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Neurotrophins and their receptors are distinctly expressed during brain development and play crucial roles in the formation, survival, and function of neurons in the nervous system. Among these molecules, brain-derived neurotrophic factor (BDNF) has garnered significant attention due to its involvement in regulating GABAergic system development and function. In this review, we summarize and compare the expression patterns and roles of neurotrophins and their receptors in both the developing and adult brains of rodents, macaques, and humans. Then, we focus on the implications of BDNF in the development and function of GABAergic neurons from the cortex and the striatum, as both the presence of BDNF single nucleotide polymorphisms and disruptions in BDNF levels alter the excitatory/inhibitory balance in the brain. This imbalance has different implications in the pathogenesis of neurodevelopmental diseases like autism spectrum disorder (ASD), Rett syndrome (RTT), and schizophrenia (SCZ). Altogether, evidence shows that neurotrophins, especially BDNF, are essential for the development, maintenance, and function of the brain, and disruptions in their expression or signaling are common mechanisms in the pathophysiology of brain diseases.
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Fator Neurotrófico Derivado do Encéfalo , Neurônios GABAérgicos , Humanos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Neurônios GABAérgicos/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/genética , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/genética , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/genética , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimentoRESUMO
OBJECTIVES: Canalith repositioning procedures to treat benign paroxysmal positional vertigo are often applied following standardized criteria, without considering the possible anatomical singularities of the membranous labyrinth for each individual. As a result, certain patients may become refractory to the treatment due to significant deviations from the ideal membranous labyrinth, that was considered when the maneuvers were designed. This study aims to understand the dynamics of the endolymphatic fluid and otoconia, within the membranous labyrinth geometry, which may contribute to the ineffectiveness of the Epley maneuver. Simultaneously, the study seeks to explore methods to avoid or reduce treatment failure. DESIGN: We conducted a study on the Epley maneuver using numerical simulations based on a three-dimensional medical image reconstruction of the human left membranous labyrinth. A high-quality micro-computed tomography of a human temporal bone specimen was utilized for the image reconstruction, and a mathematical model for the endolymphatic fluid was developed and coupled with a spherical particle model representing otoconia inside the fluid. This allowed us to measure the position and time of each particle throughout all the steps of the maneuver, using equations that describe the physics behind benign paroxysmal positional vertigo. RESULTS: Numerical simulations of the standard Epley maneuver applied to this membranous labyrinth model yielded unsatisfactory results, as otoconia do not reach the frontside of the utricle, which in this study is used as the measure of success. The resting times between subsequent steps indicated that longer intervals are required for smaller otoconia. Using different angles of rotation can prevent otoconia from entering the superior semicircular canal or the posterior ampulla. Steps 3, 4, and 5 exhibited a heightened susceptibility to failure, as otoconia could be accidentally displaced into these regions. CONCLUSIONS: We demonstrate that modifying the Epley maneuver based on the numerical results obtained in the membranous labyrinth of the human specimen under study can have a significant effect on the success or failure of the treatment. The use of numerical simulations appears to be a useful tool for future canalith repositioning procedures that aim to personalize the treatment by modifying the rotation planes currently defined as the standard criteria.
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Vertigem Posicional Paroxística Benigna , Humanos , Vertigem Posicional Paroxística Benigna/fisiopatologia , Vertigem Posicional Paroxística Benigna/diagnóstico por imagem , Microtomografia por Raio-X , Simulação por Computador , Osso Temporal/diagnóstico por imagem , Membrana dos Otólitos/fisiologia , Imageamento Tridimensional , Endolinfa/fisiologia , Orelha Interna/diagnóstico por imagem , Canais Semicirculares/diagnóstico por imagem , Canais Semicirculares/fisiologia , Posicionamento do Paciente/métodosRESUMO
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.
