Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease.

Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1ß into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 × 10-6) and IGLV3-21 (p = 6.28 × 10-3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1ß with up-regulation of IL6 (p = 7.65 × 10-8) and INHBA (p = 3.39 × 10-7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.

Balance disorders as potential confounders associated with an increased risk of acute cerebrovascular accidents.

PURPOSE: There is a higher risk of stroke after suffering from balance disorders (BDs) such as vertigo or dizziness. The causal relationship remains unclear due to the limited scope of the existing studies and the high prevalence of cardiovascular risk factors (CVRFs) in BD patients. The objective of this study is to clarify the role that BDs seem to have in the development of acute cerebrovascular accidents (ACAs). METHODS: This is an observational prospective study. The CVRFs and demographic factors of a sample of our population were noted. Five clusters of patients were tracked over the course of 2 years to detect and diagnose BDs and ACAs. The causal relationships between the CVRFs, BDs and ACAs were analyzed in a univariate analysis. A logistic regression multivariant analysis was performed on those variables that reached statistical significance. RESULTS: The sample included 7886 participants and 31 ACAs were recorded. CVRFs that reached statistical significance included age ≥ 60, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, atrial fibrillation and previous ACAs. The relationship between BDs and ACAs always reached statistical significance, regardless of how the BD variable was defined. Five different multivariate analyses were performed, but in none of them did the BD variables significantly reduce the deviance and thus, they were not taken into account when building the final model. CONCLUSION: This study shows that BDs are probably confounders that are closely linked to other CVRFs and they are also useful red flags to identify patients at a higher risk of suffering from ACAs.

Positional End-Point Nystagmus in Patients with Diagnosis of Acute Unilateral Vestibulopathy.

INTRODUCTION: Recently, end-point nystagmus, traditionally observed in an upright position, has been identified in the Dix-Hallpike position among healthy subjects, suggesting a physiological origin.However, its characteristics in individuals with vestibular hypofunction remain unexplored. OBJECTIVE: To elucidate the impact of vestibular hypofunction on the characteristics of positional end-point nystagmus. METHODS: Thirty-one patients diagnosed with acute unilateral vestibulopathy according to Bárány Society criteria were selected. A video head impulse test was conducted in all participants, followed by McClure and Dix-Hallpike maneuvers with and without gaze fixation, and with the initial position of the eye in the straight-ahead position or in the horizontal end-point position. Nystagmus direction, sense, latency, slow-phase velocity, and duration were recorded. The relationship between these characteristics and video head impulse test values was analyzed. RESULTS: Positional end-point nystagmus was observed in 92.6% of subjects with vestibular hypofunction, significantly more than in healthy individuals. Nystagmus direction varied depending on the performed positional test and on the vestibulo-ocular reflex gains. Gaze occlusion and the initial horizontal end-point position increased its frequency. CONCLUSION: Vestibular hypofunction influences the manifestation of positional end-point nystagmus. Recognizing this nystagmus can aid in resolving diagnostic uncertainties and preventing the misdiagnosis of benign paroxysmal positional vertigo in subjects with acute unilateral vestibulopathy.

Positional End-Point Nystagmus during Positional Testing: Prevalence, Characteristics and Differences with Benign Paroxysmal Positional Vertigo.

BACKGROUND: Some individuals present positional end-point nystagmus when the Dix-Hallpike tests are performed on them if they unintentionally look towards the examined ear. OBJECTIVE: To describe the prevalence and the characteristics of end-point nystagmus during positional testing in healthy subjects. METHODS: Sixty healthy subjects were included. Eight positional tests were performed on them, two Pagnini-McClure tests and six Dix-Hallpike tests, while keeping the eyes in different positions; one on each side. Two independent observers filled in a questionnaire about the presence of positional nystagmus, its latency, duration, direction, and sense. RESULTS AND CONCLUSIONS: Of the subjects, 65% showed positional end-point nystagmus. This nystagmus had a short latency and last for as long as the head is maintained in the test position. They can show any direction or sense, but the most common are torsional clockwise in left tests and anticlockwise in right tests. Unlike BPPV, this nystagmus did not appear with the eyes in the straight-ahead position, it is asymptomatic, and its intensity does not decline.

Exploring the frontiers of vestibular migraine: A case series.

