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.

Feasibility of Social-Network-Based eHealth Intervention on the Improvement of Healthy Habits among Children.

This study shows the feasibility of an eHealth solution for tackling eating habits and physical activity in the adolescent population. The participants were children from 11 to 15 years old. An intervention was carried out on 139 students in the intervention group and 91 students in the control group, in two schools during 14 weeks. The intervention group had access to the web through a user account and a password. They were able to create friendship relationships, post comments, give likes and interact with other users, as well as receive notifications and information about nutrition and physical activity on a daily basis and get (virtual) rewards for improving their habits. The control group did not have access to any of these features. The homogeneity of the samples in terms of gender, age, body mass index and initial health-related habits was demonstrated. Pre- and post-measurements were collected through self-reports on the application website. After applying multivariate analysis of variance, a significant alteration in the age-adjusted body mass index percentile was observed in the intervention group versus the control group, as well as in the PAQ-A score and the KIDMED score. It can be concluded that eHealth interventions can help to obtain healthy habits. More research is needed to examine the effectiveness in achieving adherence to these new habits.

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.

High-density lipoprotein: a novel marker for risk of in-hospital infection in acute ischemic stroke patients?

BACKGROUND: Several studies have shown that high-density lipoprotein (HDL) cholesterol provides protection against bacterial infections. Our aim was to investigate the influence of HDL cholesterol levels on the risk of developing in-hospital infectious complications after an acute ischemic stroke (IS) as well as the possible effect of prestroke statin treatment on this association. METHODS AND RESULTS: Observational study that included consecutive IS patients during a 5-year period (2006-2010). We analyzed vascular risk factors, prestroke treatments (including statins), laboratory data (including HDL cholesterol levels), stroke severity, and the development of infectious complications (pneumonia, urinary tract infection and sepsis). A multivariate analysis that included HDL cholesterol levels, prior statin treatment and the interaction between both variables was performed to identify those factors associated with the presence of infectious complications. A total of 1,385 patients were included, 130 of whom (9.4%) developed in-hospital infections. The receiver operating characteristic curve showed the predictive value of HDL cholesterol with an area under the curve of 0.597 (95% CI, 0.526-0.668; p = 0.006) and pointed to 38.5 mg/dl of HDL cholesterol (65.5% sensitivity and 53.4% specificity) as the optimal cutoff level for developing infectious complications during hospitalization. An HDL cholesterol level ≥38.5 mg/dl was an independent predictive factor for lower risk of infection (OR 0.308; 95% CI 0.119-0.795), whereas prestroke statin treatment was not associated with the development of infection. CONCLUSIONS: An HDL cholesterol level ≥38.5 mg/dl was independently associated with lower risk for developing infectious complications in acute IS patients. Statins do not influence this association.

The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Vocal fold immobility with normal LEMG: A range of possibilities.

OBJECTIVE: The objective of this paper is to study the etiology of vocal fold immobility with non-pathological LEMG. METHODS: A retrospective study was performed on patients who presented with vocal fold immobility and underwent LEMG from 2009 to 2017. Those patients with normal LEMG findings were selected. The different causes of vocal fold impairment were studied. RESULTS: Of the 120 patients included in this study, 15 had a normal LEMG recording. The different etiologies of vocal fold immobility were idiopathic, central nervous system damage, iatrogenic, and external compression. CONCLUSIONS: Vocal fold immobility and vocal fold paralysis are not equal terms. Vocal fold immobility with normal LEMG has a heterogeneous group of causes. It is not correct to assume that the major cause of immobility in patients with normal LEMG is always cricoarytenoid joint fixation.

Vocal fold immobility with normal LEMG: A range of possibilities.

OBJECTIVE: The objective of this paper is to study the etiology of vocal fold immobility with non-pathological LEMG. METHODS: A retrospective study was performed on patients who presented with vocal fold immobility and underwent LEMG from 2009 to 2017. Those patients with normal LEMG findings were selected. The different causes of vocal fold impairment were studied. RESULTS: Of the 120 patients included in this study, 15 had a normal LEMG recording. The different etiologies of vocal fold immobility were idiopathic, central nervous system damage, iatrogenic, and external compression. CONCLUSIONS: Vocal fold immobility and vocal fold paralysis are not equal terms. Vocal fold immobility with normal LEMG has a heterogeneous group of causes. It is not correct to assume that the major cause of immobility in patients with normal LEMG is always cricoarytenoid joint fixation.

