 12% hyporeflexia and 14% areflexia), the result being similar to that of the study of Kluenter et al (3). Saccular vestibular deficit in unimplanted ears was observed in our study in 46% of patients (hyporeflexia 10% and areflexia 36%), a result similar to that of Krause et al (4). There are no comparative data with Kluenter's study, which studies only the canal function. The advantage of our study is that it is superior to all the others both in terms of the number of patients in the group and the number of ears studied (45 patients and 97 ears). In the case of our study, for the group of unoperated ears, we identified 48% of ears with normal function, the remaining 52% having utricular damage, mostly areflexia (50%), only 2% being with hyporeflexia. In the group of 7 ears that were evaluated before and after cochlear implantation, preoperative tests identified a canal dysfunction associated with deafness in 28.6% of cases, and saccular and utricular dysfunction were present in 42.9% of cases, percentage results similar to those of the total group. Postoperatively, our results on the whole group showed a canal deficit in 29.8% of cases, a result similar to that in the article by Huygen et al. (5), but also those in the study of Enticott (6) et al. The saccular function deteriorated in 48.9% of cases, a result that falls within the average review published by Abouzayd (7), but which has no term of comparison in other of the few studies identified by us. Even in the review published by Abouzayd (7) the authors refer to only 16 studies identified as eligible. Regarding the utricular function, we observed its impairment in 57.4% of cases in our group, as mentioned above, having no term of comparison because we did not identify other studies in adults on utricular lesions acquired after cochlear implantation. However, we can compare this result with that of the study on children conducted by Li et al. (8), in which 64% of utricular deficits highlighted at a distance of 2 months and 65,4% at a distance of one month with the processor off are reported. On the subgroup of the 7 ears analyzed pre and postoperatively, we notice that the function of the lateral semicircular canal was not influenced by surgery, being obvious that the percentage of 28.6% cases with canal damage existing at the preoperative time is maintained in postoperative research

VIII. PREOPERATIVE AND POSTOPERATIVE VESTIBULARY STATUS IN CHILDREN WITH COCHLEAR IMPLANTS

VIII.1 Introduction The cochlear implant is the "gold standard" treatment for severe and profound hearing loss that cannot be properly rehabilitated with conventional prostheses. As a result of the optimal results obtained over time in cochlear implant patients, the indication for this type of treatment has gradually expanded. Hearing rehabilitation by cochlear implant is the only solution for children with congenital or progressive sensorineural hearing loss, bilateral implantation becoming a standard procedure in these cases. One of the complications of this intervention is the vestibular lesion which can be transient or permanent. Clinical manifestations can be acute or progressive. In the literature, the percentage of vestibular impairment due to electrode insertion is very variable (9), (10), (5). The mechanism could be represented by direct trauma but also by other pathological changes such as: perilymphatic fistula, endolymphatic hydrops, intraoperative gusher phenomenon, autoimmune reactions caused by the presence of the electrode in the inner ear, contamination with germs present in local infections, vascular lesions hemorrhagic) or direct electrical stimulation. Banakis Hartl et al. (11) analyzes the pressure caused at the labyrinthine level by the insertion of the electrode holder in a study performed on five anatomo-pathological preparations (10 temporal cliffs). Fiber optic sensors were placed at the level of labyrinthine structures (vestibular scale, tympanic scale, lateral semicircular canal) then implantation was performed using the round window approach and having at its disposal eight different types of electrode holders. The conclusion resulting from this experiment is that at the level of the labyrinthine space, high pressures are created equivalent to the energy of high frequency sounds that can cause sensory damage. The exact mechanisms are only hypothetically formulated (contact of the electrode holder with the crista fenestra, round window size, translocation of the electrode from the tympanic scale to the vestibular scale). Some children may have vestibular deficiency associated with sensorineural hearing loss as a complex pathology of the inner ear. The prevalence of vestibular deficit in children with sensorineural hearing loss is reported to vary between 20 and 85% (12) (13) (14) (15) (16) (17). In non-syndromic genetic sensorineural hearing loss, vestibular lesions are associated differently with various types of mutations. Syndromic sensorineural hearing loss is often accompanied by unilateral or bilateral, partial or complete vestibular damage. The most common syndromes with audio-vestibular manifestation are: Usher, Jervell, Lange Nielsen, CHARGE, Waardenburg, Pendred, Goldenhar, Di George (18). Isolated malformations of the inner ear such as the absence of the cochlear partition (Mondini syndrome), the single vestibular cavity (Michael syndrome), the enlarged vestibular aqueduct, involve cochleo-vestibular deficits. Cytomegalovirus infection is a risk factor for both deafness and vestibular deficiency. Ototoxic substances such as gentamicin cause sensorineural hearing loss, but also bilateral vestibulopathy. The need to practice bilateral cochlear implantation requires knowledge of preoperative vestibular status in order to minimize the risk of injury to balance receptors, as bilateral vestibulopathy is a major impediment to overall development. The vestibular deficit manifested in childhood, especially the bilateral one, leads to chronic instability that can affect the motor and cognitive acquisitions of the child. The impact is all the more severe as the onset of the pathology is earlier, before the age of one, because the child has not yet learned to walk and maintain his orthostatic position (19), (20). In these cases, axial hypotonia or problems of spatial representation may occur. Cognitive deficit is generated by errors in creating one's own image by relating to the environment (21), (22). Children may present in these cases dyspraxia, dyslexia, dysgraphia (16), (23). Given the negative effect of bilateral vestibular deficit on overall balance and development, hearing rehabilitation through CI should avoid, if possible, vestibular lesions. To achieve this goal, vestibular status must be tested and known before CI surgery. The most appropriate method for assessing vestibular status in children is, in our experience, cVEMP. It can be performed from the age of 2 months and is an objective, fast, non-invasive test. The recording depends on the contraction of the sternocleidomastoid muscle. Factors that may disrupt the test refer to the child's lack of cooperation or various neuromuscular pathologies that make it impossible to maintain muscle contraction.

