An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.

Adult-onset cerebellar ataxias are a group of neurodegenerative conditions that challenge both genetic discovery and molecular diagnosis. In this study, we identified an intronic (GAA) repeat expansion in fibroblast growth factor 14 (FGF14). Genetic analysis of 95 Australian individuals with adult-onset ataxia identified four (4.2%) with (GAA)>300 and a further nine individuals with (GAA)>250. PCR and long-read sequence analysis revealed these were pure (GAA) repeats. In comparison, no control subjects had (GAA)>300 and only 2/311 control individuals (0.6%) had a pure (GAA)>250. In a German validation cohort, 9/104 (8.7%) of affected individuals had (GAA)>335 and a further six had (GAA)>250, whereas 10/190 (5.3%) control subjects had (GAA)>250 but none were (GAA)>335. The combined data suggest (GAA)>335 are disease causing and fully penetrant (p = 6.0 × 10-8, OR = 72 [95% CI = 4.3-1,227]), while (GAA)>250 is likely pathogenic with reduced penetrance. Affected individuals had an adult-onset, slowly progressive cerebellar ataxia with variable features including vestibular impairment, hyper-reflexia, and autonomic dysfunction. A negative correlation between age at onset and repeat length was observed (R2 = 0.44, p = 0.00045, slope = -0.12) and identification of a shared haplotype in a minority of individuals suggests that the expansion can be inherited or generated de novo during meiotic division. This study demonstrates the power of genome sequencing and advanced bioinformatic tools to identify novel repeat expansions via model-free, genome-wide analysis and identifies SCA50/ATX-FGF14 as a frequent cause of adult-onset ataxia.

Catch-Up Saccades in Vestibular Hypofunction: A Contribution of the Cerebellum?

Long-term deficits of the vestibulo-ocular reflex (VOR) elicited by head rotation can be partially compensated by catch-up saccades (CuS). These saccades are initially visually guided, but their latency can greatly decrease resulting in short latency CuS (SL-CuS). It is still unclear what triggers these CuS and what are the underlying neural circuits. In this study, we aimed at evaluating the impact of cerebellar pathology on CuS by comparing their characteristics between two groups of patients with bilateral vestibular hypofunction, with or without additional cerebellar dysfunction. We recruited 12 patients with both bilateral vestibular hypofunction and cerebellar dysfunction (BVH-CD group) and 12 patients with isolated bilateral vestibular hypofunction (BVH group). Both groups were matched for age and residual VOR gain. Subjects underwent video head impulse test recording of the horizontal semicircular canals responses as well as recording of visually guided saccades in the step, gap, and overlap paradigms. Latency and gain of the different saccades were calculated. The mean age for BVH-CD and BVH was, respectively, 67.8 and 67.2 years, and the mean residual VOR gain was, respectively, 0.24 and 0.26. The mean latency of the first catch-up saccade was significantly longer for the BVH-CD group than that for the BVH group (204 ms vs 145 ms, p < 0.05). There was no significant difference in the latency of visually guided saccades between the two groups, for none of the three paradigms. The gain of covert saccades tended to be lower in the BVH-CD group than in BVH group (t test; p = 0.06). The mean gain of the 12° or 20° visually guided saccades were not different in both groups. Our results suggest that the cerebellum plays a role in the generation of compensatory SL-CuS observed in BVH patients.

Video head impulse gain is impaired in myotonic dystrophy types 1 and 2.

