Search

Carcinoma ex pleomorphic adenoma (CXPA) is a rare parotid malignancy and until today no standardized concept exists for its therapy apart from recommendations for parotid carcinoma in general. Prognosis is thought to be poorer than for other parotid malignancies. We sought to describe a general diagnostic and therapy strategy and assess factors predicting the outcome.We retrospectively analysed the courses of 22 patients with a CXPA of the parotid gland treated at a tertiary medical care centre for otorhinolaryngology. We examined parameters of medical history, diagnostics, surgical and adjunctive therapy and analysed overall and disease-specific survival.About half of the patients had evidence of a parotid mass of up to 1 year only while maximum of the others was 48 years. Nine patients were primarily operated without suspicion for malignancy. Both 5-year disease-specific and overall survival were 60%. Recurrence-free survival rate after 5 years was 85%. Any patients with a stage I or II disease had an uneventful follow-up. To date, no patient with a stage IV disease has survived longer than 5 years.Surgical therapy (total or radical parotidectomy) is the method of choice for CXPA of the parotid gland. Stage I tumors have a very good and stage IV tumors a bad prognosis.

Background. Using the rat facial nerve axotomy model, the authors recently showed that manual stimulation of denervated whiskerpad muscles reduced the posttransectional polyinnervation at the neuromuscular junctions and promoted full recovery of vibrissal whisking. Objective. Prompted by implications for rehabilitation therapy, the authors examined whether manual stimulation of denervated supra- and infrahyoid muscles would also improve recovery after unilateral lesion on the hypoglossal nerve. Methods. Adult rats underwent transection of the right hypoglossal nerve. Half of the animals received no postoperative treatment, and the other half were subjected to daily manual stimulation of the suprahyoid/sublingual region for 2 months. Recovery was assessed by measuring the angle of tongue-tip deviation from the midline, degree of collateral axonal branching at the lesion site (counts after retrograde labeling with 2 fluorescent dyes), synaptic input to the hypoglossal motoneurons using synaptophysin immunocytochemistry, tongue-muscles motor representation in the cerebral cortex after c-Fos immunocytochemistry, and portion of polyinnervated neuromuscular junctions. Results. In animals receiving manual stimulation, the tongue-tip deviation was 37.0 ± 49.37°, whereas values in control nonstimulated rats were significantly higher (50.1 ± 9.01°; P < .05; mean ± SD). Improved recovery was not associated with reduced collateral axonal branching; there were also no differences in tongue-muscles representation in the motor cortex. However, manual stimulation restored the total synaptic input to levels in intact animals and reduced the proportion of polyinnervated neuromuscular junctions compared with nonstimulated animals. Conclusion. The data show that manual stimulation of denervated muscles improves functional outcome following peripheral nerve injury. This suggests immediate potential for enhancing clinical rehabilitation strategies.

Within a recent study on the recovery of vibrissae motor performance after facial nerve repair in blind (strain SD/RCS) and sighted (strain SD) rats, we found that, despite persisting myotopic disorganization in the facial nucleus, the blind animals fully restored vibrissal whisking. Searching for the morphological substrates of this improved recovery, we compared the amount of cytoskeletal proteins in the leading edge of elongating axons between both strains. Since our results showed an enhanced expression of neuronal class III beta-tubulin in the blind rats, we wondered whether this was due to an increased synthesis or to a delayed turnover of microtubules. In the present report, we approached this question applying established pharmacological agents to the transected buccal branch of the facial nerve in sighted Wistar rats perturbing either microtubule assembly towards stabilization (enhanced polymerization with 10 microg/ml taxol) or towards increased synthesis (challenged by destabilization with 100 microg/ml nocodazole and 20 microg/ml vinblastine). Evaluation of the effect(s) 2 months later included estimation of (i) vibrissae motor performance by video-based motion analysis, (ii) the degree of collateral axonal branching by double retrograde neuronal labeling with crystals of Fluoro-Gold and DiI and (iii) the pattern of motor end-plate reinnervation (proportions of mono- and poly-reinnervated) in the largest extrinsic vibrissal muscle, the m. levator labii superioris. We found that only stabilization of microtubules with 10 microg/ml taxol reduced intramuscular axonal sprouting and polyinnervation of the motor end-plates, which was accompanied by improved restoration of function.

