Delayed Facial Nerve Dysfunction Following CyberKnife® Radiosurgery for Vestibular Schwannoma.

OBJECTIVE: The incidence and risk factors for facial nerve dysfunction (FND) following CyberKnife® therapy for vestibular schwannoma (VS) remain poorly understood. This study investigates whether differential radiation doses to vulnerable segments of the facial nerve may be associated with FND outcomes. METHODS: Patients were identified who underwent CyberKnife® radiosurgery for VS at a single institution. Basic demographics, tumor characteristics, and facial nerve function were collected. Total radiation doses to tumor, internal auditory canal (IAC), and labyrinthine segment of facial nerve (LSFN) were evaluated. RESULTS: Six out of 64 patients experienced FND following CyberKnife® treatment for VS (9.38%, 6/64). Patients with FND were compared to those without FND (control). Of the 64 patients, complete radiation records were obtained for 30 patients (6 FND vs. 24 control). There were no significant differences in demographic or tumor characteristics between control and FND cohorts. More severe FND (HB ≥ 4) had significantly larger tumors (3.74 vs. 1.27 cm3, p = 0.037) with directionally decreased time to FND (3.50 vs. 33.5 months, p = 0.106) than patients with HB < 4, respectively. There were directionally, nonsignificant differences between maximum radiation doses to the LSFN (2492.4 vs. 2557.0 cGy, p = 0.121) and IAC (2877.3 vs. 2895.5 cGy, p = 0.824) between the control and FND cohorts, respectively. CONCLUSIONS: FND may represent an underrecognized sequelae of CyberKnife® radiosurgery for VS that can occur many months following treatment. Further studies are needed to elucidate the effect of differential radiation exposure to the facial nerve with FND following treatment. LEVEL OF EVIDENCE: III (Retrospective Cohort Study) Laryngoscope, 2024.

Variability in Perioperative Steroid Therapy Regimen for Cochlear Implantation as It Relates to Hearing Preservation.

HYPOTHESIS: We aimed to identify practice trends and association between physician training and administration of perioperative steroids for cochlear implantation (CI) as it relates to hearing preservation. BACKGROUND: Perioperative steroid therapy regimens are postulated to protect residual hearing and improve hearing preservation outcomes in CI. METHODS: A 27-question online survey was developed by the senior authors using the Qualtrics Survey Tool, then distributed via email from September to November 2022 to otolaryngologists specializing in otology or neurotology and who practice in the United States or Canada. RESULTS: The survey was sent to 463 physicians, 162 (35.0%) of whom completed the survey. One hundred forty-four (31.1%) responses underwent analysis. All physicians administering preoperative steroids (n = 31) prefer preoperative oral prednisone. Of 143 physicians administering intraoperative steroids, 54.5% prefer intraoperative intravenous dexamethasone. More than half (77.6%) of 85 physicians administering postoperative steroids prefer postoperative oral prednisone. Postoperative steroid administration (p < 0.006) and taper utilization (p < 0.041) were greater among physicians who complete greater than 40 CIs annually (n = 47 [71.2%]; n = 30 [49.2%]) than physicians who complete up to 40 CIs annually (n = 37 [48.7%]; n = 20 [31.3%]), respectively. Physicians practicing for 5 to 20 years after residency are more prevalent in using postoperative steroid tapers than physicians practicing for fewer than 5 years after and more than 20 years after residency (n = 37 [51.4%] versus n = 14 [25.5%], p < 0.001). CONCLUSION: Consensus is needed about the optimal steroid treatment for CI patients. LEVEL OF EVIDENCE: 4.

A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.

BACKGROUNDWarts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined.METHODSIn this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF (G-CSF, the standard of care for severe congenital neutropenia). The treatment order was randomized for each patient.RESULTSPlerixafor was nonsuperior to G-CSF for TISS (P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/µL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/µL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events.CONCLUSIONPlerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome.TRIAL REGISTRATIONClinicaltrials.gov NCT02231879.FUNDINGThis study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Patulous Eustachian Tube Dysfunction Symptoms Following Balloon Dilation.

