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 herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

Background: Vestibular Neuritis (VN) induces Acute Vestibular Syndrome (AVS). This study aimed to identify predictive factors of VN recovery by healing and/or compensation. Methods: In this longitudinal and prospective study, 40 patients were included. The first assessment (T0) included medical history taking (general and specific), for cardiovascular risk factors (CVRFs), a battery of diagnostic tests, bithermal caloric test (BCT), video Head Impulse Test (VHIT) and skull vibration induced nystagmus (SVIN). All patients also completed a Dizziness Handicap Inventory (DHI). All assessments were repeated 90±15 days (T3) later. Subjective criteria compensation were based on DHI total score and objective criteria compensation on the instrumental test results. Four groups of patients (A, B, C, D) were delineated by combining patients with normal vs abnormal vestibular tests and patients with normal vs abnormal DH. Results: CVRFs were associated with a poorer recovery of symptoms but not the age or BMI. Vestibular tests mainly BCT (canal paresis %), VHIT (lateral semicircular canal gain) and SVINT (nystagmus slow phase velocity) recovered within normal values in 20%, 20%, 26% of cases respectively at T3 for the 40-patient group. Conclusions: Vascular risk factors (hypercholesterolemia) are correlated with patients who do not recover their symptoms either by healing or compensation. The evolution did not show any significant difference between high or low frequency vestibular tests in patients recovering from their symptoms. However, some patients with objective recovery may continue to show persisting subjective symptoms.

An ongoing EU Horizon 2020 Project called BionicVEST is investigating the effect of constant electrical stimulation (ES) of the inferior vestibular nerve in patients with bilateral vestibular dysfunction (BVD)[1]. The evidence is that constant ES results in improved postural stability and gait performance and so the question of central importance is how could constant ES of mainly saccular afferents in these BVD patients cause this improved performance? We suggest that the constant ES is substituting for the absent saccular neural input to the vestibular nuclei and the cerebellum in these BVD patients and indirectly via these structures to other structures which have been of great recent interest in motor control. One target area, the anterior midline cerebellum (the uvula) has recently been targeted as a location for deep brain stimulation in human patients to improve postural stability and gait. There are projections from midline cerebellum to basal ganglia including the striatum, structures involved in the initiation of gait. It may be that the effect of this activation of peripheral saccular afferent neurons is analogous to the effect of deep brain stimulation (DBS) by electrodes in basal ganglia acting to help alleviate the symptoms of patients with Parkinson's disease.

We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson’s disease (PD), but many unmet needs and gaps remain. Device based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies but there are concerns due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps with stimulation of the vestibular brainstem sensory network which extensively innervates brain regions regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

A correlation of basic science and clinical symptoms in the human to propose a new theory for how the vestibular system works Neil S. Longridge Professor Emeritus, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA *Arthur I. Mallinson, Clinical Associate Professor, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA NS Longridge † *AI Mallinson † These authors contributed equally to this work. ABSTRACT; Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision-making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into the type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information transmitted to the maculae simultaneously with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system through the STO causes macular otolithic membrane movement which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

(1) Background: Usually, the majority of patients suffering from vertigo and dizziness can be identified in four major categories: acute spontaneous vertigo, episodic (recurrent) vertigo, recurrent positional vertigo, chronic imbalance. Our purpose is to retrospectively evaluate the main causes of episodic vertigo and to find indications for a reliable clinical suspicion useful for a definitive diagnosis, comparing patients affected by different presenting symptomatology (acute vertigo, recurrent episodic vertigo, and imbalance) (2) Methods: we retrospectively evaluated the clinical records in a population of 249 consecutive patients observed for vertigo in our tertiary referral center in the period 1 January 2019 – 31 January 2020. On the basis of the reported clinical history, patients were divided into three groups: patients with first ever attack of vertigo, patients with recurrent vertigo and dizziness; patients with chronic imbalance. (3) Results: On the basis of the results of the instrumental examination, we arbitrary divided (for each type of symptoms) the patients in a group with a normal vestibular instrumental examination and a group of patients in which the clinical-instrumental evaluation showed some pathological results; a highly significant difference (p: 0.157) was found between recurrent and acute vertigo and between recurrent vertigo and imbalance. (4) Conclusions: patients with recurrent vertigo more frequently exhibit a negative otoneurological examination since they are often examined in the intercritical phase. A precise and in-depth research of the patient's clinical history is the key to suspect or make a diagnosis together with the search for some instrumental or clinical hallmark, especially in cases where the clinical picture does not fully meet the international diagnostic criteria.