BACKGROUND AND PURPOSE: This study was undertaken to examine vestibulo-ocular reflex (VOR) characteristics in myotonic dystrophy type 1 (DM1) and type 2 (DM2) using video head impulse testing (vHIT). METHODS: VOR gain, refixation saccade prevalence, first saccade amplitude, onset latency, peak velocity, and duration were compared in DM1, DM2, age-matched normal controls, and patients with peripheral and central vestibulopathies. RESULTS: Fifty percent of DM1 and 37.5% of DM2 patients demonstrated reduced VOR gain. Refixation saccade prevalence for horizontal canal (HC) and posterior canal (PC) was significantly higher in DM1 (101 ± 42%, 82 ± 47%) and DM2 (70 ± 45%, 61 ± 38%) compared to controls (40 ± 28% and 43 ± 33%, p < 0.05). The first saccade amplitudes and peak velocities were higher in HC and PC planes in DM1 and DM2 compared to controls (p < 0.05). HC slow phase eye velocity profiles in DM1 showed delayed peaks. The asymmetry ratio, which represents the percentage difference between the first and second halves of the slow phase eye velocity response, was therefore negative (-22.5 ± 17%, -2.3 ± 16%, and - 4.7 ± 8% in DM1, DM2, and controls). HC VOR gains were lower and gain asymmetry ratio was larger and negative in patients with DM1 with moderate to severe ptosis and a history of imbalance and falls compared to the remaining DM1 patients (p < 0.05). In peripheral vestibulopathies, saccade amplitude was larger, peak velocity was higher, and onset latency was shorter (p < 0.05) than in DM1. In central vestibulopathy (posterior circulation strokes), saccade peak velocity was higher, but amplitude and onset latency were not significantly different from DM1. CONCLUSIONS: VOR impairment is common in DM1 and DM2. In DM1, refixation saccade characteristics are closer to central than peripheral vestibulopathies. Delayed peaks in the vHIT eye velocity profile observed in patients with DM1 may reflect extraocular muscle weakness. VOR impairment and VOR asymmetry in DM1 are associated with imbalance and falls.

A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure.

BACKGROUND: Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants. METHODS: The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman's rho. RESULTS: Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit. CONCLUSION: The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.

Sensorineural Hearing Loss Negatively Impacts Cognition in Older Subjects with Normal Lateral Semi-Circular Canal Function.

INTRODUCTION: Worldwide around 400 million people suffer from hearing loss. There is increasing evidence that hearing loss is a modifiable risk factor for cognitive decline. However, several risk factors for cognition are common in hearing-impaired individuals, including vestibular dysfunction, anxiety, and depression. This study aimed to explore the effect of hearing loss on cognitive functioning in older adults, considering the effects of vestibular function, anxiety, and depression on cognitive performance. METHOD: A cross-sectional study was performed on 42 subjects with moderate-to-severe sensorineural hearing loss (SNHL) and 42 matched normal-hearing controls. Matching was based on the following factors; sex, age, education level, level of anxiety and depression, and vestibular function. The test battery consisted of a cognitive assessment (Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing Impaired [RBANS-H]), hearing assessment (Pure Tone Average and speech-in-noise testing), and vestibular assessment (video Head Impulse Test [vHIT]). Depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI) questionnaires. RESULTS: A significantly lower total cognitive (RBANS-H) score was observed in the group with SNHL compared to controls (100.93 [12.94] vs. 108.88 [10.47], p = 0.003). The difference among both groups was most pronounced in the subdomains Visuospatial/Constructional (92.90 [16.32] vs. 103.12 [12.83], p = 0.002) and Attention (96.62 [12.52] vs. 104.02 [11.81], p = 0.007). The other subdomains Immediate Memory, Language, and Delayed Memory did not differ significantly between the groups with SNHL and the normal-hearing controls. CONCLUSION: The results of this study indicate that hearing loss negatively affects cognitive functioning, even in older adults with normal vestibular function.

Compensatory strategies after an acute unilateral vestibulopathy: a prospective observational study.

