Pleomorphic Adenoma of the External Auditory Canal From Ceruminous Gland Adenoma: Case Report and Review of the Literature.

We describe a right external auditory canal (EAC) recurrent ceruminous pleomorphic adenoma (CPA) accompanied by itching and review the clinical features and histopathology of this disease. A female in her 70s presented with a right EAC mass accompanied by itching. We initially diagnosed the mass as a ceruminous gland adenoma (CGA) following excisional biopsy. Two years and nine months later, the tumor recurred at the same site. A preoperative computed tomography (CT) scan demonstrated no bone destruction, and magnetic resonance imaging (MRI) showed a 1 × 1 cm mass with a clearly defined margin in the right EAC. We completely excised the recurrent tumor using a transmeatal approach under general anesthesia. Histopathology demonstrated haphazard proliferation of tubule-glandular structures lined by two layers of the epithelium in the hypocellular stroma composed of a mucoid matrix. The recurring tumor was diagnosed as a CPA. Here, an EAC tumor-originally diagnosed as a CGA following excisional biopsy-recurred and was subsequently diagnosed as a CPA. CPA can be considered an unusual variant of CGA.

Case report: Concurrent intravestibular schwannoma mimicking Ménière's disease and cochlear hydrops detected via delayed three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging.

Objective: To present a case of intralabyrinthine schwannoma (ILS) presenting as Ménière's disease diagnosed via 4-h delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) and treated successfully using the translabyrinthine approach. Patient: A patient who was diagnosed with intravestibular ILS. Interventions: The patient underwent comprehensive preoperative neurological examinations and MRI. The tumor was resected using the translabyrinthine approach and was pathologically confirmed as schwannoma based on the surgical specimen. Main outcome measures: Preoperative audiogram and vestibular test findings and MRI images. Results: Preoperatively, pure-tone audiogram showed progressive sensorineural hearing loss only on the affected side. The video head impulse test and vestibular evoked myogenic potential test showed vestibular dysfunction on the affected ear. Immediate gadolinium-enhanced T1-weighted MRI revealed an enhanced region in the vestibule. Meanwhile, magnetic resonance cisternography showed a filling defect. Delayed 3D-FLAIR MRI revealed a signal void in the scala media of the cochlea indicative of cochlear hydrops, and a strong signal in the perilymph at the basal cochlea suggestive of impaired blood-labyrinthine barrier. Conclusion: Delayed 3D-FLAIR MRI is useful in diagnosing concurrent ILSs and endolymphatic hydrops.

A Multi-Institutional Study of Older Hearing Aids Beginners-A Prospective Single-Arm Observation on Executive Function and Social Interaction.

OBJECTIVES: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. DESIGN: Multi-institutional prospective single-arm observational study. SETTING AND PARTICIPANTS: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. METHODS: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). RESULTS: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. CONCLUSIONS AND IMPLICATIONS: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family.

A case of hypertrophic cranial pachymeningitis associated with invasive Aspergillus mastoiditis.

We report a rare case of hypertrophic cranial pachymeningitis (HCP) associated with invasive Aspergillus mastoiditis. A 63-year-old man with diabetes mellitus underwent mastoidectomy because of chronic discharge from his left ear. The mastoidectomy was unsuccessful in resolving purulent otorrhea; moreover, 7 months later, the patient developed left abducens nerve palsy. Magnetic resonance imaging revealed HCP at the left middle cranial fossa. Although the pathogen could not be identified, an Aspergillus infection was considered based on elevated serum ß-d-glucan and a positive Aspergillus antigen test result. Voriconazole treatment resolved diplopia and left otorrhea and dramatically improved HCP.

Use of ambulatory anesthesia with manually assisted ventilation for tympanic membrane regeneration therapy in children.

PURPOSE: To present the utility of ambulatory anesthesia using manually assisted ventilation via a facemask for tympanic membrane (TM) regeneration therapy in children. MATERIAL AND METHODS: The study included 10 children (age 4-11years) in whom the duration of perforation before treatment exceeded 6months and who were followed for at least 1year after treatment between December 2009 and December 2012. Under ambulatory anesthesia using manually assisted ventilation via a facemask, TM regenerative therapy with atelocollagen combined with basic fibroblast growth factor was performed in children who could not tolerate the procedure under local anesthesia alone. RESULTS: All of the children completed the TM regenerative therapy under ambulatory anesthesia in less than 5min. Complete closure was achieved in nine (81.8%) ears after 1year of postoperative follow-up. CONCLUSION: TM regenerative therapy can be performed under local anesthesia in less than 5min without a skin incision. However, local anesthesia is often insufficient in small children undergoing this procedure. Therefore, ambulatory anesthesia using manually assisted ventilation via a facemask is appropriate to complete this procedure safely in small children.

