Tumors of the nervous system and hearing loss: Beyond vestibular schwannomas.

Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease.

Diffusion MRI of the facial-vestibulocochlear nerve complex: a prospective clinical validation study.

OBJECTIVES: Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to the tumour. This study aimed to optimise a multi-shell readout-segmented diffusion-weighted imaging (rs-DWI) protocol and develop a novel post-processing pipeline to delineate the facial-vestibulocochlear complex within the skull base region, evaluating its accuracy intraoperatively using neuronavigation and tracked electrophysiological recordings. METHODS: In a prospective study of five healthy volunteers and five patients who underwent vestibular schwannoma surgery, rs-DWI was performed and colour tissue maps (CTM) and probabilistic tractography of the cranial nerves were generated. In patients, the average symmetric surface distance (ASSD) and 95% Hausdorff distance (HD-95) were calculated with reference to the neuroradiologist-approved facial nerve segmentation. The accuracy of patient results was assessed intraoperatively using neuronavigation and tracked electrophysiological recordings. RESULTS: Using CTM alone, the facial-vestibulocochlear complex of healthy volunteer subjects was visualised on 9/10 sides. CTM were generated in all 5 patients with vestibular schwannoma enabling the facial nerve to be accurately identified preoperatively. The mean ASSD between the annotators' two segmentations was 1.11 mm (SD 0.40) and the mean HD-95 was 4.62 mm (SD 1.78). The median distance from the nerve segmentation to a positive stimulation point was 1.21 mm (IQR 0.81-3.27 mm) and 2.03 mm (IQR 0.99-3.84 mm) for the two annotators, respectively. CONCLUSIONS: rs-DWI may be used to acquire dMRI data of the cranial nerves within the posterior fossa. CLINICAL RELEVANCE STATEMENT: Readout-segmented diffusion-weighted imaging and colour tissue mapping provide 1-2 mm spatially accurate imaging of the facial-vestibulocochlear nerve complex, enabling accurate preoperative localisation of the facial nerve. This study evaluated the technique in 5 healthy volunteers and 5 patients with vestibular schwannoma. KEY POINTS: • Readout-segmented diffusion-weighted imaging (rs-DWI) with colour tissue mapping (CTM) visualised the facial-vestibulocochlear nerve complex on 9/10 sides in 5 healthy volunteer subjects. • Using rs-DWI and CTM, the facial nerve was visualised in all 5 patients with vestibular schwannoma and within 1.21-2.03 mm of the nerve's true intraoperative location. • Reproducible results were obtained on different scanners.

The Vestibulocochlear Nerve: Anatomy and Pathology.

The vestibulocochlear nerve is the eighth cranial nerve, entering the brainstem in the medullopontine sulcus after crossing the internal auditory canal and cerebellopontine angle cistern. It is a purely sensitive nerve, originating from the Scarpa's and spiral ganglions, responsible for balance and hearing. It has 6 nuclei located in the lower pons. Magnetic resonance imaging (MRI) is useful for evaluating the vestibulocochlear nerve, although computed tomography may have a complementary role in assessing bone lesions. A heavily T2-weighted sequence, such as fast imaging employing steady-state acquisition (FIESTA) or constructive interference steady state (CISS), is crucial in imaging exams to depict the canalicular and cisternal segments of the vestibulocochlear nerve, as well as the fluid signal intensity in the membranous labyrinth. The vestibulocochlear nerve can be affected by several diseases, such as congenital malformations, trauma, inflammatory or infectious diseases, vascular disorders, and neoplasms. The purpose of this article is to review the vestibulocochlear nerve anatomy, discuss the best MRI techniques to evaluate this nerve and demonstrate the imaging aspect of the main diseases that affect it.

[Macroscopic and microscopic changes of the vestibulocochlear nerve after Gamma Knife treatment]. / Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie.

We report on a case in which macroscopic and microscopic changes of the vestibulocochlear nerve could be observed after radiosurgery of an intrameatal vestibular schwannoma. This case shows for the first time a morphological correlate for undesirable effects after radiosurgical treatment of a vestibular schwannoma and indicates that despite a certain distance to the actual tumor, degenerative changes in neural structures can be expected.

