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.

L-Thyroxine Improves Vestibular Compensation in a Rat Model of Acute Peripheral Vestibulopathy: Cellular and Behavioral Aspects.

Unilateral vestibular lesions induce a vestibular syndrome, which recovers over time due to vestibular compensation. The therapeutic effect of L-Thyroxine (L-T4) on vestibular compensation was investigated by behavioral testing and immunohistochemical analysis in a rat model of unilateral vestibular neurectomy (UVN). We demonstrated that a short-term L-T4 treatment reduced the vestibular syndrome and significantly promoted vestibular compensation. Thyroid hormone receptors (TRα and TRß) and type II iodothyronine deiodinase (DIO2) were present in the vestibular nuclei (VN), supporting a local action of L-T4. We confirmed the T4-induced metabolic effects by demonstrating an increase in the number of cytochrome oxidase-labeled neurons in the VN three days after the lesion. L-T4 treatment modulated glial reaction by decreasing both microglia and oligodendrocytes in the deafferented VN three days after UVN and increased cell proliferation. Survival of newly generated cells in the deafferented vestibular nuclei was not affected, but microglial rather than neuronal differentiation was favored by L-T4 treatment.

Vestibular mapping in patients with unilateral peripheral-vestibular deficits.

OBJECTIVE: To test the hypothesis that patterns of semicircular canal (SCC) and otolith impairment in unilateral vestibular loss depend on the underlying disorders, we analyzed peripheral-vestibular function of all 5 vestibular sensors. METHODS: For this retrospective case series, we screened the hospital video-head-impulse test database (n = 4,983) for patients with unilaterally impaired SCC function who also received ocular vestibular-evoked myogenic potentials and cervical vestibular-evoked myogenic potentials (n = 302). Frequency of impairment of vestibular end organs (horizontal/anterior/posterior SCC, utriculus/sacculus) was analyzed with hierarchical cluster analysis and correlated with the underlying etiology. RESULTS: Acute vestibular neuropathy (AVN) (37.4%, 113 of 302), vestibular schwannoma (18.2%, 55 of 302), and acute cochleovestibular neuropathy (6.6%, 20 of 302) were most frequent. Horizontal SCC impairment (87.4%, 264 of 302) was more frequent (p < 0.001) than posterior (47.4%, 143 of 302) and anterior (37.8%, 114 of 302) SCC impairment. Utricular damage (58%, 175 of 302) was noted more often (p = 0.003) than saccular impairment (32%, 98 of 302). On average, 2.6 (95% confidence interval 2.48-2.78) vestibular sensors were deficient, with higher numbers (p ≤ 0.017) for acute cochleovestibular neuropathy and vestibular schwannoma than for AVN, Menière disease, and episodic vestibular syndrome. In hierarchical cluster analysis, early mergers (posterior SCC/sacculus; anterior SCC/utriculus) pointed to closer pathophysiologic association of these sensors, whereas the late merger of the horizontal canal indicated a more distinct state. CONCLUSIONS: While the extent and pattern of vestibular impairment critically depended on the underlying disorder, more limited damage in AVN and Menière disease was noted, emphasizing the individual range of loss of function and the value of vestibular mapping. Likely, both the anatomic properties of the different vestibular end organs and their vulnerability to external factors contribute to the relative sparing of the vertical canals and the sacculus.

An fMRI study of visuo-vestibular interactions following vestibular neuritis.

Vestibular neuritis (VN) is characterised by acute vertigo due to a sudden loss of unilateral vestibular function. A considerable proportion of VN patients proceed to develop chronic symptoms of dizziness, including visually induced dizziness, specifically during head turns. Here we investigated whether the development of such poor clinical outcomes following VN, is associated with abnormal visuo-vestibular cortical processing. Accordingly, we applied functional magnetic resonance imaging to assess brain responses of chronic VN patients and compared these to controls during both congruent (co-directional) and incongruent (opposite directions) visuo-vestibular stimulation (i.e. emulating situations that provoke symptoms in patients). We observed a focal significant difference in BOLD signal in the primary visual cortex V1 between patients and controls in the congruent condition (small volume corrected level of p < .05 FWE). Importantly, this reduced BOLD signal in V1 was negatively correlated with functional status measured with validated clinical questionnaires. Our findings suggest that central compensation and in turn clinical outcomes in VN are partly mediated by adaptive mechanisms associated with the early visual cortex.

A Case of Bilateral Atrophy of the Inferior Vestibular Nerves.