VIII.2 Materials and methods 80 children were included in this prospective study. The group was homogeneous in terms of gender distribution: 41 boys and 39 girls. 58 (72.5%) come from urban areas and 22 (27.5%) from rural areas. The mean age upon implantation was 4.35 years. The children received cochlear implant for deep or severe hearing loss. 31.3% were implanted unilaterally, 68.8% were implanted bilaterally. The surgery was performed by the same surgeon for all cases. Cochlear devices were supplied by the brands 8

Cochlear (CI 24RE, CI 512 and CI 522), MedEl (Concerto, Pulsar, C40 and Synchrony) and Oticon/ Neurelec (Digisonic SP and Neuro ZTI CLA). The surgical approach followed the classic stages: small retroauricular incision, mastoidectomy and posterior tympanotomy. The surgeon's choice for inserting the electrode by cochleostomy or round window depends on the local anatomy. After surgery, a temporal X-ray (modified Stenvers view) was performed to verify the correct position of the stimulator-receptor and intracochlear electrodes. The preoperative test protocol (T0) included vestibular assessment of saccular function by cervical evoked myogenic potential (cVEMP). To avoid the influence of the vestibular test by external and / or middle pathology of the ear, we performed a preliminary clinical examination of the ear by otomicroscopy and impedance. cVEMP was repeated postoperatively for each implanted ear to assess the preservation of saccular otolith function. The test was scheduled at least 3 months after surgery (T1) to avoid possible transient deficiencies. For cVEMPs recordings, the child was placed in a sitting position, in the parent's arms, with the head turned to the opposite side of the tested ear, following a target of interest. To date, there is no consensus on the normative parameters necessary for the interpretation of cVEMP in children. On the other hand, VEMP registration in young children may pose particular difficulties, such as insufficient or inconsistent contraction of the SCM or non-compliance. For these reasons, we decided to report only the presence or absence of the P1-N1 complex without an assessment of its amplitude variation.

VIII.3 Results The results were archived using Microsoft Excel. Statistical processing was performed using SPSS 24.0. Statistical tests adapted to each group and subgroup of patients were applied. The results of the statistical analysis on the vestibular function of children with cochlear implants are presented below, starting with descriptive demographic statistics. The sample of 80 children included 41 boys (51.3%) and 39 girls (48.8%), statistically validated in terms of gender distribution. Of these, 55 (68.8%) received unilateral cochlear implant, and 25 (31.3%) bilateral cochlear implant (simultaneously or sequentially). The combined study of the frequency of the implant type (unilateral / bilateral) according to sex showed: of the 25 cases of unilateral cochlear implantation, 13 (52%) were female patients and 12 (48%) were patients of male sex; of the 55 cases of bilateral cochlear implantation, 26 (47.3%) were female patients and 29 (52.7%) were male patients. The distribution by origin shows that 58 (72.5%) cases come from urban areas and 22 (27.5%) cases come from rural areas. Different models of cochlear implant were used, belonging to the brands Oticon (35.6%), Medel (28.8%), Cohlear (35.6%).

Figure 8.12 Status of pre (T0) and postoperative (T1) saccular function in all implanted ears (n=135)

We analyzed the preoperative saccular function in the 135 ears, defined as T0 moment. In 75.6% of cases we obtained the present cVEMP response, while in 24.4%, the response was absent. After cochlear implantation, moment defined T1, we retested the saccular function to capture the variations of the saccular status. In 53.3% of cases we obtained present saccular potentials, and in 46.7% of cases the answer was absent. 9

Figure 8.13 Status of pre (T0) and postoperative (T1) saccular function in ears with cVEMP response present at T0 (n = 102)

In order to highlight the variation of the vestibular function, related to the cochlear surgery, we considered only the ears that presented at the moment T0 present response to cVEMP. Of the 102 ears with cVEMP saccular potential present, 70.6% retained their function after implantation, while 29.4% lost this function.

Figure 8.14 Status of the postoperative saccular function (T1) in the group with sequential bilateral CI compared to the group with simultaneous bilateral CI in children with at least one preserved saccular function at T0

Considering that bilateral vestibulopathy induces an unfavorable prognosis for the cognitive and neuro-motor development of the child, we analyzed the group of children implanted bilaterally cochlear to highlight how many have a loss of bilateral saccular function after surgery. We defined two subgroups: the group of children with sequential bilateral CI and the group of children with simultaneous bilateral CI. The children considered for this study had at least one ear with normal saccular function. This analysis highlights the evolution of patients after surgery (the other graphs presented above show statistics on the ears / sensor). In the first group (children with sequential CI), 8 patients (25%) showed a bilateral saccular vestibulopathy after surgery, they had bilateral normal saccular function before the intervention. In the second group (children with simultaneous CI), 2 patients (18.18%) also have no postoperative bilateral cVEMP response, they have only one ear with saccular function present before the intervention, a function they lose after implantation.

Unilateral vestibulopathies (patients with bilateral saccular function present preoperatively who record the loss of a sensor after implantation) are recorded in 18.75% of patients in the group with sequential CI.