Applying artificial intelligence to longitudinal imaging analysis of vestibular schwannoma following radiosurgery.

Artificial intelligence (AI) has been applied with considerable success in the fields of radiology, pathology, and neurosurgery. It is expected that AI will soon be used to optimize strategies for the clinical management of patients based on intensive imaging follow-up. Our objective in this study was to establish an algorithm by which to automate the volumetric measurement of vestibular schwannoma (VS) using a series of parametric MR images following radiosurgery. Based on a sample of 861 consecutive patients who underwent Gamma Knife radiosurgery (GKRS) between 1993 and 2008, the proposed end-to-end deep-learning scheme with automated pre-processing pipeline was applied to a series of 1290 MR examinations (T1W+C, and T2W parametric MR images). All of which were performed under consistent imaging acquisition protocols. The relative volume difference (RVD) between AI-based volumetric measurements and clinical measurements performed by expert radiologists were + 1.74%, - 0.31%, - 0.44%, - 0.19%, - 0.01%, and + 0.26% at each follow-up time point, regardless of the state of the tumor (progressed, pseudo-progressed, or regressed). This study outlines an approach to the evaluation of treatment responses via novel volumetric measurement algorithm, and can be used longitudinally following GKRS for VS. The proposed deep learning AI scheme is applicable to longitudinal follow-up assessments following a variety of therapeutic interventions.

Protective effect of lutein against acrolein-induced ototoxicity in rats.

BACKGROUND: Acrolein is a reactive aldehyde that forms during burning of wood and other fuels. It is also a product of lipid peroxidation (LPO) reactions and is present in cigarette smoke. Acrolein is known to cause oxidative stress and inflammatory nerve tissue damage. Lutein is a tetraterpenoid molecule with antioxidant and anti-inflammatory properties. There appear to be no studies on the effect of lutein on vestibulocochlear nerve damage induced by acrolein. The aim of this study was to investigate the effect of lutein on vestibulocochlear nerve damage induced by acrolein in rats using biochemical and histopathological methods. METHODS: The rats were divided into three groups (n = 6, for each group) a healthy control group (HG), an acrolein (ACR) group and a lutein and acrolein (LACR) group. In the LACR group, lutein was administered (1 mg/kg) via oral gavage. The ACR and HG groups received saline via oral gavage. Then, 1 h after the administration of lutein and saline, the LACR and ACR groups were treated with 3 mg/kg of acrolein via oral gavage. This procedure was repeated once a day for 30 days. RESULTS: The results of biochemical experiments showed that in the vestibulocochlear nerve tissues of the animals treated with acrolein, the levels of malondialdehyde, total oxidants, nuclear factor kappa b, tumor necrosis factor alpha and interleukin 1 beta significantly increased, whereas the levels of total glutathione and total antioxidants decreased as compared to those in the HG and LACR groups. In addition, severe histopathological damage was observed in vestibulocochlear nerve tissue of the acrolein group, whereas this damage was alleviated in the lutein group. CONCLUSION: Lutein protected vestibulocochlear nerve tissue from acrolein-associated oxidative and proinflammatory damage. This suggests that lutein might be useful in preventing or treating acrolein-induced ototoxicity.

Tracking Spontaneous Vestibular Schwannoma Regression with Volumetric Measurements.

OBJECTIVE: To characterize a series of patients with MRI evidence of spontaneous vestibular schwannoma (VS) regression. STUDY DESIGN: Retrospective case series. METHODS: Retrospective review between 2012 and 2020 from a single, tertiary-care center of all patients with an untreated, sporadic VS and spontaneous regression in volumetric tumor size over the course of observation. The main outcome measures included VS size and location, presenting symptoms, medication use, changes in pure-tone averages and word recognition scores. RESULTS: The 13 treatment-naïve patients (62% female, mean age 67.1 years) with spontaneous VS regression represented 3.9% of all patients undergoing observation with serial imaging during the study period. Median tumor size from initial MRI was 529.0 mm3 (range: 108 mm3 -13,180 mm3 ). The mean interval between MRI measurements was 5.5 years (SD 4.4 years). The average percent decrease in tumor size was 36.1% (SD 21.9%) and the average rate of volume decrease was 15.8 mm3 /yr (SD 25.4 mm3 /yr). Five patients were classified as having major regression, defined by a relative decrease in volume of >40%, while eight patients had minor regression (<40% relative volume reduction). No significant differences in initial tumor size, rate of regression, or audiometric changes were observed between the major and minor regression cohorts. CONCLUSIONS: Patients with evidence of a spontaneously shrinking VS have a heterogeneous presentation. Due to the scarcity of this phenomenon, predicting which tumors will eventually undergo regression remains unclear. Employing volumetric measurements to compare serial MRI scans may improve the accuracy of detecting shrinking tumors. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1647-E1652, 2021.

