Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

2011 ◽  
Vol 114 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Michael E. Sughrue ◽  
Andrea H. Yeung ◽  
Martin J. Rutkowski ◽  
Steven W. Cheung ◽  
Andrew T. Parsa
Keyword(s):  
Molecular Biology ◽  
Cranial Nerve ◽  
Single Gene ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Genetic Mutations ◽  
Chromosome 22 ◽  
Novel Therapeutics ◽  
Broad Variety ◽  
Cranial Nerve Viii

Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11–13.1. In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points. A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

The molecular biology and novel treatments of vestibular schwannomas

2011 ◽  
Vol 115 (5) ◽  
pp. 906-914 ◽  
Author(s):  
Brendan Fong ◽  
Garni Barkhoudarian ◽  
Patrick Pezeshkian ◽  
Andrew T. Parsa ◽  
Quinton Gopen ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Vestibular Schwannoma ◽  
Cranial Nerve ◽  
Molecular Mechanisms ◽  
Tumor Burden ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Novel Therapies ◽  
Phase Ii Trials

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin. Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1. A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma. Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

scholarly journals Understanding the Radiobiology of Vestibular Schwannomas to Overcome Radiation Resistance

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4575
Author(s):  
Torin P. Thielhelm ◽  
Stefania Goncalves ◽  
Scott M. Welford ◽  
Eric A. Mellon ◽  
Erin R. Cohen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Current Knowledge ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Intracranial Tumors ◽  
Treatment Protocols ◽  
Cycle Arrest ◽  
Microsurgical Resection ◽  
Cranial Nerve Viii ◽  
Key Events

Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8–10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance.

Molecular biology of sporadic vestibular schwannomas including genetic and epigenetic alterations

2020 ◽  
Vol 9 (3) ◽  
pp. 23-29
Author(s):  
Maria Makuszewska ◽  
Małgorzata Litwiniuk-Kosmala ◽  
Robert Bartoszewicz ◽  
Kazimierz Niemczyk
Keyword(s):  
Molecular Biology ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Neurofibromatosis Type ◽  
Nerve Fibers ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Slow Growth Rate ◽  
Brainstem Compression ◽  
Altered Gene

Introduction: Vestibular schwannomas (VSs) are benign tumors, developing from neoplastic Schwann cells, that produce myelin sheath covering vestibular nerve fibers. The majority of these tumors are sporadic VS and very rarely they can be associated with neurofibromatosis type 2 (NF2). VSs are usually characterized with slow growth rate, however some of them appear to have a cystic structure, grow more rapidly, can cause facial nerve palsy and brainstem compression. The molecular hallmark of both sporadic and NF-2 associated VS is the inactivation of supresor gene NF-2, also called merlin gene. Aim: In this review we summarize the current knowledge on the molecular biology of VS, including genetic and epigenetic aberrations, altered gene expression and specific microRNA expression profiles.

Radiobiology of vestibular schwannomas: mechanisms of radioresistance and potential targets for therapeutic sensitization

2009 ◽  
Vol 27 (6) ◽  
pp. E2 ◽  
Author(s):  
Andrea H. Yeung ◽  
Michael E. Sughrue ◽  
Ari J. Kane ◽  
Tarik Tihan ◽  
Steven W. Cheung ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Molecular Level ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Tumor Control ◽  
Side Effect Profile ◽  
Novel Therapies ◽  
Microsurgical Resection ◽  
Selection For ◽  
Cranial Nerve Viii

Vestibular schwannomas (VS) are benign tumors arising from the Schwann cells of cranial nerve VIII. Historically the prevailing therapy for patients with VS has been microsurgical resection. More recently, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy have gained acceptance as effective alternatives. Although the side effect profile and rates of tumor control appear to be favorable for SRS, there is a subset of radioresistant tumors that continue to progress despite properly administered radiation treatment. In this review, the authors summarize what is known about the mechanism of radioresistance in VS at the clinical and molecular level. An improved understanding of the radiobiological behavior of VS may help guide appropriate patient selection for SRS and potentially aid in the design of novel therapies to treat radioresistant tumors.

