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We present a case of a perilymphatic fistula (PLF) caused by Eustachian tube air inflation (ETAI) that was diagnosed using cochlin-tomoprotein (CTP) testing and successfully treated using transcanal endoscopic ear surgery to seal the inner ear window. A 77-year-old woman developed hearing loss and dizziness after undergoing ETAI at a local ear, nose, and throat clinic. Despite initial bed rest and steroid pulse therapy, the hearing did not improve, and transcanal endoscopic ear surgery was performed to repair the PLF. The CTP test confirmed the diagnosis of PLF, leading to a significant improvement in the patient's hearing and dizziness symptoms postoperatively. This case highlights the importance of considering PLF as a potential complication of ETAI and the value of CTP testing for diagnosing this condition., Competing Interests: Declaration of competing interest The authors declare no sources of financial support or conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors disclose no conflicts of interest.

A labyrinthine fistula is a severe complication of middle ear cholesteatoma that can cause profound sensorineural hearing loss and vertigo. However, there is no consensus regarding the transition to postoperative hearing. Although hearing deteriorates gradually with a delay in some cases of labyrinthine fistula, insufficient consideration has been given to this point. We examined perioperative changes in cases of middle ear cholesteatoma with labyrinthine fistulas. We retrospectively reviewed the medical records of 578 patients with middle ear cholesteatoma who underwent tympanoplasty at our hospital between 2016 and 2021. Patients with labyrinthine fistulas were selected; their perioperative bone-conduction hearing was assessed. Fistula depth was determined following the classification reported by Dornhoffer et al. The hearing was compared preoperatively, early postoperatively (3-6 months), and 1 year postoperatively. Forty-eight patients (8.3%) had labyrinthine fistulas. Regarding depth, 21 cases were type I, 14 were type IIa, 3 were type IIb, and 10 were type III. Preoperative bone-conduction hearing was significantly poor in invasion type IIb or deeper cases. Cases with type IIb or deeper fistulas, multiple fistulas, or vertigo deteriorated postoperatively. Type III cases or those with multiple fistulas deteriorated further from the early postoperative period to 1 year postoperatively. Concerning frequency, 500 and 2000 Hz showed a delayed deterioration. This is a valuable report of delayed hearing loss after surgery in patients with a labyrinthine fistula. This change is associated with the labyrinthine fistula's depth and multiple fistulas-this is important during preoperative counseling of patients undergoing surgery.

Objective: This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods., Methods: Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion., Results: Patients underwent fistula repair ( n = 8), canal occlusion ( n = 18) or obliteration procedures ( n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises., Conclusion: Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.

Purpose: Cholesteatoma on lateral semicircular canal (LSCC) fistula > 2 mm in size is likely to be unmanipulated due to the risk of sensorineural hearing loss. However, the matrix can be successfully removed without hearing loss when it is > 2 mm. The purpose of the study was to evaluate surgical experience over the past 10 years and to suggest the important factor for the hearing preservation in LSCC fistula surgeries., Methods: According to the fistula size and symptoms, 63 patients with LSCC fistula were grouped as follows: Type I (fistula < 2 mm), Type II (≥ 2 mm and < 4 mm without vertigo), Type III (≥ 2 mm and < 4 mm with vertigo), Type IV (≥ 4 mm), and Type V (any size fistula but with deafness at the initial visit). The cholesteatoma matrix was meticulously manipulated and removed by experienced surgeons., Results: Only two patients completely lost their hearing after surgery (4.5%). However, the loss was inevitable because their cholesteatomas were highly invasive and there was also facial nerve canal involvement; thus, the bony structure of the LSCC was already destroyed by the cholesteatoma. Unlike these two Type IV patients, Type I-III patients, and those with a fistula size < 4 mm, did not lose their sensorineural hearing. If the structure of the LSCC was maintained, hearing loss did not occur even if the fistula size ≥ 4 mm., Conclusions: The preservation of the labyrinthine structure is more important than the defect size of the LSCC fistula. If the structure is intact, cholesteatoma matrices lying on the defect can be safely removed, even though the size of bony defect is large., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of competing interest No relevant conflicts of interest or financial disclosures.

Purpose: To analyze the prevalence and associations of facial canal dehiscence (FCD), dural exposure, and labyrinthine fistula in chronic otitis media (COM) with and without cholesteatoma., Methods: This was a retrospective study performed in an academic medical center. Patients who received tympanoplasty with mastoidectomy for COM with and without cholesteatoma were included. The prevalence of FCD, dural exposure, and labyrinthine fistula in COM with and without cholesteatoma (mastoiditis) and their relationships were analyzed., Results: A total of 189 patients, including 107 (56.6%) females and 82 (43.4%) males, with 191 ears were included. There were 149 cases (78.0%) of cholesteatoma and 42 patients (22.0%) with mastoiditis. FCD was noted in 27.5% of patients with cholesteatoma and 9.5% of patients with mastoiditis. Dural exposure was found in 21 patients (14.1%) with cholesteatoma and 4 patients (9.5%) with mastoiditis. Eleven patients (7.4%) with cholesteatoma and 1 patient (2.4%) with mastoiditis had labyrinthine fistula. Patients with a labyrinthine fistula had nearly a fivefold greater chance (OR = 4.924, 95% CI = 1.355-17.896, p = 0.015) of having FCD than those without a fistula. There was a positive correlation between dural exposure and labyrinthine fistula (P = 0.011, Fisher's exact test)., Conclusion: FCD, dural exposure, and labyrinthine fistula are common complications in COM. These complications are more frequently observed in patients with cholesteatoma than in patients with mastoiditis. Surgeons should pay more attention to the treatment of COM., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: During surgery in patients with labyrinthine fistula the mandatory complete removal of the cholesteatoma while preserving inner ear and vestibular function is a challenge. Options so far have been either the complete removal of the cholesteatoma or leaving the matrix on the fistula. We evaluated an alternative "under water" surgical technique for complete cholesteatoma resection, in terms of preservation of postoperative inner ear and vestibular function., Methods: From 2013 to 2019, 20 patients with labyrinthine fistula due to cholesteatoma were operated. We used the canal wall down approach and removal of matrix on the fistula was done as the last step during surgery using the "under water technique". The pre and postoperative hearing tests and the vestibular function were retrospectively examined., Results: There was no significant difference between pre and post-operative bone conduction thresholds; 20% experienced an improvement of more than 10 dB, with none experiencing a postoperative worsening of sensorineural hearing loss. Among seven patients who presented with vertigo, two had transient vertigo postoperatively but eventually recovered., Conclusion: Our data show that the "under water technique" for cholesteatoma removal at the labyrinthine fistula is a viable option in the preservation of inner ear function and facilitating complete cholesteatoma removal., (© 2021. The Author(s).)

