In order to achieve gene transfer of cells surrounding the endolymphatic space, an adenoviral vector encoding lacZ gene was injected into the guinea pig endolymphatic sac in vivo. A large number of lacZ-positive cells were observed in the endolymphatic sac and duct, the vestibule and the ampulla. lacZ-positive cells were also detected in the cochlea, mainly in cells bordering the endolymphatic space: marginal cells in the stria vascularis and supporting cells in the organ of Corti. Because no transgene expression in the sensory hair cells was achieved in this in vivo preparation, it was examined if the cochlear and vestibular hair cells could be transfected in vitro. An adenoviral vector encoding lacZ gene was injected into the mature guinea pig cochlear and vestibular explants, which were incubated for 24-72 hrs. In the cochlea, a large number of lacZ-positive cells were found in the spiral ganglion, the spiral limbus, the Reissner's membrane, the spiral ligament, and the stria vascularis. In the organ of Corti, transgene expression was found in the outer hair cells and supporting cells, but not in the inner hair cells. When adenovirus lacZ vestors were administered to the vestibular explants following removal of the otoconia, lacZ-positive cells were observed in the sensory and supporing cells in the utricle and ampulla, and in the transitional and dark cells in the ampulla. These findings suggest that transgene expression can be achieved in the sensory epithelium in the cochlea and vestibule in certain conditions. The author also reviewed several recent in vivo studies that examined protective effects of application of an adenoviral vector encoding GDNF against aminoglycoside-induced damage to the cochlear and vestibular sensory cells and spiral ganglion cells.
Most of deafness is now incurable through conventional therapies. The application of gene transfer to cochlear gene therapy is attractive as a new medical intervention in deafness. In this study, LacZ (+)-adenoviral vectors were inoculated into the guinea pig cochlear perilymphatic space via cochleostomy. The expression of beta-galactosidase was estimated by both an enzymatic reaction with X-gal and immunohistochemical staining with an antibody to E. coli beta-galactosidase. The cells expressing beta-galactosidase were observed through all turns of cochlea. X-gal reaction demonstrated the predominant expression of beta-galactosidase in mesenchymal cells lining perilymphatic spaces and fibrocytes. The organ of Corti, stria vascularis and spiral ganglion cells were also reacted faintly with X-gal, which might indicate the beta-galactosidase expression, however, the immunohistochemical reaction resulted in the false positive X-gal reaction of these cells. The reporter gene inoculation into the perilymphatic space elucidated the ipsilateral cochlear gene expression with little damage to the tissue. No contamination could be detected in the contralateral cochlea or neighboring tissues. The perilymphatic gene transfer might develop into the cochlear gene therapy in future.
Hearing loss resulting from the death of hair cells in the organ of Corti or neurons in the spiral ganglion could be cured by the appropriate in vivo gene delivery into the cochlea. To date, less work has focused on gene delivery to the inner ear, and existing studies have primarily used adenovirus and adeno-associtated virus vectors. It has been shown that HVJ-liposome is a highly efficient vehicle for the introduction of oligonucleotides as well as for the transfer of genes <100kbp without damaging cells. The purpose of the present study was to assess the relative efficacy of gene delivery to the mouse cochlea, including cell specificity and toxicity, using HVJ-liposome. The HVJ-liposome (1000 HAU/5μl) bearing the E. Coli LacZ gene was directly injected into the scala tympani of the mouse cochlea in vivo, and the tissues were later assayed for the presence of the LacZ gene product, β-galactosidase (β-gal). The HVJ-liposome was found to infect and elicit transgene expression in many cell types of the mouse cochlea; neurons in the spiral ganglion, cells in the stria vascularis, cells in the organ of Corti, and cells in Reissner's membrane expressed β-gal. Transgene expression was persistent up to 7 days in these cells without any toxicity and inflammation. The results suggest that HVJ-liposome might be useful as a gene transfer vehicle in the inner ear and in future might be used to develop gene therapy strategies for some forms of hearing loss.
CT is the imaging investigation of choice for many lesions of the temporal bone. Recently advanced multislice CT (MSCT) with thin slice collimation (0.5mm) can provide “isotropic” voxel data, which can almost completely eliminate partial volume averaging errors related to the slice width. By using isotropic data, multiplanar reconstruction (MPR) images of any direction can be generated with spatial resolution equivalent to that of axial images. Direct coronal images, which are mandatory in the evaluation of many lesions in the temporal bone, can be replaced by MPR images. Also three-dimensional (3D) images can be obtained with high quality. MR imaging, which provides better tissue contrast than CT, is useful for characterization of “soft tissue lesions” MRI is the imaging modality of first choice for lesions in the inner ear and its central connection. In addition to Ti-, T2-weighted and contrast enhanced images, 3D heavily T2-weighted images (MR hydrography), such as CISS, FSE and FASE, are useful to estimate the inner ear, internal auditory canal, CP angle cistern, cranial nerves, and so on.
