Preoperative vestibular evoked myogenic potentials (VEMPs), caloric test, and pure tone audiometry to identify the vestibular nerve branch of schwannoma origin: preliminary results in a series of 26 cases.

Vestibular schwannoma (VS) is a benign tumor which develops in the internal auditory canal and the cerebellopontine angle, potentially diminishing hearing or balance. Most VS tumors arise from one of two vestibular branches: the superior or inferior vestibular nerve. Determining the specific nerve of origin could improve patient management in terms of preoperative counseling, treatment selection, and surgical decision-making and planning. The aim of this study was to introduce a preoperative testing protocol with high accuracy to determine the nerve branch of origin. The nerve of origin was predicted on the basis of preoperative vestibular evoked myogenic potentials (VEMPs), caloric stimulation test, and pure tone audiometry on 26 recipients. The acquired data were entered into a statistic scoring system developed to allocate the tumor origin. Finally, the nerve of origin was definitively determined intraoperatively. Receiver operating characteristic (ROC) curves analysis of preoperative testing data showed the possibility of predicting the branch of origin. In particular, ROC curve of combined VEMPs absence, nystagmus detectable at caloric stimulation, and PTA < 75 dB HL allowed to obtain high accuracy for inferior vestibular nerve implant of the tumor (area under the curve-AUC = 0.8788, p = 0.012). In 24 of 26 cases, the preoperatively predicted tumor origin was the same as the origin determined during surgery. Preoperative audiological and vestibular evaluation can predict the vestibular tumor branch of origin with high accuracy. Despite the necessity of larger prospective cohort studies, these findings may change preoperative approach, possible functional aspects, and counseling with the patients.

Sperm-associated antigen 6 (Spag6) mutation leads to vestibular dysfunction in mice.

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 plays a role in hearing and planar cell polarity (PCP) in the cochlea of the inner ear. However, a role for Spag6 in the vestibule has not yet been explored. In the present study, the function of Spag6 in the vestibule of the inner ear was examined using Spag6-deficient mice. Our results demonstrate a vestibular disorder in the Spag6 mutants, associated with abnormal ultrastructures of vestibular hair cells and Scarpa's ganglion cells, including swollen stereocilia, decreased crista in mitochondria and swollen Scarpa's ganglion cells. Immunostaining data suggests existence of caspase-dependent apoptosis in vestibular sensory epithelium and Scarpa's ganglion cells. Our observations reveal new functions for Spag6 in vestibular function and apoptosis in the mouse vestibule.

Superior vestibular neuritis: improved detection using FLAIR sequence with delayed enhancement (1 h).

INTRODUCTION: Vestibular neuritis is the second cause of vertigo and new imaging protocols using delayed FLAIR with double-dose of gadolinium are proposed for its diagnosis. Our aim is to demonstrate that a single dose of gadolinium is sufficient. METHODS: Thirty-three patients with a unilateral vestibular neuritis are compared to a control group. All patients underwent a FLAIR sequence, 1 hour after intravenous injection of a single dose of gadolinium, on a 1.5 Tesla MRI. Two radiologists analyzed the enhancement intensity of the superior (sup VN) and inferior vestibular nerve (inf VN) and ratios to the signal of the cerebellum were calculated (supVN/C). The statistics were performed using Bayesian analysis. RESULTS: A strong enhancement of the sup VN was observed on the pathological side in 85% of patients with vestibular neuritis. The average signal intensity of the pathological sup VN (139 units ± 44) was more than two times the average intensity in the control group (58.5 units ± 5). The average ratios supVN/C were significantly different between the pathological side in vestibular neuritis (2.43 units ± 0.63) and the control group [1.16 ± 0.14 (Pr(diff > 0) = 1)]. A delayed enhancement > 71.5 units had a sensitivity of 96% and a specificity of 100% for the diagnosis of superior vestibular neuritis. CONCLUSION: A delayed FLAIR sequence, acquired 1 hour after a single dose of gadolinium injection, is a useful method for the diagnosis of vestibular neuritis. An enhancement of the sup VN > 71.5 units was in favor of the diagnosis.

Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the MPZ Gene.

Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Molecular genetic testing of DNA obtained at autopsy revealed a missense variant in the MPZ gene (p.Thr65Ala), pathogenic for an autosomal-dominant form of CMT1B. The temporal bones were also prepared for light microscopy by hematoxylin and eosin and Gömöri trichome stains, and immunostaining for anti-myelin protein zero. Pathology was consistent with a myelinopathy of the auditory, vestibular, and facial nerves bilaterally. The pathophysiology of cranial nerve dysfunction in CMT is unknown. Findings in the current case suggested, at least in cranial nerves 7 and 8, that a myelinopathy may be causative.