INTRODUCTION: Patients with episodic vestibular syndrome (EVS) whose symptoms resemble those of vestibular migraine (VM) but who do not meet the criteria for it are common. OBJECTIVE: To describe those patients suffering from EVS in whom defined etiologies have been ruled out in order to determine if their symptoms can be linked to VM. MATERIAL AND METHODS: Prospective multicenter study. The medical records of patients with VM and patients with EVS suggestive of VM but not meeting the criteria for it were examined. The characteristics of headache, the number and the length of attacks, the association of vestibular symptoms and headache, the intensity of symptoms and the response to treatment were recorded. RESULTS: 58 patients met the criteria for VM or probable VM; 30 did not. All of the symptoms improved significantly in the treated patients with VM or probable VM; in the rest of the treated patients, only the vestibular symptoms improved. CONCLUSION: A subgroup of patients that cannot be attributed to any known vestibulopathy according to present day VM criteria profited from migraine treatment, suggesting that their vestibular symptoms belong to the migraine spectrum; whereas some do not, yet our analysis could not identify distinctive features that allowed subgroup attribution.

Epidemiology of balance disorders in primary care. / Epidemiología de los trastornos del equilibrio en atención primaria.

BACKGROUND AND OBJECTIVE: In our country, there are no series of patients that have described the incidence of the different diseases which cause balance disorders (BD) in primary care. The objective of this study is to calculate the incidence of each disease to propose specific training measures. MATERIALS AND METHOD: Prospective cross-sectional study. Patient data of five primary care physicians in five different primary care centres in our hospital area were collected. All patients who attended consultations for any type of vertigo, imbalance or dizziness over one year as the main reason for consultation were recruited. Using a diagnostic-therapeutic algorithm, patients were diagnosed and treated in primary care or referred for study in hospital care. RESULTS: The population studied was 7,896 people. An annual incidence of BD of 2.2% was detected. Of the cases, 56.1% could be diagnosed and treated in primary care. Of the patients, 53.8% were diagnosed with some type of positional vertigo; the next three most frequent diagnoses were vestibular migraine, central nervous system ischaemia and medication side effects. These four groups accounted for 87.9% of the population. CONCLUSIONS: The incidence of BD in primary care requires an approach that includes training in the diagnosis and treatment of benign paroxysmal positional vertigo, headache, cardiovascular risk factors and pharmacology. It is not necessary to prescribe vestibular suppressants in most patients.

Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease.

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

Clinical use of 4-aminopyridine in patients with downbeat nystagmus. / Experiencia de uso de fampridina en pacientes con nistagmo vertical inferior.

OBJECTIVE: To present the results of treatment with sustained-release fampridine (4-AP-SR) in patients with downbeat nystagmus. MATERIAL AND METHOD: Series of cases with downbeat nystagmus treated with 10 milligrams of 4-AP-SR every 12hours. The clinical improvement and the variation of the nystagmus before and after the treatment were evaluated, recording the score in the Dizziness Handicap Inventory, the velocity of the slow phase of the nystagmus and its frequency. RESULTS: Three patients were treated, none of whom reported significant subjective changes during the treatment. No significant differences were detected in the Dizziness Handicap Inventory score or in the studied videonystagmographic variables. CONCLUSION: This communication does not present positive results on the use of 4-AP-SR. The contradiction with previous studies may be caused by a small sample size, by the etiology of the cases or by the way in which the results were measured.

Inter-rater agreement in the choice of prophylactic treatment for vestibular migraine and role of an assisted algorithm for this choice. / Concordancia interevaluador en la elección de tratamiento profiláctico para la migraña vestibular y papel de un algoritmo asistido para la elección de dicho tratamiento.

BACKGROUND AND OBJECTIVE: Vestibular migraine (VM) is a cause of episodic vestibular syndrome. There are many drugs available for its prophylaxis and currently the choice is mainly made according to the patient's comorbidities. The aim of this article was to measure the agreement of a group of otorhinolaryngologists in the choice of a prophylactic treatment and to evaluate the role of an assisted algorithm in the choice of this prophylaxis. MATERIAL AND METHOD: The medical records of 10 patients with VM were offered to 10 otolaryngologists who were asked to select for each patient the drug they considered most appropriate among five possible options. The Fleiss' κ index was calculated among the 10 otolaryngologists alone, recalculating it including the algorithm as the eleventh evaluator, and Cohen's κ index was calculated between each otolaryngologist and the answers of the algorithm. The otolaryngologists were offered the option to change their responses after knowing the responses of the algorithm and then both indexes were calculated again. RESULTS: The Fleiss' κ index was .302. This index was raised to .343 after introducing the algorithm as an evaluator. After offering the responses proposed by the algorithm, Cohen's κ was improved in 9 of the 10 evaluators, and Fleiss' κ rose to .711. CONCLUSIONS: The agreement between otorhinolaryngologists in choosing prophylaxis for MV can be defined as "fair". The responses of the algorithm for the choice of prophylaxis were close to the average opinion of the otolaryngologists, raising the agreement between them to "substantial".

