Cochlear MRI Signal Change Following Vestibular Schwannoma Resection Depends on Surgical Approach.

OBJECTIVE: Information on cochlear MRI signal change following vestibular schwannoma (VS) surgery by the retrolabyrinthine approach (RLA) is nonexisting, and information using the translabyrinthine approach (TLA) is scarce. We aimed to evaluate cochlear MRI fluid signal in patients with a unilateral VS, before and after surgery by the RLA or the TLA, that can have clinical importance for subsequent cochlear implantation feasibility. STUDY DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: One hundred one patients with a unilateral VS. INTERVENTION: VS resection by the TLA or the RLA. Pre- and postoperative T2-weighted MRI. MAIN OUTCOME MEASURE: Cochlear signal change using a semiquantitative system for grading cochlear asymmetry, with grades ranging from 1 (normal fluid signal both sides) to 4 (no fluid signal one side). RESULTS: Seventy-four patients were operated by the TLA and 27 by the RLA. The number of cochleas with grade 3 and 4 asymmetries postoperative was significantly higher than preoperative. The postoperative proportions of grade 1 (TLA 20%, RLA 56%) and grade 2-4 asymmetry (TLA 80%, RLA 44%) were significantly different between the two groups. In the TLA group, 46 patients (62%) demonstrated an increased asymmetry postoperatively, as compared with three patients (11%) in the RLA group. CONCLUSIONS: Postoperative decrease of cochlear MRI fluid signal is more likely to occur after translabyrinthine surgery (occurring in 62%), as compared with retrolabyrinthine surgery (occurring in 11%). The decrease of cochlear signal may be due to compromised vascularity or fibrosis.

Reposition Chair Treatment Improves Subjective Outcomes in Refractory Benign Paroxysmal Positional Vertigo.

OBJECTIVES: Despite increasing utilization of reposition devices in the management of benign paroxysmal positional vertigo (BPPV), knowledge on subjective outcomes is insufficient. The objective of the present study was to evaluate subjective vertigo complaints and vertigo-associated emotional distress during reposition chair management for refractory BPPV. MATERIALS AND METHODS: This was a prospective observational cohort study of subjective and objective data of 31 patients suffering from refractory BPPV representing failed conventional repositioning treatment. At the beginning of each visit, the patients filled out the Dizziness Handicap Inventory (DHI), the Visual Analog Scale (VAS), and the Hospital Anxiety and Depression Scale (HADS). Treatment and re-evaluation were repeated every 2 weeks until the patient was declared disease-free. RESULTS: Complete remission of BPPV required a mean of two treatments. Mean DHI score decreased from 45 points prior to first treatment to 22 points by finished treatment (p<0.001). Similarly, mean VAS score was reduced from 58 to 25 points (p<0.001), and HADS decreased from 8 to 5 points (p<0.001). Patients with cupulolithiasis reported worse vertigo complaints than those with canalolithiasis. All scores correlated positively. CONCLUSION: Patients with refractory BPPV improved significantly by reposition chair management according to all subjective outcomes. Thus, the reposition device could significantly reduce disease burden in the group of patients with BPPV who failed to respond to conventional management. The strong correlation between the scores suggests VAS as a useful tool for vertigo-related patient complaints.

[Workup and treatment of Eustachian tube dysfunction in adults].

Symptoms of Eustachian tube dysfunction are frequent and multiple. Therefore, clear definitions and diagnostic criteria are important in order to achieve appropriate patient flow. So far, there has been a lack of consensus on this subject, but the proposed definitions and diagnostic criteria in this review may aid to achieve this. Tubomanometry is a diagnostic tool to evaluate Eustachian tube function, and balloon dilation of the Eustachian tube can be a helpful treatment in patients with Eustachian tube dysfunction.

Facial nerve schwannomas presenting with vestibular dysfunction: a case series.

Facial nerve schwannomas (FS) can symptomatically mimic vestibular schwannomas (VS). In addition, FS can be difficult to distinguish from VS on magnetic resonance imaging (MRI). Although disequilibrium is not uncommon in patients with FS, no previous studies have investigated the vestibular function in such patients. Three cases of FS presented vestibular dysfunction as measured with caloric test, video head impulse test (VHIT), and vestibular evoked myogenic potentials (VEMPs). All patients in this study had a considerable affection of the vestibular function as assessed by the vestibular test panel. Audiovestibular evaluation of FS provides important information that may influence treatment strategy. As VS, FS should be evaluated with vestibular tests prior to intervention.

Audiovestibular Loss of Function Correlates in Vestibular Schwannomas.

