Neuro-Oncology
NF2-related schwannomatosis
Dec. 13, 2024
Worddefinition
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Vestibular schwannoma …
- Updated 09.19.2024
- Released 04.07.1994
- Expires For CME 09.19.2027
Vestibular schwannoma
Introduction
Overview
In this article, the author reviews the etiology, diagnosis, and management of vestibular schwannomas. Particular attention is given to treatment controversies, including the role of observation, surgery, and stereotactic radiosurgery/fractionated radiosurgery in the management of these tumors. The molecular etiology of these tumors is reviewed as new developments may lead to new medical treatment options for these tumors. Data on the role of noise exposure and the controversial role of cell phones in the development of vestibular schwannoma are reviewed.
Key points
|
• Treatment options for vestibular schwannomas are rapidly evolving as new outcome data relevant to tumor control and quality of life are reported. | |
|
• The molecular etiology of these tumors is being elucidated, both genetically and from the microenvironment standpoint, and may soon lead to novel medical treatments. | |
|
• The causative role of cell phone usage as a cause of vestibular schwannoma continues to be controversial. |
Historical note and terminology
Previously, and incorrectly, called acoustic neuromas, vestibular schwannomas (acoustic schwannoma, acoustic neurinoma) are histologically benign neoplasms of Schwann cell origin arising from the vestibular branches of the eighth cranial nerve. Tumors originate distal to the point at which the oligodendroglial cells are replaced by Schwann cells, usually within the internal auditory canal. The majority of all schwannomas (85% to 90%) arise from the vestibular branches of cranial nerve VIII. Rarely, tumors can develop from the cochlear branch.
The tumor was described pathologically by Sandifort in 1777, but it was not for over a century that the diagnosis was first made clinically. The first successful removal was performed in 1894. However, early surgical approaches to these tumors were almost always fatal. Mortality in Henschen's series from 1910 was 85% (167). Improvements in surgical and anesthetic technique dropped this figure to 4% in Cushing's hands (87). It should be noted that Cushing restricted surgery to intracapsular decompression, believing total tumor excision to be too hazardous. Walter Dandy successfully added careful dissection of the residual capsule from surrounding structures and extirpated several acoustic tumors. The use of microsurgical techniques, a variety of surgical approaches, neurophysiological electrical monitoring, and improved neuroanesthesia have shifted the focus from patient survival to preservation of cranial nerve function.
Clinical manifestations
Presentation and course
The most common symptoms of vestibular schwannomas are unilateral sensorineural hearing loss (96%), unsteadiness (77%), tinnitus (71%), headache (29%), mastoid pain or otalgia (28%), facial numbness, diplopia, and vertigo (297; 194; 427; 263; 280). Publications have classified symptoms into four stages: intracanalicular, cisternal, brainstem compressive, and hydrocephalic (452). In the intracanalicular stage, the symptoms are hearing loss, tinnitus, and vertigo. In most patients the initial symptom is unilateral sensorineural hearing loss, which may have been present from 1 to 5 years (mean 3.7 years) (428; 280). The loss is gradually progressive in 80% to 90% of cases and sudden in 10% to 20% of cases (possibly caused by occlusion of the internal auditory artery). Sensorineural hearing loss develops from a combination of tumor-induced interference with cochlear vascular supply and compression of the cochlear nerve within the internal auditory canal. Mild unsteadiness is usually not the initial complaint but has been present for several years in most patients. Tinnitus is usually unilateral, confined to the affected ear, low grade in intensity, and constant. Tinnitus at presentation has been reported to increase the likelihood of subsequent tumor growth by 3-fold (05).
In the cisternal stage, auditory symptoms progress and headaches often occur (452). Headache, mastoid pain, and otalgia are often present in patients with larger tumors that impinge on local dural and osseous structures or have caused elevated intracranial pressure. Facial numbness is usually confined to the lower face; facial weakness is uncommon. Symptomatic paroxysmal vertigo is infrequent and is usually not accompanied by nausea.
In the brainstem compressive stage, adjacent cranial nerves may be affected, often with trigeminal symptoms or lower cranial nerve involvement with hoarseness, dysphagia, and dysarthria, and disequilibrium may worsen (452). In the hydrocephalic stage, rapid clinical deterioration can be accompanied by headache, diplopia, lower cranial nerve dysfunction, and long tract signs.
On neurologic examination of patients with vestibular schwannoma, the most common finding is unilateral sensorineural hearing loss, with loss of high frequency hearing and speech discrimination predominating (210; 297; 194; 427; 428; 263; 281). The loss of speech discrimination often exceeds the degree of pure tone loss. Approximately 90% to 95% of patients have abnormalities of hearing. Occasionally, sudden deafness or acute unsteadiness may result from occlusion of the internal auditory artery (508; 299). In 50% of patients at presentation, hearing loss is the only neurologic sign. Although the symptom of unsteadiness is common, most patients have normal or mildly affected gait and station. In many of these patients, unsteadiness is related to dizziness and other signs of vestibular dysfunction (281). Large tumors may cause frank ataxia or dysmetria from brainstem or cerebellar compression, but these signs are infrequent. In 7% to 15% of patients, particularly those with tumors larger than 4 cm in diameter, papilledema is present (297; 263). Horizontal nystagmus is often noted in patients with tumors greater than 2 cm in diameter (297; 263). Trigeminal dysfunction, typically in the form of a diminished corneal reflex or partial facial hypesthesia, is noted in more than half the patients; hemifacial anesthesia is rare (427). Diminished corneal sensation is present in 30% of medium- and 60% of large-sized vestibular tumors. The seventh nerve is resistant to stretch injury and is involved in less than 10% of cases (428). Paresis of the lower cranial nerves (IX, X, XI, XII) is uncommon and appears as a late sign in large tumors that grow in a medial and inferior direction toward the jugular foramen. Long tract signs (eg, hemiparesis, spasticity, hyperactive reflexes) from severe brainstem compression are rare in modern series (427).
In patients with bilateral tumors or a family history of nervous system tumors, a diagnosis of neurofibromatosis type 2 should be considered. In addition to bilateral vestibular schwannomas, neurofibromatosis type 2 is associated with cataracts, skin nodules and cafe au lait spots, peripheral nerve schwannomas, seizures, and other central nervous system tumors such as meningiomas and gliomas (315).
Prognosis and complications
In general, these tumors are slow-growing, benign neoplasms that have an indolent evolution. In 75% to 80% of cases, the growth rate is estimated to be 1 to 2 mm per year (489; 467; 35; 317). The rate of growth may be slower in older patients. Tumor growth is rarely predictable. Charabi and colleagues followed 127 tumors with serial neuroimaging studies over several years (70). They noted some growth in over 80% of tumors, although growth patterns were varied and changing for individual tumors. Clinical deterioration is to be expected in vestibular schwannomas that are symptomatic and growing.
Clinical vignette
A 44-year-old man with an unremarkable past medical history developed episodes of dizziness, tinnitus, and mild left-sided hearing loss. The symptoms presented over several months and were slowly progressive. The initial evaluation by his physician was unremarkable with a normal neurologic examination. No stigmata of neurofibromatosis type 1 or type 2 were present. Audiometry revealed a mild degree of hearing loss on the left side. MRI demonstrated an enhancing mass 1.3 cm in diameter in the left cerebellopontine angle, with a tail that entered the internal auditory canal, but did not reach the fundus. The tumor was diagnosed as a vestibular schwannoma, and the patient elected surgery over observation or radiosurgery. Due to the presence of serviceable hearing, a suboccipital approach was used to expose the tumor. The cochlear division of cranial nerve VIII was draped over the mass but not adherent to it and a clean cleavage plane was found between the tumor capsule and the cochlear and facial nerves. The mass arose from and was attached to the inferior vestibular division of VIII. After the mass was dissected away from the cochlear division, the inferior vestibular nerve was divided and the tumor was removed piecemeal, with preservation of cranial nerve VII. After surgery the patient did well, with some preservation of left-sided hearing and only mild left facial weakness. The facial weakness improved to normal after several months. Recurrent tumor was not seen on follow-up MRI.
Biological basis
Etiology and pathogenesis
Concern has risen in recent years about the potential role of microwave radiation from cellular telephones in the genesis of brain tumors, including vestibular schwannomas. At least 40 epidemiological studies have been published (236; 235; 157; 153; 186; 383). Some studies have implicated long-term cellular phone use with an increased risk of vestibular schwannomas or other cranial tumors (308; 74; 236; 256; 422; 157; 153; 154), especially with long latency and onset of use before the age of 20 (153; 62). Kundi reviewed 33 published studies and concluded that, although methodological flaws were found in every study, the weight of the evidence favored an increased risk for ipsilateral vestibular schwannomas with increasing duration of cellular phone usage, but the magnitude of that risk could not be assessed (236; 235). A similar conclusion was reached in a meta-analysis by Hardell in 2008 for ipsilateral glioma and vestibular schwannomas (156). Studies in rats and mice suggest a carcinogenic effect of whole body exposure to radiofrequency radiation (155). Cell cultures of human Schwann cells exposed to electromagnetic fields showed alterations in proliferation, intracellular signaling, metabolic pathways, and in the expression of genes related to hearing loss (79). In 2013 and 2019, Hardell and Carlberg concluded that emissions from wireless phones should be regarded as group 1 carcinogens (154; 155; 295).
Some are skeptical of this interpretation, citing the fact that cell phone emissions are not energetic enough to break molecular bonds within cells, a necessary step toward oncogenesis (294). For example, cell phone emissions were noted to be 240,000 times weaker than the green light photons that activate the rhodopsin molecules in the retina (294). Additionally, some epidemiologic evidence does not appear to implicate cellular telephone use in the etiology of vestibular schwannomas (300) or other brain tumors (06; 186; 424; 376; 238; 343; 93). A meta-analysis published in 2014 did not support the conclusion that mobile phones affect the occurrence of intracranial tumors but noted that limited data are available beyond 15 years of exposure (238). A meta-analysis of 88 studies in which human cells were exposed to radiofrequency fields and analyzed for genetic damage in the form of single or double strand breaks, chromosomal aberrations, micronuclei, and sister chromatid exchange did not find any support for a genotoxicity-based mechanism (484). The fact that tumor incidence rises in the elderly and not in younger patients with the heaviest cell phone usage does not support an etiological link (93; 383).
At least two studies have implicated loud noise exposure in the genesis of vestibular schwannoma (113; 57), but others have shown no increased risk (114; 386; 02) or an indeterminate risk (91). Childhood radiation to the head and neck has also been linked to increased risk of vestibular schwannoma (417). Inactivating mutations in the NF2 gene were found more commonly in the tumor specimens of smokers than in never smokers (243). At this time there is no definitive evidence for a genetic/molecular signature suggestive of radiation-related vestibular schwannoma.
An inherited but nonsyndromic contribution to sporadic vestibular schwannoma has been suggested by genealogic studies in veterans and residents of Utah (141).
Pathologic features. The tumors are variegated in color, with areas of gray, red, and yellow corresponding to areas of dense cellularity, increased vascularity, and xanthomatous degeneration (486). Histologically, the tumors are formed of interweaving bundles of spindle-shaped cells with cigar-shaped nuclei.
Distinct areas designated as Antoni A and B are seen. Antoni A areas are densely cellular and interwoven, whereas Antoni B areas are less cellular, less structured, and often contain areas of microcyst formation and hemorrhage. Occasional cells with large pleomorphic nuclei are common but are not indicative of anaplasia, which is rare or nonexistent in these tumors (486; 306). Reticulin stains or electron microscopy reveal a distinct basement membrane external to the plasma membrane, which distinguishes vestibular schwannoma from meningiomas with a similar appearance. Although the tumor surface is covered with connective tissue, this "capsule" is often no thicker than 3 to 5 µm in most areas (237). A nodular architecture has been reported to occur in 40% of NF2-associated tumors but is rare in sporadic cases (128). Bi and Santagata reviewed the neuropathologic features of schwannomas (42).
The distal location of the glia to Schwann cell transition in the vestibular nerves distinguishes them from other cranial nerves and has been thought to predispose them to neoplastic transformation (486). This theory has been questioned, and the incidence of vestibular tumors remains unexplained (462; 505). Because the Schwann cell-glial junction is variable, the tumor location may vary and can range from a lateral position near the inner ear, to a medial position at the porus acusticus, to entirely within the cerebellopontine angle (297; 263). Schwannomas can develop from either the superior or inferior division of the vestibular nerve, with an approximately equal incidence (194).
Molecular genetics. Specific loss of genetic material on chromosome 22 was a feature of 44% of informative cases of sporadic vestibular tumors when analyzed by the RFLP approach (426). This loss has been attributed to partial deletion or mitotic recombination (205). Further work with schwannomas from multiple locations narrowed the region of interest to an area between the CRYB2A and the MB loci (43), but cloning of the candidate gene came from analysis of neurofibromatosis type 2 cases.
Neurofibromatosis type 2 is an autosomal dominant disorder that occurs in 1 in 25,000 to 100,000 births (315; 22; 103; 515). The hallmark of this disease is bilateral vestibular tumors, and individuals with the neurofibromatosis type 2 gene are greater than 95% likely to develop these lesions (471). In addition to eighth nerve tumors, multiple spinal and intracranial schwannomas, meningiomas, and ependymomas are common in this disease. The molecular genetics of neurofibromatosis type 2 were advanced significantly because cytogenetic analysis of meningiomas had already suggested that chromosome 22 was frequently abnormal (426; 110; 330). Analysis of a large family carrying this disorder using linkage analysis with special attention to chromosome 22 showed the responsible gene to be located on chromosome 22q12 and linked to the marker D22S1 (387). By using deletion mapping (389) and a patient with a constitutional breakpoint, the neurofibromatosis type 2 gene was mapped between markers D22S1 and LIF. Using positional cloning, a candidate gene was identified in 1993 and called merlin/schwannomin (17; 388; 471). Nonoverlapping deletions affecting this gene were detected in two independent families, suggesting that merlin/schwannomin is the neurofibromatosis type 2 gene product. Half of patients inherit a germ-line mutation and half acquire a new mutation (22; 103). Mosaicism is seen in a third to as high as 60% of patients (118; 120). The gene contains 17 coding exons spanning approximately 95 kilobases and encodes a protein of 595 residues, which is widely expressed and which has high homology to a family of proteins linking cytoskeletal components to the cell membrane, the band 4.1 superfamily, containing proteins such as ezrin, radixin, and moesin (37; 128). Transfection of abnormal proteins into mammalian cells has been shown to alter their adhesion to the substrate (448).
The occurrence of vestibular schwannomas and meningiomas in association with the loss of function of a gene suggests that the neurofibromatosis type 2 gene is a tumor suppressor gene involved with the growth control of cells of neural crest origin (276; 389). The protein is thought to exist in both an unfolded and a folded form, with the latter mediating the tumor suppressor activity (285). Missense mutations may disrupt the folded state (329). The protein PAK phosphorylates merlin at S518, disrupting the maintenance of the folded state and tumor suppressor function (221; 328).
Early transfection experiments suggest an anti-ras function for the protein (468; 37). The NF2 gene product inhibits directly the kinase PAK1, which is essential for ras transformation, and may be a target for therapy in NF2 (169). Merlin tumor suppressor ability is also thought to relate to inhibition of the Rac pathway (128). Inhibition of PAK might allow merlin to continue to inhibit the Rac pathway. Merlin has been shown to be a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1) with elevated mTORC1 signaling in NF2 tumors (135). Merlin has a FERM (four point one/ezrin/radixin/moesin) domain and is involved in the regulation of cell proliferation in response to adhesive signaling, activates anti-mitogenic signaling at intercellular tight junctions, and inhibits oncogene expression (103). Multiple publications provide an extensive discussion of knowledge of merlin molecular biology (128; 95; 84).
Merlin-deficient cells also have a larger non-inactivating outward potassium ion current than control cells, and blockage of this current with quinidine can reduce cellular proliferation (475). The role of the gene product in embryonic development, cellular adherence, and Schwann cell-axon interactions are slowly being elucidated (491). Valproic acid has the ability to induce neuronal differentiation, possibly through the upregulation of merlin and its interaction with the focal adhesion protein, paxillin (506). Aberrant EGFR activity has been detected in human vestibular schwannomas (12) and in the livers of mice, from which the merlin gene has been deleted (38).
It is possible that multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the altered gene activity (68). The lack of mutations in the neurofibromatosis-2 gene in some patients with clinical disease has been attributed to mosaicism, found in 24.8% of cases in one study, 30% to 33% of new mutations in another study, and as high as 59.7% with next-generation sequencing (222; 305; 118; 120). Genotype-phenotype correlation has also been noted, with constitutional missense mutations, splice-site mutations, large deletions, and somatic mosaicism associated with fewer tumors than constitutional nonsense or frameshift mutations (334; 122; 29; 118; 430; 146; 103). Additional mutations outside the NF-2 locus may herald more aggressive tumor behavior (59). Specific genetic and epigenetic changes in NF-2 may be related to the risk of hearing loss and other clinical manifestations of the disease (103).
The observation by Rouleau and colleagues of somatic mutations in the neurofibromatosis type 2 gene in sporadic schwannomas made it likely that the merlin/schwannomin gene would be involved in the pathogenesis of vestibular schwannomas not associated with neurofibromatosis type 2 as well (388). The presence of a variety of mutations in the merlin/schwannomin gene in sporadic schwannomas from multiple sites has been confirmed by other investigators (44; 190; 59). However, no merlin/schwannomin mutations were found in six families with unilateral vestibular schwannomas (45). Hypermethylation of the gene has not been demonstrated to be a means of silencing of merlin/schwannomin function (233; 246; 103).
The role of micro RNAs (miRNAs) in schwannoma development is also being investigated (117; 248). Alterations in various miRNAs have been correlated with radiographic tumor growth rate (412).
For completeness, the schwannomatosis genes have also been traced to chromosome 22, located proximally to the neurofibromatosis type 2 gene, and they appear to involve the INI1/SMARCB1 and/or LZTR1 genes (502; 56). Vestibular schwannoma can be seen in schwannomatosis, and in the presence of (140) or in the absence of a detected LZTR1 mutation (289). Schwannomatosis should be considered when a unilateral vestibular schwannoma is found in conjunction with other neural tumors or in very young patients (140; 442; 396). Several syndromes are now recognized, including SMARCB1-related (SWNTS1), LZTR1-related (SWNTS2), and SMARCB1/LZTR1-negative schwannomatosis (56). Whole gene deletion of LZTR1 does not appear to predispose to schwannomatosis, and only one patient in 110 with an apparently sporadic schwannoma had a constitutional whole gene deletion of LZTR1 (121). In contrast to patients harboring rhabdoid tumors, thought to be due to complete loss of SMARCB1 function, schwannomatosis may be due to hypofunctioning protein(s) in combination with a second hit at the NF2 gene site (208; 442). In a British population, the birth incidence of schwannomatosis was 1 out of 27,956 versus NF-2 in 1 out of 68,956, making it more common than NF-2 (119).
Oncogenes, growth factors, and other biochemical observations.
Genetic events underlying Schwann cell transformation have been reviewed in 2021 (482). NF1 or NF2 loss are necessary but not sufficient for transformation; other genetic changes are also required. These include progressive loss of Sox10, S100, and GFAP positivity and other noncell autonomous contributions.
A preliminary report of detection of the neu oncogene in nearly all 3T3 cells transformed by DNA from a group of rodent schwannomas induced by transplacental N-nitrosoethylurea has appeared (378). The neu oncogene is a transmembrane receptor protein with tyrosine kinase activity like the epidermal growth factor receptor. Almost all of the transformants contained a neu gene with an activating point mutation, which was not present in any glial tumors tested. The same finding was present in several rodent species. Neu mutation may, therefore, represent a major pathway for transformation of nerve sheath tissue.
Transforming growth factor beta-1 has been shown to stimulate DNA synthesis in cultured human vestibular schwannoma cells, and these same cells express transforming growth factor beta-1 mRNA (490). This suggests that transforming growth factor beta-1 may participate in an autocrine loop in vivo. Basic fibroblast growth factor had no effect in the same model.
Schwann cells from neurofibromatosis type 2 patients have been shown to have larger outward potassium currents than those from control subjects (384). Inhibitors of potassium currents, such as quinidine, have been shown to slow the growth of neurofibromatosis type 2 Schwann cells in culture, but not the growth of normal Schwann cells (384).
CDK2, part of the retinoblastoma protein cyclin-dependent kinase pathway, has been shown to be underexpressed in seven or eight vestibular schwannomas examined (242).
Altered structure, increased expression, and an increase in the phosphorylated form of the Rb1 (retinoblastoma) gene have been demonstrated in human vestibular schwannoma tissue (466). This altered pattern of expression suggests an antiapoptotic function in these tumors.
The concentration of vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, have been found to correlate with tumor growth rate, indicating a possible role for this molecule in the growth of vestibular schwannoma (65; 232). Another study of 182 sporadic tumors found expression of both VEGF and its receptors in 100% of tumors, and a correlation with expression and recurrence (232). VEGF was expressed in 100% of 22 sporadic tumors and 21 associated with NF2 (351). In addition, neuregulin-1, a glial growth factor, and its receptor, ErbB2, have been found in vestibular schwannoma cells and may constitute an autocrine pathway driving the growth of tumor cells (151). Upregulation of the related hepatocyte growth factor and its receptor cMET is also found in tumor samples with upregulated VEGF-A signaling (100). Simultaneous inhibition of c-Met and Src suppresses the growth of schwannoma cells and can induce apoptosis (131).
Intratumoral macrophages have been of interest in many tumor types, including vestibular schwannomas (94). M2 macrophages positive for CD163, which have been associated with angiogenesis, tumor growth, and interference with antitumor immune responses, have been reported to be significantly higher in vestibular schwannomas growing rapidly on MRI prior to surgery (94). Increased levels of M1, CD 163+ tumor-associated macrophages have also been reported in tumors progressing after subtotal resection in association with PD-L1 expression, which might be a potential treatment target (341). The entire inflammatory microenvironment in vestibular schwannoma is now an area of intense interest (148). The presence of an elevated C-reactive protein level prior to surgery has also been linked to shortened progression-free survival (487).
Human primary schwannoma cell cultures show enhanced basal Raf/mitogen-activated protein/ERK kinase/ERK1/2 pathway activity when compared with healthy Schwann cells (13). Due to overexpression and activation of PDGF receptor beta, ERK1/2 and AKT activation is also detected in schwannoma, leading to proliferative increases. Specific inhibitors for these pathways may lead to new treatment options (13).
Microarray analysis of tumors examining 23,055 genes detected 1650 differentially expressed genes when compared to tibial nerve (01). The ERK pathway was involved in many of the differentially expressed genes. Downregulation of the CAV1 gene was notable as this gene is normally expressed in Schwann cells. Another gene expression profile of 49 schwannomas and seven control vestibular nerves identified over 4000 differentially expressed genes (04). No subtypes of tumors were identified and no differences between sporadic and NF2-associated tumors were detected. The P13K/AKT/mTOR pathway overexpression was frequently seen. Fourteen pathways were found to be associated with faster growing tumors when global gene expression was examined in 16 human tumors for which preoperative growth rates were determined (411). Gene expression profiles may differ in solid and cystic vestibular schwannomas (507) and in cyst and previously irradiated tumors, which may have an increased mutation burden compared to sporadic tumors (03).
