Vestibular Syndrome Research Articles

RFC1 Gene: Function and Intronic Repeat Expansion Causing Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome

Biallelic intronic repeat expansion in the RFC1 gene was reported as a cause of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Its clinical features include late-onset cerebellar ataxia, sensory neuropathy (or neuronopathy), bilateral vestibular impairment, autonomic dysfunction, chronic cough, pyramidal sign, or parkinsonism. Repeat conformations heterogeneity is observed along with the possible phenotype-genotype correlation while its molecular pathogenesis remains uncovered.

Whole-Genome and Long-Read Sequencing Identify a Novel Mechanism in RFC1 Resulting in CANVAS Syndrome.

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) results from biallelic intronic pentanucleotide repeats in RFC1. We describe an adult male proband with progressive imbalance, cerebellar atrophy, somatosensory neuronopathy, and absence of peripheral vestibular function for whom clinical testing demonstrated a heterozygous RFC1 expansion consistent with an unaffected carrier. We performed whole-genome sequencing (WGS) on peripheral blood DNA samples from the proband and his unaffected mother. We performed DNA long-read sequencing and synthesized complementary DNA from RNA using peripheral blood from the proband. WGS confirmed the maternally inherited RFC1 expansion and identified a rare, nonsense RFC1 variant: c.C1147T; p.R383X in the proband but not the maternal DNA sample. RFC1 variants were confirmed in trans with long-read sequencing. Functional studies demonstrated the absence of complementary DNA (cDNA) transcript from the c.C1147T; p.R383X variant supporting nonsense-mediated decay of this transcript. We report an adult with CANVAS due to compound heterozygous pathogenic RFC1 variants: the pathogenic intronic pentanucleotide expansion confirmed in trans with a nonsense variant. This report represents a novel molecular mechanism for CANVAS. Sequencing for RFC1 should be considered for adults meeting clinical criteria for the CANVAS phenotype if only a heterozygous pathogenic RFC1 expansion is identified.

RFC1 CANVAS/Spectrum Disorder: Historical Details and Clinical Diversity

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) refers to a multi-system neurodegenerative disorder, with middle-age onset, which mainly presents with progressive imbalance. Imbalance is attributable to isolated or combined impairment of the cerebellar, proprioceptive, and vestibular systems. Chronic spasmodic cough, which usually precedes neurological symptoms, serves as a useful diagnostic clue to CANVAS. Diagnostic criteria have been proposed for CANVAS in 2016, based on 3 cardinal features. In 2019, a biallelic intronic AAGGG repeat expansion (AAGGG)exp in the replication factor complex subunit 1 gene (RFC1) was identified as a genetic contributor to CANVAS, and (ACGGG)exp in RFC1 was subsequently confirmed as a causative factor for CANVAS. Genetic screening for RFC1 has shown that CANVAS is an overlooked entity in patients with cerebellar ataxia or sensory neuropathy, which highlights more restricted phenotypes that exclusively involve one of the aforementioned systems. The phenotypic spectrum of RFC1-related disorders has been expanding since the discovery of (AAGGG)exp or (ACGGG)exp in the RFC1. Studies have reported atypical features, including parkinsonism, motor neuron involvement, cognitive decline, and sleep disorders. Currently, a wide variety of clinical conditions associated with biallelic intronic pentanucleotide repeat expansion in RFC1 are classified as RFC1 CANVAS/spectrum disorder.

Motor Neuron Involvement in RFC1 CANVAS/Spectrum Disorders

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by the triad of cerebellar ataxia, bilateral vestibular impairment, and sensory neuropathy. The responsible anatomical region for the sensory disturbance in CANVAS is reportedly the dorsal root ganglion, which suggests neuronopathy rather than neuropathy as the pathomechanism of this peripheral nervous system disorder. Early on, motor neuron involvement was considered rare in CANVAS. The etiology of CANVAS includes the homozygous pentanucleotide repeat expansion within the RFC1 gene, resulting in diverse phenotypes and motor deficits such as brisk reflex, extensor plantar responses, or spasticity of the upper motor neurons and muscle wasting, weakness, cramp, or fasciculation of the lower motor neurons. CANVAS patients with AAGGG repeat expansions may show motor neuron involvement, with considerable variation in the reported frequencies. In contrast, although some patients with ACAGG repeat expansions also show motor neuron involvement, its frequency remains elusive.