Preoperative determination of nerve of origin in patients with vestibular schwannoma.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor that develops in the internal auditory canal and the cerebellopontine angle, potentially diminishing hearing or balance. Most VS tumors arise from one of two vestibular branches: the superior or inferior vestibular nerve. Determining the specific nerve of origin could improve patient management in terms of preoperative counseling, treatment selection, and surgical decision-making and planning. The aim of this study was to introduce a novel scoring system that was designed to determine the nerve of origin. METHODS: The nerve of origin was predicted based on video head impulse assessments of all semicircular channels, together with cervical/ocular vestibular-evoked myogenic potential tests. The acquired data were entered into a scoring system developed to allocate the tumor origin. Finally, the nerve of origin was definitively determined intraoperatively. RESULTS: The novel scoring system was applied to five consecutive patients undergoing surgical VS treatment. In one case, no determination was possible. In all other cases, the preoperatively predicted tumor origin was the same as the origin determined during surgery. CONCLUSION: The scoring system predicts the nerve of origin and will be evaluated in a larger prospective cohort study of VS patients in the near future.

[Preoperative determination of nerve of origin in patients with vestibular schwannoma. German version]. / Präoperative Bestimmung des Ursprungsnervs von Vestibularisschwannomen.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor that develops in the internal auditory canal and the cerebellopontine angle, potentially diminishing hearing or balance. Most VS tumors arise from one of two vestibular branches: the superior or inferior vestibular nerve. Determining the specific nerve of origin could improve patient management in terms of preoperative counseling, treatment selection, and surgical decision-making and planning. The aim of this study was to introduce a novel scoring system that was designed to determine the nerve of origin. METHODS: The nerve of origin was predicted based on video head impulse assessments of all semicircular channels, together with cervical/ocular vestibular-evoked myogenic potential tests. The acquired data were entered into a scoring system developed to allocate the tumor origin. Finally, the nerve of origin was definitively determined intraoperatively. RESULTS: The novel scoring system was applied to 5 consecutive patients undergoing surgical VS treatment. In one case, no determination was possible. In all other cases, the preoperatively predicted tumor origin was the same as the origin determined during surgery. CONCLUSION: The scoring system predicts the nerve of origin and will be evaluated in a larger prospective cohort study of VS patients in the near future.

[Video head impulse test for evaluation of vestibular function in patients with vestibular neuritis and benign paroxysmal positional vertigo].

Objective: To assess the clinical application of video head impulse test (vHIT) for vestibular function in vestibular neuritis (VN) and benign paroxysmal positional vertigo (BPPV) patients. Methods: Thirty-three patients with VN and 43 patients with BPPV were enrolled from Sir Run Run Shaw Hospital and Ningbo Second Hospital from March 15 to September 10, 2015; and 50 healthy controls were also enrolled in the study. vHIT was used to quantitatively test the vestibulo-ocular reflex (VOR) gains of a pair of horizontal semicircular canals. VOR gains two pairs of vertical semicircular canals, and the corresponding asymmetrical value of three VOR gains. The saccades information was also recorded. Results: Compared with the healthy control group and BPPV patients, the affected horizontal and vertical VOR gains were declined and the corresponding asymmetries were increased in VN patients (all P<0.01). BPPV group also showed higher vertical VOR gain asymmetries compared with the healthy control group (all P<0.01), but no significant difference was observed in VOR gains and horizontal VOR gain asymmetry (all P>0.05). The sensibility of vHIT in diagnosis of VN was 87.9%. Among 33 VN patients, 22 were diagnosed with superior vestibular nerve dysfunction, 7 were found with inferior vestibular nerve dysfunction and 3 were with both dysfunction; and 1 case was not distinguished. Conclusion: Video head impulse test can quantitatively evaluate the vestibular dysfunction of VN and can help early diagnosis of VN, which may be widely used in clinic.

Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2.

BACKGROUND: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve. METHODS: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve. RESULTS: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN. DISCUSSION: This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease.

Developmental changes in the protective effect of exogenous brain-derived neurotrophic factor and neurotrophin-3 against ototoxic drugs in cultured rat vestibular ganglion neurons.

