In recent years, there has been a growing interest in the study of emotion recognition through electroencephalogram (EEG) signals. One particular group of interest are individuals with hearing impairments, who may have a bias towards certain types of information when communicating with those in their environment. To address this, our study collected EEG signals from both hearing-impaired and non-hearing-impaired subjects while they viewed pictures of emotional faces for emotion recognition. Four kinds of feature matrices, symmetry difference, and symmetry quotient based on original signal and differential entropy (DE) were constructed, respectively, to extract the spatial domain information. The multi-axis self-attention classification model was proposed, which consists of local attention and global attention, combining the attention model with convolution through a novel architectural element for feature classification. Three-classification  and five-classification  tasks of emotion recognition were carried out. The experimental results show that the proposed method is superior to the original feature method, and the multi-feature fusion achieved a good effect in both hearing-impaired and non-hearing-impaired subjects. The average classification accuracy for hearing-impaired subjects and non-hearing-impaired subjects was 70.2% (three-classification) and 50.15% (five-classification), and 72.05% (three-classification) and 51.53% (five-classification), respectively. In addition, by exploring the brain topography of different emotions, we found that the discriminative brain regions of the hearing-impaired subjects were also distributed in the parietal lobe, unlike those of the non-hearing-impaired subjects. Emotion is the attitude and experience generated after human beings compare objective things with their needs. It reflects people’s current physiological and psychological state, which plays a crucial role in people’s cognition, communication, and decision making . ResearcWith the development of emotional computing and artificial intelligence, the study of emotion recognition via electroencephalogram (EEG) has been paid more attention. In recent years, EEG-based emotion recognition has mainly focused on healthy people and achieved good results . HoweverFeature extraction is particularly important in EEG emotion recognition . EEG sigEEG emotion recognition is essentially a pattern recognition problem aiming to embed highly discriminative emotion features into EEG signals and improve the accuracy of emotion recognition. Early emotion recognition models are mainly shallow machine learning models such as support vector machine  (SVM), tIn this paper, we selected the Chinese-style facial expression pictures from CFAPS as stimuli to induce subjects’ emotions by displaying corresponding facial expression pictures. Finally, 20 non-hearing-impaired subjects and 20 hearing-impaired subjects were collected based on EEG induced by five emotional images. Besides, the multi-axis self-attention module composed of the window attention module and grid attention module effectively combines local and global features to improve model classification performance and reduce model computational complexity. Promising classification results are obtained on the datasets of hearing-impaired subjects and non-hearing-impaired subjects, respectively, which proves the validity of the classification model. By drawing a brain topographic map based on DE features, we further compare and analyze the differences in brain region energy in emotion recognition between hearing-impaired subjects and non-hearing-impaired subjects. Compared with non-hearing-impaired subjects, the changes in the emotion recognition of hearing-impaired subjects are not only concentrated in the temporal lobe but also distributed in the parietal lobe. The main contributions of this study are given as follows.(1)We have constructed an emotional EEG dataset using facial expression picture stimuli, featuring both non-hearing-impaired and hearing-impaired subjects.(2)To facilitate fusion, we have developed two novel constructs—the subtract symmetric matrix (SSM) and the quotient symmetric matrix (QSM)—based on the original signal and DE feature. These matrices have been designed keeping in mind the electrode positions in the widely recognized international 10–20 system, and take into account the nature of the electrode pairs in symmetrical positions. SSM quantifies the difference between the eigenvalues of the left and right brain regions by measuring the characteristic differences of 27 pairs of symmetric electrodes. Similarly, QSM computes the difference between the eigenvalues of the left and right regions of the brain using the same methodology.(3)Our work puts forth a groundbreaking multi-axis self-attention mechanism for the recognition of emotions through EEG among both non-hearing-impaired and hearing-impaired individuals. Our multi-axis self-attention mechanism is composed of two modules that run in parallel: a window attention module which focuses on local features of the EEG signal, and a global attention module which extracts the global features.The rest of the paper is summarized as follows. In Current methods of emotion induction mainly stimulate subjects through pictures , audio , and vidIn this work, twenty subjects  with an average age of 22 years old were recruited from the School of Audiology and Artificial Sciences of Tianjin University of Technology for an emotion induction experiment. We only conducted subject-dependent experiments—the training dataset and test dataset were from the same subject—so that gender did not influence the experimental results. Basic personal information and auditory information were collected before participating in the experiment. The subjects had uncorrected or corrected vision, were right-handed, and had no history of mental illness. All of the subjects had hearing loss in both ears, 4 subjects had congenital disorders, and 18 subjects wore hearing aid devices. The situation of 20 hearing-impaired subjects was shown in In our previous research, we have found that small changes in the facial expression of hearing-impaired subjects during video stimuli watching are particularly indicative of emotional changes. In order to verify whether this conclusion is still valid under different emotional induction methods, this study used facial expression pictures as stimuli, which contain rich information about facial changes.The stimulus material of the experiment was 240 emotional images of faces selected from the Chinese Facial Affective Picture System [With reference to the SEED dataset  our dataIn this experiment, the NeuSen W 364 EEG acquisition system developed by Neuracle , was used to collect the subjects’ EEG signals. The device collects EEG signals at a sampling rate of 1 k Hz and has 64 electrode channels. According to the international 10–20 system, TP9 and TP10 are used as reference electrodes for bilateral mastoid sensors.The experiment was conducted in an isolated environment. The collected EEG signal needed to be preprocessed, and the input of the deep learning model can be obtained by feature extraction. Four eigenmatrices (SSM(OEF), QSM(OEF), SSM(DE), QSM(DE)) were extracted based on the asymmetric characteristics of the left and right brain regions. The model proposed in this paper first fuses four feature matrices and then obtains two deep features through local and global attention modules, respectively. The two deep features are fused again to obtain the feature vector with global and local representativeness, which is sent into the full connection layer to get the classification output of the model.This section introduces the EEG signal pre-processing method, EEG emotion feature extraction method, and the construction of a classifier.The EEG signals collected by experiments are inevitably mixed with various interference signals and artifacts, which need to be removed by signal pre-processing to improve the performance of subsequent emotion recognition. We used the EEGLAB toolbox to process the EEG signal. Firstly, the original EEG signal was down-sampled to 200 Hz and then we removed low-frequency drift and high-frequency noise by 1–75 Hz band-pass filter, and power frequency interference was eliminated by 49–51 HZ band-pass filtering. The bilateral mastoids of TP9 and TP10 were used as references, and then we interpolated the data to repair bad derivatives. Finally, independent component analysis (ICA) was used to remove artifacts.It is necessary to extract features from the pre-processed EEG signals to characterize the emotion-related information in the EEG signals. In this section, four different feature matrices  will be constructed according to electrode positions in the international 10–20 system as the input of the classification model. The construction process of the eigenmatrix is shown in T, E (=62) is the number of electrodes, and T. Then, In this paper, N .Differential entropy (DE) is a feature extraction method widely used in the field of EEG emotion recognition. It is an extension of Shannon entropy. For an EEG signal with a probability density function, DE can be approximately equal to the logarithm of the power spectrum at a certain frequency band. The calculation formula of electroencephalogram DE is as follows:It can be seen from the formula that, for EEG sequences of the same length, the differential entropy in a frequency band is equivalent to the logarithmic value of its energy in the frequency band.B (=5) is the number of bands, and b. Then, In order to construct the DE feature matrix, the differential entropy features of five frequency bands  were extracted from EEG samples using a one-second time window. bWe find the 27 pairs of symmetric electrodes and construct the subtract symmetric matrix using the following formula:The subtract symmetric matrix (SSM) based on the original signal and DE are respectively constructed by the above methods, as shown in the following formula:b, and The symmetry quotient feature is the quotient of the feature values of the left and right brain symmetric electrodes. The same as the SSM, it is necessary to find out the symmetric electrodes and eliminate the electrodes in the middle position. Use the following formula to construct the symmetric quotient matrix:According to (6), the quotient symmetric matrix (QSM) based on the original signal and DE show in the following formula:In order to avoid the influence of too large a numerical difference on the subsequent processing, we carried out normalization processing on each two-dimensional matrix constructed.In the previous section, we introduced the extraction process of the feature matrix, and in this section, we focus on the proposed model. The model proposed by us takes four dimensions as the input of the feature matrix. Firstly, through the feature fusion network, the fusion feature matrix of dimension  is obtained. Then, the fusion feature matrix is fed into the multi-axis attention module which is composed of the global attention module and local attention module. Finally, the output of the global attention module and the local attention module are fused again and fed into the classification network to get the classification results of the model. The model proposed in this paper is introduced in the following two parts: feature fusion network and classification model.Different features contain different emotional information. In order to consider the complementarity of multiple features, four different feature matrices are sent into the feature fusion network for feature fusion. The fusion network mainly includes 1 × 1 convolution layer, normalization layer, and ReLU activation function. The convolution of 1 × 1 can unify the channel dimensions without changing the dimension of the eigenmatrix, and the activation function can solve the problem of insufficient linear model capability and possible gradient explosion. In addition, in order to capture more details of the feature matrix and optimize the classification effect, we used cubic spline interpolation on the matrix . The matFinally, the four processed feature matrices were spliced to obtain the fused feature matrix (200 × 64 × 64), where 200 corresponds to the number of samples, and 64 × 64 is the size of the feature map after interpolation. The fused feature matrix was used as the input of the classification network.To combine local and global features, global self-attention  is takenAt first, the network has two layers of convolutional networks to capture the feature information adequately, and