Chronic Cough in CANVAS

Among patients with RFC1 spectrum disorders represented by the phenotype of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS), at least 60% are known to manifest chronic, paroxysmal, and spasmodic dry cough. Chronic cough is a key diagnostic feature of RFC1-related diseases. It is often the first symptom and, in some cases, precedes neurological symptoms such as ataxia and sensory disturbance for more than 30 years. Although the pathogenesis of the cough remains unclear, it is possible that impairment of the vagus nerve, which includes an afferent pathway of the cough reflex, or the cerebellum would have contributed to the generation of the cough.

Investigating the significance of vestibular aqueduct pneumatization and pediatric hearing loss.

Vestibular aqueduct enlargement on imaging is associated with pediatric hearing loss, though the mechanism is not well understood. After reviewing temporal bone imaging in pediatric patients from our institution with no obvious cause of hearing loss, we postulate that pneumatization of bone surrounding the vestibular aqueduct may also be associated with hearing loss. 342 temporal bone CT scans performed at Children's Hospital of Michigan between January 2018 and December 2020 were reviewed. Scans were assessed for the presence, laterality, and degree of vestibular aqueduct pneumatization (PVA). Electronic medical record data was collected on age, gender, hearing status, medical comorbidities, and otologic comorbidities. Cases were secondarily reviewed to ensure validity. 159 patients were included in the final analysis; excluded scans included duplicates, patients with unknown hearing status, patients older than 21 years old, and patients with another known cause of hearing loss including inner ear malformations. 17.6% of patients demonstrated vestibular aqueduct pneumatization. Hearing loss percentage was comparable between the PVA and non-pneumatized group (42.9% vs 42.0%), but hearing loss was more likely to be sensorineural in the PVA group (91.7% vs 80.0%). When patients with only newborn hearing data available were excluded from the PVA group, hearing loss percentage was higher in the PVA group (50% vs 42.0%). Patients with hearing loss in the PVA group were older than those without hearing loss (14.92 years old vs 10.67 years old). Hearing loss in enlarged vestibular aqueduct syndrome is typically progressive, bilateral, and sensorineural. Our preliminary findings suggest that vestibular aqueduct pneumatization may be another anomaly associated with a primarily sensorineural hearing loss. Further studies are needed to strengthen this postulated link.

Vestibular Dysfunction in Replication Factor C Subunit 1 (RFC1) Spectrum Disorder

More than 90% of replication factor c subunit 1 (RFC1) gene-related spectrum disorders such as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) have bilateral vestibular dysfunction. A case with CANVAS presented in this paper showed repeat extension of AAGGG in the intron region of the RFC1 gene, and showed bilateral vestibular dysfunction in caloric test, vestibular evoked myogenic potential, video Head Impulse Test and rotary chair test. Visual enhanced vestibulo-ocular reflex tests also revealed abnormalities, suggesting the presence of combined lesions of the cerebellum and brainstem including vestibular nuclei.

A taxonomy for brainstem cavernous malformations: subtypes of pontine lesions. Part 2: inferior peduncular, rhomboid, and supraolivary.

Part 2 of this 2-part series on pontine cavernomas presents the taxonomy for subtypes 4-6: inferior peduncular (IP) (subtype 4), rhomboid (5), and supraolivary (6). (Subtypes 1-3 are presented in Part 1.) The authors have proposed a novel taxonomy for pontine cavernous malformations based on clinical presentation (syndromes) and anatomical location (MRI findings). The details of taxonomy development are described fully in Part 1 of this series. In brief, pontine lesions (323 of 601 [53.7%] total lesions) were subtyped on the basis of predominant surface presentation identified on preoperative MRI. Neurological outcomes were assessed according to the modified Rankin Scale, with score ≤ 2 defined as favorable. The 323 pontine brainstem cavernous malformations were classified into 6 distinct subtypes: basilar (6 [1.9%]), peritrigeminal (53 [16.4%]), middle peduncular (100 [31.0%]), IP (47 [14.6%]), rhomboid (80 [24.8%]), and supraolivary (37 [11.5%]). Subtypes 4-6 are the subject of the current report. IP lesions are located in the inferolateral pons and are associated with acute vestibular syndrome. Rhomboid lesions present to the fourth ventricle floor and are associated with disconjugate eye movements. Larger lesions may cause ipsilateral facial weakness. Supraolivary lesions present to the surface at the ventral pontine underbelly. Ipsilateral abducens palsy is a strong localizing sign for this subtype. A single surgical approach and strategy were preferred for subtypes 4-6: for IP cavernomas, the suboccipital craniotomy and telovelar approach predominated; for rhomboid lesions, the suboccipital craniotomy and transventricular approach were preferred; and for supraolivary malformations, the far lateral craniotomy and transpontomedullary sulcus approach were preferred. Favorable outcomes were observed in 132 of 150 (88%) patients with follow-up. There were no significant differences in outcomes between subtypes. The neurological symptoms and signs associated with a hemorrhagic pontine subtype can help define that subtype clinically with key localizing signs. The proposed taxonomy for pontine cavernous malformation subtypes 4-6 meaningfully guides surgical strategy and may improve patient outcomes.