Cerebral hemodynamics and vasoconstriction in preeclampsia: From diagnosis to resolution.

OBJECTIVES: To evaluate maternal cerebral hemodynamics in patients with preeclampsia (PE) from diagnosis to clinical resolution using transcranial Doppler (TCD) and compare these findings with those of healthy pregnant women. Furthermore, we sought to describe the prevalence of vasoconstriction (VC) and related clinical parameters in PE. STUDY DESIGN: Case-control study including consecutive patients with PE at diagnosis and healthy pregnant women at week 36 of pregnancy. We prospectively collected clinical and neuroimaging data. TCD was repeated at inclusion and on days 1, 7, and 30 postpartum. MAIN OUTCOME MEASURES: Evolution of intracranial arteries hemodynamics (mean velocities (MV), resistance index). VC diagnosis and related features are described. RESULTS: A total of 165 patients (80 with PE) underwent 467 TCD procedures. Patients with PE presented higher MAP. Intracranial arteries MV were significantly higher in patients with PE (at diagnosis and days 1 and 7 postpartum) but were normalized by day 30, without correlation with MAP evolution or treatment. VC was present in 32.5% of patients with PE (p < 0.001) and was mainly mild according to the Lindegaard index. Severe PE was associated with VC (50.0% vs. 22.6%; odds ratio 3.484; 95% confidence interval 1.425-8.520; p = 0.014). No other independent risk factors for reversible VC were identified. CONCLUSIONS: Patients with PE presented significantly higher MV in the anterior circulation compared to healthy controls, which worsened by day 7 and reverted by day 30 after delivery. VC was present in one-third of PE but was mainly mild and asymptomatic. Severe PE was associated with VC development.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease.

Vestibular Migraine (VM) and Meniere's Disease (MD) are episodic vestibular syndromes defined by a set of associated symptoms such as tinnitus, hearing loss or migraine features during the attacks. Both conditions may show symptom overlap and there is no biological marker to distinguish them. Two subgroups of MD patients have been reported, according to their IL-1ß profile. Therefore, considering the clinical similarity between VM and MD, we aimed to investigate the cytokine profile of MD and VM as a means to distinguish these patients. We have also carried out gene expression microarrays and measured the levels of 14 cytokines and 11 chemokines in 129 MD patients, 82 VM patients, and 66 healthy controls. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in MD patients with high and low basal levels of IL- 1ß and VM patients. MD patients with high basal levels of IL- 1ß (MDH) had overall higher levels of cytokines/chemokines when compared to the other subsets. CCL4 levels were significantly different between MDH, MD with low basal levels of IL- 1ß (MDL), VM and controls. Logistic regression identified IL- 1ß, CCL3, CCL22, and CXCL1 levels as capable of differentiating VM patients from MD patients (area under the curve = 0.995), suggesting a high diagnostic value in patients with symptoms overlap.

Inmovilidad de cuerdas vocales con electromiografía laríngea normal: un abanico de posibilidades / Vocal fold immobility with normal LEMG: A range of possibilities

Objective: The objective of this paper is to study the etiology of vocal fold immobility with non-pathological LEMG. Methods: A retrospective study was performed on patients who presented with vocal fold immobility and underwent LEMG from 2009 to 2017. Those patients with normal LEMG findings were selected. The different causes of vocal fold impairment were studied. Results: Of the 120 patients included in this study, 15 had a normal LEMG recording. The different etiologies of vocal fold immobility were idiopathic, central nervous system damage, iatrogenic, and external compression. Conclusions: Vocal fold immobility and vocal fold paralysis are not equal terms. Vocal fold immobility with normal LEMG has a heterogeneous group of causes. It is not correct to assume that the major cause of immobility in patients with normal LEMG is always cricoarytenoid joint fixation. (AU)