COX-2 expression was detected in 29 of 30 vestibular schwannomas from both sporadic and NF2-associated cases, and the expression of COX-2 was found to correlate with the Ki-67 index of proliferative activity (172). However, clinical studies found no correlation between aspirin or other NSAID use and tumor growth or growth rate on serial MRIs (181; 36).
The phosphatidylinositol 3-kinase/AKT pathway has been found to activated in vestibular schwannomas, promoting cell proliferation and survival. This has led to testing of a compound called AR42, a novel histone deacetylase inhibitor, to inactivate AKT. AR42 was shown to suppress the growth of both murine schwannoma allografts and murine human vestibular schwannoma xenografts with no detectable toxicity (195).
The merlin/schwannomin gene has been shown to regulate angiogenesis through a Rac1/semaphoring 3F dependent pathway (501). Reintroduction of semaphoring 3F was therapeutic in nude mice bearing merlin-deficient tumors.
Aberrations of the p14ARF/MDM2/p53 pathway have been found in a high percentage of 58 sporadic vestibular schwannomas (72).
In a gene wide association analysis, dysregulation of gene products arising within the INK4 locus on 9p21.3 are thought to be involved in vestibular schwannoma tumorigenesis (395).
Tumor microenvironment is now thought to be an important part of the cellular and noncellular component interacting to affect tumorigenesis, drug response, and treatment outcomes (66).
Epidemiology
Schwannomas account for 6% to 8% of all primary brain tumors, with the majority occurring in adulthood (318). Over 85% to 90% of intracranial schwannomas affect the vestibular portion of cranial nerve VIII in the cerebellopontine angle (297; 194; 263). The great majority of schwannomas are sporadic and unrelated to either neurofibromatosis type 1, neurofibromatosis type 2, or to a third entity, schwannomatosis (375; 502).
Vestibular schwannomas are most common in the fifth and sixth decades of life and occur with a slight female preponderance (486). In the era of magnetic resonance imaging, vestibular schwannomas have been estimated to afflict 19.3 persons per million per year, with 2000 to 3000 new tumors per year in the United States (315; 83; 446; 499). A steadily rising incidence in Denmark from 1976 to 2001 has been attributed to better detection rather than to an increase in the actual number of tumors (446). An international systematic review concluded that the incidence was more likely to be 5 per 100,000 in all age groups and 20 per 100,000 in higher risk older patients, with a lifetime prevalence of 1 per 500 persons (269). Approximately 95% of tumors are unilateral, whereas 5% are bilateral and are associated with neurofibromatosis type 2. Asymptomatic tumors have been found at autopsy in 0.8% to 2.7% of cases (83).
Pediatric tumors are rare but have been described (266). In a meta-analysis of 96 cases, the average age at presentation was 12.1 years and tumors were more likely to recur than in older patients (266).
Prevention
Although not currently available, further understanding of the molecular genetics of schwannoma pathogenesis could conceivably lead to both specific therapy for existing tumors and preventative strategies for patients with neurofibromatosis type 2.
Differential diagnosis
Vestibular schwannomas make up 80% to 90% of the masses found in the cerebellopontine angle (239; 441; 287). The differential diagnosis of a mass in the cerebellopontine angle includes meningioma, epidermoid cyst, arachnoid cyst, exophytic glioma, cerebellar hemangioblastoma, metastasis, choroid plexus papillomas, glomus tumor, and primary bone tumors. Meningioma is the second most common cerebellopontine angle tumor (10% to 15% of cerebellopontine angle lesions). Distinguishing clinical features of meningiomas include their propensity to cause facial nerve dysfunction or trigeminal neuralgia rather than isolated hearing loss. Radiologically, meningiomas often lack extension into and expansion of the internal auditory canal, have a sessile base, cause underlying hyperostosis of the petrous bone, tend to be more homogeneously enhancing, have a "dural tail," and sometimes allow visualization of the seventh and eighth nerve complex, even in large tumors (307).
The third most common mass of the cerebellopontine angle is the epidermoid inclusion cyst, making up 5% to 9% of all lesions (239; 441). Patients often have a long history of hearing loss and tinnitus. On CT, epidermoid cysts are usually hypodense compared to brain (similar to water or CSF). Calcification of the cyst rim is noted in 25% of cases. Enhancement is negligible within the cyst but may occur along the rim. On MRI, epidermoid cysts are usually isointense to CSF (ie, low signal intensity on T1 images and high signal intensity on T2 images) and may have a lamellated appearance. Similar to CT, the cyst does not enhance with gadolinium, except for the rim.
Arachnoid cysts can also occur in the cerebellopontine angle. They have signal intensity and attenuation characteristics identical to CSF and do not enhance with contrast. Many other lesions can arise in the cerebellopontine angle, each of which accounts for less than 1% of all cases. Tumors that may extend into, but not arise from, the cerebellopontine angle include exophytic brainstem gliomas, ependymomas, choroid plexus papillomas, schwannomas of cranial nerves V, VII, IX, X, and XI, jugular foramen paragangliomas, lipomas, and metastases (239; 441). Facial nerve schwannoma can be difficult to distinguish from vestibular schwannoma on imaging (262). Vascular processes such as aneurysm, malformations, and aberrant loops of normal blood vessels can develop in the cerebellopontine angle. Enhancement on CT and a flow void on MRI are diagnostic of a vascular process. Rarely, infectious processes can develop in the cerebellopontine angle, such as tuberculomas and cysticercosis. Benign vestibular conditions (eg, Meniere disease) can suggest vestibular schwannoma with symptoms and signs of hearing loss, tinnitus, nystagmus, and vertigo (265). However, tumor can be ruled out by a careful history (ie, fluctuating symptoms that occur in attacks, bilateral involvement in approximately 20%) and a normal enhanced MRI scan.
Diagnostic workup
Delays in the diagnosis of vestibular schwannoma are reported to be common (479), but the progressive decrease in the size of detected tumors indicates that the diagnosis is being made earlier with MRI and other modalities (452). Cost considerations in evaluating patients who may potentially harbor a vestibular schwannoma (asymmetric hearing loss, tinnitus, vertigo) are an important consideration (225). After appropriate history and physical examination, the evaluation of a patient suspected of harboring a vestibular schwannoma usually begins with audiometry. A standard audiogram should be performed, including speech reception thresholds and speech discrimination testing. Very specific audiometric protocols might improve the early detection of vestibular schwannoma and obviate some MRI scans (485). Brainstem auditory evoked responses and assessment of the acoustic reflex threshold and decay are of additional value in diagnosis (210; 315). Brainstem auditory evoked response has a 94% to 96% detection rate, an 8% false-positive rate, and a 4% false-negative rate (429; 315), and it has been shown to be sensitive to even small tumors (106), but other studies have called these data into question (55; 311; 391; 332). The false negative rate in intracanalicular tumors may be as high as 17% (498; 332). A technique called stacked derived band auditory brainstem response has been reported to be more sensitive to smaller tumors than conventional auditory brainstem response (105; 452). The cost savings of obtaining auditory brain responses prior to MRI does not outweigh the number of potentially missed vestibular schwannomas or other clinically important pathologies that would be discovered with MRI alone (496). One study reports the actual costs of diagnostic tests (225).
The typical audiometry profile in a patient with a vestibular schwannoma is unilateral sensorineural hearing loss with speech discrimination impairment worse than pure tone loss, normal tympanometry and compliance, an absent acoustic reflex (the contraction of the stapedius muscle in response to a high-intensity sound) or reflex decay, and delayed conduction on brainstem auditory evoked response (210; 452). Auditory brainstem response (ABR) testing is non-invasive, painless, and not affected by patient cooperation, but can be unreliable when hearing is poor (452). The sensitivity of ABR has been reported to be between 63% and 95%, with lower sensitivity for tumors less than 1 cm in diameter. Stacked ABR may improve detection of smaller tumors. In a large study, over 10% of tumors were missed on audiologic screening; these atypical tumors were larger and presumably less likely to be successfully treated (298).
CT scan shows an isodense, enhancing mass, originating at the internal auditory meatus and occupying the cerebellopontine angle. Bone window settings on CT often show internal auditory canal erosion, even by small tumors.
MRI is the definitive diagnostic test, especially for small, intracanalicular tumors (85). However, due to its expense, the recommendation in the past has been that MRI should be reserved for patients whose history, examination, and audiometry are suggestive of a tumor; MRI should not be recommended as a screening tool according to multiple authors (210; 315; 125). However, some authors report that a limited MRI examination may be more cost effective in some patients, and careful clinical decision analysis has shown that the most cost-effective diagnostic pathway is dependent on the value assigned to a missed diagnosis (27; 397; 63; 498; 452; 459). Reviews of the auditory brainstem response versus MRI debate concluded that a limited enhanced or non-enhanced MRI may be the most cost-effective screen (498; 452). No comparison has yet appeared between limited MRI and stacked derived band auditory brainstem response for sensitivity, specificity, and cost effectiveness. In a systematic review from 2018, MRI was recommended for patients with unilateral hearing loss greater than or equal to 10 dB at two frequencies or greater than or equal to 15 dB at one frequency, especially at 3000 Hz (459). MRI was recommended for unilateral tinnitus, but the yield was expected to be less than 1%, but for sudden unilateral hearing loss the yield was expected to be greater than 3%.
When imaged by MRI, about two thirds of tumors are hypointense when compared to brain on T1-weighted images; about one third are isointense (307). Tumors are characteristically hyperintense compared to brain on T2-weighted sequences. About two thirds of tumors enhance homogeneously with contrast; about one third enhance inhomogeneously.
Intratumoral areas of cystic degeneration and peritumoral arachnoid cysts are common. A “dural tail” is seen in less than 10% of tumors but might be indicative of tumor adherence and more difficulty separating the tumor from the facial nerve at surgery (338). The technique of Eigen image filtering has been reported to give more accurate volume determinations and, thereby, growth rate estimates for vestibular schwannomas and may be a promising clinical research tool (302).
Diffusion imaging tractography may improve the visualization of the distorted cranial nerves in the region of the tumor (71; 503), especially with larger tumors (390), but even when combined with FIESTA imaging, the overall rate of detection of the facial and cochlear nerves was low (513). Multishell diffusion tractography may improve facial nerve detection preoperatively (64).
When gadolinium enhancement cannot be used or cost saving is important, heavily T2-weighted fast spin echo imaging or 3-dimensional Fourier transform-constructive interference in steady state (3DFT-CISS) imaging can provide high-resolution imaging of the cerebellopontine angle sufficient to detect most vestibular schwannomas (452). Gadolinium may be also be unnecessary for routine surveillance imaging (347).
Protein profiling of cerebrospinal fluid may show some promise in presurgical confirmation of vestibular schwannoma (177). This is not yet part of routine care, however.
Management
Treatment options include observation, subtotal resection, total resection, radiation, and potentially, chemotherapy. Although total excision has been considered the treatment of choice (315), this issue has been debated (83; 199; 227; 92; 207). Considerable controversy still exists about the roles of surgery and radiosurgery (207; 352; 28, 78; 309; 500). Treatment algorithms have been published based on patient age, hearing status, tumor size, and symptoms (437) as well as cost of care (28) and patient satisfaction (310). Some of these studies report better outcomes for radiosurgery than surgery (309; 493; 500), but others have reported no differences with observation, surgery, or radiosurgery (101; 380).
Observation. With the increasing rate of discovery of small or asymptomatic tumors, observation has been advocated, especially in older patients or patients with bilateral tumors and useful hearing. Indeed, there has been some concern that the general approach to these tumors has been too aggressive, although debate is ongoing (83; 370; 244; 273). The growth rate of vestibular tumors is highly variable, and regression or stabilization after a period of growth is possible (435; 33; 176; 180; 421; 272; 270). In a number of series, approximately half of tumors observed with serial imaging did not grow at all, and the growth rate of those that did enlarge averaged less than 2 mm per year (35; 83; 385; 449; 495; 435; 472; 488; 512; 33; 145; 23; 180; 272). In several studies, the growth rate in the first year of follow-up was predictive of subsequent growth (35; 472). A 2005 meta-analysis of 1345 patients reported that 57% of tumors were stable or regressed over an average of 3.2 years, and a growth rate average of 1.9 mm/year in those that did enlarge (443). A similar literature analysis showed that for 1340 reported cases followed for a mean of 38 months: 46% enlarged, 8% regressed, and 18% required treatment (512). Another single-center series reported the need for intervention in 23.7% of patients initially treated conservatively (23). In a large series of 564 patients observed for an average of 23 months, 40.8% demonstrated growth and 32.1% underwent intervention (180). Larger tumors and those presenting with disequilibrium were more likely to enlarge. In a series of 178 patients managed with observation, the mean growth rate was 0.66 mm per year or 0.19 cubic cm per year, and the volume doubling time was 4.40 years (481). Two thousand three hundred and twelve patients in Denmark were treated initially with observation, of whom 434 (19%) had converted to active treatment at a mean of 7.33 years (377). Using receiver operating characteristic curve analysis, the volume doubling time was found to be the most realistic growth model, with a cutoff of 5.22 years distinguishing growing from nongrowing tumors. In 243 patients initially selected for observation, local control was still present at 10 years in 58% (393). Initial conservative management does not appear to jeopardize results of future treatment (145; 275) and offers better cranial nerve preservation rates than primarily surgically treated tumors (275), but one report suggested better facial nerve outcomes with earlier surgery (361). Serial volumetric analysis has been reported to be more sensitive than linear tumor measurements in detecting significant changes in tumor size (160; 247; 421). In a series of 212 patients followed volumetrically, a volumetric growth rate of 33.5% per year was observed (421). A lobulated appearance has been associated with a more aggressive course (184) as has a cystic appearance (111). Tumor growth rate has not been associated with any specific genetic abnormality (188). Tolerating some early growth without intervention has been advocated by some (272; 273).
Of 466 patients treated with initial observation and hearing, serviceable hearing was maintained in 94% at 1 year, 66% at 5 years, and 44% at 10 years (179). Tumors more than 5 mm in size are associated with progressive hearing loss even without growth, whereas nongrowing tumors less than 5 mm were not associated with ongoing hearing loss (260). In another systematic review of 3652 observation patients from 26 studies, a conservative benchmark was suggested that serviceable hearing would be retained in 75% at 3 years, 60% at 5 years, and 42% at 10 years (213). It has been noted that hearing may decline even without obvious tumor growth and that tumors less than 5 mm can maintain good hearing over long periods (212).
Determining how much growth and/or at what rate of growth intervention should be offered has not been established. One study suggests that the probability of less optimal surgical outcomes begins to significantly increase when the extra-meatal size of the tumor reaches 14 to 20 mm and that this threshold should trigger intervention rather than a criterion like more than 2 mm of growth in a year, as suggested by others (264). Cochlear implant is an option for patients with poor hearing and tumors under observation without treatment (255).
Guidelines from the Congress of Neurological Surgeons in 2018 suggested MRIs be obtained yearly for 5 years, then less frequently if stability has been confirmed (111). More frequent imaging was recommended in patients with NF-2. However, no definite monitoring interval could be recommended by another study (423). There is interest in using noncontrast MRI monitoring to avoid repeated exposure to enhancing agents and for cost saving (86; 219).
Sporadic vestibular schwannomas have been retrospectively observed to grow less in aspirin users than in those who did not use aspirin (204) but other studies could not confirm this (181; 36).
Prediction of tumor growth rate in neurofibromatosis type 2 patients does not seem possible based on tumor behavior in other affected family members, but tumors do seem to grow faster in younger patients (30; 282; 344). In a report of NF2-associated tumors, 29.6% exhibited linear growth, 11.2% exponential growth, and 59.2% saltatory growth (104). Therefore, caution is needed in analyzing short-term growth patterns in these patients. Another report noted that mean tumor growth rate in 92 tumors in 46 NF2 patients was 1.8 mm/year and the surgery free rate was 88% at 5 years (344). The United Kingdom NF2 Genetic Severity Score may be useful in predicting aspects of clinical severity, with constitutional truncating NF2 mutation associated with severe disease, whereas missense or mosaic mutations present with a milder phenotype (146). Serial hearing testing in NF2-related tumors treated with observation showed that pure tone thresholds increased by 1.3 to 2 decibels per year and that patients maintained serviceable hearing for an average of 7.6 years (229). Hearing loss did not correlate with tumor growth. These authors concluded that conservative management was an attractive option for these patients (229).
A Markov decision analysis looking at the quality-adjusted life years derived from various treatment strategies concluded that a period of observation offered the best strategy for patients with tumors less than 1.5 cm in size (303). Alternatively, another meta-analysis of quality of life 5 years after treatment reported that radiosurgery had an advantage over surgery, which was, in turn, better than observation (493). One observation of worsening tinnitus in observed patients has been reported (478). Some have argued that vestibular schwannomas are currently overtreated in the United States (244).
The lack of growth in some patients makes it reasonable to follow some tumors with serial imaging when the clinical situation is appropriate. The slow growth may also support the use of subtotal resection due to the lower morbidity of this approach (257; 385). In addition, these data mandate caution in interpreting the results of therapy, as the lack of growth of some tumors may be falsely attributed to treatment, and spontaneous regression has been reported (211; 372; 33; 176; 90). Among 512 observed patients, 13% had at least one sign of tumor regression, and 6% had confirmed tumor shrinkage over mean follow up of 4 years (90). Alternatively, the view has been expressed that elderly patients tolerate surgery well and that surgical removal is the treatment of choice for patients in good health regardless of age (369; 365; 476; 261), although an increased risk of poor facial nerve function may be expected in some series (165) but not in others (261).
Biomarkers of more rapid growth are being sought to aid in determining which patients are safe to observe initially (516). These include merlin pathway proteins, inflammatory signals, tumor miRNAs, tumor proteins, and CSF components.
Surgery. If surgery is indicated, preservation of hearing and facial nerve function are now the primary goals of surgery. Surgical mortality and major morbidity have declined considerably in experienced centers (138; 280). Hearing preservation has become more common in the microsurgical era and has become the focus of work in some centers (281). The data indicate that the preservation of useful hearing is unlikely in most centers in tumors over 2 cm in diameter or if the tumor fills the fundus of the internal auditory canal, regardless of the degree of preoperative hearing (209; 434; 315). There is a 25% to 83% chance of useful postoperative hearing in favorable small tumors (136; 360). Individualizing the surgical approach when hearing preservation is the goal may improve results (18). Invasion of the eighth nerve by tumor cells may make hearing preservation difficult in some cases (279). Hearing preservation is more likely if the brainstem auditory evoked response was normal preoperatively and with subtotal resection (230; 401; 510; 257). Intraoperative brainstem auditory evoked response and cochlear nerve action potential monitoring have been reported to improve the chances for hearing preservation (514). Electrocochleography may be superior to auditory brainstem responses for predicting postoperative hearing function when these modalities were compared directly during surgery (234). Since that report, intraoperative auditory steady-state monitoring has been suggested to be superior to auditory brainstem response in predicting postoperative hearing class in hearing preservation surgery (368).
Delayed postoperative hearing loss after initial preservation of function is, unfortunately, possible but not inevitable (315; 450; 316; 473; 280; 366). Efforts are underway to standardize reporting of hearing results (81). Perioperative use of nimodipine, known to improve outcome in aneurysmal subarachnoid hemorrhage (416), and hydroxyethyl starch may improve outcome (514). The parenteral form of nimodipine may be more effective than enteral dosing (416). A subsequent study reported no benefit with nimodipine (414), but another reported significant benefit with nimodipine and hydroxyethyl starch (415). Nimodipine may be more likely to benefit male patients but larger tumors in the female group may have obscured benefit (413). A meta-analysis did find benefit from nimodipine for cochlear nerve, but not facial nerve, preservation (73).
Electrophysiologic monitoring of the facial nerve is now considered essential for preservation of function (159; 315; 407; 514). Good facial nerve function in the immediate postoperative period with an anatomically intact nerve may deteriorate subsequently but has a good long-term prognosis (21). Severely impaired function immediately postoperatively has a poorer prognosis but may still show considerable improvement. The proximal nerve stimulation threshold at the end of the procedure may be a good predictor of long-term nerve function (240; 438). In a large series of patients operated on with facial nerve monitoring, facial nerve function was good at 1 month postoperatively in 52% of tumors greater than 3 cm, 81% of tumors 2 to 3 cm, and 92% of tumors less than 2 cm (447). In most cases, function improves with time after surgery; in one series, 92.1% of patients with smaller tumors and 75% of patients with large tumors had normal function at 6 months (407). Oh and colleagues reviewed electrophysiologic monitoring techniques useful during vestibular schwannoma surgery (327).
The extent of removal is decided on an individual case basis. For some patients, total resection will be the goal. For others, subtotal or near total resection in order to preserve facial nerve function or intracapsular resection to preserve hearing may be indicated (257; 425; 460; 49). Tumor involvement of the fundus of the internal auditory canal may herald more difficulty in preserving hearing and facial nerve function (111). For large tumors, near total or subtotal resection has been reported to result in higher facial nerve function preservation and lower need for eye treatments (425), but subtotal resection may result in higher recurrence rates compared to total or near total resection in some reports (301; 224) but not in others (460; 381). In all cases, long-term follow-up is indicated to detect recurrence or growth of residual tumor. Recurrence after subtotal resection is likely, with a reported radiographic recurrence rate of 44% and need for additional therapy of 26%, at a mean follow-up of 6.2 years (116). In a long-term follow-up of 772 patients followed for 3 to 266 months, however, the risk of recurrence did not correlate with the extent of resection (456) nor was there a difference in recurrence rate between subtotal or near total resection in 42 patients with intentionally residual tumor among 450 patients in another study (460). The recurrence rate after total resection is low, and some authors have suggested that frequent imaging may not be indicated (433), but a long-term follow-up of 571 patients who underwent gross total resection at one institution showed an 8.8% recurrence rate (456). Recurrence rates may be higher in patients over age 70 (476). Surgery appears to provide durable remission, with an 89% freedom from recurrence or progression at 15 years in a series of 204 patients operated on at less than 40 years of age (455). Another long-term follow-up after gross total resection observed a recurrence free survival rate of only 56% at 20 years (314). Ki-67 index may be predictive of the probability of recurrence (185; 362). Care must be exercised in interpreting postoperative images because pseudoprogression is common (284; 111; 392).
Surgery is generally performed by an experienced team that includes neurosurgeons, neuro-otologists, and neurophysiologists. Centers caring for these patients should also be skilled in the rehabilitative aspects of care, such as facial nerve reconstruction, prosthetic hearing devices, vestibular rehabilitation, etc. Three basic surgical approaches are utilized: (1) posterior fossa, (2) translabyrinthine, and (3) subtemporal (middle fossa) approaches. A fourth avenue, an endoscopic, transcanal transpromontorial approach, has also been reported for small, intracanalicular tumors (10; 267; 268). Data from a multi-institutional series of 1579 operated patients are available (494). Individual surgeons have also accumulated considerable experience with these tumors (280).
