Cajal's contributions to vestibular research.

The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or the direction followed by nerve impulses (the principle of dynamic polarization), he described numerous details regarding the organization of the different structures of the nervous system. This task was compiled in his magnum opus, "Textura del Sistema Nervioso del Hombre y los Vertebrados," first published in Spanish between 1899 and 1904, and later revised and updated in French as "Histologie du système nerveux de l'homme et des vertébrés" between 1909 and 1911 for wider distribution among the international scientific community. Some of Cajal's findings are fundamental to our understanding of the anatomy and histology of the vestibular system. He depicted the nerve endings in the sensory epithelia, the structure of the vestibular nerve and Scarpa ganglion, afferent vestibular fibers, vestibular nuclei, lateral vestibulospinal tract, vestibulocerebellar connections, and the fine structure of the cerebellum. However, most of these pioneering descriptions were published years earlier in Spanish journals with limited circulation. Our study aimed to gather Cajal's findings on the vestibular system and identify his original publications. After this endeavor, we claim a place for Cajal among the founders of anatomy and histology of the vestibular system.

Multiomic-based immune response profiling in migraine, vestibular migraine and Meniere's disease.

Migraine (MI) is the most common neurological disease, affecting with 20% of the world population. A subset of 25% of MI patients showcase concurrent vestibular symptoms, which may classify as vestibular migraine (VM). Meniere's disease (MD) is a complex inner ear disorder defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss with a significant autoimmune/autoinflammatory contribution, which symptoms overlap with VM. Blood samples from 18 patients with MI (5), VM (5) and MD (8) and 6 controls were collected and compared in a case-control study. Droplet-isolated nuclei from mononuclear cells used to generate scRNAseq and scATACseq data sets from MI, VM and MD. MI and VM have no differences in their immune transcriptome; therefore, they were considered as a single cluster for further analyses. Natural Killer (NK) cells transcriptomic data support a polarisation triggered by Type 1 innate immune cells via the release of interleukin (IL)-12, IL-15 and IL-18. According to the monocyte scRNAseq data, there were two MD clusters, one inactive and one driven by monocytes. The unique pathways of the MI + VM cluster were cellular responses to metal ions, whereas MD monocyte-driven cluster pathways showed responses to biotic stimuli. MI and MD have different immune responses. These findings support that MI and VM have a Type 1 immune lymphoid cell response, and that there are two clusters of MD patients, one inactive and one Monocyte-driven.

Visual Fixation of Skull-Vibration-Induced Nystagmus in Patients with Peripheral Vestibulopathy.

Nystagmus induced by applying an intense vibratory stimulus to the skull (SVIN) indicates vestibular functional asymmetry. In unilateral vestibular loss, a 100 Hz bone-conducted vibration given to either mastoid immediately causes a primarily horizontal nystagmus. The test is performed in darkness to avoid visual fixation (VF) but there are no data about how much VF affects the often-intense SVIN. The aim is to analyze the amount of reduction in SVIN when VF is allowed during testing. Thus, all patients seen in a tertiary hospital for vertigo or dizziness with positive SVIN were included. SVIN was recorded for 10 s for each condition: without VF (aSVINwo) and with VF (aSVINw). We obtained an aSVINwo and an aSVINw as average slow-phase velocities (SPV) without and with VF. VF index (FISVIN) was calculated as the ratio of SPV. Among the 124 patients included, spontaneous nystagmus (SN) was found in 25% and the median slow phase velocity (mSPV) (without VF) of SN was 2.6 ± 2.4°/s. Mean FISVIN was 0.27 ± 0.29. FISVIN was 0 in 42 patients, and FISVIN between 0 and 1 was found in 82 (mean FISVIN 0.39 ± 0.02). Fixation suppression was found in all patients with SVIN in cases of peripheral vestibulopathy. FISVIN clearly delineates two populations of patients: with or without a complete visual reduction in nystagmus.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Influence of Age and Cardiovascular Risk Factors in Vestibular Neuritis: Retrospective Cohort Study.