Some patients retain their saccular status, they have preoperative unilateral saccular deficit and remain at this stage and after implantation (6.25% of the group with sequential CI and 18.18% of the group with simultaneous CI) There are also patients with bilateral saccular function present before the intervention and preserved after implantation (50% in the group with sequential CI and 63.64% in the group with simultaneous CI).

Figure 8.15 Preoperative saccular status (cVEMP) (T0) depending on the laterality of the surgery and the type of implantation (n = 135)

The preoperative saccular vestibular status, highlighted by the presence of cervical myogenic potentials of vestibular origin was analyzed taking into account several variables. Thus, in the 70 right ears the cVEMP response is present in 54 cases (77.1%) and absent in 16 cases (22.9%). Of the 65 implanted left ears, 48 (73.8%) have normal saccular function, and 17 (26.2%) have compromised saccular function. Considering the types of cochlear implantation, we noticed that out of the 79 cases of sequential bilateral CI, 63 (79.7%) have the present saccular function, and 16 (20.3%) have lost this function. Simultaneous bilateral CI (32) has preserved saccular function in 20 cases (62.5%) and absent in 12 cases (37.5%). In the case of unilateral CI (24), in 19 (79.2%) cases the cVEMP reflex is present, and in 5 (20.8%) the saccular reflex is absent.

Figure 8.16 Postoperative saccular status (cVEMP) depending on the laterality of the surgery and the type of implantation (n=135)

The postoperative saccular vestibular status was analyzed taking into account the same variables.

In the 70 right ears, the cVEMP response is present in 37 cases (52.9%) and absent in 33 cases (47.1%). Of the 65 implanted left ears, 35 (53.8%) have normal saccular function, and 30 (46.2%) have compromised saccular function. Considering the types of cochlear implantation, we observed that out of the 79 cases of sequential bilateral CI, 41 (51.9%) have the saccular function present, and 38 (48.1%) have lost this function. Simultaneous bilateral CI (32) appears with preserved saccular function in 16 cases (50%) and absent in 16 cases (50%). In the case of unilateral CI (24), 15 (62.5%) have present cVEMP reflex, and 9 (37.5%) have absent saccular reflex The variation of the vestibular function from the preoperative moment (T0) to the postoperative moment (T1), within the group of ears that had a saccular response to T0 (102 ears), was evaluated according to various factors. Comparatively, in the group of right ears 68, 5% maintain the functionality of the saccular sensor, and 31.5% lose it, compared to the group of left ears in which 72.9% retain the saccular function, and 27.1% lose it. If we perform the same type of assessment regarding the variation of the vestibular status at the level of the three implanted groups (unilateral/ bilateral simultaneously/ bilateral sequentially), we notice that the vestibular function is maintained in a higher proportion in children implanted simultaneously (80%) and in those implanted unilaterally (78.9%) compared to the group with sequential bilateral implant where the conservation percentage of the saccular sensor is 65.1%.