The posterior fossa approach is indicated for attempted hearing preservation and for large tumors. This approach requires brain retraction but is rapid, does not destroy the hearing apparatus, affords a large opening necessary for removal of large tumors, and allows exposure of all involved cranial nerves. In the Mayo Clinic series of 335 procedures, the facial nerve was preserved in 86.3% and hearing in 13.4% (158; 112). Total removal was achieved in all but eight cases; one of the eight recurred, and five of the total resections also recurred. Excellent results have been reported for this approach when treating intracanalicular tumors (404; 280). Several institutions have reported that the posterior semicircular canal can be resected with hearing preservation as part of a combined pre- and retro-sigmoid approach (333; 19). Use of endoscopes has been reported to allow better visualization through smaller craniotomies (345). This approach is described in detail by Elhammady (115).
The translabyrinthine approach is destructive of hearing and is, therefore, indicated in patients without useful hearing or for whom hearing preservation is not likely. The opening for this approach is more time consuming and is not suitable for large tumors. It has the advantages of avoiding brain retraction, exposing the entire internal auditory canal, allowing exposure of the facial nerve distal to the tumor, which some believe improves the chance of preservation of the nerve, and allowing for immediate grafting of the nerve if required. The House group has enormous experience with this technique, reporting the results of over 1600 cases (173; 51). Some large series have reported total resections in 99%, facial nerve function of House grade III or better in 86%, and mortality of 1.75% (340). Some reports indicate better facial nerve preservation rates with the translabyrinthine approach than with the posterior fossa approach (171). In a series of 512 patients treated with the translabyrinthine approach, total tumor removal was accomplished in 94.5%, and anatomic preservation of the facial nerve in 97.5% (51). At 1 year, 81% of patients had facial nerve function of House-Brackmann grade I or II. In patients with small tumors and no hearing, the translabyrinthine approach has been reported to result in less posttreatment dysequilibrium than radiosurgery with comparable morbidity (78). The recurrence rate after gross total resection may be slightly lower with the translabyrinthine approach than with other approaches (07). CSF leakage may be more common with this approach than with others but has decreased with improved closure techniques (20). This surgical technique is described in detail by Arriaga and Lin (20). The translabyrinthine approach may result in shorter hospital length of stay and lower costs than the retrosigmoid approach, even when controlled for tumor size (431). Simultaneous cochlear implant placement has been reported (89). There is insufficient evidence to recommend the translabyrinthine or posterior fossa approach in terms of extent of resection or facial nerve preservation when serviceable hearing is not present (143).
The subtemporal extradural or middle fossa approach is used by only a few centers, but is suitable for hearing preservation surgery, with tumors confined to the internal auditory canal with less than 1 cm of medial extension and in some centers for larger tumors (144; 440; 16). Tumors that do not reach the fundus of the internal auditory canal are also more suitable for attempts at hearing preservation (16). The falciform crest obscures the inferior half of the fundus of the internal auditory canal when viewed from above, which may limit the resection in this area in hearing preservation cases (142). This approach may be most useful in tumors arising from the superior vestibular nerve. Preoperative determination from which vestibular nerve the tumor arises may be improved with a sophisticated battery of testing but remains imperfect (367). It may also be used for decompression of the internal auditory canal in only hearing ears in order to temporarily preserve hearing (132). In centers using multiple approaches, hearing preservation has been reported to be more likely with the middle fossa approach (189), but others have reported equal hearing preservation with the posterior fossa approach and fewer overall complications with the latter approach (400). A meta-analysis comparing middle fossa to the retrosigmoid approach found the middle fossa approach better for hearing preservation only in intracanalicular tumors, but not for any other tumor size (331). The surgical technique is well described by Angeli (16).
Complications of surgery other than cranial nerve injury involving nerves VII and VIII have been investigated in a comprehensive review of 32,870 patients (457; 456). Twenty-two percent of patients experienced at least one surgical complication; mortality rate was 0.2%. Cerebrospinal fluid leak occurred in 8.5% of cases and was more common with the translabyrinthine approach. Ischemic stroke or hemorrhage occurred in 1% of patients. Infection developed in 3.8% of cases. Another database study reported a 30-day mortality rate of 0.5%, suggesting this is the number that should be compared to alternative treatment outcomes (286).
The vast majority of patients with vestibular schwannomas are left with some degree of hearing loss in the involved ear as a result of damage from the tumor and treatment (194; 136; 263; 408; 280). Overall, less than 10% of patients have functional hearing after surgical resection. Even as hearing preservation surgery improves, there may be some rate of progressive hearing loss over time after surgery (313; 108). About one half of patients with preoperative tinnitus may improve, but this does not appear to correlate with preservation or resection of the eighth nerve (166; 123; 202). Tinnitus may arise in the brain, such as the Heschl gyrus or other frontal, temporal, or subcortical areas, including the caudate nucleus (470) rather than the ear itself (217). Difficulties with gaze stability, mobility, and balance are seen after surgery, but the role of vestibular rehabilitation is not yet clear (335).
Although the facial nerve is anatomically intact after surgery in 90% of large tumors and almost 100% of small tumors (ie, intracanalicular and small cisternal), many patients have facial weakness (194; 304; 281). The degree of facial weakness can vary: 70% of patients with large tumors, 50% of those with medium tumors, and 30% of those with small tumors have neurapraxia of the facial nerve after resection. The weakness is permanent in 30% of cases involving large tumors and 10% of cases involving small- and medium-sized tumors. Cystic schwannomas may be more difficult to resect, with high rates of facial nerve dysfunction (293; 504). Some authors recommend aggressive, early nerve reconstruction in patients with facial nerve discontinuity (281). Using various methods of reconstruction of the severed nerve, more than 70% of patients can achieve satisfactory results (281).
Chronic postoperative headaches affect over 25% to 50% of patients and may be difficult to treat (152; 61; 08; 394); this includes some patients whose tumors are small. A C-type incision may be associated with less headache (08), as is craniotomy instead of craniectomy (394). Vertigo is a common problem postoperatively but is usually transient; persistent vertigo is rare. Vertigo occurs more often with small tumors and typically resolves after several weeks to months (406). Persistent dysequilibrium can occur, the likelihood of which has been correlated with age greater than 55 years, the presence of preoperative dysequilibrium, duration of preoperative dysequilibrium for more than 3.5 months, and central findings on electronystagmography (109). Long term dizziness has not been correlated with treatment modality but may be correlated with post treatment headache (60).
On occasion, patients have persistent cerebellar dysmetria as a result of tumor compression of the brainstem or cerebellar retraction during surgery. Impairment of the trigeminal nerve or nerves of the jugular complex (IX, X, XI) can rarely be persistent after treatment of large tumors. Other uncommon complications of schwannomas include hydrocephalus, intratumoral hemorrhage, subarachnoid hemorrhage, rapid cyst expansion, and malignant degeneration (297; 194; 263; 451). It is extremely rare for a sporadic schwannoma to degenerate into a malignant tumor (31). This complication usually occurs with tumors from patients with neurofibromatosis type 1 or neurofibromatosis type 2 or after radiation treatment. Malignant transformation may be accompanied by large copy number aberrations and homozygous deletion of the CDKN2A gene (163).
Studies attempting to assess quality of life show in many patients a significant negative impact of surgery that does not correlate with tumor size (320). In a small series, over half of the patients reported a postoperative decline in quality of life, and 20% were unable to continue their occupations following surgery. This finding has been confirmed by others (200). However, other studies have found better quality of life in patients treated with surgery than with other modalities (220) or only minor differences based on treatment modality, with declines more related to the diagnosis than the treatment (61). Quality of life in patients with tumors less than 10 mm showed a preference for observation over any active treatment (445).
Most current studies do not suggest that proliferation indices or other pathologic markers can predict the postoperative course for patients who undergo surgical resection (454), but one does suggest a correlation with Ki67 index as a predictor of recurrence (362). Macrophage infiltration may suggest a risk of recurrence (139).
Reports are appearing describing a transcanal transpromontorial microscopic/endoscopic approach for vestibular schwannomas, even with larger-sized tumors reaching the brainstem (268).
Radiosurgery. Experience with radiosurgical treatment of vestibular schwannomas generally supports its safety and effectiveness for tumors less than 3 cm in diameter. The role of radiosurgery versus open surgery continues to be debated in terms of tumor control, morbidity, and cost (227; 178; 231; 356; 359; 480; 228; 28). Attempts at direct comparison of outcomes and patient satisfaction between surgery and radiosurgery indicate an advantage for radiosurgery in the short term (206; 374; 310).
This form of treatment dates back to 1969 at the Karolinska Institute in Stockholm. Several early series reported short-term local tumor control rates of 86% to 100% (170; 127; 126; 292; 228; 193), but with higher cranial nerve injury rates at doses higher than currently recommended. New cranial neuropathies, mainly of the fifth and seventh nerve, have become less common with more advanced treatment planning (127; 126; 292; 325; 382) and dose reductions (193). New cranial neuropathy other than hearing loss more than 28 months after treatment is rare (127; 126).
A University of Pittsburgh series using currently advocated lower margin doses of 12 to 13 Gray in 829 patients reported a 10-year clinical control rate of 97%, with preservation of facial nerve function in 99% and trigeminal nerve dysfunction in 3% of tumors that reached the trigeminal nerve (259). Hearing preservation was achieved in 50% to 77%, depending on tumor size. An updated report from 2019 described 94% progression-free survival at 10 years and freedom from surgical resection in 98.7% (197). The University of Florida reported on 390 patients treated with linear accelerator-based radiosurgery (130). The 5-year actuarial control rate was 90%, with only four patients (1%) requiring subsequent surgery. After doses were reduced to 1250 cGray in 1994, trigeminal and facial nerve complications were reduced to 0.7% each. Some reports now indicate tumor control rates and complications similar to smaller tumors for tumors larger than 3 cm (324; 346).
For intracanalicular tumors with a mean follow-up of 42 months, serviceable hearing was preserved in 77.5% of those with excellent pretreatment hearing and in 85% of those with useful pretreatment hearing (321). Another series of intracanalicular tumors showed sustained tumor control in more than 90% at 10 years, freedom from need for other intervention in 98% at 10 years, and hearing preservation in 38.1% at 10 years (323). Among 74 patients with Gardner-Robertson Class I hearing treated with radiosurgery in Marseille, 78.4% had functional hearing after a minimum of 3 years of follow-up (463). Hearing preservation has been correlated to the maximum radiation dose delivered to the cochlea (463; 469; 54; 251; 278), but there is not universal agreement with this observation (196).
In a series of 51 patients followed for greater than 10 years after lower dose range radiosurgery, the local control rate was 97.7%, with only a single patient requiring surgery 10 years after treatment (382). Kaplan-Meier estimates of useful hearing preservation were 57% at 5 years and 24% at 10 years. There were no permanent new cranial nerve deficits. Indeed, progressive hearing loss may occur with longer follow up, with only 23% serviceable hearing remaining at 10 years in another long-term follow-up report (58). A 10-year follow-up study of 440 patients treated with a median marginal dose of 12.8 Gray noted 5- and 10-year progression-free survival rates of 93% and 92% (161). The 10-year facial nerve preservation rate was 97%.
Tumors growing more than 2.5 mm per year (274) or doubling times of less than 15 months (241) prior to radiosurgery may be less likely to respond to radiosurgery. It has been argued that if nongrowing tumors are excluded, 10-year local control rates may be as low as 77% (241). Cystic tumors may respond dramatically to radiosurgery (50; 102) without less effectiveness than seen in solid tumors (277). Even very large tumors (Koos grade IV) have been reported to respond to treatment with minimal facial nerve injury and acceptable other complication rates (461). Transient tumor and/or associated cyst enlargement is common after radiosurgery and so should not be used as the sole criteria for treatment failure, even up to 3.5 years after treatment (162; 352; 312; 358; 53; 32). Because radiosurgery does not often eliminate the radiographic tumor, long-term radiographic follow-up is necessary, and caution has been advised in differentiating the effect of radiosurgery from the natural history of untreated tumors (33). Retreatment with radiosurgery has also been reported with acceptable short-term morbidity and good tumor control (96; 511; 187).
Useful pretreatment hearing may be preserved in 35% to 85% of patients 2 years after treatment (127; 126; 326; 168; 193; 321; 509), but may continue to deteriorate in long-term follow-up (382; 409), leading some to recommend against prophylactic radiation and waiting for proven growth before treating (409). Some reports suggest that hearing loss is greater with radiosurgery than observation and do not recommend treatment for patients with excellent hearing under observation (129). Some report no difference in hearing loss between patients managed with radiosurgery or observation alone (420). Others have reported better long-term hearing preservation when radiosurgery was administered prior to hearing deterioration rather than after (09; 322). A group of 307 patients with serviceable hearing followed for a median of 7.6 years had 95% tumor control and serviceable hearing maintained in 77.8% at 3 years, 68.8% at 5 years, and 51.8% at 10 years (198). The Pittsburgh Hearing Prediction Score had predictive value. In a meta-analysis of 4234 cases from 45 publications, hearing preservation was noted at a mean follow-up of 44 months in 51% of patients, without correlation with age or tumor size, but with correlation to treatment doses of less than 13 Gray (509). Another meta-analysis of 2195 patients from 47 reports found 58% hearing preservation at 47 months (82), and a metaanalysis of 23 studies at a mean of 6.7 years after radiosurgery found preserved hearing in 59.4% irrespective of the technique used (26). Doses to the cochlea above 5.3 Gray may correlate with hearing loss, and newer treatment plans may try to spare the cochlea for this reason (54; 336), with suggested doses below 4 Gray (250; 77). The mean cochlear dose may be more important than the maximum dose (474). A fluid-filled gap between the tumor and the fundus may improve hearing preservation rates, possibly by reducing radiation to the labyrinth (48). Smaller tumors farther away from the cochlea may offer the best chance for long-term hearing preservation (40).
For patients with intracanalicular tumors, radiosurgery was reported to result in better hearing preservation rates that observation (373), or at least no worse hearing outcomes (25). Early radiosurgery may result in a higher hearing preservation rate than delayed treatment (09; 322). The reasons for hearing loss after radiosurgery are not well understood. One report has suggested that preoperative auditory brainstem response parameters may suggest elevated pressure in the auditory canal, which in turn may render the cochlear nerve vulnerable during the phase of transient tumor expansion frequently seen on MRI after radiosurgery (147). Genetics and epigenetics may also play a role in susceptibility to hearing loss with vestibular schwannomas (103).
In a meta-analysis of management of intracanalicular tumors, radiosurgery was found to be equivalent to microsurgery and observation in tumor control and hearing preservation, and had a better rate of facial nerve preservation when compared to surgery (25).
In a Markov decision analysis using quality-adjusted life years as the outcome measure, radiosurgery was the preferred treatment for patients with small tumors that enlarged during a period of observation (303). Similarly, an analysis of published literature led another group to also report that radiosurgery showed the best treatment outcomes when compared to surgery for tumors less than 30 mm in diameter, with no direct mortality, better facial nerve and hearing outcomes, and better quality of life (500). In a matched cohort study of surgery versus radiosurgery for tumors smaller than 2.8 cm, there was no difference in the need for subsequent intervention, but radiosurgery was associated with better hearing and facial nerve preservation (137). When radiosurgery was compared to observation, the rate of hearing loss and quality of life was similar in both groups, but the need for additional treatment was significantly less in the treated group (52). A propensity matching study for Koos grade 1 and 2 tumors enrolling 125 matched pairs with a 36 months mean follow-up found that radiosurgery produced slightly better 5- and 10-year tumor control rate than observation, with comparable hearing, facial nerve, and trigeminal nerve preservation rates (46). Radiosurgery was associated with a lower rate of tinnitus. In a prospective, randomized trial of upfront radiosurgery versus observation of newly diagnosed tumors less than 2 cm in diameter, after 4 years of follow up, tumors were smaller in the treated group, but other secondary outcomes were almost identical in both groups (98). Radiosurgery is less costly when compared to resection both in initial and follow-up costs (419).
Radiosurgery is a useful alternative in patients who have failed previous microsurgery, but the cranial nerve complication rate seems to be higher than for treating previously unoperated patients (355; 192; 175). There does not appear to be an advantage to immediate postoperative radiosurgery versus following patients with postoperative residual tumor and treating only after evidence of growth (97).
There is ongoing debate as to whether radiosurgery makes subsequent microsurgery more difficult (439; 357; 245; 249; 134; 183; 358; 405; 271). Surgery after previous partial resection and radiosurgery may be the most challenging (134), but when there is good facial nerve function preoperatively, good results can be achieved by skilled surgeons (405). Others have reported poor facial nerve recovery, more disequilibrium, and a higher risk of pneumonia postoperatively after prior radiosurgery (174), or low chances for complete resection and a significant risk of facial nerve dysfunction (271).
Repeated radiosurgery is an option for recurrence after prior radiation. Rates of tumor control, facial nerve injury, and hearing loss are similar to those reported for first radiosurgical treatment (24; 371).
Fractionated or hypofractioned stereotactic radiotherapy (a combination of stereotactic, single fraction radiosurgery, and standard radiation fractionation schemes) has been tried in several centers. Preliminary results indicate tumor control rates equivalent to single fraction radiosurgery, with a possible reduction in cranial neuropathy rates in some studies but no advantage in others (291; 290; 497; 67; 80; 150; 288; 399; 15; 363; 364; 337; 342; 253; 319; 444; 364; 432). Two studies have reported greater decrease in tumor size after fractionated treatment than after single dose treatment (418; 182). Five dose fractionation with a resulting lower biologic equivalent dose than radiosurgery may increase the risk of recurrence (214). Hearing preservation has been reported to be more likely with fractionation (215; 364). For a group of 28 patients with serviceable hearing, a three fraction, 18 Gray treatment was reported to result in 65% hearing preservation at 8 years (364). Hearing preservation may correlate with cochlear doses below 4 Gray (39). A metaanalysis comparing radiosurgery to hypofractionated radiosurgery in 13 studies showed comparable tumor control, hearing preservation, facial nerve preservation, and trigeminal nerve preservation (432). More data are needed.
Conventionally fractionated radiotherapy may still have a role for large tumors (201).
Proton irradiation has been used to treat vestibular schwannoma, but data on comparison with photon therapy are sparse (226). Hearing preservation was not better than with other treatment modalities (410).
The risk of a radiation-induced neoplasm after stereotactic surgery is low and has been estimated at 0.04% at 15 years after treatment to 0.3% at 4.9 years (339; 354). Genetic analysis of tumors resected after prior radiosurgery did not show an increased number of mutations compared to tumors not previously irradiated (164).
Radiosurgery has been reported to be effective in patients with neurofibromatosis type 2 as well (216; 75; 76; 47; 436), with high rates of local control and lower facial nerve complications than surgery, but lower hearing preservation rates than surgery (76). In one series of 81 cases followed for a mean of 125 months, no secondary malignancies were identified (436), and in another study including 328 tumors, no secondary malignancies were reported (47).
Chemotherapy. Drug therapy in the treatment of vestibular schwannoma was reviewed in 2021 (254) and 2022 (464; 515). Drugs reviewed include protein tyrosine kinase inhibitors (including ErbB family protein inhibitors, PDGFR family protein inhibitors, VGEFR inhibitors, HGFR inhibitors), inhibitors of Akt signal transduction, mTOR inhibitors, chemokine receptor-4 inhibitors, and inflammatory factor inhibitors (COX2 inhibitors, NF-kappaB inhibitors).
Reports have indicated responsiveness of some vestibular schwannomas to bevacizumab, an antivascular endothelial growth factor antibody (351; 283; 458; 218; 348; 107). In a study of 20 patients with neurofibromatosis type 2, freedom from tumor growth was 89% at 98 weeks and freedom from hearing loss was 70% at 98 weeks (348). Another report on 17 patients reported hearing improvement in 56% and decrease tumor volume in 47% (458). Toxicity may limit its use (258). Some of the systemic toxicity of bevacizumab may be avoided by selective intra-arterial infusion (379). However, intraarterial administration of bevacizumab would not be deemed routine as the systemic toxicity of bevacizumab can often be easily managed. Preoperative indium-bevacizumab scintography predicted tumor response in one of the bilateral tumors in a patient with NF2 (483). The response to radiation therapy may be enhanced by bevacizumab in an animal model (133).
The presence of proinflammatory cytokines TGF-beta1, IL-1beta, and IL-6 in vestibular schwannomas compared with normal vestibular nerves suggests a role for inflammation in the growth of these tumors (465). Chemokines known to induce monocyte chemotaxis have been detected in higher concentrations in patients with growing vestibular schwannomas (149). Aberrant COX-2 expression and aberrant expression of the downstream product prostaglandin E2 have led to trials of salicylates in primary vestibular schwannoma cell cultures and reports of reduced tumor growth in patients taking these agents (99; 203). Aspirin may be considered for use in tumors under observation (477). OSU-03012, a novel derivative of COX-2, is another potentially useful agent (254).
Erlotinib, a small molecule EGFR-specific tyrosine kinase inhibitor, has also been tried to control the tumor after contralateral resection (350); however, 11 other patients did not respond to this agent (349). It is currently not recommended for use (477). The use of trastuzumab and lapatinib have also been reported (254).
Activation of EGFR family receptors in human tissue samples leads to a trial of the small-molecule EGFR/ErbB2 kinase inhibitor, lapatinib, in an in vitro human schwannoma model (12). Antiproliferative activity was shown, and a human trial is reportedly underway. Lapatinib may be considered for use in NF-2 related tumors (477). Another EGFR tyrosine kinase inhibitor, icotinib, has also shown radiographic and hearing responses in NF2 patients (517).
PDGFR family protein inhibitors, such as imatinib, nilotinib, and ponatinib, have also been reported to have activity (254). Nilotinib alone, or in combination with selumetinib, has been shown to inhibit schwannoma growth in vitro through the platelet-derived growth factor receptor/c-KIT pathway and MEK1/2 pathway respectively (14). Similarly, imatinib has also been shown to inhibit in vitro tumor proliferation through the platelet-derived growth factor receptor/c-KIT pathway (11).
The role of c-MET inhibition is being investigated in these tumors (131). The c-MET and anaplastic lymphoma kinase inhibitor crizotinib is in phase 2 trials for NF2 patients with progressive vestibular schwannomas (254).
As merlin is thought to be a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1), the mTORC1 inhibitor rapamycin has been shown to inhibit in a mouse allograft model of NF2 schwannoma (135). By extension, the rapamycin analog sirolimus was then shown to induce tumor growth arrest in a human NF2 patient (135). Everolimus, a derivative of rapamycin, was not effective in one trial but was reported to reduce tumor growth rate in another (254). In cultured vestibular schwannoma tumor cells, a dual mTORC1/2 inhibitor and dasatinib exhibited a therapeutic effect (398).
As the molecular pathways giving rise to schwannomas are elucidated, it is expected that more novel treatment strategies will appear (128; 296; 453; 254; 515).
An association between metformin use and slower growth of vestibular schwannoma has been reported (124).
Gene therapy. Various attempts at gene therapy for merlin mutated tumors have been reported since 2010 (515). Treatment options include suicide gene therapy, gene replacement or augmentation therapy, gene knockdown and replacement therapy, and potentially gene editing therapy.