Preoperative factors affecting tympanic membrane regeneration therapy using an atelocollagen and basic fibroblast growth factor.

IMPORTANCE: The use of growth factors to achieve closure of perforated tympanic membranes (TMs) has recently become popular. However, preoperative factors affecting treatment outcomes have seldom been discussed. OBJECTIVE: To evaluate preoperative factors contributing to the success or failure of healing of perforated TMs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 153 patients (48 males and 105 females) in whom the duration of perforation was longer than 6 months prior to treatment and who were observed for at least 1 year after treatment between July 2009 and June 2012. Eight factors considered likely to affect the outcome of perforation closure were statistically evaluated using multivariate logistic regression analysis. INTERVENTIONS: Each perforated TM was filled with a synthetic graft material (atelocollagen sponge and silicone membrane) containing human basic fibroblast growth factor to promote wound healing after TM perforation closure. MAIN OUTCOMES AND MEASURES: Complete closure vs residual perforation. RESULTS: After 1 year of follow-up, 101 patients (66.0%) achieved complete closure, 30 patients (19.6%) had residual pinhole perforations (<1 mm diameter), and 22 patients (14.4%) had larger residual perforations. Multivariate logistic regression analysis adjusted for each explanatory variable identified a TM without calcification (odds ratio [OR], 2.68 [95% CI, 1.17-6.15]; P = .03) and a perforation not involving the tympanic annulus (odds ratio, 2.75 [95% CI, 1.09-6.94]; P = .04) as significant. Insignificant factors included perforation margin identified on microscopy (OR, 0.24 [95% CI, 0.99-6.27]; P < .001), perforation margin without epithelial migration (OR, 7.27 [95% CI, 0.66-80.49]; P = .11), absence of preoperative otorrhea (P = .38), no previous ear operations (P = .82), perforation size (P = .14), and patient age (P = .26). CONCLUSIONS AND RELEVANCE: Tympanic membrane regeneration therapy can be applied to all patients, except those with cholesteatoma or malignant neoplasm. However, patients with severe calcification of the TM and those with marginal perforations close to the fibrous annulus should be treated more prudently to achieve perforation closure.

Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects.

Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss.

Clinical features, presenting symptoms, and surgical results of congenital cholesteatoma based on Potsic's staging system.

CONCLUSIONS: Potsic's staging system is a clinically useful procedure for evaluating the extent of congenital cholesteatoma (CC). OBJECTIVES: We investigated the clinical features, presenting symptoms, and surgical results of CC according to Potsic's staging system. METHODS: A total of 71 patients who had undergone surgery at our hospital were retrospectively analyzed for presenting symptoms, the location of cholesteatoma, and surgical results according to Potsic's staging system. RESULTS: Of the 71 patients, 21 were classified as Potsic stage I, 9 as stage II, 31 as stage III, and 10 as stage IV. More than half of the patients with early-stage CC (stages I and II) were diagnosed asymptomatically by a chance visit to a clinic or on ear screening. Others were diagnosed following a complaint of hearing loss, acute otitis media, or otitis media with effusion. The location of CC varied somewhat by stage. In stage I CC, the most frequent location was behind the anterior-superior quadrant of the tympanic membrane; however, in stage III CC, it was behind the posterior-superior quadrant. All patients were treated surgically. Recurrence was detected in 2 of the 71 patients (2.8%); both had stage II CC. Recurrent lesions were removed during revision surgery.

Gelatin hydrogel with basic fibroblast growth factor for tympanic membrane regeneration.