PURPOSE: In case of an acute unilateral vestibulopathy (UVP), compensatory strategies such as restoration and adaptation will lead to a decrease in intensity of the symptoms. Although measurements of compensatory strategies are available, currently, an overview taking the different strategies into account is lacking. The objectives of this study are to explore compensatory strategies and to investigate the association between compensatory strategies and patient characteristics. METHODS: Restoration was objectified by the vestibulo-ocular reflex (VOR) gain on the video head impulse test, and adaptation-consisting of visual, multisensory, and behavioral substitution-was objectified by the Visual Vertigo Analog Scale (VVAS), Antwerp Vestibular Compensation Index (AVeCI), and Perez and Rey score (PR score), respectively. Adequate restoration and adaptation levels were interpreted as follows: VOR gain > 0.80, VVAS ≤ 40%, AVeCI > 0 and PR score ≤ 55. RESULTS: Sixty-two UVP patients, 34 men and 28 women, were included with an average age of 52.1 ± 17.3 years. At 10.5 ± 1.4 weeks after onset, 41.9% of the UVP patients reached adequate restoration levels and 58.1-86.9% reached adequate adaptation levels. Furthermore, significant associations were found between (1) restoration status and UVP etiology [Odds Ratio (OR) with 95% CI: 4.167 {1.353;12.828}] and balance performance (OR: 4.400 {1.258;15.386}), (2) visual sensory substitution status and perceived handicap (OR: 8.144 {1.644;40.395}), anxiety (OR: 10.000 {1.579;63.316}) and depression (OR: 16.667 {2.726;101.896}), and (3) behavioral substitution status and balance performance (OR: 4.143 {1.341;12.798}). CONCLUSION: UVP patients with adequate compensatory strategies presented with better balance performance, lower perceived handicap, and lower anxiety and depression scores.

Optimizing vestibular implant electrode positioning using fluoroscopy and intraoperative CT imaging.

PURPOSE:  Vestibular implant electrode positioning close to the afferent nerve fibers is considered to be key for effective and selective electrical stimulation. However, accurate positioning of vestibular implant electrodes inside the semicircular canal ampullae is challenging due to the inability to visualize the target during the surgical procedure. This study investigates the accuracy of a new surgical protocol with real-time fluoroscopy and intraoperative CT imaging, which facilitates electrode positioning during vestibular implant surgery. METHODS:  Single-center case-controlled cohort study with a historic control group at a tertiary referral center. Patients were implanted with a vestibulocochlear implant, using a combination of intraoperative fluoroscopy and cone beam CT imaging. The control group consisted of five patients who were previously implanted with the former implant prototype, without the use of intraoperative imaging. Electrode positioning was analyzed postoperatively with a high-resolution CT scan using 3D slicer software. The result was defined as accurate if the electrode position was within 1.5 mm of the center of the ampulla. RESULTS: With the new imaging protocol, all electrodes could be positioned within a 1.5 mm range of the center of the ampulla. The accuracy was significantly higher in the study group with intraoperative imaging (21/21 electrodes) compared to the control group without intraoperative imaging (10/15 electrodes), (p = 0.008). CONCLUSION:  The combined use of intraoperative fluoroscopy and CT imaging during vestibular implantation can improve the accuracy of electrode positioning. This might lead to better vestibular implant performance.

[Investigation of vestibular function in patients with vestibular neuritis]. / Issledovanie vestibulyarnoi funktsii u patsientov s vestibulyarnym neironitom.

Vestibular neuritis occupies the third place in terms of prevalence in the structure of peripheral vestibulopathies, therefore, the choice of optimal diagnostic and differential diagnostic tactics at different stages of the disease is an urgent task. OBJECTIVE: To optimize the diagnostic algorithm for vestibular neuritis based on an assessment of the sensitivity of clinical methods for studying vestibular function in the recovery period of the disease. MATERIAL AND METHODS: A comprehensive assessment of the sensitivity of clinical methods for the study of vestibular function in the acute (up to 14 days: at the time of initial treatment, on the 7th and 14th day) and subacute (up to 3 months: on the 28th and 90th day) periods of the disease in 52 patients with upper vestibular neuritis was carried out. RESULTS: The timing of the processes of restoration of vestibular function after a transferred vestibular neuritis is individual: after 14 days, restoration of vestibular function was recorded in 52% (n=27) patients, after 1 month - in 62% (n=32), after 3 months - in 71% (n=37) patients with upper vestibular neuritis. Statocoordination, statokinetic, oculomotor tests under visual control have the highest sensitivity in the acute period of vestibular neuritis, within up to 7 days from the onset of symptoms. In the subacute period of vestibular neuritis, the study of spontaneous nystagmus and nystagmus in the head shaking test retains high sensitivity only when using special tools (Frenzel goggles or videonystagmography). A decrease in the sensitivity of the head rotation test and the dynamic visual acuity test in the subacute period of vestibular neuritis is associated with the processes of central compensation and the formation of a latent saccade. CONCLUSION: The sensitivity of clinical tests in patients with vestibular neuritis depends on the timing of the examination.

