Nauman F. Manzoor

Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus.

Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2-3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time.

Meniere's disease

Menieres disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.

Activation of the central nervous system induced by micro-magnetic stimulation

Electrical and transcranial magnetic stimulation have proven to be therapeutically beneficial for patients suffering from neurological disorders. Moreover, these stimulation technologies have provided invaluable tools for investigating nervous system functions. Despite this success, these technologies have technical and practical limitations impeding the maximization of their full clinical and preclinical potential. Recently, micro-magnetic stimulation, which may offer advantages over electrical and transcranial magnetic stimulation, has proven effective in activating the neuronal circuitry of the retina in vitro. Here we demonstrate that this technology is also capable of activating neuronal circuitry on a systems level using an in vivo preparation. Specifically, the application of micro-magnetic fields to the dorsal cochlear nucleus activates inferior colliculus neurons. Additionally, we demonstrate the efficacy and characteristics of activation using different magnetic stimulation parameters. These findings provide a rationale for further exploration of micro-magnetic stimulation as a prospective tool for clinical and preclinical applications.

Endolymphatic sac tumors

Endolymphatic sac tumors (ELST) are slow-growing, locally aggressive, low-grade malignancies that originate from the epithelium of the endolymphatic duct and sac. ELST often present with sensorineural hearing loss, tinnitus, and vertigo, which may mimic Meniere disease. Large tumors may present with additional cranial neuropathies. Management is primarily via microsurgical excision. Radiation therapy has a limited role for residual or unresectable disease. Early detection may enable hearing preservation techniques. ELST have an association with von Hippel-Lindau disease.

Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol.

Increased spontaneous firing (hyperactivity) is induced in fusiform cells of the dorsal cochlear nucleus (DCN) following intense sound exposure and is implicated as a possible neural correlate of noise-induced tinnitus. Previous studies have shown that in normal hearing animals, fusiform cell activity can be modulated by activation of parallel fibers, which represent the axons of granule cells. The modulation consists of a transient excitation followed by a more prolonged period of inhibition, presumably reflecting direct excitatory inputs to fusiform cells and an indirect inhibitory input to fusiform cells from the granule cell-cartwheel cell system. We hypothesized that since granule cells can be activated by cholinergic inputs, it might be possible to suppress tinnitus-related hyperactivity of fusiform cells using the cholinergic agonist, carbachol. To test this hypothesis, we recorded multiunit spontaneous activity in the fusiform soma layer (FSL) of the DCN in control and tone-exposed hamsters (10 kHz, 115 dB SPL, 4h) before and after application of carbachol to the DCN surface. In both exposed and control animals, 100 μM carbachol had a transient excitatory effect on spontaneous activity followed by a rapid weakening of activity to near or below normal levels. In exposed animals, the weakening of activity was powerful enough to completely abolish the hyperactivity induced by intense sound exposure. This suppressive effect was partially reversed by application of atropine and was usually not associated with significant changes in neural best frequencies (BF) or BF thresholds. These findings demonstrate that noise-induced hyperactivity can be pharmacologically controlled and raise the possibility that attenuation of tinnitus may be achievable by using an agonist of the cholinergic system.

Impact of surgical resection on survival in patients with advanced head and neck cancer involving the carotid artery.

