[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.

[The six most frequent peripheral vestibular syndromes]. / Die sechs häufigsten peripheren vestibulären Syndrome.

Three forms of peripheral vestibular disorders, each with its typical symptoms and clinical signs, can be differentiated functionally, anatomically and pathophysiologically: 1. inadequate unilateral paroxysmal stimulation or rarely inhibition of the peripheral vestibular system, e. g., BPPV, Menière's disease, vestibular paroxysmia or syndrome of the third mobile windows; 2. acute unilateral vestibulopathy leading to an acute vestibular tone imbalance manifesting as an acute peripheral vestibular syndrome; and 3. loss or impairment of function of the vestibular nerve and/or labyrinth: bilateral vestibulopathy. For all of these diseases, current diagnostic criteria by the Bárány-Society are available with a high clinical and scientific impact, also for clinical trials. The treatment depends on the underlying disease. It basically consists of 5 principles: 1. Explaining the symptoms and signs, pathophysiology, aetiology and treatment options to the patient; this is important for compliance, adherence and persistence. 2. Physical therapy: A) For BPPV specific liberatory maneuvers, depending on canal involved. Posterior canal: The new SémontPLUS maneuver is superior to the regular Sémont and Epley maneuvers; horizontal canal: the modified roll-maneuver; anterior canal the modified Yacovino-maneuver; 3. Symptomatic or causative drug therapy. There is still a deficit of placebo-controlled clinical trials so that the level of evidence for pharmacotherapy is most often low. 4. Surgery, mainly for the syndrome of the third mobile windows. 5. Psychotherapeutic measures for secondary functional dizziness.

CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy.

[Recent progress in vestibular prosthesis].

Bilateral vestibulopathy（BVP） is one of the common diseases in the vestibular nervous system, with an incidence rate of about 4%-7% in the population, which can lead to a variety of body dysfunctions. At present, there are two main treatment methods for BVP. One is vestibular rehabilitation. However, only part of BVP patients can finally benefit from vestibular rehabilitation, and most patients will remain with permanent vestibular dysfunction. Benefiting from the maturity of cochlear implant technology, European and American countries took the lead in the development of vestibular prosthesis（VP） technology to restore the vestibular function in patients with BVP. This review will focus on the development history, principles, future applications and the related research progress of VP in China.

Clinical and pathology characterization of small nerve fiber neuro(no)pathy in cerebellar ataxia with neuropathy and vestibular areflexia syndrome.

BACKGROUND AND PURPOSE: Biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestations ranging from isolated sensory neuro(no)pathy to a complex presentation as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1 disease at different stages. METHODS: RFC1 cases were screened for SFN using the Neuropathic Pain Symptom Inventory and Composite Autonomic Symptom Score 31 questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structure innervation and compared to healthy controls (HCs). RESULTS: Forty patients, median age at onset 54 years (interquartile range [IQR] 49-61) and disease duration 10 years (IQR 6-16), were enrolled. Mild-to-moderate positive symptoms (median Neuropathic Pain Symptom Inventory score 12.1/50, IQR 5.5-22.3) and relevant autonomic disturbances (median Composite Autonomic Symptom Score 31 37.0/100, IQR 17.7-44.3) were frequently reported and showed scarce correlation with disease duration. A non-length-dependent impairment in nociception was evident in both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm, RFC1 cases 0.0 vs. HCs 20.5, p < 0.0001) and distal sites (fibers/mm, RFC1 cases 0.0 vs. HCs 13.1, p < 0.0001); instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures. CONCLUSIONS: RFC1 disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder.

Association of Bilateral Vestibulopathy With and Without Hearing Loss With Cognitive-Motor Interference.