Truncating Variants in RFC1 in Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease characterized by adult-onset and slowly progressive sensory neuropathy, cerebellar dysfunction, and vestibular impairment. In most cases, the disease is caused by biallelic (AAGGG)n repeat expansions in the second intron of the replication factor complex subunit 1 (RFC1). However, a small number of cases with typical CANVAS do not carry the common biallelic repeat expansion. The objective of this study was to expand the genotypic spectrum of CANVAS by identifying sequence variants in RFC1-coding region associated with this condition. Fifteen individuals diagnosed with CANVAS and carrying only 1 heterozygous (AAGGG)n expansion in RFC1 underwent whole-genome sequencing or whole-exome sequencing to test for the presence of a second variant in RFC1 or other unrelated gene. To assess the effect of truncating variants on RFC1 expression, we tested the level of RFC1 transcript and protein on patients' derived cell lines. We identified 7 patients from 5 unrelated families with clinically defined CANVAS carrying a heterozygous (AAGGG)n expansion together with a second truncating variant in trans in RFC1, which included the following: c.1267C>T (p.Arg423Ter), c.1739_1740del (p.Lys580SerfsTer9), c.2191del (p.Gly731GlufsTer6), and c.2876del (p.Pro959GlnfsTer24). Patient fibroblasts containing the c.1267C>T (p.Arg423Ter) or c.2876del (p.Pro959GlnfsTer24) variants demonstrated nonsense-mediated mRNA decay and reduced RFC1 transcript and protein. Our report expands the genotype spectrum of RFC1 disease. Full RFC1 sequencing is recommended in cases affected by typical CANVAS and carrying monoallelic (AAGGG)n expansions. In addition, it sheds further light on the pathogenesis of RFC1 CANVAS because it supports the existence of a loss-of-function mechanism underlying this complex neurodegenerative condition.

Acute unilateral vestibulopathy/vestibular neuritis: Diagnostic criteria.

This paper describes the diagnostic criteria for Acute Unilateral Vestibulopathy (AUVP), a synonym for vestibular neuritis, as defined by the Committee for the Classification of Vestibular Disorders of the Bárány Society. AUVP manifests as an acute vestibular syndrome due to an acute unilateral loss of peripheral vestibular function without evidence for acute central or acute audiological symptoms or signs. This implies that the diagnosis of AUVP is based on the patient history, bedside examination, and, if necessary, laboratory evaluation. The leading symptom is an acute or rarely subacute onset of spinning or non-spinning vertigo with unsteadiness, nausea/vomiting and/or oscillopsia. A leading clinical sign is a spontaneous peripheral vestibular nystagmus, which is direction-fixed and enhanced by removal of visual fixation with a trajectory appropriate to the semicircular canal afferents involved (generally horizontal-torsional). The diagnostic criteria were classified by the committee for four categories: 1. "Acute Unilateral Vestibulopathy", 2. "Acute Unilateral Vestibulopathy in Evolution", 3. "Probable Acute Unilateral Vestibulopathy" and 4. "History of Acute Unilateral Vestibulopathy". The specific diagnostic criteria for these are as follows:"Acute Unilateral Vestibulopathy": A) Acute or subacute onset of sustained spinning or non-spinning vertigo (i.e., an acute vestibular syndrome) of moderate to severe intensity with symptoms lasting for at least 24 hours. B) Spontaneous peripheral vestibular nystagmus with a trajectory appropriate to the semicircular canal afferents involved, generally horizontal-torsional, direction-fixed, and enhanced by removal of visual fixation. C) Unambiguous evidence of reduced VOR function on the side opposite the direction of the fast phase of the spontaneous nystagmus. D) No evidence for acute central neurological, otological or audiological symptoms. E) No acute central neurological signs, namely no central ocular motor or central vestibular signs, in particular no pronounced skew deviation, no gaze-evoked nystagmus, and no acute audiologic or otological signs. F) Not better accounted for by another disease or disorder."Acute Unilateral Vestibulopathy in Evolution": A) Acute or subacute onset of sustained spinning or non-spinning vertigo with continuous symptoms for more than 3 hours, but not yet lasting for at least 24 h hours, when patient is seen; B) - F) as above. This category is useful for diagnostic reasons to differentiate from acute central vestibular syndromes, to initiate specific treatments, and for research to include patients in clinical studies."Probable Acute Unilateral Vestibulopathy": Identical to AUVP except that the unilateral VOR deficit is not clearly observed or documented."History of acute unilateral vestibulopathy": A) History of acute or subacute onset of vertigo lasting at least 24 hours and slowly decreasing in intensity. B) No history of simultaneous acute audiological or central neurological symptoms. C) Unambiguous evidence of unilaterally reduced VOR function. D) No history of simultaneous acute central neurological signs, namely no central ocular motor or central vestibular signs and no acute audiological or otological signs. E) Not better accounted for by another disease or disorder. This category allows a diagnosis in patients presenting with a unilateral peripheral vestibular deficit and a history of an acute vestibular syndrome who are examined well after the acute phase.It is important to note that there is no definite test for AUVP. Therefore, its diagnosis requires the exclusion of central lesions as well as a variety of other peripheral vestibular disorders. Finally, this consensus paper will discuss other aspects of AUVP such as etiology, pathophysiology and laboratory examinations if they are directly relevant to the classification criteria.

