Shinsuke Ohshima

Transcranial photo-inactivation of neural activities in the mouse auditory cortex.

Flavoprotein fluorescence in the brain is intimately coupled with neuronal aerobic energy metabolism. If flavoproteins are photobleached, neural activities may be affected owing to dysfunction in aerobic energy metabolism in mitochondria. We tested this possibility in cortical slices from mice, and found that exposure to blue light (lambda = 475 nm) derived from a 20 mW diode laser for 50 min suppresses trans-synaptic components of field potentials. This finding formed the basis of a transcranial photo-inactivation technique, that was used to investigate auditory signal transmission between the anterior auditory field (AAF) and the primary auditory cortex (AI) in anesthetized mice. Cortical responses in AAF and AI, elicited by 5 kHz tonal stimuli, were visualized using transcranial flavoprotein fluorescence imaging. After determining responsive areas in AAF and AI, the auditory cortex was exposed to the blue diode laser via the intact skull, while either AAF or AI was protected with a piece of carbon paper. Although the photo-inactivation of AI had no significant effect on the fluorescence responses in AAF, the photo-inactivation of AAF significantly reduced the fluorescence responses in AI, indicating the presence of auditory signal transmission from AAF to AI.

Auditory cortical areas activated by slow frequency-modulated sounds in mice

Species-specific vocalizations in mice have frequency-modulated (FM) components slower than the lower limit of FM direction selectivity in the core region of the mouse auditory cortex. To identify cortical areas selective to slow frequency modulation, we investigated tonal responses in the mouse auditory cortex using transcranial flavoprotein fluorescence imaging. For differentiating responses to frequency modulation from those to stimuli at constant frequencies, we focused on transient fluorescence changes after direction reversal of temporally repeated and superimposed FM sweeps. We found that the ultrasonic field (UF) in the belt cortical region selectively responded to the direction reversal. The dorsoposterior field (DP) also responded weakly to the reversal. Regarding the responses in UF, no apparent tonotopic map was found, and the right UF responses were significantly larger in amplitude than the left UF responses. The half-max latency in responses to FM sweeps was shorter in UF compared with that in the primary auditory cortex (A1) or anterior auditory field (AAF). Tracer injection experiments in the functionally identified UF and DP confirmed that these two areas receive afferent inputs from the dorsal part of the medial geniculate nucleus (MG). Calcium imaging of UF neurons stained with fura-2 were performed using a two-photon microscope, and the presence of UF neurons that were selective to both direction and direction reversal of slow frequency modulation was demonstrated. These results strongly suggest a role for UF, and possibly DP, as cortical areas specialized for processing slow frequency modulation in mice.

Cortical depression in the mouse auditory cortex after sound discrimination learning

Cortical responses after sound discrimination learning were investigated using transcranial flavoprotein fluorescence imaging in mice. Water-deprived mice were trained to discriminate between rewarded (S+) and unrewarded (S-) sound stimuli. After the learning, they were anesthetized, and cortical responses to S+ and S- were recorded in the right auditory cortex. When a pure tone (PT) at 10 kHz and a 10 kHz amplitude-modulated (AM) sound were used as S+ and S-, the cortical responses to S- using AM were significantly depressed but those to S- using PT were not. The cortical responses to S+ showed no significant change. Upward frequency-modulated sounds from 5 kHz to 40 kHz (FM upward arrow) and downward frequency-modulated sounds from 40 kHz to 5 kHz (FM downward arrow) were also used as S+ and S-. Cortical responses to S- using FM[upward arrow] and FM[downward arrow] were significantly depressed after learning, while those to S+ were unchanged. No significant change of cortical responses to S- using FMs was observed in the left auditory cortex after learning. The learning-induced depression of S- using FMs was most clearly observed in the medial part of the tonotopic band to 40 kHz in the right primary auditory cortex, which might be involved in processing FM sounds.

Long-term follow-up results of canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction in cholesteatoma surgery.

