Cochlear Implantation in Charcot-Marie-Tooth Patients: Speech Perception and Quality of Life.

OBJECTIVES: There is a limited understanding of the impact of cochlear implantation (CI) in patients with Charcot-Marie-Tooth disease (CMT), given the scarcity of reported cases. We aim to evaluate the audiological outcomes and quality of life (QoL) after CI in CMT. METHODS: Multi-institutional, university-affiliated, tertiary-referral centers, retrospective chart review.Our cohort includes 5 patients with CMT. Patients' charts were reviewed for demographic characteristics, operation notes, and pre- and post-implantation audiology evaluation. Patients completed the Cochlear Implant Quality of Life-10 (CIQOL-10) Global questionnaire. RESULTS: Pre-implantation, the mean pure tone average was 84.1 ± 7.2 dB, and the mean word recognition score was 2.4% in the implanted ear. AzBio sentence test was performed in quiet, revealing a mean of 4 ± 1.4% in the implanted ear. Post-implantation, PTA results were all within the mild hearing loss range (mean 33.0 ± 5.9 dB). Post-CI, AZ-Bio test results were 5%, 65%, and 74% (for 3 patients), and HINT scores were 55% and 58% (for 2 patients). The mean score of the CIQOL-10 questionnaire was 42.7 ± 10.47 (range 1-100). Patients were most satisfied with their ability to listen to the television or radio, have conversations in a quiet environment, and feel comfortable being themselves. CONCLUSION: To the best of our knowledge, this is the most extensive series of CI in CMT-associated sensorineural hearing loss and auditory neuropathy. Our cohort suggests that CI is a safe and reliable method for hearing rehabilitation that can achieve good speech performance and improve QoL in CMT patients.

Predicting complications of pediatric temporal bone fractures.

OBJECTIVE: Our aim is to characterize complications of pediatric temporal bone fractures and identify predictive risk factors associated with fracture complications. METHODS: A retrospective review was conducted of all temporal bone fractures diagnosed in children (age less than or equal to 18 years) from a single academic institution between 2003 and 2017. Demographics, mechanism of injury, fracture characteristics, computed tomography evaluation and follow-up duration were recorded on each patient. Outcomes measured include facial nerve injury (FNI), cerebrospinal fluid (CSF) leak, sensorineural hearing loss (SNHL), and conductive hearing loss (CHL). RESULTS: One-hundred-seventeen patients with 129 temporal bone fractures were included in the study. Most fractures were otic capsule sparing (OCS) (96%, n = 124) and longitudinal (71%, n = 91). Otic capsule violating (OCV) fractures were associated with higher CSF leak rates (20% versus 2%, p = 0.14) and FNI rates (60% versus 5%, p = 0.002) compared to OCS fractures. Audiograms were available in 37 patients (34%). Patients with Glasgow coma scale (GCS) consistent with a mild traumatic brain injury (TBI) (GCS > 13) had significantly fewer complications (FNI and CSF leaks) compared to the group with moderate and severe TBI (GCS < 13), 5% versus 23% (p = 0.03). CONCLUSIONS: Higher complication rates are seen with OCV fractures and transverse fractures. Moderate and severe TBI as measured by GCS is predictive of FNI and CSF complications in pediatric temporal bone fractures.

State of the art regeneration of the tympanic membrane.

PURPOSE OF REVIEW: One of the most common diseases of the tympanic membrane is a perforation, and tympanoplasty is one of the more common procedures in otolaryngology. Tympanic membrane regeneration and bioengineering aim to improve the success rate of the procedure, increase the availability of different scaffolds and provide innovative tools that will simplify the surgical technique and make it accessible for surgeons with varying expertise level. This review aims to raise awareness of current tissue engineering developments in tympanic membrane regeneration and how they may augment current clinical practices. We focus here on achievements in tympanic membrane cell cultures and on innovations in development of new scaffolds and growth factors that enhance regeneration of patient's native tympanic membranes. RECENT FINDINGS: In recent years, great achievements were reached in the field of tympanic membrane regeneration in the three hallmarks of bioengineering: cells, scaffolds and bioactive molecules. New techniques for modeling normal tympanic membrane proliferation were developed, as well as for isolation and expansion of normal tympanic membrane keratinocytes from miniature samples of scarred tissue. Ongoing clinical trials aim to seal the perforation by applying different scaffolds infiltrated by growth factors on the tympanic membrane. SUMMARY: Research efforts in tympanic membrane regeneration continue to seek the ideal single tissue-engineered substitute. Recent advances in tympanic membrane bioengineering include new types of scaffolds that may augment and provide a safe and effective alternative to the current gold-standard autograft. New bioactive molecules may simplify the surgical procedure and reduce surgical time by augmenting the native tympanic membrane regeneration. Several groups of bioengineering scientists and neurotologists are continuing to move forward and develop new strategies, seeking to create a fully functional tissue-engineered tympanic membrane.