The Relation Between Tinnitus and a Neurovascular Conflict of the Cochleovestibular Nerve on Magnetic Resonance Imaging.

INTRODUCTION: Magnetic resonance (MR) imaging is often used in diagnostic evaluation of tinnitus patients. Incidental findings like a neurovascular conflict (NVC) in the cerebellopontine angle are often found; however, the diagnostic value of this finding remains unclear. The aim of this study is to investigate whether the type or degree of compression of the vestibulocochlear nerve is of diagnostic value in patients with a NVC. METHODS: A retrospective study was performed in 111 tinnitus patients with available MR imaging between 2013 and 2015. Clinical and audiometric variables were gathered and MR imaging was reevaluated by two neuroradiologists. NVCs were analyzed using a grading system based on previous research by Sirikci et al. RESULTS:: In total, 220 ears were available for assessment. In patients with unilateral tinnitus a loop compression and an indentation of the cochleovestibular nerve were more frequent than in patients with bilateral tinnitus. However, there was no significant difference in distribution of the type of compression between tinnitus and nontinnitus ears. Patient with unilateral tinnitus had a significantly higher degree of hearing loss in the symptomatic ear, compared with the asymptomatic ear and with the bilateral tinnitus group. Also, it was found that the degree of hearing loss did not differ between the various types of compression. CONCLUSION: This study did not find a diagnostic value of specific types of compression in patients with a NVC. Although the distribution of NVC classification was different in patients with unilateral and bilateral tinnitus, there was no definite relation between the type of NVC and the presence of ipsilateral tinnitus. Also, the degree of hearing loss was not related to specific types of NVC.

Pilocytic astrocytoma of the cerebellopontine angle mimicking vestibular schwannoma: report of a rare entity.

We present a rare case of a 55-yr old patient of pilocytic astrocytoma of the cerebello-pontine angle mimicking a vestibular schwannoma. The tumor protruded into the porus acusticus causing enlargement of the internal auditory meatus, which is quite an unusual feature of glial tumours.

NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss.

Vestibular schwannoma (VS) is the fourth most common intracranial tumor, arising from neoplastic Schwann cells of the vestibular nerve and often causing debilitating sensorineural hearing loss (SNHL) and tinnitus. Previous research suggests that the abnormal upregulation of inflammatory pathways plays a highly significant, though infrequently described role in VS pathobiology, and that VS-associated SNHL is due not only to mechanical compression of the auditory nerve but also to differences in the intrinsic biology of these tumors. We hypothesize that patients who present with poor hearing associated with VS experience a more robust inflammatory response to this tumor than VS patients who present with good hearing. To investigate this hypothesis, we conducted a comprehensive pathway analysis using gene expression data from the largest meta-analysis of vestibular schwannoma microarray data, comprising 80 tumors and 16 healthy peripheral nerves. We identified the NLRP3 inflammasome as a novel target worthy of further exploration in VS research and validated this finding at the gene and protein expression level in human VS tissue using qRT-PCR and immunohistochemistry. To date, NLRP3 inflammasome activation has not been reported in VS, and this finding may represent a new and potentially significant therapeutic avenue. Notably, after analysis of 30 VSs, we observe that overexpression of key components of the NLRP3 inflammasome is preferentially associated with tumors that produce increased hearing loss in VS patients. Therefore, therapeutic development for VS should include considerations for minimizing NLRP3-associated inflammation to best preserve hearing.

Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review.