Objetivo: El propósito de este artículo es estudiar la etiología de la inmovilidad de las cuerdas vocales con una EMG laríngea no patológica. Métodos: Se ha realizado un estudio retrospectivo de pacientes con inmovilidad de cuerdas vocales a los que se les hizo EMG laríngea desde 2009 a 2017. Se seleccionaron los pacientes con EMG laríngea normal. Se estudiaron las diferentes causas de inmovilidad de las cuerdas vocales. Resultados: De los 120 pacientes incluidos en el estudio, 15 tuvieron un resultado de EMG laríngea normal. Las diferentes etiologías de inmovilidad de las cuerdas vocales fueron idiopáticas, lesiones del sistema nervioso central, causas iatrogénicas y compresión externa. Conclusiones: La inmovilidad de cuerdas vocales y la parálisis de cuerdas vocales no son términos equivalentes. La inmovilidad de cuerdas vocales con EMG laríngea normal tiene un grupo de causas heterogéneo. No es correcto asumir que la principal causa de inmovilidad de cuerdas vocales en pacientes con EMG laríngea normal sea siempre la fijación cricoaritenoidea. (AU)

The effect of telestroke systems among neighboring hospitals: more and better? The Madrid Telestroke Project.

A telestroke system was established between a community hospital lacking an on-call neurologist and a comprehensive stroke center only 13 km away. Our goal was to analyze the impact of telestroke on the number of intravenous thrombolysis (IVT), door-to-needle times and stroke outcomes. An observational before-and-after study of patients with acute ischemic stroke (IS) who were attended in a community hospital during the 2 years before the telestroke system was implemented (pre-telestroke group) and the first 2 years after telestroke was established (telestroke group). The number of IVT, the door-to-needle time (min), the outcomes [modified Rankin Scale (mRS)] and the safety (mortality and hemorrhagic transformations) were compared between groups. During the pre-telestroke years, 259 patients with IS were attended (28 phone activations), 12 of whom received IVT (4.7 %). During the telestroke years, 225 patients with IS were attended (42 telestroke activations), of whom 18 (8 %) received IVT. The door-to-needle times were lower in the telestroke group [median interquartile range: 66 (54) vs. 143.5 (48) min, P < 0.0001]. The safety was similar in both groups; however, the 3-month mRS scores were lower in the telestroke group (P = 0.049). The multiple linear regression analysis showed a negative association between telestroke and door-to-needle time [ß-coefficient (SE) = -59.089 (14.461)], adjusted for confounders. In conclusion, telestroke systems are effective, even between nearby hospitals, shortening door-to-needle time and improving stroke outcomes.

Treatment with statins and ischemic stroke severity: does the dose matter?

OBJECTIVE: To examine the effects of pretreatment with statins at high doses (40 mg of rosuvastatin or 80 mg of any other statin) and low to moderate doses (<40 mg of rosuvastatin or <80 mg of any other statin) on ischemic stroke (IS) severity in clinical practice. METHODS: Observational study of IS admissions to our stroke unit over a 3-year period (2008-2010). Mild stroke severity was defined as NIH Stroke Scale score ≤5 on admission. Multivariable regression models and matched propensity score analyses were used to quantify the association of statin pretreatment at high and low to moderate doses with mild stroke severity. RESULTS: Of the 969 IS patients, 23% were taking low to moderate doses and 4.1% were taking high doses of statins prior to the stroke. Statins were associated with lower NIHSS scores on admission (median [interquartile range] 4 [9] for nonstatin patients, 4 [9] for low to moderate doses of statins, and 2 [4] for high doses of statins; p = 0.010). After multivariable adjustment, pretreatment with statins was associated with a higher probability of mild stroke severity in the unmatched analysis (odds ratio [OR] = 1.637, 95% confidence interval [CI] 1.156-2.319 for the low to moderate doses and OR = 3.297, 95% CI 1.480-7.345 for the high doses of statins) as well as in the propensity score matched analysis (OR = 2.023, 95% CI 1.248-3.281 for the low to moderate doses and OR = 3.502, 95% CI 1.477-8.300 for the high doses of statins). CONCLUSION: Pretreatment with statins is associated with lower stroke severity, at high as well as at low to moderate doses.

Fibrinólisis intravenosa en un varón de 14 años con infarto cerebral por disección de la arteria carótida interna / Intravenous fibrinolysis in a 14-year-old male with cerebral infarction due to dissection of the internal carotid artery

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