The present study evaluates the response to betahistine in patients who presented vestibular drops attacks in the context of Ménière's disease (MD) and the factors that can predict an unfavorable response to it. A total of 43 patients were analyzed, out of which 33 were diagnosed with MD. It is a descriptive, cross-sectional study with retrospective data collection. Data as regards age, accompanying symptoms, etiological diagnosis and response to MD treatment were collected. A statistical analysis was carried out, and we found that the disease evolution time and specific alterations in the vestibulospinal and oculomotor physical examination present an unfavorable response to betahistine, as opposed to the use of intratympanic gentamicin, with which symptomatic control is achieved in 100% of the cases.

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, <35 years old), and 39 with late onset MD (LOMD, > 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

This study evaluates the effectiveness of an integrated vestibular rehabilitation program in improving balance, motor control, and proprioceptive function in patients diagnosed with Benign Paroxysmal Positional Vertigo (BPPV). The prospective observational study involved 107 participants who underwent a tailored rehabilitation regimen, including the Epley maneuver, Brandt-Daroff exercises, and balance and proprioceptive training. The program was designed to address the vestibular and proprioceptive deficits caused by BPPV, with the goal of restoring normal function and reducing the risk of symptom recurrence. Dynamic Gait Index (DGI) and Balance Beam Test were used to assess progress, showing significant improvements in balance stability and dynamic motor function. The findings support the integration of vestibular rehabilitation into standard care for BPPV patients, highlighting the program's potential to enhance patient outcomes and reduce recovery time. However, the study also notes limitations such as the lack of a control group and the need for further research to explore the long-term effects of such interventions.

Objective: This review is aimed at evaluating the role of imaging evaluation in the diagnosis of peripheral vestibular disorders. Methods: The study is a literature review conducted on PubMed and the Cochrane Library. Results: Imaging is not usually recommended in initial consultations for vestibular disorders because only 5-10% of MRI scans reveal findings directly related to the disease. The study is a review of the literature that highlights the utility and limitations of imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). It follows the diagnostic approach from history and physical examination to laboratory tests and imaging. Some conditions like vestibular neuritis and BPPV have limited imaging utility due to the fine details required. Conversely, high-resolution CT and MRI are important for diagnosing Meniere's disease, acoustic neuroma, and superior canal dehiscence. Conclusion: The imaging role varies a lot among specific conditions. Advances in imaging technology, particularly high-resolution MRI, promise enhanced diagnostic capabilities.

Current consensus diagnostic criteria for vestibular migraine (VM) describes this as an episodic disorder. However, a minority of patients report prolonged (>72h duration) or even persistent VM symptoms, prompting whether a chronic variant of vestibular migraine (CVM) should be introduced to the current classification and how best to define it. Here we summarize current evidence of such a potential chronic variant of VM and critically review previously published proposed definitions for CVM. Potential approaches to establish a diagnostic framework for CVM include a) following the distinction between episodic and chronic migraine headaches; namely, frequent and/or prolonged episodes of VM (but not persistent vertigo or dizziness) in the context of chronic migraine headaches or b) daily dizzy spells over more than 6 months that responded well to prophylactic anti-migraine therapy. A key challenge when defining diagnostic criteria for CVM is how to distinguish it from other chronic vestibular syndromes such as motion sickness, persistent postural-perceptual dizziness (PPPD), and mal-de-débarquement syndrome. Indeed, more than 50% of patients with PPPD and up to 46% with mal-de-débarquement syndrome fulfill diagnostic criteria for episodic migraine headaches, suggesting these disorders may all lie along a spectrum. We propose that when VM becomes persistent, it is best classified as PPPD but that VM and PPPD are not mutually exclusive, such that patients with PPPD need not have features of VM and the triggering event for persistent dizziness may be independent of migraine.