Objective: To determine the incidence and volume of pneumolabyrinth using early temporal bone computed tomography (TBCT) findings and evaluate the correlation between pneumolabyrinth and various clinical variables., Study Design: Retrospective case review., Setting: Tertiary academic center., Patients: Fifty-three consecutive adult cochlear implantation (CI) recipients (53 ears) with normal inner ears who underwent high-resolution TBCT within 3 days after CI were included., Intervention: Axial TBCT images were used for detection and measurement of pneumolabyrinth., Main Outcome Measures: Incidence and volume of pneumolabyrinth were evaluated. In addition, the following clinical variables were analyzed to evaluate the correlation with pneumolabyrinth volume: demographics, implant type, surgical approach, postoperative dizziness, and preservation of functional residual hearing., Results: Pneumolabyrinth was present in all patients, and the average volume was 8.496 mm3. Pneumolabyrinth was confined to the cochlea (pneumocochlea) in all patients except for one who also had pneumovestibule. The pneumolabyrinth volume in patients with postoperative dizziness was significantly larger than that in patients without postoperative dizziness (10.435 mm3 vs. 8.016 mm3; p = 0.029). Multivariate analysis showed that a larger volume of pneumolabyrinth was significantly associated with postoperative dizziness (odds ratio, 1.420; 95% confidence interval, 1.114-1.808; p = 0.005)., Conclusion: A certain volume of pneumolabyrinth was always present in the early stage after CI, and the volume of pneumolabyrinth measured using early TBCT findings was significantly associated with the occurrence of postoperative dizziness., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Horizontal canal fistulas are not uncommon in patients with cholesteatoma. Patients with canal wall down cavities and exposed horizontal canal fistulas develop significant dizziness with wind or suction exposure. Obliteration of mastoid cavities in patients with exposed fistulas can be challenging. We describe a patient with horizontal canal fistula and chronic dizziness from wind exposure who underwent successful mastoid cavity obliteration with preservation of hearing. Patients with horizontal canal fistulas in a canal wall down cavity can be managed with mastoid obliteration for relief of dizziness.

Background: The presence of endolymphatic hydrops (ELH) in patients with Meniere's disease (MD) is considered a pathological hallmark., Aims/objectives: We aimed to conduct a quantitative volumetric measurement of inner ear ELH in patients with unilateral MD (uMD). The values of uMD with and without herniation into the posterior semi-circular canal (h-PSC) and the lateral semi-circular canal (h-LSC) were compared using 3 D magnetic resonance imaging., Material and Methods: This study included 130 individuals (47 controls and 83 patients with uMD). We measured the total fluid space (TFS) and endolymphatic space (ELS) volumes. We also evaluated the ELS/TFS volume ratios (%)., Results: The ELS/TFS volume ratios in the inner ear, cochlea, and vestibule were significantly different between the affected and contralateral sides in patients with h-PSC. Moreover, the ELS/TFS volume ratios of the inner ear, vestibule, and semi-circular canals in the affected ear were significantly higher in patients with h-PSC than in those without h-PSC. The vestibular ELS/TFS volume ratio in the affected ear was significantly higher in patients with h-LSC than in those without h-LSC., Conclusions and Significance: H-LSC is present in extended vestibular ELH. However, this is a result of ELH progression in the inner ear.

We introduce our horrible experience of lateral semicircular canal exposure due to unintended drilling during left facial nerve decompression. Nearly half of the canal was drilled-out, however, the membranous labyrinth was preserved and the defect was covered with temporal fascia. Immediately after surgery, the patient complained of vertigo with right beating nystagmus. However, the patient could hear an audible tuning fork sound and the Weber-test showed left-sided deviation. The vertigo gradually subsided and the facial palsy was completely recovered 3 months after the surgery. One and half years later, the patient spent a normal life with normal hearing nevertheless after this terrifying episode., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We aimed at evaluating the feasibility of using MicroRNA (miR)-34a and miR-29b to detect inner ear damage in patients with mitochondrial disease (MD) and sensorineural hearing loss (SNHL). Material and Methods: Three patients with MD and SNHL and seven healthy control subjects were included in this case series. MD patients underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brain response tests to investigate the specific cochlear and retrocochlear functions; control patients underwent PTA. MiR-34a and miR-29b were extracted from blood in all subjects included in the study. The expression of miR-34a and miR-29b in MD patients and healthy controls were statistically compared, then the expression of these two miRs was compared with DPOAE values. Results: In MD patients, miR-34a was significantly up-regulated compared to healthy controls; miR-34a and DPOAEs were negatively correlated. Conversely, miR-29b was up-regulated only in the youngest patient who suffered from the mildest forms of MD and SNHL, and negatively correlated with DPOAEs. Conclusion: In MD patients, miR-34a and miR-29b might be a marker of inner ear damage and early damage, respectively. Additional studies on larger samples are necessary to confirm these preliminary results.