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Neuroma Acústico , Neuroma Acústico/terapia , Neuroma Acústico/diagnóstico , Neuroma Acústico/diagnóstico por imagem , Humanos , Conduta ExpectanteRESUMO
Patients with bilateral vestibulopathy (BVP) suffer from postural imbalance during daily life conditions, which in turn leads to a high frequency of falls. Unfortunately, vestibular rehabilitation has only modest and somewhat inconsistent effects in this patient group. Approximately 50% of BVP patients show an improved postural control after conventional vestibular rehabilitation training. New and more promising approaches are required. The individualized vibrotactile neurofeedback training (IVNT) in stance and gait conditions has already been described as highly effective in patients with various vestibular disorders. The purpose of the present multicenter study was to determine the efficacy of the IVNT in improving balance, reducing self-perceived disability, and improving gait in patients with confirmed BVP. In total, 22 patients performed the IVNT with the Vertiguard® system for 10 daily sessions. The dizziness handicap inventory (DHI), the stance stability score of the sensory organization test (SOT) and the score for everyday life mobility in stance and gait tasks (SBDT) were obtained immediately before and after the rehabilitation training period, as well as 3 and 12 months later. All measures improved significantly after the IVNT. Between 77.3% and 94.4% of patients showed an individual benefit (depending on outcome measure). The effect was not significantly reduced within the follow-up period of 12 months. The results demonstrate a high efficacy of the IVNT for vestibular rehabilitation in BVP patients.
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INTRODUCTION: Vestibular symptoms, including vertigo, dizziness, and gait unsteadiness, are a frequent reason of urgent medical assistance. Their causes are numerous and diverse, including neurological, otorhinolaryngological, and systemic diseases. Therefore, following a systematic approach is essential to differentiate striking but benign conditions from others that can compromise the patient's life. This study is intended to review vestibular disorders from a practical perspective and provide guidance to physicians involved in the emergency care of patients with vestibular symptoms. MATERIALS AND METHODS: A narrative review was performed, revisiting the main causes of vestibular disorders. RESULTS: Based on the speed of onset, duration, and history of similar episodes in the past, vestibular disorders can be categorized into three syndromic entities (acute, recurrent, and chronic vestibular syndromes). The most representative conditions pertaining to each group were reviewed (including their diagnosis and treatment) and a practical algorithm was proposed for their correct management in the acute care setting. CONCLUSIONS: Carrying out a correct categorization of the vestibular disorders is essential to avoid diagnostic pitfalls. This review provides useful tools for clinicians to approach their patients with vestibular symptoms at the emergency room.
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Serviços Médicos de Emergência , Doenças Vestibulares , Humanos , Emergências , Vertigem/diagnóstico , Vertigem/etiologia , Vertigem/terapia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/terapia , Doenças Vestibulares/complicações , Tontura/diagnóstico , Tontura/etiologia , Tontura/terapiaRESUMO
The Head Impulse Test, the most widely accept test to assess the vestibular function, comprises rotations of the head based on idealized orientations of the semicircular canals, instead of their individual arrangement specific for each patient. In this study, we show how computational modelling can help personalize the diagnosis of vestibular diseases. Based on a micro-computed tomography reconstruction of the human membranous labyrinth and their simulation using Computational Fluid Dynamics and Fluid-Solid Interaction techniques, we evaluated the stimulus experienced by the six cristae ampullaris under different rotational conditions mimicking the Head Impulse Test. The results show that the maximum stimulation of the crista ampullaris occurs for directions of rotation that are more aligned with the orientation of the cupulae (average deviation from alignment of 4.7°, 9.8°, and 19.4° for the horizontal, posterior, and superior maxima, respectively) than with the planes of the semicircular canals (average deviation from alignment of 32.4°, 70.5°, and 67.8° for the horizontal, posterior, and superior maxima, respectively). A plausible explanation is that when rotations are applied with respect to the center of the head, the inertial forces acting directly over the cupula become dominant over the endolymphatic fluid forces generated in the semicircular canals. Our results indicate that it is necessary to consider cupulae orientation to ensure optimal conditions for testing the vestibular function.
