Erika A. Woodson

Membrane depolarization inhibits spiral ganglion neurite growth via activation of multiple types of voltage sensitive calcium channels and calpain

The effect of membrane electrical activity on spiral ganglion neuron (SGN) neurite growth remains unknown despite its relevance to cochlear implant technology. We demonstrate that membrane depolarization delays the initial formation and inhibits the subsequent extension of cultured SGN neurites. This inhibition depends directly on the level of depolarization with higher levels of depolarization causing retraction of existing neurites. Cultured SGNs express subunits for L-type, N-type, and P/Q type voltage-gated calcium channels (VGCCs) and removal of extracellular Ca(2+) or treatment with a combination of L-type, N-type, and P/Q-type VGCC antagonists rescues SGN neurite growth under depolarizing conditions. By measuring the fluorescence intensity of SGNs loaded with the fluorogenic calpain substrate t-butoxy carbonyl-Leu-Met-chloromethylaminocoumarin (20 microM), we demonstrate that depolarization activates calpains. Calpeptin (15 microM), a calpain inhibitor, prevents calpain activation by depolarization and rescues neurite growth in depolarized SGNs suggesting that calpain activation contributes to the inhibition of neurite growth by depolarization.

Long-Term Hearing Preservation After Microsurgical Excision of Vestibular Schwannoma

Objective: To examine long-term hearing outcomes after microsurgical excision of vestibular schwannoma (VS). Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Forty-nine subjects at a single institution who had undergone microsurgical excision of a VS via middle cranial fossa (MCF) approach between 1994 and 2007 with immediate postoperative (PO) hearing preservation and for whom long-term audiograms were available. Intervention: Diagnostic. Main Outcome Measures: Word Recognition Score (WRS) is defined by speech discrimination scores (SDS) greater than 70% (grade I), 50% to 70% (grade II), less than 50% (grade III), and 0% (grade IV). Results: For subjects with more than 2 years of follow-up, WRS I hearing was present PO in 42 of 49 patients and was preserved at the latest follow-up in 38 (90%) of 42 patients. No subjects fell beyond WRS II. WRS I hearing was maintained in 23 (88%) of 26 patients with more than 5 years of follow-up. Postoperative WRS I to II hearing was maintained in 28 (96%) of 29 patients with more than 5 years of follow-up. The patient who lost significant hearing in the ear operated on had sensorineural hearing loss that paralleled deterioration in her ear that was not operated on. Conclusion: Most subjects maintain their initial PO SDS after microsurgical VS removal, and therefore, the initial PO WRS is predictive of long-term hearing. Postsurgical changes do not alter the natural rate or pattern of progressive bilateral sensorineural hearing loss in individual subjects.

New Frontiers in Cochlear Implantation: Acoustic Plus Electric Hearing, Hearing Preservation, and More

As cochlear implant technology has changed, so have implantation criteria. In addition to profoundly deaf individuals, candidacy has expanded to include those with significant remaining acoustic hearing. This article describes the devices that are now in clinical trial, discusses the rationale as to why residual hearing preservation is important, details the surgical techniques for hearing preservation, and shares the clinical results of electric plus acoustic processing. That a video is available online.

Clinical Practice Guideline (Update)