New onset episodic vertigo as a presentation of vestibular neuritis.

ObjectiveVestibular neuritis (VN) is a common peripheral cause of acute vestibular syndrome, characterized by sustained vertigo and gait instability, persisting from 1 day to several weeks. With the widespread use of comprehensive vestibular function tests, patients with VN and non-sustained vertigo have drawn attention. In this study, we retrospectively analyzed the clinical presentation of patients with VN and episodic vertigo, aiming to expand the atypical clinical features of VN.MethodsThis retrospective study enrolled 58 patients with VN. Among them, 11 patients with more than 3 remissions per day, each lasting over 1 h were assigned to the episodic vertigo (EV) group, and 47 subjects without significant relief into the sustained vertigo (SV) group. Demographic information, clinical manifestations and data of supplementary examinations were collected and statistically analyzed. These patients were followed up 1 year after discharge to gather prognostic information.ResultsThe incidence of spontaneous nystagmus (SN) and proportion of severe vertigo (Dizziness Handicap Inventory questionnaire score >60) in the SV group were significantly higher than those in the EV group. Spearman correlation showed that with a longer disease course, the velocity of overt saccade was smaller (p < 0.05, Rs = −0.263) in all patients with VN.ConclusionThe non-sustained manifestations in VN overlap with a wider spectrum of other vestibular disorders and stroke-related vertigo, which add an additional layer of complexity to the differential diagnosis of new onset episodic vertigo. By retrospectively analyzing the clinical characteristics and vHIT parameters, our study has expounded on the atypical features and potential pathophysiological mechanism of episodic syndromes in VN. VOR gain and saccades measured by vHIT could be reliable indicators for vestibular rehabilitation process.

Differential diagnosis of stroke and vestibular neuritis in emergency neurology

Introduction. The differential diagnosis of vertebrobasilar stroke (VBS) and vestibular neuritis (VN) is important challenge for a neurologist when a patient presents to the emergency department with acute vertigo. Current approaches and algorithms of management need to be modified, taking into account clinical practice.&#x0D; The aim of the study was to identify the clinical features of acute vestibular syndrome that are the most helpful in the differential diagnosis of VBS and VN.&#x0D; Materials and methods. We examined 80 emergency admissions to the neurological ward with suspected stroke. A detailed otoneurological examination (including the STANDING and HINTS+ algorithms) and brain imaging (DWI MRI) were performed.&#x0D; Results. Out of 80 patients, 26 were diagnosed with VBS, 30 with VN, 11 with vestibular migraine and 2 with Meniere's disease, while the cause of vertigo could not be determined in 11 patients. The most powerful indicator of VBS in the differential diagnosis was gaze-evoked nystagmus, which had a 15.9-fold association with VBS. An increased likelihood of VBS was also associated with unsteadiness (6.3 times), age over 58 years (4.1 times), dysmetria in the finger-to-nose test (3.7 times), adiadochokinesia (3.1 times), and trunk ataxia (3 times). An increased likelihood of VN was associated with a positive unilateral head impulse test (6 times), nystagmus that followed Alexander's law (3.7 times), and presence of nausea (2.5 times). A model was developed for the differential diagnosis of VBS and VNin patients presenting with acute vertigo. The model accuracy was 100% in the validation sample.&#x0D; Conclusions. Clinical approach remains crucial when differentiating between VBS and VN. The most useful criteria for a differential diagnosis in emergency neurology were the patient's age, the type of nystagmus, head impulse test, and cerebellar dysfunction.