Background The pathogenesis of recurrent cholesteatoma can be roughly divided into residual lesions and re-retraction of the epithelium. To prevent both residual and re-retraction cholesteatoma, we performed canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction as a fundamental surgical treatment for patients with acquired cholesteatoma. We attempted to achieve the complete extirpation of cholesteatoma in the wide surgical field made by the canal wall down procedure and simultaneously prevent recurrent retraction cholesteatoma and regain the physiologic canal wall, in which patients can have a “maintenance-free ear.” Objective The surgical method used in the present study was described, and the long-term postoperative results of this method were evaluated. Study Design Retrospective study. Patients Participants were 118 patients with acquired cholesteatoma who underwent canal wall down tympanoplasty with mastoid obliteration and could be followed-up for more than 5 years. Main Outcome Measures Postoperative changes in the reconstructed canal wall, the rate of otorrhea, and exposure of the material were examined using endoscopic images, medical charts, and CT scans. Results A total of 113 ears (95.8 %) achieved the nearly physiologic appearance of the external auditory canal, and these conditions were maintained throughout the follow-up periods. However, recurrent cholesteatoma was not observed during the follow-up periods. Postoperative otorrhea was observed in 2.5% of ears. Exposure of the bone pate was only noted in 1 patient (0.8 %). Postoperative CT scans confirmed that ossification developed in the bone pate used in the reconstructed canal wall and mastoid surface. Conclusion Canal wall down tympanoplasty with mastoid obliteration using the bone pate plate for canal wall reconstruction prevents both recurrent and residual cholesteatoma and contributes to a good quality of life for the patient.

Can the Pathogenesis of Auditory Ossicular Malformations be Explained by the Branchial-based Theory?—evaluation by the Consecutive Distribution of Embryologic Foci in 87 Cases

Background Development of the auditory ossicles is initiated by induction of the cartilage primordium of each ossicle between the fifth and seventh fetal week. It is well known that primordium of the upper part of the ossicular chain is derived from the first branchial arch and that of the lower part develops from the second branchial arch. Previous studies have suggested that auditory ossicular malformations are caused by deficiencies in the early period of induction of the cartilage primordium. However, auditory ossicular malformations can occur at any developing stage, and their clinical features are very complicated. Objective The precise embryologic foci of auditory ossicular malformations were estimated by evaluating the consecutive distribution of these anomalies, and the pathogenesis of these malformations was discussed using new aspects. Study Design Retrospective study. Patients Eighty-seven ears of 78 patients that underwent surgical treatment after the diagnosis of an auditory ossicular malformation in Niigata University Hospital between 1998 and 2012. Main Outcome Measures The types of malformations were roughly divided into 4 groups based on intraoperative findings: Type A—ankylosis of the malleus head or short process of the incus; type B—defect in the connection between the incus and stapes; type C—fixation of the footplate; and type D—a complex lesion combining types B and C. Additionally, the consecutive points of the malformation were precisely evaluated, and a distribution map of the malformation was made. Foci of the malformations of each type were then estimated. Results Type A malformations were observed in 8 ears, type B in 33 ears, type C in 32 ears, type D in 6 ears, and unclassified anomalies in 8 ears. A deformity was observed in the malleus handle, which is located in the lower part of the ossicle, in 5 of 7 ears with type A malformations, which suggests that the pathogenesis of ankylosis of the malleus head or short process of the incus could not simply be explained by the branchial-based theory. The focus of the type B malformation was located on the long process of the incus and not onthe I-S joint. We suggest that pathogenesis of the defect inthe connection between the incus and stapes could not be explained by a conjugation deficiency in the cartilage primordium but could be explained by an ossification deficiency after the conjugation period. The focus of the location of the defect was shifted more medially in type D malformations than in type B malformations, and this was significantly different, which suggests that this type of malformation is not caused by 2 independent anomalies but is inducted by a monogenic abnormality. Conclusion The foci of auditory ossicular malformations were highly variable, which suggests that the pathogenesis of these malformations could not be simply explained by a branchial-based theory. Auditory ossicular malformations occur at various developmental stages of the auditory ossicles.

Creating an Optimal 3D Printed Model for Temporal Bone Dissection Training

Objective: Making a 3-dimensional (3D) temporal bone model is simple using a plaster powder bed and an inkjet printer. However, it is difficult to reproduce air-containing spaces and precise middle ear structures. The objective of this study was to overcome these problems and create a temporal bone model that would be useful both as a training tool and for preoperative simulation. Methods: Drainage holes were made to remove excess materials from air-containing spaces, ossicle ligaments were manually changed to bony structures, and small and/or soft tissue structures were colored differently while designing the 3D models. The outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of the model, comparison of computed tomography (CT) images of the model to the original CT, and assessment of tactile sensation and reproducibility by 20 surgeons performing surgery on the model. Results: Macroscopic and endoscopic inspection, CT images, and assessment by surgeons were in agreement in terms of reproducibility of model structures. Most structures could be reproduced, but the stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative tactile sensation of the model was excellent. Conclusions: Although this model still does not embody perfect reproducibility, it proved sufficiently practical for use in surgical training.