Background The facial nerve function after facial-facial nerve anastomosis, grafting, hypoglossal-facial nerve anastomosis, hypoglossal-facial interpositional jump nerve anastomosis, or a combined approach was analyzed. Methods Facial function was assessed after operation using a 7-point visual analog scale (VAS) and by electromyography (EMG) in 53 patients. The final result was judged by May’s facial nerve grading system. Results Voluntary EMG activity occurred on average 4.52 ± 1.31 months after operation. Initial facial movements were visible after 5.41 ± 1.80 months. Facial function related to the VAS finally reached 44% of normal value. The result was judged May’s grade I in 13%, grade II in 34%, grade III in 28%, and grade IV in 25% of patients. A significant difference in outcome between different reconstruction types was not seen. Age over 60 years was related to worse outcome. Conclusions A correct selection of the best method in the individual situation presumed, all analyzed facial reanimation techniques seem to lead nearly similar and satisfactory results.

It is believed that a major reason for the poor functional recovery after peripheral nerve lesion is collateral branching and regrowth of axons to incorrect muscles. Using a facial nerve injury protocol in rats, we previously identified a novel and clinically feasible approach to combat axonal misguidance--the application of neutralizing antibodies against neurotrophic factors to the injured nerve. Here, we investigated whether reduced collateral branching at the lesion site leads to better functional recovery. Treatment of rats with antibodies against nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor, insulin-like neurotrophic factor I, ciliary neurotrophic factor or glial cell line-derived neurotrophic factor increased the precision of reinnervation, as evaluated by multiple retrograde labelling of motoneurons, more than two-fold as compared with control animals. However, biometric analysis of vibrissae movements did not show positive effects on functional recovery, suggesting that polyneuronal reinnervation--rather than collateral branching --may be the critical limiting factor. In support of this hypothesis, we found that motor end-plates with morphological signs of multiple innervation were much more frequent in reinnervated muscles of rats that did not recover after injury (51% of all end-plates) than in animals with good functional performance (10%). Because polyneuronal innervation of muscle fibres is activity-dependent and can be manipulated, the present findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.

Abnormally associated movements inevitably occur after surgical repair of the facial nerve. The reason for this postparalytic syndrome is poor navigation of regrowing axons. Despite the valuable functional advantage provided by the easily detected movement of vibrissae in rats, the major investigative tools for establishing the degree of misdirected reinnervation are still electrophysiologic recordings and retrograde tracing. In the present study we complemented data from pre- and postoperative retrograde labeling (FluoroGold, Fast Blue, DiI) of facial motoneurons with an evaluation of whisker movements. Using a video-based motion analysis system, we compared the recovery of vibrissae motor performance in visually normal and blind rats of the Sprague-Dawley strain. The analysis of whisker movement after facial nerve surgery revealed a striking discrepancy between morphologic and functional estimates. Whereas retrograde labeling displayed poor accuracy of target reinnervation and supernumerary axonal branching in both groups, the video-based motion analysis showed a perfect recovery of vibrissae movements in the blind rats. Attributing the complete recovery of whisker movement in the blind rats to an extraordinary plasticity of the facial motoneurons induced by putative behavioral demand and forced overuse, we conclude that the video-based analysis of whisker movement is a valuable tool for studying the progress in functional recovery.

Because of their serious consequences for all aspects of development, severe hearing disorders in children are an important clinical entity. A better understanding of the epidemiology and etiology of acquired hearing disorders may potentially lead to more effective prevention. Marked differences in the epidemiology of acquired hearing disorders are reported in the literature. In order to illuminate the problem of acquired disorders and to define current etiological causes with special regard to ethnological factors in the Cologne area, we started a retrospective study. A total of 314 children in residence at the school for hearing impaired children in Cologne were investigated. We also obtained concise data on the structure of the population in order to determine prevalence of acquired hearing disorders in the German and immigrant portions of the population. We found an overall prevalence of 0.43 per thousand for severe hearing disorders and deafness. German children were most frequently affected by acquired, and non-German children by hereditary hearing disorders. The most common causes of acquired severe hearing disorder were the perinatal complex of premature delivery, anoxia and hyperbilirubinuria or kernicterus. Other causes were congenital rubella infections and meningitis in early childhood. The accumulation of perinatal etiologies seems to be the reason for the remarkable majority of acquired hearing disorders among German children. One reason might be progress in neonatology which exerts two effects. It decreases perinatal mortality but increases perinatal complications like acquired hearing impairment. The incidence of congenital rubella in Germany has decreased during recent years, reaching a low level.