OBJECTIVE: Clinicians increasingly perform balloon dilation of the Eustachian tube (BDET) to treat obstructive Eustachian tube dysfunction (OETD) refractory to medical management. Reported complications have been limited and include patulous Eustachian tube dysfunction (PETD). This multicenter study investigates the incidence of PETD and associated factors. METHODS: Consecutive patients at three academic centers undergoing BDET (January 2014-November 2019) for OETD refractory to medical therapy were included. PETD was diagnosed by patient-reported symptoms of autophony of voice and/or breathing. Associated factors studied include age, sex, comorbidities, balloon size, duration of inflation, repeat BDET, and adjunctive procedures. RESULTS: BDET procedures (n = 295 Eustachian tubes) were performed on 182 patients. Mean age was 38.4 years (SD 21.0; range 7-78) and 41.2% were female. Twenty cases of PETD (6.8% of procedures; 9.3% of patients) occurred following BDET. Risk of PETD did not vary by institution, comorbidities, or adjunctive procedure. Age ≤18 years (adjusted risk ratio [RR] = 3.26; 95% confidence interval [CI]: 1.24, 8.54; p = 0.02), repeat BDET (RR = 3.26; 95% CI: 2.15, 4.96; p < 0.001), and severe preoperative Eustachian tube inflammation (RR = 2.83; 95% CI: 1.10, 7.28; p = 0.03) were associated with increased risk of developing PETD in the multivariable model. Most symptoms were reported as mild or intermittent. CONCLUSION: BDET caused PETD symptoms in approximately 7% of dilated Eustachian tubes in this study with increased risk for younger patients and those with severe inflammation or undergoing repeat dilations. Although most cases were self-limited, symptoms can persist. Awareness of risk factors may aid clinicians in limiting this complication. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3152-3157, 2023.

Citations and Author Characteristics in Open-Access and Subscription-Based Otolaryngology Journals.

OBJECTIVE: To describe the academic impact and author characteristics of open-access journals in otolaryngology. METHODS: Original articles from three open-access (OTO Open, Laryngoscope Investigative Otolaryngology, and World Journal of Otorhinolaryngology) and three conventional subscription-based otolaryngology specific journals (Otolaryngology - Head & Neck Surgery, The Laryngoscope, JAMA Otolaryngology - Head & Neck Surgery) were assessed. Publication dates of articles from January 2017 to July 2020 were included. Google Scholar and Web of Science citation counts were recorded. H-indexes of first and last authors were included according to Google Scholar and Web of Science and analyzed. RESULTS: This analysis included 3284 articles. Articles published in open-access otolaryngology-specific journals had significantly fewer citations on average (6.8) than articles published in subscription-based journals (12.4, p < 0.0001). The last authors of articles published in subscription-based journals had significantly higher h-indexes (23.50) compared with the last authors of articles published in open-access journals (19.53, p < 0.0001). The first authors of articles published in open-access journals had similar h-indexes (10.26) as the first authors of articles published in subscription-based journals (10.33). CONCLUSIONS: Articles published in open-access journals in otolaryngology were cited significantly less than those published in subscription-based journals. The h-index of the last authors was significantly lower in open-access journals; however, the h-index of the first authors was similar between open-access and subscription-based journals. As measured by citations, open-access publications do not yet appear to have the impact of subscription-based publications. LEVEL OF EVIDENCE: NA Laryngoscope, 133:79-82, 2023.

Reliability of Home Sleep Apnea Testing for Diagnosing Obstructive Sleep Apnea in Patients With Spontaneous Cerebrospinal Fluid Leaks.

STUDY OBJECTIVES:  To establish the prevalence of obstructive sleep apnea (OSA) in patients with spontaneous cerebrospinal fluid (sCSF) leaks and demonstrate the reliability of home sleep apnea testing (HSAT) to screen for OSA in this population. METHODS: A literature review was performed to assess data on OSA prevalence in sCSF leaks. An institutional retrospective review was performed of 20 patients with sCSF leaks who met inclusion criteria. Patients without prior sleep studies were prospectively administered sleep studies, either HSAT or polysomnogram (PSG). RESULTS: Twenty patients met the inclusion criteria. Two patients had prior sleep studies while 18 patients obtained prospective sleep studies following diagnosis and prior to management of sCSF leaks. Nineteen patients (95%) had evidence of mild or greater OSA. CONCLUSIONS:  This study re-demonstrates the high prevalence of OSA in patients with sCSF leaks, consistent with current literature, and investigates the reliability of HSAT for diagnosis of OSA in this population.

Review of Speech Outcomes in Cochlear Implant Recipients at a Nascent Cochlear Implant Program.