Pneumolabyrinth (PL) is the presence of air within the vestibule, semicircular canals, or cochlea. It represents an abnormal connection between the inner ear and middle ear spaces. PL most commonly occurs after blunt head trauma, followed by penetrating injuries. Temporal fractures may or may not accompany. Prognosis of hearing loss is poor, while prognosis of vestibular symptoms is good. Herein we present a 45-year-old female with unilateral pneumolabyrinth, who presented with significant dizziness and unilateral total hearing loss after a car accident.

Background: We evaluated the usefulness of CT and MRI for the diagnosis of perilymphatic fistula (PLF) of the round (RW) and/or oval (OW) windows, with surgery as gold standard., Methods: We retrospectively enrolled 17 patients who presented a surgically confirmed PLF of the round (RW) or oval (OW) windows. All patients were imaged by CT + MRI (T2W SSFP without contrast) prior to surgery (= gold standard). Two radiologists, analyzed the RW and OW on the side of the clinical symptoms and sensitivity (Se) + Specificity (Sp) were calculated., Results: Round window fistula was the most frequent (71%). The best sign of PLF on imaging was a fluid filling of the window niches, which had good Se (83-100% for RW, 66-83% for OW) and Sp (60% for RW, 91-100% for OW). Disorientation of the footplate and pneumolabyrinth were also only observed in 50% of OW PLF., Conclusion: The combination of CT and MRI is a reliable tool for a fast and accurate diagnosis of round and oval window perilymphatic fistula, with good sensitivity (> 80%). The most common sign of PLF on imaging is the presence of a fluid-filling in the RW (especially if > 2/3 of the RW niche) or in the OW niches on both CT and MRI. A disorientation of the footplate or the presence of a pneumolabyrinth are clearly in favor of an oval window perilymphatic fistula.

Objectives: To analyze the clinical characteristics of cochlear fistulas (CFs) and propose a new fistula classification system with regard to the cochlea., Materials and Methods: A retrospective chart review was conducted between January 2008 and December 2015 to identify patients who had undergone surgery for cholesteatoma with an associated CF. The following data were collected: preoperative symptoms, findings of temporal bone computed tomography (TBCT), fistula stage, cholesteatoma classification, surgical technique, and pre- and postoperative pure-tone audiometry., Results: We analyzed a total of 159 patients, out of which 9 (5.7%) were diagnosed with a CF. The average duration of the chronic otitis media was 19.8 years. Cholesteatomas that induced CF rarely existed in the nonaggressive state; recurrent otorrhea was observed in all but one of our subjects. All the patients with CF had a distinct origin of cholesteatoma that developed from the retraction of posterior pars tensa; further, 88.9% cholesteatomas extended to and filled the sinus tympani. Preoperative audiometry revealed total hearing loss in 4 (44.4%) patients. Further, five patients with residual hearing before surgery had stage I fistulas, and the bone conduction thresholds remained stable after surgery., Conclusion: Cochlear fistulas were often detected in patients with (1) a history of chronic otitis media (exceeding 10 years), (2) frequently recurring otorrhea, and (3) pars tensa cholesteatomas that extended to the posterior mesotympanum and filled the sinus tympani. Such patients can suffer from potentially severe and irreparable sensorineural hearing loss.

Pneumolabyrinth is the entrapment of air within the inner ear and is a rare complication of stapes surgery. We report the case of a patient submitted to stapedectomy who, 4 weeks later, suddenly developed right hearing loss, ipsilateral tinnitus and vertigo. On the physical examination, the patient showed no signs of vestibular deficits. Audiometry was compatible with right profound mixed hearing loss and high-resolution CT of the temporal bone revealed the presence of pneumolabyrinth. During exploratory tympanotomy, the prosthesis was found dislodged; the communication between the middle and inner ear was closed with vein graft and a new prosthesis was placed. Following surgery, vestibular symptoms was abolished and the patient experienced great improvement of the hearing thresholds., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A four-year-old female French bulldog was presented for evaluation of acute, left-sided peripheral vestibular syndrome. Computed tomographic (CT) examination of the head revealed the presence of air within the left cochlea and vestibule, consistent with pneumolabyrinth. This was concurrent with ipsilateral otitis media and externa. Pneumolabyrinth is an uncommon finding in humans and is most frequently due to head trauma and temporal bone fracture. This is the first report describing pneumolabyrinth in a dog, apparently of nontraumatic origin in this case., (© 2017 American College of Veterinary Radiology.)

Objectives: To assess and monitor lateral semicircular canal (LSC) function over time in patients affected by chronic otitis media with cholesteatoma (CHO) complicated by fistula of LSC (LSC-F) before and after surgery using video Head Impulse Test (vHIT)., Materials and Methods: Eight patients aged 18-67 years affected by CHO with imaging-ascertained LSC-F were included in this preliminary prospective study. The following protocol has been applied: oto-microscopic diagnosis with patient's history; computed tomography scan of the temporal bone; surgery with concomitant resurfacing of LSF-F; audiological and vestibular evaluation before surgery (T0) and at 30 days (T1), 6 months (T2), and 1 year after surgery (T3). vHIT was used to assess vestibulo-ocular reflex (VOR) in LSC., Results: None of the patients showed deterioration of bone conduction hearing levels during the different time of evaluation. Three patients showed a reduced VOR gain and catch-up saccades at T0, with VOR gain normalization at T2. This finding remained stable at the 1-year follow-up. The VOR gain in the nonaffected side generally experienced an increase, paralleled by the normalization on the affected side, with statistically significant correlation. The subjects with normal vHIT before surgery did not show any variation following surgery., Conclusion: vHIT allows the assessment of LSC function in case of fistula. The adopted surgical fistula repair did not induce deterioration of the auditory or LSC function, but indeed, it could prevent worsening and help promoting recovery to the normal function.