This study investigates the efficacy of an integrated rehabilitation program that combines vestibular and knee-focused therapies to improve proprioceptive function, balance, and motor control in patients suffering from both Benign Paroxysmal Positional Vertigo (BPPV) and knee joint conditions. The study involved 59 participants diagnosed with both vestibular dysfunction and knee impairments, who were enrolled in a comprehensive rehabilitation program. Vestibular interventions included specific maneuvers such as the Epley maneuver and Brandt-Daroff exercises, aimed at repositioning otoliths and reducing vertigo symptoms, while balance retraining exercises were implemented to enhance stability and prevent falls. Additionally, TECAR therapy was used for its deep tissue heating and regenerative benefits, and specific proprioceptive exercises targeting the knee joint were conducted to improve joint position sense and reduce the risk of falls. The intervention resulted in significant improvements in proprioceptive accuracy, as evidenced by enhanced joint position sense measurements and increased scores on the Dynamic Gait Index (DGI). These findings suggest that the dual-targeted rehabilitation approach not only addresses the individual impairments associated with vestibular dysfunction and knee pathology but also effectively improves overall functional outcomes by tackling the complex interplay between these conditions. The study further highlights the importance of a multidisciplinary approach in rehabilitation, where addressing vestibular and musculoskeletal dysfunctions simultaneously can lead to better patient outcomes. The integrated rehabilitation strategy presented in this study offers a comprehensive approach to managing complex clinical cases, ultimately contributing to improved quality of life and functional independence in patients affected by concurrent vestibular and knee joint issues.

The healthy function of the vestibular system (VS) is of vital importance for individuals to carry out their daily activities independently and safely. This study carries out Tsallis entropy (TE)-based analysis on insole force sensor data in order to extract features to differentiate between healthy and VS-diseased individuals. Using a specifically developed algorithm, we detrend the acquired data to examine the fluctuation around the trend curve in order to consider the individual’s walking habit and thus increase the accuracy in diagnosis. It is observed that the TE-value increases for diseased people as an indicator of the problem of maintaining balance. As one of the main contributions of this study, in contrast to studies in the literature that focus on gait dynamics requiring extensive walking time, we directly process the instantaneous pressure values, enabling to reduce the data acquisition period significantly. The extracted feature set is then inputted into fundamental classification algorithms, with the Support-Vector-Machine (SVM) demonstrating the highest performance, achieving an average accuracy of 95%. This study constitutes a significant step of a large project aiming to identify specific VS disease together with its stage. The performance achieved in this study provides a strong motivation to further explore this topic.

Postoperative headaches (POH) following retrosigmoid microsurgery for ves-tibular schwannoma (VS) can significantly diminish patients' perceived health benefits (PHB). A survey of 101 VS patients, utilizing the Rostock Headache Compendium, Glasgow Benefit Inventory, Ten-Item Personality Inventory (TI-PI-G), and German pain processing questionnaire (FESV), revealed that almost half experienced POH, leading to a markedly reduced overall PHB compared to those without POH. This decrease in PHB was linked to higher levels of pain-related helplessness, depression, anxiety, and anger. Positive associations were found between PHB and action-planning competence, cognitive restruc-turing, and experience of competence. Personality traits, particularly low emo-tional stability and openness, were associated with pain-related psychological impairment. Interestingly, hearing loss and facial paresis did not impact PHB. The study underscores the influence of pain-related mental interference and coping strategies on PHB in long-term POH patients, suggesting a role for personality traits in their pain management. The findings advocate for short-term psychological interventions, emphasizing adaptive coping mecha-nisms like cognitive restructuring, to enhance PHB in VS patients post-microsurgery.

Extraocular eye muscles (EOMs) are innervated by axons of three ocular motor nuclei, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the EOMs, pro-vide an overview of vestibular pathway inputs to ocular motor nuclei, and describe congenital disorders that alter the development of ocular motor neurons. Oculomotor neurons originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae which are contra-laterally innervated. Trochlear motor neurons originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons originate variously in the rhombomeres r4-6 and innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow yielding a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. The ocular motor neurons are innervating somites, which receive innervates vestibular nuclei that connects with the brainstem motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders.