then it enters the local self-attention module and the global self-attention module, respectively, in parallel. Finally, the two are integrated and output classification after full connection. Local attention is realized by window attention. For the input eigenmatrix As shown in For global attention, inspired by window attention, we cite a simple and effective way to obtain sparse global attention—grid attention. Instead of using a fixed window size to divide the feature matrix graph, we used a 2 and W2 in the figure are set to 8, and the hyper-parameter G is set to 4. By using the same fixed window and grid size (P = G = 4), you can balance the operations between local and global, both of which have only linear complexity in terms of space size and sequence length. We put inverted mobile bottleneck convolution in front of each attention mechanism, to further improve the generalization and ability of the network model.The calculation process is shown in In this section, we conducted subject-dependent experiments to verify the emotion classification performance of the model based on EEG datasets of hearing-impaired subjects and non-hearing-impaired subjects. The training set and test set were divided in a ratio of 7:3. The experimental platform is NVIDIA GeForce RTX 3050 Ti Laptop GPU. The super parameter settings of the classification model are shown in In the three-classification task, happy was classified as a positive emotion, neutral as a neutral emotion, and sad as a negative emotion. Compared with hearing-impaired subjects, the emotion classification effect of non-hearing-impaired subjects is better. It can be speculated that this result may be related to the difficulty of facial emotion recognition of hearing-impaired subjects under the influence of physiological factors and social environment factors, which is the same as the conclusion of previous researchers ,31.To study the classification performance of each emotion based on the multi-axis self-attention network model, we used the confusion matrix. Each row of the confusion matrix represents the real category of data, and each column represents the predicted category.The results of emotion classification are shown in In the five-classification tasks, the neutral emotion classification effect of non-hearing-impaired subjects was still the best, and the happy emotion recognition effect of hearing-impaired subjects was the best. By comparison with Compared with the hearing-impaired subjects, the non-hearing-impaired subjects are better in the identification ability of negative emotion , 51%, 49%, and 49%, respectively. The difference in fear emotion classification between hearing-impaired subjects and non-hearing-impaired subjects was the largest, with a difference of 4%. Therefore, it is speculated that, compared with non-hearing-impaired subjects, hearing-impaired subjects have difficulty in recognizing negative facial emotions, which is consistent with our previous video-based study.To verify the effectiveness of the proposed feature selection method, the comparison experiments of different feature matrix combinations were carried out by both hearing-impaired subjects and non-hearing-impaired subjects. The results appear in The SSM(OEF) and QSM(OEF) represent the subtract symmetric feature matrix and the quotient symmetric matrix based on the original EEG signal. SSM(DE) and QSM(DE) represent the symmetric difference feature and the symmetric quotient feature based on the differential entropy feature. The accuracy of the three-classification and five-classification tasks of the hearing impaired and non-hearing-impaired subjects by using DE features are close to that of SSM(OEF) and QSM(OEF). Compared with SSM(OEF) and QSM(OEF), SSM(DE) and QSM(DE) have better performance in all classification tasks. Concretely, QSM(DE) has the best performance in single feature classification, SSM(DE) + QSM(DE) has the best performance when two feature matrices are fused, and SSM(OEF) + QSM(OEF) + SSM(DE) has the best classification effect when three feature matrices are fused in both three-classification and five-classification tasks. Moreover, the fusion of four feature matrices obtains the best performance. The average classification accuracy of the three-classification tasks and the five-classification tasks reached 70.2% and 50.15%, and 72.05% and 51.53% for hearing-impaired subjects and non-hearing-impaired subjects, respectively. It can be inferred that the features in different domains may be complementary in EEG emotion recognition.To reflect the effectiveness of the feature fusion matrices we chose a variety of simple machine learning methods (SVM (Linear), GNB (Default), KNN (N = 5), ResNet18) to conduct experiments on the proposed fusion feature matrix SSM(OEF) + QSM(OEF) + SSM(DE) + QSM(OEF), and the results are shown in In order to further explore the key regions affecting the emotions of hearing-impaired subjects, we drew brain topographic maps with different frequency bands based on differential entropy features. As In the process of recognizing anger and fear, it can be seen that the key areas identified by hearing-impaired subjects overlap, which is different from that of non-hearing-impaired subjects. For anger and fear, there was no significant overlap between the activated electrodes of the hearing impaired and non-hearing-impaired subjects across the five bands. The hearing-impaired subjects activated a large number of brain regions in the δ and θ bands, while the non-hearing-impaired subjects only had a small number of activated electrodes in the occipital and parietal lobes. In the latter three frequency bands, the overlap rate of the activated electrode regions between the hearing-impaired and non-hearing-impaired subjects was also very low, which partly explains why the hearing-impaired subjects were less effective in recognizing anger and fear than the non-hearing-impaired subjects. This is related to the bias of hearing-impaired subjects in recognizing negative emotions. The distribution of emotion-discriminating brain area in the temporal lobe of hearing-impaired subjects was the same as that of non-hearing-impaired subjects.The difference, however, is that the discriminative brain regions of the hearing-impaired subjects are also located in the parietal lobe. According to studies of brain function, the parietal lobe is involved in the integration of vision and visual processing. This may indicate that visual information plays a more important role in the emotional discrimination of hearing-impaired subjects due to the loss of hearing ability. In the absence of auditory channels, hearing-impaired subjects may use the coordination of multiple brain regions to complete the acquisition and expression of emotional information.In this paper, the emotional-faces-induced EEG emotion recognition scheme was proposed. We collected EEG signals from hearing-impaired subjects and non-hearing-impaired subjects when they were watching the different face pictures. To obtain the spatial domain feature, the SSM and QSM were based on the original signals and DE features, respectively, which were reflected as four feature matrices. The classification network model based on the multi-axis self-attention mechanism is used for emotion recognition. The quadratic complexity of ordinary attention is reduced to linearity by using a multi-axis self-attention module without loss of non-locality. The spatial interaction between local and global can be realized in each block, effectively combining local and global characteristics. The promising results were obtained both in hearing-impaired and non-hearing-impaired subjects for three-classification and five-classification tasks with the proposed four-feature matrix fusion strategy. It proves that the complementarity between features can be used to improve the effect of emotion classification.Based on the classification results of the three and five categories of emotion, the differences in the ability of non-hearing-impaired subjects and hearing-impaired subjects to recognize different emotions and the differences in the electrodes of active brain regions were analyzed in detail through the confusion matrix and brain topographic map. We find that the key areas identified by hearing-impaired subjects overlap and are obviously different from that of non-hearing-impaired subjects in the process of recognizing anger and fear. This is related to the bias of hearing-impaired subjects in recognizing negative emotions. Additionally, we also found that hearing-impaired subjects may use the coordination of multiple brain regions to complete the acquisition and expression of emotional information in the absence of auditory which meets the conclusion of hearing-impaired people in video stimulation.In future work, we will extend our dataset and focus on developing general feature extraction methods and classification models for hearing-impaired and non-hearing-impaired people.


The degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere’s disease.This study included 54 patients (62 ears) with Meniere’s disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and pure-tone audiometry. Endolymphatic hydrops were assessed according to Gurkov’s criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed.p < 0.05). There was no significant correlation between vestibular endolymphatic hydrops and pure-tonal audiometry or staging . The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p < 0.05). The degree of cochlear hydrops was correlated with the audiometry, low-frequency hearing thresholds, mid-frequency hearing thresholds and staging (p < 0.01).Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both The types and sites of endolymphatic hydrops based on a 3D-real inversion recovery sequence can be used to indicate the degree of hearing loss in patients with Meniere’s disease.Level III. Meniere's Disease (MD) is an inner ear disorder of unknown origin, with Endolymphatic Hydrops (EH) as the main pathological feature.The diagnosis of MD has traditionally relied on medical history, specialist examinations, and audiological findings.The degree of EH as revealed by inner ear MRI after the administration of Gd correlates with the severity of hearing loss. However, the results of studies have been inconsistent due to the varied techniques of inner ear MRI and the assessment criteria used to determine the degree of EH, as well as inter-subject variation. Three-dimensional Fluid-Attenuated Inversion Recovery (3D-FLAIR) sequences are mostly used for inner ear MRI after the administration of Gd contrast agents, but the use of Three-Dimensional real Inversion Recovery  sequences has gradually increased. An advantage of 3D-real IR over 3D-FLAIR is the high signal-to-noise ratio and contrast-to-noise ratio,This study used 3D-real IR sequences for Gd-enhanced posterior inner ear MRI, and the assessment criteria proposed by Gürkov et al.A total of 54 patients who attended a university hospital in China between April 2019 and May 2023 and were diagnosed with MD based on the 2015 guidelines and had not received previous treatment were included.All patients underwent Pure-Tone Audiometry (PTA) within 1 week of MRI. PTA was performed in a standard sound-isolation room with background noise of <30 dB(A). This test was conducted using the Otometrics audiometer (Astera), which measured the conventional frequency thresholds of 250–8000 Hz for air conduction and 500–4000 Hz for bone conduction. According to the PTA grading criteria of the 1997 World Health Group, the average thresholds of binaural air conduction at 500, 1000, 2000, and 4000 Hz were calculated as the average hearing threshold (PTA 500–4000 Hz). The average thresholds at 1000 and 2000 Hz were used as the mid-frequency hearing threshold (PTA 1000–2000 Hz) and those at 4000 and 8000 Hz were used as the high-frequency hearing threshold (PTA 4000–8000 Hz). MD staging was obtained by calculating the average hearing thresholds at 500, 1000, 2000, and 3000 Hz2, matrix 384 × 384, slice thickness 0.8 mm, PAT2, and scan time 6 min 38 s.The patient was placed in the prone position with the head tilted to the side, and the external auditory canal was locally disinfected. The tympanic membrane surface was subsequently anesthetized using tetracaine hydrochloride and punctured at the anterior lower quadrant; 0.5 mL of a Gd contrast agent  was then injected into the tympanic chamber. This procedure was repeated on the other ear. After the injection, the patient was instructed to lie in the supine position with the affected ear facing upward for