Importance: The past years, evidence suggested that the primary symptoms traditionally associated with bilateral vestibulopathy (BV) do not represent the full picture of this patient population. Recent literature also demonstrated cognitive impairment. However, although multitasking and dual-tasking are widely present in everyday activities, most of these studies assessed cognitive function only in single-task conditions. Objective: To uncover the association of BV with and without hearing loss with cognitive and motor performance and cognitive-motor interference. Design, Setting, and Participants: This prospective case-control study assessed persons with an isolated BV and persons with BV and a concomitant hearing loss compared with a healthy control group. Data were analyzed in December 2022. The study was conducted at Ghent University (Ghent, Belgium). Data collection took place between March 26, 2021, and November 29, 2022. Main Outcomes and Measures: All participants completed the 2BALANCE dual-task protocol, comprising a static and a dynamic motor task that was combined with 5 visual cognitive tasks. These cognitive tasks assessed mental rotation, visuospatial memory, working memory, response inhibition (executive function), and processing speed. All cognitive tasks were performed in a single-task condition (while seated) and in a dual-task condition (combined with a static and a dynamic motor task). The static task comprised balancing on a force platform with foam pad, and the dynamic task comprised walking at a self-selected speed on the GAITRite Walkway. Both motor tasks were performed in the single-task and dual-task condition. Results: Nineteen persons with BV and hearing loss (mean [SD] age, 56.70 [10.12] years; 10 women [52.6%]), 22 persons with an isolated BV (mean [SD] age, 53.66 [13.35] years; 7 women [31.8%]), and 28 healthy control participants were included (mean [SD] age, 53.73 [12.77] years; 12 women [42.9%]). Both patient groups had mental rotation and working memory impairment in a single-task condition and slower processing speed when walking (ie, during the dynamic dual-task condition). Additionally, the patient group with hearing loss had impaired visuospatial memory and executive function deficits in single-task and dual-task conditions, while this could only be elicited when performing a motor task in persons with isolated BV (ie, when dual-tasking). Conclusion and Relevance: The findings of this case-control study suggest an association between vestibular function and cognitive and motor performance, even greater in persons with a concomitant hearing loss than in persons with an isolated BV.

Vestibular Implantation Can Work Even After More Than 20 Years of Bilateral Vestibular Hypofunction.

OBJECTIVE: To determine whether prosthetic stimulation delivered via a vestibular implant can elicit artificial sensation of head movement despite long (23-yr) duration adult-onset ototoxic bilateral vestibular hypofunction (BVH). STUDY DESIGN: Case report. SETTING: Tertiary care center as part of a first-in-human clinical trial. PATIENTS: One. INTERVENTIONS: Unilateral vestibular implantation with an investigational multichannel vestibular implant in a 55-year-old man with a well-documented 23-year history of aminoglycoside-induced BVH. MAIN OUTCOME MEASURES: Electrically evoked vestibulo-ocular reflexes (eeVOR). RESULTS: Vestibular implant stimulation can drive stimulus-aligned eeVOR and elicit a vestibular percept 23 years after the onset of bilateral vestibulopathy. Prosthetic stimulation targeting individual semicircular canals elicited eye movements that approximately aligned with each targeted canal's axis. The magnitude of the eeVOR response increased with increasing stimulus current amplitude. Response alignment and magnitude were similar to those observed for implant recipients who underwent vestibular implantation less than 10 years after BVH onset. Responses were approximately stable for 18 months of continuous device use (24 h/d except during sleep). CONCLUSIONS: Vestibular implantation and prosthetic electrical stimulation of semicircular canal afferent nerves can drive canal-specific eye movement responses more than 20 years after the onset of ototoxic vestibular hypofunction.

Spinal cord lesion mimicking a dysimmune myelitis revealing CANVAS syndrome.

CONTEXT: Posterior spinal cord lesions are found in patients with ganglionopathy. These are normally found in later stages of the neuronopathy as a consequence of dorsal root ganglia degeneration. Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) is an emerging neurological disorder. Myelitis lesions have been described in confirmed CANVAS cases. FINDINGS: We describe a case of a 68-year-old woman with slowly progressive ataxia with paresthesia. Laboratory tests were normal. Total spine MRI showed a C4 posterior spinal cord lesion. Lumbar puncture was positive for oligoclonal bands with normal IgG index and protein level. Paraneoplastic antibodies were not detected. Electromyography showed nonlength dependent sensory neuropathy. The patient was treated with intravenous immunoglobulin for suspected dysimmune myelitis. Over 6 years, she progressively developed other neurological manifestations evoking CANVAS. Nerve conduction study showed isolated sensory impairment over the years and peripheral nerve ultrasound revealed abnormally small nerves. Further genetic testing confirmed the diagnosis. CONCLUSION: This is the first case of CANVAS syndrome presenting initially with an isolated spinal cord lesion mimicking dysimmune myelitis. The purpose of this case report is to add to the current literature about this evolving neurological syndrome and to aid clinicians in their diagnostic approach in clinical practice.