Internal auditory canal volume in normal and malformed inner ears

PurposeA narrow bony internal auditory canal (IAC) may be associated with a hypoplastic cochlear nerve and poorer hearing performances after cochlear implantation. However, definitions for a narrow IAC vary widely and commonly, qualitative grading or two-dimensional measures are used to characterize a narrow IAC. We aimed to refine the definition of a narrow IAC by determining IAC volume in both control patients and patients with inner ear malformations (IEMs).MethodsIn this multicentric study, we included high-resolution CT (HRCT) scans of 128 temporal bones (85 with IEMs: cochlear aplasia, n = 11; common cavity, n = 2; cochlear hypoplasia type, n = 19; incomplete partition type I/III, n = 8/8; Mondini malformation, n = 16; enlarged vestibular aqueduct syndrome, n = 19; 45 controls). The IAC diameter was measured in the axial plane and the IAC volume was measured by semi-automatic segmentation and three-dimensional reconstruction.ResultsIn controls, the mean IAC diameter was 5.5 mm (SD 1.1 mm) and the mean IAC volume was 175.3 mm3 (SD 52.6 mm3). Statistically significant differences in IAC volumes were found in cochlear aplasia (68.3 mm3, p < 0.0001), IPI (107.4 mm3, p = 0.04), and IPIII (277.5 mm3, p = 0.0004 mm3). Inter-rater reliability was higher in IAC volume than in IAC diameter (intraclass correlation coefficient 0.92 vs. 0.77).ConclusionsVolumetric measurement of IAC in cases of IEMs reduces measurement variability and may add to classifying IEMs. Since a hypoplastic IAC can be associated with a hypoplastic cochlear nerve and sensorineural hearing loss, radiologic assessment of the IAC is crucial in patients with severe sensorineural hearing loss undergoing cochlear implantation.

Diagnosing and localizing the acute vestibular syndrome – Beyond the HINTS exam

When assessing the acutely dizzy patient, the HINTS ‘Plus’ (Head Impulse, Nystagmus, Test of Skew, ‘Plus’ a bedside assessment of auditory function) exam is a crucial component of the bedside exam. However, there are additional ocular motor findings that can help the clinician distinguish peripheral from central etiologies and enable accurate localization, especially when the patient has acute dizziness, vertigo and/or imbalance but without spontaneous nystagmus. We will review the literature on these findings which are ‘beyond HINTS’ and include saccades/ocular lateropulsion, smooth pursuit, and provocative maneuvers including head-shaking and positional testing (not part of the HINTS exam). Additionally, we will expound on the localizing value of nystagmus, ocular alignment and the ocular tilt reaction (parts of the HINTS exam). The paper has been organized neuroanatomically, based on brainstem and cerebellar structures that have been reported to cause the acute vestibular syndrome.

A prospective study on the application of HINTS in distinguishing the localization of acute vestibular syndrome

