Nontumorous Enlargement of the Internal Auditory Canal: A Risk Factor for Sensorineural Hearing Loss? A High Resolution CT-Study.

PURPOSE: First aim of the study was to define normal shape and diameter of the internal auditory canal (IAC). In the second part the clinical relevance of IAC-enlargement was analyzed, considering also lesions of the subtle structures at the fundus of the internal auditory canal. MATERIALS AND METHODS: 440 high resolution CT-scans of the temporal bone were used for retrospective analysis of the internal auditory canal and its fundus region. RESULTS: The mean value of the IAC diameter in axial and coronal plane was determined. In 20 of 440 patients IAC enlargement was found. In the group with pronounced enlargement (3fold SD) nearly all patients suffered from hearing impairment. In some of them we found structural abnormalities near the IAC fundus in the CSF/perilymph border zone. CONCLUSION: A new CT-based definition of normal shape and diameter of the internal auditory canal is presented. There is some evidence that a pathologic transmission of CSF-pressure in case of IAC-enlargement and/or abnormal fistulous communications could play an important role in the pathophysilogy of hearing loss. KEY POINTS: • New CT-based definition of normal internal auditory canal.• Nearly all patients showing pronounced IAC-enlargement suffer from hearing impairment.• Possible pathomechanism: Transmission of CSF-pressure on the inner ear.

[Retropharyngeal tendinitis--a rare differential diagnosis of retropharyngeal abscess]. / Retropharyngeale Tendinitis--Eine seltene Differenzialdiagnose eines Retropharyngealabszesses.

Because of their similarity, clinical symptoms of a calcific retropharyngeal tendinitis can be misdiagnosed for a retropharyngeal abscess. We present two patients who were admitted for retropharyngeal abscess, however, careful examination revealed amorphous calcification anterior to C1-C2 in addition to prevertebral soft tissue swelling. Knowledge of the characteristic clinical symptoms and the pathognomonic imaging features is crucial to correctly diagnose the disease and to prevent unnecessary tests and treatment.

Otosclerosis and measles virus - association or causation?

Otosclerosis is a frequent condition which occurs exclusively in the human temporal bone. This peculiar disease affects mainly Caucasians and Indians and may cause conductive, mixed conductive-sensorineural or occasionally merely sensorineural hearing loss. Morphological investigations of the otosclerotic focus show all three phases of a chronic inflammation with bone resorption, formation of new bone and finally eburnation. Various hypotheses about the cause of inflammation were proposed in the past. Immunological reactivity to collagen, the existence of otosclerosis genes (OTSC 1-5) including mutations of the collagen gene 1A1 and 1A2 or a measles virus (MV) infection were suggested. The existence of the MV proteins and RNA within the otosclerotic tissue has been shown by several authors. However, due to mainly technical problems, no further progress to elucidate the role of the virus could be made. Epidemiological studies revealed a dramatic decrease of measles and related diseases such as the subacute sclerosing panencephalitis since the introduction of MV vaccination programs in USA and Europe. Indeed, some surgeons reported decreasing numbers of stapes surgery and a shift towards elder patients. Our epidemiological survey of all patients hospitalized with otosclerosis in Germany between 1993 and 2004 demonstrates a highly significant decrease in otosclerosis among the population vaccinated against the MV. The strong correlation makes it most plausible that the MV is at least one triggering factor for the development of otosclerosis.

Evidence of increased average age of patients with otosclerosis.

Otosclerosis is an inflammatory disease of the human temporal bone which was assumed to affect up to 10% of the Caucasians. Histologic otosclerosis has an incidence of 3.4%. It is considered as a major cause of hearing loss in Western countries while a low incidence is observed among Africans. Many hypotheses about its origin had been formulated in the past. Otosclerosis genes (OTSC1-5) and collagen 1 genes are mutated in some familial cases of otosclerosis. On this genetic background, a common environmental factor such as a measles virus infection might be the triggering factor. Studies in the past indicated a distribution of otosclerosis among men and women of 1:1.4. Our study was designed to analyze the age of patients with otosclerosis at the time of surgery in the eighties and the nineties of the last century. Patients suffering from clinical otosclerosis who underwent stapedectomy between 1978 and 1999 with complete clinical data available (n = 1,351) were included in the study. Age and gender distribution, the age difference between men and women and the influence of gender and the year of recruitment were evaluated. Statistical analyses demonstrated an increase in the average age of patients with clinical otosclerosis from the eighties to the nineties (p = 0.012). The gender distribution showed no statistically significant variation (p = 0.398). These data might reflect an improved health consciousness among the elder population or could be the result of increased health awareness in the seventies and eighties. Finally, in the early seventies, measles virus vaccination was introduced in Germany and the shift of age could be the result of the measles virus immunization campaign.