VIII.4 Discussions From the point of view of the results provided by the descriptive statistics of the group, the following observations can be made. The sample is homogeneous, as a distribution of the sexes. The majority percentage of bilaterally implanted patients in our group are in line with the latest international trends that support hearing rehabilitation of both ears due to scientific evidence on the benefits of hearing and speech comprehension in a noisy environment, but also for sound localization skills. The analysis of the environment of origin shows that most patients with cochlear implant come from urban areas. This fact can be explained taking into account the degree of culture and information of the population in the two environments, the gaps in the coverage of auditory screening in newborns, the existing socio-economic barriers, all these elements ultimately influencing the addressability to diagnostic and treatment medical services, more favorable to urban patients. In our study, the cochlear implant systems came from three manufacturing brands, and their use has a homogeneous distribution in our sample. Among the models used, it is observed that MedEl Synchrony, Digisonic SP have a majority frequency, while the three present Cohlear models have a comparable frequency distribution. The predominant use of a CI model can be explained by the fact that this model is the most advanced technological option for a period of time and therefore accessing it for patients is the best alternative. Depending on the frequency and times when brands launch new and more technologically advanced models on the market, the statistics performed indicate the dynamics of these changes and the access of patients in our group to this technological progress. From the point of view of the study of vestibular function in children, cVEMP is an adequate, fast, non- invasive test. Since there are no protocols for interpretation (24), (25), (26), (27), we analyzed only the presence or absence of the P1N1 complex. Vestibular testing of children is limited due to the difficulties of testing, but also the lack of maturity of vestibular reflexes at an early age. It was chosen as a cVEMP test method due to the fact that it is a fast, non-invasive test, possible to perform from about 2 months. Regarding the parameters of normality, as there are no official rules yet, clinicians refer to the publications of experts in the field. For example, a 2018 publication (Noij K) aimed to validate the reporting of cVEMP functional records of patients to an ideal model of normality, consisting of a matrix of the P1N1 complex obtained by mediating and processing records made in healthy subjects from vestibular point of view (28). In 2014 Papathanasiou et al. (29) published a paper that develops rules for the registration and interpretation of cVEMP. The parameters suggested by Papathanasiou et al. (29) for performing cVEMP with bone stimulus, also reported in the literature are: frequency of 100-500 Hz, impulsive stimuli (skull tap or minishakers), stimulation intensity of 150 dB FL (force level- conversion unit to define the amount of energy supplied). The saccule is the vestibular structure closest to the cochlea and has a major risk of injury, as shown in pathological studies (1). The association between sensorineural hearing loss and vestibular deficit may suggest a complex pathology of the inner ear. The documentation of this associated pathology has a long history (30), (31), one of the first researches in the field stating that vestibular pathology can be present / associated in children with sensorineural hearing loss 12 with a frequency of 20% -70% (31) (32). In our study, this association (between bilateral sensorineural hearing loss and saccular areflexia) was highlighted in 24.4% of cases. The variability of the percentages presented by the literature can be due to several considerations. In some studies, both areflexia (total deficits) and partial vestibular deficits (hyporeflexia) are considered, compared to our study that considered only saccular areflexia. Also, as testing all receptors (semicircular canals, utricle, sac), can lead to a higher percentage of vestibular damage, the present study analyzes only the saccular function. Therefore, the association rate of severe / profound sensorineural hearing loss with saccular areflexia highlighted by this study is 24.4%. Various studies on this topic confirm the above-mentioned association, but show results with great variability, between 20 and 85% (33) (34), (35). If saccular areflexia was diagnosed at the preoperative time (T0) in 24.4% of the tested ears (n = 135), and at the postoperative time (T1) in 46.67% of cases, we can conclude that the difference indirectly indicates the percentage of patients who have lost their vestibular function following surgery. In order to measure the real variation determined by the surgical act on the saccular function, the same type of analysis was performed, but considering only the ears that had a saccular reflex at the time noted T0 (preoperative). We noticed that 70.6% retain this function, while 29.4% of the ears lose it. This percentage represents the cases of deterioration of the vestibular sensory neuro-epithelia as a result of surgical maneuvers, especially the introduction of the electrode holder and indicates the increased risk of such lesions in patients that were candidates for cochlear implantation. Such a report of actual variation is presented in a study on adults published by Todt et al. which shows 19% canalicular lesions and 21% postoperative saccular lesions (patients who had resulted in preoperative vestibular tests and who changed their vestibular status after the intervention). The literature presents a risk of vestibular injury due to surgery that is between 50% and 85% (36). A recent publication (review) confirms that the variability of vestibular dysfunction in implanted children is high, between 18% and 85% (12). A review analyzing the topic of vestibular deficit in children with cochlear implant (Verbeque et al.) presents on a sample of 828 patients the preoperative saccular dysfunction in proportion of 0-53%, and postoperatively in proportion of 17-84% (12). It is noticed that the percentage of association of the saccular dysfunction with the sensorineural hearing loss shows a great variability. There are studies (37) that do not find preoperative saccular vestibular dysfunction (Christy, 2014), but also the opposite case in which preoperative dysfunction is present in all studied cases (Singh, 2012), (15). Regardless of these extreme cases, the variation of the association of the vestibular deficit with deafness is observed between 28.58% and 91.3. We mention that most studies report data to patients, but there is also a study (38) that presents the results referring to the number of ears (Zagolski). This paper tries to treat both ways of exposure, in order to have a complete vision of the phenomenon. If we consider the studies with most patients (39), (40), we notice that the preoperative vestibular dysfunction has a frequency of 41.44% (Tibukait, Xu). The percentage of 24.4% of preoperative saccular dysfunction that we highlighted through our study actually included only areflexia, as previously presented. The saccular areflexia deduced from the data presented by the review are between 0% and 66.66%. Our percentage is similar to that obtained by Cushing et al. from 2009 (13), respectively 28.58%. Data expressing postoperative vestibular involvement are similar to those representing saccular areflexia, ranging from 0% to 84.37% of cases. Our result, 46.7% is similar to that reported by Cusing et al., from 2008 (34), respectively 40%. The study performed on the largest cohort (Inoue et al. Since 2013) (16), respectively 62 patients (out of 89 enrolled), highlights only saccular hyporeflexia. Post-implantation bilateral sensory impairment, which should be avoided because it affects the overall development of the child, is mentioned by two authors: Cushing (2008) (34) with 20% of cases and Shall (2009) (41) with 62.5% of cases. Our study highlights 25% of bilateral saccular areflexia in the group of children with sequential CI and 18.18% in the group with simultaneous CI. We mention that these results were performed on the sample of children who had a saccular response to T0. Reporting one's own results to the existing ones is important in order to validate one's own examination methodology, but also to be able to improve the protocols used. Cases of bilateral vestibulopathy were identified in this study in the group of children bilaterally sequentially implanted. In the group of children implanted bilaterally simultaneously, there were no cases of bilateral areflexia due to surgery, but there were cases of bilateral areflexia due to the association between a post-surgical lesion on one ear and a pre-existing lesion at the time of implantation on the contralateral ear. Analyzing the saccular status at the level of the group of children depending on the sequential or simultaneous cochlear implantation strategy we note that: in more than half of our patients the saccular function was preserved in both ears (63.64% of cases for the group with simultaneous bilateral CI and 50% for the group with sequential CI); preservation of the only saccular function occurred in the group with sequential bilateral CI in 6.25% of cases, and 13 in the group with simultaneous CI in 18.18% of cases. 18.18% lost their only saccular function after simultaneous cochlear implantation, thus becoming patients with bilateral vestibulopathy. Loss of function of both saccular sensors was recorded in the case of sequential bilateral CI in 25% of children. The preoperative saccular status studied according to the laterality of the ear shows a relatively uniform presence of the existence of myogenic potential (77.1% in the case of right ears compared to 73.8% in the case of left ears). From the point of view of the implant typology, the presence of the P1N1 complex in the groups that were subsequently implanted unilaterally or bilaterally sequentially was similar (79%). The group that underwent CI simultaneously had a lower percentage of the presence of the saccular reflex in the preoperative period. The same analysis performed at the time of T1 (postoperative), shows a similar presence of saccular potential on the right and left ears (52.9% versus 53.8%). After implantation, the groups of ears with sequential bilateral CI and those with simultaneous CI appears with equivalent percentages of normal saccular function (51.9% versus 50%). The group of ears belonging to children implanted unilaterally, however, shows a preservation of the saccular reflex in a higher proportion (62.5%). The real variation of the saccular function (previously calculated only on the ears that presented saccular function at the preoperative moment) was reported to the total number of ears (n = 135). It was noticed that more than half (53.3%) preserved the saccular function, 22.2% lost it, while 24.4% did not suffer any variation because they already had a vestibular areflexia associated with hearing loss. If in children with bilateral sensorineural hearing loss and congenital unilateral saccular deficit the principle of cochlear implantation of the ear with vestibular deficiency had been observed in order to preserve the functional saccular receptor, this study could not have been performed because implantation on one ear with vestibular areflexia it cannot produce any variation in the activity of the sensor.