Objectives: The mitochondrial DNA (mtDNA) point mutation m.3243A>G is known to express the following two syndromes among others: maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Sensorineural hearing loss (SNHL) is the most frequent symptom in individuals harboring the m.3243A>G mutation. However, dysfunction of the vestibular organs has been scarcely examined. Therefore, the present study aimed to study the impact of the m.3243A>G mutation on the inner ear., Materials and Methods: A total of 8 subjects harboring the blood-verified m.3243A>G mutation underwent thorough audiological and vestibular examinations, including tone and speech audiometry, video head impulse test (vHIT), ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), and full otoneurological examination. The subjects also answered a Dizziness Handicap Inventory (DHI) questionnaire., Results: SNHL was identified in all the 8 subjects, with a mean pure-tone average-4 (PTA-4) of 59 dB. Speech discrimination score (n=7) ranged from 24% to 100% (mean 74%), and vHIT (n=42) detected pathology in nine lateral semicircular canals (SCCs), five posterior SCCs, and one anterior SCC, whereas three measurements were inconclusive. All oVEMPs (n=14 ears) were absent, nine cVEMPs were absent, and two were inconclusive. Based on the DHI scores, 6 subjects reported none to mild dizziness, 1 reported moderate, and 1 reported severe dizziness., Conclusion: Our study population had pathological findings from every audiological and vestibular end organs. The results indicated that the pathological findings originated from within the end organs themselves and not within the superior and inferior vestibular or cochlear nerve.

Inner ear anomalies diagnosed using a radiological study are detected in almost 30% of cases with congenital or prelingual-onset sensorineural hearing loss. Inner ear anomalies can be isolated or occur along with a part of a syndrome involving other systems. Although astonishing progress has been made in research aimed at revealing the genetic causes of hearing loss in the past few decades, only a few genes have been linked to inner ear anomalies. The aim of this review is to discuss the known genetic causes of inner ear anomalies. Identifying the genetic causes of inner ear anomalies is important for guiding clinical care that includes empowered reproductive decisions provided to the affected individuals. Furthermore, understanding the molecular underpinnings of the development of the inner ear in humans is important to develop novel treatment strategies for people with hearing loss.

Objective: To evaluate the association between mastoid encephalocele or cerebrospinal fluid (CSF) otorrhea and concurrent superior semicircular canal dehiscence (SSCD)., Study Design: Retrospective case-control study with chart and imaging review., Setting: University-affiliated tertiary referral center., Patients: A chart review was conducted of all patients greater than 18 years of age who had primary surgery for CSF otorrhea or encephalocele at our university-affiliated tertiary center from 2000 to 2016. Eighty-three patients matched inclusion criteria for case subjects, and 100 patients without CSF otorrhea or encephalocele were included for controls., Main Outcome Measure: High-resolution computed tomography (CT) scans were reviewed to assess superior semicircular canal roof integrity. Student's t test was used to determine significance of continuous variables. Odds ratio (OR) and χ test was used to determine the association between SSCD and concurrent mastoid encephalocele or CSF otorrhea compared with the control population., Results: The mean age of the 83 case subjects was 54 years, and 73% were women. In patients with confirmed encephalocele and CSF otorrhea, the prevalence of SSCD was 35%, which was significantly greater than controls (2%) (OR = 26.1, p < 0.001). In patients with only CSF otorrhea, 21% had concurrent SSCD (OR = 10.3, p = 0.001). In patients with SSCD, 46% had bilateral canal dehiscence., Conclusions: This is the largest study to evaluate the prevalence of SSCD in patients with concurrent mastoid encephalocele. This study showed a significant association between SSCD and the presence of both mastoid encephalocele and CSF otorrhea. This data suggests that surgeons should have a high suspicion for SSCD in patients presenting with encephalocele or CSF otorrhea.

Objective: To describe a series of patients with iatrogenic inner ear dehiscence after lateral skull base surgery and discuss treatment options., Patients: Three patients with history of recent lateral skull base surgery, symptoms consistent with inner ear dehiscence, and radiographically proven bony dehiscence on postoperative imaging., Interventions: All patients were initially managed conservatively with serial outpatient visits. Two patients with large cochlear and vestibular dehiscences had round window reinforcement procedures. One patient had transmastoid resurfacing for repair of an iatrogenic posterior semicircular canal dehiscence., Main Outcome Measures: Anatomical location of dehiscences; treatment options; subjective auditory and vestibular symptoms pre-dehiscence, post-dehiscence and after dehiscence repair; pre- and post-audiogram when available., Results: Patient ages were 46, 52, and 60 with two of three being women. None of the patients had subjective auditory or vestibular symptoms of inner ear dehiscence before initial skull base surgery, but they all had development of these symptoms afterwards. All patients were initially managed conservatively, but all ultimately required a surgical procedure. The two patients who elected for round window reinforcements, and the one patient who required transmastoid resurfacing, had significant improvement of symptoms., Conclusions: Iatrogenic inner ear dehiscence after skull base surgery is best dealt with and repaired intraoperatively. Should intraoperative repair not be possible, transcanal round window reinforcement is a minimally invasive option for medial otic capsule dehiscence, although long-term outcomes are unclear. For lateral otic capsule dehiscence, a transmastoid approach is recommended., Level of Evidence: IV.