Hypoglossal facial anastomosis (HFA) is a standard surgical technique for restoration of facial movements in cases of intratemporal lesions of the facial nerve. Case reports provide evidence that an affected trigeminal system reduces functional outcome. In order to detect morphological changes in the hypoglossal nucleus responsible for this phenomenon, we used 18 Wistar rats and performed three different surgical combinations. In group 1, six animals received HFA only. In group 2, HFA was combined with resection of the contralateral infraorbital nerve. In group 3, HFA was combined with resection of the ipsilateral infraorbital nerve. Fifty-six days after the operation, horseradish peroxidase (HRP) was injected into the whisker pad. As shown in previous studies using HRP, retrograde-labelled motoneurons occurred in the hypoglossal and facial nuclei. Counts of the labelled motoneurons showed no change in the number of projecting hypoglossal motoneurons in group 2 when compared to HFA only, but a significantly smaller number in group 3 (-35%). Furthermore, the number of projecting facial motoneurons was significantly reduced in group 2 (-85%) and group 3 (-45%). These morphological findings indicate an absent or insufficient functional connection between the contralateral infraorbital nerve and the hypoglossal nucleus, and a strong influence of the infraorbital nerve to the ipsi- and contralateral facial nuclei. Additionally, our study provides morphological evidence that the integrity of the sensory trigeminal system is very important in reconstructive facial nerve surgery.

In clinical practice, the lesioned facial nerve is usually restored by facial-facial nerve anastomosis (FFA) with some delay. The optimal time-point for facial nerve reconstruction is still unknown. This study, using rats, compared the effects of immediate and delayed FFA, i.e. FFA 7-56 days after interruption of the facial nerve. Muscle reinnervation was studied 42 days after nerve suture by counting all retrogradely labelled facial motoneurons after injection of horseradish peroxidase (HRP) into the whiskerpad of the rats. Immediate FFA caused a local hyperinnervation of the target muscle, i.e. the projection of more neurons into the whiskerpad muscles than under normal conditions. FFA delayed for 7 days resulted in a significant suppression of this hyperinnervation, whereas longer delay times of 10-56 days showed no difference from immediate FFA.

Injection of Fluoro-Gold (FG) into the whisker pad of rats yields a stable retrograde labeling of facial motoneurons. After removal of 10 mm from the facial nerve the microglia phagocytose the FG-prelabeled dead neurons and assume the label. A subsequent brightfield immunostaining of the sections with HRP-DAB as end-product fully quenches the fluorescence of FG from all specifically stained structures (immuno-quenching). Combining FG-labeling of neuronophages with immunoquenching, we recently described a population of enigmatic fluorescent cells, found in immediate vicinity to the motoneurons after the general neuronofugal migration of microglia. As the fluorescence of these cells was not quenched after a triple immunostaining with anti neuron-specific enolase, anti-GFAP, and OX-42 (quenching all fluorescence from neurons and glial, they seemed to represent a new, immunologically not identified neuronophage. Now we have further characterized this cell type. Following triple immunostaining, we tested a broad panel of mabs (OX-33, OX-19, OX-18, OX-6, R73, ED1, and ED2) to stain, quench fluorescence, and thus immunotype the unknown phagocytes. Only the mab ED2, the classical marker for perivascular cells, specifically stained the small round neuronophages. This surprising migration of perivascular cells toward decaying neurons was additionally tested and confirmed by intracerebroventricular application of FG prior to resection of the facial nerve Providing evidence for neuronophagia by ED2-positive cells, our results strongly support the hypothesis that the latter are the APC (antigen presenting cells) of the CNS.