IX THE EFFECTS OF INSERTING ELECTRODE HOLDER BY COCHLEOSTOMY VERSUS ROUND WINDOW ON THE VESTIBULAR FUNCTION

IX.1 Introduction The third study direction of the PhD thesis consists in evaluating the impact of inserting electrode holder by cochleostomy versus round window on the vestibular function. With the increase in the number of surgeries for cochlear implantation, due to the extension of indications and due to the accessibility guaranteed by national health programs, the number of patients at risk of vestibular injury has also increased accordingly. To limit these undesirable effects, medical research has adopted two directions of study and action, both in order to reduce the perioperative traumatic component of the inner ear: creating devices with electrode port as small and fine as possible and establishing surgical techniques to insert the electrode as less traumatic. Thus, the surgical approach (through the round window or cochleostomy) is a factor worth studying because the choice of a minimally invasive technique can lead to better results by preserving vestibular receptors. The principle of introducing the electrode holder is subject to the need to position it in the tympanic scale, exceptions being very rare. Access through the round window is a method that explores an anatomical area with lower resistance, so there is no need for milling, unless the access is hampered by the upper frame of the window that can be protruded, and in this case is removed by milling. Cochleostomy is the approach to the cochlea in specified areas from an anatomical-surgical point of view, which involves milling. The methodology of removing bone areas by milling has several disadvantages: heating of the bone with the consequences of thermal aggression on neighboring tissues (e.g. facial nerve), the production of bone powder that can penetrate from the cochleostomy into the otic capsule, but also vibration intense mechanics that can represent a labyrinthine trauma/ concussion. There are data in the literature that support both types of methods. Different authors present the advantages and disadvantages of the two possible approaches of the inner ear: the insertion of the electrode by cochleostomy or by round window. The variability of such data can be determined by several considerations: the surgeon's experience for one method or another, the type of methods used for vestibular testing, and the time of testing in relation to the time of intervention, the anatomical-surgical nomenclature used. The aim of our study was to assess the status of vestibular peripheral sensors and to analyze a possible correlation with the type of surgical approach: cochleostomy and round window. The analysis was performed for both the adult group and the children's group

IX.2 Materials and methods For this direction of study of the thesis we took into account the same groups, of adults and children, to which we reported the vestibular sensory status depending on the method used to insert the electrode holder. The methods for testing vestibular status are those described in the chapter "Materials and methods" for the group of adult patients and for the group of children, respectively. The available data were analyzed by the same statistical methodologies, in the sense required by the purpose we set ourselves: analyzing the impact of the electrode holder insertion path on the vestibular sensors.

IX.3 Results The data were collected using Microsoft Excel. Statistical processing was performed with SPSS 24.0. The same groups (children and adults) were analyzed, from the perspective of the type of electrode holder insertion, through the round window or by cochleostomy, in order to correlate this aspect with the postoperative vestibular deficit. In the first phase we report the results of the statistical analysis of the data from the adult group.

29,8%

70,2% CO FR

Figure 9.1 Percentage frequency of types of surgical approach

Of the 47 ears at 70.2%, the approach by cochleostomy was used, while access through the round window was used only in 29.8% of cases (data of statistical significance).

Figure 9.3 Analysis of the vestibular status of the three sensors according to the surgical approach to the operated ears (n=47)

The analysis of the vestibular status in the operated ears depending on the surgical approach highlights the following: - for the lateral canal, the group with cochleostomy presents 69.7% cases with preserved function, 24.2% cases of hyporeflexia and 6.1% cases of areflexia; the group with access through a round window has 71.4% cases with normal function, 14.3% cases of hyporeflexia and 14.3% cases of areflexia. - for the statistical saccule, in the case of the group with access by cochleostomy, 51.5% of cases with normal function are highlighted. 9.1% cases of hyporeflexia and 39.4% cases of areflexia; the group with access through a round window has 50% cases with normal function, 7.1% cases of hyporeflexia and 42.9% cases of areflexia. - for the utricle, the group with cochleostomy presents 42.2% cases with preserved function, no case of hyporeflexia and 57.6% cases of areflexia, with no cases of hyporeflexia; the group with access through a round window has 42.9% cases with normal function, 7.1% cases of hyporeflexia and 50% cases of areflexia.