INTRODUCTION: The use of cochlear implantation to rehabilitate moderate to profound sensorineural hearing loss has become more widespread; however, the adult utilization rate of cochlear implant candidates is still very less. The study aims to examine the percentage of adult patients in a heterogeneous group of cochlear implant recipients at a nascent cochlear implant program who demonstrate improvements in speech outcomes. METHODS: Speech outcome scores were assessed preoperatively and postoperatively at three, six, and 12-month intervals using consonant-nucleus-consonant (CNC) words and AzBio sentences in quiet. Mean speech outcome scores at each time point and binomial distribution tables with 95% CI were used to assess individual improvement in speech understanding. RESULTS: 45 patients underwent a total of 49 cochlear implantation surgeries. The mean age at surgery was 62 years. The mean preoperative CNC score in the ear to be implanted was 18%±18, while the mean postoperative CNC score at three, six, and 12 months was 35%±21, 44%±23, and 45%±25, respectively. The mean preoperative AzBio score in the ear to be implanted was 22%±26 while the mean postoperative AzBio score at three, six, and 12 months was 50%±29, 56%±27, and 63%±26, respectively. Of the implantations, 74% (32 of 43) and 69% (22 of 32) showed significant improvement at six months or one year using AzBio and CNC binomial distribution tables, respectively. CONCLUSIONS: Findings demonstrate significant improvements in speech perception following cochlear implantation for patients not benefiting from hearing aid aural rehabilitation. The study provides realistic expectations for new and emerging programs hoping to demonstrate cochlear implant utility for improving patients' speech outcomes.

Multimodal Atlas of the Murine Inner Ear: From Embryo to Adult.

The inner ear is a complex organ housed within the petrous bone of the skull. Its intimate relationship with the brain enables the transmission of auditory and vestibular signals via cranial nerves. Development of this structure from neural crest begins in utero and continues into early adulthood. However, the anatomy of the murine inner ear has only been well-characterized from early embryogenesis to post-natal day 6. Inner ear and skull base development continue into the post-natal period in mice and early adulthood in humans. Traditional methods used to evaluate the inner ear in animal models, such as histologic sectioning or paint-fill and corrosion, cannot visualize this complex anatomy in situ. Further, as the petrous bone ossifies in the postnatal period, these traditional techniques become increasingly difficult. Advances in modern imaging, including high resolution Micro-CT and MRI, now allow for 3D visualization of the in situ anatomy of organs such as the inner ear. Here, we present a longitudinal atlas of the murine inner ear using high resolution ex vivo Micro-CT and MRI.

Study of comparative surgical exposure to the petroclival region using patient-specific, petroclival meningioma virtual reality models.

OBJECTIVE: Despite advancement of surgical techniques, the attachments of petroclival meningiomas near the central clival depression (CCD) remain difficult to visualize. With existing methods, the amount of tumor near the CCD that is inaccessible through various approaches cannot be compared. Tumors distort the brainstem, changing the size of the operative corridor for some but not all approaches; therefore, using cadavers with normal posterior fossae makes it impossible to compare different approaches to the tumor. The authors used virtual reality (VR) models created from the imaging data of patients to compare various surgical approaches that have otherwise been incomparable in previous studies. METHODS: CT and MRI data obtained in 15 patients with petroclival meningiomas were used to create anatomically accurate 3D VR models. For each model, various surgical approaches were performed, and the surgical freedom to 6 targets of the regions were measured. Furthermore, portions of the tumor that were visually blocked by the brainstem or bony structures were segmented and recorded as blinded volumes for comparison. RESULTS: The extended retrosigmoid approach generated excellent exposure of the petroclival region, but for most specimens, there was inaccessible tumor volume adjacent to the brainstem (mean 641.3 mm3, SE 161.8). In contrast, the brainstem sides of the tumors were well-visualized by all the transpetrosal approaches. The blinded volume of the tumor was largest for the retrolabyrinthine approach, and this was statistically significant compared with all other approaches (mean 2381.3 mm3, SE 185.4). CONCLUSIONS: The authors performed a novel laboratory study by using patient CT and MRI data to generate 3D virtual models to compare surgical approaches. Since it is impossible to perform various approaches in separate surgeries in patients for comparison, VR represents a viable alternative for such comparative investigations.

Reconstruction of the Anterior External Auditory Canal With Mastoid Cortex Autologous Bone Graft.