Objective This update of the 2008 American Academy of Otolaryngology—Head and Neck Surgery Foundation cerumen impaction clinical practice guideline provides evidence-based recommendations on managing cerumen impaction. Cerumen impaction is defined as an accumulation of cerumen that causes symptoms, prevents assessment of the ear, or both. Changes from the prior guideline include a consumer added to the development group; new evidence (3 guidelines, 5 systematic reviews, and 6 randomized controlled trials); enhanced information on patient education and counseling; a new algorithm to clarify action statement relationships; expanded action statement profiles to explicitly state quality improvement opportunities, confidence in the evidence, intentional vagueness, and differences of opinion; an enhanced external review process to include public comment and journal peer review; and 3 new key action statements on managing cerumen impaction that focus on primary prevention, contraindicated intervention, and referral and coordination of care. Purpose The primary purpose of this guideline is to help clinicians identify patients with cerumen impaction who may benefit from intervention and to promote evidence-based management. Another purpose of the guideline is to highlight needs and management options in special populations or in patients who have modifying factors. The guideline is intended for all clinicians who are likely to diagnose and manage patients with cerumen impaction, and it applies to any setting in which cerumen impaction would be identified, monitored, or managed. The guideline does not apply to patients with cerumen impaction associated with the following conditions: dermatologic diseases of the ear canal; recurrent otitis externa; keratosis obturans; prior radiation therapy affecting the ear; previous tympanoplasty/myringoplasty, canal wall down mastoidectomy, or other surgery affecting the ear canal. Key Action Statements The panel made a strong recommendation that clinicians should treat, or refer to a clinician who can treat, cerumen impaction, defined as an accumulation of cerumen that is associated with symptoms, prevents needed assessment of the ear, or both. The panel made the following recommendations: (1) Clinicians should explain proper ear hygiene to prevent cerumen impaction when patients have an accumulation of cerumen. (2) Clinicians should diagnose cerumen impaction when an accumulation of cerumen, as seen on otoscopy, is associated with symptoms, prevents needed assessment of the ear, or both. (3) Clinicians should assess the patient with cerumen impaction by history and/or physical examination for factors that modify management, such as ≥1 of the following: anticoagulant therapy, immunocompromised state, diabetes mellitus, prior radiation therapy to the head and neck, ear canal stenosis, exostoses, and nonintact tympanic membrane. (4) Clinicians should not routinely treat cerumen in patients who are asymptomatic and whose ears can be adequately examined. (5) Clinicians should identify patients with obstructing cerumen in the ear canal who may not be able to express symptoms (young children and cognitively impaired children and adults), and they should promptly evaluate the need for intervention. (6) Clinicians should perform otoscopy to detect the presence of cerumen in patients with hearing aids during a health care encounter. (7) Clinicians should treat, or refer to a clinician who can treat, the patient with cerumen impaction with an appropriate intervention, which may include ≥1 of the following: cerumenolytic agents, irrigation, or manual removal requiring instrumentation. (8) Clinicians should recommend against ear candling for treating or preventing cerumen impaction. (9) Clinicians should assess patients at the conclusion of in-office treatment of cerumen impaction and document the resolution of impaction. If the impaction is not resolved, the clinician should use additional treatment. If full or partial symptoms persist despite resolution of impaction, the clinician should evaluate the patient for alternative diagnoses. (10) Finally, if initial management is unsuccessful, clinicians should refer patients with persistent cerumen impaction to clinicians who have specialized equipment and training to clean and evaluate ear canals and tympanic membranes. The panel offered the following as options: (1) Clinicians may use cerumenolytic agents (including water or saline solution) in the management of cerumen impaction. (2) Clinicians may use irrigation in the management of cerumen impaction. (3) Clinicians may use manual removal requiring instrumentation in the management of cerumen impaction. (4) Last, clinicians may educate/counsel patients with cerumen impaction or excessive cerumen regarding control measures.

p75NTR is highly expressed in vestibular schwannomas and promotes cell survival by activating nuclear transcription factor κB

Vestibular schwannomas (VSs) arise from Schwann cells (SCs) and result from the loss of function of merlin, the protein product of the NF2 tumor suppressor gene. In contrast to non‐neoplastic SCs, VS cells survive long‐term in the absence of axons. We find that p75NTR is overexpressed in VSs compared with normal nerves, both at the transcript and protein level, similar to the response of non‐neoplastic SCs following axotomy. Despite elevated p75NTR expression, VS cells are resistant to apoptosis due to treatment with proNGF, a high affinity ligand for p75NTR. Furthermore, treatment with proNGF protects VS cells from apoptosis due to c‐Jun N‐terminal kinase (JNK) inhibition indicating that p75NTR promotes VS cell survival. Treatment of VS cells with proNGF activated NF‐κB while inhibition of JNK with SP600125 or siRNA‐mediated knockdown reduced NF‐κB activity. Significantly, proNGF also activated NF‐κB in cultures treated with JNK inhibitors. Thus, JNK activity appears to be required for basal levels of NF‐κB activity but not for proNGF‐induced NF‐κB activity. To confirm that the increase in NF‐κB activity contributes to the prosurvival effect of proNGF, we infected VS cultures with Ad.IκB.SerS32/36A virus, which inhibits NF‐κB activation. Compared with control virus, Ad.IκB.SerS32/36A significantly increased apoptosis including in VS cells treated with proNGF. Thus, in contrast to non‐neoplastic SCs, p75NTR signaling provides a prosurvival response in VS cells by activating NF‐κB independent of JNK. Such differences may contribute to the ability of VS cells to survive long‐term in the absence of axons. GLIA 2014;62:1699–1712