To analyze the influence of age and cardiovascular risk factors (CVRFs) in the evolution of vestibular neuritis (VN). METHODS: Retrospective cohort study. VN-diagnosed patients were included and divided into two groups: those with and without CVRFs. We analyzed the mean vestibular-ocular reflex (VOR) gain, measured through the video head impulse test (vHIT) at the diagnosis and one-year follow-up. We conducted a factorial analysis of variance (ANOVA) to evaluate the effect of age, sex, and CVRFs in the mean VOR gain. RESULTS: Sixty-three VN-diagnosed patients were included. There were no statistically significant differences in the mean VOR gain between both groups. However, in the subgroup analysis, there were statistically significant differences when comparing the mean VOR gain at the one-year follow-up between the group over 55 years of age 0.77 ± 0.20 and the group under 55 years 0.87 ± 0.15 (p = 0.036). Additionally, the factorial ANOVA demonstrated a significant main effect of age group on the mean VOR gain at the one-year follow-up (p = 0.018), and it also found a significant interaction between the factors of gender, age group, HTN (p = 0.043). CONCLUSIONS: CVRFs do not independently affect the mean VOR gain in VN patients' follow-ups. However, age significantly impacts VOR gain in VN and could be modulated by gender and hypertension.

The vestibular system: Contributions of Lorente de Nó.

BACKGROUND: Rafael Lorente de Nó was a neuroscientist that worked alongside two of the giants of Medicine, the Nobel Prize winners Cajal and Bárány. OBJECTIVE: To describe the contributions of Lorente de Nó to vestibular neuroscience. METHODS: Detailed review of the publications of Lorente de Nó and analysis of the archives from Junta para Ampliación de Estudios e Investigaciones Científicas at Residencia de Estudiantes (Madrid, Spain), Casa de Salud Valdecilla at Hospital Universitario Marqués de Valdecilla (Santander, Spain), Becker Medical Library at Washington University (St. Louis, MO, USA), Rockefeller Archive Center (Sleepy Hollow, New York, NY, USA), Archivo Fernando de Castro (Madrid, Spain), Biblioteca Nacional de España (Madrid, Spain) and Legado Cajal at Instituto Cajal (Madrid, Spain). Most of this material is unpublished and includes over a hundred letters to or from Lorente. RESULTS: Lorente de Nó made a substantial contribution to our understanding of the vestibular system. Amongst these, he meticulously detailed the course of the vestibular nerve and its central projections. He described the vestibulo-ocular reflex as the consequence of an integration of the various nuclei and connections across the vestibular system, rather than a simple three-neuron arc. He also highlighted the role of the reticular formation in the generation of the fast phase of the nystagmus. CONCLUSIONS: Lorente de Nó was a pioneer of modern neuro-otology, having made outstanding contributions to vestibular neuroscience, forging novel discoveries that still burn true today.

Factors Impacting the Use or Rejection of Hearing Aids-A Systematic Review and Meta-Analysis.

PURPOSE: To examine the prevalence of adherence to hearing aids and determine their rejection causes. METHODS: This study was conducted according to the Preferred Reporting terms for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an electronic search using PubMed, BVS, and Embase. RESULTS: 21 studies that met the inclusion criteria were selected. They analyzed a total of 12,696 individuals. We observed that the most common causes for positive adherence to hearing aid use included having a higher degree of hearing loss, patients being aware of their condition, and requiring the device in their daily life. The most common causes for rejection were the lack of perceived benefits or discomfort with the use of the device. The results from the meta-analysis show a prevalence of patients who used their hearing aid of 0.623 (95% CI 0.531, 0.714). Both groups are highly heterogeneous (I2 = 99.31% in each group, p < 0.05). CONCLUSIONS: A significant proportion of patients (38%) do not use their hearing aid devices. Homogeneous multicenter studies using the same methodology are needed to analyze the causes of rejection of hearing aids.

Early Diagnosis of Central Disorders Mimicking Horizontal Canal Cupulolithiasis.