OBJECTIVE: To describe the surgical management of temporomandibular joint (TMJ) herniation with external auditory canal (EAC) reconstruction using autologous bone grafting from the mastoid cortex. STUDY DESIGN: Retrospective case series. SETTING: A tertiary university medical center. PATIENTS: Three patients who presented to our Otolaryngology clinic with evidence of TMJ herniation through an anterior EAC defect, both on otoscopy and computed tomography (CT) imaging. INTERVENTIONS: Reconstruction of the anterior EAC with mastoid cortex bone grafting using an endaural approach. MAIN OUTCOME MEASURES: Successful reconstruction of anterior EAC bony defect without recurrence of herniation. RESULTS: All three patients presented with otalgia, hearing loss, and either tinnitus or a clicking sensation with jaw movement. Etiologies for TMJ herniation included osteoradionecrosis following external beam radiation therapy for head and neck carcinoma and iatrogenic injury following multiple tympanoplasties and canalplasties. A mastoid cortex bone graft was placed and secured anterior to the bony EAC defect through an endaural approach. Two patients wore a dental retainer postoperatively to keep the condyle in an open position. After reconstruction, patients reported an improvement in their presenting symptoms. There was no recurrence of TMJ herniation in all cases after 1, 4, and 9 years. CONCLUSIONS: Anterior EAC reconstruction with autologous bone grafting can be an effective definitive treatment in TMJ herniation. To our knowledge, this is the first report of the use of bone grafting to reconstruct the canal defect in TMJ herniation.Level of Evidence: V.

Adult diagnosis of congenital serine biosynthesis defect: A treatable cause of progressive neuropathy.

A woman with ichthyosis, contractures, and progressive neuropathy represents the first case of phosphoserine aminotransferase deficiency diagnosed and treated in an adult. She has novel compound heterozygous mutations in the gene PSAT1. Treatment with high dose oral L-serine completely resolved the ichthyosis. Consideration of this diagnosis is important because early treatment with L-serine repletion can halt progression of neurodegeneration and potentially improve neurological disabilities. As exome sequencing becomes more widely implemented in the diagnostic evaluation of progressive neurodegenerative phenotypes, adult neurologists and geneticists will increasingly encounter later onset manifestations of inborn errors of metabolism classically considered in infancy and early childhood.

A Prospective Evaluation of Swallowing and Speech in Patients with Neurofibromatosis Type 2.

Objective Neurofibromatosis type 2 (NF2) patients report that swallowing and speech problems significantly affect their quality of life, but the etiology of these phenomena is poorly understood. Swallowing and speech deficits may arise due to the neuropathy of involved nerves, due to posterior fossa tumor growth, or as iatrogenic effects from neurosurgical procedures to remove these tumors. This study aims to identify the natural history of swallowing and speech deficits in an NF2 cohort and to characterize the factors that may lead to those deficits. Methods Subjects ( n = 168) were enrolled in a prospective, longitudinal study of NF2 with yearly imaging and clinical exams. The patients completed a self-reported questionnaire that included responses regarding subjective swallowing and speech dysfunction. A formal speech-language pathology evaluation and modified barium swallow (MBS) study (reported as American Speech-Language Hearing Association [ASHA] swallowing independency score from 1 through 7) was obtained when a speech/swallowing deficit was reported on the questionnaire. Results Of the 168 enrolled subjects, 55 (33%, median age = 31 years) reported subjective speech and/or swallowing deficits. These patients underwent one ( n = 37) or multiple ( n = 18) MBS studies during 44.8 ± 10.4 months follow-up. During MBS, a majority demonstrated near-normal swallowing (ASHA score >6, 82%), and no evidence of aspiration (aspiration/laryngeal penetration score = 1, 96%). Prior to initial MBS consultation, 38 (69%) patients had undergone relevant neurosurgical procedures. In those with recent (<1 week) posterior fossa surgery ( n = 12), 2 (17%) patients had severe dysphagia and high aspiration risk on postoperative MBS. Both of these patients recovered to functionally independent swallowing status. Unilateral ( n = 10) or bilateral ( n = 6) tongue deficits unrelated to previous history suggestive of hypoglossal nerve injury were detected on clinical examination. There was a correlation between the presence of dysarthria and tongue deficits and tumors associated with the hypoglossal canal noted on imaging. Conclusion A large proportion of patients with NF2 report speech and swallow deficits that are not evident on objective measurements. We also found hypoglossal neuropathy unrelated to prior surgical interventions. Our findings suggest that swallowing and speech problems in NF2 are associated with lower cranial nerve neuropathy, some due to compressive effects of posterior fossa tumors. Adaptation over the course of the disease allows for the compensation of these deficits and subsequent normal findings on objective testing.