Neurolymphomatosis mimicking chemotherapy-induced ototoxicity.

Objective: To present an unusual cause of bilateral sensorineural hearing loss mimicking chemotherapy-induced ototoxicity. Patient: A 76-year-old woman with bilateral sudden sensorineural hearing loss after chemotherapy for non-Hodgkin lymphoma was referred for cochlear implantation. Interventions: Prednisone and acyclovir were administered empirically during the course of the diagnostic evaluation. Main Outcome Measures: Diagnostic tests were obtained, including audiometry, positron emission tomography/computed tomographic imaging, and magnetic resonance imaging scan of the brain with gadolinium. Results: Audiometry revealed bilateral profound sensorineural hearing loss without improvement after steroid and acyclovir treatment. Postchemotherapy positron emission tomography/computed tomographic imaging obtained 1 week after onset of hearing loss suggested the lymphoma to be in remission. However, magnetic resonance imaging obtained a few weeks later, concurrent with progression of symptoms to include facial palsy and numbness, demonstrated enhancement and thickening of multiple cranial nerves, consistent with neurolymphomatosis (malignant lymphocytic infiltration of nerves). Conclusion: Particular vigilance must be given to the potential for malignant invasion of the peripheral nervous system in the context of new-onset sensorineural hearing loss after chemotherapy. Such a neurologic deficit should not be assumed to be chemotherapy induced even if the hearing loss is bilaterally symmetric and the only neurologic abnormality.

Clinical Practice Guideline (Update): Earwax (Cerumen Impaction) Executive Summary

The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue of Otolaryngology–Head and Neck Surgery featuring the updated Clinical Practice Guideline: Earwax (Cerumen Impaction). To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 11 recommendations emphasize proper ear hygiene, diagnosis of cerumen impaction, factors that modify management, evaluating the need for intervention, and proper treatment. An updated guideline is needed due to new evidence (3 guidelines, 5 systematic reviews, and 6 randomized controlled trials) and the need to add statements on managing cerumen impaction that focus on primary prevention, contraindicated intervention, and referral and coordination of care.

Safety of Monopolar Electrocautery in Patients With Cochlear Implants

Objective: The outcomes of 2 patients with cochlear implants (CIs) who underwent adenotonsillectomy (AT) with inadvertent use of monopolar cautery are presented. The safety data regarding monopolar cautery use in CI recipients is also reviewed. Study Design: This is a retrospective case series of 2 CI recipients that underwent AT with monopolar cautery and literature review of electrocautery safety in the setting of CI. Results: Two patients with CIs underwent AT with use of monopolar cautery inadvertently by surgeons that do not routinely perform cochlear implants as part of his or her clinical practice. Patient 1 was a 9-year-old female who had AT for obstructive sleep apnea (OSA) after undergoing unilateral CI for profound congenital sensorineural hearing loss (SNHL) 8 years ago. Patient 2 was a 7-year-old female who underwent AT for OSA 4 months after undergoing unilateral CI for congenital SNHL. Both patients had no immediate signs of complications with their CI use postoperatively. Both patients demonstrated unchanged postoperative neural response telemetry and behavioral audiometric testing. Patient 1 continues to have no CI-related complications 3.5 years after the procedure. Patient 2 has been followed for at least 3 months by audiometric testing and 10 months by otolaryngologist with no CI-related complications. Conclusion: Although animal and cadaveric studies suggest that monopolar cautery may be safely used in patients with cochlear implants, there have been no in vivo human studies that have evaluated the risk to the patient or implant. This is a report of a small, unintended experience with 2 patients, both of whom exhibit no complications or changes to CI function thus far.