Recently, we devised and validated a novel strategy in rats to improve the outcome of facial nerve reconstruction by daily manual stimulation of the target muscles. The treatment resulted in full recovery of facial movements (whisking), which was achieved by reducing the proportion of pathologically polyinnervated motor endplates. Here, we posed whether manual stimulation could also be beneficial after a surgical procedure potentially useful for treatment of large peripheral nerve defects, i.e., entubulation of the transected facial nerve in a conduit filled with suspension of isogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) in collagen. Compared to control treatment with collagen only, entubulation with BM-MSCs failed to decrease the extent of collateral axonal branching at the lesion site and did not improve functional recovery. Post-operative manual stimulation of vibrissal muscles also failed to promote a better recovery following entubulation with BM-MSCs. We suggest that BM-MSCs promote excessive trophic support for regenerating axons which, in turn, results in excessive collateral branching at the lesion site and extensive polyinnervation of the motor endplates. Furthermore, such deleterious effects cannot be overridden by manual stimulation. We conclude that entubulation with BM-MSCs is not beneficial for facial nerve repair.

Invasive aspergillosis and fulminant aspergillosis are rarities with a high mortality. In the literature there is no patient surviving an extended invasive aspergillosis of the paranasal sinuses and skull base after failure of operative intervention and of postoperative amphotericin B therapy. We report a complete remission of an invasive, partially fulminant aspergillosis. After an incomplete removal of the mycotic mass, we started postoperative drug therapy with amphotericin B. Under this treatment, the mycosis progressed. Additionally, the patient developed severe side effects, so that the treatment was interrupted. At this moment, we started a combined antimycotic drug therapy with liposomal amphotericin B and itraconazole. Within 10 weeks, clinically and radiologically, there was complete remission. The patient died 63 weeks after this treatment, due to a fulminant bacterial pneumonia. Postmortem histologic examination showed no aspergillosis in the skull base, paranasal sinuses, or lung.

We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage.

Objectives: Analyze the postoperative quality of life (QoL) in patients after surgical nerve repair for facial nerve lesion. Study Design: Descriptive study using questionnaire data and medical chart review. Methods: Forty-nine patients answered the Short Form-36 (SF-36), the European Organization for Research and Treatment (EORTC) questionnaires QLQ-C30 and QLQ-HN35, and a modification of the Acoustic Neuroma Hospital of Norway Survey. Facial function was self-evaluated by the patients using the House-Brackmann (HB) scale and the Stennert index (SI). The questionnaire data were analyzed in relation to the medical chart data. Results: The follow-up time ranged from 12 to 202 months. The underlying disease was benign in 34 (61%) patients and malignant in 15 (39%) patients. Facial nerve repair was successful in all patients, with a mean HB scale of 3.1, a mean SI of 4.9, and a mean May grading of 2.7. The facial function self-evaluation was not significantly different. Seventy-five percent of the patients were satisfied with the operation. The SF-36 demonstrated a significantly lower social functioning, emotional role, general mental health, and vitality lower than in the normal German population. In the EORTC QLQ C30, emotional function was low and the insomnia rate high. EORTC QLQ HN35 showed a high rate of trouble with social eating, less sexuality, problems opening mouth, and weight gain problems. Age 45 years or older, female sex, May grading 3 or greater, SI self-assessment 5 or greater, HB self-assessment greater than 2 had a significant negative effect on some QoL items, but not factors such as type or histology of the disease or delayed reconstruction. Conclusions: Although grading of facial function after nerve repair revealed satisfying results, the patients experience a reduced QoL.

The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2-5 microm). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen-filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle-treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.

Many patients suffer lifelong disabilities after peripheral nerve injury. Insufficient recovery has been attributed to excessive axonal branching, axonal regrowth to improper targets and polyneuronal reinnervation of motor endplates. We used the rat facial nerve transection/suture model to quantify the effects of mechanical stimulation on the paralyzed whisker musculature. "Manual" stimulation involved briskly stroking the whiskers by hand in a manner that specifically mimicked normal whisker movement. "Environmental" stimulation involved enhanced whisker use as rats encountered objects in an enriched environment. Manual and environmental stimulation were also combined. Video-based motion analysis of vibrissal motor performance showed that daily manual, but not environmental, stimulation for 2 months resulted in full recovery of whisking. Polyneuronal reinnervation of motor endplates was reduced but not misdirected axonal regrowth. Our findings indicate the potential of use-specific training to enhance appropriate functional outcome after peripheral nerve injury and may be useful in a clinical rehabilitation setting.