OBJECTIVES: The aim of the present study was to investigate the relationships between tumor size, hearing, and vestibular outcomes in patients with vestibular schwannomas (VSs). MATERIALS AND METHODS: Adult patients (n=124) with unilateral extrameatal VS prior to surgery were included in the study. This was a retrospective cohort study of preoperative audiovestibular investigations including audiometry, discrimination test, caloric test, cervical vestibular evoked myogenic potential (c-VEMP), and ocular vestibular evoked myogenic potential (o-VEMP). RESULTS: The difference between lesioned and non-lesioned ear was significant for all audiovestibular outcomes. The mean caloric deficit was 74%. No tumor sided o-VEMPs were elicited. Caloric deficit correlated with hearing loss measured with pure tone average and discrimination score. c-VEMP deficit was significantly associated with severe hearing loss and larger tumors. CONCLUSION: The presence of VS leads to a significant deterioration of audiovestibular function in all objective measures. Caloric test and o-VEMPS are sensitive though unspecific measures of VSs. Increasing tumor size is not directly associated with hearing loss and only somewhat to vestibular deficit. However, audiovestibular findings are correlated.

[Benign paroxysmal positional vertigo treatment].

Benign paroxysmal positional vertigo (BPPV) remains the most frequent cause of vertigo. The TRV chair is a mechanical device suited for optimization of managing complex cases of BPPV. Although the use of repositioning devices in the management of BPPV is increasing, no applicable guide for the TRV management of the different BPPV subtypes exists. This article presents the techniques for addressing canalolithiasis and cupulolithiasis in the TRV chair for each affected semicircular canal. In a tertiary referral centre like our unit the TRV chair is an asset in the management of BPPV.

Neuronal Fibers and Neurotransmitter Receptor Expression in the Human Endolymphatic Sac.

INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may have multiple functions, including an ion-transport capacity comparable to the kidney, an immunological capacity and a possible natriuretic capacity. Further, there have been speculations of a yet undefined role in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES. STUDY DESIGN: DNA micro-arrays and immunohistochemistry were used for analyses of fresh human ES tissue samples. METHODS: A total of 30 tissue samples from the human ES were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample gene expression, using adjacent dura mater as control. The expression of genes specific for neuronal signaling was determined and results for selected key molecules verified by immunohistochemistry. Transmission electron microscopy was used for ultrastructural analysis. RESULTS: For the transmission electron microscopy analysis, a direct innervation of the ES was observed with unmyelinated fibers imbedded in the ES epithelial lining. The microarrays confirmed, that several molecules involved in neuronal signaling were found expressed significantly in the ES DNA profile, such as the Cholecystokinin peptide and related receptors, Dopamine receptors 2 and 5, vesicular monoamine transporter 2 (VMAT2), plasma monoamine transporter (PMAT), and Serotonin 1D. All peptides were verified by immunohistochemistry. CONCLUSIONS: Based on global gene expression profiling and immuno-histochemical labeling, we conclude that the human ES expresses neuropeptide receptors and monoamine transporters. Combined with the ultrastructural demonstration of unmyelinated axons imbedded within the epithelial lining, the findings suggest that neuro-signaling mechanisms are involved in functions exerted by the ES.

The human endolymphatic sac expresses natriuretic peptides.

OBJECTIVES/HYPOTHESIS: The function of the human endolymphatic sac (ES) has been enigmatic for decades. Hypotheses include controlling endolymphatic fluid homeostasis and inner ear immunological defense. Additionally, several studies indicate a possible endocrine capacity and a yet undefined role in intracranial pressure homeostasis. However, no direct evidence of such capacity exists. This study aims to explore and identify the hypothesized endocrine capacity of the human ES. STUDY DESIGN: DNA microarrays and immunohistochemistry were used for analyses of fresh human ES tissue samples. METHODS: Twelve tissue samples from the human ES were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample gene expression. Genes specific for an endocrine function were determined, and results were verified by immunohistochemistry. RESULTS: Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were verified by immunohistochemistry. CONCLUSION: The present data support the hypothesis that the human ES may have an endocrine/paracrine capacity through expression of several peptides with potent natriuretic activity. Furthermore, the ES may influence the hypothalamo-pituitary-adrenal axis and may regulate vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct and indirect action on the vascular system and the kidney. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E201-E208, 2017.

The Forgotten Syndrome? Four Cases of Gradenigo's Syndrome and a Review of the Literature.

