Systematic Review and Meta-Analysis of the Diagnostic Accuracy of a Graded Gait and Truncal Instability Rating in Acutely Dizzy and Ataxic Patients.

BACKGROUND: In patients presenting with acute prolonged vertigo and/or gait imbalance, the HINTS [Head-Impulse, Nystagmus, Test-of-Skew] are very valuable. However, their application may be limited by lack of training and absence of vertigo/nystagmus. Alternatively, a graded gait/truncal-instability (GTI, grade 0-3) rating may be applied. METHODS: We performed a systematic search (MEDLINE/Embase) to identify studies reporting on the diagnostic accuracy of bedside examinations in adults with acute vestibular syndrome. Diagnostic test properties were calculated for findings using a random-effects model. Results were stratified by GTI-rating used. RESULTS: We identified 6515 articles and included 18 studies (n = 1025 patients). Ischemic strokes (n = 665) and acute unilateral vestibulopathy (n = 306) were most frequent. Grade 2/3 GTI had moderate sensitivity (70.8% [95% confidence-interval (CI) = 59.3-82.3%]) and specificity (82.7 [71.6-93.8%]) for predicting a central cause, whereas grade 3 GTI had a lower sensitivity (44.0% [34.3-53.7%] and higher specificity (99.1% [98.0-100.0%]). In comparison, diagnostic accuracy of HINTS (sensitivity = 96.8% [94.8-98.8%]; specificity = 97.6% [95.3-99.9%]) was higher. When combining central nystagmus-patterns and grade 2/3 GTI, sensitivity was increased to 76.4% [71.3-81.6%] and specificity to 90.3% [84.3-96.3%], however, no random effects model could be used. Sensitivity was higher in studies using the GTI rating (grade 2/3) by Lee (2006) compared to the approach by Moon (2009) (73.8% [69.0-78.0%] vs. 57.4% [49.5-64.9%], p = 0.001). CONCLUSIONS: In comparison to HINTS, the diagnostic accuracy of GTI is inferior. When combined with central nystagmus-patterns, diagnostic accuracy could be improved based on preliminary findings. GTI can be readily applied in the ED-setting and also in patients with acute imbalance syndrome.

Acute truncal ataxia without nystagmus in patients with acute vertigo.

BACKGROUND AND PURPOSE: Differentiating between peripheral and central aetiologies can be challenging in patients with acute vertigo, given substantial symptom overlap. A detailed clinical history and focused physical eye movement examination such as the HINTS eye examination appear to be the most reliable approach to identify acute cerebellar/brainstem stroke, outperforming even acute brain imaging. We have observed, however, that isolated vertigo of central cause may be accompanied by acute truncal ataxia, in the absence of nystagmus. METHODS: We explored the frequency of ataxia without concurrent nystagmus in a cross section of patients with acute vertigo who presented to the emergency department at two centres in Argentina (Group A) and the UK (Group B). Patients underwent detailed clinical neuro-otological assessments (Groups A and B), which included instrumented head impulse testing and oculography (Group B). RESULTS: A total of 71 patients in Group A and 24 patients in Group B were included in this study. We found acute truncal ataxia-without nystagmus-in 15% (n = 14) of our overall cohort. Lesions involved stroke syndromes affecting the posterior inferior cerebellar artery, anterior inferior cerebellar artery, and superior cerebellar artery, thalamic stroke, cerebral hemisphere stroke, multiple sclerosis, and a cerebellar tumour. Additional oculomotor deficits did not reliably identify a central cause in these individuals, even with oculography. CONCLUSIONS: We have identified a significant subpopulation of patients with acute vertigo in whom the current standard approaches such as the HINTS examination that focus on oculomotor assessment may not be applicable, highlighting the need for a formal assessment of gait in this setting.

Vestibular Drop Attack: An Analysis of the Therapeutic Response.