Genetic Hearing Loss Associated With Autoinflammation.

Sensorineural hearing loss can result from dysfunction of the inner ear, auditory nerve, or auditory pathways in the central nervous system. Sensorineural hearing loss can be associated with age, exposure to ototoxic drugs or noise, or mutations in nuclear or mitochondrial genes. However, it is idiopathic in some patients. Although these disorders are mainly caused by dysfunction of the inner ear, little of the pathophysiology in sensorineural hearing loss is known due to inaccessibility of the living human inner ear for biopsy and pathological analysis. The inner ear has previously been thought of as an immune-privileged organ. We recently showed that a missense mutation of the NLRP3 gene is associated with autosomal-dominant sensorineural hearing loss with cochlear autoinflammation in two unrelated families. NLRP3 encodes the NLRP3 protein, a key component of the NLRP3 inflammasome that is expressed in immune cells, including monocytes and macrophages. Gain-of-function mutations of NLRP3 cause abnormal activation of the NLRP3 inflammasome leading to IL-1ß secretion in a spectrum of autosomal dominant systemic autoinflammatory phenotypes termed cryopyrin-associated periodic syndromes. The affected subjects of our two families demonstrated atypical phenotypes compared with those reported for subjects with cryopyrin-associated periodic syndromes. These observations led us to test the hypothesis that macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The inflammasome can indeed be activated in macrophage/monocyte-like cells of the mouse cochlea, with secretion of IL-1ß. The macrophage/monocyte-like cells in the cochlea were also found to be associated with hearing loss in a Slc26a4-insufficient mouse model of human deafness. This review addresses our understanding of genetic hearing loss mediated by autoinflammation and macrophage/monocyte-like cells in the cochlea.

Middle Fossa Approach for Resection of an Intracanalicular Vestibular Schwannoma.

Objective This video was aimed to demonstrate the middle fossa approach for the resection of an intracanalicular vestibular schwannoma. Design Present study is a video case report. Setting The operative video is showing a microsurgical resection. Participant The patient was a 59-year-old man who presented with worsening headache and right-side hearing loss. He was found to have a right intracanalicular vestibular schwannoma. After weighing risks and benefits, he chose surgery to remove his tumor. Since his hearing remained "serviceable," a middle fossa approach was chosen. Main Outcome Measures Pre- and postoperative patient photographs evaluated the muscles of facial expression as a marker for facial nerve preservation. Results A right middle fossa craniotomy was performed which allowed access to the floor of the middle cranial fossa. The greater superficial petrosal nerve (GSPN) and arcuate eminence were identified. Using these two landmarks, the internal acoustic canal (IAC) was localized. After drilling the petrous bone, the IAC was unroofed. The facial nerve was identified by stimulation and visual inspection and the tumor was separated from it with microsurgical dissection. In the end, the tumor was fully resected. Both the facial and cochlear nerves were preserved. Postoperatively, the patient experienced no facial palsy and his hearing is at baseline. Conclusion With radiosurgery gaining increasing popularity, patients with intracanalicular vestibular schwannomas are frequently treated with it, or are managed with observation. The middle fossa approach is therefore becoming a "lost art," but as demonstrated in this video, remains an effective technique for tumor removal and nerve preservation. The link to the video can be found at: https://youtu.be/MD6o3DF6jYg .

ACR Appropriateness Criteria® Hearing Loss and/or Vertigo.

This article presents guidelines for imaging utilization in patients presenting with hearing loss or vertigo, symptoms that sometimes occur concurrently due to proximity of receptors and neural pathways responsible for hearing and balance. These guidelines take into account the superiority of CT in providing bony details and better soft-tissue resolution offered by MRI. It should be noted that a dedicated temporal bone CT rather than a head CT best achieves delineation of disease in many of these patients. Similarly, optimal assessment often requires a dedicated high-resolution protocol designed to assess temporal bone and internal auditory canals even though such a study will be requested and billed as a brain MRI. Angiographic techniques are helpful in some patients, especially in the setting of vertigo. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Review of the Neurological Implications of von Hippel-Lindau Disease.