Bilateral tumors. A patient with bilateral vestibular schwannomas represents a more difficult situation. Intervention risks bilateral hearing loss and bilateral facial paralysis, both of which are major deficits. If one tumor progresses more rapidly or one ear loses useful hearing, then the side of first intervention may be dictated by clinical circumstances. Intracapsular, subtotal resection may be indicated to preserve hearing in the remaining hearing ear, or internal auditory canal decompression without tumor resection may also preserve hearing for some time (41; 49). Radiosurgery may be indicated in some patients (252; 150; 75). However, sudden deafness complicates radiosurgery in some of these cases, particularly with larger tumors (191; 69). Some argue for early intervention when the chances for hearing preservation are highest, whereas others prefer observation for as long as possible. Bevacizumab may offer some hope for these patients (350; 351), as do some other novel therapies (453). All agree that patients and their family should learn to sign while still able to hear.
Simultaneous tumor resection and cochlear implantation is now being reported (88; 492).
Special considerations
Pregnancy
Pregnancy does not appear to influence the growth of vestibular schwannomas (34).
Malignancy
Atypical vestibular schwannomas are rare but have been reported (223).
Media
References
- 01
- Aarhus M, Bruland O, Saetran HA, Mork SJ, Lund-Johansen M, Knappskog PM. Global gene expression profiling and tissue microarray reveal novel candidate genes and down-regulation of the tumor suppressor gene CAV1 in sporadic vestibular schwannomas. Neurosurg 2010;67(4):998-1019. PMID 20881564
- 02
- Aarhus L, Kjaerheim K, Heikkinen JI, et al. Occupational noise exposure and vestibular schwannoma: a case-control study in Sweden. Am J Epidemiol 2020;189;1342-7. PMID 32440685
- 03
- Aaron KA, Manojlovic Z, Tu N, et al. What genes can tell: a closer look at vestibular schwannoma. Oto Neurotol 2020;41(4):522-9. PMID 32176142
- 04
- Agnihotri S, Gugel I, Remke M, et al. Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannomas. J Neurosurg 2014;121(6):1434-45. PMID 25245477
- 05
- Agrawal Y, Clark JH, Limb CJ, Niparko JK, Francis HW. Predictors of vestibular schwannoma growth and clinical implications. Otol Neurotol 2010;31(5):807-12. PMID 20502379
- 06
- Ahlbom A, Feychting M, Green A, Kheifets L, Savitz DA, Swerdlow AJ. Epidemiologic evidence on mobile phones and tumor risk: a review. Epidemiology 2009;20:639-52. PMID 19593153
- 07
- Ahmad RA, Sivalingam S, Topsakal V, Russo A, Taibah A, Sanna M. Rate of recurrent vestibular schwannoma after total removal via different surgical approaches. Ann Otol Rhinol Laryngol 2012;121(3):156-61. PMID 22530474
- 08
- Aihara N, Yamada H, Takahashi M, Inagaki A, Murakami S, Mase M. Postoperative headache after undergoing acoustic neuroma surgery via the retrosigmoid approach. Neurol Med Chir (Tokyo) 2017;57(12):634-40. PMID 29021412
- 09
- Akpinar B, Mousavi SH, McDowell MM, et al. Early radiosurgery improves hearing preservation in vestibular schwannoma patients with normal hearing at the time of diagnosis. Int J Radiat Oncol Biol Phys 2016;95(2):729-34. PMID 26975929
- 10
- Alicandri-Ciufelli M, Federici G, Anscheutz L, et al. Transcanal surgery for vestibular schwannomas: a pictorial review of radiographic findings, surgical anatomy, and comparison to the traditional translabyrinthine approach. Eur Arch Otorhinolaryngol 2017;274(9):3295-302. PMID 28597129
- 11
- Altuna X, Lopez JP, Yu MA, et al. Potential role of imatinib mesylate (Gleevec, STI-571) in the treatment of vestibular schwannoma. Otol Neurotol 2011;32(1):163-70. PMID 21157293
- 12
- Ammoun S, Cunliffe CH, Allen JC, et al. ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma. Neuro Oncol 2010;1298:834-43. PMID 20511180
- 13
- Ammoun S, Flaiz C, Ristic N, Schuldt J, Hanemann CO. Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-related kinase pathway in human schwannoma. Cancer Res 2008;68:5236-45. PMID 18593924
- 14
- Ammoun S, Schmid MC, Triner J, Manley P, Hanemann CO. Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2. Neuro Oncol 2011;13(7):759-66. PMID 21727212
- 15
- Anderson BM, Khuntia D, Bentzen SM, et al. Single institution experience treating 104 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery. J Neuronocol 2014;116(1):187-93. PMID 24142200
- 16
- Angeli S. Middle fossa approach. indications, technique, and results. Otolaryngol Clin North AM 2012;45(2):417-38. PMID 22483825
- 17
- Arai E, Tokino T, Imai T, et al. Mapping the breakpoint of a constitutional translocation on chromosome 22 in a patient with NF-2. Genes Chromosom Cancer 1993;6:235-8. PMID 7685627
- 18
- Arriaga MA, Chen DA, Fukushima T. Individualizing hearing preservation in acoustic neuroma surgery. Laryngoscope 1997;107:1043-7. PMID 9261005
- 19
- Arriaga MA, Gorum M. Enhanced retrosigmoid exposure with posterior semicircular canal resection. Otolaryngol Head Neck Surg 1996;115:46-8. PMID 8758629
- 20
- Arriaga MA, Lin J. Translabyrinthine approach: indications, techniques, and results. Otolaryngol Clin North Am 2012;45(2):399-415. PMID 22483824
- 21
- Arriaga MA, Luxford WM, Atkins JS, Kwartler JA. Predicting long-term facial nerve outcome after acoustic neuroma surgery. Otolaryngol Head Neck Surg 1993;108:220-4. PMID 8464633
- 22
- Asthagiri AR, Parry DM, Butman JA, et al. Neurofibromatosis type 2. Lancet 2009;373:1974-86. PMID 19476995
- 23
- Bakkouri W, Kania RE, Guichard JP, Lot G, Herman P, Huy PT. Conservative management of 386 cases of unilateral vestibular schwannoma: tumor growth and consequences for treatment. J Neurosurg 2009;110:662-9. PMID 19099381
- 24
- Balossier A, Regis J, Reyns N, et al. Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis. Neurosurg Rev 2021;44(6):3177-88. PMID 33847846
- 25
- Balossier A, Sahgal A, Kotecha R, et al. Management of sporadic intracanalicular vestibular schwannomas: a critical review and International Stereotactic Radiosurgery Society (ISRS) practice guidelines. Neuro Oncol 2024;429-43. PMID 38134966
- 26
- Balossier A, Tuleasca C, Delsanti C, et al. Long-term hearing outcome after radiosurgery for vestibular schwannoma: a systematic review and meta-analysis. Neurosurgery 2023;92:1130-41. PMID 36735500
- 27
- Bance ML, Hyde ML, Malizia K. Decision and cost analysis in acoustic neuroma diagnosis. J Otolaryngol 1994;23:109-20. PMID 8028068
- 28
- Banerjee R, Moriarty JP, Foote RL, Pollock BE. Comparison of the surgical and follow-up costs associated with microsurgical resection and stereotactic radiosurgery for vestibular schwannoma. J Neurosurg 2008;108:1220-4. PMID 18518731
- 29
- Baser ME, Kuramoto L, Joe H, et al. Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population based study. Am J Hum Genet 2004;75(2):231-9. PMID 15190457
- 30
- Baser ME, Makariou EV, Parry DM. Predictors of vestibular schwannoma growth in patients with neurofibromatosis Type 2. J Neurosurg 2002;96:217-22. PMID 11838793
- 31
- Bashir A, Poulsgaard L, Broholm H, Fugleholm K. Late malignant transformation of vestibular schwannoma in the absence of irradiation: case report. J Neurosurg 2015;1-6. PMID 26613171
- 32
- Bathla G, Mehta PM, Benson JC, et al. Imaging findings post stereotactic radiosurgery for vestibular schwannoma: Primary for the radiologist. AJNR Am J Neuroradiol 2024;45(9):1194-201. PMID 38553015
- 33
- Battaglia A, Mastrodimos B, Cueva R. Comparison of growth patterns of acoustic neuromas with and without radiosurgery. Otol Neurotol 2006;27(5):705-12. PMID 16868519
- 34
- Beatty CW, Scheithauer BW, Katzmann JA, Roche PC, Kjeldahl KS, Ebersold MJ. Acoustic schwannoma and pregnancy: a DNA flow cytometric, steroid hormone receptor, and proliferation marker study. Laryngoscope 1995;105:693-700. PMID 7603272
- 35
- Bederson JB, von Ammon K, Wichmann WW, Yasargil MG. Conservative treatment of patients with acoustic neuromas. Neurosurgery 1991;28:646-51. PMID 1876241
- 36
- Behling F, Ries V, Skardelly M, et al. COX2 expression is associated with proliferation and tumor extension in vestibular schwannoma but is not influenced by acetylsalicylic acid intake. Acta Neuropathol Commun 2019;7(1):105. PMID 31291992
- 37
- Belliveau MJ, Lutchman M, Claudio JO, Marineau C, Rouleau GA. Schwannomin: new insights into this member of the band 4.1 superfamily. Biochem Cell Biol 1995;73:733-7. PMID 8714694
- 38
- Benhamouche S, Curto M, Saotome I, et al. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev 2010;24(16):1718-30. PMID 20675406
- 39
- Bennion NR, Nowak RK, Lyden ER, Thompson RB, Li S, Lin C. Fractionated stereotactic radiation therapy for vestibular schwannomas: dosimetric factors predictive of hearing outcomes. Pract Radiat Oncol 2016;6(5):e155-62. PMID 26961715
- 40
- Berger A, Alzate JD, Bernstein K, et al. Modern hearing preservation outcomes after vestibular schwannoma stereotactic radiosurgery. Neurosurg 2022;91(4);648-57. PMID 35973088
- 41
- Bernardeschi D, Peyre M, Collin M, Small M, Sterkers O, Kalmarides M. Internal auditory canal decompression for hearing maintenance in neurofibromatosis type 2 patients. Neurosurgery 2016;79(3):370-7. PMID 26579965
- 42
- Bi WL, Santagata S. Skull base tumors: neuropathology and clinical implications. Neurosurgery 2022;90(3):243-61. PMID 34164689
- 43
- Bijlsma EK, Brouwer-Mladin R, Bosch DA, Westerveld A, Hulsebos TJM. Molecular characterization of chromosome 22 deletions in schwannomas. Genes Chromosom Cancer 1992;5:201-5. PMID 1384671
- 44
- Bijlsma EK, Merel P, Bosch DA, et al. Analysis of mutations in the SCH gene in schwannomas. Genes Chromosom Cancer 1994;11:7-14. PMID 7529050
- 45
- Bikhazi PH, Lalwani AK, Kim EJ, et al. Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma. Otolaryngol Head Neck Surg 1998;119:1-6. PMID 9674507
- 46
- Bin-Alamer O, Abou-Al-Shaar H, Peker S, et al. Vestibular schwannoma International study of active surveillance versus stereotactic radiosurgery: The VISAS study. Int J Radiat Oncol Biol Phys 2024;120(2):454-64. PMID 38588868
- 47
- Bin-Alamer O, Faramand A, Alarifi NA, et al. Stereotactic radiosurgery for vestibular schwannoma in neurofibromatosis type 2: An international multicenter case series of response and malignant transformation risk. Neurosurgery 2023;92(5):934-44. PMID 36861994
- 48
- Bojrab DI, Fritz CG, Lin KF, et al. Fundal fluid cap is associated with hearing preservation win the radiosurgical treatment of vestibular schwannoma. Oto Neurotol 2021;42(1):137-44. PMID 33055496
- 49
- Bonne NX, Risoud M, Hoa M, et al. Hearing response following internal auditory canal decompression in neurofibromatosis type 2. Neurosurgery 2019;85(3):E560-E7. PMID 30888036
- 50
- Bowden G, Cavaleri J, Monaco E III, Niranjan A, Flickinger J, Lunsford LD. Cystic vestibular schwannomas respond best to radiosurgery. Neurosurgery 2017;81(3):490-7. PMID 28368501
- 51
- Brackmann DE, Cullen RD, Fisher LM. Facial nerve function after translabyrinthine vestibular schwannoma surgery. Otolaryngol Head Neck Surg 2007;136(5):773-7. PMID 17478214
- 52
- Breivik CN, Nilsen MR, Myrseth E, et al. Conservative management or Gamma Knife radiosurgery for vestibular schwannoma: tumor growth, symptoms, and quality of life. Neurosurgery 2013;73(1):48-57. PMID 23615094
- 53
- Breshears JD, Chang J, Molinaro AM, et al. Temporal dynamics of pseudoprogression after Gamma Knife radiosurgery for vestibular schwannomas – a retrospective volumetric study. Neurosurgery 2019;84(1):123-31. PMID 29518221
- 54
- Brown M, Ruckenstein M, Bigelow D, et al. Predictors of hearing loss after gamma knife radiosurgery for vestibular schwannomas: age, cochlear dose, and tumor coverage. Neurosurg 2011;69(3):605-13. PMID 21471832
- 55
- Burkey JM, Rizer FM, Schuring AG, Fucci MJ, Lippy WH. Acoustic reflexes, auditory brainstem response, and MRI in the evaluation of acoustic neuromas. Laryngoscope 1996;106:839-41. PMID 8667979
- 56
- Caltabiano R, Magro G, Polizzi A, et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF-2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017;33(6):933-40. PMID 28365909
- 57
- Cao Z, Zhao F, Mulugeta H. Noise exposure as a risk factor for acoustic neuroma: a systematic review and meta-analysis. Int J Audiol 2019;58(9):525-32. PMID 31012775
- 58
- Carlson ML, Jacob JT, Pollock BE, et al. Long-term hearing outcomes following stereotactic radiosurgery for vestibular schwannoma: patterns of hearing loss and variables influencing audiometric decline. J Neurosurg 2013;118(3):579-87. PMID 23101446
- 59
- Carlson ML, Smadbeck JB, Link MJ, Klee EW, Vasmatzis G, Schimmenti LA. Next generation sequencing of sporadic vestibular schwannoma: necessity of biallelic NF2 inactivation and implications of accessary non-NF2 variants. Otol Neurotol 2018;39(9):e860-71. PMID 30106846
- 60
- Carlson ML, Tvetien OV, Driscoll CL, et al. Long-term dizziness handicap in patients with vestibular schwannoma: a multicenter cross-sectional study. Otolaryngol Head Neck Surg 2014;151(6):1028-37. PMID 25273693
- 61
- Carlson ML, Tveiten OV, Driscoll CL, et al. Long-term quality of life in patients with vestibular schwannoma: an international multicenter cross-sectional study comparing microsurgery, stereotactic radiosurgery, observation, and nontumor controls. J Neurosurg 2015;122(4):833-42. PMID 25555165
- 62
- Carpenter DO. Electromagnetic fields and cancer: the cost of doing nothing. Rev Environ Health 2010;25(1):75-80. PMID 20429163
- 63
- Carrier DA, Arriaga MA. Cost-effective evaluation of asymmetric sensorineural hearing loss with focused magnetic resonance imaging. Otolaryngol Head Neck Surg 1997;116:567-74. PMID 9215364
- 64
- Castellaro M, Moretto M, Baro V, et al. Multishell diffusion MRI-based tractography of the facial nerve in vestibular schwannoma. AJNR Am J Neuroradiol 2020;41:1480-6. PMID 32732265
- 65
- Caye-Thomasen P, Werther K, Nalla A, et al. VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate. Otol Neurotol 2005;26(1):98-101. PMID 15699727
- 66
- Cazzador D, Astolfi L, Daloiso A, et al. Tumor microenvironment in sporadic vestibular schwannoma: a systematic, narrative review. Int J Mol Sci 2023;24:6522. PMID 37047498
- 67
- Chan AW, Black PMcL, Ojemann RG, et al. Stereotactic radiotherapy for vestibular schwannomas: Favorable outcome with minimal toxicity. Neurosurgery 2005;57:60-70. PMID 15987541
- 68
- Chang LS, Akhmametyeva EM, Wu Y, Zhu L, Welling DB. Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts. Genomics 2002;79:63-76. PMID 11827459
- 69
- Chang SD, Poen J, Hancock SL, Martin DP, Adler JR Jr. Acute hearing loss following fractionated stereotactic radiosurgery for acoustic neuroma. Report of two cases. J Neurosurg 1998;89:321-5. PMID 9688131
- 70
- Charabi S, Thomsen J, Tos M, Charabi B, Mantoni M, Borgesen SE. Acoustic neuroma/vestibular schwannoma growth: past, present and future. Acta Otolaryngol 1998;118:327-32. PMID 9655205
- 71
- Chen DQ, Quan J, Guha A, Tymianski M, Mikulis D, Hodaie M. Three-dimensional in vivo modeling of vestibular schwannomas and surrounding cranial nerves with diffusion imaging tractography. Neurosurg 2011;68(4):1077-83. PMID 21242825
- 72
- Chen Y, Wang ZY, Wu H. P14ARF deficiency and it correlation with overexpression of p53/MDM2 in sporadic vestibular schwannomas. Eur Arch Otorhinolaryngol 2015;272(9):2227-34. PMID 24964769
- 73
- Chorath K, Go BC, Kaufman A, Brant J, Moreira A, Rajasekaran K. Perioperative nimodipine to improve cranial nerve function: a systematic review and meta-analysis. Otol Neurotol 2021;42(6):783-91. PMID 33710143
- 74
- Christensen HC, Schuz J, Kosteljanetz M, Poulsen HS, Thomsen J, Johansen C. Cellular telephone use and risk of acoustic neuroma. Am J Epidemiol 2004;159:277-83. PMID 14742288
- 75
- Chung LK, Nguyen TP, Sheppard JP, et al. A systematic review of radiosurgery versus surgery for neurofibromatosis type 2 vestibular schwannomas. World Neurosurg 2017;109:47-58. PMID 28882713
- 76
- Chung LK, Nguyen TP, Sheppard JP, et al. A systematic review of radiosurgery versus surgery for neurofibromatosis type 2 vestibular schwannomas. World Neurosurg 2018a;109:47-58. PMID 28882713
- 77
- Chung LK, Ung N, Sheppard JP, et al. Impact of cochlear dose on hearing preservation following stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma. J Neurol Surg B Skull Base 2018b;79(4):335-42. PMID 30009113
- 78
- Coelho DH, Roland JTJr, Rush SA, et al. Small vestibular schwannomas with no hearing: comparison of functional outcomes in stereotactic radiosurgery and microsurgery. Laryngoscope 2008;118:1909-16. PMID 18849856
- 79
- Colciago A, Audano M, Bonalume V, et al. Transcriptomic profile reveals deregulation of hearing-loss related genes in vestibular schwannoma cells following electromagnetic field exposure. Cells 2021;10(7):1840. PMID 34360009
- 80
- Combs SE, Volk S, Shulz-Ertner D, Huber PE, Thilmann C, Debus J. Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys 2005;63(1):75-81. PMID 16111574
- 81
- Committee on Hearing and Equilibrium. Guidelines for the evaluation of hearing preservation in acoustic neuroma (vestibular schwannoma). Otolaryngol Head Neck Surg 1995;113:179-80. PMID 7675475
- 82
- Coughlin AR, Willman TJ, Gubbels SP. Systematic review of hearing preservation after radiotherapy for vestibular schwannoma. Otol Neurotol 2018;39(3):273-83. PMID 29342035
- 83
- Cox GJ. Intracanalicular acoustic neuromas: a conservative approach. Clin Otolaryngol 1993;18:153-4. PMID 8364998
- 84
- Coy S, Rashid R, Stemmer-Rachamimov A, Santagata S. An update on the CNS manifestations of neurofibromatosis type 2. Acta Neuropathol 2020;139:643-65. PMID 31161239
- 85
- Curati WL, Graif M, Kingsley DP, Niendork HP, Young IR. Acoustic neuromas: Gd-DTPA enhancement in MR imaging. Radiology 1986;158:447-51. PMID 3484555
- 86
- Currie S, Saunders D, Macmullen-Price J, et al. Should we be moving to a national standardized non-gadolinium MR imaging protocol for the surveillance of vestibular schwannomas? Br J Radiol 2019;92(1096):20180833. PMID 30633539
- 87
- Cushing H. The surgical mortality percentages pertaining to a series of two thousand verified intracranial tumors. Arch Neurol Psychiatry 1932;27:1273-80.