Objective: To analyze surgical results on hearing and vestibular symptoms in patients with barotraumatic perilymphatic fistula (PLF) according to diagnostic criteria., Methods: A total of 39 patients (41 ears) who underwent surgery on suspicion of barotraumatic PLF from January 2005 to December 2017 were included. Pure tone audiometry and videonystagmography (VNG) recording for spontaneous nystagmus and positional tests were performed preoperatively and postoperatively at 1 week and 1 month. Surgical outcomes were analyzed based on hearing results, subjective dizziness, and change of nystagmus., Results: Preoperative hearing level was 75.5 ± 28.7 dB for definite PLF and 88.5 ± 22.8 dB for probable PLF, and levels were not significantly different between groups. Preoperatively, subjective dizziness was present in 18 (94.7%) and 19 (95%) in each group. Among 39 patients, 24 had VNG recordings. Positional nystagmus was recorded in 87.5% (7/8) and 87.5% (14/16) of the definite and probable PLF groups, respectively. Postoperatively, hearing was improved in 65% (13/20 ears) of definite PLF and 61.9% (13/21 ears) of probable PLF. There was no significant difference between the two groups. Hearing gain was significantly correlated with the time interval between symptom onset and surgical timing. Subjective dizziness was improved immediately after surgical repair in 97.4% (17/18) of definite PLF patients and 100% (19/19) of probable PLF patients. Even though dizziness was improved in most patients, some had persistent positional nystagmus and recurrent dizziness., Conclusions: Surgical sealing of both windows in suspected barotraumatic PLF is an effective treatment to improve hearing and subjective dizziness.

Introduction: Labyrinthine fistula is one of the most common complications associated with cholesteatoma. It represents an erosive loss of the endochondral bone overlying the labyrinth. Reasons for cholesteatoma-induced labyrinthine fistula are still poorly understood., Objective: Evaluate patients with cholesteatoma, in order to identify possible risk factors or clinical findings associated with labyrinthine fistula. Secondary objectives were to determine the prevalence of labyrinthine fistula in the study cohort, to analyze the role of computed tomography and to describe the hearing results after surgery., Methods: This retrospective cohort study included patients with an acquired middle ear cholesteatoma in at least one ear with no prior surgery, who underwent audiometry and tomographic examination of the ears or surgery at our institution. Hearing results after surgery were analyzed according to the labyrinthine fistula classification and the employed technique., Results: We analyzed a total of 333 patients, of which 9 (2.7%) had labyrinthine fistula in the lateral semicircular canal. In 8 patients, the fistula was first identified on image studies and confirmed at surgery. In patients with posterior epitympanic and two-route cholesteatomas, the prevalence was 5.0%; and in cases with remaining cholesteatoma growth patterns, the prevalence was 0.6% (p=0.16). In addition, the prevalence ratio for labyrinthine fistula between patients with and without vertigo was 2.1. Of patients without sensorineural hearing loss before surgery, 80.0% remained with the same bone conduction thresholds, whereas 20.0% progressed to profound hearing loss. Of patients with sensorineural hearing loss before surgery, 33.33% remained with the same hearing impairment, whereas 33.33% showed improvement of the bone conduction thresholds' Pure Tone Average., Conclusion: Labyrinthine fistula must be ruled out prior to ear surgery, particularly in cases of posterior epitympanic or two-route cholesteatoma. Computed tomography is a good diagnostic modality for lateral semicircular canal fistula. Sensorineural hearing loss can occur post-surgically, even in previously unaffected patients despite the technique employed., (Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Post-traumatic pneumolabyrinth is an uncommon clinical entity, particularly in the absence of temporal bone fracture. We report the case of a patient who presented to our emergency department with a headache, sudden left hearing loss and severe dizziness which began after a traumatic brain injury 3 days earlier. On examination, the patient presented signs of left vestibulopathy, left sensorineural hearing loss and positive fistula test, normal otoscopy and without focal neurological signs. The audiometry confirmed profound left sensorineural hearing loss. Cranial CT revealed a right occipital bone fracture and left frontal subdural haematoma, without signs of temporal bone fracture. Temporal bone high-resolution CT scan revealed left pneumolabyrinth affecting the vestibule and cochlea. Exploratory tympanotomy revealed perilymphatic fistula at the location of the round window. The sealing of defect was performed using lobule fat and fibrin glue. He presented complete resolution of the vestibular complaints, though the hearing thresholds remained stable., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To measure the outcomes of laser treatment of cholesteatoma covering cochlear and vestibular fistulas., Methods: Cholesteatoma matrix over the fistula was denatured; the power density was sufficient only to gradually heat, but not vaporise, the keratin-forming matrix. The denaturing speed was controlled so that the integrity of the fistula cover was maintained. The change in bone conduction threshold and the residual rate of cholesteatoma at the fistula were measured., Results: Thirty-six fistulas were assessed. There were seven cochlear fistulas. All were 5 mm or less in maximum length. For the entire group, the average change in bone conduction threshold was -0.3 dB. For cochlear fistulas, the average change in bone conduction was + 0.2 dB. The distribution of hearing results for the entire group was Gaussian; the apparent changes in hearing could be attributed to errors associated with testing. All patients underwent second-stage surgery. In all cases, the cholesteatoma was completely cleared from the fistula site. There were no facial palsies., Conclusion: Laser denaturing of cholesteatoma matrix over fistulas measuring 5 mm or less of vestibular apparatus and the cochlea is effective at eliminating cholesteatoma, and is not associated with cochlear hearing loss or facial palsy.