A rare case of extraventricular neurocytoma (EVN) arising from the VIIIth cranial nerve in a 34-year-old woman is reported. The patient had a 20-year history of hearing loss and facial palsy. Computed tomography showed a 3-cm enhancing lesion in the left cerebellopontine angle (CPA). At operation, the tumor was seen to originate from the cochlear and vestibular nerves. The tumor was subtotally resected. Histologically, the tumor consisted of uniform cells with oval to round nuclei and scant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, but negative for glial fibrillary acid protein and S-100 protein. The Ki-67 labeling index was 0%. Twelve years after the operation, magnetic resonance imaging (MRI) showed tumor recurrence at the left CPA. The tumor was subtotally resected, and radiation therapy was given. Histologically, the tumor consisted of round cells with mild atypia and one mitosis/20 high-power fields (HPF). Immunohistochemically, tumor cells showed the same findings as the first operation sample, except for the Ki-67 labeling index (3%). Twelve years after the second operation, MRI showed a second tumor recurrence at the left CPA and surroundings of the brain stem. The tumor was subtotally resected. Histologically, the tumor consisted of anaplastic short spindle cells and five mitoses/10 HPF. The immunohistochemical findings were almost the same as the earlier operation samples. However, the Ki-67 labeling index was 20%. In addition, tumor cells from the third specimen were more strongly and more diffusely positive for GAB1 (growth factor receptor-bound protein 2-associated binding protein 1) compared to those of the earlier specimens. Electron microscopy showed the presence of numerous cell processes with a dense core and clear vesicles and microtubules. GAB1 immunostaining also indicated that malignant progression might be associated with the sonic hedgehog signaling pathways. To the best of our knowledge, this is the first report of an EVN arising from the VIIIth cranial nerve with malignant progression.

Complications in translabyrinthine surgery of vestibular schwannoma.

OBJECTIVE: To evaluate the risk of complications associated with tumor size and patient's age in translabyrinthine vestibular schwannoma surgery. METHODS: 700 patients with vestibular schwannoma primarily underwent translabyrinthine surgery between 1988 and 2014. Pre- and postoperative data were collected in a database and incidence of the postoperative complications cerebrospinal fluid leakage, meningitis, intracranial hemorrhage (ICH), facial nerve function and mortality were assessed and related to the tumor size and patient's age and retrospectively evaluated. RESULTS: The tumor size significantly influenced the incidence of ICH and facial nerve dysfunction whereas age was correlated to facial nerve outcome. CONCLUSIONS: The translabyrinthine approach is a safe surgical procedure with relatively low risks of complications. The tumor size was significantly associated with a higher risk of ICH and facial nerve dysfunction whereas age only influenced the facial nerve outcome.

YAP, TAZ and AREG expression in eighth cranial nerve schwannoma.

BACKGROUND: Although the diagnosis and treatment of eighth cranial nerve (VIII CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable of predicting tumor growth have been identified as yet. This study is a preliminary investigation of the expression in sporadic VIII CN schwannomas of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of tumors on contrast-enhanced magnetic resonance imaging (ceMRI). METHODS: YAP, TAZ and AREG expression was assessed immunohistochemically in surgical specimens of 36 consecutive sporadic VIII CN schwannomas. 3D reconstructions of the tumors and their corresponding volumes in cm3 were obtained from measurements on ceMRI images using the OsiriX® software. RESULTS: We found a significant direct correlation between TAZ expression and VIII CN schwannoma volumes on latest preoperative ceMRI (p<0.0003). Mean TAZ expression was also significantly higher in VIII CN schwannomas with a volume ≥2.1 cm3 than in those with a volume <2.1 cm3(p<0.0018). No significant correlations emerged for YAP or AREG expression and VIII CN schwannoma volume. CONCLUSIONS: The immunohistochemical expression of TAZ (but not YAP or AREG) correlated significantly with schwannoma volume measured on ceMRI. Further investigations are needed to identify the biological factors influencing tumor proliferation (ideally secreted proteins like AREG) that might be detected using non-invasive approaches (i.e., blood samples).

Characteristics of hearing loss in patients with herpes zoster oticus.