- 88
- Dahm V, Auinger AB, Honeder C, et al. Simultaneous vestibular schwannoma resection and cochlear implantation using electrically evoked auditory brainstem response audiometry for decision-making. Otol Neurotol 2020;41(9):1266-73. PMID 32925856
- 89
- DeHart AN, Broaddus WC, Coelho DH. Translabyrinthine vestibular schwannoma resection with simultaneous cochlear implantation. Cochlear Implants Int 2017;18(5):278-84. PMID 28602150
- 90
- Daoudi H, Le Diagon P, Alciato L, et al. Spontaneous shrinkage of sporadic vestibular schwannomas: clinical and radiological analysis. J Neurosurg 2023;140:856-65. PMID 37878002
- 91
- Deltour I, Schlehofer B, Massardier-Pilonochery A, et al. Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case-control study. Scand J Work Environ Health 2019;45(2):183-93. PMID 30614502
- 92
- DeSalles AA, Frighetto L, Selch M. Stereotactic and microsurgery for acoustic neuroma: the controversy continues. Int J Radiation Oncology Biol Phys 2003;56:1215-7. PMID 12873663
- 93
- de Vocht F. Analyses of temporal and spatial patterns of glioblastoma multiforme and other brain cancer subtypes in relation to mobile phones using synthetic counterfactuals. Environ Res 2019;168:329-35. PMID 30384227
- 94
- de Vries M, Briaire-de Bruijn I, Malessy MJ, de Bruine SF, van der Mey AG, Hogendoorn PC. Tumor-associated macrophages are related to volumetric growth of vestibular schwannomas. Otol Neurotol 2013;34(2):347-52. PMID 23295727
- 95
- de Vries M, van der Mey AG, Hogendoorn PC. Tumor biology of vestibular schwannoma: a review of experimental data on the determinants of tumor genesis and growth characteristics. Otol Neurotol 2015;36(7):1128-36. PMID 26049313
- 96
- Dewan S, Noren G. Retreatment of vestibular schwannomas with Gamma Knife surgery. J Neurosurg 2008;109:144-8. PMID 19123901
- 97
- Dhayalan D, Perry A, Graffeo CS, et al. Salvage radiosurgery following subtotal resection of vestibular schwannomas: does timing influence tumor control? J Neurosurg 2022;138(2):420-9. PMID 35907189
- 98
- Dhayalan D, Tveiten OV, Finnkirk M, et al. Upfront radiosurgery vs a wait-and-scan approach for small- or medium-sized vestibular schwannoma: the V-REX randomized clinical trial. JAMA 2023;330:421-31. PMID 37526718
- 99
- Dilwali S, Kao SY, Fujita T, Landegger LD, Stankovic KM. Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannnomas. Transl Res 2015a;166(1):1-11. PMID 25616959
- 100
- Dilwali S, Roberts D, Stankovic KM. Interplay between VEGF-A and cMET signaling in human vestibular schwannomas and schwann cells. Cancer Biol Ther 2015b;16(1):170-5. PMID 25692621
- 101
- Di Maio S, Akagami R. Prospective comparison of quality of life before and after observation, radiation, or surgery for vestibular schwannomas. J Neurosurg 2009;111:855-62. PMID 19301957
- 102
- Ding K, Ng E, Romiyo P, et al. Meta-analysis of tumor control rates in patients undergoing stereotactic radiosurgery for cystic vestibular schwannomas. Clin Neurol Neurosurg 2019;188:105571. PMID 31756616
- 103
- Dinh CT, Nisenbaum E, Chyou D, et al. Genomics, epigenetics, and hearing loss in neurofibromatosis type 2. Otol Neurotol 2020;41(5):e529-37. PMID 32150022
- 104
- Dirks MS, Butman JA, Kim HJ, et al. Long-term natural history of neurofibromatosis Type 2-associated intracranial tumors. J Neurosurg 2012;117(1):109-17. PMID 22503123
- 105
- Don M, Masuda A, Nelson R, Brackmann D. Successful detection of small acoustic tumors using the stacked derived-band auditory brainstem response amplitude. Am J Otol 1997;18:608-21. PMID 9303158
- 106
- Dornhoffer JL, Helms J, Hoehmann DH. Presentation and diagnosis of small acoustic tumors. Otolaryngol Head Neck Surg 1994;11:232-5. PMID 8084630
- 107
- Douwes JPJ, Hensen EF, Jansen JC, Gelderblom H, Schopman JE. Bevacizumab treatment for patients with NF-2 related schwannomatosis: A single center experience. Cancers (Basel) 2024;16:1479. PMID 38672561
- 108
- Dowling EM, Patel NS, Lohse CM, et al. Durability of hearing preservation following microsurgical resection of vestibular schwannoma. Otol Neurotol 2019;40(10):1363-72. PMID 31725593
- 109
- Driscoll CL, Lynn SG, Harner SG, Beatty CW, Atkinson EJ. Preoperative identification of patients at risk of developing persistent dysequilibrium after acoustic neuroma removal. Am J Otol 1998;19:491-5. PMID 9661760
- 110
- Dumanski JP, Carlbom E, Collins VP, Nordenskjold M. Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma. Proc Natl Acad Sci U S A 1987;84:9275-9. PMID 2892198
- 111
- Dunn IF, Bi WL, Mukandan S, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines on the role of imaging in the diagnosis and management of patients with vestibular schwannomas. Neurosurgery 2018;82(2):E32-4. PMID 29309686
- 112
- Ebersold MJ, Harner SG, Beatty CW, Harper CM Jr, Quast LM. Current results of the retrosigmoid approach to acoustic neurinoma. J Neurosurg 1992;76:901-9. PMID 1588422
- 113
- Edwards CG, Schwartzbaum JA, Lonn S, Ahlbom A, Feychting M. Exposure to loud noise and risk of acoustic neuroma. Am J Epidemiol 2005;163(4):327-33. PMID 16357108
- 114
- Edwards CG, Schwartzbaum JA, Nise G, et al. Occupational noise exposure and risk of acoustic neuroma. Am J Epidemiol 2007;165:1252-8. PMID 17804860
- 115
- Elhammady MS, Telischi FF, Morcos JJ. Retrosigmoid approach: indications, techniques, and results. Otolaryngol Clin North Am 2012;45(2):375-97. PMID 22483823
- 116
- El-Kashlan HK, Zeitoun H, Arts HA, Hoff JT, Telian SA. Recurrence of acoustic neuroma after incomplete resection. Am J Otol 2000;21:389-92. PMID 10821553
- 117
- Erkan EP, Breakefield XO, Saydam O. miRNA signature of schwannomas: possible role(s) of “tumor suppressor” miRNAs in benign tumors. Oncotarget 2011;2(3):265-70. PMID 21454924
- 118
- Evans DG. Neurofibromatosis 2. Genet Med 2009;11:599-610. PMID 19652604
- 119
- Evans DG, Bowers NL, Tobi S, Hartley C, et al. Schwannomatosis: a genetic and epidemiological study. J Neurol Neurosurg Psychiatry 2018;89(11):1215-9. PMID 29909380
- 120
- Evans DG, Hartley CL, Smith PT, et al. Incidence of mosaicism in 1055 de novo NF2 cases: much higher than previous estimates with high utility of next-generation sequencing. Genet Med 2020;22(1):53-9. PMID 31273341
- 121
- Evans DG, Messiaen LM, Foulkes WD, et al. Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma. Genet Med 2021;23(9):1779-82. PMID 33879870
- 122
- Evans DG, Trueman L, Wallace A, et al. Genotype/phenotype correlations and type II neurofibromatosis (NF 2), evidence for more severe disease associated with truncating mutations. J Med Genet 1998;35:450-5. PMID 9643284
- 123
- Fahy C, Nikolopoulos TP, O’Donoghue GM. Acoustic neuroma surgery and tinnitus. Eur Arch Otorhinolaryngol 2002;259:299-301. PMID 12115076
- 124
- Feng AY, Enriquez-Marulanda A, Kouhi A, Ali N-E-S, Moore JM, Vaisbuch Y. Metformin potential impact on the growth of vestibular schwannomas. Otol Neurotol 2020;41(3):403-10. PMID 31913209
- 125
- Fisher EW, Parikh AA, Harcourt JP, Wright A. The burden of screening for acoustic neuroma: asymmetric otological symptoms in the ENT clinic. Clin Otolaryngol 1994;19:19-21. PMID 8174295
- 126
- Flickinger JC, Kondziolka D, Pollock BE, Lunsford LD. Evolution in technique for vestibular schwannoma radiosurgery and effect on outcome. Int J Radiat Oncol Biol Phys 1996;36:275-80. PMID 8892449
- 127
- Flickinger JC, Lunsford LD, Linskey ME, Duma CM, Kondziolka D. Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results. Radiother Oncol 1993;27:91-8. PMID 8356233
- 128
- Fong B, Barkhoudarian G, Pezeshkian P, Parsa AT, Gopen Q, Yang I. The molecular biology and novel treatments of vestibular schwannomas. J Neurosurg 2011;115(5):906-14. PMID 21800959
- 129
- Fouad A, Tran ED, Feng AY, et al. Stereotactic radiosurgery for vestibular schwannoma outcomes in patients with perfect word recognition – a retrospective cohort study. Otol Neurotol 2021;42(5):755-64. PMID 33443977
- 130
- Friedman WA, Bradshaw P, Myers A, Bova FJ. Linear accelerator radiosurgery for vestibular schwannomas. J Neurosurg 2006;105(5):657-61. PMID 17121123
- 131
- Fuse MA, Plati SK, Burns SS, et al. Combination therapy with c-Met and Src inhibitors induces caspase-dependent apoptosis of merlin-deficient Schwann cells and suppresses growth of schwannoma cells. Mol Cancer Ther 2017;16(11):2387-98. PMID 28775147
- 132
- Gadre AK, Kwartler JA, Brackmann DE, House WF, Hitselberger WE. Middle fossa decompression of the internal auditory canal in acoustic neuroma surgery: a therapeutic alternative. Laryngoscope 1990;100:948-52. PMID 2395403
- 133
- Gao X, Zhao Y, Stemmer-Rachamimov AO, et al. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model. Proc Natl Acad Sci USA 2015;112(47):14676-81. PMID 26554010
- 134
- Gerganov VM, Giordano M, Samii A, Samii M. Surgical treatment of patients with vestibular schwannomas after failed previous radiosurgery. J Neurosurg 2012;116(4):713-20. PMID 22264180
- 135
- Giovannini M, Bonne NX, Vitte J, et al. mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma. Neuro Oncol 2014;16(4):493-504. PMID 24414536
- 136
- Glasscock ME, Hays JW, Minor LB, Haynes DS, Carrasco VN. Preservation of hearing in surgery for acoustic neuromas. J Neurosurg 1993;78:864-70. PMID 8487067
- 137
- Golfinos JG, Hill TC, Rokosh R, et al. A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas. J Neurosurg 2016;125(6):1472-82. PMID 27035174
- 138
- Gormley WB, Sekhar LN, Wright DC, Kamerer D, Schessel D. Acoustic neuromas: results of current surgical management. Neurosurgery 1997;41:50-60. PMID 9218295
- 139
- Graffeo CS, Perry A, Raghunathan A, et al. Macrophage density predicts facial nerve outcome and tumor growth after subtotal resection of vestibular schwannoma. J Neurol Surg B Skull Base 2018;79(5):482-8. PMID 30210976
- 140
- Gripp KW, Baker L, Kandula V, et al. Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager. Clin Genet 2017;9(5)2:540-3. PMID 28295212
- 141
- Gurgel RK, Couldwell WT, Patel NS, Cannon-Albright LA. Is there an inherited contribution to risk for sporadic unilateral vestibular schwannoma? Evidence of familial clustering. Otol Neuotol 2022;43(10):e1157-63. PMID 36113461
- 142
- Haberkamp TJ, Meyer GA, Fox M. Surgical exposure of the fundus of the internal auditory canal: anatomic limits of the middle fossa versus the retrosigmoid transcranial approach. Laryngoscope 1998;108:1190-4. PMID 9707242
- 143
- Hadjipanayis CG, Carlson ML, Link MJ, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines on surgical resection for treatment of patients with vestibular schwannomas. Neurosurgery 2018;82(2):E40-3. PMID 29309632
- 144
- Haines SJ, Levine SC. Intracanalicular acoustic neuroma: early surgery for preservation of hearing. J Neurosurg 1993;79:515-20. PMID 8410219
- 145
- Hajioff D, Raut VV, Walsh RM, et al. Conservative management of vestibular schwannomas: third review of a 10-year prospective study. Clin Otolarygol 2008;33:255-99. PMID 18559034
- 146
- Halliday D, Emmanouil B, Pretorius P, et al. Genetic severity score predicts clinical phenotype in NF2. J Med Genet 2017;54(10):657-64. PMID 28848060
- 147
- Han JH, Kim DG, Chung HT, Paek SH, Jung HW. Hearing outcomes after stereotactic radiosurgery for vestibular schwannomas: mechanism of hearing loss and how to preserve hearing. Adv Tech Stand Neurosurg 2016;43:3-36. PMID 26508404
- 148
- Hannan CJ, Lewis D, O’Leary C, et al. The inflammatory microenvironment in vestibular schwannoma. Neurooncol Adv 2020;2(1):vdaa023. PMID 32642684
- 149
- Hannan CJ, Lewis D, O’Leary C, et al. Increased circulating chemokines and macrophage recruitment in growing vestibular schwannomas. Neurosurg 2023;92:581-9. PMID 36729787
- 150
- Hansasuta A, Choi CY, Gibbs IC, et al. Multisession stereotactic radiosurgery for vestibular schwannomas: single-institution experience with 383 cases. Neurosurgery 2011;69(6):1200-9. PMID 21558974
- 151
- Hansen MR, Roehm PC, Chatterjee P, Green SH. Constitutive neuregulin-ErbB signaling contributes to human vestibular schwannoma proliferation. Glia 2006;15:593-600. PMID 16432850
- 152
- Hanson MB, Glasscock ME 3rd, Brandes JL, Jackson CG. Medical treatment of headache after suboccipital acoustic tumor removal. Laryngoscope 1998;108:1111-4. PMID 9707226
- 153
- Hardell L, Carlberg M. Mobile phones, cordless phones, and the risk for brain tumours. Int J Oncol 2009;35:5-17. PMID 19513546
- 154
- Hardell L, Carlberg M. Using the Hill viewpoints from 1965 for evaluating strengths of evidence of the risk for brain tumors associated with use of mobile and cordless phones. Rev Environ Health 2013;28(2-3):97-106. PMID 24192496
- 155
- Hardell L, Carlberg M. Comments on the US National Toxicology Program technical reports on toxicology and carcinogenesis study in rats exposed to whole-body radiofrequency radiation at 900 MHz and in mice exposed to whole-body radiofrequency radiation at 1900 MHz. Int J Oncol 2019;54(1):111-27. PMID 30365129
- 156
- Hardell L, Carlberg M, Soderqvist F, Hansson Mild K. Meta-analysis of long-term mobile phone use and the association with brain tumours. Int J Oncol 2008;32:1097-103. PMID 18425337
- 157
- Hardell L, Mild KH, Carlberg M, Soderqvist F. Tumour risk associated with cellular telephones or cordless desktop telephones. World J Surg Oncol 2006;4:74. PMID 17034627
- 158
- Harner SG, Beatty CW, Ebersold MJ. Retrosigmoid removal of acoustic neuroma: experience 1978-1988. Otolaryngol Head Neck Surg 1990;103:40-5. PMID 2117729
- 159
- Harner SG, Daube JR, Ebersold MJ, Beatty CW. Improved preservation of facial nerve function with use of electrical monitoring during removal of acoustic neuromas. Mayo Clin Proc 1987;62:92-102. PMID 3807440
- 160
- Harris GJ, Plotkin SR, MacCollin M, et al. Three-dimensional volumetrics for tracking vestibular schwannoma growth in neurofibromatosis type II. Neurosurg 2008;62:1314-20. PMID 18824998
- 161
- Hasegawa T, Kida Y, Kato T, Iizuka H, Kuramitsu S, Yamamoto T. Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery. J Neurosurg 2013;118(3):557-65. PMID 23140152
- 162
- Hasegawa T, Kida Y, Yoshimoto M, Koike J, Goto K. Evaluation of tumor expansion after stereotactic radiosurgery in patients harboring vestibular schwannomas. Neurosurgery 2006;58:1119-28. PMID 16723891
- 163
- Havik AL, Bruland O, Miletic H, et al. Genetic alterations associated with malignant transformation of sporadic vestibular schwannomas. Acta Neurochir (Wien) 2022;164(2):343-52. PMID 34816314
- 164
- Havik AL, Bruland O, Myrseth E, et al. Genetic landscape of sporadic vestibular schwannoma. J Neurosurg 2018;128(3):911-22. PMID 28409725
- 165
- Helal A, Graffeo CS, Perry A, et al. Differential impact of advanced age on clinical outcomes after vestibular schwannoma resection in the very elderly: cohort study. Oper Neurosurg (Hagerstown) 2021;21(3):104-10. PMID 34038941
- 166
- Henrich DE, McCabe BF, Gantz BJ. Tinnitus and acoustic neuromas: analysis of the effect of surgical excision on postoperative tinnitus. Ear Nose Throat J 1995;74:464-6. PMID 7671834
- 167
- Henschen F. Ueber Geschwulste der hintern Schadelgrube, inbesondere des Kleinhirnbruckenwinkels: klinische and anatomische Studien. Jena: Gustav Fischer, 1910.
- 168
- Hirato M, Inoue H, Nakamura M, et al. Gamma knife radiosurgery for acoustic schwannoma: early effects and preservation of hearing. Neurol Med Chir (Tokyo) 1995;35:737-41. PMID 8532129
- 169
- Hirokawa Y, Tikoo A, Hunyh J, et al. A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor. Cancer J 2004;10-20-6. PMID 15000491
- 170
- Hirsch A, Noren G. Audiological findings after stereotactic radiosurgery in acoustic neurinomas. Acta Otolaryngol 1988;106:244-51. PMID 3051887
- 171
- Ho SY, Hudgens S, Riet RJ. Comparison of postoperative facial nerve outcomes between translabyrinthine and retrosigmoid approaches in matched-pair patients. Laryngoscope 2003;113:2014-20. PMID 14603066
- 172
- Hong B, Krusche CA, Schwabe K, et al. Cyclooxygenase-2 supports tumor proliferation in vestibular schwannomas. Neurosurg 2011; 68(4):1112-7. PMID 21221032
- 173
- House WF, Hitselberger WE. The neurotologists view of the surgical management of acoustic neuromas. Clin Neurosurg 1985;32:214-22. PMID 3905138
- 174
- Huang B, Ren Y, Liu X, et al. Does preoperative gamma knife treatment affect the result of microresection of vestibular schwannoma? J Neurooncol 2022;160(2):321-9. PMID 36316569
- 175
- Huang MJ, Kano H, Mousavi SH, et al. Stereotactic radiosurgery for recurrent vestibular schwannoma after previous resection. J Neurosurg 2017;126(5):1506-13. PMID 27471891
- 176
- Huang X, Caye-Thomasen P, Stangerup SE. Spontaneous tumour shrinkage in 1261 observed patients with sporadic vestibular schwannoma. J Laryngol Otol 2013;127(8):739-43. PMID 23866680
- 177
- Huang X, Xu J, Shen Y, et al. Protein profiling of cerebrospinal fluid from patients undergoing vestibular schwannoma surgery and clinical significance. Biomed Pharmacother 2019;116:108985. PMID 31146115
- 178
- Hudgins WR. Patients' attitude about outcomes and the role of gamma knife radiosurgery in the treatment of vestibular schwannomas. Neurosurgery 1994;34:459-65. PMID 8190221
- 179
- Hunter JB, Dowling EM, Lohse CM, et al. Hearing outcomes in conservatively managed vestibular schwannoma patients with serviceable hearing. Otol Neurotol 2018;39(8):e704-11. PMID 30036205
- 180
- Hunter JB, Francis DO, O’Connell BP, et al. Single institutional experience with observing 564 vestibular schwannomas: factors associated with tumor growth. Otol Neurotol 2016;37(10):1630-6. PMID 27668793
- 181
- Hunter JB, O’Connell BP, Wanna GB, et al. Vestibular schwannoma growth with aspirin and other nonsteroidal anti-inflammatory drugs. Otol Neurotol 2017;38:1158-64. PMID 28692590
- 182
- Huo M, Foley H, Pinkham M, et al. Stereotactic radiotherapy for large vestibular schwannomas: volume change following single fraction versus hypofractionated approaches. J Radiosurg SBRT 2020;7:11-7. PMID 32802574
- 183
- Husseini ST, Piccirillo E, Taibah A, Almutair T, Sequino G, Sanna M. Salvage surgery of vestibular schwannoma after failed radiosurgery: the Gruppo Otologico experience and review of the literature. Am J Otolaryngol 2013;34(2):107-14. PMID 23177377
- 184
- Hwang SK, Kim DG, Paek SH, et al. Aggressive vestibular schwannomas with postoperative rapid growth: clinicopathological analysis of 15 cases. Neurosurgery 2002;51:1381-91. PMID 12445343
- 185
- Iannella G, de Vincentiis M, Di Gioia C, et al. Subtotal resection of vestibular schwannoma: evaluation with Ki-67 measurement, magnetic resonance imaging, and long-term observation. J Int Med Res 2017;45(3):1061-73. PMID 28447494
- 186
- INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol 2010;39(3):675-94. PMID 20483835
- 187
- Iorio-Morin C, Liscak R, Vladyka V, et al. Repeat stereotactic radiosurgery for progressive or recurrent vestibular schwannomas. Neurosurg 2019;85(4):535-42. PMID 30189018
- 188
- Irving RM, Harada T, Moffat DA, et al. Somatic neurofibromatosis type 2 gene mutations and growth characteristics in vestibular schwannoma. Am J Otol 1997;18:754-60. PMID 9391673
- 189
- Irving RM, Jackler RK, Pitts LH. Hearing preservation in patients undergoing vestibular schwannoma surgery: comparison of middle fossa and retrosigmoid approaches. J Neurosurg 1998;88:840-5. PMID 9576251
- 190
- Irving RM, Moffat DA, Hardy DG, Barton DE, Xuereb JH, Maher ER. Somatic NF2 mutations in familial and non-familial vestibular schwannoma. Hum Mol Gen 1994;3:347-50. PMID 8004107
- 191
- Ito K, Kurita H, Sugasawa K, Mizuno M, Sasaki T. Analyses of neuro-otological complications after radiosurgery for acoustic neurinomas. Int J Radiat Oncol Biol Phys 1997;39:983-8. PMID 9392535
- 192
- Ito K, Shin M, Matsuzaki M, Sugasawa K, Sasaki T. Risk factors for neurological complications after acoustic neuroma radiosurgery: refinement from further experiences. Int J Radiat Oncol Biol Phys 2000;48:75-80. PMID 10924974
- 193
- Iwai Y, Yamanaka K, Shiotani M, Uyama T. Radiosurgery for acoustic neuromas: Results of low-dose treatment. Neurosurgery 2003;53:282-8. PMID 12925242
- 194
- Jackler RK, Pitts LH. Selection of surgical approach to acoustic neuroma. Otolaryngol Clin North Am 1992;25:361-87. PMID 1630834
- 195
- Jacob A, Oblinger J, Bush ML, et al. Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas. Laryngoscope 2012;122(1):174-89. PMID 22109824
- 196
- Jacob JT, Carlson ML, Schiefer TK, Pollock BE, Driscoll CL, Link MJ. Significance of cochlear dose in the radiosurgical treatment of vestibular schwannoma: controversies and unanswered questions. Neurosurgery 2014;74(5):466-74. PMID 24476904
- 197
- Johnson S, Kano H, Faramand A, et al. Long term results of primary radiosurgery for vestibular schwannomas. J Neurooncol 2019b;145(2):247-55. PMID 31535315
- 198
- Johnson S, Kano H, Faramand A, Niranjan A, Flickinger JC, Lunsford LD. Predicting hearing outcomes before primary radiosurgery for vestibular schwannomas. J Neurosurg 2019a:1-7. PMID 31491764
- 199
- Jones KD. Summary: vestibular schwannoma consensus development conference [letter]. Neurosurgery 1993;32:878. PMID 8492871
- 200
- Jufas N, Flanagan S, Biggs N, Chang P, Fagan P. Quality of life in vestibular schwannoma patients managed by surgical or conservative approaches. Otol Neurotol 2015;36(7):1245-54. PMID 26075673
- 201
- Kalogeridi MA, Kougioumtzopoulou A, Zygogianni A, Kouloulias V. Stereotactic radiosurgery and radiotherapy for acoustic neuromas. Neurosurg Rev 2020;43(3):941-9. PMID 30982152
- 202
- Kameda K, Shono T, Hashiguchi K, Yoshida F, Sasaki T. Effect of tumor removal on tinnitus in patients with vestibular schwannoma. J Neurosurg 2010;112(1):152-7. PMID 19480542
- 203
- Kandathil CK, Cunnane ME, McKenna MJ, Curtin HD, Stankovic KM. Correlation between aspirin intake and reduced growth of human vestibular schwannoma: volumetric analysis. Otol Neurotol 2016;37(9):1428-34. PMID 27631829
- 204
- Kandathil CK, Dilwali S, Wu CC, et al. Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in vivo. Otol Neurotol 2014;35(2):353-7. PMID 24448296
- 205
- Kaplan JC, Aurius A, Julier C, Prieur M, Szajnert MF. Human chromosome 22. J Med Genet 1987;24:65-78. PMID 3550088
- 206
- Karpinos M, Teh BS, Zeck O, et al. Treatment of acoustic neuroma: stereotactic radiosurgery vs. microsurgery. Int J Radiat Oncol Biol Phys 2002;54:1410-21. PMID 12459364
- 207
- Kaylie DM, McMenomey SO. Microsurgery vs Gamma Knife radiosurgery for the treatment of vestibular schwannomas. Arch Otolaryngol Head Neck Surg 2003;129:903-6. PMID 12925354
- 208
- Kehrer-Sawatzki H, Farschtschi S, Mautner VF, Cooper DN: The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis. Hum Genet 2017;136(2):129-48. PMID 27921248
- 209
- Kemink JL, LaRouere MJ, Kileny PR, Telian SA, Hoff JT. Hearing preservation following suboccipital removal of acoustic neuromas. Laryngoscope 1990;100:597-602. PMID 2348738
- 210
- Kenan PD. Tumors of the cerebellopontine angle: neurotologic aspects of diagnosis. In: Wilkins RH, Rengachary SS, editors. Neurosurgery. New York: McGraw-Hill, 1985:698-704.