HYPOTHESIS: In this developmental research study that aimed to develop tympanic membrane regeneration therapy, we devised a method of sustained bFGF formulation release using gelatin hydrogel in a guinea pig eardrum perforation model. BACKGROUND: Basic fibroblast growth factor (bFGF) can promote perforation closure. In addition, several studies of bFGF formulations have used gelatin hydrogel-bFGF coupled electrostatically to a gelatin polymer. BFGF is released gradually as a result of degradation of the gelatin polymer, and studies have shown that the long-term pharmacologic effects of bFGF can be maintained. METHODS: Using a CO(2) laser, total tympanic membrane perforations were created in 24 guinea pig ears and divided into 3 groups: the bFGF-gelatin hydrogel group(n = 8), the saline-gelatin hydrogel group (n = 8), and the control group (n = 8). Either a bFGF formulation or saline was impregnated into gelatin hydrogen and implanted into the perforated tympanic membrane. RESULTS: All ear drums of the control group showed large perforations at even the 30th postoperative day. The perforation persisted in 3 of 8 ears in the saline-gelatin hydrogel group, and the tympanic membranes that had achieved closure were thinned, whereas all ears in the bFGF-gelatin hydrogel group achieved closure of the perforation. In the ears in which a normal tympanic membrane had regenerated, histologic observation with hematoxylin and eosin staining revealed that, although mucosal and epithelial layer regeneration had occurred in the saline-gelatin hydrogel group, the bFGF-gelatin hydrogel group showed regeneration of the fibrous layer in addition to the other 2 layers. CONCLUSION: These data suggest that hydrogel impregnated with bFGF induces regeneration of the tympanic membrane and can conservatively treat tympanic membrane perforation.

Air-bone gap in ears with a well-repaired tympanic membrane after Type III and Type IV tympanoplasty.

OBJECTIVE: To investigate the air-bone conduction hearing gap (A-B gap) after Type III and Type IV stapes columella tympanoplasty in ears with mobile stapes and a well repaired tympanic membrane (TM). METHODS: Those patients who underwent tympanoplasty in our hospital between 2003 and 2009 and satisfied the following criteria were eligible: (1) good stapes mobility, confirmed intraoperatively; (2) postoperative TM and/or computed tomography (CT) findings that showed a well-aerated tympanic cavity without TM perforation, otorrhea, or middle ear effusion; and (3) measurable air and bone conduction hearing thresholds 1 year postoperatively at all test frequencies (250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz). RESULTS: Hearing results were better after Type III tympanoplasty than after Type IV tympanoplasty. After Type III (n=70) and Type IV (n=24) tympanoplasty, the respective mean A-B gaps were 16.4 ± 7.2 dB and 20.1 ± 5.6 dB, respectively. The mean A-B gap was significantly smaller after Type III tympanoplasty than after Type IV tympanoplasty (p<0.05). Regardless of the type of tympanoplasty, the postoperative A-B gap was greatest at 4 kHz. CONCLUSION: The mean A-B gap was smaller after Type III tympanoplasty than after Type IV tympanoplasty. The magnitude of the A-B gap was greatest at 4 kHz in both procedures.

Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia: an experimental study in the gerbil.

The effects of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, were experimentally investigated in gerbils in the context of alleviation of hearing loss after transient cochlear ischemia. Animals were randomly assigned to receive 2 mL/kg of either LEH (P50O2=15 mmHg) or saline 1h after the experimental induction of 15 min of ischemia. Sequential recordings of auditory brainstem response (ABR) showed that administration of LEH prevented hearing loss due to cochlear ischemia. The mean ABR threshold at 32 kHz on day 1 was 21 ± 7 dB in the LEH group (n=6) and 45 ± 6 dB in the saline group (n=6). Thereafter, hearing impairment gradually improved up to day 7 in both groups. The animals were then subjected to histological study, which revealed that there was more substantial loss of the inner hair cells, but not the outer hair cells, in the saline group as compared to the LEH group. These results suggest that LEH is an efficient agent with regard to protection against hearing loss and underlying hair cell damager due to ischemic insult.

Treatment of neural anosmia by topical application of basic fibroblast growth factor-gelatin hydrogel in the nasal cavity: an experimental study in mice.

IMPORTANCE: A new treatment of neural anosmia. OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF)-gelatin hydrogel on recovery of neural anosmia in mice. DESIGN: Anosmia was induced by intraperitoneal injection of 3-methylindole, 200 mg/kg. One week later, the animals underwent 1 of the following 3 procedures bilaterally: (1) group A: single-shot intranasal drip infusion of phosphate-buffered saline, (2) group B: single-shot intranasal drip infusion of bFGF, and (3) group C: placement of bFGF-gelatin hydrogel in the nasal cavity. The olfactory function of the animal was evaluated by the odor-detection test (ODT) 2 and 4 weeks later. Following the testing, the animal was killed, the thickness of the olfactory epithelium was measured, and the number of olfactory marker protein (OMP)-positive cells was counted. SETTING: Research installation. PARTICIPANTS: Mice. INTERVENTION: The placement of bFGF-gelatin hydrogel in the nasal cavity. MAIN OUTCOMES AND MEASURES: An ODT, thickness of olfactory epithelium, the number of OMP-positive cells RESULTS: The ODT proved that neural anosmia recovered in group C but not in groups A and B. Histologically, olfactory epithelium became thicker and the number of OMP-positive cells increased in group C, while such functional and histologic recovery was poor in groups A and B. These findings suggested that placement of bFGF-gelatin hydrogel in the nasal cavity was an efficient way to facilitate recovery of neural anosmia. CONCLUSIONS AND RELEVANCE: As a gelatin hydrogel degrades slowly in the body, bFGF is gradually released around the site of the lesion; thus, it constantly exerts its effects on neural regeneration.