approximately 30 min, with minimal talking and swallowing. MRI was performed 24 h later. The specific parameters of the 3D-real IR sequence were as follows: echo time 187 ms, repetition time 6000 ms, Inversion Time (TI) 1730 ms, bandwidth 501 Hz/Px, echo train length 124, flip angle 120°, field-of-view 200 × 200 mmThe MRI results were classified according to the degree of EH using the criteria described by Gürkov et al.t-test was used to compare the mean hearing thresholds at different hydrops sites. The Mann–Whitney U test was used to compare the clinical staging of different sites. The correlations among the degree of EH, PTA, and the clinical stage were analyzed using the Spearman rank correlation test; p < 0.05 was considered to indicate statistical significance. All data were analyzed using SPSS 25.0.Measurement data and count data are reported as the mean ± standard deviation and rate (%), respectively. Fisher's exact test was used to analyze EH in different locations within the cochlea. The The PTA 500–4000, 250–500, 1000–2000, and 4000–8000 Hz values for the 62 affected ears were 58.97 ± 18.15, 59.48 ± 18.27, 57.34 ± 20.21, and 64.84 ± 18.95 dBHL, respectively. The staging results for the 62 affected ears were as follows: 5 ears in stage 1, 6 ears in stage 2, 36 ears in stage 3, and 15 ears in stage 4.t = 2.150, p < 0.05) but did not significantly differ from that of the no hydrops group . Staging in the isolated cochlear or vestibular EH group was longer than that in the cochlear and vestibular EH group  but did not significantly differ from that in the no hydrops group .There were 2 ears with no hydrops, 8 ears with isolated cochlear EH, 3 ears with isolated vestibular EH, and 49 ears with cochlear and vestibular EH. The PTA 500–4000 Hz value was 61.25 ± 17.79 dBHL for the cochlear and vestibular EH group, 48.52 ± 17.73 dBHL for the isolated cochlear or vestibular EH group, and 54.38 ± 2.65 dBHL for the no hydrops group. The PTA of the cochlear and vestibular EH group was higher than that of the isolated cochlear or vestibular EH group (p > 0.05). There was also no significant correlation between the vestibular EH of the affected ear and the PTA 250–500, 1000–2000, and PTA 4000–8000 Hz values .In terms of the degree of vestibular EH in the 62 affected ears, 10 ears were grade 0, 29 ears were grade 1, and 23 ears were grade 2 . There wr = 0.417, p = 0.001; r-values of 0.479 and 0.426, respectively; both p < 0.01). There was no significant correlation between the degree of cochlear EH in the affected ear and the PTA 4000–8000 Hz value (p > 0.05). However, the degree of cochlear EH in the affected ear was significantly correlated with staging , while the PTA 4000–8000 Hz value in the affected ear was not significantly correlated with the degree of basal turn EH (p > 0.05) , the middle turn EH rate was 91.94% (57/62), and the basal turn EH rate was 90.32% (56/62); the differences among these three rates were not significant ( > 0.05) .Table 2EMRI after administration of Gd contrast agents is a commonly employed clinical tool to assess inner ear EH. While Gd contrast agents penetrate the perilymphatic space of the inner ear, they cannot penetrate the endolymphatic space due to the blood-labyrinth barrier. Perilymphatic spaces with injected Gd contrast agents appear hyperintense, while hypointensity is observed in endolymphatic spaces without Gd contrast agents; this allows for differentiation of the endolymphatic and perilymphatic spaces, and thus the objective assessment of EH. The administration of Gd contrast agents to the inner ear involves delivery via the middle ear using intravenous injection. After Gd contrast agents are injected via a tympanic membrane puncture, they pass through the round window membrane into the perilymphatic space. Tympanic membrane puncture contrast is superior to intravenous administration.The TI of 3D-FLAIR is set to the endolymph over the zero point, at which the endolymph and cerebrospinal fluid are suppressed and appear as a hypointense area. In contrast, the perilymph is observed as a hyperintense region on the image. Since the surrounding bone is also hypointense, it is difficult to completely distinguish it from the boundary of the endolymph. This leads to some difficulties in the determination of EH. In this study, a 3D-real IR sequence was used for real-part reconstruction, and the TI of the inversion recovery sequence was at the middle of the point at which the endolymph and perilymph crossed zero. The perilymph, surrounding bone tissue, and endolymph appeared hyperintense, isointense, and hypointense, respectively, on the image. This greatly facilitated a more accurate distinction and identification of the site and degree of EH.7The various criteria used for the identification of EH differ slightly among researchers, and an international standard is lacking. In 2009, Nakashima et al.MD is one of the most common causes of peripheral vertigo and is often associated with recurrent fluctuating hearing loss. Hearing loss often differs in the distinct regions of the inner ear in which EH occurs. The PTA of patients with vestibular and cochlear EH was previously found to be higher than that of patients with isolated cochlear or vestibular EHThe association between the degree of EH and the hearing threshold has also been reported previously. Yang et al.Some studies have focused on the association between hearing thresholds in different frequency bands and the degree of effusion. For example, Zhang et al.The cochlear structure produces a specific frequency-location map due to its frequency specificity for sound encoding. Therefore, different locations of cochlear EH may cause hearing loss with different frequency characteristics. Our evaluation of hearing thresholds for different EH sites in the cochlea revealed that cochlear middle turn EH was significantly correlated with the mid-frequency hearing threshold, while no such association was found between basal turn EH and the high-frequency threshold. This may be attributed to the possibility that MD causes some alteration of the original cochlear frequency-position map after EH.This study has a few limitations. Our results showed that PTA in patients with both vestibular and cochlear EH was higher than that of patients with isolated cochlear or vestibular EH. However, as there were too few ears with isolated vestibular EH, we combined isolated vestibular EH and isolated cochlear EH into one group for analysis. There is a need for further studies with larger sample sizes, particularly for cases with no hydrops. Furthermore, due to the difficulty and subjectivity in determining the degree of apical turn EH, this study only evaluated the presence or absence of hydrops and did not grade cochlear parietal rotation EH.In summary, the greater the degree of EH in patients with MD, the greater the hearing loss. This association is particularly evident in cases of cochlear EH. A significant correlation is reported between EH in different cochlear sites and hearing loss in different frequency bands, mainly between cochlear middle turn EH and the mid-frequency PTA hearing threshold.The authors declare no conflicts of interest.


Sensorineural hearing loss associated with Kawasaki disease has been increasingly reported, but its etiology remains unclear. Most reported cases of sensorineural hearing loss associated with Kawasaki disease have been mild and reversible during acute or subacute phases. However, bilateral severe hearing loss as a complication of Kawasaki disease can cause delays in cognitive and speech development. A 4-year-old Japanese boy treated for Kawasaki disease had right-side moderate and left-side profound sensorineural hearing loss on the 141st day after onset of Kawasaki disease. Despite systemic steroid pulse treatment, hearing loss remained in both sides. After the recurrence of Kawasaki disease, hearing on the right side progressively worsened, meaning there was now severe hearing loss on both sides. Left cochlear implantation performed on the 1065th day after the onset of Kawasaki disease improved the patient's hearing and his ability to communicate. Sensorineural hearing loss associated with Kawasaki disease may progress over a long period and cause bilateral severe hearing loss, although past reports showed occurrence during acute or subacute phases. The clinical course of our patient suggests that intense inflammation caused by Kawasaki disease could be related to prolonged hearing loss. Cochlear implantation seems to be effective for sensorineural hearing loss associated with Kawasaki disease. BesidesThe clinical course of SNHL associated with KD varies between patients. Although most SNHL associated with KD usually develops within the first 30 days of disease onset and is reversible, 5.5%–14% of patients have persistent SNHL . ProgresHerein, we describe the case of a 4-year-old Japanese boy with KD with bilateral severe SNHL that progressed over 2 years. This report shows the efficacy of cochlear implantation for SNHL associated with KD.2.The patient is 4-year-old Japanese boy who had no notable past clinical history or family history but developed KD. From the fourth day after onset, he began treatment with IVIG and oral aspirin (30 mg/kg/day). However, he was persistently febrile and was treated with cyclosporin  and subsequent oral prednisolone  in the pediatrics department. Blood examinations showed the persistent elevation of white blood cell (WBC) count and C-reactive protein (CRP), anemia and thrombocytosis during the treatment for KD. Blood concentrations of cyclosporine were also monitored to be within therapeutic range but not ototoxic levels as maximum 80.4 ng/ml. After the first treatment, he had no complications, including coronary aneurysm or the need for continuous medications. From the 130th day after onset of KD, his family noticed that he had impaired hearing. On the 141st day after onset of KD, he was presented to the otorhinolaryngology-head and neck surgery department. The pure tone audiometry and auditory steady-state response (ASSR) test showed right-side moderate and left-side severe sensory hearing loss ,B. The tOn the 510th day after the first onset, there was relapse of KD. He recovered after immediate IVIG treatment, but his right-side SNHL worsened. After treatment for KD, systemic steroid treatment for right-side SNHL was reintroduced, but there was no improvement of hearing loss, rather, there was progressive deterioration. Blood examinations showed persistent mild anemia and thrombocytosis during the progression of hearing loss, although there was no elevation of WBC count. Finally, the patient developed severe hearing loss on the right side ,D. The tWe applied a cochlear implant to the left ear. As preoperative evaluation by CT  and MRI 3.SNHL associated with KD is generally reported to be temporary with acute or subacute onset and is often reversible. This patient's course provides two important clinical suggestions: First, SNHL associated with KD could progress over the long term and result in severe hearing loss. Second, efficacy of cochlear implantation for bilateral severe SNHL associated with KD was demonstrated in this patient.SNHL associated with KD could progress over a long term and result in severe hearing loss. SNHL is associated with about 30% of patients with KD and 73% of those patients develop bilateral hearing loss –7. SNHL Development of severe hearing loss also seems to be rare in SNHL associated with KD –12. EtioUntil now, gene mutations or variants responsible for SNHL associated with KD have not been identified, although some relating to coronary artery aneurysms have been reported . In our Cochlear implantation could be effective for SNHL associated with KD. In terms of long-term outcomes of cochlear implantation to SNHL caused by autoimmune vasculitis, Bacciu et al. reported about Cogan syndrome, which is systemic vasculitis characterized by inflammation of the eyes and inner ears, and manifesting as interstitial keratitis and audiovestibulary dysfunction . CochleaIn conclusion, in our patient, SNHL associated with KD progressed over more than two years. This case suggests the importance of long-term auditory follow up among patients with KD, especially for children during cognitive and speech development. Cochlear implantation could be an effective therapeutic option for patients with SNHL associated with KD. Present report would provide the valuable evidence about the incidence, outcome and treatment for hearing loss associated with Kawasaki disease that have still not been well-established.