Patients with herpes zoster oticus (HZO) may commonly show symptoms associated with 7th and 8th cranial nerve (CN VII and CN VIII) dysfunction. The aim of this study is to investigate the characteristics of hearing loss in patients with HZO and discuss possible mechanisms.Ninety-five HZO patients who showed at least one of the symptoms of CN VII and CN VIII dysfunction between January 2007 and October 2014 were included in this study. Hearing loss was defined when the mean thresholds of pure tone audiometry (PTA) in speech frequency (0.5 kHz + 1 kHz + 2 kHz/3) or isolated high frequency (4 kHz + 8 kHz/2) were greater than 10 dB in the affected ear compared with the healthy ear, and a total of 72 patients were classified as the hearing loss group.The difference of mean PTA thresholds between affected and healthy ears was significantly greater in the high frequency range than in low range (20.0 ±â€Š11.5 dB vs. 12.9 ±â€Š15.7 dB, P = 0.0026) in patients with hearing loss (n = 72). The difference between affected and healthy ear was significantly greater in patients with vertigo (n = 34) than those without vertigo (n = 38) in both the high (P = 0.033) and low (P = 0.024) frequency ranges. In contrast, the differences between affected and healthy ears were not significantly different between patients with facial palsy (n = 50) and those without facial palsy (n = 22) in both the high (P = 0.921) and low (P = 0.382) frequency ranges.In patients with HZO, hearing loss is more severe in the high frequency range than in the low frequency range. Hearing impairment is more severe in patients with vertigo than in those without vertigo in both the high and low frequency ranges, even though the degree of hearing impairment is not significantly different between patients with and without facial palsy. These findings indicate that the mechanisms of viral spread from CN VII to CN VIII may differ between vestibular and audiologic deficits.

[Microanatomy of the cranial segment of the vestibulocochlear nerve. Possible correlations with the symptoms of neurovascular compression syndrome].

The objective of the present study was to elucidate the topographic features of the nerve fibers belonging to the acoustic and vestibular analyzers located in the intracranial cranial segment of human vestibulocochlear nerve (VCN). A total of 16 samples of the intracranial cranial segment of the human vestibulocochlear nerve isolated from the region enclosed between the exit of VCN from the brainstem and its entrance into the internal acoustic meatus were available for the investigation. Prior to fixation of the samples, the VCN segments were marked in correspondence with their intravital anatomical location in the posterior cranial fossa. Cross sections of the PCN segments were stained with hematoxylin and eosin as well as according to the van-Hison method. The cross sections were made either at the exit of the nerve from the brainstem (N1), its entrance into the internal acoustic meatus (N3) or in-between these sites (N2). The morphometric analysis of the sections and the statistical treatment of the data obtained were performed with the use of the Diamfor hardware and software complex («Diamfor¼, Russia). The digitized images of the PCN sections were prepared using amVizo 103 microvisor (Russia). It was shown that the intracranial segment of the human vestibulocochlear nerve consists of two isolated groups of nerve fibers differing in terms of staining density, size, and the degree of myelinization. The mutual location of the fibers forming the cochlear and vestibular nuclei (CN and VN respectively) varies. Namely, CN near the internal acoustic foramen occupies the antero-posterior position with respect to VN. In the middle part of VCN, CN-forming fibers are located at the anetro-inferoposterior surface of the nerve. The nerve fibers of both CN and VN are similarly arranged near the lateral surface of the brain stem.

Central nervous system infections caused by varicella-zoster virus.

We carried out a clinical and epidemiological study of adult patients with varicella-zoster virus central nervous system infection diagnosed by PCR in cerebrospinal fluid. Twenty-six patients were included. Twelve (46.2 %) patients were diagnosed with meningitis and fourteen (53.8 %) with meningoencephalitis. Twelve (46.2 %) had cranial nerves involvement (mainly the facial (VII) and vestibulocochlear (VIII) nerves), six (23.1 %) had cerebellar involvement, fourteen (53.8 %) had rash, and four (15.4 %) developed Ramsay Hunt syndrome. Three (11.5 %) patients had sequelae. Length of stay was significantly lower in patients diagnosed with meningitis and treatment with acyclovir was more frequent in patients diagnosed with meningoencephalitis. We believe routine detection of varicella-zoster virus, regardless of the presence of rash, is important because the patient may benefit from a different clinical management.