[Rehabilitation in bilateral vestibulopathy: trends and perspectives]. / Reabilitatsiya patsientov s dvustoronnei vestibulopatiei: tendentsii i perspektivy razvitiya.

A review of the literature on rehabilitation methods for bilateral vestibulopathy is presented using RSCI, Scopus and PubMed databases. The principles and effectiveness of physical vestibular rehabilitation, vestibular implants, galvanic vestibular stimulation, and biofeedback-based sensory substitution and augmentation systems are described. The advantages and disadvantages of each method and perspectives for their improvement are presented.

[Bilateral vestibulopathy and sensorineural hearing loss in necrobiotic xanthogranuloma, multiple myeloma and amiloidosis]. / Dvustoronnyaya vestibulopatiya i sensonevral'naya tugoukhost' u patsienta s nekroticheskoi ksantogranulemoi, mnozhestvennoi mielomoi i amiloidozom.

This article describes a rare case of necrotic xanthogranuloma in a 46-year-old patient who presented with the development of periorbital xanthelasms, progressive bilateral sensorineural hearing loss and bilateral vestibulopathy, followed by multiple myeloma and amyloidosis. For several years, the patient underwent standard rehabilitation for chronic sensorineural hearing loss and was fitted with a hearing aid. During hospitalisation for exacerbation of chronic bronchitis, monoclonal gammopathy was identified, and later, after careful examination and repeated biopsies, necrotic xanthogranuloma, multiple myeloma and AL-amyloidosis were confirmed. Targeted immunochemotherapy resulted in improvement of hearing and significant recovery of the vestibuloocular reflex bilaterally.

Cognitive deficits in patients with peripheral vestibular dysfunction.

BACKGROUND AND PURPOSE: Previous studies demonstrated cognitive deficits in patients with peripheral vestibulopathy (PVP) with dysfunction of spatial navigation and orientation, but also documented cognitive decline in nonspatial abilities. This study evaluates cognitive deficits in patients with unilateral vestibulopathy (UVP) as well as bilateral vestibulopathy (BVP) in multiple cognitive domains using common screening tests to reliably detect these deficits in clinical practice. METHODS: This prospective study compared patients with UVP and BVP to age- and sex-matched healthy controls (HC). Tests included the Alzheimer's Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Trail Making Test Part A and B, Clock Drawing Task, Executive Interview-25 (EXIT25), Dementia Detection (DemTect), and the Judgment of Line Orientation (JLO). The Montgomery-Åsberg Depression Rating Scale was used to control for depression. Videonystagmography objectively reconfirmed PVP. The Vertigo Symptoms Scale and the Dizziness Handicap Inventory were used to assess for symptom severity and restrictions of activities of daily living. RESULTS: Eighty-one patients (65 UVP, 16 BVP) were compared to 55 HC. Patients showed impairment in ADAS, MMSE, DemTect, EXIT25, and JLO. No differences between UVP and BVP were detected. The relative risk (RR) estimates of developing cognitive deficits following PVP were increased. The RR for the ADAS was higher in BVP (RR = 4.91, 95% confidence interval [CI] = 1.87-12.9, p = 0.001) than in UVP (RR = 3.75, 95% CI = 1.65-8.51, p = 0.002), but was similar for the MMSE and DemTect between groups. CONCLUSIONS: Patients with PVP showed deficits in multiple cognitive domains including nonspatial cognitive abilities. Vestibulopathy could be a risk factor for the development of cognitive impairment.

Recurrent Vestibulopathy: Comparison of Vestibular Test Results with Ménière's Disease and Vestibular Migraine.