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Simulação por Computador , Teste do Impulso da Cabeça , Ductos Semicirculares , Humanos , Ductos Semicirculares/diagnóstico por imagem , Canais Semicirculares , Microtomografia por Raio-X , Doenças Vestibulares , Medicina de PrecisãoRESUMO
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.
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Perda Auditiva Neurossensorial , Doença de Meniere , Humanos , Doença de Meniere/complicações , Doença de Meniere/epidemiologia , Vertigem/complicações , Citocinas , Perda Auditiva Neurossensorial/complicações , Síndrome , Imunoglobulina ERESUMO
BACKGROUND: Essential tremor (ET) is a neurological disorder characterized primarily by action tremor. Balance impairments in ET patients were formerly considered to be uncommon and simply age-related. However quantitative assessment with posturography has revealed impairments in control of both static and dynamic balance. RESEARCH QUESTION: The aim of the present study is to assess postural stability with different posturographic techniques in ET patients. METHODS: A prospective cross-sectional study conducted in two University Hospitals. Eleven patients diagnosed with essential tremor and twelve healthy controls were included. Balance assessment were performed with: sensory organization test (SOT) and limits of stability (LOS) of the computer dynamic posturography (CDP), results of free-field body sway analysis with mobile posturography (Vertiguard®), modified timed up and go test (TUG), Dizziness handicap inventory (DHI) and activities-specific balance confidence scale (ABC). RESULTS: Patients with ET showed poorer scores in the SOT than controls for composite balance and somatosensory input. They also performed worse in LOS tests and Vertiguard® device indicated a higher risk of falling. There were no differences in the modified TUG. The mean score of DHI was 15.64 and 85.16 for ABC. SIGNIFICANCE: Posturography assessment (CDP and Vertiguard®) is more accurate in showing balance impairment in ET patients than clinical evaluation (modified TUG). Balance impairment involves deteriorated processing of somatosensory input which could be explained by cerebellar dysfunction. Balance deficits could be included into future diagnostic criteria.
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Tremor Essencial , Equilíbrio Postural , Humanos , Estudos Transversais , Tontura/diagnóstico , Tontura/etiologia , Tremor Essencial/diagnóstico , Estudos Prospectivos , Estudos de Tempo e Movimento , VertigemRESUMO
Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed on MD. Here we performed whole-genome bisulfite sequencing in 14 MD patients and six healthy controls, with the aim of identifying an MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (n= 9545), several of them in hearing loss genes, such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including two UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows distinguishing between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.
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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.
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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.
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Predisposição Genética para Doença , Variação Genética , Sinapses/genética , Zumbido/diagnóstico , Zumbido/genética , Alelos , Animais , Encéfalo/metabolismo , Biologia Computacional/métodos , Feminino , Ontologia Genética , Estudos de Associação Genética , Humanos , Masculino , Camundongos , Fenótipo , Índice de Gravidade de Doença , Suécia , Sequenciamento do ExomaRESUMO
BACKGROUND: Vestibular rehabilitation (VR), specifically, VR with dynamic computerized posturography (CDP) has proven to be useful to improve balance and reduce the risk of falling in old patients. Its major handicap is probably its cost, which has hindered its generalisation. One solution to reduce this cost is performing VR with mobile posturography systems, which allow assessment of stability at the center of body mass in daily-life conditions. Also, rehabilitation with vibrotactile neurofeedback training could be used in dynamic tasks. OBJECTIVE: To assess whether two different protocols of vestibular rehabilitation (using CDP and the Vertiguard system) show significant differences in the improvement of balance among older persons with imbalance METHODS: A clinical trial comparing VR with CDP exercises and VR with mobile posturography (Vertiguard) exercises, was designed. The participants were people over 65 years, with imbalance. The composite (average balance) in the sensory organization test (SOT) of the CDP was the main outcome measure; it was compared before and 3 weeks after VR, and between both intervention groups. RESULTS: 40 patients were included in the study (19 in the CDP-VR group and 21 in the Vertiguard-VR group). Average balance was significantly improved in both intervention groups (51% pre-VR vs 60% post-VR, p = 0.002, CDP-VR group; 49% pre-VR vs 57% post-VR, p = 0.008, Vertiguard-VR group); no significant differences in this improvement were found comparing both groups (p = 0.580). DISCUSSION AND CONCLUSIONS: VR using mobile posturography is useful to improve stability in old people with instability, showing similar improvement rates to those of VR using CDP. UNIQUE IDENTIFIER: NCT03034655 www.clinicaltrials.gov Registered on 25 January 2017.