The middle cerebellar peduncle (MCP) is the most common site associated with hearing impairment in acute ischaemic stroke. Narrowing or occlusion of the vertebrobasilar artery due to atherosclerosis is thought to be the main pathogenesis of MCP infarction. Most previous reports of MCP infarction have not been clear whether the patient's hearing impairment is localized to the center or periphery.We report 44-year-old man with vertigo, tinnitus, and bilateral sudden sensorineural hearing loss (SSNHL) as the first symptoms. Pure Tone Audiogram revealed complete hearing loss in both ears. Acute bilateral MCP infarction was diagnosed by repeated brain magnetic resonance imaging (MRI). The brainstem auditory evoked potential (BAEP) and the electrocochleography were normal. The otoacoustic emissions showed binaural cochlear dysfunctions. After the antiplatelet, lipid-lowering, steroids and hyperbaric oxygen therapy, the pure-tone average (PTA) showed a clear improvement with 67 decibels (dB) on the right and 73 dB on the left at the 3-month follow-up.Vertebrobasilar diseases due to atherosclerosis should be routinely considered in middle-aged and elderly patients with vascular risk factors and bilateral hearing loss. Bilateral SSNHL can be a prodrome of acute MCP infarction and it can be peripheral. Brain MRI, brain magnetic resonance angiogram (MRA), brain and neck computed tomography angiography (CTA), BAEP, otoacoustic emissions, and Pure Tone Audiogram help to localize and qualify the diagnosis. Bilateral SSNHL localized to the periphery usually improves better and has a good prognosis. Early detection of hearing loss and intervention can help patients recover. SSNHL refers to a rapid-onset hearing loss occurring within 3 days, with hearing loss ≥30 dB in at least three contiguous audiometric frequencies . The gloA 44-year-old man with hypertension, suddenly developed vertigo, tinnitus, and bilateral hearing loss 1 day before admission. The patient was hospitalized in Tianjin Huanhu Hospital after the above symptoms persisted without improvement. Up on physical examination, he did not have dysarthria, limb weakness, ataxia, or spontaneous nystagmus, but sustained horizontal gaze-evoked nystagmus to the right or left in both eyes, abnormal horizontal head impulse test and absent skew. PTA showed a total SSNHL of 112 dB in the right ear and 115 dB in the left ear , and no Three days after the initial onset of the hearing loss and vertigo, the patient's symptoms worsened. Clinical neurological examination revealed cerebellar dysarthria, gaze-evoked nystagmus, and ataxia. Reexamination of the brain MRI demonstrated an acute infarction in the bilateral cerebellum , B.After 10 days of hospitalization, the patient developed left-limb weakness and worsening ataxia. A brain MRI revealed a new acute infarction extending to the bilateral MCP , D. LaboThe patient's symptoms improved after several days of antiplatelet, lipid-lowering, steroids and hyperbaric oxygen therapy. The patient was given oral prednisone at a dose of 60 mg for 4 consecutive days, followed by a reduction of 10 mg every 2 days. Hyperbaric oxygen therapy was administered once a day for 10 sessions. Three months later, Pure Tone Audiogram showed that SSNHL persisted; however, there was a clear improvement, with PTA average of 67 dB on the right and 73 dB on the left . The speBilateral SSNHL is rare, accounting for approximately 4.9% of all SSNHL , and cern = 1), facial sensory disturbance (n = 1), ataxia (n = 3), and nystagmus (n = 4), also reported. All new AICA infarcts were seen from 0 to 7 days after the onset of symptoms, such as hearing loss. Two patients  had moderately severe to total hearing loss with normal BAEP, and our patient had normal electrocochleography, abnormal otoacoustic emissions indicating cochlear dysfunction and horizontal semicircular canal low-frequency dysfunction; one patient (patient 3) had moderate to moderately severe hearing loss with good speech discrimination. All these findings suggested that the hearing impairment was localized to the cochlea, and the central system function was intact. The patients' other neurological symptoms were mild and most of the hearing impairment had improved significantly (mild to severe hearing loss) at follow-up. Patients are detected early, without vertigo, with mild hearing loss and an upwards-sloping audiogram, which is considered to be associated with a good prognosis . A–7. A4–7)rognosis . Timely rognosis . Previourognosis . Lee et rognosis . AnotherAll patients had one or more risk factors associated with systemic diseases, such as hypertension, diabetes, or hyperlipidemia. This is consistent with the literature, which reported that 38% of bilateral SSNHL were associated with such systemic diseases . Most anThe purpose of this case report was to characterize the nature of deafness in the patient by performing detailed audiological and neurological investigations, such as the head MRI, pure tone audiometry, speech audiometry, acoustic immittancemetry, BEAP, and otoacoustic emissions to define the location of lesions associated with hearing loss. Our patient had persistent, bilateral, severe hearing loss on PTA, but limb strength and coordination gradually resolved over time, with no significant abnormalities in BEAP. At the same time, the symptoms of the facial and abducens nuclei and sensory tracts did not manifest during the course of the disease. We determined that bilateral hearing loss was affecting the cochlear rather than the retrocohlear sites such as the vestibulocochlear nerve, brainstem nucleus or other central pathways, as a result of ischemic infarction. Moreover, the retrocochlear acoustic nerve is believed to have an abundant collateral blood supply, which has a lower probability of injury . Meanwhin = 5) of patients within 1–10 days before the onset of the brainstem and cerebellar symptoms  for the publication of any potentially identifiable images or data included in this article.Material preparation was performed by RL. Data analysis was performed by ZY and LX. The first draft of the manuscript was written by ZY. WY contributed to the study conception and approved the final manuscript. All authors commented on previous versions of the manuscript. All authors contributed to the article and approved the submitted version.


Mucormycosis is a rare, opportunistic, and emerging fungal infection that can rapidly develop into a severe, highly fatal clinical picture. In most cases, it is caused by fungi of the order Mucorales, which are usually avirulent but become pathogenic when the host’s immune system is compromised. This systematic review was conducted according to PRISMA guidelines. The databases searched included PubMed, Scopus, and Web of Science. We chose articles that analyzed the oral manifestations of patients with mucormycosis, were published between 2018 and 2023, and met our search terms. The risk of bias in the articles was assessed using the CARE guideline for case reports and STROBE for a cross-sectional study. After the selection process, 20 articles were included in this review, all containing information about the different oral manifestations presented by people with mucormycosis. The most common oral manifestations are mainly bone exposures and oral ulcers, halitosis, pus discharge, gingival thickening, and periodontitis. However, despite the importance of recognizing these oral manifestations in the early stages of mucormycotic infection, providing early treatment, and reducing the high mortality rate of the infection, more studies are needed. Mucormycosis, also known as zygomycosis, was first described in humans in 1885 by the German pathologist Paultauf ,3.Rhizopus oryzae, of the order Mucorales [In most cases, it is caused by the fungus ucorales . It is aucorales . Its moducorales . These fucorales .Lichtheimia [The incidence varies according to geographical area and study period. The highest number of cases has been reported in India, with up to 140 cases per million inhabitants ,7, likelThus, there are many predisposing factors, such as renal failure, liver failure, prolonged treatment with immunosuppressive therapy, leukemia, organ transplants, polytrauma, AIDS, or tuberculosis. However, the main factor is uncontrolled diabetes, which is present in 60–80% of mucormycosis cases . HyperglCurrently, as the number of people undergoing treatment with chemotherapy or immunotherapy increases, this factor is becoming more important . FurtherDepending on its clinical forms, mucormycosis can be classified into five types: rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated. The rhinocerebral form is the most common, as well as the most important for dentists, due to the oral manifestations it can present . These aCommon primary extra-oral signs of infection include headache, sinus pain, congestion, and bloody nasal discharge . Other sMucormycosis has a rapid progression and an incubation period that is not well established, depending on the patient’s risk factors; therefore, rapid recognition of signs and symptoms is crucial. In first few days, fever, decreased visual acuity, and facial edema will appear. After 1–2 weeks, bone exposure and oral ulcers can be observed in some cases ,9,11. ThHowever, these clinical signs cannot provide a definitive diagnosis of mucormycosis; therefore, a histological diagnosis is needed, where mucorales appear as hyaline filaments in the form of strips and hyphae with variable diameters ,6. UsualThere are four critical factors for adequate treatment: early diagnosis, control of underlying predisposing factors, extensive surgical debridement with margins of healthy tissue, and appropriate antifungal therapy . The maiOnce the risk factors are under control and successful surgical and pharmacological treatment is completed, the patient’s oral rehabilitation begins via free flaps or by constructing prosthetic devices .Currently, research has focused on adjuvant therapies, especially modulating the tissue microenvironment to deter fungus and enhance the host’s immune response .Nowadays, mucormycosis is an infection with increasing incidence. Its rhinocerebral form is the most common and usually presents oral manifestations. Knowledge of these manifestations facilitates early diagnosis and allows the initiation of treatment immediately, thus increasing the possibility of survival. Therefore, knowing the oral manifestations associated with mucormycosis and conducting a systematic review is essential.The main objective of this systematic review was to conduct a qualitative synthesis of studies referring to the oral manifestations of mucormycosis.This systematic review was conducted according to the PRISMA 2020 guidelines, an acronym for “Preferred Reporting Items for Systematic reviews and Meta-Analyses”. It was designed to help authors document their reasons for conducting the review, how they conducted it and what was found during the review. These guidelines help authors conduct a more adequate, structured, and systematic review . AdditioTo guide this systematic review, we followed the PICO method, which is used to conduct correct searches for scientific information. Hence, our research question was: What are the oral manifestations of patients with mucormycosis .Articles were included or excluded according