BACKGROUND: Horizontal Canal Cupulolithiasis (hc-BPPV-cu) can mimic a pathology of central origin, so a careful examination is essential to prevent misdiagnosis. METHODS: Retrospective cross-sectional cohort study of 45 patients suffering from suspected hc-BPPV-cu. We recorded whether patients first presented through an ENT Emergency Department (ED) or through an Outpatient Otolaryngology Clinic (OC). RESULTS: We found statistically significant differences (p < 0.05) between the OC versus the ED in relation to the time between symptom onset and first assessment (79.7 vs. 3.6 days, respectively), the number of therapeutic maneuvers (one maneuver in 62.5% vs. 75.9%, and more than one in 25.1% vs. 13.7%), and multi-canal BPPV rate (43.8% vs. 3.4%). hc-BPPV-cu did not resolve in 2 patients (12.5%) from the OC and in 3 (10.3%) from de ED, all of which showed central pathology. DISCUSSION: There are no prior studies that analyze the approach to hc-BPPV-cu in the ED. The benefits of early specialist input are early identification of central positional nystagmus, a decrease in symptom duration, reduced number of therapeutic maneuvers required for symptom resolution, and lower rates of iatrogenic multi-canal BPPV. CONCLUSION: A comprehensive approach to hc-BPPV-cu in the ED allows both more effective treatment and early identification of central disorder mimics.

Single-cell immune profiling of Meniere Disease patients.

BACKGROUND: Meniere Disease (MD) is an inner ear syndrome, characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. The pathological mechanism leading to sporadic MD is still poorly understood, however an allergic inflammatory response seems to be involved in some patients with MD. OBJECTIVE: Decipher an immune signature associated with the syndrome. METHODS: We performed mass cytometry immune profiling on peripheral blood from MD patients and controls. We analyzed differences in state and differences in abundance of the different cellular subsets. IgE levels were quantified through ELISA on supernatant of cultured whole blood. RESULTS: We have identified two clusters of individuals according to the single cell cytokine profile. These clusters presented differences in IgE levels, immune cell population abundance, including a reduction of CD56dim NK-cells, and changes in cytokine expression with a different response to bacterial and fungal antigens. CONCLUSION: Our results support a systemic inflammatory response in some MD patients that show a type 2 response with allergic phenotype, which could benefit from personalized IL-4 blockers.

Skull Vibration-Induced Nystagmus and High Frequency Ocular Vestibular-Evoked Myogenic Potentials in Superior Canal Dehiscence.

BACKGROUND: Although diagnostic criteria have been established for superior canal dehiscence syndrome, cases in which the diagnosis is not easy are frequent. On those occasions, some tests such as vibration-induced nystagmus or vestibular-evoked myogenic potentials can offer invaluable help due to their high sensitivity and specificity. METHODS: We studied 30 patients showing superior canal dehiscence or "near-dehiscence" in a CT scan. Skull vibration-induced nystagmus and high frequency ocular vestibular-evoked myogenic potentials are performed in each patient. The aim of the study is to determine how useful both tests are for detection of superior canal dehiscence or near-dehiscence. RESULTS: Of the 60 temporal bones studied, no dehiscence was the result in 22, near-dehiscence in 17 and a definite finding in 21. In 10/30 patients, there was no SVIN (Skull vibration induced nystagmus) during otoneurological testing, while in 6/30, induced nystagmus was mainly horizontal, and in 14/30 there was vertical up-beating. All patients had a positive oVEMP (Ocular vestibular evoked myiogenic potentials) at 0.5 kHz in both ears and the HFoVEMP (High frequency ocular vestibular evoked myiogenic potentials) response was positive in 25/60 (41.6%) of the ears studied and in 19/30 of the patients evaluated (in 6 it was positive in both ears). Up-beat SVIN will point to a SCD (Superior Canal Dehiscence) mainly when HFoVEMP are present, and when this is negative there is a high probability that it is not a SCD. CONCLUSIONS: When SVIN and HFoVEMP results are added (or combined), they not only improve the possibilities of detecting SCD, but also the affected side.

Prevention of Severe Vestibular Hypofunction after Systemic Gentamicin.