Figure 9.4 Impact of the surgical approach on the impairment of one or more sensors of the same operated ear (n = 47) (0- functional vestibular sensors, 1- one impaired vestibular sensor, 2- two impaired vestibular sensors, 3- three impaired vestibular sensors)

In order to highlight the impact that the insertion mode of the electrode holder has on the vestibular function, a statistical calculation was performed to highlight the number of damaged receptors on each operated ear. Thus for the group with access by cochleostomy (33 ears) we notice the preservation of the function of all 3 sensors in 36.4% of cases, the involvement of a single vestibular sensor in 12.1% of cases, the impairment of two vestibular sensors in 30.3% of cases, and the impairment of all three sensors in 21.2% of cases. For the group with access through a round window (14 ears) we observe the preservation of function in 28.6% of cases, the impairment of a single vestibular sensor in 21.4% of cases, the impairment of two vestibular sensors in 35.7% of cases, and the impairment all three sensors in 14.3% of cases.

In the group of children with ears operated for cochlear implantation we obtained the following results: Of the 135 ears at 58.51%, the cochleostomy approach was used, while access through the round window was used in 41.49% of cases).

Figure 9.7 Distribution of the frequency of types of surgical approach depending on the sequence of surgery

From the perspective of how to use the surgical approach (cochleostomy / round window) depending on the type and sequence of the intervention (unilateral / bilateral sequential cochlear implant / simultaneous cochlear implant) we obtained the following data: in the case of sequentially implanted bilateral ears (79), 43 ( 54.4%) had a cochleostomy as a surgical approach, and 36 (45.6%) using the round window as access; in the case of ears implanted bilaterally simultaneously (32), at 25 (78.1%) cochleostomy was used as access, and at 7 (21.9%) the round window was used; in the ears of unilaterally implanted patients (24), cochleostomy was used in 11 cases 17

(45.8%), and the round window in 13 cases (54.2%).

Figure 9.8 The status of the postoperative saccular function (T1) in the group of ears with cVEMP present preoperatively (T0) in relation to the surgical approach (n=102)

The following figure shows the variation of the vestibular function in the group of 102 ears (which showed a saccular response to the preoperative evaluation), depending on the surgical access (cochleostomy/ round window). In the group of ears implanted with access by cochleostomy (57 ears), 68.40% preserved the cVEMP response, while 31.60% lost the saccular electrical potential. In the group of ears with surgical access through a round window, 73.33% maintained the physiological saccular response, and 26.67% had postoperative saccular areflexia.

a) ) preoperative (T0) saccular status (cVEMP b) postoperative saccular status (cVEMP) depending on depending on the surgical approach the surgical approach

Figure 9.9 Comparison between the preoperative and postoperative saccular status (n=135)

Comparing the preoperative saccular status to the postoperative one, we notice that the group of ears that was implanted using cochleostomy varied from a percentage of 27.8% of vestibular damage before implantation to 50.6% of cases of vestibular areflexia after implantation. In the case of the implanted group using access through the round window, the vestibular damage varied from 19.6% at the preoperative moment to 41.1% at the postoperative moment. Physiological results were obtained at: - Preoperative time in 72.2% of cases for those who subsequently underwent an approach by cochleostomy and in 80.4% of cases in which an approach was subsequently performed through the round window - Postoperative time in 49.4% of cases with cochleostomy and in 58.9% of cases with round window

IX.4 Discussions

In the group of adults we observe a predominance of cases in which the insertion of the electrode was performed by cochleostomy (70.2%) compared to those in which the insertion was chosen through the round window (29.8%). The dominance of cochleostomy insertion is also valid in the group of children, but the difference between cases with cochleostomy insertion and those through the round window is smaller: 79 ears implanted by cochleostomy insertion (58.51%) and 56 ears implanted by insertion through round window (41.49%). This difference between the group of adults and the group of children can be explained by the context in which the study was conducted. Thus, for adults operated a few years ago there was no special concern regarding the preservation of the functions of vestibular structures, while for children operated more and more for bilateral cochlear implantation in recent years, the period of evaluation and implantation of patients overlapped with the desire of the medical team to limit as much as possible the lesions at the vestibular level, an idea that was supported by the literature. This implies a moving surgical population, as there are still many implanted patients with access by cochleostomy, but conceptually the transition is made to choosing the round window as a preferential access due to the lower risks involved. Probably, if the study had been performed at a later time than the one we performed, most patients would have been implanted with access through the round window. Thus, the numerical shortcoming manifested to the detriment of one method or the other is manifested depending on the time placement of the study. Multiple publications have supported cochleostomy as a surgical technique with arguments about how to perform it and the most appropriate anatomical area to minimize potential vestibular lesions (42), (43), (44). The risk involved by this procedure is represented by the maneuver of milling the bone which can produce mechanical and thermal aggression. In addition, particles resulting from milling can penetrate the inner ear and initiate and encourage ossification. The ambiguity of the nomenclature for the topography of the coachostomy is also widely debated, which makes it difficult to understand anatomical concepts related to the procedures for inserting the electrode holder into the cochlea. Another concern, apart from the direct damage of the vestibular system, is the one related to the possible slippage of the electrode holder in the cochlea and the tissue and sensory damage that they induce. For example, the electrode holder, after exceeding the plane of the insertion hole (cohleostome or round window), depending on the angle of inclination and the force and speed of insertion applied, can cross the basilar membrane at the cost of damage to the organ Corti, and can be placed in vestibular ramp, with decreased efficiency in stimulating the cochlear nerve, but with impaired vestibular function and the likelihood of favoring the phenomena of intracochlear fibrosis. Therefore, maintaining the insertion course in the tympanic ramp after performing the cochlear approach is particularly important for the patient, but also for many authors of the latest studies in the field. Wanna et al. (45) demonstrated that access through the round window (including the variant of this method which involves milling the edge of the round window for a better view of the window) guarantees the insertion in the tympani scale in 91% (respectively 84%) of cases, compared to cochleostomy which allows access to the tympanic scale in 37% of cases. O ’Connel (46) confirms these data in an even more recent study (2016). Connor (47), using lateral electrodes and postoperative imaging, states that the frequency of translocation (displacement in the vestibular scale) of the electrode in the basal flow of the cochlea is higher for cochleostomy than for access through the round window, in turn supporting the same conclusions previously presented. The risk of cochleostomy is manifested even from the beginning of the execution of this operatory time, by the possibility of inserting the electrode holder directly into the vestibule scale, as the locations of the cochleostomy on such a small area of the procedure may be different (48), (49). The risk of insertion into the vestibule scale is more present if the cochleostomy is anterior to the round window compared to the lower location than the round window (50), (51). Thus it was raised the problem was to identify the ideal place to perform the cochleostomy, which should affect the vestibular function the least and to avoid as much as possible the placement of the electrode in the 19 vestibular ramp and also to reduce the risk of translocation of the electrode during its introduction into the cochlea. The comparison of the two ways of access is the topic of an article published by Todt et al. (43) which refers to the anterior cochleostomy and the round window (with the removal of the upper edge of the round window). The conclusion of the study by Todt et al. is that the differences identified by them are statistically significant and recommend the use of access through the round window as it is less traumatic. Regarding Todt's article, Sylvette Wiener-Vacher (44) replies that the traditional access through the round window may be more difficult for the child due to the lack of pneumatization of the mastoid and due to the narrow space provided by the tympanotomy. The technique adopted is adapted for pediatric age, attempts are made to save the chorda tympani nerve and a lower and vertical cochleostomy is performed against the round window niche in order to avoid spiral lamina lesions and insertion of the electrode holder in the vestibular scale. According to Wiener- Vacher S., using this technique, the rate of vestibular lesions reaches about 10%, similar to the 13% reported by Todt et al. for the traditional round window approach, being much lower than the one associated with cochleostomies (50%). Our study on the pediatric group with the 102 units that had normal saccular function at the preoperative time shows a saccular impairment of 26.7% of implanted children with access through the round window compared to 31.6% in those implanted using cochleostomy. However, if we report to the whole group of 135 children, the saccular damage is 41.15% for those who used the round window as a method of inserting the electrode holder and 50.6% for those who used cochleostomy, the evidence of the potential lesion being smaller on the side of the approach through the round window, our results being in agreement with those communicated by the most prestigious recent studies. Like the French group led by Wiener-Vacher (44), Todt (52) confirms that the round window approach can be a way to better preserve the vestibular function, especially the saccular response.