The present study evaluates the response to betahistine in patients who presented vestibular drops attacks in the context of Ménière's disease (MD) and the factors that can predict an unfavorable response to it. A total of 43 patients were analyzed, out of which 33 were diagnosed with MD. This is a descriptive, cross-sectional study with retrospective data collection. Data as regards age, accompanying symptoms, etiological diagnosis and response to MD treatment were collected. A statistical analysis was carried out, and we found that the disease evolution time and specific alterations in the vestibulospinal and oculomotor physical examination present an unfavorable response to betahistine. Failures for betahistine were treated with intratympanic gentamicin, with which symptomatic control was achieved in all cases.

Computational Design of Inhibitors Targeting the Catalytic ß Subunit of Escherichia coli FOF1-ATP Synthase.

With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search for new therapeutic targets, to develop drugs with novel modes of bactericidal action. FoF1-ATP synthase plays a crucial role in bacterial bioenergetic processes, and it has emerged as an attractive antimicrobial target, validated by the pharmaceutical approval of an inhibitor to treat multidrug-resistant tuberculosis. In this work, we aimed to design, through two types of in silico strategies, new allosteric inhibitors of the ATP synthase, by targeting the catalytic ß subunit, a centerpiece in communication between rotor subunits and catalytic sites, to drive the rotary mechanism. As a model system, we used the F1 sector of Escherichia coli, a bacterium included in the priority list of multidrug-resistant pathogens. Drug-like molecules and an IF1-derived peptide, designed through molecular dynamics simulations and sequence mining approaches, respectively, exhibited in vitro micromolar inhibitor potency against F1. An analysis of bacterial and Mammalia sequences of the key structural helix-turn-turn motif of the C-terminal domain of the ß subunit revealed highly and moderately conserved positions that could be exploited for the development of new species-specific allosteric inhibitors. To our knowledge, these inhibitors are the first binders computationally designed against the catalytic subunit of FOF1-ATP synthase.

Atypical Positional Vertigo: Definition, Causes, and Mechanisms.

Paroxysmal positional vertigo is a frequent cause for consultation. When approaching these patients, we try to differentiate central from peripheral causes, but sometimes we find manifestations that generate diagnostic doubts. In this review, we address atypical paroxysmal positional vertigo, reviewing the literature on the subject and giving a provisional definition of atypical positional vertigo as well as outlining its causes and pathophysiological mechanisms.

Corrective Saccades in Unilateral and Bilateral Vestibular Hypofunction During Slow Rotation Expressed by Visually Enhanced VOR and VOR Suppression: Role of the Cerebellum.

In clinical practice, the head impulse test paradigm (HIMP) and the suppression head impulse paradigm (SHIMP) stimulate high-frequency head movements so that the visual system is temporarily suppressed. The two tests could also be useful tools for vestibular assessment at low frequencies: VVOR (visually enhanced vestibulo-ocular reflex) and VORS (vestibulo-ocular reflex suppression). The aim of this study is to analyze the eye movements typically found during VVOR and VORS testing in patients with unilateral and bilateral vestibular hypofunction. Twenty patients with unilateral vestibular hypofunction, three patients with bilateral vestibular hypofunction, and ten patients with normal vestibular function (control group) were analyzed through VVOR and VORS testing with an Otometrics ICS Impulse system. During the VVOR test, patients with unilateral vestibular hypofunction exhibited corrective saccades to the same direction of the nystagmus fast phase toward the healthy side when the head rotates toward the affected side, while patients with bilateral vestibular hypofunction exhibited corrective saccades to the opposite side of head movements to each side. During the VORS test, patients with unilateral vestibular hypofunction seem to exhibit larger corrective saccades to the healthy side when the head was moved to this side, while patients with bilateral vestibular hypofunction did not exhibit corrective saccades during head movements to either side. Our data suggest that the VVOR and VORS tests yield the same diagnostic information as the HIMP and SHIMP tests in unilateral and bilateral vestibular hypofunction, and can contribute to the diagnosis of a peripheral vestibular loss as well as the affected side.

Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

LigQ: A Webserver to Select and Prepare Ligands for Virtual Screening.

Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compounds is directly proportional to the cost, and thus, the best possible set of ligands is the one with the highest number of true binders, for the smallest possible compound set size. Therefore, methods that are able to trim down large universal data sets enriching them in potential binders are highly appreciated. Here we present LigQ, a free webserver that is able to (i) determine best structure and ligand binding pocket for a desired protein, (ii) find known binders, as well as potential ligands known to bind to similar protein domains, (iii) most importantly, select a small set of commercial compounds enriched in potential binders, and (iv) prepare them for virtual screening. LigQ was tested with several proteins, showing an impressive capacity to retrieve true ligands from large data sets, achieving enrichment factors of over 10%. LigQ is available at http://ligq.qb.fcen.uba.ar/ .

Head-shaking tilt suppression: a clinical test to discern central from peripheral causes of vertigo.

Tilt suppression refers to both tilting the head away from an Earth vertical axis and a reduction of an induced horizontal nystagmus. This phenomenon of reducing an induced horizontal nystagmus involves a circuitry of neurons within the vestibular nuclei and the cerebellum (collectively referred to as velocity storage) and signals from the otolith end organs. Lesions involving this circuitry can disrupt tilt suppression of induced horizontal nystagmus. We investigated the clinical value of combining the horizontal head-shaking nystagmus test with tilt suppression in 28 patients with unilateral peripheral vestibular hypofunction and 11 patients with lesions affecting the central nervous system. Each of the subjects with peripheral vestibular lesions generated an appropriately directed horizontal nystagmus after head shaking that then suppressed the induced angular slow phase velocity on average 52 ± 17.6% following tilt down of the head. In contrast, patients with central lesions had very little ability to suppress post-head-shaking nystagmus (mean 3.4 ± 56%). We recommend tilting the head after head shaking as a useful clinical test to assist in the differential diagnosis of vertiginous patients. In the case of unilateral peripheral vestibular hypofunction, head tilt suppresses the induced nystagmus via influence of the otolith organ. In the case of central pathology, the inability to suppress the nystagmus is from lesions impairing the otolith mediation on the velocity storage circuitry.

Diagnostic Bedside Vestibuloocular Reflex Evaluation in the Setting of a False Negative Fistula Test in Cholesteatoma of the Middle Ear.

Background. False negative fistula testing in patients with chronic suppurative otitis media is a dilemma when proceeding to surgery. It is imperative to rule out a dead labyrinth or a mass effect secondary to the cholesteatoma in an otherwise normally functioning inner ear. We present a case series of three patients in whom a bedside vestibuloocular reflex (VOR) evaluation using a head impulse test was used successfully for further evaluation prior to surgery. Results. In all three cases with a false negative fistula test we were able to further evaluate at the bedside and were not only able to register the abnormal VOR but also localize its deterioration to a particular semicircular canal eroded by the fistula. Conclusion. Vestibuloocular reflex evaluation is mandatory in patients with suspected labyrinthine fistula due to cholesteatoma of the middle ear before proceeding to surgery. We demonstrate successful use of a bedside head impulse test for further evaluation prior to surgery in patients with false negative fistula test.

Impacto del implante coclear en la función vestibular periférica / Impact of cochlear implantation in peripheral vestibular function / Impacto do implante coclear na função vestibular periferica