Expression of collagens in the otosclerotic bone.

The etiopathogenesis of otosclerosis is still controversially discussed. The major hypotheses discussed are a viral infection on a genetic background and an (autoimmune) collagen disease. The aim of our study was to investigate by immunohistochemistry the expression pattern of collagens within the otosclerotic focus. Stapes footplates from 30 patients with clinical otosclerosis undergoing stapedectomy were formalin fixed, decalcified and paraffin embedded. As controls, 30 autoptic temporal bone specimens were employed. We investigated the expression of collagens I-V with immunohistochemistry. The expression of collagen I showed a diffuse homogeneous distribution with increased staining of the otosclerotic focus. Collagen II was exclusively expressed in chondrocytes including the globuli interossei. The pattern of collagen III in the otosclerotic bone was web-like in contrast to a lamellar pattern in the control bone. The mucoperiosteal layer and connective tissue such as the vessels of the resorption lacunae expressed collagen IV. An increased expression of collagen V around osteocytes was observed in the otosclerotic focus. In conclusion, in the otosclerotic tissue, in comparison with the control bone, a high expression of collagen IV occurred. The immunohistochemical analysis of collagen II, which has been suggested to be implicated in the etiopathogenesis of otosclerosis, revealed no differences between control and otosclerotic bones. The intense staining of the otosclerotic focus with collagen I is in good agreement with an inflammatory process but in contrast with lesions like those in osteogenesis imperfecta.

Measles virus and otosclerosis.

Measles virus (MeV) might play an important role as an environmental stimulus in the etiopathogenesis of otosclerosis. Chronic inflammation was shown in morphologic investigations of otosclerotic foci and MeV N, P, and F proteins were detected within cells of the otosclerotic focus by immunohistochemical investigations. MeV RNA was extracted from fresh-frozen otosclerotic tissue by the use of in vitro RT-PCR. This result was validated through amplification of MeV genome sequences by RT-PCR from celloidin-embedded sections with morphologically ascertained otosclerotic foci. In searching for an immune response of the inner ear immune system against MeV proteins, elevated anti-MeV IgG levels were detected in the perilymph of patients with otosclerosis in comparison with the serum levels. In situ RT-PCR allowed the localization of MeV sequences in osteoclasts, osteoblasts, chondrocytes, macrophages, and epithelial cells in middle ear mucosa of otosclerotic tissue. Further evidence for MeV persistence has recently been given. Genotyping of MeV in otosclerotic foci demonstrated the presence of MeV genotype A, which circulated in Europe around 1960. All the above results confirm a strong association between MeV and otosclerosis.

Diagnostics of the cochlear amplifier by means of distortion product otoacoustic emissions.

Distortion product otoacoustic emission (DPOAE) growth functions reflect the active nonlinear cochlear sound processing when using a primary-tone setting which accounts for the different compressions of the two primaries at the DPOAE generation site and hence provide a measure for objectively assessing cochlear sensitivity and compression. DPOAE thresholds can be derived from extrapolated DPOAE input/output (I/O) functions independently of the noise floor and consequently can serve as a unique measure for reading DPOAE measurements. The thus-estimated DPOAE thresholds exhibit a close correspondence to behavior audiometric thresholds and thus can be used for reconstructing an audiogram, i.e., a DPOAE audiogram. The DPOAE I/O functions' slope increases with cochlear hearing loss and thus provides a measure for assessing recruitment. Hence, DPOAE I/O functions can give more information for diagnostic purposes than those of DP grams, transiently evoked OAEs (TEOAEs), or auditory brain stem responses (ABRs). DPOAE audiograms can be applied in pediatric audiology to assess cochlear dysfunction in a couple of minutes. In newborn hearing screening, they are able to detect transitory sound-conductive hearing loss and thus can help to reduce the rate of false-positive TEOAE responses in the early postnatal period. Since DPOAE I/O functions are correlated with loudness functions, DPOAEs offer the possibility of basic hearing aid adjustments, especially in infants and children. Extrapolated DPOAE I/O functions provide a tool for a fast automated frequency-specific and quantitative evaluation of hearing loss.