Associations of Bilateral Vestibulopathy With Cognition in Older Adults Matched With Healthy Controls for Hearing Status.

Importance: Recent literature suggests there may be a significant effect of the vestibular system on cognition and visuospatial processing. Given the increasing prevalence of dementia and individuals at risk for it, exploring possible modifiable risk factors, including vestibular dysfunction, is vital. Objectives: To explore the association of bilateral vestibulopathy (BV) with cognitive function in older adults, taking hearing status into account, and to explore multiple vestibular characteristics and their potential associations with cognition in patients with BV. Design, Setting, and Participants: This cross-sectional study assessed older adults (age 55-84 years) with diagnosed BV from a single center using baseline measurements from the Gehoor, Evenwicht en Cognitie (GECKO) study, an ongoing prospective longitudinal cohort study. Each participant was individually matched with a healthy control based on age, sex, and hearing performance. Data were analyzed in January 2022. Main Outcomes and Measures: The primary outcome measure was cognition, measured by the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H). Results: A total of 68 patients were assessed, including 34 patients with BV (mean [SD] age, 63.3 [6.0] years; 18 [53%] men) matched with 34 control individuals without BV. Overall, participants with BV had a clinically meaningful lower score on the RBANS-H total scale compared with those without BV (mean [SD] score, 98.62 [12.70] vs 105.91 [11.03]). This decline was most pronounced in the subdomains of immediate memory (mean [SD] score, 107.74 [10.66] vs 112.26 [10.66]), visuospatial cognition (mean [SD] score, 90.06 [13.34] vs 100.47 [13.91]), and attention (mean [SD] score, 94.79 [16.39] vs 102.06 [12.97]). There were no differences in language or delayed memory subdomains. Within the BV population, 1 vestibular parameter (the Performance-Oriented Mobility Assessment, in particular the balance subscale) was associated with lower cognitive scores (r32 = 0.51; 95% CI, 0.20 to 0.72; η2 = 0.26). Other vestibular parameters, including measurements of the peripheral vestibular end organ and questionnaires, showed no association. Conclusions and Relevance: These findings suggest there was an association between vestibular loss and cognitive impairment. Further research on the causal mechanisms underlying this association and the possible impact of vestibular rehabilitation on cognition is needed.

Sound localization in patients with bilateral vestibulopathy.

PURPOSE: The goal of this study was to evaluate if bilaterally (partially) absent vestibular function during static sound localization testing, would have a negative impact on sound localization skills. Therefore, this study compared horizontal static sound localization skills of normal-hearing patients with bilateral vestibulopathy (BV) and healthy controls. METHODS: Thirteen normal-hearing patients with BV and thirteen age-matched healthy controls were included. Sound localization skills were tested using seven loudspeakers in a frontal semicircle, ranging from - 90° to + 90°. Sound location accuracy was analyzed using the root-mean-square error (RMSE) and the mean absolute error (MAE). To evaluate the severity of the BV symptoms, the following questionnaires were used: Dizziness Handicap Inventory (DHI), Oscillopsia severity questionnaire (OSQ), 12-item Spatial, Speech, and Qualities Questionnaire (SSQ12), and Health Utilities Index Mark 3 (HUI3). RESULTS: The RMSE and MAE were significantly larger (worse) in the BV group than in the healthy control group, with respective median RMSE of 4.6° and 0°, and a median MAE of 0.7° and 0°. The subjective reporting of speech perception, spatial hearing, and quality of life only demonstrated a moderate correlation between DHI (positive correlation) and HUI total score (negative correlation), and localization scores. CONCLUSION: Static sound localization skills of patients with BV were only mildly worse compared to healthy controls. However, this difference was very small and therefore most likely due to impaired cognitive function. The vestibular system does not seem to have a modulating role in sound localization during static conditions, and its impact is negligible in contrast to the impact of hearing impairment. Furthermore, the subjective reporting of speech perception, spatial hearing, and quality of life was not strongly correlated with localization scores.