BACKGROUND: Gradenigo's Syndrome (GS) is defined as the clinical triad of acute otitis media, ipsilateral sixth nerve palsy, and pain in the distribution of the first and the second branches of the fifth nerve. The purpose of this study is to review the literature and report 4 cases of GS. METHODS: The study is a retrospective case series and a review of the literature. Four consecutive patients (aged 5-70 years) treated by otolaryngologists and ophthalmologists for GS in the Capital region of Denmark from 2003 to 2015 are presented. Diagnosis is based on the clinical triad, and in 3 of 4 patients, neuroimaging supports the diagnosis. Follow-up was continued until both the sixth nerve palsy and the ear infection had resolved. Diagnostic work-up and treatment profile are described. RESULTS: In 3 of our 4 reported patients, the presentation of GS was classic with a history of acute otitis media and ipsilateral sixth nerve palsy. One case presented as a chronic case with a sixth nerve palsy secondary to chronic suppurative otitis media (CSOM), with a relapse 6 years later. CONCLUSION: GS is a rare and potentially life-threatening complication to otitis media. GS can present in an acute and chronic form, and should be a differential diagnosis in the workup of unexplained sixth nerve palsy.

Repositioning chairs in benign paroxysmal positional vertigo: implications and clinical outcome.

The objective was to evaluate the clinical value of repositioning chairs in management of refractory benign paroxysmal positional vertigo (BPPV) and to study how different BPPV subtypes respond to treatment. We performed a retrospective chart review of 150 consecutive cases with refractory vertigo referred to our clinic within a 10-month period. The BPPV patients were managed with classical manual manoeuvres, the Epley Omniax(®) rotator (EO) or the TRV chair (TRV). In addition, a comprehensive review of the literature was performed. BPPV was identified in 95 cases. The number of needed treatments for posterior canalolithiasis versus posterior cupulolithiasis, horizontal cupulolithiasis and multi-canal affection was significant (p < 0.01). Thirty-seven (38 %) patients required only one repositioning manoeuvre and the overall symptom relief was 91.7-100 % after 3 treatments. Eleven patients (12 %) experienced relapse within the ½-year follow-up period. Horizontal cupulolithiasis and multi-canal affection constituted the most resilient cases. The literature search identified 9 repositioning chair studies. The EO and the TRV are highly valuable assets in diagnosis and management of BPPV of particularly complex and refractory cases. However, further validation is anticipated through controlled clinical trials.

Peripheral Vestibular System Disease in Vestibular Schwannomas: A Human Temporal Bone Study.

INTRODUCTION: Dizziness is a common symptom in patients with vestibulo-cochlear schwannoma (VS), and several recent studies have identified this symptom as the single most important concerning the quality of life. Clinical and histological observations regarding hearing loss have suggested that this may be caused by both cochlear and retrocochlear mechanisms. Multiple mechanisms may also be at play in the case of dizziness, which may broaden perspectives of therapeutic approach. This study presents a systematic and detailed assessment of vestibular histopathology in temporal bones from patients with VS. METHODS: Retrospective analysis of vestibular system histopathology in temporal bones from 17 patients with unilateral VS. The material was obtained from The Copenhagen Temporal Bone Collection. RESULTS: Vestibular schwannomas were associated with atrophy of the vestibular ganglion, loss of fiber density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which opens perspectives of differentiated clinical assessment and subsequent, targeted therapy.

Gene expression demonstrates an immunological capacity of the human endolymphatic sac.

OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear. STUDY DESIGN: DNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic-sac tissue samples. METHODS: Twelve tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample gene expression using adjacent dura mater as control. The expression of genes specific for the innate immune system was determined and results for selected key molecules verified by immunohistochemistry. RESULTS: A comprehensive overview of expressed genes of the innate immune system was obtained. Multiple key elements of both the cellular and humoral innate immune system were expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and lactoferrin. CONCLUSIONS: The present data provides the first direct evidence of an immunological capacity of the human endolymphatic sac. At the molecular level, the endolymphatic sac is capable of antigen recognition and processing for initiation of an immune response. In addition, potent molecules directly toxic to invading pathogens are expressed by the sac epithelium. This evidence strongly supports the endolymphatic sac as a significant immunological entity of the inner ear. LEVEL OF EVIDENCE: N/A.

Gene expression in the human endolymphatic sac: the solute carrier molecules in endolymphatic fluid homeostasis.

OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the solute carrier (SLC) molecules of ion transporters in the human endolymphatic sac. STUDY DESIGN: cDNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic sac tissue samples. METHODS: Twelve tissue samples of the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used to investigate tissue sample expression of solute carrier family genes, using adjacent dura mater as control. Immunohistochemistry was used for verification of translation of selected genes, as well as localization of the specific protein within the sac. RESULTS: An extensive representation of the SLC family genes were upregulated in the human endolymphatic sac, including SLC26a4 Pendrin, SLC4a1 sodium-bicarbonate transporter, SLC9a2 sodium-hydrogen transporter, SLC12a3 thiazide-sensitive Na-Cl transporter, and SLC34a2 sodium-phosphate transporter. CONCLUSIONS: Several important ion transporters of the SLC family are expressed in the human endolymphatic sac, including Pendrin, the thiazide-sensitive Na-Cl transporter, and the Na-phosphate transporter SLC34a2. The data provide a new knowledge base considering the ion-dependent metabolic mechanisms maintaining inner ear homeostasis. More specifically, the results indicate a strong similarity with the ion transportation occurring in the kidney collecting ducts. In addition, the findings prompt a revision of the theories behind contemporary pharmacological treatment of Ménière's disease and may broaden the understanding of the pathogenesis of BPPV.

Endolymphatic sac involvement in bacterial meningitis.

The commonest sequelae of bacterial meningitis are related to the inner ear. Little is known about the inner ear immune defense. Evidence suggests that the endolymphatic sac provides some protection against infection. A potential involvement of the endolymphatic sac in bacterial meningitis is largely unaccounted for, and thus the object of the present study. A well-established adult rat model of Streptococcus pneumoniae meningitis was employed. Thirty adult rats were inoculated intrathecally with Streptococcus pneumoniae and received no additional treatment. Six rats were sham-inoculated. The rats were killed when reaching terminal illness or on day 7, followed by light microscopy preparation and PAS-Alcian blue staining. The endolymphatic sac was examined for bacterial invasion and leukocyte infiltration. Neither bacteria nor leukocytes infiltrated the endolymphatic sac during the first days. Bacteria invaded the inner ear through the cochlear aquaduct. On days 5-6, the bacteria invaded the endolymphatic sac through the endolymphatic duct subsequent to invasion of the vestibular endolymphatic compartment. No evidence of direct bacterial invasion of the sac through the meninges was found. Leukocyte infiltration of the sac occurred prior to bacterial invasion. During meningitis, bacteria do not invade the endolymphatic sac through the dura, but solely through the endolymphatic duct, following the invasion of the vestibular system. Leukocyte infiltration of the sac occurs prior to, as well as concurrent with bacterial invasion. The findings support the endolymphatic sac as part of an innate immune defense system protecting the inner ear from infection.

[Balloon dilation of Eustachian tube is a new treatment of chronic otitis media].

Balloon dilation of Eustachian tube is a novel method for managing chronic ventilatory dysfunction in patients with chronic otitis media, as an alternative to classic grommet insertion. Although few retrospective studies have been conducted the method seems to be rapid, simple and safe with promising short-term results. This paper presents the method and summarizes the results of available studies. Optimization of patient selection is needed and we discuss the development of better objective measurement methods as well as the need for randomized prospective studies, which are currently being conducted.

Bacterial invasion of the inner ear in association with pneumococcal meningitis.

OBJECTIVE: To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. STUDY DESIGN: A well-established adult rat model of Streptococcus pneumoniae meningitis was used. METHODS: Thirty rats were inoculated intrathecally with S. pneumoniae serotype 1, 3 or 9 V and received no additional treatment. The rats were sacrificed when reaching terminal illness or on Day 7 and then prepared for serial sectioning and PAS-Alcian blue staining for light microscopy. RESULTS: During the first few days after inoculation, bacteria invade the inner ear through the cochlear aqueduct, into the scala tympani of the cochlea (perilymphatic space). From here, bacteria spreads apically toward the helicotrema and subsequently basally through the scala vestibuli, toward the vestibule and the vestibular system. When the bacteria after 5 to 6 days had reached scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. CONCLUSION: From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral ligament capillary bed occur at later stages. Although internal barriers exist within the inner ear, the spreading of bacteria occurs via the natural pathways of the fluid compartments. Bacterial elimination occurs by local macrophage engulfment.

Oxygenated fixation demonstrates novel and improved ultrastructural features of the human endolymphatic sac.