We examine developmental changes in the responsiveness of rat vestibular ganglion neurons (VGNs) to two neurotrophic factors (NTFs), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and investigate the protective effects of these NTFs against ototoxic drugs during postnatal development in dissociated cultures. VGNs were obtained from rats on postnatal days (P) 1, 3, 7 and 14. BDNF facilitated neuronal survival as well as neurite sprouting of VGNs obtained from younger rats (P1 and P3), whereas these effects were not observed in older rats (P7 and P14). BDNF was also effective in facilitating neurite extension in VGNs at each of the postnatal ages. NT-3 also facilitated neuronal survival and neurite extension of VGNs from younger rats but these effects were significantly smaller than those of BDNF (p < 0.05). The protective effects of BDNF and NT-3 against ototoxic drugs, gentamicin and cisplatin, were also age-dependent: they were effective for neuronal survival, neurite sprouting and neurite extension in VGNs from younger rats, whereas these effects tended to disappear in VGNs from older rats. Analysis of the changes in the expression of the receptors of NTFs revealed that expression of TrkB and TrkC proteins and their mRNA did not change during the developmental period, whereas expression of p75(NTR) protein was down-regulated together with that of p75(NTR) mRNA during the developmental period. Developmental changes in the responsiveness to exogenous NTFs in VGNs, which is not caused by the changes of their receptors but probably caused by changes in the intracellular signaling pathways, should be taken into consideration in the prevention of neuronal degeneration caused by ototoxic drugs.

Multiple Intracranial Schwannomas of the Vestibular and Trigeminal Nerves: A Technical Note.

BACKGROUND: A schwannoma is a nerve sheath tumor that is formed by Schwann cells. Vestibular schwannomas are thought to account for the majority of intracranial schwannomas. Nonvestibular schwannomas account for about 10%, about half of which are trigeminal schwannomas. Multiple intracranial schwannomas originating from different cranial nerves are extremely rare. METHODS: We describe the clinical case of a 42-year-old female patient with vestibular schwannoma and multiple trigeminal schwannomas. RESULTS: That case shows how multiple trigeminal schwannomas were identified intraoperatively during elective surgery for vestibular schwannoma removal, most of which were resected. No new neurological deficits were observed in the patient. CONCLUSIONS: The presence of multiple intracranial schwannomas is extremely rare in neurosurgical practice and can change the intraoperative strategy and the course of the surgery.

Cellular Processes Induced by HSV-1 Infections in Vestibular Neuritis.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of the herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illustrative examples.

What is the site of origin of cochleovestibular schwannomas?

The belief that cochleovestibular schwannomas arise from the glial-Schwann cell junction has repeatedly been quoted in the literature, although there is no published evidence that supports this statement. A systematic evaluation of the nerve of origin and the precise location of cochleovestibular schwannomas using our respective archival temporal bone collections was conducted. Forty tumors were within the internal auditory canal (IAC), while 10 were intralabyrinthine neoplasms. Of the 40 IAC schwannomas, 4 arose from the cochlear nerve, and 36 from the vestibular nerve. Twenty-one tumors clearly arose lateral to the glial-Schwann cell junction, while 16 tumors filled at least two thirds of the IAC, with the epicenter of the neoplasm located in the mid part or the lateral part of the IAC. Only 3 schwannomas were located in the medial one third of the IAC in the area of the glial-Schwann cell junction. We concluded that cochleovestibular schwannomas may arise anywhere along the course of the axons of the eighth cranial nerve from the glial-Schwann sheath junction up until their terminations within the auditory and vestibular end organs.

Cross-sectional vestibular nerve analysis in vestibular neuritis.

OBJECTIVES: We examined the association between the size and cross-sectional area of the superior vestibular nerve as measured on constructive interference in steady-state (CISS) parasagittal magnetic resonance imaging (MRI) and the vestibular nerve function as measured by electronystagmography. METHODS: The retrospective observational cohort study took place at an academic tertiary referral center. Twenty-six patients who met established clinical and electronystagmographic criteria for vestibular neuritis and who underwent parasagittal CISS MRI were identified. Two blinded investigators measured vestibular nerve height and width bilaterally at the level of the fundus of the internal auditory canal and calculated the cross-sectional nerve areas. The inter-rater reliability and agreement were analyzed. Symptom duration, age, and gender were also examined. RESULTS: A statistically significant decrease was observed in both vestibular nerve cross-sectional area and height as compared to the contralateral vestibular nerve. A non-statistically significant trend was observed for a relative decreased cross-sectional nerve area with increased age, as well as a decrease in nerve area with an increase in symptom duration. CONCLUSIONS: Decreases in both vestibular nerve cross-sectional area and height are observed in patients with unilateral vestibular neuritis as measured on parasagittal CISS MRI.