[Correction of ear malformations with autologous rib cartilage]. / Versorgung von Ohrmuschelfehlbildungen mit autologem Rippenknorpel.

INTRODUCTION: Ear malformations are mainly isolated deformations but exist also in combination with various syndromes. A visible malformation in cases of microtia is a problem for the entire family. Auricular reconstruction with autologous cartilage has been well established in the last decade. Optimization of the technique has led to improved and reliable results. OPERATION AND RESULTS: Based on the experience of 120 cases we developed a concept that allows total ear reconstruction in two operative steps. In the first operation autologous rib cartilage is harvested and a natural framework is created following the template from the opposite ear. The ear remnant is transposed and the framework placed in a subcutaneous pocket on the mastoid plane. After a healing period of around 6 weeks the second operation reconstructs the auricular projection and the retroauricular fold. CONCLUSION: Based on an individualized surgical treatment, auricular reconstruction with autologous rib cartilage are possible from the age of around 8 to the advanced period of life with reproducibly good results.

Persistent measles virus infection and otosclerosis.

The cause of otosclerosis is still unknown. Recently, measles virus involvement has been implicated. The aim of this study was to analyze the presence of measles virus RNA within the otosclerotic focus and to evaluate the perilymphatic antibody pattern. Bone and perilymph specimens from 40 patients with the spontaneous form of otosclerosis and from control patients were investigated by reverse transcription polymerase chain reaction (RT-PCR), Western blot techniques, and cell culture. By the use of RT-PCR, measles virus RNA could be detected in 32 patients, but not in controls. Analysis of perilymph revealed the presence of antibodies to N, F1, and M measles virus proteins in all cases, and antibodies against H protein in 2 additional cases. In preosteoblasts cultured from otosclerotic bone chips, no measles virus RNA could be amplified. We conclude that the spontaneous form of otosclerosis is, in the vast majority of cases, a measles virus-associated disease of the otic capsule.

Shift of the distribution of age in patients with otosclerosis.

Morphological and biochemical investigations have shown evidence of an association between measles virus and otosclerosis. Epidemiological analysis of age and gender distributions in the 1960s and 1970s revealed a higher incidence of otosclerosis in women, the average age of onset of clinical disturbances and need for surgery being between 15 and 40 years. In the late 1960s and early 1970s a campaign to vaccinate children against measles was started in Germany. The aim of our study was to evaluate whether this campaign has had any influence on the distributions of the age and gender of patients affected by otosclerosis over the past 20 years. The study included patients suffering from clinical otosclerosis who had undergone stapedectomy between 1978 and 1999 and whose clinical data were complete (n = 1351). Statistical analysis during the recruitment period indicated a significant increase in the average age of the otosclerosis patients (p = 0.012). With regard to the gender distribution it was found that the increase of otosclerosis in women compared to men was statistically insignificant (p = 0.418). These data strongly support the hypothesis of a measles virus involvement in otosclerosis and may reflect a decreased incidence of otosclerosis in the generation of patients vaccinated against measles virus.

Persistent measles virus infection as a possible cause of otosclerosis: state of the art.

The etiopathogenesis of otosclerosis is still largely unexplained and remains controversial. Morphologic examinations have shown the presence of a chronic inflammation in otosclerotic tissue. Among the proposed explanations for this inflammation are an immunologic reaction against collagen, mutations of collagen gene 1A1, and a viral infection. In this paper, we focus on the role of measles virus in otosclerosis, and we review the current literature, devoting particular attention to a suspected paramyxoviral etiopathogenesis in Paget's disease. Our examination of footplate fragments by reverse transcription polymerase chain reaction testing in 95 patients with otosclerosis revealed the presence of measles virus RNA in 83% of cases. Quantification of measles virus immunoglobulin G (IgG) in otosclerosis patients indicated that the ratio of antimeasles virus IgG in total IgG was higher in perilymph than in serum. Furthermore, an almost identical incidence of otosclerosis and measles virus-caused mortality in women suggests that women are more susceptible to measles virus infection. Finally, since the introduction of the measles virus vaccination program in Europe, there has been a decline in the incidence of otosclerosis. Moreover, the average age of patients at diagnosis and surgery at our hospital has increased to 54 years. Our findings, when they are considered along with findings regarding the presence of paramyxoviral RNA in Paget's disease, support the hypothesis that measles virus is involved in the etiopathogenesis of otosclerosis.

Herpes simplex virus antibodies in the perilymph of patients with Menière disease.