BackgroundAcute vestibular syndrome (AVS) is a common clinical syndrome in neurology clinics and emergency department. Canonical standard for AVS diagnosis requires the presence of persistent vertigo for more than 24 h. HINTS (head impulse-nystagmus-test of skew) is an emerging scheme in the diagnosis of AVS. In this prospective study, we evaluated the specificity and sensitivity of HINTS in distinguishing between central and peripheral AVS.MethodsA cohort of 239 cases with complete clinical record was recruited in the study. All patients completed emergency brain CT examination to exclude hemorrhagic stroke. HINTS examination was conducted to distinguish between central AVS and peripheral AVS, and all patients completed head MRI, BAEP and vestibular function examinations within one week. Patients diagnosed as central AVS were subject to angiography (CTA/MRA/DSA), and patients with peripheral AVS were considered for a 3-month follow-up to correct the initial diagnosis.ResultsPatients with central AVS were associated with an elder age, higher incidences of hypertension, atrial fibrillation, family history of stroke and previous history of stroke. Posterior circulation cerebral infarction, vestibular migraine and cerebellitis were the dominant diseases associated with central AVS. The sensitivities of HIT, GE, and TS in the diagnosis of central AVS were 73.5%, 61.2%, and 26.5%, and the specificities were 97.9%, 92.6%, and 93.2% respectively.ConclusionsThe sensitivity of HINTS for central AVS diagnosis is 89.8% and the specificity is 84.2%. HINTS is an easy-to-operate, low-cost, high-sensitivity and specific examination technique, which is practical in neurology outpatient clinics and emergency departments.

Positive horizontal-canal head impulse test is not a benign sign for acute vestibular syndrome with hearing loss.

BackgroundDiagnosis of acute vestibular syndrome (AVS) with hearing loss is challenging because the leading vascular cause—AICA territory stroke—can appear benign on head impulse testing. We evaluated the diagnostic utility of various bedside oculomotor tests to discriminate imaging-positive and imaging-negative cases of AVS plus hearing loss.MethodWe reviewed 13 consecutive inpatients with AVS and acute unilateral hearing loss. We compared neurologic findings, bedside and video head impulse testing (bHIT, vHIT), and other vestibular signs (including nystagmus, skew deviation, and positional testing) between MRI+ and MRI– cases.ResultsFive of thirteen patients had a lateral pontine lesion (i.e., MRI+); eight did not (i.e., MRI–). Horizontal-canal head impulse test showed ipsilateral vestibular loss in all five MRI+ patients but only in three MRI– patients. The ipsilesional VOR gains of horizontal-canal vHIT were significantly lower in the MRI+ than the MRI– group (0.56 ± 0.11 vs. 0.87 ± 0.24, p = 0.03). All 5 MRI+ patients had horizontal spontaneous nystagmus beating away from the lesion (5/5). One patient (1/5) had direction-changing nystagmus with gaze. Two had skew deviation (2/5). Among the 8 MRI– patients, one (1/8) presented as unilateral vestibulopathy, four (4/8) had positional nystagmus and three (3/8) had isolated posterior canal hypofunction.ConclusionThe horizontal-canal head impulse test poorly discriminates central and peripheral lesions when hearing loss accompanies AVS. Paradoxically, a lateral pontine lesion usually mimics unilateral peripheral vestibulopathy. By contrast, patients with peripheral lesions usually present with positional nystagmus or isolated posterior canal impairment, risking misdiagnosis as central vestibulopathy.

Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats.

The aim of this study was to assess the effect of Vertigoheel on central vestibular compensation and cognitive deficits in rats subjected to peripheral vestibular loss. Young adult male Long Evans rats were subjected to bilateral vestibular insults through irreversible sequential ototoxic destructions of the vestibular sensory organs. Vestibular syndrome characteristics were monitored at several time points over days and weeks following the sequential insults, using a combination of behavioral assessment paradigms allowing appreciation of patterns of change in static and dynamic deficits, together with spatial navigation, learning, and memory processes. Vertigoheel administered intraperitoneally significantly improved maximum body velocity and not moving time relative to its vehicle control on days 2 and 3 and on day 2, respectively, after unilateral vestibular lesion (UVL). It also significantly improved postural control relative to its vehicle 1 day after UVL. Conversely, Vertigoheel did not display any significant effect vs. vehicle on the severity of the syndrome, nor on the time course of other examined parameters, such as distance moved, mean body velocity, meander, and rearing. Spatial cognition testing using Y- and T-maze and eight-radial arm maze did not show any statistically significant difference between Vertigoheel and vehicle groups. However, Vertigoheel potentially enhanced the speed of learning in sham animals. Evaluating Vertigoheel's effect on thigmotaxis during the open-field video tracking test revealed no significant difference between Vertigoheel and its vehicle control groups suggesting that Vertigoheel does not seem to induce sedative or anxiolytic effects that could negatively affect vestibular and memory function. Present observations reveal that Vertigoheel improves central vestibular compensation following the unilateral peripheral vestibular loss as demonstrated by improvement of specific symptoms.

Vestibular syndromes after COVID-19 vaccination: A prospective cohort study.