Although the main pathological finding in patients with Meniere's disease is distention of the entire endolymphatic system i.e. endolymphatic hydrops, its diagnosis depends primarily upon a history of fluctuating hearing loss and tinnitus, episodic vertigo associated with vegetative symptoms. Therefore, development of a practical tool to obtain objective evidence of the existence of endolymphatic hydrops is important. We applied a high-resolution magnetic resonance imaging devices running at 2.11T, 4.7T and 7.05T for the non-invasive depiction of the fine structure of the inner ear in the human and guinea pig. We have succeeded in depicting the basilar membrane and Reissner's membrane of the basal turn of the cochlea. In this paper, we showed our results of the fine MRI picture and raised the possibility of using MRI for the morphological diagnosis of endolymphatic hydrops (Meniere's disease).
Thanks to development of computed tomography (CT) and magnetic resonance imaging (MRI), preoperative informations of middle ear disease are more and more increasing in recent years. Especially, development of multi-slice CT clearly demonstrates 3D reconstruction of ossicules and temporal bone fracture, which enable us to diagnose middle ear malformation and site of temporal bone injury. On the other hand, diagnosis of recurrent cholesteatoma is still difficult even by both CT and MRI, because tissue contrast and enhancement are similar to those of surroundinjg connective tissue and granulation. MRI has been useful in facial nerve disorders. With use of gadolinium enhancement (Gd-MRI), lesion of the disease is clearly demonstrated, which makes differential diagnosis of viral etiology and others. The mechanism of contrast enhancement of the facial nerve by Gd is thought to relate to the disruption of the blood-nerve barrier as result of inflammation. However, it is still difficult to differentiate from Bell's palsy to Ramsay Hunt syndrome, because patterns of Gd enhancement in both disease is very similar. Moreover, there is little information between Gd-MRI findings and severity or prognosis of facial palsy. A reliable and widely available imaging for early identification of Bell's palsy and Ramsay Hunt syndrome as well as early prediction of facial nerve recovery must be developed as soon as possible.
The internal auditory meatus (IAM) is a bony canal which contains nerves and vessels. The inside of the IAM is covered with dura mater and arachnoid and, the IAM is filled with cerebro-spinal fluid (CSF). Because of advantage that bone causes no artifact, MRI is now the gold standard in the image diagnosis of lesions in the IAM and surrounding areas such as acoustic neuromas, petrous ridge meningiomas or facial neurinomas. Recent advances in MRI technology enables detailed study of the lesions and, especially, the constructive interference in steady state (CISS) pulse sequence clearly visualize the nerves and vessels in the IAM and cerebello-pontine angle. By CISS image, the state of the fundus of IAM, whether it is invaded by the tumor or not, can be recognized, and the possibility of success can be roughly predicted in hearing preservation surgery of acoustic neuromas. The X-ray CT also plays an important roll in the diagnosis of lesions eroding temporal bone or in the treatment of the lesions.
For the evaluation of the temporal bone tumors, especially for their qualitative diagnosis, detection of exact location of the tumor and appropriate selection of treatment modality, CT and MR imaging are indispensable. In this paper, representative CT and MR imaging of glomus tympanicum, glomus jugulare, facial schwannoma, jugular foramen schwannoma and various stages of the temporal bone carcinomas are presented and typical imaging findings of those tumors are described.
The aim of this study was to evaluate the correlation between pure tone audiograms and the patients'satisfaction with tympanoplasty. This is a questionnaire survey of patients who had tympanoplasty between 1989 and 2000. There were 212 patients (99 male and 113 female). The median age was 56 years old. The time after surgery and the number of patients were as follows. Forty five patients were followed-up for 1-3 years. 54 patients, for 4-6 years, and 113 patients longer than 7 years. The success rate of tympanoplasties was analyzed using the three criteria suggested by the Committee of Japan Society of Otology (CJSO) The questionnaire was about the post operative hearing, tinnitus, otorrhea, vertigo and the results in general. One hundred and twenty seven patients (59.9%) were aware of improvement of hearnig ; 67 patients (31.6%) no change of hearing; 11 patients (5.2%) worsened hearing;7 patients (3.3%) their good hearing same as before the operation. According to the criteria of Japan Society of Otology, in the 127 patients who improved hearing, 113 patients (89%) were success; In the 67 patients who have no change of hearing, 44 patients (65.7%) were success; in the 11 patients who had worsend hearing, 9 patients (81.8%) were success. Sixty four patients (30.2%) disappeared tinnitus ; 203 patients (95.7%) recognized no otorrhea;10 patients (4.7%) complained of the disturbed taste sensation; 15 patients (7.1%) complained of still continuing dizziness ; 48 patients (22.6%) complained of fullness of the ear. The rate of patient's satisfaction was the following. 104 patients (49.1%) were satisfied with the result of the operation ; 63 patients (29.7%) were next to satisfaction;32 patients (15.1%) couldn't evaluate the operation; 13 patients (6.1%) were not satisfied. Again according to CJSO, in the 104 patients who satisfied with the operation, 89 patient (85.6%) had a ‘success’; In the 63 patients who almost satisfied, 51 patients (81%) were ‘success’; In the 32 patients who couldn't judge the result of the operation, 21 patients (65.6%) were ‘success’; In the 13 patients who did not satisfy with the result of the operation, 11 patients (84.6%) were ‘success’. There were thus considerable discrepancies between the subjective satisfaction and the objective findings or pure tone audiograms. There were no significant differences between the patient's satisfaction and the patient's age and the time after the operation. The present results may indicate to include patient's subjective evaluations for assessment of tympanoplasty.