Treatment of Temporal Bone Fractures.

Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted.

Laryngotracheal transplantation: technical modifications and functional outcomes.

OBJECTIVES/HYPOTHESIS: Laryngeal transplantation offers the potential for patients without a larynx to recover their voice, which is critical in our communication age. We report clinical and functional outcomes from a laryngotracheal transplant. Widespread adoption of this technique has been slowed due to the ethical concerns of life-long immunosuppression after a nonvital organ transplant. Our patient was already on immunosuppressive medication from prior kidney-pancreas transplantation, and therefore was not exposed to added long-term risk. We describe the unique technical advances, clinical course, and rehabilitation of this patient and the implications for future laryngeal transplantation. STUDY DESIGN: Case report. METHODS: A laryngotracheal transplantation was performed in a 51-year-old prior kidney-pancreas transplant recipient presenting with complete laryngotracheal stenosis. Surgical modifications were made in the previously described technique related to retrieval, vascular supply, and reinnervation. This resulted in a robustly vascularized organ with well-perfused long-segment tracheal transplant and early return of motor reinnervation. RESULTS: A multidisciplinary approach resulted in a successful transplant without evidence of rejection to date. Postoperatively, the patient continues to rely on a tracheotomy but has had the return of an oral and nasal airway, vocalization, smell, and taste, all experienced for the first time in 11 years. CONCLUSIONS: We have demonstrated that our methods may result in a successful laryngotracheal transplant. We describe the preparation, surgical technique, rehabilitation, and interventions employed in achieving optimal outcomes. This report contributes valuable information on this rarely performed composite transplant.

Long-term hearing loss in gerbils with bacterial meningitis treated with superoxide dismutase.

HYPOTHESIS: The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only prevent cochlear fibrosis and neo-ossification but also reduce hearing loss. BACKGROUND: SOD an O2-scavenger, has been shown to prevent cochlear fibrosis and neo-ossification in gerbils infected with bacterial meningitis when injected intrathecally. The objective of this study is to investigate the effects of SOD on long-term hearing loss in gerbils infected with bacterial meningitis and to assess the relationship between hearing results and the amount of fibrosis. The effectiveness of middle ear infusion of SOD will also be examined. METHODS: Meningitis was induced in 3 groups of 10 gerbils with injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received intrathecal SOD, group 2 received a middle ear infusion of SOD, and group 3, the control group, received no SOD. Histologic data and auditory brainstem responses were obtained from each gerbil. RESULTS: In the intrathecal SOD group, the average deterioration in pure tone thresholds between the preoperative baseline and 15 weeks after induction of meningitis at 4, 8, 16, and 32 kHz was significantly less than that of the middle ear SOD and the control group (p = 0.001). There was no significant difference between the middle ear SOD and the control group. There was no fibrosis in the intrathecal SOD group, 15% of the gerbils developed an average of 11% fibrosis in the middle ear SOD group, and 20% of the gerbils developed an average of 15% in the control group. CONCLUSION: Intrathecal infusion of SOD not only prevented cochlear fibrosis and neo-ossification after bacterial meningitis but also decreased subsequent hearing loss.

Role of tumor necrosis factor-alpha in sensorineural hearing loss after bacterial meningitis.

HYPOTHESIS: Blockade of tumor necrosis factor-alpha with tumor necrosis factor-alpha antibody will reduce the extent of cochlear injury and hearing loss associated with Streptococcus pneumoniae meningitis. BACKGROUND: Inflammatory mediators play a significant role in the morbidity associated with bacterial meningitis, including hearing loss and labyrinthitis ossificans. Previous studies have shown the attenuation of hearing loss by the nonspecific blockade of such pathways. METHODS: Fifty Mongolian gerbils were divided into four groups. Auditory brainstem response testing was conducted to measure hearing thresholds. Streptococcus pneumoniae meningitis was induced in Groups 1 and 2. Group 2 was then given a single intraperitoneal injection of tumor necrosis factor-alpha antibody, whereas Group 1 received phosphate-buffered saline. Uninfected animals in Groups 3 and 4 were implanted with osmotic pumps that delivered a continuous 8-day intrathecal flow of either tumor necrosis factor-alpha (Group 4) or phosphate-buffered saline (Group 3). After 6 weeks, auditory brainstem response testing was repeated. The cochleas were harvested and analyzed histomorphometrically. RESULTS: Group 2 animals with Streptococcus pneumoniae meningitis that also received tumor necrosis factor-alpha antibody developed significantly less hearing loss than Group 1 animals with meningitis alone. The decrease in the average threshold at 4, 8, 16, and 32 kHz was 31, 30, 25, and 28 dB sound pressure level, respectively (p < 0.0092 for each). Furthermore, histomorphometric analysis showed significantly less damage to the organ of Corti, spiral ganglion, spiral ligament, and stria vascularis in Group 2. Conversely, tumor necrosis factor-alpha induced meningitis animals (Group 3) showed increased hearing loss compared with phosphate-buffered saline controls (Group 4), with p < 0.0001 at all frequencies. CONCLUSION: Tumor necrosis factor-alpha plays an important role in cochlear injury after bacterial meningitis. Blockade of tumor necrosis factor-alpha reduces postmeningitic hearing loss and cochlear injury. Induction of meningitis with intrathecal tumor necrosis factor-alpha also resulted in hearing loss and cochlear injury similar to bacterial meningitis.