- 211
- Kesterson L, Shelton C, Dressler L, Berliner KI. Clinical behavior of acoustic tumors. Arch Otolaryngol Head Neck Surg 1993;119:269-71. PMID 8435163
- 212
- Khandalavala KR, Marinelli JP, Lohse CM, et al. Natural history of serviceable hearing during active surveillance of not growing sporadic vestibular schwannoma supports consideration of initial wait and see management. Otol Neurotol 2024;45:e42-8. PMID 38085766
- 213
- Khandalavala KR, Saba ES, Kocharyan A, et al. Hearing preservation in observed sporadic vestibular schwannoma: a systematic review. Otol Neurotol 2022;43(6):604-10. PMID 35261385
- 214
- Khattab MH, Newman MB, Wharton DM, et al. Longitudinal radiographic outcomes of vestibular schwannoma in single and fractionated stereotactic radiosurgery: a retrospective cohort study. J Neurol Surg B Skull Base 2020;81(3):308-16. PMID 32500007
- 215
- Khattab MH, Sherry AD, Whitaker R, et al. A retrospective cohort study of longitudinal audiologic assessment in single and fractionated stereotactic radiosurgery for vestibular schwannoma. Neurosurgery 2019;85(6):E1078-83. PMID 31215628
- 216
- Kida Y, Kobayashi T, Tanaka T, Mori Y. Radiosurgery for bilateral neurinomas associated with neurofibromatosis type 2. Surg Neurol 2000;53:383-89. PMID 10825525
- 217
- Kilicarslan R, Alkan A, Aralasmak A, et al. Magnetic resonance spectroscopy features of Heschl’s gyri in patients with unilateral acoustic neuroma: preliminary study. Acad Radiol 2014;21(12):1501-5. PMID 25172413
- 218
- Killeen DE, Klesse L, Tolisano AM, Hunter JB, Kutz JW Jr. Long-term effects of bevacizumab on vestibular schwannoma volume in neurofibromatosis type 2 patients. J Neurol Surg B Skull Base 2019;80(5):540-6. PMID 31534897
- 219
- Kim DH, Lee S, Hwang SH. Non-contrast magnetic resonance imaging for diagnosis and monitoring of vestibular schwannomas: a systematic review and meta-analysis. Otol Neurotol 2019;40(9):1126-33. PMID 31469788
- 220
- Kim HJ, Jin Roh K, Oh HS, Chang WS, Moon IS. Quality of life in patients with vestibular schwannomas according to management strategy. Otol Neurotol 2015;36(10):1725-9. PMID 26529056
- 221
- Kissil JL, Johnson KC, Eckman MS, Jacks T. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J Biol Chem 2002;277(12):10394-9. PMID 11782491
- 222
- Kluwe L, Mautner V, Heinrich B, et al. Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 2003;40:459-63. PMID 12566519
- 223
- Kocharyan AH, Briggs S, Cosetti MK, Heman-Ackah SM, Golfinos JG, Roland JT Jr. Atypical schwannoma: a 10-year experience. Am J Otolaryngol 2020;41(1):102309. PMID 31727334
- 224
- Kocharyan A, Daher GS, Curry SD, et al. Outcomes of near-total and subtotal resection of sporadic vestibular schwannoma: A systematic review and meta-analysis. Otolaryngol Head Neck Surg 2024;171(3):642-57. PMID 38822753
- 225
- Koester SW, Bishay AE, Rogers JL, et al. Cost considerations for vestibular schwannoma screening and imaging: a systematic review. Neurosurg Rev 2024;47:59. PMID 38252395
- 226
- Koetsier KS, Hensen EF, Niemierko A, et al. Outcome and toxicity of proton therapy for vestibular schwannoma: a cohort study. Otol Neurotol 2021;42(10):1560-71. PMID 34538850
- 227
- Kondziolka D, Lunsford LD. Preservation of hearing in acoustic neurinoma surgery. J Neurosurg 1993;8:154-6. PMID 8416234
- 228
- Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. Long term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 1998;339:1426-33. PMID 9811917
- 229
- Kontorinis G, Nichani J, Freeman SR, et al. Progress of hearing loss in neurofibromatosis type 2: implications for future management. Eur Arch Otorhinolaryngol 2015;272(11):3143-50. PMID 25294053
- 230
- Koos W, Perneczky A. Suboccipital approach to acoustic neurinomas with emphasis on preservation of facial nerve and cochlear nerve function. In: Rand RW, editor. Microneurosurgery. St. Louis: Mosby, 1985:335-65.
- 231
- Koos WT, Matula Ch, Levy D, Kitz K. Microsurgery versus radiosurgery in the treatment of small acoustic neuromas. Acta Neurochir Suppl (Wien) 1995;63:73-80. PMID 7502733
- 232
- Koutsimpelas D, Bjelopavlovic M, Yetis R, et al. The VEGF/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence. ORL J Otorhinolaryngol Relat Spec 2012a;74(6):330-8. PMID 23344215
- 233
- Koutsimpelas D, Ruerup G, Mann WJ, Brieger J. Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas. ORL J Otorhinolaryngol Relat Spec 2012b;74:33-7. PMID 22249120
- 234
- Krieg SM, Kempf L, Droese D, Rosahl SK, Meyer B, Lehmberg J. Superiority of tympanic ball electrodes over mastoid needle electrodes for intraoperative monitoring of hearing function. J Neurosurg 2014;120(5):1042-7. PMID 24559226
- 235
- Kundi M. The controversy about a possible relationship between mobile phone use and cancer. Environ Health Perspect 2009;117:316-24. PMID 19337502
- 236
- Kundi M, Mild K, Hardell L, Mattsson MO. Mobile telephones and cancer--a review of epidemiological evidence. J Toxicol Environ Health B Crit Rev 2004;7(5):351-84. PMID 15371240
- 237
- Kuo TC, Jackler RK, Wong K, Blevins NH, Pitts LH. Are acoustic neuromas encapsulated tumors. Otolaryngol Head Neck Surg 1997;117:606-9. PMID 9419086
- 238
- Lagorio S, Roosli M. Mobile phone use and risk of intracranial tumors: a consistency analysis. Bioelectromagnetics 2014;35(2):79-90. PMID 24375548
- 239
- Lalwani AK. Meningiomas, epidermoids, and other nonacoustic tumors of the cerebellopontine angle. Otolaryngol Clin North Am 1992;25:707-28. PMID 1625871
- 240
- Lalwani AK, Butt FY, Jackler RK, Pitts LH, Yingling CD. Facial nerve outcome after acoustic neuroma surgery: a study from the era of cranial nerve monitoring. Otolaryngol Head Neck Surg 1994;11:561-70. PMID 7970793
- 241
- Langenhuizen PPJH, Zinger S, Hanssens PEJ, et al. Influence of pretreatment growth rate on Gamma Knife treatment response for vestibular schwannoma: a volumetric analysis. J Neurosurg 2018:1-8. PMID 30497177
- 242
- Lasak JM, Welling DB, Akhmametyeva EM, Salloum M, Chang LS. Retinoblastoma-cyclin-dependent kinase pathway deregulation in vestibular schwannomas. Laryngoscope 2002;112:1555-61. PMID 12352662
- 243
- Lassaletta L, Torres-Martin M, Pena-Granero C, et al. NF2 genetic alterations in sporadic vestibular schwannomas: clinical implications. Otol Neurotol 2013;34(7):1355-61. PMID 23921927
- 244
- Lau T, Olivera R, Miller T Jr, et al. Paradoxical trends in the management of vestibular schwannoma in the United States. J Neurosurg 2012;117(3):514-9. PMID 22725981
- 245
- Lee DJ, Westra WH, Staecker H, Long D, Niparko JK, Slattery WH 3rd. Clinical and histopathologic features of recurrent vestibular schwannoma (acoustic neuroma) after stereotactic radiosurgery. Otol Neurotol 2003;24:650-60. PMID 12851560
- 246
- Lee JD, Kwon TJ, Kim UK, Lee WS. Genetic and epigenetic alterations in the NF2 gene in sporadic vestibular schwannomas. PLoS One 2012;7(1):e30418. PMID 22295085
- 247
- Lees KA, Tombers NM, Link MJ, et al. Natural history of sporadic vestibular schwannoma: A volumetric study of tumor growth. Otollaryngol Head Neck Surg 2018;159(3):535-42. PMID 29685084
- 248
- Li SL, Ma XH, Ji JF, et al. miR-1 association with cell proliferation inhibition and apoptosis in vestibular schwannoma by targeting VEGFA. Genet Mol Res 2016;15(4). PMID 27819721
- 249
- Limb CJ, Long DM, Niparko JK. Acoustic neuromas after failed radiation therapy: challenges of surgical salvage. Laryngoscope 2005;115(1):93-8. PMID 15630374
- 250
- Lin RH, Wang TC, Lin CD, et al. Predictors of hearing outcomes following low-dose stereotactic radiosurgery in patients with vestibular schwannomas: a retrospective cohort review. Clin Neurol Neurosurg 2017;162:16-21. PMID 288892717
- 251
- Linskey ME, Johnstone PA, O’Leary M, Goetsch S. Radiation exposure of normal temporal bone structures during stereotactically guided gamma knife surgery for vestibular schwannomas. J Neurosurg 2013;119:S800-6. PMID 25077324
- 252
- Linskey ME, Lunsford LD, Flickinger JC. Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors. Neurosurgery 1992;31:829-39. PMID 1436407
- 253
- Lo A, Avre G, Ma R, et al. Population-based study of stereotactic radiosurgery or fractionated stereotactic radiation therapy for vestibular schwannoma: long-term outcomes and toxicities. Int J Radiat Oncol Phys 2018;100(2):443-51. PMID 29066124
- 254
- Long J, Zhang Y, Huang X, Ren J, Zhong P, Wang B. A review of drug therapy in vestibular schwannoma. Drug Des Devel Ther 2021;15:75-85. PMID 33447015
- 255
- Longino ES, Manzoor NF, Cass ND, et al. Cochlear implantation outcomes in observed vestibular schwannoma: a preliminary report. Otolaryngol Head Neck Surg 2022;167(1):149-54. PMID 34546801
- 256
- Lonn S, Ahlbom A, Hall P, Feychting M. Mobile phone use and the risk of acoustic neuroma. Epidemiology 2004;15(6):653-9. PMID 15475713
- 257
- Lownie SP, Drake CG. Radical intracapsular removal of acoustic neurinomas. J Neurosurg 1991;74:422-5. PMID 1993907
- 258
- Lu VM, Ravindran K, Graffeo CS, et al. Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes. J Neuroncol 2019;144(2):239-48. PMID 31254266
- 259
- Lunsford LD, Niranjan A, Flickinger JC, Maitz A, Kondziolka D. Radiosurgery of vestibular schwannomas: summary of experience in 829 cases. J Neurosurg 2013;119:S195-9. PMID 25077305
- 260
- Luryi AL, Babu S, Bojrab DI, Kveton JF, Schutt CA. Progression of hearing loss in observed non-growing vestibular schwannoma. Otol Neurotol 2022;43(7):e767-72. PMID 35763454
- 261
- Luryi AL, Babu S, Bojrab DI, Kveton JF, Schutt CA. Surgical outcomes after conservative resection of vestibular schwannoma in the elderly. Otol Neurotol 2021;42(9):e1358-61. PMID 34172668
- 262
- Luryi AL, Michaelides EM, Babu S, et al. Reliability of clinical diagnosis of masses of the cerebellopontine angle: a retrospective multi-institutional study. Am J Otolaryngol 2019;40(2):133-6. PMID 30717992
- 263
- Macfarlane R, King TT. Acoustic neurinomas (vestibular schwannoma). In: Kaye AH, Laws ER, editors. Brain tumors. An encyclopedic approach. Edinburgh: Churchill Livingstone, 1995;31:577-622.
- 264
- Macielak RJ, Wallerius KP, Lawlor SK, et al. Defining clinically significant tumor size in vestibular schwannoma to inform timing of microsurgery during wait-and-scan management: moving beyond minimum detectable growth. J Neurosurg 2021:1-9. PMID 34653971
- 265
- Mafee MF. MR imaging of intralabyrinthine schwannoma, labyrinthitis, and other labyrinthine pathology. Otolaryngol Clin North Am 1995;28:407-30. PMID 7675462
- 266
- Malina GEK, Heiferman DM, Riedy LN, et al. Pediatric vestibular schwannomas: case series and a systematic review with meta-analysis. J Neurosurg Pediatr 2020;26(3):302-10 PMID 32470932
- 267
- Marchioni D, Alicandri-Ciufelli M, Rubini A, Masotto B, Pavesi G, Presutti L. Exclusive endoscopic transcanal transpromontorial approach: new perspective for internal auditory canal vestibular schwannoma treatment. J Neurosurg 2017;126(1):98-105. PMID 26967786
- 268
- Marchioni D, Carner M, Soloperto D, et al. Expanded transcanal transpromontorial approach: A novel surgical technique for cerebellopontine angle vestibular schwannoma removal. Otolaryngol Head Neck Surg 2018;158(3):710-5. PMID 29405836
- 269
- Marinelli JP, Beeler CJ, Carlson ML, et al. Global incidence of sporadic vestibular schwannoma: a systematic review. Otolaryngol Head Neck Surg 2022;167(2):209-14. PMID 34464224
- 270
- Marinelli JP, Carlson ML, Hunter JB, et al. Natural history of growing sporadic vestibular schwannomas during observation: an international multi-institutional study. Otol Neurotol 2021;42(8):e1118-24. PMID 34121081
- 271
- Marinelli JP, Herberg HA, Moore LS, et al. Salvage microsurgery following failed primary radiosurgery in sporadic vestibular schwannoma. JAMA Otolaryngol Head Neck Surg 2024;150:287-94. PMID 38358763
- 272
- Marinelli JP, Lees KA, Lohse CM, et al. Natural history of growing sporadic vestibular schwannomas: an argument for continued observation despite documented growth in selective cases. Otol Neurotol 2020;41(9):e1149-53. PMID 32925859
- 273
- Marinelli JP, Lohse CM, Carlson ML. Introducing an evidence-based approach to wait-and-scan management of sporadic vestibular schwannoma: size threshold surveillance. Otolaryngol Clin North Am 2023;56:445-57. PMID 37019767
- 274
- Marston AP, Jacob JT, Carlson ML, Pollock BE, Driscoll CL, Link MJ. Pretreatment growth rate as a predictor of tumor control following Gamma Knife radiosurgery for sporadic vestibular schwannoma. J Neurosurg 2017;127(2):380-7. PMID 27885952
- 275
- Martin TP, Tzifa K, Kowalski C, Holder RL, Walsh R, Irving RM. Conservative versus primary surgical treatment of acoustic neuromas: a comparison of rates of facial nerve and hearing preservation. Clin Otolaryngol 2008;33:228-35. PMID 18559028
- 276
- Martuza RL, Eldridge R. Neurofibromatosis 2. N Engl J Med 1988;318:684-8. PMID 3125435
- 277
- Massaad EL, Hamidi N, Goetz J, et al. Equivalent efficacy and safety of radiosurgery for cystic and solid vestibular schwannomas: a systematic review. World Neurosurg 2021;146:322-31. PMID 33212274
- 278
- Massager N, NIssim O, Delbrouck C, et al. Irradiation of cochlear structures during vestibular schwannoma radiosurgery and associated hearing outcome. J Neurosurg 2013;119:S733-9. PMID 25077314
- 279
- Matsunaga T, Kanzaki J, Igarashi M. The limitations of hearing preservation in acoustic neuroma surgery: histological study of the interface between the eighth cranial nerve and the tumor. Acta Otolaryngol 1995;115:269-72. PMID 7610819
- 280
- Matthies C, Samii M. Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation. Neurosurgery 1997a;40:1-10. PMID 8971818
- 281
- Matthies C, Samii M. Management of vestibular schwannomas (acoustic neuromas): the value of neurophysiology for intraoperative monitoring of auditory function in 200 cases. Neurosurgery 1997b;40:459-68. PMID 9055284
- 282
- Mautner VF, Baser ME, Thakkar SD, Feigen UM, Friedman JM, KluweL. Vestibular schwannoma growth in patients with neurofibromatosis Type 2: a longitudinal study. J Neurosurg 2002;96:223-8. PMID 11838794
- 283
- Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol 2010;12(1):14-8. PMID 20150363
- 284
- Mazzoni A, Calabrese V, Moschini L. Residual and recurrent acoustic neuroma in hearing preservation procedures: neuroradiologic and surgical findings. Skull Base Surg 1996;62:105-12. PMID 17170984
- 285
- McClatchey A, Fehon RG. Merlin and the ERM proteins – regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol 2009;19(5):198-206. PMID 19345106
- 286
- McClelland S III, Kim E, Murphy JD, Jaboin JJ. Operative mortality rates of acoustic neuroma surgery: a national cancer database analysis. Otol Neurotol 2017;38(5):751-3. PMID 28187056
- 287
- McKenzie JD. Magnetic resonance imaging of cerebellopontine angle masses. BNI Q 1994;10:9-18.
- 288
- McWilliams W, Trombetta M, Werts ED, Fuhrer R, Hilliman T. Audiometric outcomes for acoustic neuroma patients after single versus multiple fraction stereotactic irradiation. Otol Neurotol 2011;32(2):297-300. PMID 21192276
- 289
- Mehta GU, Feldman MJ, Wang H, Ding D, Chittiboina P. Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation. J Neurosurg 2016;125(6):1469-71. PMID 26848914
- 290
- Meijer OW, Vandertop WP, Baayen JC, Slotman BJ. Single-fraction vs. fractionated linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study. Int J Rad Oncol Biol Phys 2003;56:1390-6. PMID 12873685
- 291
- Meijer OW, Wolbers JG, Baayen JC, Slotman BJ. Fractionated stereotactic radiation therapy and single high dose radiosurgery for acoustic neuroma: early results of a prospective clinical study. Int J Radiat Oncol Biol Phys 2000;46:45-9. PMID 10656371
- 292
- Mendenhall WM, Friedman WA, Bova FJ. Linear accelerator based stereotactic radiosurgery for acoustic schwannomas. Int J Radiat Oncol Biol Phys 1994;28:803-10. PMID 8138432
- 293
- Metwali H, Samii M, Samii A, Gerganov V. The peculiar cystic vestibular schwannoma: a single-center experience. World Neurosurg 2014;82(6):1271-5. PMID 25045792
- 294
- Michael S. Can you hear me now. Sci Am 2010;303(4):98. PMID 20923137
- 295
- Miller AB, Sears ME, Morgan LL, et al. Risks to health and well-being from radio-frequency radiation emitted by cell phones and other wireless devices. Front Public Health 2019;7:223. PMID 31457001
- 296
- Miller C, Igarashi S, Jacob A. Molecular pathogenesis of vestibular schwannomas: insights for the development of novel medical therapies. Otolaryngol Pol 2012;66(2):84-95. PMID 22500497
- 297
- Miller NR. Tumors of cranial and peripheral nerves. In: Miller NR, editor. Walsh and Hoyt's clinical neuro-ophthalmology. Vol. 3. 4th ed. Baltimore: Williams & Wilkins, 1988;50:1543-67.
- 298
- Moffat DA, Baguley DM, Beynon GJ, Da Cruz M. Clinical acumen and vestibular schwannoma. Am J Otol 1998;19:82-7. PMID 9455955
- 299
- Moffat DA, Baguley DM, von Blumenthal H, Irving RM, Hardy DG. Sudden deafness in vestibular schwannoma. J Laryngol Otol 1994;108:116-9. PMID 8163910
- 300
- Momoli F, Siemiatycki J, McBride ML, et al. Probabilistic multiple-bias modeling applied to the Canadian data from the Interphone Study of Mobile Phone Use and risk of glioma, meningioma, acoustic neuroma, and parotid gland tumors. Am J Epidemiol 2017;186(7):885-93. PMID 28535174
- 301
- Monfared A, Corrales CE, Theodosopoulos PV, et al. Facial nerve outcome and tumor control rate as a function of degree of resection in treatment of large acoustic neuromas: preliminary report of the acoustic neuroma subtotal resection study (ANSRS). Neurosurgery 2016;79(2):194-203. PMID 26645964
- 302
- Monsell EM, Cody DD, Spickler E, Windham JP. Segmentation of acoustic neuromas with magnetic resonance imaging and Eigen image filtering. Am J Otol 1997;18:602-7. PMID 9303157
- 303
- Morrison D. Management of patients with acoustic neuromas: a Markov decision analysis. Laryngoscope 2010;120(4):783-90. PMID 20213657
- 304
- Moulin G, Dessi P, Andre P, et al. Role of magnetic resonance imaging in predicting late facial motor function after removal of vestibular schwannomas by the translabyrinthine approach. J Laryngol Otol 1995;109(5):394-8. PMID 7797994
- 305
- Moyhuddin A, Baser ME, Watson C, et al. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 2003;40:459-63. PMID 12807969
- 306
- Mrak RE, Flanigan S, Collins CL. Malignant acoustic schwannoma. Arch Pathol Lab Med 1994;118:557-61. PMID 8192564
- 307
- Mulkens TH, Parizel PM, Martin JJ, et al. Acoustic schwannoma: MR findings in 84 tumors. AJR Am J Roentgenol 1993;160:395-8. PMID 8424360
- 308
- Muscat JE, Malkin MG, Shore RE, et al. Handheld cellular telephones and risk of acoustic neuroma. Neurology 2002;58:1304-6. PMID 11971109
- 309
- Myrseth E, Moller P, Pedersen PH, Lund-Johansen M. Vestibular schwannoma: surgery or gamma knife radiosurgery. A prospective, nonrandomized study. Neurosurgery 2009;64(4):654-61. PMID 19197222
- 310
- Myrseth E, Moller P, Pedersen PH, Vassbotn FS, Wentzel-Larsen T, Lund-Johansen M. Vestibular schwannomas: Clinical results and quality of life after microsurgery or gamma knife radiosurgery. Neurosurgery 2005;56:927-35. PMID 15854240
- 311
- Naessens B, Gordts F, Clement PA, Buisseret T. Re-evaluation of the ABR in the diagnosis of CPA tumors in the MRI-era. Acta Otorhinolarygol Belg 1996;50:99-102. PMID 8767252
- 312
- Nagano O, Higuchi Y, Serizawa T, et al. Transient expansion of vestibular schwannoma following stereotactic radiosurgery. J Neurosurg 2008;109:811-6. PMID 18976069
- 313
- Nakamizo A, Mori M, Inoue D, et al. Long-term hearing outcome after retrosigmoid removal of vestibular schwannoma. Neurol Med Chir (Tokyo) 2013;53(10):688-94. PMID 24077269
- 314
- Nakatomi H, Jacob JT, Carlson ML, et al. Long-term risk of recurrence and regrowth after gross-total and subtotal resection of sporadic vestibular schwannoma. J Neurosurg 2017:1-7. PMID 28524795
- 315
- National Institute of Health Consensus Statement. Acoustic neuroma. Vol. 9. 1991.