OBJECTIVE: A clinical staging system for children with lymphatic malformations that would allow for a standardized comparison of disease and treatment outcomes. METHODS: We developed an examination sheet for the determination of a disease score ranging from 0 (worst) points to 10 (best) points, Cologne Disease Score (CDS). Disfigurement, dysphagia, dysphonia, dyspnea and an observer statement towards progression were contributing to CDS. Each parameter yielded two, one or zero points. Two points were given when no limitation was seen in the patient concerning the respective item. One point was given at mild limitation and zero points were given when considerable limitation in the respective item could be observed. We evaluated 26 patients with lymphatic malformations of the head and neck retrospectively by completing one examination sheet for each patient-visit. RESULTS: Four patients had an initial CDS value of three or less points (severe disease-group). After therapy the mean value of their score increased only slightly to 3.9+/-2.6 points. Six patients had an initial CDS value of four, five or six points (advanced disease-group). After treatment their mean score value increased dramatically to 9.0+/-1.5 points (P

Despite the availability of antibiotics, acute otitis media can still lead to major complications. Bezold's abscesses are very rare complications and are usually found only in adults with well-pneumatized mastoid bones. We present the case of a 10-week-old newborn with a Bezold's abscess. It is stressed that acute otitis media can be silent and undetected in infants and can lead to major complications such as Bezold's abscess.

The ability of four different brainstem motoneuron pools to perform a newly acquired motor task was studied in alert cats. A classical conditioning of eyelid responses was carried out in (i). unoperated animals, and in animals with (ii). transection, 180 degrees rotation, and re-suture of the zygomatic facial nerve branch, (iii). a crossed anastomosis of the buccal to the zygomatic facial nerve branch and (iv). a hypoglossal-facial nerve anastomosis. Animals were conditioned with a delay paradigm using a tone (350 ms, 600 Hz, 90 dB) as conditioned stimulus, followed 250 ms later by an air puff (100 ms, 3 kg/cm2) as unconditioned stimulus. Animals with zygomatic nerve rotation performed conditioned responses (CRs) at control rate, with significantly larger amplitude, area and velocity, but a de-synchronized oscillatory pattern. Animals with buccal-zygomatic anastomosis acquired CRs at control rate, but these CRs had significantly smaller amplitude than those of controls and a de-synchronized pattern. Animals with a hypoglossal-facial anastomosis were unable to perform CRs. The trigeminal hyper-reflexia triggered by the axotomy was probably the origin of the large CRs after zygomatic nerve rotation. Trigeminal hyper-reflexia could also contribute to generation of the small CRs recorded after buccal-zygomatic anastomosis. Although trigeminal hyper-reflexia was also present following hypoglossal-facial anastomosis, hypoglossal motoneurons did not reach their firing threshold to perform CRs. In accordance with the embryonic origin of involved motoneurons, animals with buccal-zygomatic and hypoglossal-facial anastomoses moved the ipsilateral eyelid synchronously to mouth-related activities. It is suggested that there is a gradient of adaptability in motoneuron pools forced to perform new motor tasks through foreign muscles, which depends on their embryological origins and functional properties.

To improve functional recovery after peripheral nerve suture, we characterized the quality of target reinnervation in rats in which the afferent trigeminal connection to facial motoneurons had been altered.Employing an improved lesion model and a refined mode of retrograde tracer application, we studied the accuracy of reinnervation in rats which underwent buccal-buccal nerve anastomosis (BBA) alone (group 1), BBA plus excision of the ipsilateral infraorbital nerve (ION; group 2), and BBA plus excision of the contralateral ION (group 3). This was done by comparison between the number of double-labeled motoneurons after pre-operative injection of Fluoro-Gold (FG) and post-operative injection of Fast Blue (FB) into the whisker pad muscles.In the first group we counted 398 +/- 80 FG+FB double labeled cells (mean +/- SD; n = 9 rats), i.e., only 27% of all motoneurons that grew axons into the whisker pad had projected to these muscles before surgery. In group 2, this value was increased marginally to 436 +/- 68 (32%). In group 3,. we counted 580 +/- 63 double-labeled neurons. This is the first morphological report demonstrating significantly improved specificity of reinnervation. Indeed, 41% of the motoneurons innervating the target in group 3 belonged to the original neuron pool. These morphological findings are supported by evidence obtained from electrophysiological recordings and behavioural studies.The principle finding of the present study is that a peripheral lesion to the contralateral trigeminal nerve improves the quality of reinnervation of the whisker pad musculature by its original nerve. The contralateral trigeminal lesion may trigger behavioural demand and forced overuse of the axotomized facial nerve, which may be a key issue for recovery of vibrissae rhythmical whisking after facial nerve surgery.