INTRODUCTION: Recurrent and episodic vestibular symptoms not fulfilling criteria for known episodic vestibular syndromes are named as recurrent vestibulopathy (RV). We aimed to compare the vestibular test results of RV patients with vestibular migraine (VM) and Ménière's disease (MD). METHODS: Twenty patients with MD, 20 patients with VM, 18 patients with RV, and 20 healthy volunteers (HC) were evaluated. Pure-tone hearing thresholds (PTHTs), video head impulse test (vHIT), functional head impulse test (fHIT), and cervical vestibular evoked myogenic potentials (cVEMPs) were studied. RESULTS: PTHT of the MD-affected ears were significantly high, and cVEMP-corrected amplitudes were low when compared with the VM, RV, and HC (p < 0.001 for all). Amplitude asymmetry ratio was significantly high in MD-affected ears when compared with the HC (p = 0.014), VM (p = 0.038), and RV (p = 0.045). VEMP latencies and lateral canal vHIT gain were not different between groups (p > 0.05). The percentage of correctly identified optotypes on fHIT of the MD (p > 0.001), VM (p = 0.004), and RV (p = 0.001) patients were low in comparison with the HC. CONCLUSION: Apart from hearing loss, low cVEMP amplitudes on the affected side were the main feature in MD differentiating it from VM and RV. Vestibular test results of patients with RV and VM were similar. Low fHIT results in all groups indicate a functional deficit in gaze stabilization. Disabling vertigo attacks disturbing attention may be the cause of this functional impairment. MD, VM, and RV may be parts of a broad-spectrum disorder, RV patients representing milder forms not associated with cochlear or migrainous features.

Direction-changing spontaneous nystagmus in patients with dizziness.

PURPOSE: The present study aimed to investigate the clinical features of patients with direction-changing spontaneous nystagmus (DCSN) and gain insight into its underlying mechanisms. METHODS: Medical records and vestibular function test results collected in our dizziness clinic between February 2013 and February 2020 were retrospectively reviewed. Spontaneous nystagmus was recorded while sitting upright using videonystagmography for 2 min to confirm the spontaneous changes in nystagmus direction. Causative disease diagnoses were based on the patients' clinical history, audiometry results, vestibular function tests, and imaging studies. RESULTS: Of 4786 patients, DCSN was observed in 41 (0.86%). Causative disease diagnoses included vestibular neuritis (n = 9), lateral semicircular canal cupulopathy (n = 9), cerebellopontine angle tumor (n = 8), vestibular paroxysmia (n = 2), vestibular migraine (n = 2), vestibular nucleus infarction (n = 1), sudden sensorineural hearing loss with vertigo (n = 2), Meniere's disease (n = 2), Ramsay Hunt syndrome (n = 1), labyrinthine fistula due to middle ear cholesteatoma (n = 1), lateral semicircular canal dysplasia (n = 1), post tympanomastoidectomy dizziness (n = 1), and head trauma (n = 2). CONCLUSIONS: Although the periodicity of DCSN could not be determined because of insufficiently long observation times, it was observed in various central and peripheral vestibulopathies. Careful examination of spontaneous nystagmus over a sufficient period may ensure the detection of DCSN when evaluating dizziness.

Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

Altered Resting-State Intranetwork and Internetwork Functional Connectivity in Patients With Chronic Unilateral Vestibulopathy.

BACKGROUND: Chronic unilateral vestibulopathy (CUVP) is often accompanied by dizziness and postural instability, which restrict patients' daily activities. It is important to understand central compensation mechanisms underlying these symptoms in patients with CUVP by evaluating their brain functional status. PURPOSE: To analyze the changes in resting-state intranetwork and internetwork functional connectivity (FC) and explore the state of central vestibular compensation in patients with CUVP. STUDY TYPE: Retrospective. POPULATION: Eighteen patients with right-sided CUVP and 18 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE: A 3.0 T, three-dimensional magnetization-prepared rapid gradient-echo (MP-RAGE) and resting-state echo-planar imaging (EPI) functional MRI sequences. ASSESSMENT: FC alterations were explored using independent component analysis (ICA). Twelve independent components were identified via ICA. Dizziness Handicap Inventory (DHI) score for all patients was determined. STATISTICAL TESTS: Two-sample t test, family-wise error (FWE) correction, Pearson correlation coefficient (r). A P value <0.05 was considered statistically significant. RESULTS: Compared with healthy controls, patients with CUVP showed significantly decreased FC in the right middle occipital gyrus within the lateral visual network, and significantly increased FC in the right supplementary motor area within the sensorimotor network. The FC was decreased between the medial visual and auditory networks, the right frontoparietal and posterior default networks, as well as the sensorimotor and auditory networks. There was a significant negative correlation between the FC changes in the visual, auditory networks and the DHI score in patients with CUVP (r = -0.583). DATA CONCLUSION: Compared to healthy controls, the FC was significantly decreased in the right visual cortex and significantly enhanced in the right sensorimotor network in patients with CUVP. Patients with CUVP showed decreased FC between multiple whole-brain networks, suggesting that abnormal integration of multisensory information may be involved in the occurrence of chronic dizziness and instability in patients with CUVP. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