OBJECTIVES/HYPOTHESIS: The purpose of the present study is to describe in detail the ultrastructure of the human endolymphatic sac using a new and improved method of fixation as well as a refined surgical approach in obtaining specimens. STUDY DESIGN: Transmission electron microscopy of the human endolymphatic sac, employing an oxygenated fixative. METHODS: Eighteen tissue samples of the human endolymphatic sac were obtained during surgery for vestibular schwannoma using the translabyrinthine approach. The specimens were fixed in 2% glutaraldehyde in an oxygenated fluorocarbon blood substitute vehicle before preparation by routine methods for transmission electron microscopy. We focused on the epithelial cell layer, subepithelial tissue, intraluminal content, and vascular tissue in both the intra- and extraosseous part of the endolymphatic sac. RESULTS: We observed well-defined endolymphatic sac epithelial cell lining in all 18 specimens. In general, we found very well-preserved specimens with well-defined intracellular structures. In contrast to the results in former studies, a minimum of fixation artifacts was observed in the present study. Three different cell types were observed in the intraosseous part of the sac: mitochondria-rich cells, ribosome-rich cells, and nonclassifiable cells. A fourth cell type was found in the extraosseous part. Novel ultrastructural features of the epithelial lining and the subepithelial layer are described and discussed. CONCLUSIONS: The results in the present study indicate an improvement in obtaining human tissue with optimal fixation for ultrastructural analysis and provide several novel morphologic observations. The potential functions of the endolymphatic sac are discussed with reference to former studies.

Submandibular gland excision: long-term clinical outcome in 139 patients operated in a single institution.

In transcervical resection of the submandibular gland for benign lesions, only a limited risk of damage to neural structures can be accepted and a cosmetically satisfactory result is mandatory. In this retrospective case series, we evaluated 139 patients operated over a 10-year period and completed long-term clinical follow-up of 113 of these patients after a median of 81 months. In all patients, the operation was effective. We found a 4.3 % risk of reoperation for wound infection or postoperative hematomas and an 18.7 % risk of early paresis of the marginal branch of the facial nerve, which decreased to 2.7 % on long-term follow-up. We found a 4.4 % risk of permanent lingual nerve paresis, and no patients had damage to the hypoglossal nerve. Xerostomia was found in 22.1 % of the patients and could be quantified by the easily performed biscuit test. Only 2.5 % reported an unsatisfactory cosmetic result and all scars were ≤ 6 on the Vancouver Scar Scale. Problems with scarring were more common if there had been postoperative infection. We continue to use the lateral transcervical approach as standard in our institution for patients who cannot be managed by gland-sparing procedures.

Risk of marginal mandibular nerve injury in neck dissection.

The immediate and permanent frequency of injury to the marginal mandibular branch of the facial nerve (MMN) after neck dissection has only scarcely been addressed in the medical literature. We investigated the risk of injury in 159 consecutive patients after neck dissection for various reasons in level I B and level II A, respectively. In 95 patients with oral cancer 13 (14%) of the cases had malfunction of the lower lip domain 2 weeks after neck dissection in level I B indicating paresis to the MMN. Follow-up analyses 1-2 years after the operation showed permanent paralysis in 4 to 7% of the cases in whom two of them had the nerve sacrificed for oncologic reasons during the operation. In 18 patients with parotic cancer the corresponding permanent frequency of MMN paralysis was 11.1%. In 46 patients with neck dissection in level II A but not in level I B, no paresis of the MMN was registered. Recognition of the MMN during the operation, pre- or postoperative radiation therapy, re-operation for deep hemorrhage, age, gender or postoperative infection did not have any statistically significant influence on the frequency of MMN injury. In conclusion we found a moderate risk of injury to the MMN after neck dissection in level I B whereas the corresponding risk after level II A dissection was negligible.

Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1.

OBJECTIVES/HYPOTHESIS: Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study targets the angiogenic process by investigation of tumor expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored. STUDY DESIGN: Prospective vestibular schwannoma tissue sampling for ELISA and immunohistochemical determination of MMP-2, MMP-9 and TIMP-1. METHODS: Thirty-four patients with a sporadic, noncystic, vestibular schwannoma were selected prospectively. Repeated, preoperative magnetic resonance imaging determined the tumor growth pattern. Following translabyrinthine resection, an enzyme-linked immunosorbent assay was used for determination of the MMP-2, MMP-9, and TIMP-1 concentration in tumor sample homogenates. Immunohistochemical labeling was performed in 12 randomly selected tumors. RESULTS: : All tumor homogenates expressed measurable MMP-9, MMP-2, and TIMP-1. Immunolabeling localized MMP-9 expression to the tumor cells, whereas MMP-2 and TIMP-1 was found interstitially. A significant correlation existed between the concentration MMP-9 and absolute tumor growth rate, whereas a weak correlation occurred for the relative growth rate. CONCLUSIONS: Vestibular schwannomas express MMP-2, MMP-9, and TIMP-1 and the tumor concentration of MMP-9 correlates with absolute tumor growth rate, but not with age, gender, symptom duration, or preoperative tumor size. No correlations existed between any clinical parameter and MMP-2 or TIMP-1 expression. We conclude that MMP-9 appears to be involved in the growth of vestibular schwannomas.