The present case was a 38-year-old male who presented with progressive hearing loss, resulting in profound bilateral hearing loss. He had a past history of childhood medulloblastoma, which was treated with posterior fossa craniotomy and radiotherapy. A ventriculoperitoneal (VP) shunt was put in place to manage the hydrocephalus. Cochlear implantation (CI) was carried out on his right ear by a standard procedure. At CI activation, the electric impedance of the electrode was very high, and computed tomography revealed that there was no area of liquid density, suggesting depletion of the perilymph in the cochlea and vestibule. Eight months later, the impedance improved gradually, and the cochlea was filled with perilymph. Consequently, one of the causes of the pneumolabyrinth in the present case was that a scarred stenotic cochlear canaliculus secondary to surgery or radiation therapy might have prevented the CSF from filling the scala. In addition, it is also possible that the VP shunt might have altered the CSF pressure, leading to depletion of the perilymph., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: To demonstrate imaging of labyrinthine fistula due to cholesteatoma and illustrate outcome following repair with bone pate., Study Design: Retrospective review., Methods: Patients with labyrinthine fistula due to cholesteatoma were identified, and pre- and postoperative imaging was assessed. Method of repair was recorded. The fistula site was examined for patency and bone density after repair., Results: Twenty-nine fistulae were seen in a cohort of 375 cholesteatoma cases (8%). Preoperative computed tomography (CT) imaging for fistula detection showed sensitivity of 96% and specificity of 90%. The lateral semicircular canal was the most common site of dehiscence occurring in all cases. Facial nerve dehiscence is observed in 91% of fistula cases and stapes erosion in 69%. Severe hearing loss was present preoperatively in four (14%) cases. Bone pate was used to repair the fistula with CT-documented restoration of the otic capsule in 11/13 cases with postoperative imaging. When bone pate was not used, the otic capsule defect persisted., Conclusions: Spontaneous repair of the otic capsule following treatment of cholesteatoma is expected to be an uncommon occurrence. Repair of the fistula with bone can result in long-lasting restoration of the otic capsule., Level of Evidence: 4. Laryngoscope, 128:1643-1648, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

An elderly male patient diagnosed with a right-sided cystic vestibular schwannoma (CVS) at our center underwent a translabyrinthine approach with a subtotal excision to preserve the facial nerve (FN). The tumor grew slowly for the first 9 years but in the subsequent 2 years grew rapidly, with the patient developing a FN paralysis. Using the previous approach, a second surgery was done and the tumor was excised, leaving behind a sheath of tumor on the facial and lower cranial nerves. This case demonstrates that CVSs show unpredictable growth patterns and need to be followed up for a longer period of time. Laryngoscope, 128:1649-1652, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: A distinct subgroup of patients, presenting with apparently spontaneous onset of vertigo, is described., Results: Although vestibular evaluation revealed caloric weakness, the proximate cause of vertigo was not labyrinthine dysfunction, but rather the loss of vestibular compensation for an older and previously compensated labyrinthine injury., Conclusion: Instead of addressing the vestibular weakness, effective management needs to focus on the condition that has caused the loss of compensation.

Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid (perilymph)-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces. PLF is located in the round or oval window, fractured bony labyrinth, microfissures, anomalous footplate, and can occur after head trauma or barotrauma, chronic inflammation, or in otic capsule dehiscence. This clinical entity was initially proposed more than a century ago, yet it has remained a topic of controversy for more than 50 years. The difficulty of making a definitive diagnosis of PLF has caused a long-standing debate regarding its prevalence, natural history, management and even its very existence. In this present study, we will discuss the symptoms, physiological tests (focusing on vestibular assessment) and imaging studies. Referring to a previous criticism, we will share our classification of PLF into 4 categories. Furthermore, we will summarize a nationwide survey using a novel and widely used biomarker (Cochlin-tomoprotein [CTP]) for PLF diagnosis in Japan and present the results of the new diagnostic criteria. PLF is surgically correctable by sealing the fistula, and appropriate recognition and treatment of PLF can improve hearing and balance, and in turn, improve the quality of life of afflicted patients. Therefore, PLF is an especially important treatable disease for otologists., (© 2018 S. Karger AG, Basel.)

The objective of the study was to evaluate postoperative hearing and disease control after cholesteatoma surgery for labyrinthine fistulas. In a retrospective cohort study, we evaluated a consecutive cohort comprising 44 patients (45 ears) with labyrinthine fistulas associated with chronic otitis media with cholesteatoma who underwent surgery between 2002 and 2015. We looked at patient characteristics, pre- and postoperative bone conduction thresholds (BCT), operative approach and findings, extent of disease and the occurrence of residual disease. All deaf ears (24%) presented preoperatively with a large fistula. Opening the membranous labyrinth resulted in significantly worse postoperative BCT (p = 0.01). Neither the present study nor a literature search revealed a significant positive effect of corticosteroids on postoperative hearing preservation. Large fistulas were correlated with poorer preoperative BCTs, but not with poorer postoperative BCTs. Opening the membranous labyrinth during surgery is correlated with poorer postoperative BCTs and can be seen as a predictive parameter. The use of corticosteroids in the perioperative management of labyrinthine fistula was not found to result in any improvement in postoperative BCTs.

Pneumolabyrinth has been considered an indicator of otic capsule involvement in temporal bone fractures. We present a novel theory for the etiology of pneumolabyrinth in a trauma patient without an otic capsule fracture: passage of intrathecal air into the labyrinth. Our patient experienced transient bilateral pneumolabyrinth after head trauma due to a motor vehicle collision. The patient was noted to have extensive pneumocephalus and a unilateral temporal bone fracture that spared the otic capsule. Initial computed tomography (CT) scans demonstrated air in the cochlea and both internal auditory canals. A high-resolution CT scan 6 hours later showed resolution of this air. Pneumolabyrinth may not be a sensitive indicator of otic capsule involvement in temporal bone fractures. In addition to middle ear sources, air in the labyrinth can also plausibly originate intrathecally, especially in the setting of pneumocephalus.

Objective: To determine signs and symptoms for superior canal dehiscence syndrome caused by the superior petrosal sinus., Methods: A review of the English-language literature on PubMed and Embase databases was conducted, in addition to a multi-centre case series report., Results: The most common symptoms of 17 patients with superior petrosal sinus related superior canal dehiscence syndrome were: hearing loss (53 per cent), aural fullness (47 per cent), pulsatile tinnitus (41 per cent) and pressure-induced vertigo (41 per cent). The diagnosis was made by demonstration of the characteristic bony groove of the superior petrosal sinus and the 'cookie bite' out of the superior semicircular canal on computed tomography imaging., Conclusion: Pulsatile tinnitus, hearing loss, aural fullness and pressure-induced vertigo are the most common symptoms in superior petrosal sinus related superior canal dehiscence syndrome. Compared to superior canal dehiscence syndrome caused by the more common apical location of the dehiscence, pulsatile tinnitus and exercise-induced vertigo are more frequent, while sound-induced vertigo and autophony are less frequent. There is, however, considerable overlap between the two subtypes. The distinction cannot as yet be made on clinical signs and symptoms alone, and requires careful analysis of computed tomography imaging.