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

BACKGROUND AND PURPOSE: Dizziness 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. METHODS: Of 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. RESULTS: Symptom 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. CONCLUSIONS: Newly 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.

Chronic vestibular syndromes in the elderly: Presbyvestibulopathy-an isolated clinical entity?

BACKGROUND AND PURPOSE: Recently, the Classification Committee of the Bárány Society defined the new syndrome of "presbyvestibulopathy" for elderly patients with chronic vestibular symptoms due to a mild bilateral peripheral vestibular hypofunction. However, control of stance and gait requires multiple functioning systems, for example, the somatosensory, visual, auditory, musculoskeletal, and cardio- and cerebrovascular systems. The aim of this cross-sectional database-driven study was to evaluate the frequency and characteristics of presbyvestibulopathy and additional gait-relevant comorbidities. METHODS: In total, 707 patients aged ≥60 years with chronic vertigo/dizziness were admitted to our tertiary hospital and received detailed neurological, neuro-orthoptic, and laboratory audiovestibular examination. Medical history, comorbidities, functional impairment, and quality of life (Dizziness Handicap Inventory [DHI], European Quality of Life Scale, Vestibular Activities and Participation) were compared between presbyvestibulopathy and bilateral vestibulopathy in a matched-paired study. RESULTS: In 95.5% of patients, complaints were better accounted for by another vestibular, neurological, cardiac, or psychiatric disease, and 32 patients (4.5%) met the diagnostic criteria for presbyvestibulopathy. Of these 32 patients, the majority showed further relevant comorbidities in other sensorimotor systems. Only one patient of 707 had "isolated" presbyvestibulopathy (0.14%). The mean total DHI scores indicated lower moderate impairment in presbyvestibulopathy than in bilateral vestibulopathy (40.6 vs. 49.0), which was confirmed by significant differences in the matched-paired analysis (p < 0.001). CONCLUSIONS: Isolated presbyvestibulopathy is a very rare entity. It is regularly accompanied by other multisensory dysfunctions. These results indicate a potential role of mild vestibular hypofunction as a cofactor in multifactorial impairment. Thus, patients should be treated in an interdisciplinary setting with an awareness of diverse comorbidities.

Corticosteroids in patients with vestibular neuritis: An updated meta-analysis.

Vestibular neuritis is a common neuro-otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta-analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970-2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta-analysis using a commercially available software program (www.meta-analysis.com). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2-7.8; p = .015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4-23). The odds ratio (OR) for restoration of vestibular function in the follow-up was 2.4 (95% CI 1.3-4.4; p = .004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5-18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3-93.8; p = .015) and an estimated number needed to harm (NNH) = 4 (95% CI 3-19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non-randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low-grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well-designed randomized controlled trial to re-evaluate the effectiveness of corticosteroids.

Optimized Signal Analysis to Quantify the Non-Linear Behaviour of the Electrically Evoked Vestibulo-Ocular Reflex in Patients with a Vestibular Implant.