scholarly journals Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Anne Balossier ◽  
Jean Régis ◽  
Nicolas Reyns ◽  
Pierre-Hugues Roche ◽  
Roy Thomas Daniel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Hearing Loss ◽  
Facial Nerve ◽  
Stereotactic Radiosurgery ◽  
Cranial Nerve ◽  
Meta Analysis ◽  
Cranial Nerves ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Tumor Control

AbstractVestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2–3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44–64). The median marginal dose prescribed at first SRS was 12 Gy (range 8–24) and at second SRS was 12 Gy (range 9.8–19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2–39%, I2 = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7–75.1%, I2 = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5–29.7%, I2 = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4–18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4–7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8–83.8%, I2 = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.

scholarly journals Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

2021 ◽  
Author(s):  
Constantin Tuleasca ◽  
Mohamed Faouzi ◽  
Philippe Maeder ◽  
Raphael Maire ◽  
Jonathan Knisely ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Effective Dose ◽  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Vestibular Schwannomas ◽  
Benign Tumors ◽  
Biologically Effective Dose ◽  
Volume Changes ◽  
Single Fraction

AbstractVestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1–73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3–9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

scholarly journals Hemorrhagic vestibular schwannoma: an unusual clinical entity

1998 ◽  
Vol 5 (3) ◽  
pp. E14 ◽  
Author(s):  
Dean Chou ◽  
Prakash Sampath ◽  
Henry Brem
Keyword(s):  
Vestibular Schwannoma ◽  
Cranial Nerve ◽  
Unusual Case ◽  
Case Reports ◽  
Clinical Entity ◽  
Vestibular Schwannomas ◽  
Presenting Symptoms ◽  
Cranial Nerve Dysfunction ◽  
Nerve Dysfunction ◽  
Management Issues

Hemorrhagic vestibular schwannomas are rare entities, with only a few case reports in the literature during the last 25 years. The authors review the literature on vestibular schwannoma hemorrhage and the presenting symptoms of this entity, which include headache, nausea, vomiting, sudden cranial nerve dysfunction, and ataxia. A very unusual case is presented of a 36-year-old man, who unlike most of the patients reported in the literature, had clinically silent vestibular schwannoma hemorrhage. The authors also discuss the management issues involved in more than 1000 vestibular schwannomas treated at their institution during a 25-year period.

Hearing Preservation After Translabyrinthine Vestibular Schwannoma Excision: Audiometry and Electrocochleography Results

2018 ◽  
Vol 127 (8) ◽  
pp. 563-567 ◽  
Author(s):  
Kenneth Akakpo ◽  
William J. Riggs ◽  
Michael S. Harris ◽  
Edward E Dodson
Keyword(s):  
Hair Cell ◽  
Vestibular Schwannoma ◽  
Cranial Nerve ◽  
Cell Activity ◽  
Internal Auditory Canal ◽  
Hearing Preservation ◽  
Healthy Patient ◽  
Cochlear Hair Cell ◽  
Translabyrinthine Approach ◽  
Cranial Nerve Viii

Objectives: To describe a case of inadvertent hearing preservation following a classical translabyrinthine resection of a vestibular schwannoma of the internal auditory canal in an otherwise healthy patient. Methods: Herein, we describe the case of an otherwise healthy patient who underwent resection of an intracanalicular vestibular schwannoma via a translabyrinthine approach. Furthermore, as part of an ongoing study aimed at characterizing hearing changes due to intraoperative events, cochlear hair cell and nerve activity were monitored using electrocochleography throughout surgery. Unexpectedly, the patient maintained serviceable hearing following surgery. As a result, we are able to provide electrophysiologic evidence of cochlear hair cell activity at various stages of this surgery. Results: Hair cell responses across tested frequencies were detectable prior to and following completion of the translabyrinthine procedure. Neural integrity of the auditory division of cranial nerve VIII was maintained throughout. Lastly, postoperative audiometric testing supported the patient’s subjective assertion of serviceable hearing in the surgical ear. Conclusion: Our results suggest that some degree of hair cell and neural integrity can be maintained throughout the course of the translabyrinthine approach, and if preservation of the auditory division of cranial nerve VIII is feasible, a functional amount of hearing preservation is attainable.