The importance of early evaluation by a neurotologist in patients with infective endocarditis treated with systemic gentamicin and its impact on the patients' quality of life was evaluated. This is a longitudinal retrospective cohort study of 29 patients who received intravenous gentamicin for the treatment of infective endocarditis. Patients were classified into two groups: group A, before a neurotologist was included in the treatment protocol, and group B, after the inclusion of a neurotologist. The frequency of the different symptoms in each group was measured, and the gain of the vestibulo-ocular reflex (VOR) and its relationship with the presence of oscillopsia. In total, 13 and 16 patients were assigned to groups A and B, respectively. The mean gain of the VOR measured using the video head impulse test in group A was 0.44 in the best side and 0.39 in the worst side. In group B, the mean gain was 0.71 (best side) and 0.64 (worst side) (p < 0.0001). The patients who complained about oscillopsia had a main gain of 0.41 in the best side and 0.35 in the worst side. Evaluation of vestibular function should be included in the infective endocarditis treatment protocol, including the adverse effects of systemic gentamicin.

A Predictive Model of Bilateral Sensorineural Hearing Loss in Meniere Disease Using Clinical Data.

OBJECTIVES: Meniere disease (MD) is defined by a clinical syndrome of recurrent attacks of spontaneous vertigo associated with tinnitus, aural fullness, and sensorineural hearing loss (SNHL). Most patients have unilateral SNHL, but some of them will develop contralateral SNHL during the course of the disease. Several studies have reported a frequency of 2 to 73% SNHL in the second ear, according to the duration of disease and the period of follow-up. We hypothesize that unilateral and bilateral MD are different conditions, the first would initially involve the apical turn of the cochlea, while bilateral MD would affect the entire length of the cochlea. The aim of the study is to search for clinical predictors of bilateral SNHL in MD to build a predictive model of bilateral involvement. DESIGN: A retrospective, longitudinal study including two cohorts with a total of 400 patients with definite MD was carried out. The inception cohort consisted of 150 patients with MD and the validation cohort included 250 cases. All of the cases were diagnosed of unilateral MD according to their hearing loss thresholds. The following variables were assessed as predictors of bilateral SNHL for the two cohorts: sex, age of onset, familiar history of MD, migraine and high-frequency hearing loss (HFHL, defined if hearing threshold >20 dB in two or more consecutive frequencies from 2 to 8 KHz). A descriptive analysis was carried out according to the presence of HFHL in the first audiogram for the main variables. By using multiple logistic regression, we built-up several predictive models for the inception cohort and validated it with the replication cohort and merged dataset. RESULTS: Twenty-three (19.3%) and 78 (41%) of patients with HFHL developed contralateral SNHL during the follow-up, in the inception and validation cohorts, respectively. In the inception cohort, the best predictive model included HFHL in the first audiogram (OR = 6.985, p = 0.063) and the absence of migraine (OR = 0.215, p = 0.144) as clinical predictors for bilateral SNHL [area under the curve (AUC) = 0.641, p = 0.002]. The model was validated in the second cohort (AUC = 0.621, p < 0.001). Finally, we merged both datasets to improve the precision of the model including HFHL in the first audiogram (OR = 3.168, p = 0.001), migraine (OR = 0.482, p = 0.036) and age of onset >35 years old (OR = 2.422, p = 0.006) as clinical predictors (AUC = 0.639, p < 0.001). CONCLUSIONS: A predictive model including the age of onset, HFHL in the first audiogram and migraine can help to assess the risk of bilateral SNHL in MD. This model may have significant implications for clinical management of patients with MD.

Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study.

BACKGROUND: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype. METHODS: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus. FINDINGS: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E-04), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E-02). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. INTERPRETATION: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons.

Vibration-induced nystagmus and head impulse test screening for vestibular schwannoma.