to the criteria shown in We conducted an exhaustive search was to identify and analyze articles containing relevant information for our systematic review. The following databases were utilized: PubMed, Scopus, and Web of Science. The initial search was conducted on 15 November 2022, and the updated search was performed on 3 February 2023.The terms used for our search were: “fungal infection”, “mucormycosis”, “dental”, “oral manifestation*”, and “oral disease”. Boolean operators (“AND” and “OR”) were employed to establish relationships between these terms. We exported the results to the EndNote bibliographic manager  after the bibliographic search. First, we eliminated duplicate articles; then, based on the title and abstract, we exclude articles that did not meet our inclusion and exclusion criteria. In cases where information was inconclusive, the full text was read and analyzed to determine eligibility.For data extraction, the following categories were considered in each article: author, year of publication, type of study, medical history, dental history, and the most prevalent oral manifestations and localizations. Other data were also extracted, such as country, number of patients in each study, gender, and age.We followed two different guidelines to analyze the quality of the articles selected for this systematic review: the ‘CAse Reports’ (CARE) and ‘Strengthening the Reporting of Observational Studies in Epidemiology’ (STROBE).The CARE guideline, consisting of a checklist with 13 items , was useWe used the STROBE guide to conduct a cross-sectional study, which is based on 22 points related to different parts of the articles . The artFinally, each point assessed by the guidelines was marked with a tick (✓) if the requirement was met and a cross (✕) if it was not met.We conducted an exhaustive search of the databases, identifying 953 references related to the oral manifestations of mucormycosis. Of these, 406 were from PubMed, 411 from Scopus, and 136 from Web of Science. Then, we used the bibliographic manager EndNote to remove 241 duplicate articles. A total of 712 articles were analyzed based on their titles and abstracts. However, 678 articles did not meet the inclusion criteria and were excluded.Three articles met the criteria and were requested for retrieval but could not be obtained. As a result, only 31 articles were read in full text. Among these, five included cases of COVID-19 that were not mentioned in the title or abstract, five did not present oral manifestations, and only one was a systematic review that was consequently discarded. Finally, 20 articles were selected for analysis .Most articles presented diabetes as the main medical history associated with mucormycosis, except for four articles. The dental history associated with mucormycosis mainly included a history of previous extractions and previous or recent cases of periodontitis.All the analyzed articles reported oral manifestations associated with mucormycosis. Oral ulcers and areas of exposed bone, often associated with necrosis, were the most common manifestations. These lesions were predominantly located in the maxilla, affecting the hard palate and the alveolar ridge. Only one atypical case involving the mandible was observed in this review.The analysis revealed a moderate–low risk of bias among the articles, with 11 studies showing moderate bias and 7 with low risk; only two articles were found to have a high risk of bias .Following the quality analysis, we decided to exclude two articles with a high risk of bias from the discussion of results to avoid affecting the quality of our findings.A relevant aspect of our review is that all case reports fulfilled items 5 and 6, which refer to patient information and clinical findings. Only two articles ,27 did nOnly item 12 was addressed by all articles, as none included the patient’s perspective or experience.Finally, not all case reports provided information on informed consent from patients ,21,24,35The articles were distributed according to year of publication, country of publication, journal of publication, and type of article.Regarding the year of publication , the peaRegarding countries of publication , there wRegarding published journals , the anaConcerning the type of article published , case reMucormycosis is an opportunistic fungal infection that progresses rapidly if not diagnosed early and treated immediately . The incWe analyzed twenty articles that met the inclusion criteria in this review. After assessing their quality, two articles were excluded from the discussion due to a high risk of bias.As observed, mucormycosis, mainly in its rhinocerebral form, clearly affects the orofacial region. Therefore, knowing the oral manifestations that patients may present is crucial.In the cross-sectional study conducted by Nezafati et al. between 2007 and 2017 in an Iranian hospital, 40 patients with rhinocerebral mucormycosis were identified, with 72.5% exhibiting oral manifestations. Palatal necrosis was the most frequent manifestation, followed by palatal ulcers, aphthous ulcers, and tongue lesions. Another important finding was that seven of the cases evaluated in the study developed rhinocerebral mucormycosis after tooth extraction, and all had diabetes as a predisposing factor . Thus, tGholinejad Ghadi et al., Prabhu et al., Rai et al., Rani et al., Pandilwar et al., and Rajashri et al. reported cases of mucormycosis in patients with uncontrolled diabetes and a history of tooth extraction, suggesting that tooth extraction is an important dental history to consider, because it participates in the development of mucormycosis, especially in diabetic patients ,26,29,31Atypical cases have also been identified, such as those reported by Nilesh et al. and Venkatesh et al., where immunocompetent patients developed fungal infections after tooth extraction. Consequently, the extraction of teeth, particularly maxillary molars, may increase a patient’s susceptibility to mucormycosis due to the proximity of the maxillary sinus, which is often affected by inhalation of the spores ,23.In the reported cases by Rai et al., Venkatesh et al., and Deshpande et al., cases of periodontitis have been found to act as a dental antecedent of mucormycosis. Although not the only antecedent, periodontal disease was associated with tooth extractions in all three cases. Therefore, patients with periodontitis should follow a strict periodontal protocol to prevent tooth extraction since, as mentioned previously, the extraction of teeth, especially maxillary molars, increases susceptibility to mucormycosis ,22,23.In addition to dental history, Beiglboeck et al. reported a case of mucormycosis in which the patient had undergone molar endodontic treatment a week before, which may have caused or at least favored the fungal infection .Only cases published by Ramadorai et al., Srivastava et al. Ramesh et al., Verma et al., and Anwar et al. had no dental history highlighted ,32,33,34In terms of medical history, more than half of the cases analyzed had a history of uncontrolled diabetes. Only Panneerselvam et al. and Verma et al. reported mucormycosis in patients with controlled diabetes ,33. OnlyThus, as mentioned by Anwar et al., diabetes interferes with the body’s immune response to infection. A high glycemic index increases fungal proliferation and reduces chemotaxis and phagocytic efficacy .Our next step is to analyze its oral manifestations, having described the medical and dental history associated with several cases of mucormycosis.In their prospective analysis, Ramadorai et al. presented a series of ten case reports, all with uncontrolled diabetes, where swelling in the maxillary region around the face was the main symptom. Intraorally, the two most frequent oral manifestations of mucormycosis could be observed: palatal ulcers and areas of bone exposure. Only one patient showed signs of oroantral communication, indicating an advanced stage of mucormycosis . This arSome articles, such as those by Rai et al. and Deshpande et al., indicate oral ulceration as the pathognomonic lesion typical of rhinocerebral mucormycosis, usually followed by necrotic bone exposure ,22. HoweApart from prevalent manifestations, there are also less frequent manifestations, such as halitosis, pus secretion, gingival thickening, or periodontitis.Halitosis and pus secretion are usually associated with bone exposures and oral ulcers, which are the most frequent manifestations ,28,29,30Another atypical manifestation worth considering is periodontitis, which can also be a predisposing factor for developing mucormycosis. Deshpande et al. reported an infrequent case where mucormycosis simulated severe periodontitis, causing delayed diagnosis and a worse prognosis. Thus, although the main oral manifestations of mucormycosis are ulcers and bone exposures, other non-specific presentation forms may delay diagnosis, such as warty lesions, painful indurated ulcers, or periodontal signs .In terms of the locations of oral manifestations, most cases in this review involved the hard palate, followed by the alveolar ridge and the alveolar bone. These results agree with Venkatesh et al., Ramesh et al., and Verma et al., who established the palate as the most frequent oral location for these manifestations ,32,33.However, Rai et al. showed less frequent locations of involvement, such as the gums, cheeks, tongue, and jaw , which wIn this review, practically all of the articles were case reports, which had a relatively low level of scientific evidence. However, they were included because no articles with a high level of evidence met the established inclusion criteria for this review. Another relevant aspect is that most articles focused on the infection’s systemic manifestations. In other words, information about oral manifestations was scarce.As observed throughout this systematic review, knowledge of oral manifestations, which often appear in patients with mucormycosis in its rhinocerebral form, can aid in early diagnosis and improve patient survival with immediate treatment. This review also demonstrates how certain dental histories can increase the likelihood of developing this infection. Dentists and other healthcare professionals should be mindful of these factors to mitigate complications and reduce mucormycosis mortality rates.Mucormycosis is an opportunistic fungal infection that can rapidly progress when the host’s immunity is compromised. The rhinocerebral form mainly affects the oral cavity, since the maxillary sinus and hard palate can be directly infected when spores are inhaled nasally.Mucormycosis development is more likely in individuals with specific medical and dental antecedents that compromise their immune status, particularly uncontrolled diabetes. Nevertheless, previous histories of tooth extraction and, less commonly, periodontitis and endodontic procedures have also been associated with an increased risk of mucormycosis.The most common oral manifestations are mainly bone exposures and oral ulcers, halitosis, pus discharge, gingival thickening, and periodontitis.However, despite the importance of recognizing oral manifestations in the early stages of mucormycotic infection to initiate immediate treatment and reduce the high mortality rate of the infection, there are still scarce studies on these manifestations.