Dyslexia & the Pons

2021 ◽  
Vol 7 (1) ◽  
pp. 01-06
Author(s):  
Paul T E
Keyword(s):  
Facial Expression ◽  
Left Hemisphere ◽  
Rem Sleep ◽  
Cranial Nerve ◽  
Lateral Geniculate Body ◽  
Visual Signal ◽  
Learning Disorder ◽  
Communication Disorder ◽  
Pass Through ◽  
Cranial Nerve Viii

Introduction Dyslexia is a learning disorder. It is centered on the Pons. It affects between 5 to 17% of the population. The Pons is where the balance takes place. People with Dyslexia have trouble with balance. The Pons is also central to the sub consciousness, which is tied in with REM sleep. The sleep equation therefore applies. The Pons is involved in communication by facial expression. People with Dyslexia is a communication disorder since those with it have trouble linking visual and hearing senses. The Cranial Nerve VIII, Vestibular Nerve, responsible for hearing comes out of the Pons. The tracts for sight and hearing pass through the Lateral Geniculate Body (LGB) and the Medical Geniculate Body. (MGB) which are located on the anterior of the Thalamus. Reading and wringing, which is a problem with Dyslexia, involves both seeing and hearing. We translate visual signal to vocal words and writing. Dyslexia also have trouble with writing letters. They do letter backwards. The is an orientation problem. It may have to do with the left hemisphere which usually is responsible for language (Broca’s and Wernicke’s Areas). The Pons too is responsible for communication, especially the nonverbal facial recognition.

Lipochoristomas (Lipomatous Tumors) of the Acoustic Nerve

2003 ◽  
Vol 127 (11) ◽  
pp. 1475-1479 ◽  
Author(s):  
Sandy S. Wu ◽  
William W. M. Lo ◽  
Donald L. Tschirhart ◽  
William H. Slattery ◽  
Joseph N. Carberry ◽  
...  
Keyword(s):  
Cranial Nerve ◽  
Cerebellopontine Angle ◽  
Frozen Section ◽  
Fibrous Tissue ◽  
Clinical Manifestations ◽  
Clinicopathologic Features ◽  
Management Protocol ◽  
Acoustic Nerve ◽  
Cranial Nerve Viii ◽  
Internal Acoustic Canal

Abstract Context.—Lipochoristomas (lipomatous choristomas) are rare tumors of the acoustic nerve (cranial nerve VIII/vestibulocochlear nerve) within the internal acoustic canal and sometimes the cerebellopontine angle, and are histogenetically believed to be congenital malformations. Their clinically indolent behavior has recently prompted a more conservative management protocol in a quest for maximal nerve/hearing preservation. This approach contrasts sharply with that for the common internal acoustic canal/cerebellopontine angle tumors, the neuroepithelial neoplasms (acoustic schwannomas and meningiomas), which behave more aggressively and have more prominent clinical manifestations. Owing to their rarity, the clinicopathologic features of cranial nerve VIII lipochoristomas have been obtained mainly through case reports. Objective.—We present the clinicopathologic features of 11 cases of lipochoristomas of cranial nerve VIII. Design.—The 11 cases were documented between 1992 and 2003. We performed complete clinical reviews with histologic, histochemical, and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. Results.—The patients were 8 men and 3 women with hearing loss of the right ear (5 patients) or the left ear (6 patients). No patient had bilateral tumors. All lipochoristomas histologically possessed mature adipose tissue admixed with varied amounts of mature fibrous tissue, tortuous thick-walled vessels, smooth muscle bundles, and skeletal muscle fibers, the latter verified with immunohistochemistry. Conclusions.—The histomorphologic and immunophenotypic evidence showed that these tumors are better characterized as choristomas than as simple “lipomas,” as they have been labeled in the past. Their overall nonaggressive clinical nature in addition to the characteristic radiologic and histomorphologic findings are important clinicopathologic features for the pathologist to recognize and differentiate, especially during frozen section evaluations, in order to direct the neurosurgeon to a more appropriate conservative therapeutic intervention.

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