OBJECTIVE: To evaluate the presence of IgG antibodies directed to herpes simplex virus (HSV) in the perilymph of patients with Menière disease. DESIGN: Antibodies to HSV, Epstein-Barr virus, cytomegalovirus, and measles virus were analyzed in serum and perilymph samples by enzyme-linked immunosorbent assay. Total IgG and albumin in serum and perilymph samples were measured by nephelometer analysis. The relation of specific antivirus IgG in the perilymph vs the serum was expressed as an index. PATIENTS: Perilymph and serum samples from 7 patients with long-standing, disabling Menière disease were collected during therapeutic vestibulotomy. Perilymph and serum samples from 7 patients with otosclerosis and 2 recipients of cochlear implants were used as controls. RESULTS: Compared with the corresponding serum sample, the perilymph from the patients with Menière disease disclosed a higher level of specific anti-HSV IgG. An elevated level of specific anti-measles virus IgG in the perilymph was detected in patients with otosclerosis. Patients of all groups showed no variation of specific anti-Epstein Barr virus IgG and anti-cytomegalovirus IgG in the serum or in the perilymph. CONCLUSIONS: Our results show the presence of HSV IgG in the perilymph of patients with Menière disease and support the hypothesis that HSV may play an important role in the etiopathogenesis of Menière disease.

Measles virus in otosclerosis and the specific immune response of the inner ear.

Histologic and immunohistochemical studies of otosclerotic lesions have shown that there is a chronic inflammatory reaction of the otic capsule with bone resorption resulting from vascular invasion accompanied by inflammatory cells. During the active lytic stage of otosclerosis, paramyxoviral structures have been identified by electron microscopy and measles virus antigen expression by immunohistochemistry. Recently, measles virus related sequences have been detected in tissue of otosclerotic lesions. Because the otosclerotic focus has a close relation to the perilymphatic space, the expression of measles virus antigens within it should represent an immunologic challenge to the immune system of the endolymphatic sac. In this study, measles virus specific antibodies were detected in all of the perilymph samples from 19 patients suffering from otosclerosis, and the relative amount of these IgG antibodies was much higher than in serum samples of the same patients or in perilymph of control patients. These findings support the hypothesis that measles viruses play an crucial role in the pathogenesis of otosclerosis.

Pilomatrix carcinoma with multiple visceral metastases. Report of a case.

BACKGROUND: The malignant variant of pilomatrixoma is pilomatrix carcinoma, a low-grade, malignant lesion with a tendency to recur. Only three cases with visceral metastases, occurring some years after primary diagnosis, have been reported. METHODS: A case of metastatic pilomatrix carcinoma of the neck in a patient, age 50 years, is presented. RESULTS: Histologic examination of the cutaneous lesion showed a dense infiltrate of basaloid cells, an abrupt transition to shadow cells, and central necrosis. Two months after primary diagnosis, pulmonary and brain metastases developed. Despite chemotherapy and irradiation, the patient died a widespread disease 18 months after the primary diagnosis. An autopsy confirmed the diagnosis of pilomatrix carcinoma with metastases to several organs including the heart, lung, brain, liver, pancreas, kidney, adrenal gland, gastric and colorectal submucosa, skin, and bone. CONCLUSIONS: Pilomatrix carcinoma is very rare and usually behaves like a low-grade, malignant lesion with a tendency to recur. This patient's tumor is unique because of its highly aggressive behavior and visceral metastases.

[Pathogenesis of otosclerosis. "State of the art"]. / Zur Pathogenese der Otosklerose. "State of the Art".