Acute hydrocephalus secondary to subarachnoid fat migration after cranial base surgery.

Autologous abdominal fat is frequently used to fill temporal bone defects after lateral cranial base surgery. Subarachnoid fat (SAF) migration is an uncommon but recognized phenomenon that may occur after lateral cranial base surgery. Previous case reports have demonstrated SAF on computed tomographic imaging (1,2). We present a case of significant SAF causing obstructive hydrocephalus (OH) and review the appearance of SAF on magnetic resonance imaging. Our patient is a 46-year-old man with neurofibromatosis type 2 and large bilateral vestibular schwannomas (VSs) compressing the brainstem. At presentation, the tumors measured 3.2 and 4.3 cm on the right and left, respectively, in their largest dimensions. Previous treatment of his VSs included bilateral partial excisions via suboccipital craniectomies. Subsequently, the patient underwent radiosurgery to each lesion to manage persistent growth of the residual tumors. Despite radiosurgery, the patient’s residual tumors continued to grow. Therefore, we used a transcochlear approach to remove the larger VS with closure of the external auditory canal. During closure, autologous abdominal fat, cut into strips, was placed into the temporal bone defect. Because of the patient’s previous craniectomies, we used a large titanium plate to secure the fat in the mastoid defect. On postoperative day 4, the patient developed Serratia marcesens meningitis. After initiating antibiotics, the patient’s condition improved clinically until postoperative day 13, when the patient again became febrile with decreased mental status. A magnetic resonance image revealed SAF in the pontine cistern, fourth ventricle, and bilateral lateral ventricles (Fig. 1). The axial T1-weighted images demonstrate a fluid-fluid level in the lateral ventricles, with the anterior fluid being brightly hyperintense. On fat-saturated T1weighted imaging with gadolinium contrast, the hyperintense anterior ventricular fluid signal becomes attenuated and does not enhance. This fluid is also hypointense on T2-weighted imaging, relative to the cerebrospinal fluid (CSF). On diffusion imaging, the anterior ventricular fluid has a total signal void.

Zygomatic root abscess: a rare complication of otitis media.

Extracranial complications of acute otitis media are rare. Friedrich Bezold (1824Y1908) was one of the first to describe routes of infection from the mastoid extending through the incisura digastrica into the neck or through the zygomatic root (1). Extracranial extension of mastoid infections was further characterized by Henri Luc in 1900 when he described the Bsubperiosteal temporal abscess of otitic origin without intraosseous suppuration.[(2) Zygomatic root abscesses have only been described in a few scattered case reports (1,3Y5). We report on an otherwise healthy 41-year-old man who presented with a 3-month history of left temporal swelling. His symptoms included decreased hearing and otalgia without associated otorrhea, tinnitus, vertigo, or constitutional symptoms. He had 20 10 cm of left temporal induration and swelling. The affected external auditory canal was swollen and erythematous. His facial nerve was intact. A temporal bone computed tomography showed bony erosion at the zygomatic root with extensive soft tissue swelling (Fig. 1, A). Magnetic resonance imaging confirmed a rim-enhancing lesion within the mastoid extending extracranially (Fig. 1, BYD). An incision and drainage were performed with expression of copious purulent material, which grew >-hemolytic streptococcus. We initiated intravenous antibiotics, which resulted in notable improvement. After resolution of his acute symptoms, the patient underwent a canal wall up mastoidectomy. There was an organized, granular soft tissue mass filling the mastoid cavity with destruction of the mastoid air cells and erosion of the zygomatic root. Histologic samples did not show any malignancy. His symptoms completely resolved after medical and surgical management. The diagnosis of zygomatic root abscesses can be difficult due to variable clinical presentations often distinct from suppurative mastoiditis. Patients may lack constitutional symptoms. Workup typically includes computed