Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells

Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/β, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/β, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation

Tympanic membrane breakdown after intratympanic injection of steroids in irradiated ears

To describe a rare complication of intratympanic injection of steroids in susceptible ears. We present two patients with a history of irradiation involving the injected ear. Therapeutic. Tympanic membrane condition after intratympanic injection of steroids. Total or near-total breakdown of the irradiated tympanic membrane. Tympanic membranes with an impaired wound-healing ability, together with exposure to intratympanic steroids, may be at risk for total or near-total breakdown

Blast Injuries to the Facial Nerve

The recommended treatment of penetrating traumatic facial nerve injuries associated with Immediate, total paralysis of the ipsilateral facial muscles generally includes facial nerve exploration and repair. We reviewed our experience with bullet injuries to the extratemporal facial nerve to determine the efficacy of this approach. Five patients with immediate, total facial nerve paralysis caused by bullet wounds near the extratemporal facial nerve were seen between July 1990 and December 1992. Of four patients who underwent surgical exploration, only one demonstrated complete transection of the facial nerve. Two of these four were followed up with serial electroneuronography, which demonstrated complete degeneration within the first week after injury. The fifth patient was followed up with serial electroneuronography without complete degeneration, and partial recovery was observed. We conclude that penetrating bullet injuries with immediate, total facial paralysis may not necessarily be associated with transection of the facial nerve. We propose a method of treating patients with these Injuries using electroneuronography

Long-Term Efficacy of Endolymphatic Sac Surgery for Vertigo in Meniere's Disease

The long-term efficacy of endolymphatic sac procedures for control of vertigo in Melnere's disease has been controversial. We evaluated results of sac shunt surgery for 234 patients having at least 10 years followup (mean, 13.5 years). All patients had persistent vestibular symptoms despite medical therapy. All underwent endolymphatic subarachnoid shunt as their original operation. Data were collected by chart review and questionnaire regarding: (1) the number of additional surgical procedures to control vertigo, (2) remaining dizziness, and (3) level of disability. One hundred forty-seven of the patients (63%) did not undergo any further surgery to control vertigo, and an additional 17% had only revisions of the endolymphatic sac shunt. Thus, 80% never required a destructive procedure. Long-term effectiveness of surgery in regard to dizziness and disability was determined from the questionnaire. Of the 147 patients with only the original sac shunt surgery, 93% reported no dizziness or mild to no disability. Of the group who underwent only revisions of the original shunt, 96% stated they had no more dizziness or mild to no disability. We conclude that endolymphatic sac shunt operations are effective as Initial surgical procedures for long-term control of disabling vertigo of Meniere's disease

Transcanal Approach for Removal of Displaced Petrous Carotid Aneurysm Embolization Coil in the Middle Ear

Introduction: Aneurysms arising from the petrous segment of the internal carotid artery (ICA) are rare. Surgical treatment of petrous ICA aneurysms can be challenging due to their close proximity to inner ear structures. In this case, a rare complication of endovascular coiling is described of a patient who presented with ear bleeding, pulsatile tinnitus, and hearing loss shortly after undergoing the embolization procedure. This case report describes our unique management of the patient through intraoperative removal of the displaced coil through a transcanal approach and correction of the tympanic membrane perforation. Case Description: Patient is a 55-year-old woman who was found to have a left petrous ICA aneurysm coursing through the middle ear cavity over the cochlear promontory. She underwent endovascular stenting and coiling of the left petrous ICA. However, immediately after the surgery, the patient had ear bleeding, acute loss of hearing in the left ear, as well as complaints of pulsatile popping and crackling sounds in the ear. Physical examination revealed a tympanic membrane perforation and extrusion of the embolization coil through the perforation. She was scheduled to undergo a transcanal approach to access, clip, and remove the coil from the middle ear. Procedure: Exploration of the middle ear revealed that the ossicular chain was eroded at the level of the incus, and that the coil was filling the majority of the middle ear space. Excess coil was clipped and removed from the middle ear. A conchal bowl cartilage graft was removed and fashioned to be placed medial to the tympanic membrane remnant and lateral to the remaining middle ear, coiling to prevent future extrusion of the coil. Follow-Up: On follow-up 1 month after the procedure, the patient was satisfied to have resolution of her pulsatile crackling and popping sounds. On examination, the cartilage graft was well in place, with complete epithelialization of the tympanic membrane perforation. On 4-month follow-up, she remained free of any ear infections, continued to demonstrate full closure of the perforation with cartilage graft in place, and had no symptoms of tinnitus. Conclusions: This case is a rare example of a complication arising from endovascular treatment of petrous ICA aneurysms using coil embolization. As evidenced in this case, close attention should be given to otologic symptoms postoperatively after endovascular embolization of petrous ICA aneurysms. Our surgical technique to remove the excess coil, and repair the tympanic membrane provided the patient with improvement of her symptoms. In particular, the use of a cartilage graft to protect the remaining coil from protruding through the tympanic membrane proved especially useful

A model of real time monitoring of the cochlear function during an induced local ischemia

The aim of this study was to investigate the utility of distortion product otoacoustic emissions (DPOAEs) in intraoperative monitoring (IM) of cochlear ischemic episodes in animals during internal auditory artery (IAA) compression. The IAA was exposed using the posterior fossa approach and then compressed for 3 and 5 min intervals to effect ischemia. DPOAE amplitudes and phases were measured at 4, 8, and 12 kHz geometric mean frequency (GMF). In each monitored ear, laser-Doppler cochlear blood flow (CBF) was measured. All IAA compressions resulted in rapid decrease of DPOAE amplitude and CBF, with simultaneous DPOAE phase increase. DPOAE phase changes were found to increase consistently within several seconds of IAA compression, while corresponding DPOAE amplitudes changed more slowly, with up to 30–40 s delays. Following IAA release, DPOAEs at 12 kHz GMF were characterized by longer delays in returning to baseline than those measured at lower frequencies. In some cases, CBF did not return to baseline. In this animal model, DPOAEs were found to be sensitive measures of cochlear function during transient cochlear ischemic episodes, suggesting the utility of DPOAE monitoring of auditory function during surgery of cerebello-pontine angle tumors

Cochlear implant fixation and dura exposure

To determine the current common practices and techniques used to fixate and stabilize internal receivers. Retrospective, anonymized, cross-sectional survey. William House Cochlear Implant Study Group Meeting in September 2008. A total of 62 surveys were received of the 106 people who had signed in. In adults, 83.3% of the respondents said that they always, 6.7% usually, 3.3% sometimes, 3.3% rarely, and 3.3% never drilled wells for the internal receiver. In pediatric patients, respondents said that they would always 78.6%, usually 8.9%, sometimes 3.6%, rarely 5.4%, and never 3.6% drill wells. Regarding the securing of the internal receiver, 56.1% always, 10.5% usually, 3.5% sometimes, 12.3% rarely, and 17.5% never secured the internal receiver in adults. In the pediatric patient population, 50% always, 12.5% usually, 7.1% sometimes, 12.5% usually, and 17.9% never secured the device. In adults, 50% reported using bone holes, 30% fascial sutures, and 20% screws. In the pediatric population, 45.5% indicated that they used bone holes, 34.5% fascial sutures, and 20% screws. Most respondents rarely or never drilled down to the dura for bone holes. Whereas the majority of respondents do drill wells for the internal receiver in both adults and children, those that did not were represented. The result of this survey emphasizes that alternatives are available and acceptable. There is no significant evidence in the literature to support 1 specific method of fixation