Video head impulse test in bilateral vestibulopathy / Teste do impulso efálico com vídeo (vHIT) na vestibulopatia bilateral

Abstract Introduction: Bilateral vestibulopathy is a rare chronic condition with multiple etiologies. Bilateral vestibulopathy is characterized mainly by unsteadiness when walking or standing, which worsens in darkness, as well as oscillopsia. The degree of handicap caused by bilateral vestibulopathy is variable and remains controversial. Objectives: To determine the value of the video Head Impulse Test in quantifying vestibular deficit and to establish its impact on the quality of life. Methods: Twenty patients (mean age, 41.9 years; range 14-80 years) fulfilling the recent Barany criteria of bilateral vestibulopathy, responded to the Situational Vertigo Questionnaire and underwent vestibular examination including fixation, positional tests, oculomotor test battery and video head impulse test. Results: The relation between each of the video head impulse test parameters and the scores from the questionnaire were statistically analyzed. We observed that patients with covert saccades on the video head impulse test were more likely to have a better quality of life than those with both covert and overt saccades, regardless of the vestibulo-ocular reflex gain in each semicircular canal. The presence of covert saccades was found to be associated with an improved quality of life regardless of the severity of vestibule ocular reflex-deficit. Our conclusion was that vestibule ocular reflex gain, measured by video head impulse test, does not quantify the severity of affection of quality of life in patients with bilateral vestibulopathy. Conclusion: Covert saccades are strategies aiming at minimizing the blurring of vision during head movement, that is an adaptive mechanism that improves quality of life. Therefore, we recommend that video head impulse test should be a part of the routine diagnostic workup of bilateral vestibulopathy.

Resumo Introdução: A vestibulopatia bilateral é uma condição crônica rara, com múltiplas etiologias. É caracterizada principalmente por instabilidade ao caminhar ou ficar de pé, que piora na escuridão, e oscilopsia. O grau de deficiência causado pela vestibulopatia bilateral é variável e permanece controverso. Objetivos: Determinar o valor do teste do impulso cefálico na quantificação do déficit vestibular e estabelecer seu impacto na qualidade de vida. Método: Vinte pacientes (média de 41,9 anos; variação de 14 a 80) que atendiam aos critérios recentes da Bárány Society de vestibulopatia bilateral responderam ao Situational Vertigo Questionnaire e foram submetidos a exame vestibular, inclusive fixação, testes posicionais, bateria de testes oculomotores e teste do impulso cefálico com vídeo. Resultados: A relação entre cada um dos parâmetros do teste do impulso cefálico com vídeo e os escores do questionário foram analisados estatisticamente. Observamos que pacientes com sacadas corretivas cobertas do tipo covert no teste de impulso cefálico com vídeo tinham maior probabilidade de ter melhor qualidade de vida do que aqueles com ambas sacadas corretivas cobertas e sacadas corretivas abertas do tipo overt, independentemente do ganho no reflexo vestíbulo-ocular em cada canal semicircular. Verificou-se que a presença de sacadas corretivas do tipo covert está associada a uma melhor qualidade de vida, independentemente da gravidade do déficit no reflexo vestibulo-ocular. Concluímos que o ganho no reflexo vestíbulo-ocular, medido pelo teste do impulso cefálico com vídeo, não quantifica a gravidade do comprometimento da qualidade de vida em pacientes com vestibulopatia bilateral. Conclusão: As sacadas corretivas do tipo covert são estratégias que visam minimizar o embaçamento da visão durante o movimento da cabeça, ou seja, um mecanismo adaptativo que melhora a qualidade de vida. Portanto, recomendamos que o teste do impulso cefálico com vídeo faça parte da rotina de diagnóstico da vestibulopatia bilateral.