In recent years, there have been many reports on the so-called autoimmune sensorineural hearing loss. But there are a number of unclarified points regarding the mechanism of this disease. We had four cases of sensorineural hearing loss related with anti-neutrophil cytoplasmic antibodies against myeloperoxidase (MPO-ANCA)-associated vasculitis. Four patients who had been treated at the Department of Otolaryngology, Jichi Medical School with MPO-ANCA-associated sensorineural hearing loss (2 males and 2 females) were selected for this study. All patients had been complicated by autoimmune diseases (glomerulonephritis, pulmonary fibrosis, arthritis and Sjogren's syndrome) and had positive MPO-ANCA titer. They were referred to us for the sudden onset of bilateral hearing loss. Pure tone audiometry revealed bilateral moderate to severe sensorineural hearing loss. Three of them complained of vertigo and had nystagmus. Electronystagmogram (ENG) revealed unilateral canal paresis (CP) in two patients. These results indicated that MPO-ANCA-associated vasculitis could cause not only hearing loss but also vestibular disturbance. All the patients received high-dose adrenocorticosteroid. With the treatment, they had marked improvement of hearing loss and vertigo as well as systemic disease, and titer of serum MPO-ANCA decreased. Although any organ may be affected by MPO-ANCA-associated vasculitis, there are few reports on cases of MPO-ANCA-associated progressive hearing loss and vestibular disturbance.The present cases suggest the possibility of hearing loss and vestibular disturbance resulted from small vessel vasculitis in the inner ear. It is expected that MPO-ANCA is possibly a good marker for diagnosis and follow-up of some of autoimmune sensorineural hearing loss.
Two cases of combination anomaly of ossicules and inner ear window were operated. Before the operation, they were suspected to have unilateral, congenital hearing loss due to ossicular anomaly because of normal ear drum. The operative findings showed unexpectedly missing of the inner ear window in combination with ossicular anomaly. As the result, inner ear was fenesterated at the vestibular scala of the cochlear basal turn for construction of sound conduction. In the first case, an 8-year-old girl had conductive hearing loss in the left ear from her birth. The operation of the affected ear showed congenital teratoma in the middle ear cleft, loss of stapes and incuidal long process, complete missing of vestibular and cochlear window. Cochlea was drilled at the supposed site of the vestibular window, and total ossicular replacement prosthesis (TORP) was placed in the fenesteration. Her hearing after the operation was improved temporarily up to 30 dB, but it again became down to the preoperative level within three months after the surgery. It seemed that bony regrowth of the fenesterated window caused declined hearing. In the second case, a 12-year-old girl presented with severe conductive hearing loss in the left ear. In the operation, partial absence of the stapedial crus and loss of the vestibular window were observed. Inner ear was fenesterated more windely in this case than in the first case and TORP was also used. Hearing improvement was better and more stable in the latter than in the former. The difference of change of hearing in two cases seemed to result from the width of fenesteration and limited anomaly. Fenesteration of the inner ear in these cases of unidentified inner ear window seems to have more risk of inner ear damage, i.e. postoperative deaf than stapedial surgery in otosclerosis. Therefore, operative case should not be selected for fenesteration in the case of gusher or severe inner anomaly, and careful procedure is inevitable to avoid hearing loss. Our two cases fortunately showed no vertigo neither damage of inner ear function, but hearing improvement was stable only in the second case and temporarily in the first case. Although the very small number of the cases with combined anomaly of the ossicules and inner ear window, site of fenesteration of the inner ear and prosthesis for sound conduction should be further studied.
Lateral temporal bone resection (lateral TBR) is indicated for malignant neoplasms localized to the osseous and cartilaginous external auditory canal (EAC) with no encroachment on the medial mesotympanum. Because of the good prognosis after lateral TBR, few publications treated with the postoperative complications, hearing loss accompanied the stenosis and obstruction of the EAC as a result of healing by granulation. In this report, two cases of primary squamous cell carcinoma and adenoid cystic carcinoma arising from the EAC undergoing lateral TBR was described. The experience of stenosis and obstruction of the EAC and hearing loss after lateral TBR were described.