Introducción: el implante coclear (IC) se ha convertido en el tratamiento más efectivo para la hipoacusia neurosensorial severa-profunda. En los últimos años se han ampliado sus indicaciones, especialmente los casos bilaterales. Es por ello que en la comunidad otológica surge el interrogante de cómo puede afectar a la función vestibular la inserción de un array de electrodos intracocleares. Material y método: Estudio descriptivo, de tipo longitudinal, entre diciembre de 2013 y julio de 2016. Se realizó una revisión de 92 historias clínicas de pacientes que se sometieron a implante coclear en el mismo centro por el mismo equipo y cumplían criterios de inclusión. Resultados: De los 92 pacientes evaluados en el preoperatorio se observaron: Normofunción vestibular bilateral: 56 pacientes (60,8%), Hipofunción vestibular bilateral: 13 pacientes (14,1%), Hipofunción vestibular unilateral: 21 pacientes (22,8%). De los 46 oídos evaluados pre y post IC, un 14,8% (7 pacientes) presentaron hipofunción vestibular post IC, con normofunción previa. Solo 2 pacientes del total de la muestra presentaron sintomatología vestibular severa, con hipovalencias objetivadas en el post operatorio. Conclusiones: Se recomienda evaluar la función vestibular periférica en todos los pacientes candidatos a implante coclear, ya que de no existir otras consideraciones podría ser de utilidad a la hora de definir el lado a implantar.

Introduction: cochlear implant (IC) has become the most effective treatment for severe-deep neurosensory hearing loss. In recent years, indications have been extended, especially bilateral cases. This is why in the otological community the question arises as to how insertion of an array of intracochlear electrodes can affect the vestibular function. Material and method: A descriptive longitudinal study between december 2013 and july 2016. A review of 92 clinical records of patients who underwent cochlear implantation at the same center by the same team and met inclusion criteria were performed. Results: Of the 92 patients evaluated in the preoperative period, bilateral vestibular normobility: 56 patients (60.8%), bilateral vestibular hypofunction: 13 patients (14.1%), unilateral vestibular hypofunction: 21 patients (22.8%). Of the 46 ears assessed pre- and post-IC, 14.8% (7 patients) presented vestibular hypofunction post-IC, with previous normofunction. Only 2 patients from the total sample had severe vestibular symptoms, with postoperative hypovalences. Conclusions: It is recommended to evaluate the peripheral vestibular function in all patients candidates for cochlear implants since, if there were no other considerations, it might be useful to define the side to be implanted.

Introdução: el implante coclear (IC) se ha transformado no tratamento mais efectivo para a hipoacusia neurosensorial severa-profunda. Os últimos juros se han ampliado sus indicaciones, especialmente os casos bilaterais. É por isso que na comunidade otológica surge o interrogante de como pode afetar a função vestibular a inserção de uma matriz de eletrodos intracocleares. Material e método: Estudo descritivo, de tipo longitudinal, entre dezembro de 2013 e julho de 2016. Se realizou uma revisão de 92 historias clínicas de pacientes que se tornaram mais importantes um implante coclear em si mesmo por meio do mesmo e consideramos critérios de inclusão. Resultados: De los 92 pacientes avaliados no pré- operatório observado: Normofunção vestibular bilateral: 56 pacientes (60,8%), Hipofunção vestibular bilateral: 13 pacientes (14,1%), Hipofunção vestibular unilateral: 21 pacientes (22,8%). De los 46 oídos avaliados e pós IC, un 14,8% (7 pacientes) apresentaram hipofunção vestibular post IC, con normofunción previa. Solo 2 pacientes do total da amostra apresentaram sintomatologia vestibular severa, com hipovalencias objetivadas no pós-operatório. Conclusões: verificar a função vestibular periférica em todos os pacientes candidatos a implante coclear ya que não existe de outras formas consideradas poder ser de utilidade à hora de definir o lado a implantar.

The Diagnostic Accuracy of Truncal Ataxia and HINTS as Cardinal Signs for Acute Vestibular Syndrome.