Radial spoiled gradient T1 weighted imaging of the internal auditory canal: Is Scarpa's ganglion now an expected finding and source of fundal enhancement?

StarVIBE is a 3D gradient-echo sequence with a radial, stack-of-stars acquisition having spatial resolution and tissue contrast. With newer sequences, it is important to be familiar with sequence tissue contrasts and appearance of anatomical variants. We evaluated 450 patients utilizing this sequence; 35 patients demonstrated fluffy "cotton wool" enhancement at the internal auditory canal fundus without clear pathology. We favor this represents anatomic neurovascular enhancement that StarVIBE is sensitive to and is a touch-me-not finding.

Voxel-based morphometry depicts central compensation after vestibular neuritis.

OBJECTIVE: Patients who have had vestibular neuritis (VN) show a remarkable clinical improvement especially in gait and posture >6 months after disease onset. METHODS: Voxel-based morphometry was used to detect the VN-induced changes in gray and white matter by means of structural magnetic resonance imaging. Twenty-two patients were compared an average 2.5 years after onset of VN to a healthy sex-and age-matched control group. RESULTS: Our analysis revealed that all patients had signal intensity increases for gray matter in the medial vestibular nuclei and the right gracile nucleus and for white matter in the area of the pontine commissural vestibular fibers. A relative atrophy was observed in the left posterior hippocampus and the right superior temporal gyrus. Patients with a residual canal paresis also showed an increase of gray matter in middle temporal (MT)/V5 bilaterally. INTERPRETATION: These findings indicate that the processes of central compensation after VN seem to occur in 3 different sensory systems. First of all, the vestibular system itself showed a white matter increase in the commissural fibers as a direct consequence of an increased internuclei vestibular crosstalk of the medial vestibular nuclei. Second, to regain postural stability, there was a shift to the somatosensory system due to an elevated processing of proprioceptive information in the right gracile nucleus. Third, there was a bilateral increase in the area of MT/V5 in VN patients with a residual peripheral vestibular hypofunction. This seems to be the result of an increased importance of visual motion processing.

Optimized preoperative determination of nerve of origin in patients with vestibular schwannoma.

In vestibular schwannoma (VS) patients hearing outcome and surgery related risks can vary and depend on the nerve of origin. Preoperative origin differentiation between inferior or superior vestibular nerve may influence the decision on treatment, and the selection of optimal treatment and counselling modalities. A novel scoring system based on functional tests was designed to predict the nerve of origin for VS and was applied to a large number of consecutive patients. A prospective, double blind, cohort study including 93 patients with suspected unilateral VS was conducted at a tertiary referral centre. Preoperatively before tumor resection a functional test battery [video head-impulse test (vHIT) of all semicircular canals (SCC)], air-conducted cervical/ocular vestibular evoked myogenic potential tests (cVEMP, oVEMP), pure-tone audiometry, and speech discrimination was applied. Sensitivity and specificity of prediction of intraoperative finding by a preoperative score based on vHIT gain, cVEMP and oVEMP amplitudes and asymmetry ratios was calculated. For the prediction of inferior vestibular nerve origin, sensitivity was 73% and specificity was 80%. For the prediction of superior vestibular nerve origin, sensitivity was 60% and specificity was 90%. Based on the trade-off between sensitivity and specificity, optimized cut-off values of - 0.32 for cVEMP and - 0.11 for oVEMP asymmetry ratios and vHIT gain thresholds of 0.77 (anterior SCC), 0.84 (lateral SCC) and 0.80 (posterior SCC) were identified by receiver operator characteristic curves. The scoring system based on preoperative functional tests improves prediction of nerve of origin and can be applied in clinical routine.

Arachnoid Cysts of the Internal Auditory Canal: Multiplanar Magnetic Resonance Imaging With Audio-Vestibular Correlates.