IMPORTANCE The present study addresses the survival benefit of aggressive surgical treatment of head and neck cancer involving the carotid artery. OBJECTIVE To assess survival outcomes in patients treated for advanced squamous cell carcinoma involving the carotid artery using different treatment strategies. DESIGN, SETTING, AND PARTICIPANTS Retrospective study at a tertiary care center of 44 consecutive patients with squamous cell carcinoma involving the carotid artery from 2005 to 2012 with a median follow-up of 12 months. The radiologist was blinded to the outcome of surgical procedures. INTERVENTIONS Surgery with or without radiotherapy, and definitive chemoradiation. MAIN OUTCOMES AND MEASURES Overall survival and rates of locoregional and distant failures. The hypothesis was formulated before data collection. RESULTS Of 44 patients, 35 (80%) were treated with curative intent with surgery with or without adjuvant therapy (n = 27 [61%]) or definitive chemoradiation therapy (n = 8 [18%]), while 9 patients (21%) were treated in a palliative fashion. Patients treated with curative intent had improved overall survival (median survival, 13.5 months) compared with the palliative group (median survival, 3.6 months) (P = .001). Of patients treated with curative intent, those with previously untreated disease (n = 14 [40%]) had an improved outcome relative to patients with recurrent or persistent disease (n = 21 [60%]), with median survival of 38.7 and 9.6 months, respectively (P = .008). Patients were treated with curative intent using 3 different treatment strategies (ie, carotid artery resection with or without reanastamosis) (n = 6 [17%]), curative peeling with or without adjuvant therapy (n = 21 [ 60%]), and definitive chemoradiation therapy (n = 8 [23%]). Survival outcome was not significantly different between subgroups treated with curative intention (P = .47). When reviewed by a head and neck radiologist in a blinded fashion (n = 30), preintervention imaging had a positive predictive value of 72.7% for resectability of cancer involving the carotid artery. In cases with almost circumferential involvement (>270°) and narrowing of the carotid artery, the disease was unresectable (n = 3). CONCLUSIONS AND RELEVANCE Advanced head and neck cancer involving the carotid artery can be treated with curative intent with favorable results in most patients. If disease burden merits, an aggressive approach involving resection with or without reanastamosis of the carotid artery can be used without significant added morbidity.

Mapping and morphometric analysis of synapses and spines on fusiform cells in the dorsal cochlear nucleus

Fusiform cells are the main integrative units of the mammalian dorsal cochlear nucleus (DCN), collecting and processing inputs from auditory and other sources before transmitting information to higher levels of the auditory system. Despite much previous work describing these cells and the sources and pharmacological identity of their synaptic inputs, information on the three-dimensional organization and utltrastructure of synapses on these cells is currently very limited. This information is essential since an understanding of synaptic plasticity and remodeling and pathologies underlying disease states and hearing disorders must begin with knowledge of the normal characteristics of synapses on these cells, particularly those features that determine the strength of their influence on the various compartments of the cell. Here, we employed serial block face scanning electron microscopy (SBFSEM) followed by 3D reconstructions to map and quantitatively characterize synaptic features on DCN fusiform cells. Our results reveal a relative sparseness of synapses on the somata of fusiform cells but a dense distribution of synapses on apical and basal dendrites. Synapses on apical dendrites were smaller and more numerous than on basal dendrites. The vast majority of axosomatic terminals were found to be linked to other terminals connected by the same axon or different branches of the same axon, suggesting a high degree of divergent input to fusiform cells. The size of terminals was correlated with the number of mitochondria and with the number of active zones, which was highly correlated with the number of postsynaptic densities, suggesting that larger terminals exert more powerful influence on the cell than smaller terminals. These size differences suggest that the input to basal dendrites, most likely those from the auditory nerve, provide the most powerful sources of input to fusiform cells, while those to apical dendrites (e.g., parallel fiber) are weaker but more numerous.

Contemporary management of carotid blowout syndrome utilizing endovascular techniques

To illustrate complex interdisciplinary decision making and the utility of modern endovascular techniques in the management of patients with carotid blowout syndrome (CBS).