Falls Among People With Bilateral Vestibulopathy: A Review of Causes, Incidence, Injuries, and Methods.

Importance: People with bilateral vestibulopathy experience severe balance and mobility issues. Fear and anxiety are associated with reduced activity, which can further affect balance and fall risk. Understanding and intervening on falls in this population is essential. The aims of this narrative review are to provide an overview of the current knowledge and applied methods on fall incidence, causes, and injuries in bilateral vestibulopathy. Observations: Eleven articles reporting falls incidence in people with bilateral vestibulopathy were deemed eligible, including 3 prospective and 8 retrospective studies, with a total of 359 participants, of whom 149 (42%) fell during the assessed period. When reported, the most common perceived causes of falls were loss of balance, darkness, and uneven ground. Information on sustained injuries was limited, with bruises and scrapes being the most common, and only 4 fractures were reported. As most studies included falls as a secondary, descriptive outcome measure, fall data obtained using best practice guidelines were lacking. Only 6 studies reported their definition of a fall, of which 2 studies explicitly reported the way participants were asked about their fall status. Only 3 studies performed a prospective daily fall assessment using monthly fall diaries (a recommended practice), whereas the remaining studies retrospectively collected fall-related data through questionnaires or interviews. While most studies reported the number of people who did and did not fall, the number of total falls in individual studies was lacking. Conclusions and Relevance: The findings from this review suggest that falls in people with bilateral vestibulopathy are common but remain an understudied consequence of the disease. Larger prospective studies that follow best practice guidelines for fall data collection with the aim of obtaining and reporting fall data are required to improve current fall risk assessments and interventions in bilateral vestibulopathy.

Pattern analysis of peripheral-vestibular deficits with machine learning using hierarchical clustering.

Background Disorders affecting the vestibular organs (semicircular canals, utriculus, sacculus), may result in distinct patterns of peripheral-vestibular loss that may facilitate the diagnostic assessment. When neuropathological tests of these sensors are available, it is possible to classify responses as being due to different deficit types. Objective To provide a topical review and to summarize recent advances in pattern-recognition of unilateral and bilateral vestibular disease by use of hierarchical cluster analysis (HCA) as published by the authors. Hypothesis We propose that certain patterns of peripheral-vestibular loss are associated with specific underlying disorders and that HCA is a suitable approach to identify such patterns. Discussion In the studies reviewed, disease-specific patterns could be recognized in different patient cohorts, with anterior-canal sparing being a hallmark feature in aminoglycoside-related bilateral vestibulopathy, Menière's disease and vestibular Schwannoma. The reasons for such anterior-canal sparing remain subject to debate, but potential explanations include reduced toxic exposure, faster recovery and lower vulnerability of the anterior canals. The pattern observed in acute superior-branch vestibular neuropathy, i.e., involvement of the horizontal and anterior canal and the utricle, matches neural inner-ear physiology. The broadly varying extent of damage to the different vestibular sensors even within given disorders underlines the necessity for detailed vestibular-testing. Conclusion HCA significantly facilitates pattern-identification in unilateral and bilateral vestibulopathies and underlines the extensive range of vestibular end-organ damage in the different study populations and subgroups. The large number of existing clustering algorithms with distinct strengths and weaknesses emphasizes the need for careful selection of the most suitable algorithm.

CANVAS: A New Genetic Entity in the Otorhinolaryngologist's Differential Diagnosis.

OBJECTIVE: The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. STUDY DESIGN: A retrospective descriptive study from an ataxia database comprising 500 patients. SETTING: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. METHODS: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. RESULTS: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. CONCLUSION: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (canvas): an important cause of late-onset ataxia with unique clinical features.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)exp, in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.

RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy.