The comorbidities related to obesity are already extensive, but as the prevalence of obesity increases globally, so do the number of its associated conditions. The relationship between hearing impairment and obesity is a relatively recent research interest, but is significant as both conditions have the ability to substantially reduce an individual's quality of life both physically and psychologically. Obesity has a significant effect on vascular function, and this may have an impact on highly vascular organs such as the auditory system. This review aims to provide an overview of the existing literature surrounding the association between hearing loss and obesity, in order to emphasise these two highly prevalent conditions, and to identify areas of further investigation. Our literature search identified a total of 298 articles with 11 articles of relevance to the review. The existing literature in this area is sparse, with interest ranging from obesity and its links to age-related hearing impairment (ARHI) and sudden sensorineural hearing loss (SSNHL), to animal models and genetic syndromes that incorporate both disorders. A key hypothesis for the underlying mechanism for the relationship between obesity and hearing loss is that of vasoconstriction in the inner ear, whereby strain on the capillary walls due to excess adipose tissue causes damage to the delicate inner ear system. The identified articles in this review have not established a causal relationship between obesity and hearing impairment. Further research is required to examine the emerging association between obesity and hearing impairment, and identify its potential underlying mechanisms.

Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., for delivery of glucocorticosteroids, antiapoptotic substances, or neurotrophins to the inner ear. The performance of cochlear implants may thus be improved by protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can also be achieved by use of a biocompatible, resorbable controlled-release drug-delivery system. Two case reports for intracochlear controlled release drug delivery in combination with cochlear implants are presented. In order to treat progressive reduction in speech discrimination and increased impedance, two cochlear implant patients successfully underwent intracochlear placement of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using a computer model. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies., Competing Interests: Compliance with ethical guidelinesConflict of interestS.K. Plontke, G. Götze, T. Rahne, and A. Liebau declare that they have no competing interests.All patients were informed about the off-label use of the controlled-release drug-delivery system and signed an informed consent form.

Introduction: Pneumolabyrinth is defined as the presence of air within the inner ear causing cochleovestibular signs and symptoms. Twenty-seven cases of pneumolabyrinth are published in the literature of which only two were described as delayed pneumolabyrinth as a complication of stapes surgery., Case Report: A 45-year-old male patient presented with vertigo after Valsalva maneuver 12 years after stapedectomy. He was diagnosed with delayed pneumolabyrinth on high resolution computed tomography and underwent an exploratory tympanotomy with surgical repair., Discussion: Delayed pneumolabyrinth is a rare complication of stapes surgery and should be considered in patients presenting with vestibulocochlear symptoms even many years later. An exploratory tympanotomy is recommended for patients diagnosed with pneumolabyrinth and having a sensorineural hearing loss and/or persistent vertigo., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: The aim of this work was to describe acoustic neuromas as the first signs of inner ear functional disorders., Material and Methods: The study covered 3,456 audiological and otoneurological patients, who were treated in the Department of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics Military Medical Academy University Teaching Hospital in Lodz within the period of 2011-2016. Among the studied subjects, an acoustic neuroma on the vestibulocochlear nerve was diagnosed in 13 cases (5,16%), including 9 women and 4 men. Each patient underwent a medical interview and an objective examination with static and dynamic tests, pure tone audiometry and speech audiometry tests, impedance audiometry tests, characteristics of tinnitus, videonystagmography and auditory brainstem evoked potentials (ABR) in crack. In each case of an incorrect ABR recording, contrast-enhanced MRI was performed., Study Results: The conducted tests showed an incorrect ABR recording in 252 patients (7,29%, including 54,37% women and 45,63% men). In the performed contrast-enhanced MRI, 13 patients (5,16%), including 3,57% women and 1,59% men, had an image typical to neuroma of the vestibulocochlear nerve. Each one of the studied patients showed signs and symptoms typical to an acoustic neuroma such as hypoacusia and balance disorders, tinnitus in 12 subjects, headaches in the temporal and occipital area in 4 subjects, trigeminal neuralgia symptoms in 2 subjects and vision problems like scotoma and blurred vision reported by 1 patient., Conclusion: Each case of sensorineural hearing loss, particularly unilateral sensorineural hearing loss, requires expanded hearing tests and auditory brainstem evoked potentials tests. An incorrect brainstem evoked potentials recording such as: an elongated latency of the 5th wave, an elongated interlatency of 1-2-3 and 1-2-3-4 waves, requires a contract-enhanced magnetic resonance imaging to diagnose cerebellopontine angle tumours.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease with unknown etiology. Although sacroiliac joint involvement is the classic sign along with the formed immune mediators, it may result in immune-mediated inner ear disease and may cause damage to the audiovestibular system. Vestibular evoked myogenic potentials (VEMP) is a clinical reflex test used in the diagnosis of vestibular diseases and is performed by recording and evaluating the muscle potentials resulting from the stimulation of the vestibular system with different stimuli. The aim of this study is to evaluate the cervical VEMP test results in AS patients without vestibular symptoms. Thirty-three patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. VEMP wave latency, P13-N23 wave amplitude, and VEMP asymmetry ratio (VAR) values were compared between the groups. The relationship between clinical and laboratory findings of the AS patients and VEMP data were also investigated. Compared with healthy people, this study shows the response rate of patients with ankylosing spondylitis was reduced in the VEMP test, and P13-N23 wave amplitude showed a decrease in AS patients who had VEMP response (p < 0.001). There was no correlation between the clinical and laboratory findings and VEMP findings in patients with ankylosing spondylitis. The data obtained from this study suggest that AS may lead to decreased sensitivity of the vestibular system.