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Equilíbrio Postural , Doenças Vestibulares , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Terapia por Exercício , Humanos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
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.
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Perda Auditiva Neurossensorial , Doença de Meniere , Zumbido , Estudos de Casos e Controles , Testes Genéticos , Perda Auditiva Neurossensorial/genética , Humanos , Glicoproteínas de Membrana , Doença de Meniere/genéticaRESUMO
Objective: To assess the perception of disability in patients with presbyvestibulopathy and to determine the factors (demographic, balance test scores, and comorbidities) that determine higher levels of disability. Material and Methods: This was a cross-sectional study conducted in a tertiary university hospital. There were 103 patients who fulfilled the diagnostic criteria for presbyvestibulopathy and were included. Dizziness Handicap Inventory (DHI) score was the main variable used to quantify disability. Influence on DHI score, sex, age, time of evolution, equilibriometric parameters (posturographic scores and timed up and go test), history of falls, comorbidities (high blood pressure, diabetes, and dyslipidemia), psychotropic drug use, tobacco or alcohol use, living environment (urban or rural), and active lifestyle were analyzed. Results: Most of the DHI scores showed a moderate (46 patients, 44.7%) or severe (39 participants, 37.9%) handicap. DHI scores were higher in women (59.8 vs. 36.1, p < 0.001), patients with obesity (58.92 vs. 48.68; p = 0.019), benzodiazepine (59.9 vs. 49.1, p = 0.008) or other psychotropic drug (60.7 vs. 49.2, p = 0.017) users, and fallers (57.1 vs. 47.3, p = 0.048). There was also a significant positive correlation between DHI score, time (Rho coefficient: 0.371, p < 0.001), and steps (Rho coefficient: 0.284, p = 0.004) used in the TUG and with the short FES-I questionnaire (a shortened version of the Falls Efficacy Scale-International) score (Rho coefficient: 0.695, p < 0.001). DHI scores were lower in alcohol consumers than in non-drinkers (46.6 vs. 56, p = 0.048). No significant correlation was found between DHI scores and age, time of evolution, posturographic scores, comorbidities, environment (rural or urban), or active lifestyle. Conclusion: Most patients with presbyvestibulopathy show an important subjective perception of disability in relation to their symptoms. This perception is substantially higher in women than in men. The most influential factors are difficulties in walking, fear of falling, and obesity. Unique Identifier: NCT03034655, www.clinicaltrials.gov.
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PURPOSE: Vestibular rehabilitation (VR) using posturography systems has proved useful in improving balance among elderly patients with postural instability. However, its high cost hinders its use. The objective of this study is to assess whether two different protocols of VR with posturography, one of them longer (ten sessions) and the other shorter (five sessions), show significant differences in the improvement of balance among old patients with instability. PATIENTS AND METHODS: This is a prospective, experimental, single-center (Department of Otorhinolaryngology of a tertiary referral hospital), randomized (into balanced patient blocks) study with two parallel arms, in 40 people over 65 years of age, with instability and at a high risk of falling. The percentage of the average balance (composite) in the sensory organization test (SOT) of the CDP (main outcome measure), other CDP scores, time and steps in the "timed up and go" test, scores of Dizziness Handicap Inventory (DHI), short Falls Efficacy Scale - International (short FES-I), and Vertiguard were compared before and 3 weeks after VR between both intervention groups. RESULTS: The two treatment groups (20 patients per group) were comparable in age, sex, and pre-VR balance evaluation. In both groups, we observed a significant improvement in global balance (composite) after VR (49±11.34 vs 57±13.48, p=0.007, in the group undergoing 10 sessions; 51±12.55 vs 60±12.99, p=0.002, 5 sessions). In both groups, we also observed improvements in other posturographic parameters (in the SOT and limits of stability) but not in the timed up and go scores or in the questionnaires. Comparison of the improvement level achieved in both groups revealed no significant differences between them. CONCLUSION: The protocols of vestibular rehabilitation by posturography of 5 sessions in elderly patients with postural instability are as effective as those of 10 sessions for improving balance among elderly patients with postural instability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03034655. Registered on 25 January 2017.