The head impulse, nystagmus type, test of skew (HINTS) protocol set a new paradigm to differentiate peripheral vestibular disease from stroke in patients with acute vestibular syndrome (AVS). The relationship between degree of truncal ataxia and stroke has not been systematically studied in patients with AVS. We studied a group of 114 patients who were admitted to a General Hospital due to AVS, 72 of them with vestibular neuritis (based on positive head impulse, abnormal caloric tests, and negative MRI) and the rest with stroke: 32 in the posterior inferior cerebellar artery (PICA) territory (positive HINTS findings, positive MRI) and 10 in the anterior inferior cerebellar artery (AICA) territory (variable findings and grade 3 ataxia, positive MRI). Truncal ataxia was measured by independent observers as grade 1, mild to moderate imbalance with walking independently; grade 2, severe imbalance with standing, but cannot walk without support; and grade 3, falling at upright posture. When we applied the HINTS protocol to our sample, we obtained 100% sensitivity and 94.4% specificity, similar to previously published findings. Only those patients with stroke presented with grade 3 ataxia. Of those with grade 2 ataxia (n = 38), 11 had cerebellar stroke and 28 had vestibular neuritis, not related to the patient's age. Grade 2-3 ataxia was 92.9% sensitive and 61.1% specific to detect AICA/PICA stroke in patients with AVS, with 100% sensitivity to detect AICA stroke. In turn, two signs (nystagmus of central origin and grade 2-3 Ataxia) had 100% sensitivity and 61.1% specificity. Ataxia is less sensitive than HINTS but much easier to evaluate.

[Guidelines for diagnosis, monitoring and treatment of Fabry disease]. / Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry.

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry / Guidelines for diagnosis, monitoring and treatment of Fabry disease

La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X, ocasionado por el déficit de la enzima alfa galactosidasa A. El conocimiento sobre esta patología, y en particular su manejo médico, ha progresado notablemente en la última década, incluyendo el desarrollo de su tratamiento específico. La presente guía fue desarrollada por profesionales médicos de diversas especialidades involucrados en la atención de pacientes con enfermedad de Fabry. La discusión y análisis de las evidencias científicas disponibles, sumado a la experiencia de cada uno de los participantes, ha permitido desarrollar los conceptos vertidos en esta guía con el objetivo de brindar una herramienta útil para todos los profesionales que asisten a pacientes con enfermedad de Fabry.(AU)

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.(AU)

Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry / Guidelines for diagnosis, monitoring and treatment of Fabry disease

La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X, ocasionado por el déficit de la enzima alfa galactosidasa A. El conocimiento sobre esta patología, y en particular su manejo médico, ha progresado notablemente en la última década, incluyendo el desarrollo de su tratamiento específico. La presente guía fue desarrollada por profesionales médicos de diversas especialidades involucrados en la atención de pacientes con enfermedad de Fabry. La discusión y análisis de las evidencias científicas disponibles, sumado a la experiencia de cada uno de los participantes, ha permitido desarrollar los conceptos vertidos en esta guía con el objetivo de brindar una herramienta útil para todos los profesionales que asisten a pacientes con enfermedad de Fabry.

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry. / [Guidelines for diagnosis, monitoring and treatment of Fabry disease].

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Galvanic vestibular stimulation improves the results of vestibular rehabilitation.

Here, we present findings from a three-step investigation of the effect of galvanic vestibular stimulation (GVS) in normal subjects and in subjects undergoing vestibular rehabilitation (VR). In an initial study, we examined the body sway of 10 normal subjects after one minute of 2 mA GVS. The effect of the stimulation lasted for at least 20 minutes in all subjects and up to two hours in 70% of the subjects. We then compared a group of patients who received conventional VR (40 patients) with a group that received a combination of VR and GVS. Results suggest a significant improvement in the second group. Finally, we attempted to establish the optimal number of GVS sessions and to rule out a placebo effect. Fifteen patients received "systematic" GVS: five sessions, once a week. Five patients received "nonsystematic" galvanic stimulation in a sham protocol, which included two stimulations of the clavicle. These data were analyzed with Fisher's exact test and indicated that the best results were obtained after three sessions of GVS and no placebo effect was observed.