- 316
- Nedzelski JM, Chiong CM, Cashman MZ, Stanton SG, Rowed DW. Hearing preservation in acoustic neuroma surgery: value of monitoring cochlear nerve action potentials. Otolaryngol Head Neck Surg 1994;111:703-9. PMID 7991247
- 317
- Nedzelski JM, Schessel DA, Pfleiderer A, Kassel EE, Rowed DW. Conservative management of acoustic neuromas. Otolaryngol Clin North Am 1992;25:691-705. PMID 1625870
- 318
- Newton HB. Primary brain tumors: review of etiology, diagnosis, and treatment. Am Fam Physician 1994;49:787-97. PMID 8116514
- 319
- Nguyen T, Duong C, Sheppard JP, et al. Hypo-fractionated stereotactic radiotherapy of five fractions with linear accelerator for vestibular schwannomas: A systematic review and meta-analysis. Clin Neurol Neurosurg 2018;166:116-23. PMID 29414150
- 320
- Nikolopoulos TP, Johnson I, O'Donoghue GM. Quality of life after acoustic neuroma surgery. Laryngoscope 1998;108:1382-5. PMID 9738762
- 321
- Niranjan A, Mathieu D, Flickinger JC, Kondziolka D, Lunsford LD. Hearing preservation after intracanalicular vestibular schwannoma radiosurgery. Neurosurg 2008;63:1054-63. PMID 19057318
- 322
- Ogino A, Long H, Johnson S, et al. Useful hearing preservation is improved in vestibular schwannoma patients who undergo stereotactic radiosurgery before hearing deterioration ensues. J Neurooncol 2021b;152(3):559-66. PMID 33733428
- 323
- Ogino A, Lunsford LD, Long H, et al. Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas. J Neurosurg 2021a;135(4):1051-7. PMID 34600434
- 324
- Ogino A, Lunsford LD, Long H, et al. Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas. J Neurosurg 2021c;135(4):1058-66. PMID 33578383
- 325
- Ogunrinde OK, Lunsford LD, Flickinger JC, Kondziolka D. Facial nerve preservation and tumor control after gamma knife radiosurgery of unilateral acoustic tumors. Skull Base Surg 1994a;4:87-92. PMID 17170933
- 326
- Ogunrinde OK, Lunsford LD, Flickinger JC, Kondziolka D. Stereotactic radiosurgery for acoustic nerve tumors in patients with useful preoperative hearing: results at 2-year follow-up examination. J Neurosurg 1994b;80:1011-7. PMID 8189256
- 327
- Oh T, Nagasawa DT, Fong BM, et al. Intraoperative neuromonitoring techniques in the surgical management of acoustic neuromas. Neurosurg Focus 2012;33(3):E6. PMID 22937857
- 328
- Okada T, Lopez-Lago M, Giancotti FG. Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane. J Cell Biol 2005;171(2):361-71. PMID 16247032
- 329
- Okada T, You L, Giancotti FG. Shedding light on Merlin’s wizardry. Trends Cell Biol 2007;17(5):222-9. PMID 17442573
- 330
- Okazaki M, Nishisho I, Tateishi H, et al. Loss of genes on the long arm of chromosome 22 in human meningiomas. Mol Biol Med 1988;5:15-22. PMID 2897611
- 331
- Palavani LB, Batista S, Andreao FF, et al. Retrosigmoid versus middle fossa approach for hearing and facial nerve preservation and vestibular schwannoma surgery: A systematic review and comparative meta-analysis. J Clin Neurosci 2024;124:1-14. PMID 38615371
- 332
- Park MJ, Ahn JH, Park JH, Chung JW, Kang WS. Diagnostic validity of auditory brainstem response for the initial screening of vestibular schwannoma. J Audiol Otal 2022;26(1):36-42. PMID 34706492
- 333
- Parnes LS, McClure JA. Posterior semicircular canal occlusion in the normal hearing ear. Otolaryngol Head Neck Surg 1991;104:52-7. PMID 1900630
- 334
- Parry DM, MacCollin MM, Kaiser-Kupfer MI, et al. Germline mutations in the neurofibromatosis 2 gene, correlations with disease severity and retinal abnormalities. Am J Hum Genet 1996;59(3):529-39. PMID 8751853
- 335
- Passier L, Doherty D, Smith J, McPhail SM. Vestibular rehabilitation following the removal of acoustic neuroma: a systematic review of randomized trials. Head Neck Oncol 2012;4(2):59.
- 336
- Patel KS, Ng E, Kaur T, et al. Increased cochlear radiation dose predicts delayed hearing loss following both stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannoma. J Neurooncol 2019;145(2):329-37. PMID 31552587
- 337
- Patel MA, Marciscano AE, Hu C, et al. Long-term treatment response and patient outcomes for vestibular schwannoma patients treated with hypofractionated stereotactic radiotherapy. Front Oncol 2017;7:200. PMID 28929084
- 338
- Patel NS, Van Abel KM, Link MJ, et al. Prevalence and surgical implications of dural enhancement at the porus acusticus in vestibular schwannomas. Otolaryngol Head Neck Surg 2016;155(6):1021-7. PMID 27703093
- 339
- Patel TR, Chiang VL. Secondary neoplasms after stereotactic radiosurgery. World Neurosurg 2014;81(3-4):594-9. PMID 24148883
- 340
- Pellet W, Emram B, Cannoni M, Pech A, Zanaret M, Thomassin M. Les resultats fonctionnels de la chirurgid des neurinomes de l'acoustique unilateraux. Neurochirurgie 1993;39:24-41. PMID 8377882
- 341
- Perry A, Graffeo CS, Carlstrom LP, et al. Predominance of M1 subtype among tumor-associated macrophages in phenotypically aggressive sporadic vestibular schwannoma. J Neurosurg 2020;133:1635. PMID 31585433
- 342
- Persson O, Bartek J Jr, Shalom NB, Wangerid T, Jakola AS, Forander P. Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in vestibular schwannoma patients: a systematic review. Acta Neurochir (Wien) 2017;159(6):1013-21. PMID 28409393
- 343
- Pettersson D, Mathiesen T, Prochazka M, et al. Long-term mobile phone use and acoustic neuroma risk. Epidemiology 2014;25(2):233-41. PMID 24434752
- 344
- Peyre M, Goutagny S, Bah A, et al. Conservative management of bilateral vestibular schwannomas in neurofibromatosis type 2 patients: hearing and tumor growth results. Neurosurgery 2013;72(6):907-14. PMID 23407292
- 345
- Pieper DR. The endoscopic approach to vestibular schwannomas and posterolateral skull base pathology. Otolaryngol Clin North Am 2012;45(2):439-54. PMID 22483826
- 346
- Pikis S, Mantziaris G, Anand RK, et al. Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a multi-institutional study. J Neurosurg 2022;138(2):405-12. PMID 36303474
- 347
- Pizzini FB, Sarno A, Boscolo Galazzo I, et al. Usefulness of high resolution T2-weighted images in the evaluation and surveillance of vestibular schwannomas? Is gadolinium needed? Otol Neurotol 2020;41(1):e103-10. PMID 31789801
- 348
- Plotkin SR, Allen J, Dhall G, et al. Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF 2 related schwannomatosis and progressive vestibular schwannoma. Neuro Oncol 2023;25:1498-506. PMID 37010875
- 349
- Plotkin SR, Halpin C, McKenna MJ, Loeffler JS, Batchelor TT, Barker FG 2nd. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol 2010;31(7):1135-1143. PMID 20736812
- 350
- Plotkin SR, Singh MA, O’Donnell CC, Harris GJ, McClatchey AI, Halpin C. Audiologic and radiographic response of NF-2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol 2008;5:487-91. PMID 18560388
- 351
- Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 2009;361:358-67. PMID 19587327
- 352
- Pollock BE. Management of vestibular schwannomas that enlarge after stereotactic radiosurgery: treatment recommendations based on a 15 year experience. Neurosurgery 2006;58:241-8. PMID 16462477
- 353
- Pollock BE, Driscoll CLW, Foote RL, et al. Patient outcomes after vestibular schwannoma management: A prospective comparison of microsurgical resection and stereotactic radiosurgery. Neurosurgery 2006;59:77-85. PMID 16823303
- 354
- Pollock BE, Link MJ, Stafford SL, Parney IF, Garces YI, Foote RL. The risk of radiation-induced tumors or malignant transformation after single-fraction intracranial radiosurgery: results based on a 25-year experience. Int J Radiat Oncol Biol Phys 2017;97:919-23. PMID 28333013
- 355
- Pollock BE, Lunsford LD, Flickinger JC, Clyde BL, Kondziolka D. Vestibular schwannoma management. Part I. Failed microsurgery and the role of delayed stereotactic radiosurgery. J Neurosurg 1998a;89:944-8. PMID 9833820
- 356
- Pollock BE, Lunsford LD, Kondziolka D, et al. Outcome analysis of acoustic neuroma management: a comparison of microsurgery and stereotactic radiosurgery. Neurosurgery 1995;36:215-29. PMID 7708162
- 357
- Pollock BE, Lunsford LD, Kondziolka D, et al. Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg 1998b;89:949-55. PMID 9833821
- 358
- Pollock BE, Lunsford LD, Kondziolka D, et al. Vestibular schwannoma management: Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg 2013;119:S949-55. PMID 25077309
- 359
- Pollock BE, Lunsford LD, Noren G. Vestibular schwannoma management in the next century: a radiosurgical perspective. Neurosurgery 1998c;43:474-83. PMID 9733302
- 360
- Post KD, Eisenberg MB, Catalano PJ. Hearing preservation in vestibular schwannoma surgery: what factors influence outcome. J Neurosurg 1995;83:191-6. PMID 7616260
- 361
- Prasad SC, Patnaik U, Grinblat G, et al. Decision making in the wait-and-scan approach for vestibular schwannomas: Is there a price to pay in terms of hearing, facial nerve, and overall outcome? Neurosurgery 2018;83(5):858-70. PMID 29281097
- 362
- Prueter J, Norvell D, Backous D. Ki-67 index as a predictor of vestibular schwannoma regrowth or recurrence. J Laryngol Otol 2019;133(3):205-7. PMID 30983565
- 363
- Puataweepong P, Dhanachai M, Dangprasert S, et al. Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannomas: comparative observations of 139 patients treated at a single institution. J Radiat Res 2014;55(2):351-8. PMID 24142966
- 364
- Puataweepong P, Dhanachai M, Swangsilpa T, et al. Long-term clinical outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy using the Cyberknife robotic radiosurgery system for vestibular schwannoma. Asia Pac J Clin Oncol 2022;18(5):e247-54. PMID 34310064
- 365
- Pulec JL, Giannotta SL. Acoustic neuroma surgery in patients over 65 years of age. Ear Nose Throat J 1995;74:2127. PMID 7867527
- 366
- Quist TS, Givens DJ, Gurgel RK, Chamoun R, Shelton C. Hearing preservation after middle fossa vestibular schwannoma removal: are the results durable? Otolargygol Head Neck Surg 2015;152(4):706-11. PMID 25628370
- 367
- Rahne T, Plontke SK, Frohlich L, Strauss C. Optimized preoperative determination of nerve of origin in patients with vestibular schwannoma. Sci Rep 2021;11(1):8608. PMID 33883565
- 368
- Rampp S, Rensch L, Simmermacher S, Rahne T, Strauss C, Prell J. Intraoperative auditory steady-state monitoring during surgery in the cerebellopontine angle for estimation of postoperative hearing classes. J Neurosurg 2017;127(3):559-66. PMID 27739939
- 369
- Ramsay HA, Luxford WM. Treatment of acoustic tumours in elderly patients: is surgery warranted. J Laryngol Otol 1993;107:295-7. PMID 8320512
- 370
- Ramsden RT, Moffat DA. Intracanalicular acoustic neuromas: the case for early surgery. Clin Otolaryngol 1994;19:1-2. PMID 8174293
- 371
- Rapp CT, Amdur RJ, Bova FJ, Foote KD, Friedman WA. Repeat single-fraction radiosurgery for recurrent vestibular schwannoma. Rep Pract Oncol Radiother 2022;27(4):655-8. PMID 36196424
- 372
- Redleaf MI, McCabe BF. Disappearing recurrent acoustic neuroma in an elderly woman. Ann Otol Rhinol Laryngol 1993;102:518-20. PMID 8333673
- 373
- Regis J, Carron R, Park MC, et al. Wait-and-see strategy compared with proactive Gamma Knife surgery in patients with intracanalicular vestibular schwannomas: clinical article. J Neurosurg 2013;119:S105-11. PMID 25077326
- 374
- Regis J, Pellet W, Delsanti C, et al. Functional outcome after gamma knife surgery or microsurgery for vestibular schwannomas. J Neurosurg 2002;97:1091-100. PMID 12450031
- 375
- Reinders JW, Koehler PJ. Familial schwannomatosis, a new entity distinct from neurofibromatosis type 1 and 2. Ned Tijdschr Geneeskd 2007;151:1891-5. PMID 17902564
- 376
- Repacholi MH, Lerchl A, Roosli M, et al. Systematic review of wireless phone use and brain cancer and other head tumors. Bioelectromagnetics 2012;33(3):187-206. PMID 22021071
- 377
- Reznitsky M, Petersen MMBS, West N, Stangerup SE, Caye-Thomasen P. The natural history of vestibular schwannoma growth – prospective 40-year data from an unselected national cohort. Neuro Oncol 2021;23(5):827-36. PMID 33068429
- 378
- Rice JM, Perantoni AO, Reed C, Majumdar C, Higinbotham KG. Selective activation of the neu oncogene by point mutation in chemically induced schwannomas in rodents. J Neurooncol 1989;7:S23.
- 379
- Riina HA, Burkhardt JK, Santillan A, Bassani L, Patsalides A, Boockvar JA. Short-term clinico-radiographic response to super-selective intra-arterial cerebral infusion of Bevacizumab for the treatment of vestibular schwannomas in Neurofibromatosis type 2. Interv Neuroradiol 2012;18(2):127-132. PMID 22681725
- 380
- Robinett ZN, Walz PC, Miles-Markley B, Moberly AC, Welling DB. Comparison of long-term quality-of-life outcomes in vestibular schwannoma patients. Otolaryngol Head Neck Surg 2014;150(6):1024-32. PMID 24596235
- 381
- Roethlisberger M, Moffa G, Rychen J, et al. Long-term tumor control in Koos grade IV vestibular schwannoma without the need for gross-total resection. J Neurosurg 2024;140(6):1591-604. PMID 38039537
- 382
- Roos DE, Potter AE, Brophy BP. Stereotactic radiosurgery for acoustic neuromas: what happens long term. Int J Radiat Oncol Biol Phys 2012;82(4):1352-5. PMID 21700400
- 383
- Roosli M, Lagorio S, Schoemaker MJ, Schuz J, Feychting M. Brain and salivary gland tumors and mobile phone use: evaluating the evidence from various epidemiological study designs. Annu Rev Public Health 2019;40:221-38. PMID 30633716
- 384
- Rosenbaum C, Kamleiter M, Grafe P, et al. Enhanced proliferation and potassium conductance of Schwann cells from NF2 schwannomas can be reduced by quinidine. Neurobiol Dis 2000;7:483-91. PMID 10964617
- 385
- Rosenberg SI, Silverstein DH, Gordon MA, Flanzer JM, Willcox TO, Silverstein J. A comparison of growth rates of acoustic neuromas: nonsurgical patients vs. subtotal resection. Otolaryngol Head Neck Surg 1993;109:482-7. PMID 8414567
- 386
- Roswall N, Stangerup SE, Caye-Thomasen P, et al. Residential traffic noise exposure and vestibular schwannoma – a Danish case-contral study. Acta Oncol 2017;56(10):1310-6. PMID 28609173
- 387
- Rouleau G, Wertelecki W, Haines JL, et al. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 1987;329:246-8. PMID 2888021
- 388
- Rouleau GA, Merel P, Lutchman M, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature 1993;363(6429):515-21. PMID 8379998
- 389
- Rouleau GA, Seizinger BR, Wertelecki W, et al. Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22. Am J Hum Genet 1990;46(2):323-8. PMID 2105641
- 390
- Roundy N, Delashaw JB, Cetas JS. Preoperative identification of the facial nerve in patients with large cerebellopontine angle tumors using high-density diffusion tensor imaging. J Neurosurg 2012;116(4):697-702. PMID 22283188
- 391
- Ruckenstein MJ, Cueva RA, Morrison DH, Press G. A prospective study of ABR and MRI in the screening for vestibular schwannomas. Am J Otol 1996;17:317-20. PMID 8723969
- 392
- RueB D, Schűtz B, Celik E, et al. Pseudoprogression of vestibular schwannoma after stereotactic radiosurgery with Cyberknife: proposal for new response criteria. Cancers (Basel) 2023;15(5):1496. PMID 36900290
- 393
- Ruiz-Garcia H, Peterson J, Leon J et al. Initial observation among patients with vestibular schwannoma. J Neurol Surg B Skull Base 2021;82(Suppl 3):e15-21. PMID 34306913
- 394
- Sabab A, Sandhu J, Bacchi S, Jukes A, Zacest A. Postoperative headache following treatment of vestibular schwannoma: a literature review. J Clin Neurosci 2018;52:26-31. PMID 29656878
- 395
- Sadler KV, Bowes J, Rowlands CF, et al. Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21. Brain 2023;146(7):2861-8. PMID 36546557
- 396
- Sadler KV, Bowers NL, Hartley C, et al. Sporadic vestibular schwannoma: a molecular testing summary. J Med Genet 2021;58(4):227-33. PMID 32576656
- 397
- Saeed SR, Woolford TJ, Ramsden RT, Lye RH. Magnetic resonance imaging: a cost effective first line investigation in the detection of vestibular schwannomas. Br J Neurosurg 1995;9:497-503. PMID 7576276
- 398
- Sagers JE, Beauchamp RL, Zhang Y, et al. Combination therapy with mTOR kinase inhibitor and dasatinib as a novel therapeutic strategy for vestibular schwannoma. Sci Rep 2020;10(1):4211. PMID 32144278
- 399
- Sakanaka K, Mizowaki T, Arakawa Y, et al. Hypofractionated stereotactic radiotherapy for acoustic neuromas: safety and effectiveness over 8 years of experience. Int J Clin Oncol 2011;16(1):27-32. PMID 20830603
- 400
- Sameshima T, Fukushima T, McElveen JT Jr, Friedman AH. Critical assessment of operative approaches for hearing preservation in small acoustic neuroma surgery: retrosigmoid vs middle fossa approach. Neurosurg 2010;67(3):640-4. PMID 20647969
- 401
- Samii M. Microsurgery of acoustic neurinomas with special emphasis on preservation of seventh and eighth cranial nerves and the scope of facial nerve grafting. In: Rand RW, editor. Microneurosurgery. St. Louis: Mosby, 1985:366-88.
- 402
- Samii M, Matthies C. Management of 1000 vestibular schwannomas (acoustic neuromas): surgical management and results with an emphasis on complications and how to avoid them. Neurosurgery 1997a;40:11-23. PMID 8971819
- 403
- Samii M, Matthies C. Management of 1000 vestibular schwannomas (acoustic neuromas): hearing function in 1000 tumor resections. Neurosurgery 1997b;40:248-62. PMID 9007856
- 404
- Samii M, Matthies C, Tatagiba M. Intracanalicular acoustic neurinomas. Neurosurgery 1991;28:189-99. PMID 1886656
- 405
- Samii M, Metwali H, Gerganov V. Microsurgical management of vestibular schwannoma after failed previous surgery. J Neurosurg 2016;125(5):1198-203. PMID 26771854
- 406
- Samii M, Metwali H, Gerganov V. Efficacy of microsurgical tumor removal for treatment of patients with intracanalicular vestibular schwannoma presenting with disabling vestibular symptoms. J Neurosurg 2017;126:1514-9. PMID 27315031
- 407
- Sampath P, Holliday MJ, Brem H, Niparko JK, Long DM. Facial nerve injury in acoustic neuroma (vestibular schwannoma) surgery: etiology and prevention. J Neurosurg 1997;87:60-6. PMID 9202266
- 408
- Sanna M, Karmarkar S, Landolfi M. Hearing preservation in vestibular schwannoma surgery: fact or fantasy. J Laryngol Otol 1995;109:374-80. PMID 7797990
- 409
- Santa Maria PL, Yangyang S, Gurgel RK, et al. Long-term hearing outcomes following stereotactic radiosurgery in vestibular schwannoma patients – a retrospective cohort study. Neurosurgery 2019;85(4):550-9. PMID 30247723
- 410
- Saraf A, Pike LRG, Franck KH, et al. Fractionated proton radiation therapy and hearing preservation for vestibular schwannoma: preliminary analysis of a prospective phase 2 clinical trial. Neurosurg 2022;90(5):506-14. PMID 35229827
- 411
- Sass HC, Borup R, Alanin M, Nielsen FC, Caye-Thomasen P. Gene expression, signal transduction pathways, and functional networks associated with growth of sporadic vestibular schwannomas. J Neuroncol 2017;131(2):283-92. PMID 27752882
- 412
- Sass HCR, Hansen M, Borup R, Nielsen FC, Caye-Thomasen P. Tumor mi RNA expression profile is related to schwannoma growth rate. Acta Neurochir (Wien) 2020;162(5):1187-95. PMID 32016588
- 413
- Scheller C, Rampp S, Leisz S, et al. Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial. Neurosurg Rev 2021;44(3):1729-35. PMID 32827307
- 414
- Scheller C, Wienke A, Tatagiba M, et al. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial. J Neurosurg 2016;124(3):657-64. PMID 26274985
- 415
- Scheller C, Wienke A, Tatagiba M, et al. Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study. J Neurosurg 2017;127(6):1376-83. PMID 28298021
- 416
- Scheller C, Wienke A, Wurm F, et al. Neuroprotective efficacy of prophylactic enteral and parenteral nimodipine treatment in vestibular schwannoma surgery: a comparative study. J Neurol Surg A Cent Eur Neurosurg 2014;75(4):251-8. PMID 24114058
- 417
- Schneider AB, Ron E, Lubin J, et al. Acoustic neuromas following childhood radiation treatment for benign conditions of the head and neck. Neuro Oncol 2007;10(1):73-8. PMID 18079359
- 418
- Schneider T, Chapiro J, Lin M, et al. 3D quantitative assessment of response to fractionated stereotactic radiotherapy and single-session stereotactic radiosurgery of vestibular schwannoma. Eur Radiol 2016;26(3):849-57. PMID 26139318
- 419
- Schnurman Z, Golfinos JG, Epstein D, Friedmann DR, Roland TJr, Kondziolka D. Comparing costs of microsurgical resection and stereotactic radiosurgery for vestibular schwannoma. J Neurosurgery 2018;1-10. PMID 30497146
- 420
- Schnurman Z, Gurewitz J, Smouha E, et al. Matched comparison of hearing outcomes in patients with vestibular schwannoma treated with stereotactic radiosurgery or observation. Neurosurg 2022;91(4):641-7. PMID 36001782
- 421
- Schnurman Z, Nakamura A, McQuinn MW, Golfinos JG, Roland JT, Kondziolka D. Volumetric growth rates of untreated vestibular schwannomas. J Neurosurg 2019:1-7. PMID 31374553
- 422
- Schoemaker MJ, Swerdlow AJ, Ahlbom A, et al. Mobile phone use and risk of acoustic neuromas: results of the Interphone case-control study in five Northern European countries. Br J Cancer 2005;93(7):842-8. PMID 16136046
- 423
- Scholte M, Hentschel MA, Hannink G, et al. In search of the most cost-effective monitoring strategy for vestibular schwannoma: a decision analytical modelling study. Clin Otolaryngol 2019;44(4):525-33. PMID 30864276
- 424
- Schuz J, Steding-Jessen M, Hansen S, et al. Long-term mobile phone use and the risk of vestibular schwannoma: a Danish nationwide cohort study. Am J Epidemiol 2011;174(4):416-22. PMID 21712479
- 425
- Schwartz MS, Kari E, Strickland BM, et al. Evaluation of the increased use of partial resection of large vestibular schwannomas: facial nerve outcomes and recurrence/regrowth rates. Otol Neurotol 2013;34(8):1456-64. PMID 23928516
- 426
- Seizinger BR, Martuza RL, Gusella JF. Loss of genes of chromosome 22 in tumorigenesis of human acoustic neuroma. Nature 1986;322:644-7. PMID 3092103
- 427
- Selesnick SH, Jackler RK. Clinical manifestations and audiologic diagnosis of acoustic neuromas. Otolaryngol Clin North Am 1992;25:521-51. PMID 1625864
- 428
- Selesnick SH, Jackler RK, Pitts LW. The changing clinical presentation of acoustic tumors in the MRI era. Laryngoscope 1993;103:431-6. PMID 8459753
- 429
- Selters WA, Brackmann DE. Brainstem electric response audiometry in acoustic tumor detection. In: House WF, Luetje CM, editors. Acoustic tumors. Vol I. Diagnosis. Baltimore: University Park Pr, 1979:225-35.