Figure 9.13 Areas for performing cochleostomy (A- anterior cochleostomy, B-antero-inferior cochleostomy, C- inferior cochleostomy, I- incus, S- stapes) Modified according to Badr et al. (232)

In order to clarify the ideal site of cochleostomy, so that this technique also benefits from a safety in the insertion of the electrode holder, Badr A et al. (53) shows three areas in which it is possible to perform cochleostomy, areas that are illustrated according to Figure 9.13: upper cochleostomy, antero-inferior cochleostomy and lower cochleostomy. The anatomical landmarks are tangent to the lower edge of the round window (X axis), tangent to the anterior edge of the round window (Y axis), the parabola tangent to the upper edge of the round window and the lower plane represented by the mastoid segment of the facial nerve. The safest area for cochleostomy seems to be the intersection between area B and C because it guarantees the introduction of the electrode holder in the tympany scale. There are also studies showing that the results of vestibular tests were not significantly different before and after the cochlear implant (IC) surgery between cochleostomy and round-window groups, as is the study by Kluenter et al. (3) which finds no significant changes between the two methods of surgical approach (patients being evaluated using computerized posturography and caloric test). We mention that posturography is not the ideal tool to highlight a vestibular lesion, especially since it is performed at a postoperative distance, when the lesions will be compensated. VEMP records are useful to study this aspect (of the vestibular lesion depending on the method of inserting the 20 electrode) because the otolith organs, especially the saccule, are the most exposed to damage. Even in our adult group there are no statistically significant differences between the two methods, although in the pediatric group there is an obvious better preservation of saccular function by using access through the round window. Considering the group of children, when analyzing the frequency of the type of surgical approach (cochleostomy/ round window) at the level of groups with unilateral CI, simultaneous bilateral and sequential bilateral, it was noticed that in the case of ears with unilateral CI more access was used through the round window ( 54.2%) compared to access by cochleostomy (45.8%). In the ears with bilateral CI, the use of cochleostomy is more frequent: for the group with simultaneous bilateral CI in 78.1% of cases, and for the group with sequential bilateral CI in 54.4% of cases. The trend in choosing the insertion method was to perform both types of insertion on one bilaterally implanted patient (one ear with round window insertion and the other ear with cochleostomy insertion), a decision that is reflected in the group of those operated sequentially and which gives the study the possibility to compare the induced vestibular effects. There have been cases where the choice of surgeon was guided by particular anatomical conditions, choosing the safest method for the patient regarding the success of the intervention. This finding does not apply in adult patients with cochlear implants, probably due to the small number of ears (19). Analyzing the loss of saccular function depending on the sequentiality of the intervention in the group of children with cochlear implant in our study we notice that, for both sequential and simultaneous cochlear implantation, cases implanted through the round window have a better percentage of saccular function preservation than those operations in which the insertion of the electrode holder was performed by cochleostomy.