: We report a case of a 62-year-old woman who was found to have bilateral atrophy of the inferior vestibular nerves on magnetic resonance imaging (MRI) after presenting to our clinic with 6 years of intermittent vertigo and residual unsteadiness. The nerve atrophy may be associated with an episode of vestibular neuritis, a common cause of vertigo that exclusively involves the inferior vestibular nerve in less than 3% of cases. While MRI may demonstrate vestibular nerve enhancement in cases of acute vestibular neuritis, no single MRI finding has been demonstrated consistently among cases of acute or chronic vestibular neuritis. Physical therapy is likely an effective long-term treatment for this patient to achieve central compensation for symptomatic relief.

Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the Superior and Inferior Divisions of the Vestibular Ganglia: Implications for Vestibular Neuritis.

Controversy still surrounds both the etiology and pathophysiology of vestibular neuritis (VN). Especially uncertain is why the superior vestibular nerve (SVN) is more frequently affected than the inferior vestibular nerve (IVN), which is partially or totally spared. To address this question, we developed an improved method for preparing human vestibular ganglia (VG) and nerve. Subsequently, macro- and microanatomical as well as PCR studies were performed on 38 human ganglia from 38 individuals. The SVN was 2.4 mm longer than the IVN, and in 65% of the cases, the IVN ran in two separate bony canals, which was not the case for the SVN. Anastomoses between the facial and cochlear nerves were more common for the SVN (14/38 and 9/38, respectively) than for the IVN (7/38 and 2/38, respectively). Using reverse transcription-quantitative PCR (RT-qPCR), we found only a few latently herpes simplex virus 1 (HSV-1)-infected VG (18.4%). In cases of two separate neuronal fields, infected neurons were located in the superior part only. In summary, these PCR and micro- and macroanatomical studies provide possible explanations for the high frequency of SVN infection in vestibular neuritis.IMPORTANCE Vestibular neuritis is known to affect the superior part of the vestibular nerve more frequently than the inferior part. The reason for this clinical phenomenon remains unclear. Anatomical differences may play a role, or if latent HSV-1 infection is assumed, the etiology may be due to the different distribution of the infection. To shed further light on this subject, we conducted different macro- and microanatomical studies. We also assessed the presence of HSV-1 in VG and in different sections of the VG. Our findings add new information on the macro- and microanatomy of the VG as well as the pathophysiology of vestibular neuritis. We also show that latent HSV-1 infection of VG neurons is less frequent than previously reported.

Clinical Significance of Arterial Stiffness and Metabolic Syndrome Scores in Vestibular Neuritis.

OBJECTIVE: To investigate the clinical significance of cardiovascular factors, including arterial stiffness and metabolic syndrome scores, in the development of vestibular neuritis. STUDY DESIGN: A prospective, case-control study. SETTING: Tertiary referral center. PATIENTS: Fifty-eight adult patients with vestibular neuritis (VN) and 58 age- and sex-matched controls were evaluated between January 2015 and January 2016. INTERVENTION: Measurement of arterial stiffness. MAIN OUTCOME MEASURES: Arterial stiffness was assessed from brachial-ankle pulse wave velocity (baPWV), and cardiovascular markers including blood pressure, body mass index and lipid profiles, and metabolic syndrome scores were determined. The dizziness handicap inventory (DHI) and vestibular function tests, including the caloric test and video head impulse test were evaluated. The correlations between cardiovascular factors and clinical parameters of VN were assessed. RESULTS: Blood pressure, baPWV, and metabolic syndrome scores were higher in the VN group than in the control group (p = 0.002, p = 0.001, and p = 0.001, respectively), whereas comorbidity, anthropometric characteristics, and lipid profiles did not differ significantly. baPWV and metabolic syndrome scores were not correlated with the clinical parameters of the DHI scores, canal paresis, and spontaneous nystagmus duration. In addition, cardiovascular factors did not associate with the vestibular compensation. CONCLUSIONS: Higher baPWV, representative of arterial stiffness, and higher metabolic syndrome scores, are associated with the development of VN. This supports the hypothesis of a vascular etiology of the disease. However, cardiovascular risk factors had limited value in predicting the clinical course of VN.

Facial and vestibular neuropathy of unknown origin in 16 dogs.

OBJECTIVES: The aim of this study was to describe the signalment, clinical presentation, diagnostic findings and long-term follow-up in dogs with concomitant facial and vestibular neuropathy of unknown origin. METHODS: Appropriate cases were located through medical record searches. Inclusion criteria comprised dogs that had: clinical signs of facial paralysis with concomitant peripheral vestibular syndrome, thyroid function tests, no abnormalities on magnetic resonance imaging of the brain and tympanic bullae, and cerebrospinal fluid analysis. RESULTS: Sixteen dogs met the inclusion criteria. Facial paralysis had acute onset (<24 hours) in all dogs, thyroid function was within normal limits. There was albuminocytologic dissociation in cerebrospinal fluid of 69% of the dogs. There was complete resolution of clinical signs in 31% of the dogs but 38% showed long-term vestibular deficits, 46% developed hemifacial contracture, 15% had permanent facial paralysis and 15% relapsed. CLINICAL SIGNIFICANCE: Facial and vestibular neuropathy of unknown origin shares similarities with idiopathic facial paralysis. The prognosis for return of normal facial and vestibular function is guarded and there may be relapse after recovery.