Background and purposeDizziness and vertigo are common symptoms after COVID‐19‐vaccination. We aimed to prospectively evaluate objective central or peripheral vestibular function in patients with dizziness, vertigo, and postural symptoms that started or worsened after COVID‐19‐vaccination.MethodsOf 4137 patients who presented between January 2021 and April 2022 at the German Center for Vertigo and Balance Disorders, Ludwig Maximilian University of Munich, we identified 72 patients (mean age = 47 years) with enduring vestibular symptoms following COVID‐19 vaccination. All underwent medical history‐taking, and neurological and neuro‐otological workup with bithermal caloric test, video head‐impulse test, orthoptics, and audiometry. Diagnoses were based on international criteria. The distribution of diagnoses was compared to a cohort of 39,964 patients seen before the COVID‐19 pandemic.ResultsSymptom onset was within the first 4 weeks postvaccination. The most prevalent diagnoses were somatoform vestibular disorders (34.7%), vestibular migraine (19.4%), and overlap syndromes of both (18.1%). These disorders were significantly overrepresented compared to the prepandemic control cohort. Thirty‐six percent of patients with somatoform complaints reported a positive history of depressive or anxiety disorders. Nine patients presented with benign paroxysmal positional vertigo, three with acute unilateral vestibulopathy, and seven with different entities (vestibular paroxysmia, Ménière disease, polyneuropathy, ocular muscular paresis). Causally related central vestibular deficits were lacking. Novel peripheral vestibular deficits were found in four patients.ConclusionsNewly induced persistent vestibular deficits following COVID‐19 vaccination were rare. The predominant causes of prolonged vestibular complaints were somatoform vestibular disorders and vestibular migraine, possibly triggered or aggravated by stress‐related circumstances due to the COVID‐19 pandemic or vaccination. An increase of other central or peripheral vestibular syndromes after COVID‐19 vaccination was not observed.

Vestibular Neuritis after COVID-19 Vaccination

Coronavirus disease 2019 (COVID-19) spread rapidly and was declared a pandemic. In this situation, vaccination for COVID-19 is important and has been prompted in many countries. However, a number of adverse events have been reported for the Pfizer, Moderna, and AstraZeneca vaccines. Otolaryngologic adverse events after COVID-19 vaccination were reported, including several cases of sudden sensorineural hearing loss. Vestibular neuritis (VN) is an acute vestibular syndrome that causes acute and spontaneous vertigo due to unilateral vestibular deafferentiation, leading to nausea or vomiting and unsteadiness that can last from days to weeks. Neurotropism for the cochleovestibular nerve, immunoglobulin G mediated immune off-target reaction, and reactivation of latent viruses are hypothesized to be etiologies. Herein, the case of a 49-year-old female who developed VN after COVID-19 vaccination is presented. Although the association between VN and COVID-19 vaccination remains unclear, clinicians should be aware that VN may occur as an adverse event of COVID-19 vaccination.

Prevalence of stroke in acute vertigo presentations: A UK tertiary stroke centre perspective

The reported prevalence of stroke amongst patients presenting to hospital with acute vertigo and/or imbalance is c. 5%, leading to the pervasive notion amongst emergency and stroke physicians, that stroke is uncommon in this cohort.To interrogate the veracity of this notion, we systematically and retrospectively screened the electronic care records in our institution of patients referred as suspected stroke, to a hyperacute stroke service at a large tertiary referral centre.We screened 24,310 consecutive patients' electronic case records presenting to our hospital as an emergency over a 4-month period, 332 of whom were referred as suspected stroke whose case records were assessed via structured review. Of these 332 cases, 61 presented with a vestibular syndrome, i.e. having at least one of imbalance, dizziness or vertigo. Of the 61 vestibular cases, 38 (62%) were diagnosed as stroke confirmed by imaging in 25/38 or upon clinical grounds only (13/38). None of the 38 vestibular stroke cases received thrombolysis or thrombectomy treatment.In a UK urban population (2.5mn), acute vestibular syndrome cases referred to stroke services have a 50% stroke prevalence. None of the vestibular stroke cases received hyperacute stroke treatment e.g., thrombolysis, due to delay in diagnosis. The high stroke prevalence in our cohort may indicate an excessively high threshold for referring acute vestibular cases for stroke, implying a high number of missed stroke cases. We suggest that early access to vestibular neurologists in acute vestibular cases should improve the proportion of vestibular stroke cases receiving definitive stroke treatment.