Women suffer from otosclerosis 1.6 times more often than males. Histologically, otosclerotic foci can be found in temporal bones of females 1.9 times more often than in those of males. Characteristic topographic regions are the oval window, round window niche and promontory. Otosclerosis can also occur principally in any area of the enchondral/periosteal layer of the otic capsule. Evidence is presented that otosclerosis is an inflammatory tissue reaction associated with macrophages, T- and B-lymphocytes, HLA-DR positive cells and plasma cells. Dependent on the stage of the osteolytic bone disease present deposits of complement and immunoglobulins (IgG, IgA) can be found. These immunoglobulins have been identified as antibodies to measles virus proteins. Using the polymerase chain reaction we were successful in demonstrating RNA sequences of measles viruses in otosclerotic bone from footplates removed during stapes surgery. Since most of the otosclerotic lesions were in direct contact to the perilymphatic space, it may be expected that the endolymphatic sac--as the immune competent organ of the inner ear--specifically reacts to antigens delivered from the otosclerosis focus into the perilymph. Perilymph samples from patients were collected during stapes surgery and their antibody titers against measles were compared with that in corresponding blood serum. All samples revealed a significantly elevated-specific anti-measles IgG amount which was significantly higher than in the corresponding serum. In contrast, antibody titer in the perilymph against herpes simplex or cytomegalo viruses did not differ from that of the serum. These findings indicate that otosclerosis is a measles virus associated inflammatory osteolytic disease of the temporal bone. Since women suffer from severe measles virus infections more often than males, it can be hypothesized that females have a higher susceptibility of their cochleo-vestibular tissues to these infections (organotropism). In addition, estrogens are well-known stimulators of osteocytic activity and may play a dominant role during ossification of an otospongeotic bone lesion. This may explain the onset of a conductive hearing loss due to otosclerosis during pregnancy.

Otosclerosis: a measles virus associated inflammatory disease.

The etiology of otosclerosis is still unknown. Immunohistochemical studies have revealed the characteristics of chronic inflammation in the otospongiotic area. Paramyxoviral structures have been identified by electron microscopy and the expression of measles virus antigen has been observed by immunohistochemistry in active otosclerotic tissue. By use of the polymerase chain reaction, measles virus related sequences have been detected in otosclerotic bone tissue but not in control specimens. The aim of our study was i) to detect measles virus genome in affected patients using a more sensitive PCR system and ii) to search for anti-measles virus IgG in the perilymph. In 13 out of 14 specimens of bone fragments from surgically removed stapedes of patients suffering from otosclerosis, measles virus RNA sequences could be detected while other tissues from the same patients and from a negative control group lacked such sequences. Furthermore, IgG anti-measles virus antibodies were detected in the perilymph of 6 patients. Our results support our previously stated hypothesis that otosclerosis is a measles virus associated disease which provokes a local immune response within the inner ear.

Identification of p53 gene mutations in gastrointestinal and pancreatic carcinoids by nonradioisotopic SSCA.

A nonisotopic screening method based on single-strand DNA conformation analysis (SSCA) was established for the identification of p53 gene alterations in achieved tissue samples. The sensitivity of this approach was validated by testing mutations previously identified by direct sequencing. Applying this assay, 40 samples of formalin-fixed, paraffin-embedded tumors, including 33 gastrointestinal carcinoids and seven endocrine pancreatic tumors, were screened. Only one mutation (codon 283, CGC to CCC) was identified in a single clinically benign rectal carcinoid. This mutation occurred during the development of the tumor and was accompanied by loss of the wild-type gene. Our data indicate, that, in contrast to gastrointestinal carcinomas, alterations of the p53 gene are infrequent events in the development of gastrointestinal and pancreatic carcinoids. In addition, there was no evidence for the involvement of p53 in the malignant metastatic progression of carcinoids.

Implantation of self-expanding esophageal metal stents for palliation of malignant dysphagia.

Eleven self-expanding metal stents were perorally implanted in ten patients with locally advanced malignant obstruction of the esophagus. After bougienage of the strictures, the stents were painlessly inserted and properly released by means of an 18 French gauge delivery catheter. In all cases, the endoprostheses expanded to a diameter of 14-20 mm and achieved immediate improvement of dysphagia. One perforation was seen after a single session of dilatation and subsequent stent insertion. No other early complication was observed. After a median follow-up of 74 days (Range, 33-252 days), one of eight patients is still alive and 7 died of non-procedural causes. The grade of dysphagia improved from a mean of 2.9 to a mean of 1.6 and 2.0, respectively, depending on the follow-up period (scale 0-4). Esophageal reobstruction occurred in four patients due to food impaction (two patients) or tumor ingrowth into the stent through the wire mesh (two patients). Recanalisation of the obstructed stent lumen was achieved by endoscopic irrigation (two patients), laser therapy only (one patient) or diathermia with subsequent insertion of a conventional plastic endoprosthesis into the metal stent (one patient). The initial results are promising. The delivery system, the wide-bore diameter, the macroporous configuration and the low mass of the self-expanding stents would seem to be associated with a less traumatic insertion procedure and a lower rate of stent migration as compared with conventional prostheses. Technical improvement may be required for prevention of tumor infiltration. Controlled trials are warranted to determine the future role of metallic stents for palliation of esophagocardial tumors.