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Acidentes por Quedas/prevenção & controle , Equilíbrio Postural , Doenças Vestibulares/reabilitação , Idoso , Tontura/prevenção & controle , Feminino , Avaliação Geriátrica , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Modalidades de Fisioterapia/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Doenças Vestibulares/diagnósticoRESUMO
Objective: To compare the results from the modified Timed Up and Go Test (TUG) with posturographic variables, the subjective perception of disability due to gait instability, and the number of falls in a sample of the elderly population with imbalance, to confirm that the TUG Test is a useful clinical instrument to assess the tendency to fall in individuals of this age group. Materials and Methods: Cross-sectional study conducted in a tertiary university hospital, in 174 people aged 65 years or older with gait instability. Modified TUG Test was performed; time, step count and the need for support during the test were the analyzed variables. They were compared with the number of falls, Computerized Dynamic Posturography scores, and questionnaires scores (Dizziness Handicap Inventory and a shortened version of the Falls Efficacy Scale-International). Results: The average time to complete the TUG Test was 21.24 ± 8.18 s, and the average step count was 27.36 ± 7.93. One hundred two patients (58.6%) required no support to complete the test, whereas the other 72 (41.4%) used supports. The time taken to complete the Test was significantly related with having or not having fallen in the previous year, with the scores of the questionnaires, and with various parameters of dynamic posturography. A higher percentage of patients who took more than 15 s had fallen in the previous year than those who took up to 15 s to complete the test [P = 0.012; OR = 2.378; 95% CI (1.183, 4.780)]. No significant correlation was found between the step count and the number of falls in the previous year, with falling during the test or not, or with being a single or a frequent faller. No relation was found between the need for supports and the number of falls, with having or not having fallen in the previous year, or with being a single or frequent faller. Conclusion: The modified TUG Test is in relation with the presence or absence of falls. Time is the essential parameter for analyzing the risk of falling and the 15-s threshold is a good value to differentiate elderly patients at high risk of falling. Unique Identifier: NCT03034655, www.clinicaltrials.gov.
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BACKGROUND: Patients with liver cirrhosis may develop hepatic encephalopathy. Rats with chronic hyperammonemia exhibit neurological alterations mediated by peripheral inflammation and neuroinflammation. Motor incoordination is due to increased TNF-a levels and activation of its receptor TNFR1 in the cerebellum. The aims were to assess (a) whether peripheral inflammation is responsible for TNF-a induction in hyperammonemic rats, (b) the cell type(s) in which TNF-a is increased, (c) whether this increase is associated with increased nuclear NF-κB and TNFR1 activation, (d) the time course of TNF-a induction, and (e) if TNF-a is induced in the Purkinje neurons of patients who die with liver cirrhosis. METHODS: We analyzed the level of TNF-a mRNA and NF-κB in microglia, astrocytes, and Purkinje neurons in the cerebellum after 1, 2, and 4 weeks of hyperammonemia. We assessed whether preventing peripheral inflammation by administering an anti-TNF-a antibody prevents TNF-a induction. We tested whether TNF-a induction is reversed by R7050, which inhibits the TNFR1-NF-κB pathway, in ex vivo cerebellar slices. RESULTS: Hyperammonemia induced microglial and astrocyte activation at 1 week. This was followed by TNF-a induction in both glial cell types at 2 weeks and in Purkinje neurons at 4 weeks. The level of TNF-a mRNA increased in parallel with the TNF-a protein level, indicating that TNF-a was synthesized in Purkinje cells. This increase was associated with increased NF-κB nuclear translocation. The nuclear translocation of NF-κB and the increase in TNF-a were reversed by R7050, indicating that they were mediated by the activation of TNFR1. Preventing peripheral inflammation with an anti-TNF-a antibody prevents TNF-a induction. CONCLUSION: Sustained (4 weeks) but not short-term hyperammonemia induces TNF-a in Purkinje neurons in rats. This is mediated by peripheral inflammation. TNF-a is also increased in the Purkinje neurons of patients who die with liver cirrhosis. The results suggest that hyperammonemia induces TNF-a in glial cells and that TNF-a released by glial cells activates TNFR1 in Purkinje neurons, leading to NF-κB nuclear translocation and the induction of TNF-a expression, which may contribute to the neurological alterations observed in hyperammonemia and hepatic encephalopathy.