Primary paraganglioma in the facial nerve canal

OBJECTIVE To describe primary paraganglioma in the facial nerve canal and discuss the characteristics of facial nerve paraganglioma in contrast with other tumors. CASE REPORT A 23-year-old man developed gradually progressive right facial palsy as the initial symptom. One year later, he exhibited hearing loss without tinnitus in his right ear. CT demonstrated an enlarged facial nerve canal with irregular bony erosion of the circumference. MRI showed a well-enhanced heterogeneous mass with hypo-intensity spots inside it. During surgery, a blood-rich tumor was observed along the facial nerve: however, extensive bleeding interfered with tumor removal. The surgical specimen demonstrated paraganglioma. The tumor was completely removed in the second surgery in combination with arterial embolization. Facial nerve function was reconstructed with a free muscle flap more than one year following resection. CONCLUSION Because paraganglioma is a blood-rich tumor, it is important to perform angiography and embolization. If preoperative facial nerve palsy is demonstrated, careful management of facial nerve function is needed. Paraganglioma must be considered in the differential diagnosis of a facial nerve tumor.

Risk Factors of Recurrence in Pediatric Congenital Cholesteatoma

OBJECTIVE To examine the risk factors of recurrence in pediatric congenital cholesteatoma. STUDY DESIGN Retrospective chart review. SETTING University hospital. PATIENTS Sixty-seven patients having tympanic type of congenital cholesteatoma under 15-years old at surgery. INTERVENTIONS Canal wall-up tympanomastoidectomy (n = 30) or transcanal atticotomy/tympanoplasty (n = 37) was performed depending on cholesteatoma extension, 16 of which were followed by second-look surgery. Preoperative computed tomography (CT) before second-look surgery or follow-up CT was performed to detect residual recurrence 1 year after the surgery. Cholesteatoma found at the second surgery was also included in the recurrence. All patients had no recurrent cholesteatoma at the last follow-up (median, 61 mo after surgery). MAIN OUTCOME MEASURES Possible predictive factors were compared between the groups. RESULTS Residual cholesteatoma and retraction cholesteatoma occurred in 21 and 6%, respectively. There was no significant difference in age, sex, and type of cholesteatoma (open or closed) between the groups; however, Potsic stage and status of stapes involvement were more advanced in the residual cholesteatoma group. All residual lesions could be detected by follow-up CT or by second-look surgery. All of four retraction cholesteatoma patients were male, young at the surgery and in stage IV. CONCLUSION Recurrence mostly occurred as residual cholesteatoma, suggesting that CT is recommended as a follow-up tool for congenital cholesteatoma. Advanced lesions had the risk of residual cholesteatoma, suggesting that complete removal of epithelium is important. Although rare, young advanced-stage patients had risk of retraction cholesteatoma and therefore normal mucosa should be preserved as much as possible for these patients.

Vestibular Involvement in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE Otitis media (OM) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a novel concept of ear disease that is characterized by progressive mixed or sensorineural hearing loss with occasional systemic involvement. Considering the accumulating knowledge about the characteristics of and treatment for auditory dysfunction in OMAAV, the objective of this study was to investigate the vestibular function and symptoms of patients with OMAAV. STUDY DESIGN Retrospective chart review. SETTING University hospital. PATIENTS Thirty-one OMAAV patients met criteria proposed by the OMAAV study group in Japan. MAIN OUTCOME MEASURES Clinical characteristics and vestibular tests. RESULTS Eleven of 31 OMAAV patients had vestibular symptoms; 3 patients had acute vertigo attack with sudden hearing loss and 8 patients had chronic dizziness. Episodic vertigo was not seen in any of the patients. Three patients who received a less intensive therapy without immunosuppressive agents developed intractable persistent dizziness. All symptomatic patients and six of the nine OMAAV patients without vestibular symptoms showed unilateral or bilateral caloric weakness; therefore, vestibular involvement was present in 84% of OMAAV patients. Gain of vestibulo-ocular reflex was reduced in symptomatic patients. The eye-tracking test and optokinetic nystagmus revealed no evidence of central dysfunction. CONCLUSION Vestibular dysfunction was seen in 84% of OMAAV patients. One-third of OMAAV patients showed vestibular symptoms such as acute vertigo attack or chronic dizziness, which are of peripheral origin. One-third of the symptomatic patients developed intractable dizziness. Initial intensive treatment by combination therapy with steroid and immunosuppressive agents may be essential for preventing the development of intractable dizziness.

Bone Density Development of the Temporal Bone Assessed by Computed Tomography

HYPOTHESIS The temporal bone shows regional differences in bone development. BACKGROUND The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. METHODS Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. RESULTS The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. CONCLUSION To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.