The occurrence of abnormally associated movements is inevitable after facial nerve transection. The reason for this post-paralytic syndrome is poor guidance of regrowing axons, whereby a given muscle group is reinnervated by misrouted axonal branches. Olfactory ensheathing glia have been shown to reduce axonal sprouting and stimulate axonal regeneration after transplantation into the spinal cord. In the present study, we asked whether transplantation of olfactory mucosa (OM) would also reduce sprouting of a damaged peripheral pure motor nerve. The adult facial nerve was transected, and the effect of the OM placed at the lesion site was analyzed with regard to the accuracy of target reinnervation, axonal sprouting of motoneurons, and vibrissal motor performance. Accuracy of target reinnervation and axonal sprouting were studied using preoperative/postoperative labeling and triple retrograde labeling of facial motoneurons, respectively. The vibrissal motor performance was monitored using a video-based motion analysis. We show here that implantation of OM, compared with simple facial–facial anastomosis, (1) improved the protraction, amplitude, angular velocity, and acceleration of vibrissal movements up to 80% of the control values, (2) reduced the percentage of branching motoneurons from 76 to 39%, and (3) improved the accuracy of reinnervation from 22 to 49%. Moreover, we present evidence, that transplanted OM but not buccal mucous membrane induced a sustained upregulation of trophic factors at the lesion site. It is concluded that transplantation of OM to the transected facial nerve significantly improves nerve regeneration.

Hypertrophy of the cricopharyngeal muscle is a serious clinical condition that can cause severe dysphagic symptoms, including prolonged deglutition and postdeglutitive aspiration. Although the therapeutical concepts are well established, the pathogenic mechanism of cricopharyngeal hypertrophy remains unclear. We present a patient with a ten-year history of progressive dysphagia. The neurological and MRI findings were normal. However, videocineradiography showed severe hypertrophy of the cricopharyngeal muscle. This condition was first treated by injections of botulinum toxin, which did not alleviate the symptoms. Next, myotomy and muscle biopsy were performed. Histological evaluation disclosed lymphoplasmacellular florid myositis, single-fiber atrophy, and muscle fiber necrosis with phagocytosis. There were no signs of inclusion body myositis or oculopharyngeal muscular dystrophy. Our finding of severe cricopharyngeal muscle hypertrophy associated with myositis has been published previously (n = 34). The study presented here shows cricopharyngeal dysphagia associated with various systemic diseases, including motor neuron disease, general granulomatous disease, dermatomyositis, or inclusion body myositis. Isolated changes of the cricopharyngeal muscle were described in 65% of the cases.

To establish the influence of prolonged denervation on the recovery of a motor nerve, the rat facial nerve was transected and denervated for 0 to 224 days. Then, the freshly transected hypoglossal nerve was sutured to the predegenerated facial nerve (hypoglossal–facial nerve anastomosis, HFA). Using this nerve cross-anastomosis paradigm we analyzed the nerve regeneration and muscle reinnervation 7 to 112 days post-suture operation (DPSO). After HRP injection into the whiskerpad 931 ± 27 hypoglossal neurons were labeled at 112 DPSO after immediate HFA. Following 14 to 112 days denervation the number of labeled neurons increased to 138% (14 days delay), 154% (56 days), and 145% (112 days). In contrast, the reinnervation was poorer after 7 days denervation with the number of neurons increasing to 84%, and after long-term denervation of 224 days the number of neurons increased to 81%. The increase in amplitude of evoked electromyography wave after nerve suture correlated with the number of labeled neurons. After immediate HFA each regenerated motoneuron established on average 5.1 myelinated sprouts at 112 DPSO. The number of sprouts remained constant after delayed suture of 14 to 112 days, whereas the slower reinnervation after 7 or 224 days delay was accompanied by a massive sprouting of 9.1 or 8.1, respectively, sprouts per neuron. The muscles showed recovery after any denervation time. The muscle cross-sectional area continuously decreased with longer denervation time. This decrease was only significant after 224 days denervation (67% of the normal value). We conclude that motor nerve reconstruction achieves better functional results after a definite period of denervation when using a nerve cross-anastomosis paradigm.