- 430
- Selvanathan SK, Shenton A, Ferner R, et al. Further genotype--phenotype correlations in neurofibromatosis 2. Clin Genet 2010;77(2):163-70. PMID 19968670
- 431
- Semaan MT, Wick CC, Kinder KJ, Stuyt JG, Chota RL, Megerian CA. Retrosigmoid versus translabyrinthine approach to acoustic neuroma resection: a comparative cost-effectiveness analysis. Laryngoscope 2016;126 Suppl 3:S5-S12. PMID 26490680
- 432
- Sharma M, Papisetty S, Dhawan S, et al. Comparison of stereotactic radiosurgery and hypofractionated radiosurgery for vestibular schwannomas: a meta-analysis of available literature. World Neurosurg 2024;182:e742-54. PMID 38092351
- 433
- Shelton C. Unilateral acoustic tumors: how often do they recur after translabyrinthine removal. Laryngoscope 1995;105:958-66. PMID 7666732
- 434
- Shelton C, Hitselberger WE, House WF, Brackmann DE. Hearing preservation after acoustic tumor removal: long-term results. Laryngoscope 1990;100:115-9. PMID 2299949
- 435
- Shin YJ, Fraysse B, Cognard C, et al. Effectiveness of conservative management of acoustic neuromas. Am J Otol 2000;21:857-62. PMID 11078076
- 436
- Shrivastava M, Emmanouil B, Mathew R, et al. Laryngoscope 2024;134:2364-71. PMID 37983868
- 437
- Silverstein H, Rosenberg SI, Flanzer JM, Wanamaker HH, Seidman MD. An algorithm for the management of acoustic neuromas regarding age, hearing, tumor size, and symptoms. Otolaryngol Head Neck Surg 1993;108:1-10. PMID 8437867
- 438
- Silverstein H, Willcox TO Jr, Rosenberg SI, Seidman MD. Acoustic neuroma resection using intraoperative facial nerve stimulation. Laryngoscope 1994;104:539-44. PMID 8189983
- 439
- Slattery WH III, Brackmann DE. Results of surgery following stereotactic irradiation for acoustic neuromas. Am J Otol 1995;16:315-21. PMID 8588625
- 440
- Slattery WH III, Brackmann DE, Hitselberger W. Middle fossa approach for hearing preservation with acoustic neuromas. Am J Otol 1997;18:596-601. PMID 9303156
- 441
- Smirniotopoulos JG, Yue NC, Rushing EJ. Cerebellopontine angle masses: radiologic-pathologic correlation. Radiographics 1993;13:1131-47. PMID 8210595
- 442
- Smith MJ, Bowers NL, Bulman M, et al. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis. Neurology 2017;88(1):87-92. PMID 27856782
- 443
- Smouha EE, Yoo M, Mohr K, Davis RP. Conservative management of acoustic neuroma: a meta-analysis and proposed treatment algorithm. Laryngoscope 2005;115(3):450-4. PMID 15744156
- 444
- Soderlund Diaz L, Hallqvist A. LINAC-based stereotactic radiosurgery versus hypofractionated stereotactic radiotherapy delivered in 3 or 5 fractions for vestibular schwannomas: comparative assessment from a single institution. J Neurooncol 2020;147(2):351-9. PMID 32036575
- 445
- Soulier G, van Leeuwen BM, Putter H, et al. Quality of life in 807 patients with vestibular schwannoma: comparing treatment modalities. Otolaryngol Head Neck Surg 2017;157(1):92-8. PMID 28319458
- 446
- Stangerup SE, Tos M, Thomsen J, Caye-Thomasen P. True incidence of vestibular schwannoma. Neurosurg 2010;67(5):1335-40. PMID 20871439
- 447
- Sterkers JM, Morrison GA, Sterkers O, Badr El-Dine MM. Preservation of facial, cochlear, and other nerve functions in acoustic neuroma treatment. Otolaryngol Head Neck Surg 1994;110:146-55. PMID 8108149
- 448
- Stokowski RP, Cox DR. Functional analysis of the neurofibromatosis type 2 protein by means of disease-causing point mutations. Am J Hum Genet 2000;66:873-91. PMID 10712203
- 449
- Strasnick B, Glasscock ME, Haynes D, McMenomey SO, Minor LB. The natural history of untreated acoustic neuromas. Laryngoscope 1994;104:1115-9. PMID 8072358
- 450
- Strauss C, Fahlbusch R, Romstock J, et al. Delayed hearing loss after surgery for acoustic neurinomas: clinical and electrophysiological observations. Neurosurgery 1991;28:559-65. PMID 1709726
- 451
- Strauss R, Post KD. Other schwannomas of cranial nerves. In: Kaye AH, Laws ER, editors. Brain tumors. An encyclopedic approach. Edinburgh: Churchill Livingstone, 1995;33:643-64.
- 452
- Stucken EZ, Brown K, Selesnick SH. Clinical and diagnostic evaluation of acoustic neuromas. Otolaryngol Clin North Am 2012;45(2):269-84. PMID 22483815
- 453
- Subbiah V, Slopsis J, Hong DS, et al. Treatment of patients with advanced neurofibromatosis type 2 with novel molecularly targeted therapies: from bench to bedside. J Clin Oncol 2012;30(5):e64-8. PMID 22203760
- 454
- Sughrue ME, Fung KM, Van Gompel JJ, Peterson JEG, Olson JJ. Congress of neurological surgeons systematic review and evidence-based guidelines on pathological methods and prognostic factors in vestibular schwannoma. Neurosurgery 2018;82(2):E47-8. PMID 29309662
- 455
- Sughrue ME, Kaur R, Rutkowski MJ, et al. A critical evaluation of vestibular schwannoma surgery for patients younger than 40 years of age. Neurosurgery 2010;67(6):1646-53. PMID 21107195
- 456
- Sughrue ME, Kaur R, Rutkowski MJ, et al. Extent of resection and long-term durability of vestibular schwannoma surgery. J Neurosurg 2011b;114(5):1218-23. PMID 21250800
- 457
- Sughrue ME, Yang I, Aranda D, et al. Beyond audiofacial morbidity after vestibular schwannoma surgery. J Neurosurg 2011a;114(2):367-74. PMID 19943734
- 458
- Sverak P, Adams ME, Haines SJ, et al. Bevacizumab for hearing preservation in neurofibromatosis type 2: emphasis on patient-reported outcomes and toxicities. Otolaryngol Head Neck Surg 2018;194599818809085. PMID 30373466
- 459
- Sweeney AD, Carlson ML, Shepard NT, et al. Congress of neurological surgeons systematic review and evidence-based guidelines on otologic and audiologic screening for patients with vestibular schwannomas. Neurosurgery 2018;82(2):E29-31. PMID 29309699
- 460
- Syed MI, Wolf A, Ilan O, et al. The behaviour of residual tumor after the intentional incomplete resection of vestibular schwannoma: is it such a bad thing to leave some behind? Clin Otolaryngol 2017;42(1):92-7. PMID 27158933
- 461
- Szymoniuk M, Kochanski M, Wilk K, et al. Stereotactic radiosurgery for Koos grade IV vestibular schwannoma: a systematic review and meta-analysis. Acta Neurochir Wien 2024;166:101. PMID 38393397
- 462
- Tallan EM, Harner SG, Beatty CW. Does the distribution of Schwann cells correlate with the observed occurrence of acoustic neuromas. Am J Otol 1993;14:131-4. PMID 8503485
- 463
- Tamura M, Carron R, Yomo S, et al. Hearing preservation after gamma knife radiosurgery for vestibular schwannomas presenting with high-level hearing. Neurosurg 2009;64:289-96. PMID 19057423
- 464
- Tamura R, Toda M. A critical overview of targeted therapies for vestibular schwannoma. Int J Mol Sci 2022;23(10):5462. PMID 35628268
- 465
- Taurone S, Bianchi E, Attanasio G, et al. Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue. Mol Med Rep 2015;12(1):737-45. PMID 25738867
- 466
- Thomas R, Prabhu PD, Mathivanan J, Rohini, et al. Altered structure and expression of RB1 gene and increased phosphorylation of pRb in human vestibular schwannomas. Mol Cell Biochem 2005;271(1-2):113-21. PMID 15881662
- 467
- Thomsen J, Tos M. Acoustic neuroma: clinical aspects, audiovestibular assessment, diagnostic delay, and growth rate. Am J Otol 1990;11:12-9. PMID 2305850
- 468
- Tikoo A, Varga M, Ramesh V, Gusella J, Maruta H. An anti-Ras function of neurofibromatosis type 2 gene product (NF2/Merlin). J Biol Chem 1994;269:23387-90. PMID 8089100
- 469
- Timmer FC, Hanssens PE, van Haren AE, et al. Gamma knife radiosurgery for vestibular schwannomas: results of hearing preservation in relation to the cochlear radiation dose. Laryngoscope 2009;119:1076-81. PMID 19399836
- 470
- Trakolis L, Bender B, Ebner FH, Ernemann U, Tatagiba M, Naros G. Cortical and subcortical gray matter changes in patients with chronic tinnitus sustaining after vestibular schwannoma surgery. Sci Rep 2021;11:8411. PMID 33863965
- 471
- Trofatter JA, MacCollin MM, Rutter JL, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 1993;72:791-800. PMID 8453669
- 472
- Tschudi DC, Linder TE, Fisch U. Conservative management of unilateral acoustic neuromas. Am J Otol 2000;21:722-8. PMID 10993466
- 473
- Tucci DL, Telian SA, Kileny PR, Hoff JT, Kemink JL. Stability of hearing preservation following acoustic neuroma surgery. Am J Otol 1994;15:183-8. PMID 8172299
- 474
- Tuleasca C, Toma-Dasu J, Duroux S, et al. Impact of the mean cochlear biologically effective dose on hearing preservation after stereotactic radiosurgery for vestibular schwannoma: a retrospective longitudinal analysis. Neurosurg 2024;94:174-82. PMID 37431994
- 475
- Utermark T, Alekov A, Lerche H, Abramowski V, Giovannini M, Hanemann CO. Quinidine impairs proliferation of neurofibromatosis type 2-deficient human malignant mesothelioma cells. Cancer 2003;97:1955-62. PMID 12673723
- 476
- Van Abel KM, Carlson ML, Driscoll CL, Neff BA, Link MJ. Vestibular schwannoma surgery in the elderly: a matched cohort study. J Neurosurg 2014;120(1)207-17. PMID 23870020
- 477
- Van Gompel JJ, Agazzi S, Carlson ML, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines on emerging therapies for the treatment of patients with vestibular schwannomas. Neurosurgery 2018;82:E52-4. PMID 29309638
- 478
- Van Gompel JJ, Patel J, Danner C, et al. Acoustic neuroma observation associated with an increase in symptomatic tinnitus: results of the 2007-2008 Acoustic Neuroma Association survey. J Neurosurg 2013;119(4):864-8. PMID 23790115
- 479
- van Leeuwen JP, Harhangi BS, Thewissen NP, Thijssen HO, Cremers CW. Delays in the diagnosis of acoustic neuromas. Am J Otol 1996;17:321-5. PMID 8723970
- 480
- van Roijen L, Nijs HG, Avezaat CJ, et al. Costs and effects of microsurgery versus radiosurgery in treating acoustic neuroma. Acta Neurochir (Wien) 1997;139:942-8. PMID 9401654
- 481
- Varughese JK, Breivik CN, Wentzel-Larsen T, Lund-Johansen M. Growth of untreated vestibular schwannoma: a prospective study. J Neurosurg 2012;116(4):706-12. PMID 22264178
- 482
- Vasudevan HN, Lucas CHG, Villaneuva-Meyer JE, Theodosopoulos PV, Raleigh DR. Genetic events and signaling mechanisms underlying Schwann cell fate in development and cancer. Neurosurg 2021;88(2):234-45. PMID 33094349
- 483
- Versleijen MW, Verbist BM, Mulder JJ, de Geus-Oei LF, van Herpen CM. Avastin scintigraphy in surveillance of bevacizumab treatment in a patient with neurofibromatosis type 2: a case report. Clin Nucl Med 2014;39(3):277-80. PMID 24445270
- 484
- Vijayalaxmi, Prihoda TJ. Genetic damage in human cells exposed to non-ionizing radiofrequency fields: A meta-analysis of the data from 88 publications (1990-2011). Mutat Res 2012;749(1-2):1-16. PMID 23022599
- 485
- Vnencak M, Huttunen E, Aarnisalo AA, Jero J, Liukkonen K, Sinkkonen ST. Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening. J Otol 2021;16(3):138-43. PMID 34220982
- 486
- Vogel FS. Tumors of the cerebellopontine angle: pathology. In: Wilkins RH, Rengachary SS, editors. Neurosurgery. New York: McGraw-Hill, 1985:694-8.
- 487
- Wach J, Guresir A, Borger V, et al. Elevated baseline C-reactive protein levels predict poor progression free survival in sporadic vestibular schwannoma. J Neurooncol 2022;156(2):365-75. PMID 34882287
- 488
- Walsh RM, Bath AP, Bance ML, Keller A, Tator CH, Rutka JA. The natural history of untreated vestibular schwannomas. Is there a role for conservative management. Rev Laryngol Otol Rhinol (Bord) 2000;121:21-6. PMID 10865479
- 489
- Wazen J, Silverstein H, Norrell H, Besse B. Preoperative and postoperative growth rates in acoustic neuromas documented with CT scanning. Otolaryngol Head Neck Surg 1985;93:151-5. PMID 3921903
- 490
- Weerda HG, Gamberger TI, Siegner A, Gjuric M, Tamm ER. Effects of transforming growth factor beta 1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma. Acta Otolaryngol 1998;118:337-43. PMID 9655207
- 491
- Wellington DB, Packer MD, Chang LS. Molecular studies of vestibular schwannomas. A review. Curr Opin Otolaryngol Head Neck Surg 2007;15:341-6. PMID 17823551
- 492
- West N, Sass S, Caye-Thomasen P. Sporadic and NF-2 associated vestibular schwannoma surgery and simultaneous cochlear implantation: a comparative systematic review. Eur Arch Otorhinolaryngol 2020;277(2):333-42. PMID 31802225
- 493
- Whitmore RG, Urban C, Church E, Ruckenstein M, Stein SC, Lee JY. Decision analysis of treatment options for vestibular schwannoma. J Neurosurg 2011;114(2):400-13. PMID 20397894
- 494
- Wiegand DA, Ojemann RG, Fickel V. Surgical treatment of acoustic neuroma (vestibular schwannoma) in the United States: report from the acoustic neuroma registry. Laryngoscope 1996;106:58-66. PMID 8544629
- 495
- Wiet RJ, Zappia JJ, Hecht CS, O'Connor CA. Conservative management of patients with small acoustic tumors. Laryngoscope 1995;105:795-800. PMID 7630289
- 496
- Wijn SRW, Hentschel MA, Beynon AJ, Kunst HPM, Rovers MM. Auditory brainstem response prior to MRI compared to standalone MRI in the detection of vestibular schwannoma: a modelling study. Clin Otolarygol 2022;47(2):295-303. PMID 34784107
- 497
- Williams JA. Fractionated stereotactic radiotherapy for acoustic neuromas. Acta Neurochir 2002;144:1249-54. PMID 12478335
- 498
- Wilson DF, Talbot JM, Mills L. A critical appraisal of the role of auditory brain stem response and magnetic resonance imaging in acoustic neuroma diagnosis. Am J Otol 1997;18:673-81. PMID 9303169
- 499
- Withrow DR, Devesa SS, Deapen D, et al. Nonmalignant meningioma and vestibular schwannoma incidence trends in the United States, 2004-2017. Cancer 2021;127(19):3579-90. PMID 34160068
- 500
- Wolbers JG, Dallenga AH, Mendez Romero A, van Linge A. What intervention is best practice for vestibular schwannomas? A systematic review of controlled studies. BMJ Open 2013;3(2):e001345. PMID 23435793
- 501
- Wong HK, Shimizu A, Kirkpatrick ND, et al. Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism. Neoplasia 2012;14(2):84-94. PMID 22431917
- 502
- Wu J, Kong M, Bi Q. Identification of a novel germline SMARCB1 nonsense mutation in a family manifesting both schwannomatosis and unilateral vestibular schwannoma. J Neurooncol 2015;125(2):439-41. PMID 26342709
- 503
- Wu X, Li M, Zhang Z, et al. Reliability of preoperative prediction of the location of the facial nerve using diffusion tensor imaging-fiber tracking in vestibular schwannoma: a systematic review and meta-analysis. World Neurosurg 2021;146:351-361.e3. PMID 33130136
- 504
- Wu X, Song G, Wang X, et al. Comparison of surgical outcomes in cystic and solid vestibular schwannomas: a systematic review and meta-analysis. Neurosurg Rev 2021b;44(4):1889-902. PMID 33009643
- 505
- Xenellis JE, Linthicum FH Jr. On the myth of the glial/schwann junction (Obersteiner-Redlick zone): origin of vestibular nerve schwannomas. Otol Neurotol 2003;24:1. PMID 12544018
- 506
- Yamauchi J, Miyamoto Y, Kusakawa S, et al. Neurofibromatosis 2 tumor suppressor, the gene induced by valproic acid, mediates neurite outgrowth through interaction with paxcillin. Exp Cell Res 2008;314:2279-88. PMID 18486129
- 507
- Yan S, Wang Q, Huo Z, et al. Gene expression profiles between cystic and solid vestibular schwannoma indicate susceptible molecules and pathways in the cystic formation of vestibular schwannoma. Funct Integr Genomics 2019;19(4):673-84. PMID 30953268
- 508
- Yanagihara N, Asai M. Sudden hearing loss induced by acoustic neuroma: significance of small tumors. Laryngoscope 1993;103:308-11. PMID 8441318
- 509
- Yang I, Sughrue ME, Han SJ, et al. A comprehensive analysis of hearing preservation after radiosurgery for vestibular schwannoma. J Neurosurg 2010;112(4):851-9. PMID 19747043
- 510
- Yokoh A, Kobayashi S, Tanaka Y, Gibo H, Sugita K. Preservation of cochlear nerve function in acoustic neurinoma surgery. Acta Neurochir 1993;123:8-13. PMID 8213282
- 511
- Yomo S, Arkha Y, Delsanti C, Roche PH, Thomassin JM, Regis J. Repeat gamma knife surgery for regrowth of vestibular schwannomas. Neurosurgery 2009;64(1):48-54. PMID 19050660
- 512
- Yoshimoto Y. Systematic review of the natural history of vestibular schwannoma. J Neurosurg 2005;103:59-63. PMID 16121974
- 513
- Yoshino M, Kin T, Ito A, et al. Combined use of diffusion tensor tractography and multifused contrast enhanced FIESTA for predicting facial and cochlear nerve positions in relation to vestibular schwannoma. J Neurosurg 2015;123(6):1480-8. PMID 26053235
- 514
- Youssef AS, Downes AE. Intraoperative neurophysiological monitoring in vestibular schwannoma surgery: advances and clinical implications. Neurosurg Focus 2009;27(4):E9. PMID 19795957
- 515
- Yuan R, Wang B, Wang Y, Liu P. Gene therapy for neurofibromatosis type 2-related schwannomatosis: recent progress, challenges, and future directions. Oncol Ther 2024;12(2):257-62. PMID 38760612
- 516
- Zhang Y, Long J, Ren J, Huang X, Zhong P, Wang B. Potential molecular biomarkers of vestibular schwannoma growth: progress and prospects. Front Oncol 2021;11:731441. PMID 34646772
- 517
- Zhao F, Li SW, Zhang S, et al. Phase II trial of icotinib in adult patients with neurofibromatosis type 2 and progressive vestibular schwannoma. J Neurosurg 2022;1-8. PMID 36272122
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Donald A Ross MD
Dr. Ross of Oregon Health and Science University has no relevant financial relationships to disclose.
See Profile
Editor
-
Deric M Park MD FACP
Dr. Park of the University of Chicago has no relevant financial relationships to disclose.
See Profile
Former Authors
- Rimas V Lukas MD
Patient Profile
- Age range of presentation
-
- 2 to 65+ years
- Sex preponderance
-
- female>male, >1:1
- Heredity
-
- heredity typical
- heredity may be a factor
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-10
-
- Benign neoplasm of cranial nerves: D33.3
- ICD-11
-
- Benign neoplasm of cranial nerves: 2A02.3
- OMIM
-
- Acoustic schwannomas, bilateral: #101000
This is an article preview.
Start a Free Account
to access the full version.
-
Nearly 3,000 illustrations, including video clips of neurologic disorders.
-
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
-
Full spectrum of neurology in 1,200 comprehensive articles.
-
Listen to MedLink on the go with Audio versions of each article.
Questions or Comment?
MedLink®, LLC
3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122
Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
Also in This Category
-
-
Neuro-Oncology
Tumors of the skull base
Dec. 05, 2024
-
Neuro-Ophthalmology & Neuro-Otology
Common maculopathies
Dec. 02, 2024
-
Neuro-Ophthalmology & Neuro-Otology
Toxic and nutritional deficiency optic neuropathies
Nov. 24, 2024
-
Neuro-Ophthalmology & Neuro-Otology
Third nerve palsy
Nov. 22, 2024
-
Neuro-Ophthalmology & Neuro-Otology
Nystagmus
Nov. 22, 2024
-
Neuromuscular Disorders
Chronic progressive external ophthalmoplegia
Oct. 29, 2024
-
Neuro-Oncology
Ganglioglioma
Oct. 15, 2024