Fine structure histopathology of labyrinthitis ossificans in the gerbil model.

Labyrinthitis ossificans (LO) is the pathological deposition of new bone within the lumen of the cochlea and labyrinth. This process occurs most commonly as a result of infection or inflammation affecting the otic capsule. Trauma and vascular compromise can also lead to neo-ossification within the otic capsule. The mechanism that regulates this process remains unestablished. This study details the end-stage histopathology in high-resolution plastic thin sections. Twenty Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3 followed by subcutaneous penicillin G procaine (8 days) and were painlessly sacrificed 3 months later. The cochleas were serially divided and sectioned for light and electron microscopy. Sixteen of 20 animals (27 of 40 cochleas) demonstrated LO. Cochlear damage was most extensive in the vestibule and basal turn and decreased toward the apex, which often appeared normal. The histopathologic findings consisted of 1) new bone, calcospherites, osteoid, and fibrosis without dense connective tissue or osteoblasts extending from the endosteal wall into the lumen of the vestibule and scala tympani; 2) areas of dense connective tissue and osteoid enclosed by epithelial cells conjoined with the organ of Corti, stria vascularis, spiral ligament, and vestibular (Reissner's) membrane; and 3) partial to complete loss of the organ of Corti, spiral ligament cell bodies, stria vascularis, and spiral ganglion cells. Osteoblastic activity was not demonstrated in end-stage ossification in LO in the gerbil model. Neo-ossification appears to occur by calcospherite deposition along collagen-like fibrils within osteoid. The destruction of the organ of Corti, spiral ganglion cells, stria vascularis, and cells of Reissner's membrane and the spiral ligament occurs even in the absence of ossification of the cochlear duct.

The effects of superoxide dismutase in gerbils with bacterial meningitis.

BACKGROUND: Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments. OBJECTIVE: To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis. STUDY DESIGN: Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline. Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil. RESULTS: Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs. IM: P = 0.010; IT vs. control group: P = 0.001). The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = -0.753, P < 0.00001). CONCLUSIONS: IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

Location and timing of initial osteoid deposition in postmeningitic labyrinthitis ossificans determined by multiple fluorescent labels.

OBJECTIVES/HYPOTHESIS: Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis. The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3-month period after infection. STUDY DESIGN: Randomized, double-blind study. METHODS: Fluorochromes are compounds that specifically incorporate into ossifying bone. Sequential addition of different colored fluorochromes during osteoneogenesis define the timing and location of osteoid deposition and mineralization. Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3, and control gerbils received saline. Both groups were injected with calcein on postoperative day 3, followed by xylenol orange, oxytetracycline, and alizarin red on days 7, 14, and 28 respectively. Ten experimental gerbils were killed 24 hours after each label, and an additional group at 84 days after infection. Two groups of 10 control gerbils were killed at 29 and 84 days after treatment. The temporal bones and tibias were harvested, embedded in plastic, and sliced with a diamond saw. Wafers at a thickness of 200 microm were mounted in sequence and examined. RESULTS: Sixteen of 49 experimental animals (33%) were positive for at least one of the fluorescent labels. Fluorescent labeled osteoid was present at all sampling times. Label extended from the endosteal wall into the lumen of the scala tympani between the vestibule and the round window membrane. Discrete sites of fluorescence varied among specimens and were associated with the opening of the cochlear aqueduct, the scala tympani, organ of Corti, and the stria vascularis and spiral ligament in all turns from base to apex. CONCLUSION: The results indicate that osteoid is deposited and begins mineralization by day 3 after infection, at least, and continues, at least, through the first 28 days after infection. There was no apparent resorption of new bone and remodeling by 84 days after infection.