Pathophysiological alterations in the cochlea and functional tests of the auditory pathway support that in diabetes both vasculopathy and neural changes could be present. The aim of our research was to study the differential effect of type 1 diabetes mellitus (T1DM) on two different age groups. Audiological investigation was carried out in 42 patients and 25 controls at the same age groups. Investigation of the conductive and sensorineural part of the hearing system by pure tone audiometry, distortion product otoacoustic emission measurement and acoustically evoked brainstem response registration were evaluated. Among the 19-39-year-old people the incidence of hearing impairment was not different in the diabetes and control groups. Among the 40-60-year-old people hearing impairment was more common in the diabetes group (75%) than in the control group . Among patients with type 1 diabetes, the mean threshold values were higher in both age groups at all frequencies although significant difference was in 19–39 years old group: 500-4000Hz right ear, 4000Hz left ear, in 40–60 years old group: 4000–8000 Hz both ears. In the 19–39 years old diabetes group only at 8000 Hertz on the left side was a significant  difference in otoacoustic emissions. In the 40–60 years old diabetes group significantly less otoacoustic emissions at 8000 Hz on the right side  and at 4000-6000-8000 Hertz on the left side,  was present compared to the control group. According to ABR (auditory brainstem response) latencies and wave morphologies, a possible retrocochlear lesion arose in 15% of the 19–39 years old and 25% of the 40–60 years old diabetes group. According to our results, T1DM affects negatively the cochlear function and the neural part of the hearing system. The alterations are more and more detectable with aging. As one of our most important senses, the ability to hear enables us to connect to the world for many very important, even vital, reasons. Most importantly, hearing connects us to people enabling us to communicate in a way that none of our other senses can achieve. As the famed 20th-century activist and educator, Helen Keller, once said, “Blindness cuts us off from things, but deafness cuts us off from people”. People who can’t hear well may become depressed, or they may withdraw from others because they feel frustrated or embarrassed about not understanding what is being said. Around the world, approximately more than 1,5 billion people have impaired hearing .–17.14–17More and more evidence supports the theory, that retrocochlear neural structures can be damaged in type 1 diabetes. In a group of T1DM patients, the pure tone audiometry thresholds were higher than in the control group. As proof of normal cochlear function, there wasn’t a significant difference in otoacoustic emissions compared to controls and in the ABR measurement, the first wave was also in the normal range. The III and V waves—which are generated in the brainstem- were significantly delayed. These findings aid the hypothesis of neural changes in diabetes . In one In addition to the above, microscopic histopathological examination of the temporal bone revealed differences in the samples from T1DM patients compared to non-diabetes individuals. The walls of vessels of the basilar membrane and of the stria vascularis were found to be thicker. In addition, the atrophy of the stria vascularis was also observed. The number of outer hair cells in the basal turn of the cochlea was significantly less. Loss of the spiral ligament cells was observed in the area of the middle and apical turn of the cochlea . The cocIn a previous study, the evaluation of the PTA, ABR, and OAE results of young adults and T1DM patients (age between 17–46 years) showed the following alterations: Although the T1DM patients had significantly higher thresholds at 250, 1000, 2000, 4000, and 8000 Hz on the right and 250, 500, 1000, 4000, and 8000 Hz on the left ear than controls, the average PTA thresholds were less than 25 dB in both groups. Neural conduction in the auditory pathway was slowed down. Waves III and V were delayed and interpeak latencies between I-V waves were prolonged at both ears. 60% of the diabetics showed alterations by analyzing the otoacoustic emissions .Using subjective and objective audiological methods, we tried to answer the question of whether T1DM and its complications accelerate the aging of the auditory system and to what extent are they causing hearing loss. Is the involvement of the inner ear or the damage to the central structures decisive in this population? The present study was designed to test these hypotheses that T1DM is one of the factors causing hearing loss, and to describe the characteristics of this hearing impairment.The study was approved by the Regional and Institutional Committee of Science and Research Ethics, Semmelweis University (TUKEB 137-1/2010) and conducted in accordance with the regulations of the WMA Declaration of Helsinki and the General Data Protection Regulation issued by the European Union. All participants gave written informed consent prior any study specific procedures.A prospective observational study was conducted at the Department. of Otorhinolaryngology, Head- and Neck Surgery, Semmelweis University, Budapest, Hungary, between 2017–2019. A total of 42 T1DM patients and 25 control subjects were included. T1DM patients were maintained and regularly checked-up at the Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary. The exclusion criteria included age < 18 years, occupational noise exposure, any sign of inflammation of the middle ear or even with acute upper airway infection the patients, and any previous ear diseases or other known disease related to the hearing system.1C) and creatinine level of patients was measured at the Central Laboratory of Semmelweis University. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease-Epidemiology Collaboration equations [Medical history data including co-morbidities and recent medications were collected. T1DM was confirmed using c-peptide, islet-cell- and/or glutamic acid decarboxylase antibody measurements. In the T1DM group, glycated hemoglobin . We insert earplugs into the ear canals, which hermetically close them. Three tube goes through each earplug. They contain a tone loudspeaker, a microphone, and a pressure pump/manometer device. The acoustic admittance of the middle ear was measured by changing the air pressure in the ear canal and testing how the test tone (226Hz) is transmitted through the tympanic membrane and the ossicular chain. In general, healthy adults have the best tone transmission when the pressure in the ear canal is equal to the atmospheric pressure. In this case, the peak of the tympanogram is about 0 daPa If the pressure in the ear canal changes, the tone transmission gets less efficient . All thePTA measurements were evaluated in an audiological, sound-isolated cabin with a GSI 61 clinical audiometer . The hearing thresholds were measured with air conduction (AC) at 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, 8000 Hz and with bone conduction (BC) at 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz. Hearing impairment was detected when the threshold in either studied frequency was 25 dB or greater. The measurement procedure was performed according to the British Society of Audiology Guidelines.We used a Madsen Capella  diagnostic OAE system to test distortion product OAE between 1000 and 8000 Hz: 1–1.5-2-3-4-6-8 kHz respectively. Otoacoustic emission is described by David Kemp . This meDistortion product otoacoustic emissions are based on that, two simultaneous voices (f1 and f2) are given into the external auditory canal. Healthy outer hair cells produce a specific tone that can be detected with a probe microphone beside the first two tones (f1 and f2). A higher tone is marked with f1. The exact frequency of the DPOAE can be calculated according to the following formula: 2f1-f2 . The f2:A GSI Audera  device was used to test ABR. We measured the brainstem responses with electrodes on the forehead and on the mastoids. The evoked responses were detected by giving 70 and 90 dB click tone into the ear canal through ear plugs. The measurements were performed in a soundproof room by using 2024 clicks of alternating polarity. The repetition rate of the stimuli was 33.1 Hz. The wave reproducibility was measured as well, which helped establish the reliability of the measurement. See on .Statistical analysis was performed with R version 4.0.3 . Welch’s two sample t-test, Fisher’s exact test and the Cochran–Mantel–Haenszel chi-squared test were used to compare groups. To determine the trends in pure tone threshold and otoacoustic emission, linear and logistic mixed effect models were used , creatinine (p = 0.6784) and eGFR (p = 0.2601) levels did not differ between the two patient groups. Of the investigated complications neuropathy was more pronounced in the T1DM40-60 group, compared to that of the T1DM19-39 group (p = 0.0015), while no difference in nephropathy (p = 0.6879), retinopathy (p = 1.0000) and hyperlipidemia (p = 0.4649) could be justified . Similarly, HbAustified .19-39 and Control19-39 groups, 15,4% and 16,6%, respectively. In contrast, hearing impairment was more common in the T1DM40-60 group (75%) than in the Control40-60 group . In the diabetes study group the mean threshold values were higher in both age groups at all frequencies. In the T1DM19-39 group the hearing threshold in the middle to high frequency area (500–4000 Hz) on the right and in 2000 Hz on the left side were significantly higher than that of the Control19-39 group. The mean hearing thresholds in both groups were at all frequencies below 25 dB. Among 40–60 years-old study subjects, at 4000 and 8000 Hz, there was a significant difference between the T1DM40-60 and the Control40-60 results. In this high frequency region, the control subjects had a normal hearing, while the T1DM patients had usually a slight or mild hearing loss (n = 7), while some patients have had moderate or moderately severe (n = 3) or even severe (n = 2) hearing loss . Further analyses revealed that neither the duration of T1DM (p = 0.2950), nor actual HbA1C levels (p = 0.3079) were associated with hearing loss, however, eGFR was significantly associated with hearing loss (p = 0.0285).Analyzing the pure tone threshold altogether in a single statistical model showed that both T1DM  and older age  worsened the hearing of study subjects. According to the results of the model, the impaired hearing of the T1DM19-39 and the T1DM19-39 groups was good at almost all frequencies, and only at 8000 Hz was a slight difference between the two groups (p < 0.05), where a moderate impairment in the left ear of the T1DM19-39 group was found. Diabetes patients of the 19–39 age group had tendentiously less OAE-s at 8000 Hz on the right (p = 0.0834) and at 6000 Hz on the left side . In contrast, OAE was severely impaired at the higher frequencies in the T1DM40-60 group, compared to that of the Control40-60 group: At 8000 Hz on the right side (p < 0.01) and at 4000 Hz (p <0.05), 6000 Hz (p < 0.01) and 8000 Hz (p < 0.05) on the left side. At 3000 Hz on the right side in the T1DM group, tendentiously fewer OAE responses could be detected  were not associated with OAE.The aggravating effect of T1DM (right ear: odds ratio (OR) = 6.46, p = 0.0006; left ear: OR = 4.90, p = 0.0013) on otoacoustic emission is more severe in both age groups than that of older age . Similarly to that of pure tone audiometry, sidedness (p = 0.7565), the duration of T1DM (p = 0.5438) and the actual HbA19-39 group, followed by the Control40-60  and the two T1DM groups . The signal  and noise  level was significantly lower in the T1DM40-60 study group, compared to that of the T1DM19-39 group. The duration of T1DM  and the actual HbA1C levels  had no effect neither on the signal nor on the noise levels  and noise (dB SPL) level results of the OAE measurements were also compared between the study groups. No difference was found between the left and right ears . For both parameters, the clinically best results were found in the Controle levels .19-39 and T1DM40-60 patients (p = 0.4538), respectively.ABR waves were analyzed only in the diabetes patient groups. A possible retrocochlear lesion arose in 15% and 25% of the T1DM40-60 group: + 0.089 milliseconds; p = 0.0167). Wave 3 was significantly and marginally affected by higher HbA1C values  and age , but no difference was found regarding sidedness. And in wave 5 only sidedness affected latencies . No additional effector could be identified when investigating interpeak latencies. Averaged latency data of the four study groups are summarized in Latency data of waves 1, 3 and 5, and interpeak latencies of waves 1–3 and 3–5 at 70 dB and 90 dB were compared. It was found that wave 1 at 70 dB in average had a ~0.06 milliseconds longer latency in the right ear of the patients (p = 0.0213). No further differences could be found regarding the 70 dB measurements. In the 90 dB measurements wave 1 was affected by sidedness  and age  have also been showed [Hearing loss occurs more often in diabetes and a few hypotheses have emerged as to what might be behind this phenomenon including but not limited to role of glycated metabolites, microvascular causes and oxidative stress. The detrimental effect of glycated metabolites is theoretically based on the positive correlation between HbAn showed . A possin showed . During n showed . These fn showed . In thein showed . Moreoven showed . Animal n showed , 35. Dian showed . It has 40-60 group than in control subjects of the same age. In the non-T1DM group the mean hearing thresholds were in the normal hearing region of all studied frequencies. Although in the T1DM19-39 group we could detect significantly higher thresholds , the mean hearing thresholds were also in the normal ranges. A similar observation was reported by Hou et al. They found that the mean thresholds of diabetes patients in any studied frequencies were less than 25 dB [40-60 group had significantly worse hearing on 4 and 8 kHz, on both the right and left ear than the controls. This result differs from the results of Celik et al., who reported significantly higher hearing thresholds among T1DM patients at all measured frequencies [40-60 patients usually had a slight or mild hearing loss on 4–8 kHz. It is important to note, that moderate and severe hearing loss also occurred. Other publications also reported that hearing loss occurs more at higher frequencies [40-60 group had a significantly poorer outer hair cell function at 8 kHz than the corresponding aged control group. A similar observation was made for the left ear of T1DM19-39 patients. The ABR analysis showed, that a notable proportion of diabetes patients had signs of a retrocochlear lesion. Prolonged absolute and interpeak latencies may be a sign of such damage. Prolonged wave V latency and I-V interpeak latency have been described in other reports [40-60 group, but without statistical difference, suggesting that this observation might be a combined effect of aging and T1DM, but the role of the different T1DM subtypes  should be also considered as a significant proportion of the patients in the T1DM40-60 had LADA. An interesting observation of our study was that the right and left ear was differently affected in the T1DM groups, the most impairment was found in the right ear of the patients. We consider further investigations necessary to find out what could be behind this observation.In our investigation, hearing loss was the most frequent in the T1DMan 25 dB . The T1Dquencies . Most ofquencies , 37. All reports , 21. It Interventions to prevent, identify and address hearing loss are cost-effective and can bring great benefit to individuals. These are the main purposes of newborn hearing screening programs around the world. From birth the aging of the hearing system depends on genetics and other intrinsic and extrinsic factors. The starting point can be detected by the newborn hearing screening . People This study has some limitations, including the high heterogeneity of patients, and the small sample sizes. Number of control subjects was even smaller than that of the diseased group.Summarizing the result of the current study, changes of the hearing system caused by type 1 diabetes mellitus can be detected in the young adulthood and are more pronounced with aging. The cochlear and the retrocochlear parts of the auditory system are also affected.