LEVEL OF EVIDENCE: II-2. BACKGROUND: Vestibular schwannomas are benign tumors of the eight cranial nerve that may cause asymmetric sensorineural hearing loss (ASHL) and vestibular dysfunction. OBJECTIVE: The aim of this study was to assess the role of the video head impulse test (vHIT) and vibration-induced nystagmus (VIN) test in diagnosing vestibular schwannoma in a population of patients with Asymmetric sensorineural hearing loss. MATERIAL AND METHODS: For this prospective case-control study, 23 consecutive patients with ASHL and normal magnetic resonance were enrolled in the control group, and 33 consecutive patients with ASHL and vestibular schwannoma were enrolled in the case group. Gold standard was magnetic resonance imaging. Audiometry, vHIT, and VIN tests were performed for each patient. Significance of VIN and vHIT testing was determined by evaluation of their sensitivity, specificity, and correlation with vestibular function tests. RESULTS: Regarding the vHIT, sensitivity and specificity were 45.5% and 82.6%, respectively, for horizontal canal gain, 60.6% and 87.6%, respectively, for posterior canal gain, and 45.5% and 78.3%, respectively, when analyzing superior canal gains. Regarding the VIN test, the sensitivity and specificity were 81.8% and 73.9%, respectively, when based on the presence of a VIN with any mastoid stimulation. CONCLUSIONS: Our results suggest that using the VIN test may be an efficient approach to screen for vestibular schwannoma in patients with asymmetric sensorineural hearing loss. SIGNIFICANCE: Our results suggest that using the VIN test may be an efficient approach to screen for vestibular schwannoma in patients with ASHL.

Burden of Rare Variants in the OTOG Gene in Familial Meniere's Disease.

OBJECTIVES: Meniere's disease (MD) is a rare inner ear disorder characterized by sensorineural hearing loss, episodic vertigo, and tinnitus. Familial MD has been reported in 6 to 9% of sporadic cases, and few genes including FAM136A, DTNA, PRKCB, SEMA3D, and DPT have been involved in single families, suggesting genetic heterogeneity. In this study, the authors recruited 46 families with MD to search for relevant candidate genes for hearing loss in familial MD. DESIGN: Exome sequencing data from MD patients were analyzed to search for rare variants in hearing loss genes in a case-control study. A total of 109 patients with MD (73 familial cases and 36 early-onset sporadic patients) diagnosed according to the diagnostic criteria defined by the Barany Society were recruited in 11 hospitals. The allelic frequencies of rare variants in hearing loss genes were calculated in individuals with familial MD. A single rare variant analysis and a gene burden analysis (GBA) were conducted in the dataset selecting 1 patient from each family. Allelic frequencies from European and Spanish reference datasets were used as controls. RESULTS: A total of 5136 single-nucleotide variants in hearing loss genes were considered for single rare variant analysis in familial MD cases, but only 1 heterozygous likely pathogenic variant in the OTOG gene (rs552304627) was found in 2 unrelated families. The gene burden analysis found an enrichment of rare missense variants in the OTOG gene in familial MD. So, 15 of 46 families (33%) showed at least 1 rare missense variant in the OTOG gene, suggesting a key role in familial MD. CONCLUSIONS: The authors found an enrichment of multiplex rare missense variants in the OTOG gene in familial MD. This finding supports OTOG as a relevant gene in familial MD and set the groundwork for genetic testing in MD.

Skull vibration-induced nystagmus in vestibular neuritis.

BACKGROUND: As described by Dumas, an 80-100 Hz vibration applied to the mastoid produces a horizontal nystagmus, with quick phases beating away from the affected side in patients with unilateral vestibular loss (UVL). AIM/OBJECTIVES: To elucidate the characteristics of skull vibration-induced nystagmus (SVIN) in patients suffering from vestibular neuritis and how these characteristics are related to information provided by the video head impulse test (vHIT). MATERIAL AND METHODS: Sixty-three patients were enrolled to perform a vHIT to measure the gain in both ears. SVIN was induced with stimulation at 30 Hz, 60 Hz, and 100 Hz. The slow phase velocity (SPV) of the SVIN was measured. RESULTS: The SVIN test was positive in 25/63 patients at 30 Hz, 36/63 at 60 Hz and 46/63 at 100 Hz. Mean gain difference between both ears to obtain a positive SVIN at 30 Hz was observed to be 0.38 ± 0.25, decreasing to 0.35 ± 0.23 at 60 Hz, and 0.31 ± 0.24 at 100 Hz (p = .025). We found a significant positive linear correlation between the gain asymmetry measured using horizontal vHIT and SPV in SVIN at 100 Hz. CONCLUSIONS AND SIGNIFICANCE: There is a close relationship between the difference in the gains of both ears as measured using VHIT and the SPV of the nystagmus induced by SVIN at 100 Hz.