OBJECTIVES/HYPOTHESIS: To investigate prevalence, radiological characteristics, and functional correlates of arachnoid cysts (AC) of the internal auditory canal (IAC) region, including associations of nerve compression with auditory/vestibular symptoms and asymmetrical audiogram or vestibular testing. STUDY DESIGN: Retrospective study. METHODS: T2-weighted magnetic resonance imaging (MRI) studies of IACs were retrospectively analyzed from 1247 patients with asymmetric auditory or vestibular symptoms. Patients with radiological findings of AC of the IAC were identified. Multiplanar analysis was used to analyze cyst position in the IAC and assess nerve displacement or compression. Size, position, and presence of nerve compression were correlated with symptoms. RESULTS: Twenty-four patients had a cyst in the middle or fundus in the IAC. Diameter (P = .04) and position (P = .002) of AC were associated with symptoms. Sagittal analyses identified displacement versus compression (P = .003) more reliably than axial imaging. Symptom laterality was associated with the site of radiological abnormality. Vestibular nerve compression was associated with vertigo (P = .0001), and cochlear nerve compression was associated with auditory symptoms (P < .0001). CONCLUSIONS: In a retrospective series of patients undergoing MRI of IACs for asymmetric auditory or vestibular impairment, clinical symptom profile correlated with blinded assessment of IAC lesions. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2323-2331, 2021.

Changes in TNFα, NFκB and MnSOD protein in the vestibular nuclei after unilateral vestibular deafferentation.

BACKGROUND: Unilateral vestibular deafferentation results in strong microglial and astroglial activation in the vestibular nuclei (VN) that could be due to an inflammatory response. This study was aimed at determining if markers of inflammation are upregulated in the VN after chemical unilateral labyrinthectomy (UL) in the rat, and if the inflammatory response, if any, induces the expression of neuroprotective factors that could promote the plasticity mechanisms involved in the vestibular compensation process. The expressions of inflammatory and neuroprotective factors after chemical or mechanical UL were also compared to verify that the inflammatory response was not due to the toxicity of sodium arsanilate. METHODS: Immunohistological investigations combined the labeling of tumor necrosis factor α (TNFα), as a marker of the VN inflammatory response, and of nuclear transcription factor κB (NFκB) and manganese superoxide dismutase (MnSOD), as markers of neuroprotection that could be expressed in the VN because of inflammation. Immunoreactivity (Ir) of the VN cells was quantified in the VN complex of rats. Behavioral investigations were performed to assess the functional recovery process, including both static (support surface) and dynamic (air-righting and landing reflexes) postural tests. RESULTS: Chemical UL (arsanilate transtympanic injection) induced a significant increase in the number of TNFα-Ir cells in the medial and inferior VN on both sides. These changes were detectable as early as 4 h after vestibular lesion, persisted at 1 day, and regained nearly normal values at 3 days. The early increase in TNFα expression was followed by a slightly delayed upregulation of NFκB 8 h after chemical UL, peaking at 1 day, and regaining control values 3 days later. By contrast, upregulation of MnSOD was more strongly delayed (1 day), with a peak at 3 days, and a return to control values at 15 days. Similar changes of TNFα, NFκB, and MnSOD expression were found in rats submitted to mechanical UL. Behavioral observations showed strong posturo-locomotor deficits early after chemical UL (1 day) and a complete functional recovery 6 weeks later. CONCLUSIONS: Our results suggest that the upregulation of inflammatory and neuroprotective factors after vestibular deafferentation in the VN may constitute a favorable neuronal environment for the vestibular compensation process.

Treatment of idiopathic hemifacial spasm with radiosurgery or hypofractionated stereotactic radiotherapy: preliminary results.

INTRODUCTION: Microvascular decompression in the posterior cranial fossa is the first treatment option for hemifacial spasm. For patients not suitable for surgery because of advanced age, poor general conditions or patients who refuse surgery, radiotherapeutic treatment could be an alternative. Only one case of resolution of hemifacial spasm in a patient undergoing radiosurgery for an intracanalicular vestibular schwannoma has been described in the literature. In this article we present three patients affected by idiopathic hemifacial spasm, refractory to medical therapy and botulinum toxin injections, who were treated by radiosurgery in one case and hypofractionated stereotactic radiotherapy in the other two. METHODS: Radiosurgery, with a single dose of 8 Gy, was used in the first patient affected by idiopathic hemifacial spasm and autoimmune polyneuropathy with severe hypoacusia; hypofractionated stereotactic radiotherapy, with 15 Gy in 5 fractions of 3 Gy each, was preferred in the other 2 cases. In all patients, the target consisted of the vestibulocochlear-facial bundle immediately before its entry into the internal acoustic foramen. RESULTS: A marked improvement of symptoms was observed in 2 patients, and almost complete disappearance in the other case, with no complications, particularly, auditory. CONCLUSION: The mean follow-up time of 24 months reported here could be judged too short, and our series too small, but the good results observed so far lead us to underline that, as in trigeminal neuralgia, radiosurgery or hypofractionated stereotactic radiotherapy could represent a therapeutic alternative to microvascular decompression for idiopathic hemifacial spasm for patients not suitable for surgery.