AHI1c.2023G > A associated with JBTS type 3 andGJB2c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygousAHI1c.2023G > A andGJB2c.71G > A in the patient's parents. This study confirms the diagnosis of JBTS by WES helps identify the genetic causes of hereditary disorders that accelerate genetic evaluation and counseling for at-risk families.Joubert syndrome (JBTS) is a rare autosomal recessive or X-linked congenital brain malformation with strong genetic heterogeneity. Other neurological features of JBTS include hypotonia, ataxia, developmental delay, and cognitive impairment. Hearing loss with JBTS has been reported in the literature. We present the case of a 3.5-year-old boy born to a healthy consanguineous South Indian couple who was presented with ataxic cerebral palsy (CP) and hearing impairment; medical reports confirmed typical brain malformations of JBTS. Hearing impairment was screened by audiological assessment, which confirmed the presence of severe-profound hearing loss with outer hair cell dysfunction. Whole-exome sequencing (WES) was performed to know the molecular aspects of the condition and to detect any novel mutations. The homozygous mutation AHI1, which encodes the Jouberin protein at the JBTS3 locus, cause JBTS andGJB2, which encodes Connexin 26 protein, causes deafness in a south Indian patient.Joubert syndrome (JBTS) is a rare neurodevelopmental ciliopathy characterized by cerebellar and brainstem malformation, hypotonia, respiratory deficit, ataxia, developmental delay, and cognitive impairment with congenital onset.AHI1loci using the primers  and theGJB2loci were amplified using the primers  for a total volume of 10 μL. An initial denaturation step at 95°C for 2 minutes was followed by 35 cycles of 98°C for 25 seconds, 65°C for theAHI1variant, and 60.3°C for theGJB2variant for 45 seconds for annealing, 72°C for 30 seconds for elongation, and final extension at 72°C for 7 minutes. The polymerase chain reaction (PCR) products were evaluated using a 2% agarose gel electrophoresis. PCR products were labeled with BigDye Terminator v3.1 Cycle Sequencing Kit . The above-mentioned PCR primers (AHI1forward andGJB2forward) were used as sequencing primers and then analyzed by ABI 3500 Genetic Analyzer . Sequence data were analyzed with SeqScape v3 software .The proband, a 3.5-year-old boy, was born to a healthy consanguineous couple. He was born full term and was delivered through cesarean section weighing 3,500 g, with no birth asphyxia. He was hypotonic as an infant and presented with ataxia and global developmental delay. Delayed speech and language and severe mental retardation were noted . AudiolAHI1andGJB2genes in a patient clinically diagnosed with JBTS and hearing impairment. TheAHI1variant (NM_001134831.2) c.2023G > A p.D675N and theGJB2variant (NM_004004.6) c.71G > A p.W24X, consistent with the clinical findings of Joubert syndrome 3 (JBTS3) and hearing impairment, respectively, were identified. The mutationAHI1c.2023G > A p.D675N is a classical feature of JBTS3 (OMIM #608629).AHI1c.2023G > A p.D675N and heterozygousGJB2c.71G > A p.W24X were detected in the mother and father of the proband, which revealed the autosomal recessive mode of inheritance  in many populations, is also being reported in subjects with auditory neuropathy spectrum disorder.GJB2gene is located on chromosome 13q12.11, has two exons, and encodes connexin 26, a cochlear gap junction protein; mutations lead to an altered or loss of function of connexin 26, which appears to disrupt the assembly or function of gap junctions that alter the levels of potassium ions, which may damage the cells that are required for hearing.We present mutations in NM_00113831.2 c.2ritance and2. AHI1c.2023G > A p.D675N mutation has been previously reported only once in the literature.AHI1c.2023G > A associated JBTS and the first in India that is linked withGJB2c.71G > A associated hearing impairment. The only case report with sensorineural deafness in JBTS has also been reported from India.GJB2mutations have minimal or missing DPOAE.GJB2-related deafness; mutations in gap junctions can lead to the apoptosis of hair cells.AHI1and other associated genes are linked with human brain development; changes inAHI1between hominids suggest a positive evolutionary selection in the lineage leading to humans.AHI1is vital for axonal pathfinding mechanisms from the cortex to the spinal cord and mutations inAHI1cause neurological diseasesAHI1is also essential for synchronized movements of the hands and feet and might have been involved in the evolution of gait, which is distinctive of humans.AHI1c.2023G > A p.D675N mutation that is associated with JBTS3, which prevents the misleading presentation.TheAHI1c.2023G > A andGJB2c.71G > A of JBTS3 and hearing impairment, respectively. Despite its low incidence, JBTS should be considered a differential diagnosis that can accelerate the genetic evaluation process and make an informed decision for at-risk families for accurate genetic evaluation and counseling.To conclude, this study presented the molecular etiology of JBTS and hearing loss in a patient by detecting the disease-causing mutations


To review hearing and surgical outcomes after reconstructive middle ear surgery in class 4 congenital middle ear anomalies (CMEA), e.g., patients with oval- or round window atresia of dysplasia.Pubmed/Medline, Embase and Cochrane library.Articles containing data on hearing outcomes and complications after reconstructive ear surgery in class 4 anomalies were analyzed and critically appraised. The following data were included and reviewed: patient demographics, audiometric testing, surgical techniques, complications, revision surgeries and their outcomes. Risk of bias was determined, and GRADE certainty of evidence was assessed. Primary outcomes were postoperative air conduction thresholds (AC), change in AC, and success rates (closure of the ABG to within 20 dB), the occurrence of complications  and the long-term stability of hearing results (> 6-month follow-up) and occurrence of recurrence of preoperative hearing loss.Success rates varied from 12.5 to 75% at long-term follow-up with larger cohorts reporting success rates around 50%, mean postoperative gain in AC varied from 4.7 to 30 dB and − 8.6 to 23.6 dB at, respectively, short- and long-term follow-up. No postoperative change in hearing occurred in 0–33.3% of ears, and recurrence of hearing loss occurred in 0–66.7% of ears. SNHL occurred in a total of seven ears across all studies of which three experienced complete hearing loss.Reconstructive surgery can be an effective treatment option which should be considered in patients with very favorable baseline parameters, while also considering the substantial risk of recurrence of hearing loss, the possibility of unchanged hearing despite surgery and the rare occurrence of SNHL.2c.The online version contains supplementary material available at 10.1007/s00405-023-08091-w. Congenital middle ear anomalies (CMEA) are a very rare cause of conductive hearing loss (CHL) in children (1–2% of diagnosed middle ear hearing losses) –7. This Non-favorable hearing outcomes after surgery occur in the minority of CMEA cases and are more likely in ears with concomitant syndromal diagnoses (around 25% of CMEA patients) and in class 4 anomalies, which are oval- and/or round window anomalies with a possible abnormal course of the facial nerve . In clasThis systematic review was reported according to the PRISMA guidelines. Our protocol was registered in the National Institute for Health Research’s PROSPERO before commencing (Prospero ID: CRD42021229898) . All metThe reviewers searched PubMed/Medline, Embase and Cochrane library, most recently in July 2022. The search terms are available in the supplementary materials.Studies were selected using the in- and exclusion criteria as defined in the study protocol. Studies were included if: reporting hearing outcome on reconstructive surgery in patients with congenital absence or dysplasia of the oval or round windows, published between 1985 and July 2022 in English, French, Spanish and Dutch. Studies were excluded if surgical methods were not specified or inadequately described, if conducted on animals or cadavers, if less than 5 patients were included or if surgical results were not reported separately from results of non-class 4 CMEA patients.The reviewers independently selected articles from the search by screening titles and abstracts and analyzed the full texts of all remaining relevant articles.Assessment of risk of bias and overall study quality was performed using the National Heart, Lung and Blood institute’s Quality Assessment Tool for Before–After (Pre–Post) Studies With No Control Group –18. CritData were extracted independently by the reviewers using a preset data extraction sheet, disagreement was solved by consensus.The following data were extracted: study and patient demographics, surgical techniques, results of preoperative and postoperative audiometric testing, i.e., air conduction (AC) pure-tone average (PTA), bone conduction (BC) PTA and air–bone gap (ABG), peri- and postoperative complications, need for revision surgery and findings during revision surgery. For each study, audiometric results were made complete using two out of AC, BC and ABG reported by authors. Audiometric data were extracted in accordance to the committee of hearing and equilibrium guidelines averaging audiometric measures at 0.5, 1, 2, and 3 or 4 kHz. As stated in these guidelines, 3 and 4 kHz were equally accepted and applied accordingly to calculate the PTA .The primary outcome measures were: postoperative AC and postoperative gain in AC. Audiometric results measured at ≤ 3-month and ≥ 6-month follow-up were used as short- and long-term follow-up. Surgical success was defined by closure of the ABG to within 20 dB. Other definitions of