Superior Versus Inferior Vestibular Neuritis: Are There Intrinsic Differences in Infection, Reactivation, or Production of Infectious Particles Between the Vestibular Ganglia?

HYPOTHESIS: Intrinsic differences in neurons of the vestibular ganglia result in the increased likelihood of superior vestibular ganglion involvement in vestibular neuritis. BACKGROUND: Vestibular neuritis is hypothesized to result from herpes simplex type I (HSV1) infection or reactivation in vestibular ganglia. Involvement of the inferior vestibular ganglion is extremely rare in patients with vestibular neuritis. METHODS: Primary cultures of rat superior and inferior vestibular ganglion neurons (VGNs) were cultivated separately. Neurons were lytically and latently infected with HSV1 with a US11-green fluorescent protein (GFP) chimera. Percentage lytic infection and baseline reactivation was assessed by microscopy for GFP fluorescence. Trichostatin-A (TSA) was used to stimulate HSV1 reactivation. Virion production was assessed by viral titers. Relative numbers of latency-associated (LAT) transcripts were determined by real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). RESULTS: Lytic infection rates were equivalent between the two ganglia (p > 0.05). Lytic infections yielded similar amounts of plaque-forming units (p > 0.05). Relative amounts of LAT transcripts did not differ between latently infected superior and inferior VGNs. Latently infected cultures showed no differences in rates of baseline and TSA-induced HSV1 reactivation (p > 0.05). Production of virions was not significantly different between reactivated, latently infected superior versus inferior VGNs (p = 0.45). CONCLUSION: Differences in prevalence of superior and inferior vestibular neuritis do not result from intrinsic differences in HSV1 infection or virion production of these neurons. Other factors, such as the length and width of the bony canal containing the ganglia and nerves, account for the greater involvement of the superior vestibular ganglion in vestibular neuritis.

Hyperventilation-induced nystagmus in patients with vestibular schwannoma.

MAIN OBJECTIVE: To determine the utility of the hyperventilation test (HVT) in the diagnosis of vestibular schwannoma (VS). STUDY DESIGN: A retrospective analysis of hyperventilation-induced nystagmus (HVIN) in 45 patients with unilateral VS. SETTING: A tertiary referral center. PATIENTS: Forty-five patients with VS; 30 patients with chronic vestibular neuritis; 20 healthy subjects with normal hearing and without symptoms or a history of vertigo, migraine, or neurological diseases (control group). INTERVENTIONS: Audiological and vestibular examination; "side-stream" measurement of end-tidal CO2 pressure (P(EtCO2)) to standardize the procedure; magnetic resonance imaging (MRI) centered on the cerebellopontine angle. MAIN OUTCOME MEASURES: An analysis of HVIN, its patterns, and its appearance threshold via the measurement of P(EtCO2) correlations with the tumor size. RESULTS: HVIN was observed in 40 of 45 cases (88.9%) in the schwannoma group and in 12 of 30 cases (40%) in the chronic vestibular neuritis group; HVIN was not observed in the control group (0/20 cases) (p < 0.001). In the schwannoma group, HVIN was evoked at a mean P(EtCO2) value of 16.5 ± 1.15 mm Hg. The hypofunctional labyrinth was identified with high sensibility and specificity through caloric test, head shaking test, and head thrust test. The excitatory pattern, which included HVIN with slow phases that beat toward the hypofunctional side, and the paretic pattern, which included HVIN with slow phases that beat toward the hypofunctional side, were not significantly associated with VS size (19.04 ± 10.56 mm for the excitatory pattern and 19.06 ± 11.01 mm for the paretic pattern). The difference in the VS size in HVIN+ (19.05 ± 10.60 mm) and HVIN- (8.40 ± 2.19 mm) cases was significant (p = 0.009). CONCLUSIONS: A 60-second hyperventilation event causes metabolic changes in the vestibular system and reveals a latent vestibular asymmetry. The presence of an excitatory pattern is the major criterion that suggests VS in patients with signs of unilateral vestibular deficit.

Changes in the gray matter volume during compensation after vestibular neuritis: a longitudinal VBM study.