INTRODUCTION: Different eye movement analysis algorithms are used in vestibular implant research to quantify the electrically evoked vestibulo-ocular reflex (eVOR). Often, standard techniques are used as applied for quantification of the natural VOR in healthy subjects and patients with vestibular loss. However, in previous research, it was observed that the morphology of the VOR and eVOR may differ substantially. In this study, it was investigated if the analysis techniques for eVOR need to be adapted to optimize a truthful quantification of the eVOR (VOR gain, orientation of the VOR axis, asymmetry, and phase shift). METHODS: "Natural" VOR responses were obtained in six age-matched healthy subjects, and eVOR responses were obtained in eight bilateral-vestibulopathy patients fitted with a vestibular implant. Three conditions were tested: "nVOR" 1-Hz sinusoidal whole-body rotations of healthy subjects in a rotatory chair, "eVOR" 1-Hz sinusoidal electrical vestibular implant stimulation without whole-body rotations in bilateral-vestibulopathy patients, and "dVOR" 1-Hz sinusoidal whole-body rotations in bilateral-vestibulopathy patients using the chair-mounted gyroscope output to drive the electrical vestibular implant stimulation (therefore also in sync 1 Hz sinusoidal). VOR outcomes were determined from the obtained VOR responses, using three different eye movement analysis paradigms: (1) peak eye velocity detection using the raw eye traces; (2) peak eye velocity detection using full-cycle sine fitting of eye traces; (3) peak eye velocity detection using half-cycle sine fitting of eye traces. RESULTS: The type of eye movement analysis algorithm significantly influenced VOR outcomes, especially regarding the VOR gain and asymmetry of the eVOR in bilateral-vestibulopathy patients fitted with a vestibular implant. Full-cycle fitting lowered VOR gain in the eVOR condition (mean difference: 0.14 ± 0.06 95% CI, p = 0.018). Half-cycle fitting lowered VOR gain in the dVOR condition (mean difference: 0.08 ± 0.04 95% CI, p = 0.009). In the eVOR condition, half-cycle fitting was able to demonstrate the asymmetry between the excitatory and inhibitory phases of stimulation in comparison with the full-cycle fitting (mean difference: 0.19 ± 0.12 95% CI, p = 0.024). The VOR axis and phase shift did not differ significantly between eye movement analysis algorithms. In healthy subjects, no clinically significant effect of eye movement analysis algorithms on VOR outcomes was observed. CONCLUSION: For the analysis of the eVOR, the excitatory and inhibitory phases of stimulation should be analysed separately due to the inherent asymmetry of the eVOR. A half-cycle fitting method can be used as a more accurate alternative for the analysis of the full-cycle traces.

Effect of convergence on the horizontal VOR in normal subjects and patients with peripheral and central vestibulopathy.

BACKGROUND: Vestibular compensatory eye movements provide visual fixation stabilization during head movement. The anatomic pathways mediating a normal horizontal vestibulo-ocular reflex (h-VOR), when lesioned, cause spontaneous nystagmus. While previous reports address the effect of convergence on different spontaneous nystagmus types, to our knowledge, a study of acute vestibular nystagmus suppression viewing near targets comparing patients with peripheral or central vestibular lesions has not been previously reported. METHODS: We attempt to clarify potential vestibular and near-reflex interaction by comparing near and far h-VOR gain in 19 healthy controls, six patients with acute/subacute peripheral vestibular lesion (PVL), and one patient with unilateral vestibular nuclear lesion (VNL) in the pontine tegmentum. RESULTS: The horizontal (h)-VOR in normal subjects increased with convergence in both eyes (P = 0.027, P < 0.001). In unilateral PVL patients, gain failed to increase in either direction (P = 0.25, P = 0.47). In contrast, when fixating at 15 cm, the h-aVOR in the VNL lesion, gain did not increase, and a right h-nystagmus developed. Even though we found inability to increase gain in PVL with near target fixation, this did not interfere with h-nystagmus suppression upon converging. Our VNL patient had normal h-nystagmus suppression viewing far distance targets and lacked near target h-nystagmus suppression. CONCLUSION: We hypothesize that normal IO/flocculus pathway suppressed spontaneous nystagmus in PVL. Impaired h-VOR near adaptation in the medial vestibular nucleus was responsible for h-nystagmus direction with fixation block. Additionally, impaired viewing distance estimate contributed to near h-nystagmus suppression failure.