surgical success used in the literature: postoperative AC ≤ 30dB and gain in AC ≥ 15 dB were also extracted if available.As secondary outcome measures, the incidence of the following complications was defined: postoperative sensorineural hearing loss (SNHL) due to damage to the inner ear during surgery, perilymph gusher, persistent or temporary vertigo/dizziness, postoperative facial nerve weakness, extrusion of prosthesis material and wound infection such as otitis media with or without concomitant labyrinthitis. SNHL was defined as a postoperative decline in BC ≥ 10 dB.Furthermore, data on stability of hearing results were collected. If reported, results of audiometric testing shortly after surgery (within three months) and at ≥ 6 months were compared. Studies that did not report individual but generic hearing outcome data were also included. Hearing was defined as stable if AC PTA remained within 5 dB of fluctuation from AC PTA measured at short-term follow-up. Other outcome parameters were: (1) need for revision surgery and (2) the incidence of fenestral re-obliteration (diagnosed during revision surgery or on radiologic imaging such as HR-CT).P values < 0.05 were considered as statistically significant. A meta-analysis was not performed as we expected included studies to have a low number of patients due to the rarity of the condition and a high heterogeneity in reported data. Collected data were analyzed in a descriptive manner.11 articles, making a total of 188 operated ears were included in this review. The PRISMA flow chart is displayed in Fig. Outcome of critical appraisal is displayed in Table Six studies reported hearing outcomes at ≤ 3 months postoperatively, see Table Eleven studies reported hearing outcomes at ≥ 6 months postoperatively, see Table Seidman et al., Su et al., Lambert et al., Sterkers et al. and Farrior et al. reported no postoperative change in hearing in, respectively, 7.7% (1/13) of ears, 17.9% (10/56) of ears, 33.3% (2/6) of ears, 12.5% (1/8) of ears and 6.1% (2/33) of ears.Six studies reported on the stability of postoperative hearing results. Three studies reported stable hearing results in all ears: Han et al. with a mean follow-up duration of 17.5 months and Seidman et al. and Sterkers et al. both with > 1-year follow-up duration in all ears.Farrior et al. reported complete loss of gained AC in 6% (2/33) of operated ears within 6 months after surgery and that 69% (23/33) of ears remained at < 30 dB at 2-year follow-up compared to 78.8% (26/33) ears at short-term follow-up (duration not specified). Lambert et al., reported loss of most of the gained AC in 66.7% (4/6) of operated ears during follow-up . De Alarcon et al. reported loss of gained AC in 40% (4/13 ears), with a mean AC loss of 11.6 dB at > 6 m compared to < 3 m postoperatively. Thomeer et al. reported loss of gained AC in 50% (4/8 ears), with a mean AC loss of 13.3 dB at > 6 m compared to < 3 m postoperatively.Complications are displayed in Table SNHL was reported in three articles. Thomeer et al. reported SNHL in 50% (4/8) of ears; one of these ears resulted in total hearing loss after a period of otitis media; in the other ear, BC changed from 20 dB pre-operatively to 80 dB postoperatively without a reasonable explanation; the other two ears experienced BC losses of 14 dB and 18 dB. Seidman et al. reported SNHL  in one of thirteen ears (7.7%) after revision surgery. Ito et al. reported BC loss > 10 dB in two of thirteen ears (15.4%). Re-obliteration of the oval window was discovered in 6.1% (2/33)–15.4% (2/13) of patients in three different studies. Revision surgery was performed on 16 ears reported by six different studies; findings and outcomes are available in Table In this systematic review, we reported hearing outcomes of reconstructive surgery in class 4 CMEA patients. A total of 188 ears were included across 11 different studies. Overall, the reviewed data showed promising results. Six of seven studies that reported mean gain in AC ≥ 6 months reported AC gain > 15 dB, four of six studies that reported success rates (closure of the ABG to ≤ 20 dB or AC < 30 dB) ≥ 6 months reported rates > 50%, thereby proving that fenestration surgery can greatly improve hearing in some patients.However, there also seems to be a varying percentage of ears in which hearing remains unchanged after surgery  and in which hearing loss recurs after improvement by surgery . Major permanent complications, i.e., decreased AC and SNHL reportedly occurred in eleven of 188 ears (5.9%) and SNHL specifically in seven of 188 ears (3.7%) ranging from 0 to 50%  in indivOur results negate the belief that surgery in class 4 ears should be avoided entirely, but confirm the belief that fenestration surgery in class 4 ears is less favorable than reconstructive surgery in class 1–3 ears, where success rates vary from 56 to 75% .. Unfortunately, the individual causes of complications and disappointing results could not be included in all the cases because of lack of reporting in the included studies.A recurrence of hearing loss and unchanged hearing was reported by several studies in varying percentages. Recurrent hearing loss can be caused by several factors like prosthesis displacement, adhesions in the middle ear, or re-obliteration of the artificially fenestrated area. Surgery is performed to restore the normal ossicular chain conducted acoustic hearing. However, in ears with severe anatomic variations/deformities, as is often the case in syndromal ears, the success rates might be lower . SimilarThe most feared complication, complete SNHL or ‘deaf ears’ after surgery occurred in three ears reported by two studies. Partial SNHL occurred in an additional four ears, reported by two studies. Although the incidence of complete SNHL might indeed be low, it is essential to obtain patient informed consent including considering the alternatives, i.e., hearing amplification devices (air and bone conduction hearing aids). Revision surgeries were performed revealing a myriad of different operative findings and varying postoperative results from complete SNHL to great improvement of AC thresholds. Due to disappointing long-term results , the vibrant soundbridge and regular hearing aids. Especially in children, alternative treatment modalities (hearing aids) should be considered to start treatment as soon as possible given that surgery is not recommended during the first 6–8 years of life due to the higher prevalence of recurrent otitis media. Other reasons for choosing alternative strategies are ears with an extensive history of middle ear problems (or previous surgeries) as these are at risk for disappointing results due to adhesions and overall rigidity in the ossicular chain and are renowned for their challenging surgical management.It is of importance to note that despite the mentioned risks, surgery in class 4 ears can be of great benefit to the patient by either improving hearing thresholds to functional levels or to make hearing rehabilitation using hearing aids more accessible. Our treatment strategy would be to attempt reconstructive surgery in patients with very favorable baseline parameters, i.e., non-syndromal, no middle ear history and with an accessible operating area . It is, therefore, of utmost importance to obtain a high-resolution computed tomography scanning (HR-CT) of the temporal bone before discussing surgery as an option, to be acquainted with the middle- and inner-ear anatomy for optimal preparation and surgical feasibility. During the decision-making process, patients (and their families) should be informed about the successful long-term hearing outcome rate of around 50%, based on the findings of this review, that some patients might benefit from reconstructive surgery while in other cases surgery might have to be aborted due to unfavorable anatomy and that in some cases hearing is not improved after surgery. Furthermore, patients and family should be informed about the occurrence of re-obliteration, prosthesis misplacement, need for revision surgery and that facial nerve damage or vestibular complaints might happen more frequently than in other CMEAs or in the general population needing middle ear surgery. Lastly, patients should be informed that, although rare, complete hearing loss and postoperative dizziness (vertigo), are a real risk.The following limitations should be noted: (1) the studies included were heterogenous in patient size, class of surgery conducted and duration of follow-up. Also, audiometric assessment, outcomes and reporting thereof were variable and often incomplete; (2) most of the included studies reported on small patient cohorts or case series; (3) certain important primary and secondary outcome measures reviewed here might be underreported due to vague, or lack of, reporting of individual hearing results in some of the included studies; (4) some studies only mentioned stability of results without providing the most recent hearing outcomes and (5) it was not possible to carry out a meta-analysis due to aforementioned limitations. Lastly, it should be noted that many studies aborted surgery in ears in which the facial nerve completely blocked the original oval window site; therefore, data on surgery in these kinds of ears are very limited.We used the GRADE method to assess the certainty of the evidence and strength of recommendation in this review, see Table Fenestration surgery can be an effective treatment in improving hearing in ears with aplasia or dysplasia of the oval or round window in selected cases. However, the substantial risk of recurrence of hearing loss, the possibility of unchanged hearing after surgery and the rare occurrence of total SNHL should be taken into consideration before opting for surgery.Supplementary file 1 Appendix: Table 1. Search terms (XLSX 11 KB)Below is the link to the electronic supplementary material.