[Evaluation of hearing results after tympanoplasty according to the classification of the development degree for pars flaccid cholesteatoma].

Our surgical treatment for middle ear cholesteatoma is based on the following 2 concepts: (1) Preservation of the physiological morphology and function of the middle ear, that is, maximal preservation of the posterior wall of the external auditory meatus and the middle ear mucosa and (2) Careful resection of the matrix membrane of the cholesteatoma through the continuity of the matrix membrane. In case the cholesteatoma matrix membrane is ruptured, a staged operation should be performed to prevent the development of residual cholesteatoma from the residual matrix. In this study, we classified a total of 238 cases of the pars flaccida cholesteatoma primary operated on Osaka Red Cross Hospital between January 2006 and March 2008 according to the Classification and Staging of Cholesteatoma proposed in 2010. The age of the patients ranged from 4 to 79 years (average: 49.8 years) and there were 123 males and 115 females. Follow up ranged from 1 year to 5 years with a mean follow-up period of 47.8 months. Regarding the stage, 38 (16.0%) ears had stage I cholesteatoma, 155 (65.1%) ears had stage II, and 45 (18.9%) ears had stage III. The successful outcome rate was 97.4% for stage I, 78.7% for stage II and 60.0% for stage III. The rate of the residue and the postoperative recurrence was 2.5% and 4.2%.

Objective assessment of the severity of unilateral facial palsy using OKAO Vision® facial image analysis software.

CONCLUSION: Severity of ipsilateral facial palsy (UFP) can be assessed objectively by use of OKAO Vision®. Facial symmetry percentage (FSP) values were well correlated with the results by two conventional grading systems. OBJECTIVES: To introduce the basic principle of facial motion analysis using OKAO Vision®, to represent the data measured in patients with UFP, and to show the correlation between the severity of facial palsy assessed by this method and conventional systems. METHODS: Two independent facial motions, closing the eyes and grinning, were recorded with a video camera. By comparing the movement distances between right and left sides, the eye symmetry ratio (ESR) and grin symmetry ratio (GSR) were obtained. The degree of UFP was assessed by FSP, which was calculated by the formula: FSP = (ESR + GSR)/2 × 100 (%). FSP was measured in 12 normal volunteers and in 30 patients with UFP. RESULTS: In patients with UFP, varying degrees of FSP were noted corresponding to the grade of facial palsy. The severity of facial palsy assessed by FSP was closely correlated with the Yanagihara score (r = 0.88, p < 0.05) and was inversely related to the House-Brackmann grade (r = -0.90, p < 0.05).

Myogenin expression in facial muscle following damage to the facial nerve.

CONCLUSION: Gene analysis of facial muscle may be a promising way to detect denervation of facial muscle, helping to determine the prognosis of a facial palsy early in its progression. OBJECTIVES: In the treatment of intratemporal facial palsy, early diagnosis of neural damage is important in deciding about therapeutic modalities. In this study, we investigated the relationship between the severity of facial palsy and the level of myogenin expressed in the facial muscle. METHODS: The animals were divided into two groups, depending on whether the facial nerve was resected or compressed. Expression of myogenin mRNA was examined using real-time PCR and in situ hybridization of the facial muscle following the nerve damage. RESULTS: Increased expression of myogenin was observed in the nerve resection group, while no such increase was seen in the nerve compression group. In situ hybridization indicated that myogenin was expressed exclusively in satellite cells around the denervated muscle fibers.

Galectin-7 as a marker of cholesteatoma residue and its detection during surgery by an immunofluorescent method--a preliminary study.