Identifying Training, Diagnostic and Therapeutic Needs From a Comparison in the Distribution of Vestibular Disorders in Primary Care and in a Neurotology Unit.

Introduction: Several epidemiological studies in Neurotology have been previously carried out in the general population. This approach is useful for learning about the most common disorders in clinical population, but it may fail when one is trying to help professionals to guide their training, to optimize their resources and to decide on the highest-priority research objectives. Objective: To identify which of the neurotological diseases are most common in two different populations, those who attended a consultation in the Neurotology Unit of a tertiary level hospital and those who did so in Primary Care in order to infer which of them requires more attention in each context and their specific needs. Methods: All the diagnoses made in Hospital Care between October 15, 2017 and October 14, 2018 were reviewed. These diagnoses were coded and classified into syndromes and diseases. Later, the proportions of each category were compared with the proportions of the neurotological diagnoses made in five Primary Care centers over the same period of time. Results: BPPV is the most common cause of vestibular symptoms in both contexts. Vestibular migraine, ischemic vestibular symptoms, orthostatic hypotension and side effects of drugs are common in Primary Care, whereas Ménière's disease and undifferentiated episodic vestibular syndrome are common in specialized centers. Conclusion: The proportion of diagnoses in neurotologic patients is different in the general population and in the specialized center population, and therefore they have different needs. Primary Care professionals would benefit from training on maneuvers for repositioning otoliths, the treatment of headache, the identification of cardiovascular risk factors, the orthostatic hypotension and the side effects of the most commonly used drugs. The professionals who work in specialized centers need strategies for dealing with cases of BPPV associated to other vestibular diseases and refractory cases and their research should focus on the development of new diagnostic tools for the diagnosis of undifferentiated episodic vestibular syndrome and new therapeutic options for Ménière's disease.

Subjective benign paroxysmal positional vertigo in patients with osteoporosis or migraine.

INTRODUCTION: Subjective benign paroxysmal positional vertigo is a form of benign paroxysmal positional vertigo in which during the diagnostic positional maneuvers patients only present vertigo symptoms with no nystagmus. OBJECTIVE: To study the characteristics of subjects with subjective benign paroxysmal positional vertigo. METHODS: Prospective multicenter case-control study. All patients presenting with vertigo in the Dix-Hallpike test that presented to the participating hospitals were included. The patients were separated into two groups depending on whether nystagmus was present or not. An Epley Maneuver of the affected side was performed. In the follow-up visit, patients were checked to see if nystagmus and vertigo were present. Both groups of patients were compared to assess the success rate of the Epley maneuver and also to compare the presence of 19 variables. RESULTS: 259 patients were recruited, of which 64 belonged to the subjective group. Nystagmus was eliminated in 67.2% of the patients with benign paroxysmal positional vertigo. 89.1% of the patients with subjective benign paroxysmal positional vertigo remained unaffected by nystagmus, thus showing a significant difference (p=0.001). Osteoporosis and migraine were the variables which reached the closest to the significance level. In those patients who were taking vestibular suppressors, the percentage of subjective benign paroxysmal positional vertigo was not significantly higher. CONCLUSIONS: Subjective benign paroxysmal positional vertigo should be treated using the Epley maneuver. More studies are needed to establish a relationship between osteoporosis, migraine and subjective benign paroxysmal positional vertigo. The use of vestibular suppressants does not affect the detection of nystagmus.

Three new strategies to improve the accuracy of monothermal caloric screening testing.

OBJECTIVE: The objective was to find a way to estimate the value of inter-ear difference (IED) through monothermal caloric screening testing (MCST) that can be used at any laboratory, controlling and minimising the resulting error. METHODS: We retrospectively included in this study 2304 patients from our department to whom a videonystagmography with caloric testing was performed between 2003 and 2011. The IED was calculated in 3 different ways: Using the values of the 4 caloric stimulations (bithermal form) and using only the 2 same-temperature values (warm monothermal and cool monothermal forms). We studied 3 strategies to improve the accuracy of MCST: Analysis of variables that could impair the prediction, delimitation of a grey area of insufficient prediction and location of a maximum utility cut-off point. RESULTS: Correcting Jongkees' formula with the value for spontaneous nystagmus makes it possible to include subjects with spontaneous nystagmus or nystagmus inversion. Establishing 2 cut-off points to classify the subjects avoids approximately 38% of bithermal stimulations performed with a sensitivity and specificity of 95%. Maximum utility was obtained diagnosing as healthy those subjects with IED values lesser than or equal to 16% in warm MCST when the pathological IED was set as greater than 20%. CONCLUSION: New statistical tools help clinicians to make decisions that affect their patients based on the results of MCST.