Importance: von Hippel-Lindau (VHL) disease-associated central nervous system (CNS) lesions include hemangioblastomas and endolymphatic sac tumors (ELSTs), which are associated with significant neurological morbidity and mortality. Recent studies provide critical new biological, diagnostic, and management insights into these tumors. Observations: Biological features, natural history, clinical findings, and management strategies of VHL disease-associated CNS tumors are reviewed. The VHL disease results from a germline mutation of the VHL gene (located on the short arm of chromosome 3), a tumor suppressor that encodes for the VHL protein. Whereas VHL disease is associated with visceral manifestations, CNS lesions are the most common source of morbidity and mortality. Craniospinal hemangioblastomas are almost entirely (99%) found in the cerebellum, brainstem, and spinal cord. These tumors arise from multipotent hemangioblasts. Peritumoral cysts frequently underlie the clinical findings associated with hemangioblastomas (>90% of symptomatic tumors). Prospective natural history studies demonstrate that CNS hemangioblastomas typically grow in a saltatory pattern. Due to this unpredictable growth pattern, surgical resection is reserved for symptomatic lesions, as many tumors do not become symptomatic. Recent studies indicate that VHL disease-associated ELSTs cause audiovestibular morbidity (hearing loss, tinnitus, and vertigo) via 3 mechanisms-otic capsule invasion, intralabyrinthine hemorrhage, and endolymphatic hydrops. Specialized magnetic resonance imaging techniques have been defined to elucidate each of these mechanisms, even when a tumor mass is not identified on imaging. Endolymphatic sac tumors cause audiovestibular morbidity unrelated to size or progression, and resection is now recommended at initial discovery of a tumor mass or a tumor-associated mechanism of morbidity. Conclusions and Relevance: New insights into the development, pathobiological origin, natural history, and long-term outcomes of VHL disease-associated CNS tumors have redefined their management and treatment indications and potentially provide new targeted therapeutic strategies. Resection is reserved for symptomatic hemangioblastomas, but early resection of newly detected ELSTs is now recommended.

Gradual Symmetric Progression of DFNA34 Hearing Loss Caused by an NLRP3 Mutation and Cochlear Autoinflammation.

OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34 hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3 encodes a critical component of the NLRP3 inflammasome that is activated in innate immune responses. STUDY DESIGN: This study was conducted under protocol 01-DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and developmental history interviews and physical and audiological examinations of affected individuals with DFNA34 HL caused by the p.Arg918Gln mutation of NLRP3. We retrospectively reviewed audiological reports, when available, from other health care centers. SETTING: Federal biomedical research facility. SUBJECTS: Eleven members of a North American family segregating p.Arg918Gln. MAIN OUTCOME MEASURES: Pure-tone thresholds, rates of pure-tone threshold progression, and speech discrimination scores. RESULTS: Eight subjects had bilateral sensorineural HL with an onset in the late 2nd to 4th decade of life. Slowly progressive HL initially primarily affected high frequencies. Low and middle frequencies were affected with advancing age, resulting in moderate HL with a downsloping audiometric configuration. The average annual threshold deterioration was 0.9 to 1.5 dB/yr. Speech recognition scores ranging from 60 to 100% were consistent with cochlear, but not retrocochlear, etiology. Three subjects (16, 22, and 32 yr old) had normal hearing thresholds. CONCLUSION: DFNA34 HL has an onset during early adulthood and progresses approximately 1.2 dB/yr.

Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia.