OBJECTIVES: To visualize the distribution of galectin-7 in middle ear cholesteatomas using an immunofluorescent method and to establish whether galectin-7 can be used as a marker of cholesteatoma residue at the time of operation. METHODS: Middle ear cholesteatomas were obtained at surgery from 30 patients. Samples were frozen and preserved in a freezer until histological study. After serial sectioning with a cryostat, 2 of the specimens were processed with primary antibody and Zenon rabbit immunoglobulin G labeling kits. After sufficient reaction time, the samples were observed using a confocal laser microscope. In the remaining 28 specimens, the cholesteatoma was treated as 1 block and stained with the same solution. It was then observed using a fluorescent stereomicroscope. RESULTS: Confocal microscopic analyses showed that galectin-7 was distributed in the cholesteatoma matrix. Because this area strongly stained green, it was easily recognized using a confocal laser microscope. In the stereomicroscopic study using the 1-block specimen in which the cholesteatoma was processed together with the surrounding granulation and mucosal tissue, only the matrix and overlying debris was yellow-green in response to excitation by light; the surrounding granulation and mucosal tissues did not respond in 7 specimens. In the remaining 21 specimens, the whole sample was composed of cholesteatoma and responded well to excitation by light. These findings suggest that galectin-7 might be a useful marker of cholesteatoma residue that can be visualized using this immunofluorescent method. CONCLUSION: Because residual cholesteatoma matrix is considered to be one of the main causes of cholesteatoma recurrence, staining with galectin-7 at the time of operation would be a promising way to facilitate complete removal of the residue.

Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia and reperfusion in the gerbil.

To test liposome-encapsulated hemoglobin (LEH) in transient cochlear ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P5002 = 40 mm Hg), high-affinity LEH (h-LEH, P5002 = 10 mm Hg), homologous red blood cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the bilateral vertebral arteries and reperfusion. Sequential changes in hearing were assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion, when the animals were sacrificed for pathological studies. h-LEH was significantly more protective than l-LEH in suppressing hearing loss, in contrast to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most severe (P < 0.05 between any two groups) on the first day after cochlear ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups, with a significant difference among groups up to 7 days, when morphological studies revealed that the inner hair cells but not the outer hair cells, were significantly lost in the groups in the same order. The results suggest that pretreatment with h-LEH is significantly more protective than l-LEH in mitigating hearing loss and underlying pathological damage, in contrast to transfusion or saline infusion 7 days after transient cochlear ischemia/reperfusion.

Protection against ischemic cochlear damage by intratympanic administration of AM-111.

OBJECTIVE: AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils. METHODS: Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for l5 minutes. Then, 10 µl of AM-111 at a concentration of l, 10, or 100 µM in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear. RESULTS: In controls, transient cochlear ischemia caused a 25.0 ± 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 ± 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 µM, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 ± 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 ± 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 µM was more effective than 1 or 10 µM. CONCLUSION: Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia.

Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils.

BACKGROUND: Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. RESULTS: Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals. CONCLUSION: These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.

Local hypothermia in the treatment of idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The additive effects of local hypothermia and restricted activity in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) were investigated by case-matched study as a multicenter (13 hospitals) pilot trial. PATIENTS AND METHODS: In a preliminary experiment, we evaluated the effects of cooled water pillow (15 degrees C). Cooling the neck and mastoid with the pillow decreased the tympanic membrane temperature for 1.4 degrees C in 2h without causing uncomfortable sensation or frostbite. In this study, 86 patients with ISSHL were enrolled in the hypothermic group, which received hypothermic treatment with restricted activity in addition to medication, and 86 ISSHL patients constituted the control group, which received the same medication but without cooling and rest. Control patients were selected retrospectively from case records by matching the experimental patients with respect to age, gender, days until the start of treatment, hearing loss, shape of the audiogram, and accompanying vertigo. The patients in the hypothermic group were admitted and treated with a cooled water pillow for 48h, in addition to conventional drug treatment (e.g., 60 mg of prednisone) for 7 days. The water pillow was cooled to 15 degrees C and was changed 4-5 times per day. The patients used the water pillow for the first 48 h after admission, with restricted activity. The control patients received only the medications. RESULTS: Hearing results were evaluated using criteria proposed by the Sudden Sensorineural Hearing Loss Research Group of the Japanese Ministry of Health and Welfare. The recovery rates were judged 6 months after onset. The recovery rate in the hypothermic group was significantly (p<0.05) better than that in the control group. When the comparison was limited to younger patients, the use of the cooled water pillow was effective in facilitating the recovery of hearing. CONCLUSIONS: Hearing restoration in ISSHL may be improved by adding mild hypothermia and restricted activity to the conventional treatment.