X. GENERAL CONCLUSIONS

1. The treatment of various forms of hearing loss by cochlear implantation may expose the patient to risks of damage to the vestibular system induced by cochlear implant surgery. These lesions have a different impact on the balance and vestibular status of the patient, depending on the time when it is installed, the most dramatic situation being that of the young child with postimplantation bilateral vestibular deficits. In this context, the study we proposed on the influence of cochlear implantation on the sensors of the vestibular system involved a series of features on data collection, reflected in a special selection and organization of the patient group and subgroups of analysis. 2. The groups and subgroups were homogeneous in terms of gender distribution and the group and subgroups of children were homogeneous in terms of age. Patients from urban areas predominate as a result of a better degree of culture and information, due to easier accessibility to medical services and a more favorable socio-economic situation. 3. The evaluation of patients was performed with tests established as standard methods of vestibular diagnosis in the field of audiovestibulogy in the most developed and high-performance profile centers in the world, including the latest validated objective tests available. For the adult group, it was possible to perform functional quantification for three of the five existing vestibular sensors in the inner ear, and for the children's group, an objective vestibular diagnostic tool was used according to age, evaluating the saccular sensor. 4. Patients with severe or profound sensorineural hearing loss may associate vestibular deficits, also confirmed in our study group. In the case of the analysis of the results in adults, it can be argued that severe/ profound sensorineural hearing loss is mainly associated with otolith deficits. 5. The postoperative assessment of the vestibular damage to implanted ears in adults showed that: - the utricle is the sensor with the greatest damage, the saccule is affected to a lesser extent and the lateral canal is the least affected; - postoperatively there is no case in our group of adults in which only one vestibular sensor was affected. - postoperative vestibular impairment persists in adults, an aspect highlighted by the quantification of the compensation deficit by computerized posturographic evaluation. 6. In our group of children with cochlear implant, with preoperative saccular function present, it was noticed: - a deterioration of post-implantation saccular function (areflexia) in 29.4% of implanted ears, which confirms a real surgical iatrogenic risk; - bilateral vestibular areflexia was surgically induced only in children implanted bilaterally sequentially, but was also present in children implanted bilaterally simultaneously due to the association between a surgically induced lesion on one ear and a pre-existing lesion implantation on the contralateral ear; - the higher percentage of bilateral vestibular lesion by inducing a saccular deficit in the second ear operated on in children in the sequential group supports the idea that the decision of the moment of implantation of the second ear in case of evidence of vestibular deficit on the first implanted ear must be taken in such a way as to provide sufficient time for the development of gait and for the avoidance of the child's cognitive retardation 7. The manner to perform the cochlear implant intervention by observing minimally invasive criteria could minimize the vestibular lesions induced by this surgery. Cochlear postimplantation vestibular sensory status in adults and children in the presented groups was analyzed comparatively in our study for the two main ways of inserting the electrode holder: by cochleostomy, the classical approach, and by the round window, proposed as less traumatic. 8. For the adult group, no significant differences were observed between the two methods of electrode insertion. However, as the adult has developed locomotion strategies, the consequences of permanent vestibular lesions after cochlear implant surgery are less important than in the young child. Utricular impairment in the adult group is more important at insertion by cochleostomy in situations with postoperative involvement the utricular function is always completely lost. According to the statistical analysis, regardless of the type of insertion used, the sensors most exposed to the risk of injury are the otolith ones, especially the utricle. 9. In the case of the group of children, the saccular sensor was monitored and it was shown that the insertion of the electrode holder through the round window has a higher potential for saccular preservation, the lesions being significantly lower than in cases with access by cochleostomy. 10. The present study indicates that the insertion of the cochlear implant electrode holder through the round window is the most indicated method whenever it is possible in both children and adults, as it offers more chances of preservation of vestibular sensors compared to cochleostomy, which is extremely important especially in the bilateral cochlear implantation of the young child before the acquisition of gait. 11. In young children, vestibular evaluation before and after surgery is essential in rehabilitating deafness by cochlear implant, because the child's neuro-motor and cognitive development depends on the functioning of the 22 vestibular sensory structures. In the case of young children, pre-existing vestibular deficits for cochlear or surgically induced implantation must urgently benefit from a vestibular rehabilitation program that takes place simultaneously with the auditory-verbal habilitation/ rehabilitation, a process that we can define as an “early intervention in vestibular rehabilitation”. Partial and unilateral vestibular deficits in both children and adults can be successfully compensated by restorative physical therapy, but bilateral vestibular areflexia remains a challenge whereas the absence of any peripheral vestibular input causes persistent imbalance, delayed acquisition of gait in children and decreased autonomy of adult patients and does not favor vestibular rehabilitation. These cases could represent candidates for cochlear-vestibular implantation in the future 12. Vestibular impairment is therefore possible and probable during cochlear implantation, and the vestibular diagnostic protocol performed before cochlear implantation can highlight pre-existing vestibular deficits associated with deafness. This helps to formulate the surgical indication which must observe the principle of functional rescue of at least one vestibule in order to avoid bilateral deficit, the latter presenting a significant risk of decreasing the patient's quality of life, being an extremely difficult deficit to rehabilitate. In this regard, the possible vestibular lesion associated with surgery should be discussed with the patient when filling in the informed consent. Given the arguments resulting from this PhD research regarding the vestibular sensory functional importance in adults and especially in children, we support: a. introducing the obligation to perform the vestibular balance of each patient candidate for cochlear implantation, both preoperatively to establish the medical strategy for the treatment of deafness and 3 months postoperatively, in order to identify possible iatrogenic vestibular deficits and to establish recovery treatment as early as necessary; b. use of the round window for the insertion of the electrode holder whenever possible, in order to minimize postoperative vestibular deficits, especially in children.

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