BACKGROUND: A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. "Chronic Idiopathic Axonal Polyneuropathy" (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations. METHODS: We screened 234 probands diagnosed with CIAP for a pathogenic biallelic RFC1 AAGGG repeat expansion. Patients were selected from 594 consecutive patients with neuropathy referred to our tertiary-care center for a sural nerve biopsy over 10 years. RESULTS: The RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. The mutation was associated with sensory ataxia (τb = 0.254, P < 0.001), autonomic disturbances (35% vs 8%, Prevalence Odds Ratio-POR 6.73 CI 95% 2.79-16.2, P < 0.001), retained deep tendon reflexes (score 18.0/24 vs 11.5/24, R = 0.275, P < 0.001). On pathology, we observed absent/scant regenerative changes (τb = - 0.362, P < 0.001), concomitant involvement of large (100% and 99%, n.s.), small myelinated (97% vs 81%, POR 7.74 CI 95% 1.03-58.4, P = 0.02) and unmyelinated nerve fibers (85% vs 41%, POR 8.52 CI 95% 3.17-22.9, P < 0.001). Cerebellar or vestibular involvement was similarly rare in the two groups. CONCLUSIONS: This study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.

[Screening for bilateral vestibulopathy in outpatients with unsteadiness].

Objective:This study aimed to find bilateral vestibulopathy（BVP） patients in outpatients with unsteadiness and investigate their clinical characteristics. Methods:According to the common manifestation and etiologies of BVP, 2075 outpatients who were diagnosed as imbalance, follow up on chemotherapy, bilateral Menière's disease, systemic lupus erythematosus（SLE） and vasculitis from January 2018 to October 2019 were searched based on the hospital information system. After completing a telephone screening interview, eligible individuals whose symptoms were in consistent with the diagnostic criteria of BVP were scheduled for questionnaires and video head impulse test（vHIT）. Results:A total of 131 patients replied and complained chronic unsteadiness. The response rates of patients with bilateral Menière's disease, chemotherapy, SLE and vasculitis were 10.0%, 0%, 0.3% and 1.2%, respectively. Unsteadiness is uncommon or mild in outpatients with vasculitis, SLE and chemotherapy. Twenty-nine patients presented with typical symptoms of BVP and only 3 were diagnosed as BVP after vHIT. The horizontal vHIT gain was significantly lower among patients who reported very severe life impact than those reported mild to severe impact in older patients, as well as in male patients（both P<0.01）. However, no significant differences were noted in younger and female patients（P=0.396, 0.180, respectively）. Conclusion:BVP accounts for 2.3% in outpatients with unsteadiness, and only 10.3% of patients who presents with typical symptoms meet the diagnostic criteria, suggesting vestibular function test is of great significance in making diagnosis.

Management of vestibular dysfunction and hearing loss in intralabyrinthine schwannomas.

PURPOSE: Intralabyrinthine schwannomas (ILS) are rare, benign, slow-growing tumors arising from schwann cells of the cochlear or vestibular nerves within the bony labyrinth. This study provides insight into the management of this rare tumor through a large case series. MATERIALS AND METHODS: After Institutional Review Board approval, a retrospective chart review was performed of all ILS patients treated at our institution between 2007 and 2019. RESULTS: 20 patients (9 male, 11 female) with ILS were managed at our institution. The right ear was affected in 9 patients (45%) and the left in 11 (55%). Subjective hearing loss was endorsed by all 20 patients. Average pure tone average at presentation was 72 dB nHL. Nine tumors (45%) were intravestibular, 6 (30%) were intracochlear, 4 (20%) were transmodiolar and 1 (5%) was intravestibulocochlear. Hearings aids were used in 3 patients (15%), BiCROS in 2 (10%), CI in 2 (10%), and bone conduction implant in 1 (5%). Vestibular rehabilitation was pursued in 5 patients. Surgical excision was performed for one patient (5%) via translabyrinthine approach due to intractable vertigo. No patients received radiotherapy or intratympanic gentamicin injections. CONCLUSION: ILS presents a diagnostic and management challenge given the similarity of symptoms with other disorders and limited treatment options. Hearing loss may be managed on a case-by-case basis according to patient symptoms while vestibular loss may be mitigated with vestibular therapy. Surgical excision may be considered in patients with intractable vertigo, severe hearing loss with concurrent CI placement, or in other case-by-case situations.