Bilateral Sequential cochlear implantation in patients with enlarged vestibular aqueduct (EVA) syndrome

Objectives: To analyze audiometric outcomes after bilateral cochlear implantation in patients with isolated enlarged vestibular aqueduct (EVA) syndrome and associated incomplete partition (IP) malformations. Secondary objective was to analyze rate of cerebrospinal fluid (CSF) gusher in patients with IP-EVA spectrum deformities and compare this with the existing literature. Study Design: Retrospective chart review. Methods: Thirty-two patients with EVA syndrome who received unilateral or bilateral cochlear implants between June 1999 and January 2014 were identified in the University Hospitals Case Medical Center cochlear implant database. Isolated EVA (IEVA) and Incomplete Partition Type II (IP-II) malformations were identified by reviewing high-resolution computed tomography (HRCT) imaging. Demographic information, age at implantation, surgical details, postimplantation audiometric data including speech reception thresholds (SRT), word, and sentence scores were reviewed and analyzed. Intra- and postoperative complications were analyzed as well and compared with the literature. Results: Seventeen patients (32 implanted ears) had pediatric cochlear implantation for EVA-associated hearing loss. Data from 16 controls (32 implanted ears) were used to compare audiometric and speech outcomes of EVA cohort. Mean age at implantation was 6.8 years for EVA cohort and 6.0 years for controls. There was no statistically significant difference in long-term postoperative SRT, monaurally aided word scores, and binaurally tested word scores between pediatric EVA group and controls. The EVA patients had a long-term mean sentence score of 85.92%. A subset of EVA patients implanted at mean age of 3.18 years (n = 15 ears) had similar audiometric outcomes to another control group with Connexin 26 mutations (n = 20 ears) implanted at a similar age. Further subset analysis revealed no significant differences in age at implantation, SRT, and word scores in patients with IEVA and IP-II malformation. There was no significant association between size of vestibular aqueduct and age at implantation. There was no CSF gusher or other intra- or postoperative complications reported in our series. Conclusion: Bilateral sequential cochlear implantation can be performed safely in patients with EVA. Audiometric outcomes are excellent and comparable to pediatric cochlear implant patients with no malformations. CSF gusher rates can be minimized by trans-round window approach. Further long-term studies are needed to identify differences within IP-EVA spectrum deformities, audiometric outcomes, and proportions of EVA patients who will need cochlear implantation for hearing rehabilitation.

Vestibular Aqueduct Midpoint Width and Hearing Loss in Patients With an Enlarged Vestibular Aqueduct

Importance Elucidating the relationship between vestibular aqueduct size and hearing loss progression may inform the prognosis and counseling of patients who have an enlarged vestibular aqueduct (EVA). Objectives To examine the association between vestibular aqueduct size and repeated measures of hearing loss. Design, Setting, and Participants For this retrospective medical record review, 52 patients with a diagnosis of hearing loss and radiologic diagnosis of EVA according to the Valvassori criterion were included. All available speech reception threshold and word recognition score data was retrieved; mixed-effects models were constructed where vestibular aqueduct size, age at diagnosis of hearing loss, and time since diagnosis of hearing loss were used to predict repeated measures of hearing ability. This study was performed at an academic tertiary care center. Exposures Variable vestibular aqueduct size, age at first audiogram, length of time after first audiogram. Main Outcomes and Measures Speech reception threshold (dB) and word recognition score (%) during routine audiogram. Results Overall, 52 patients were identified (29 females [56%] and 23 males [44%]; median age at all recorded audiograms, 7.8 years) with a total of 74 ears affected by EVA. Median (range) vestibular aqueduct size was 2.15 (1.5-5.9) mm, and a median (range) of 5 (1-18) tests were available for each patient. Each millimeter increase in vestibular aqueduct size above 1.5 mm was associated with an increase of 17.5 dB in speech reception threshold (95% CI, 7.2 to 27.9 dB) and a decrease of 21% in word recognition score (95% CI, −33.3 to −8.0 dB). For each extra year after a patient’s first audiogram, there was an increase of 1.5 dB in speech recognition threshold (95% CI, 0.22 to 3.0 dB) and a decrease of 1.7% in word recognition score (95% CI, −3.08 to −0.22 dB). Conclusions and Relevance Hearing loss in patients with an EVA is likely influenced by vestibular aqueduct midpoint width. When considering hearing loss prognosis, vestibular aqueduct midpoint width may be useful for the clinician who counsels patients affected by EVA.