A 49-year-old man who underwent a left surgery for otitis media 30 years ago. He had also undergone surgery for left middle ear cholesteatoma in another hospital. After the surgery, he had left purulent-bloody aural discharge, and received the third operation for partial removement of cholesteatoma in our hospital. Tympanic cavity and mastoid were filled with cholesteatoma, which adhered to the posterior cranial dura and the sigmoid sinus tightly and moreover invaded the temporal bone toward the jugular foramen and carotid canal. Therefore cholesteatoma was not completely removed. After surgical treatment, the patient was followed up regularly with CT and MRI of the skullbase including the internal and middle ear, however cholesteatoma accelerated to grow into the brain stem with bone destruction, and the patient died. This drastic course gave us a doubt of malignant change of squamous epithelium, though histopathologic examinations of all specimens showed stratified squamous epithelium and granulation tissue.
A 75-year-old male with a past history of chronic renal failure (under maintenance hemodialysis), bronchial asthma, old myocardial ifarction and angina pectoris was complaining of pain and hearing loss in the left ear. Cranial nurve palsies (IX X XI XII) and Horner syndrome were noted on the affected side. Mastoidectomy was performed because CT and MRI suggested a diagnosis of acute mastoiditis. Although his symptoms temporarily improved after surgery, he died of complicated pneumonia with recurrence of multiple cranial nerve palusies. Villaret syndrome caused by acute mastoiditis has rarely been reported in the literature. We reported the first case of Villare syndrome caused by acute mastoiditis and hypertrophic pachymeningitis that was confirmed at autopsy.
A 45-year-old man presented with right otorrhea, headache, fever and nausea. Audiogram showed moderately conductive hearing loss in the right ear and total deafness in the left ear. In addition, complete left hemifacial palsy and a hard mass in the right lateral neck were observed. CT revealed that a soft tissue density in the middle ear, bone destruction in the tegmen tympani, erosion of the sinus plate with air bubbles in the lateral sinus in the right ear; destruction of the petrous bone including the cochlea, superior semicircular canal and internal auditory canal in the left ear. MRI depicted a thrombus in the right transverse sinus, lateral sinus and internal jugular vein and a large cholesteatoma mass invading the left petrous bone and extending to the left cellebro-pontine angle. The treatment of the right ear consisted of internal jugular vein ligation with incision of the lateral sinus for drainage of abscess, modified radical mastoidectomy for eradication of cholesteatoma and staged tympanoplasty for preservastion of hearing. Seventy days after the right ear surgery, the patient underwent the left ear surgery, which consisted of combined transmastoid / subtemporal presigmoid approach. Postoperative hearing in the right ear was improved and no recurrent cholesteatoma was depicted on imaging study in both ears for 11 months.
Delayed onset facial palsy eleven days after uneventful middle ear surgery was presented. An exploratory tympanoplasty was performed on the right ear of a 58-year-old woman under general anesthesia, with a likely diagnosis of cholesteatoma. The post-operative definite diagnosis was tympanosclerosis with adhesion of the eardrum. The operation was uncomplicated with no exposure of facial nerve during the surgery. On the eleventh postoperative day, a facial palsy on the operated side appeared. Elevated anti-varicella antibody titer was seen while no zoster was found in the auricle through the course. It was suggested that the delayed facial palsy (DFP) resulted from zoster sine herpete by reactivation of latent varicella-zoster virus (VZV) stimulated by surgery. The weakness of the right side of the face progressed to complete palsy with no voluntary motion. The patient was, however, unwilling to have another operation to decompress the facial nerve. She was conservatively treated with intravenous steroid and acyclovir. The facial palsy gradually improved from a regional grading system score of 2/40 to 40/40 at five months following the onset. The incidence of DFP after uneventful middle ear surgery has been reported as 0.2 to 1% in the literature. The most plausible cause of the DFP would be reactivation of either VZV or herpes simplex virus or both. Surgeons should know that minimal stimulation of the facial nerve during surgery could result in a viral reactivation even though direct mechanical injury to the nerve does not occur.
Present state of the regenerative medicine. Recently, the new interdisciplinary studies of the regenerative medicine are progressing remarkably. In the in vitro method, the living cells are picked out and cultured to make some tissues and organs. After that, the tissue or organs are implanted into patient's body. In the in vivo method, the extracellural matrix which cells can use to make their own environment is settled in the internal body. At that time the stem cells, the precursor cells, and the DDS of cell growth factors to acceralate the growth speed are administrated into the artificial extracellural matrix. Regeneration of almost all of the tissues and organs have already been studied and some of them are tried to apply in clinical patients. Applying this new technology, the medical therapy will be able to progress and change the thought of the medical therapeutology.