Subjective benign paroxysmal positional vertigo in patients with osteoporosis or migraine / Vertigem posicional paroxística benigna subjetiva em pacientes com osteoporose ou migrânea

Abstract Introduction Subjective benign paroxysmal positional vertigo is a form of benign paroxysmal positional vertigo in which during the diagnostic positional maneuvers patients only present vertigo symptoms with no nystagmus. Objective To study the characteristics of subjects with subjective benign paroxysmal positional vertigo. Methods Prospective multicenter case-control study. All patients presenting with vertigo in the Dix-Hallpike test that presented to the participating hospitals were included. The patients were separated into two groups depending on whether nystagmus was present or not. An Epley Maneuver of the affected side was performed. In the follow-up visit, patients were checked to see if nystagmus and vertigo were present. Both groups of patients were compared to assess the success rate of the Epley maneuver and also to compare the presence of 19 variables. Results 259 patients were recruited, of which 64 belonged to the subjective group. Nystagmus was eliminated in 67.2% of the patients with benign paroxysmal positional vertigo. 89.1% of the patients with subjective benign paroxysmal positional vertigo remained unaffected by nystagmus, thus showing a significant difference (p = 0.001). Osteoporosis and migraine were the variables which reached the closest to the significance level. In those patients who were taking vestibular suppressors, the percentage of subjective benign paroxysmal positional vertigo was not significantly higher. Conclusions Subjective benign paroxysmal positional vertigo should be treated using the Epley maneuver. More studies are needed to establish a relationship between osteoporosis, migraine and subjective benign paroxysmal positional vertigo. The use of vestibular suppressants does not affect the detection of nystagmus.

Resumo Introdução A vertigem posicional paroxística benigna subjetiva é um tipo de vertigem posicional paroxística benigna na qual, durante as manobras posicionais diagnósticas, os pacientes apresentam apenas sintomas vertiginosos sem nistagmo. Objetivo Estudar as características de indivíduos com vertigem posicional paroxística benigna subjetiva. Método Estudo prospectivo multicêntrico de caso-controle. Foram incluídos todos os pacientes com vertigem no teste de Dix-Hallpike, que se apresentaram nos hospitais participantes. Os pacientes foram separados em dois grupos, dependeu da presença ou não do nistagmo. Uma manobra de Epley foi realizada no lado afetado. Na consulta de seguimento, os pacientes foram avaliados para verificar a presença ou não do nistagmo e da vertigem. Ambos os grupos de pacientes foram comparados para avaliar a taxa de sucesso da manobra de Epley e também para comparar a presença de 19 variáveis. Resultados Foram recrutados 259 pacientes, dos quais 64 pertenciam ao grupo subjetivo. O nistagmo foi eliminado em 67,2% dos pacientes com vertigem posicional paroxística benigna. Em 89,1% dos casos, os pacientes com vertigem posicional paroxística benigna subjetiva mantiveram-se não afetados pelo nistagmo, mostraram uma diferença significativa (p = 0,001). Osteoporose e enxaqueca foram as variáveis que atingiram o nível mais próximo ao de significância. Nos pacientes que tomavam supressores vestibulares, a porcentagem de vertigem posicional paroxística benigna subjetiva não foi significativamente maior. Conclusões A vertigem posicional paroxística benigna subjetiva deve ser tratada com a manobra de Epley. Mais estudos são necessários para estabelecer uma relação entre osteoporose, enxaqueca e vertigem posicional paroxística benigna subjetiva. O uso de supressores vestibulares não afeta a detecção do nistagmo.

[Benign paroxysmal positional vertigo: analysis of our population and role of caloric tests]. / Vértigo posicional paroxístico benigno: análisis de nuestra población y del papel de las pruebas calóricas.

INTRODUCTION AND OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in those patients who seek medical care. Although videonystagmography seems the most indicated diagnostic test, we tried to decrease the requested caloric tests to optimise resources and reduce associated costs. METHODS: We developed a diagnostic-therapeutic algorithm for patients with suspected BPPV whose provocation tests are positive to evaluate the need for caloric testing. We analysed the results of its application on 98 patients who were referred to our Neuro-otology Unit over 15 months requesting videonystagmography and caloric tests. RESULTS: Only 24% of the requested tests were performed. No significant difference was found in our recurrence rate compared with other series of Spanish patients. CONCLUSIONS: Videonystagmography and caloric tests are not strictly necessary in most patients with BPPV and they should be performed only in patients whose diagnosis is unclear.