Relevance of Artifact Removal and Number of Stimuli for Video Head Impulse Test Examination.

OBJECTIVE: To evaluate the effect of artifacts on the impulse and response recordings with the video head impulse test (VHIT) and determine how many stimuli are necessary for obtaining acceptably efficient measurements. METHODS: One hundred fifty patients were examined using VHIT and their registries searched for artifacts. We compared several variations of the dataset. The first variation used only samples without artifacts, the second used all samples (with and without artifacts), and the rest used only samples with each type of artifact. We calculated the relative efficiency (RE) of evaluating an increasingly large number of samples (3 to 19 per side) when compared with the complete sample (20 impulses per side). RESULTS: Overshoot was associated with significantly higher speed (p = 0.005), higher duration (p < 0.001) and lower amplitude of the impulses (p = 0.002), and consequent higher saccades' latency (p = 0.035) and lower amplitude (p = 0.025). Loss of track was associated with lower gain (p = 0.035). Blink was associated with a higher number of saccades (p < 0.001), and wrong way was associated with lower saccade latency (p = 0.012). The coefficient of quartile deviation escalated as the number of artifacts of any type rose, indicating an increment of variability. Overshoot increased the probability of the impulse to lay on the outlier range for gain and peak speed. Blink did so for the number of saccades, and wrong way for the saccade amplitude and speed. RE reached a tolerable level of 1.1 at 7 to 10 impulses for all measurements except the PR score. CONCLUSIONS: Our results suggest the necessity of removing artifacts after collecting VHIT samples to improve the accuracy and precision of results. Ten impulses are sufficient for achieving acceptable RE for all measurements except the PR score.

Oscillopsia in Bilateral Vestibular Hypofunction: Not Only Gain But Saccades Too.

OBJECTIVES: Oscillopsia is a disabling condition for patients with bilateral vestibular hypofunction (BVH). When the vestibulo-ocular reflex is bilaterally impaired, its ability to compensate for rapid head movements must be supported by refixation saccades. The objective of this study is to assess the relationship between saccadic strategies and perceived oscillopsia. DESIGN: To avoid the possibility of bias due to remaining vestibular function, we classified patients into two groups according to their gain values in the video head impulse test. One group comprised patients with extremely low gain (0.2 or below) in both sides, and a control group contained BVH patients with gain between 0.2 and 0.6 bilaterally. Binary logistic regression (BLR) was used to determine the variables predicting oscillopsia. RESULTS: Twenty-nine patients were assigned to the extremely low gain group and 23 to the control group. The BLR model revealed the PR score (saccades synchrony measurement) to be the best predictor of oscillopsia. Receiver operating characteristic analysis determined that the most efficient cutoff point for the probabilities saved with the BLR was 0.518, yielding a sensitivity of 86.6% and specificity of 84.2%. CONCLUSIONS: BVH patients with higher PR values (nonsynchronized saccades) were more prone to oscillopsia independent of their gain values. We suggest that the PR score can be considered a useful measurement of compensation.

Lorente de Nó: From Neuroanatomy to Neurophysiology.

Rafael Lorente de Nó (1902-1990) was the youngest and last of Santiago Ramón y Cajal's students. With Fernando de Castro, Lorente de Nó helped to transition the focus of Ramón y Cajal's School from neuroanatomy to neurophysiology. His main contributions to neuroscience concerned the cytoarchitecture of the cerebral isocortex and hippocampus, neural networks, central vestibular system anatomy, vestibulo-ocular reflex physiology, cochlear nuclei anatomy, and synaptic transmission mechanisms. This article pays tribute to the memory of Lorente de Nó by providing a comprehensive review of the life and work of this giant of neuroscience. Anat Rec, 303:1221-1231, 2020. © 2019 American Association for Anatomy.