The objective of this retrospective study was to present the authors' experience on the management of labyrinthine fistula secondary to cholesteatoma. 695 patients, who underwent tympanoplasty for cholesteatoma, in a University Hospital between 1993 and 2013 were reviewed, to select only those with labyrinthine fistulas. 42 patients (6%) had cholesteatoma complicated by fistula of the lateral semicircular canal (LSCC). The following data points were collected: symptoms, pre- and postoperative clinical signs, surgeon, CT scan diagnosis, fistula type, surgical technique, preoperative vestibular function and audiometric outcomes. Most frequent symptoms were unspecific, such as otorrhea, hearing loss and dizziness. However, preoperative high-resolution computed tomography predicted fistula in 88 %. Using the Dornhoffer and Milewski classification, 16 cases (38 %) were identified as stage 1, 22 (52 %) as stage II, and 4 (10 %) as stage III. The choice between open or closed surgical procedure was independent of the type of fistulae. The cholesteatoma matrix was completely removed from the fistula and immediately covered by autogenous material. In eight patients (19 %), the canal was drilled with a diamond burr before sealing with autologous tissue. After surgery, hearing was preserved or improved in 76 % of the patients. There was no statistically significant relationship between the extent of the labyrinthine fistula and the hearing outcome. In conclusion, a complete and nontraumatic removal of the matrix cholesteatoma over the fistula in a one-staged procedure and its sealing with bone dust and fascia temporalis, with sometimes exclusion of the LSCC, is a safe and effective procedure to treat labyrinthine fistula.

Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Introduction: Recreational technical diving, including the use of helium-based mixes (trimix) and the experimentation of new decompression algorithms, has become increasingly popular. Inner-ear decompression sickness (DCS) can occur as an isolated clinical entity or as part of a multi-organ presentation in this population. Physiological characteristics of the inner ear make it selectively vulnerable to DCS. The inner ear has a slower gas washout than the brain thus potentially making it more vulnerable to deleterious effects of any bubbles that cross a persistent foramen ovale (PFO) and enter the basilar artery, whilst the inner ear remains supersaturated but the brain does not., Methods: A questionnaire was made widely available to divers to analyse the incidence of inner-ear DCS after technical dives. One-hundred-and-twenty-six divers submitted completed questionnaires, and we studied each incident in detail., Results: Nine (7.1%) of the 126 responders reported to have had at least one episode of inner-ear DCS, of which seven occurred without having omitted planned decompression stops. Of these seven, four suffered from DCS affecting just the inner ear, while three also had skin, joint and bladder involvement. Five of the nine divers affected were found to have a PFO. All affected divers suffered from vestibular symptoms, while two also reported cochlear symptoms. Three divers reported to have balance problems long after the accident., Conclusions: This small study is consistent with a high prevalence of PFO among divers suffering inner-ear DCS after trimix dives, and the pathophysiological characteristics of the inner ear could contribute to this pathology, as described previously. After an episode of DCS, vestibular and cochlear injury should always be examined for.

Objective: Embolization of cranial dural sinus arteriovenous fistulae with transvenous occlusion of the involved sinuses is an established strategy when the collateral brain drainage allows it. We aimed to investigate the frequency and types of complications after endovascular occlusion of the sigmoid sinus., Methods: From our database, we detected 52 endovascularly treated consecutive cases of cranial dural arteriovenous shunts involving the sigmoid sinus. The cases treated through the transvenous approach alone or combined with the transarterial one were analyzed retrospectively. Previously reported series and cases were reviewed and critically analyzed., Results: In 15 cases, a transvenous approach was used and in 4 combined a transvenous approach with a transarterial approach. Two patients (13.3%) both treated with the transvenous approach alone presented postoperatively with vertigo and hearing loss. In the first case, the sinus occlusion involved the whole sigmoid sinus, whereas in the second case the occlusion was restricted to a parallel channel posteriorly to the proximal segment of the sigmoid sinus. Magnetic resonance imaging and ear, nose, and throat investigations failed to elucidate the cause and pathomechanism of these symptoms. No other complications occurred., Conclusions: Although the transvenous occlusion of the sigmoid sinus generally is a safe therapeutic option for the treatment of dural arteriovenous fistulae, inner ear dysfunction is still a possible complication. The combined analysis of the reported and our cases did not allow a plausible explanation of this complication and its pathomechanism remains obscure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pneumolabyrinth is a rare condition with air bubbles existing in the vestibule and/or cochlea. We report a case of pneumolabyrinth without trauma that was suspected to be caused by labyrinthitis. A 65-year-old man presented with vertigo and hearing loss in the left ear after catching a cold. Computed tomography performed after there had been no improvement in the patient's symptoms showed the presence of air bubbles in the vestibule, semicircular canals and cochlea. The patient was transferred to our hospital with suspected perilymphatic fistula. Bacterial infection was suspected after the laboratory tests had indicated a severe inflammatory response, and the patient was treated with antibiotics. However, no bacteria were detected in a bacterial culture of the otorrhea. An exploratory tympanotomy was performed to improve the patient's staggering gait and to examine the middle ear, with no obvious fistula being observed. Subsequent fenestration of the round window revealed a white mass that appeared to contain bacteria which was collected from the cochlea and submitted for analysis and bacterial culture. However, no bacteria were detected and the mass contained white blood cells. We suspected pneumolabyrinth following labyrinth infection. However, the cause of air bubble formation remains unclear and needs to be validated with further research., (© 2016 S. Karger AG, Basel.)