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Cerebelo/metabolismo , Hiperamonemia/metabolismo , Células de Purkinje/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Idoso , Animais , Cerebelo/imunologia , Humanos , Hiperamonemia/complicações , Hiperamonemia/imunologia , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/imunologia , NF-kappa B/metabolismo , Neuroglia/imunologia , Neuroglia/metabolismo , Células de Purkinje/imunologia , Ratos , Ratos Wistar , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Although patient environment is a factor to consider when planning a vestibular rehabilitation program, there are no studies correlating this factor to outcomes of balance assessment. AIM: To evaluate whether there are differences in objective evaluation of balance in elderly patients at risk of falls according to the environment in which they live (urban or rural) and their lifestyle (considering cardiovascular risk factors). METHODS: Cross-sectional study of a sample of 139 elderly patients with high risk of falls assessed with objective outcome measures: Computer Dynamic Posturography (CDP), and the modified Timed Up-and-Go (TUG) test; and subjective outcome measures: Dizziness Handicap Inventory (DHI) and short Falls Efficacy Scale-International (short FES-I). Rural or urban environment was defined according to administrative and legal criteria. RESULTS: Elderly patients at risk of fall living in rural environment show better composite results in SOT with better scores in Condition 6 and fewer falls during the CDP. They also require fewer steps to perform the TUG test. DISCUSSION: The present study provides evidence that patient environment has an influence in balance. CONCLUSION: Patient environment should be considered when analyze tests evaluating static and dynamic balance.
Assuntos
Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Tontura , Feminino , Humanos , Masculino , Modalidades de Fisioterapia , Equilíbrio PosturalRESUMO
Objectives: Dietary changes are useful in the management of Menière's disease; regarding alcohol, many clinicians recommend to avoid or reduce its consumption. However, there are no researches aimed to evaluate whether habitual alcohol consumption is more prevalent and/or more intense in patients with Menière's disease.Methods: Cross-sectional, observational, case-control study, including three groups: patients with Menière's disease, patients with vertigo of other origins, and control subjects. Alcohol consumption was compared between these three groups. Participants in this study were grouped according to alcohol consumption as follows: categorization A1 (nonalcohol vs. alcohol consumers), categorization A2 (nonalcohol, low, moderate, and high alcohol consumers), and categorization A3 (light alcohol consumers: nonconsumers plus low consumers; heavy alcohol consumers: moderate plus high consumers).Results: A total of 180 subjects were included in this study (72 in group A, 72 in group B, and 36 in control group); 117 were women. The mean age was 52.7 years. Mean alcohol consumption was 41.22â g/week. Average consumption of alcohol in group A (50.42â g/week) was higher than in other two groups (36.53â g/week in B and 32.22â g/week in C), but differences were not statistically significant. In Menière's group, light alcohol consumers showed age at onset of symptoms (49.39 years) lower than heavy alcohol consumers (55.51 years). No relationship was observed between alcohol consumption and uni or bilateral affectation.Discussion: It is possible that alcohol consumption delays the age at onset of Menière's disease. A hypothetical explanation is the inhibitory effect of alcohol on hypothalamic production of vasopressin. A reduced release of this neurohormone would increase diuresis and decrease endolymphatic pressure.