PURPOSE: Peripheral vestibular dysfunction following vestibular neuritis (VN) often persists but functional recovery of balance can be variable. The authors compared structural changes in the brain before and after post-VN compensation and related it to the functional recovery. METHODS: Nine patients diagnosed with unilateral VN were included. Brain MRI and clinical observation were performed within 2 days of acute VN diagnosis and were repeated 3 months after the first exam. Voxel-based morphometry (VBM) analysis for longitudinal data was performed using VBM8 toolbox running within SPM8. Changes in local grey matter volume (GMV) were examined using a paired t-test and clinical relevance was tested using correlation analyses with functional improvement. RESULTS: Significant increases in GMV were observed in the vestibular cortex, bilateral hippocampus, visual cortices and the cerebellum. GMV decreased in cerebellar regions, including the vermis, and in the prefrontal cortex. Increases in GMV in visual cortices and cerebellum were associated with the poorest recovery of balance, which might be explained by functional substitution. CONCLUSIONS: The structural layout of vestibular compensation suggests that memory and motor planning are closely related to this process. Vision seems to be a major source of functional substitution, as has been previously demonstrated. This study, however, is the first longitudinal analysis of brain structural changes associated with recovery of balance following unilateral VN.

A perspective on recurrent vertigo.

The recurrent nature of the 3 most common vestibulopathies suggests a recurrent cause. Histopathology in temporal bones from patients with these syndromes - vestibular neuronitis (VN, n = 7), Ménière's disease (MD, n = 8) and benign paroxysmal positional vertigo (BPPV, n = 5) - shows focal degeneration of vestibular nerve axons and degenerated nearby facial nerve meatal ganglion cells. Transmission electron microscopic confirmation of intracytoplasmic viral particles in surgically excised vestibular nerves from patients with VN and MD support a viral etiology in these vestibulopathies. Antiviral treatment of these syndromes in a series of 211 patients with a 3- to 8-year follow-up resulted in complete control of vertigo in VN (88%), MD (90%) and BPPV (60%).

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.

Contribution of intracranial vertebral artery asymmetry to vestibular neuropathy.

OBJECTIVES: To test the hypothesis that vertebral artery hypoplasia (VAH) may affect the lateralisation of vestibular neuropathy (VN), probably through haemodynamic effect on the vestibular labyrinth. METHODS: 69 patients with unilateral VN were examined with a magnetic resonance angiographic (MRA) and caloric test. 50 healthy subjects served as controls. The diagnosis of intracranial VAH was based on MRA if <0.22 cm in VA diameter and a diameter asymmetry index >40%. The authors then correlated the canal paretic side with the VAH side. RESULTS: MRA study revealed 29 VAH (right/left: 23/6) in VN subjects and six VAH in controls (right/left: 5/1). The RR of VAH in VN subjects compared with controls was elevated (RR=2.2; 95% CI 1.8 to 2.8). There was a high accordance rate between the side of VAH and VN. Among 29 patients with unilateral VAH, 65.5% (N=19) had an ipsilateral VN, in which left VAH showed a higher accordance rate (83.3%) than the right side (60.9%). VN subjects with vascular risk factors also had a higher VAH accordance rate (81%) than those without (25%). CONCLUSIONS: VAH may serve as a regional haemodynamic negative contributor and impede blood supply to the ipsilateral vestibular labyrinth, contributing to the development of VN, which could be enhanced by atherosclerotic risk factors and the left-sided location.

[Vertigo due to neurovascular cross-compression: diagnosis and treatment].

OBJECTIVE: To explore the clinical characteristics, pathological mechanism, diagnose, differential diagnosis and the treatment of vascular compressive vestibular neuropathy. METHOD: The authors retrospectively studied 2 cases of vascular compressive vestibular neuropathy about clinical characteristics, auditory tests, vestibular tests and imaging examine results, pharmacotherapy results and reviewed the related documents. RESULT: There were some common clinical characteristics: (1) Vertigo and disequilibrium could be elicited by any physical activity and head movement and abated with complete bed rest; (2) Symptoms and signs can't be improved by vestibular suppressant medications; (3) When taken Dix-Hallpike test, true vertigo or a spinning sensation appeared during head movement, when head skilled at any position,the symptoms disappeared; (4) The suffering lateral often showed high frequency sensorineural hearing loss ,the ABR of the suffering lateral showed prolonged inter wave latency of I-III wave; (5) Vestibular tests showed central lesion; (6) Occupying lesion can be ruled out by CT and MRI, MRI showed neurovascular compression of vestibular nerve; (7) Taking carbamazepine plus baclofen or only Tegretol orally can alleviate symptoms. A great deal of surgeries confirmed neurovascular compression of cranial nerve U as a disease entity, the offending artery mainly anterior inferior cerebellar artery. Microvascular decompression of cranial nerve VIII can successfully relieve vertigo. CONCLUSION: Neurovascular compression of cranial nerve VIII is a disease entity beyond question. It's major characters were vertigo and disequilibrium which elicited by any physical activity and head movement, magnetic resonance tomographic angiography can give valuable information for diagnosis and treatment. Microvascular decompression can effectively relieve vertigo.

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.