Recent studies have revealed marked differences in the prevalence of hearing impairment in childhood. It remains unknown whether this is caused by geographic, sociocultural or ethnic factors. In order to provide consistent data, 314 children in residence at a school for hearing impaired children of a well-defined German area were investigated retrospectively. We estimated an overall prevalence of .43/1000 of hearing impairment for this area. A striking variability between different nationalities could be observed. For German children, the prevalence was .36/1000, for Turkish 1.04/1000 and for Italian children 1.37/1000. Hereditary hearing losses and, in particular, autosomal recessive caused hearing disorders were the most common cause of hearing impairment in foreign but not in native children. One reason might be the frequency of marriages between relatives resulting from the social isolation of the foreign groups in German society.

Background Facial electroneurography is an objective measurement of a muscle compound action potential. The amplitude ratio between the paretic and the normal side is used as a basis for estimating the prognosis of facial palsy. According to Esslen, the difference of amplitudes in healthy subjects is only 3%. Twenty healthy test persons were investigated with the aim of 1. reproducing the published data on the left-right difference in normal test subjects and 2. determining whether the amplitude ratio is constant over time after repeated measurements. Study design Bilateral electroneurography was conducted on 20 healthy volunteers (age range, 23-36 y; 12 men, eight women). Two investigators performed four measurements at 1-week intervals on every subject. Results Mean amplitude ratio was 32.5%. Repeated measurements on the same individual differed considerably-- from 0% to 80%. The 99% confidence interval computed from the data ranged from 26% to 39% amplitude ratio. Conclusion The symmetry of facial evoked compound potentials postulated by Esslen and Fisch is not supported by these data. As have other investigators, the authors found significant left-right differences in healthy subjects. Furthermore, they showed for the first time that the amplitude ratio is not constant in every individual at repeated measurements. In light of these data, prognosis of facial palsy based on electroneurographic data alone seems doubtful.

Axotomy induces a profound modification of Ca2+ homeostasis in injured neurons which may lead to neuronal death. Remarkably, after axotomy and resection of the hypoglossal nerve, 65-75% of the hypoglossal motoneurons survive in the long term and this suggests some adaptive mechanisms compensating the massive calcium influx. As potential components of this adaptation, we have examined calmodulin and calbindin-D28k by in situ hybridisation and immunohistochemistry in motoneurons of the rat after hypoglossal nerve transection. Neuronal calbindin mRNA and protein content was low in normal state, transiently increased to 200% of the basal expression at 8 days post-operation (dpo), then declined to normal again until 28 dpo. Calmodulin mRNA was highly expressed in normal hypoglossal motoneurons and remained constant after axotomy. Calmodulin protein immunoreactivity, however, was transiently decreased in axotomised motoneurons suggesting post-transcriptional modification. The upregulation of calbindin expression may facilitate the survival of injured motoneurons.

Calbindin D28K, an intracellular calcium-binding protein, acts as Ca2+ buffering system in the cytoplasm. By means of this property, calbindin may protect neurons against large fluctuations in free intracellular Ca2+ and, hence, may prevent cell death. Although axotomy causes a massive influx of calcium into the lesioned neurons, resection of the hypoglossal nerve does not induce extensive neuronal cell death in rats. Even several weeks after axotomy, about 70% of the motoneurons survive despite permanent target deprivation. The mechanisms responsible for this remarkable survival rate are unknown. In this study, we have looked at the modification of calbindin immunoreactivity in axotomized hypoglossal motoneurons. In non-axotomized motoneurons, no calbindin is detectable by immunocytochemistry. Axotomy induced an increase of calbindin immunoreactivity in lesioned motoneurons. This increase, visualised by the number of calbindin-immunoreactive neurons extended from 1 day to 28 days. At this time most, but not all, motoneurons located on the side of the lesion were calbindin-positive as shown by retrograde labeling and immunoquenching. From 14 days post operation, calbindin immunoreactivity decreased and reached its basal value after 35 days post operation. At that time, only fibres were still calbindin immunoreactive. Interestingly, calbindin-immunoreactivity was also increased in almost all cell nuclei, compatible with a nuclear regulation. These data are consistent with the hypothesis that, as a reaction to axotomy, motoneurons trigger an increase in calbindin expression which acts as a compensatory Ca(2+)-buffering system, enabling neurons to maintain Ca2+ homeostasis and the survival of many motoneurons after axotomy.