Importance: Fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) are rare bone and endocrine disorders in which expansile fibro-osseous lesions result in deformity, pain, and functional impairment. The effect of FD on hearing and otologic function has not been established. Objectives: To characterize audiologic and otologic manifestations in a large cohort of individuals with FD/MAS and to investigate potential mechanisms of hearing loss. Design, Setting, and Participants: In this natural history study, individuals with craniofacial FD seen at a clinical research center underwent clinical, biochemical, computed tomographic, audiologic, and otolaryngologic evaluations. Main Outcomes and Measures: Clinical and radiologic features associated with hearing loss and otologic disease were evaluated. Conductive hearing loss was hypothesized to be associated with narrowing of the external auditory canal (EAC), FD involving the epitympanum, and FD crowding the ossicular chain. Sensorineural hearing loss was hypothesized to be associated with FD affecting the internal auditory canal (IAC) and otic capsule. Results: Of the 130 study participants with craniofacial FD who were evaluated, 116 (89.2%) had FD that involved the temporal bone (median age, 19.6 years; range, 4.6-80.3 years; 64 female [55.2%]), whereas 14 (10.8%) had craniofacial FD that did not involve the temporal bone. Of the 183 ears with temporal bone FD, hearing loss was identified in 41 ears (22.4%) and was conductive in 27 (65.9%), sensorineural in 12 (29.3%), and mixed in 2 (4.9%). Hearing loss was mild and nonprogressive in most participants. Whereas EACs were narrower in ears with FD (mean difference [MD], 0.33 mm; 95% CI, 0.11-0.55 mm), this finding was associated with conductive hearing loss in only 4 participants. Fibrous dysplasia crowding of the ossicles was associated with conductive hearing loss (odds ratio [OR], 5.0; 95% CI, 2.1-11.6). The IAC length was not different between ears with and without FD (MD, -0.37; 95% CI, -0.95 to 0.211); however, canals were elongated in ears with sensorineural hearing loss (MD, -1.33; 95% CI, -2.60 to -0.07). Otic capsule involvement was noted in only 4 participants, 2 of whom had sensorineural hearing loss. Both MAS-associated growth hormone excess (OR, 3.1; 95% CI, 1.3-7.5) and neonatal hypercortisolism (OR, 11; 95% CI, 2.5-55) were associated with an increased risk of hearing loss . Conclusions and Relevance: Hearing loss in craniofacial FD is common and mild to moderate in most individuals. It typically arises from FD crowding of the ossicular chain and elongation of the IAC, whereas EAC stenosis and otic capsule invasion are less common causes. Individuals with craniofacial FD should undergo otolaryngologic evaluation and monitoring, including assessment to identify those with high-risk features.

NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy.

The NLRP3 inflammasome is an intracellular innate immune sensor that is expressed in immune cells, including monocytes and macrophages. Activation of the NLRP3 inflammasome leads to IL-1ß secretion. Gain-of-function mutations of NLRP3 result in abnormal activation of the NLRP3 inflammasome, and cause the autosomal dominant systemic autoinflammatory disease spectrum, termed cryopyrin-associated periodic syndromes (CAPS). Here, we show that a missense mutation, p.Arg918Gln (c.2753G > A), of NLRP3 causes autosomal-dominant sensorineural hearing loss in two unrelated families. In family LMG446, hearing loss is accompanied by autoinflammatory signs and symptoms without serologic evidence of inflammation as part of an atypical CAPS phenotype and was reversed or improved by IL-1ß blockade therapy. In family LMG113, hearing loss segregates without any other target-organ manifestations of CAPS. This observation led us to explore the possibility that resident macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The NLRP3 inflammasome can indeed be activated in resident macrophage/monocyte-like cells in the mouse cochlea, resulting in secretion of IL-1ß. This pathway could underlie treatable sensorineural hearing loss in DFNA34, CAPS, and possibly in a wide variety of hearing-loss disorders, such as sudden sensorineural hearing loss and Meniere's disease that are elicited by pathogens and processes that stimulate innate immune responses within the cochlea.

Venous sinus compromise after pre-sigmoid, transpetrosal approach for skull base tumors: A study on the asymptomatic incidence and report of a rare dural arteriovenous fistula as symptomatic manifestation.

The sigmoid sinus is routinely exposed and manipulated during pre-sigmoid, transpetrosal approaches to the skull base, but there is scant data available on the incidence of venous sinus compromise after surgery. We encountered a dural arteriovenous fistula as a result of sigmoid sinus occlusion and examined the incidence of venous sinus thrombosis or narrowing after transpetrosal surgeries. We performed a retrospective analysis of a series of patients treated by the senior surgeons (WCJ, MH, HJK), who underwent either a posterior petrosectomy or translabyrinthine approach for various skull base tumors. All available clinical and radiographic data were thoroughly examined in each patient to determine the post-operative fate of the venous sinuses. Of the 52 available patients, five patients were discovered post-operatively to have a narrowed or constricted sigmoid sinus ipsilateral to the surgery, whereas another five patients were diagnosed with asymptomatic sinus thrombosis either in the transverse or sigmoid or both. None of these patients experienced symptoms, nor were there any instance of ischemic or hemorrhagic complications. However, there was one additional patient who presented with pulsatile tinnitus 2years after surgery. His angiogram showed an occlusion of the ipsilateral sigmoid sinus and a posterior fossa dural arteriovenous fistula. A two-stage transvenous and transarterial embolization was successful in eliminating the fistula. Technical considerations to avoid sinus injuries during pre-sigmoid, transpetrosal surgery are discussed.