Background: Wideband tympanometry (WBT) has the potential to distinguish various mechanical middle ear and inner ear pathologies noninvasively. This study investigated the diagnostic value of WBT in the diagnosis of enlarged vestibular aqueduct (EVA). Methods: The absorbance and resonance frequency (RF) of patients with EVA (40 ears, 25 patients) and matched population controls (39 ears, 28 subjects) were compared, alongside receiver operating characteristic (ROC) analysis. Correlations between VA width and RF were also examined. Results: Patients with EVA had higher absorbance at low frequencies (226–917 Hz) and lower absorbance at high frequencies (2,520–4,896 Hz) compared to controls. The RF of the EVA group was significantly lower versus controls (751 [391–1,165] vs. 933 [628–1,346] Hz). ROC analysis revealed area under the curve values of 0.771 and 0.801 respectively, for absorbance and RF. RF had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.4%, 82.5%, 76.7%, and 80.6%, respectively, for diagnosing EVA. In the EVA group, the VA midpoint width (r = −0.334) and VA petrous width (r = −0.402) both significantly correlated with RF. Conclusion: Our findings support the utility of WBT for diagnosing EVA, with RF as the optimal index used.

Low-intensity noisy galvanic vestibular stimulation (nGVS) can improve static and dynamic postural deficits in patients with bilateral vestibular loss (BVL). In this study, we aimed to explore the neurophysiological and neuroanatomical substrates underlying nGVS treatment effects in a rat model of BVL. Regional brain activation patterns and behavioral responses to repeated 30-min nGVS treatment in comparison to sham stimulation were investigated by serial whole-brain [18F]-FDG-PET measurements and quantitative locomotor assessments before and at 9 consecutive time points up to 60 days after chemical bilateral labyrinthectomy (BL). [18F]-FDG-PET revealed a broad nGVS-induced modulation on regional brain activation patterns encompassing biologically plausible brain networks in the brainstem, cerebellum, multisensory cortex and basal ganglia during the entire observation period post-BL. nGVS broadly reversed brain activity adaptions occurring in the natural course post-BL. Parallel behavioral locomotor assessment demonstrated a beneficial treatment effect of nGVS on sensory-ataxic gait alterations, particularly in the early stage of post-BL recovery. Stimulation-induced locomotor improvements were finally linked to nGVS brain activity responses in the brainstem, hemispheric motor and limbic networks. In conclusion, combined [18F]-FDG-PET and locomotor analysis discloses the potential neurophysiological and neuroanatomical substrates that mediate previously observed therapeutic nGVS effects on postural deficits in patients with BVL.

Quick and appropriate diagnostics and the use of intraoperative monitoring (IM) of hearing during vestibular schwannoma (VS) resection increase the likelihood of hearing preservation. During surgery, various methods of IM can be used, i.e. auditory brainstem responses (ABR), transtympanic electrocochleography (TT-ECochG) and direct cochlear nerve action potentials. The aim of the study was to evaluate the prognostic values of IM of hearing using ABR and TT-ECochG in predicting postoperative hearing preservation, as well as to evaluate relationships between them during various stages of surgery. This retrospective study presents the pre- and postoperative audiological test results and IM of hearing records (TT-ECochG and ABR) in 75 (43 women, 32 men, aged 18-69) patients with diagnosed VS. The preoperative pure tone average hearing threshold was 25.02 dB HL, while after VS resection it worsened on average by 30.03 dB HL. According to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Hearing Classification, before and after (pre/post) the surgery, there were 47/24 patients in hearing class A, 9/8-B, 2/1-C, and 17/42-D. In speech audiometry, the average preoperative speech discrimination score at an intensity of 60 dB SPL was 70.93%, and after VS resection it worsened to 38.93%. The analysis of electrophysiological tests showed that before the tumor removal the I-V ABR interlatencies was 5.06 ms, and after VS resection it was 6.43 ms. The study revealed correlations between worse postoperative hearing and changes in intraoperatively measured ABR and TT-ECochG. IM of hearing is very useful in predicting postoperative hearing in VS patients and increases the chance of postoperative hearing preservation in these patients.

Cerebellar ataxia, neuronopathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two-step PCR consisting of a short-allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection. Exome sequencing of RFC1 was additionally foreseen to resolve potential compound heterozygosity cases. Specificity of our approach was evaluated using ataxia patients with known non-CANVAS diagnoses, and optimized using Southern blot confirmed CANVAS patients. We evaluated our approach by testing patients consecutively referred for clinically suspected CANVAS using first the two-step PCR, followed by exome sequencing. Our approach was able to accurately identify negative and confirm positive cases in prospectively collected suspected CANVAS patients presenting with at least three typical clinical signs. The proposed testing approach provides an alternative method able to clearly distinguish between CANVAS negative and positive cases and can be easily incorporated into the genetic diagnostic laboratory workflow.