Facial-facial anastomosis (FFA), i.e., suture of transected facial nerve, was performed in adult Wistar rats. For 10–112 d post-operation (DPO), half of the animals received standard food (placebo) and half received food pellets containing 1000 ppm nimodipine, a Ca2+ channel blocker. The time course of mimetic reinnervation between these two groups was compared by counting all retrogradely labeled motoneurons after injection of horseradish peroxidase (HRP) into the whiskerpad. In unoperated animals, injection of HRP labeled 1280 +/- 113 motoneurons. After FFA, this number dropped to zero, and the first HRP-labeled facial motoneurons reappeared in both placebo- and nimodipine-treated animals at 14 DPO. The treatment with nimodipine yielded two beneficial effects. (1) It accelerated axonal sprouting until 28 DPO. Whereas the number of HRP-labeled cells in the placebo group was 171 +/- 9 (mean +/- SD) at 16 DPO, 372 +/- 43 at 21 DPO, and 636 +/- 187 at 28 DPO, the number of sprouted motoneurons in nimodipine-treated rats was twice as high: 386 +/- 34 at 16 DPO, 620 +/- 28 at 21 DPO, and 756 +/- 257 at 28 DPO. (2) Nimodipine reduced the polyneuronal innervation of the target muscles. Whereas the number of HRP-labeled cells in the placebo group increased to 1430 +/- 36 at 56 DPO and 1600 +/- 31 at 112 DPO, the number of labeled motoneurons in nimodipine-treated rats remained almost within the normal range: 1315 +/- 31 at 56 DPO and 1354 +/- 33 at 112 DPO.

The unsatisfactory results obtained from tone and speech audiometric studies in identifying the effects of hearing disability, in particular the psychosocial factors, prompted us to adopt a psychological test to determine the "social hearing ability". The test consists of 20 questions which all relate to "social hearing ability" in urban society. Ten questions concern hearing ability in situations where background noise plays either a negligible role or none at all. The remaining 10 questions concern selectivity ability, that is hearing with additional background noise. The evaluation of the questionnaire results in a classification of the so-called Social Hearing Handicap Index (SHHI) in percentages together with a breakdown of the deafness components and the selectivity components into percentages. This differentiation provides additional information about the demands placed on the hearing ability of humans in quiet or noisy surroundings. The information obtained from the test enables longitudinal studies on the course of a hearing disability or the effectivity of a particular therapy, e.g. hearing aid, to be carried out in the elderly.

Microglial activation in response to pathological stimuli is characterized by increased migratory activity and potential cytotoxic action on injured neurons during later stages of neurodegeneration. The initial molecular changes in the CNS favoring neuronofugal migration of microglia remain, however, largely unknown. We report that the extracellular matrix protein tenascin-R (TN-R) present in the intact CNS is antiadhesive for activated microglia, and its downregulation after facial nerve axotomy may account for the loss of motoneuron protection and subsequent neurodegeneration. Studies on the protein expression in the facial and hypoglossal nucleus in rats demonstrate that TN-R is a constituent of the perineuronal net of motoneurons and 7 d after peripheral nerve injury becomes downregulated in the corresponding motor nucleus. This downregulation is reversible under regenerative (nerve suture) conditions and irreversible under degenerative (nerve resection) conditions. In short-term adhesion assays, the unlesioned side of brainstem cryosections from unilaterally operated animals is nonpermissive for activated microglia, and this nonpermissiveness is almost abolished by a monoclonal antibody to TN-R. Microglia-conditioned media and tumor necrosis factor-alpha downregulate TN-R protein and mRNA synthesis by cultured oligodendrocytes, which are one of the sources for TN-R in the brainstem. Our findings suggest a new role for TN-R in neuronal protection against activated microglia and the participation of the latter in perineuronal net destruction, e.g., downregulation of TN-R.