Wuehr M.,German Center for Vertigo and Balance Disorders |
Decker J.,German Center for Vertigo and Balance Disorders |
Krafczyk S.,German Center for Vertigo and Balance Disorders |
Straube A.,German Center for Vertigo and Balance Disorders |
And 4 more authors.
Neurology | Year: 2016
To examine the effects of imperceptible levels of white noise galvanic vestibular stimulation (nGVS) on dynamic walking stability in patients with bilateral vestibulopathy (BVP). Methods: Walking performance of 13 patients with confirmed BVP (mean age 50.1 ± 5.5 years) at slow, preferred, and fast speeds was examined during walking with zero-amplitude nGVS (sham trial) and nonzero-amplitude nGVS set to 80% of the individual cutaneous threshold for GVS (nGVS trial). Eight standard gait measures were analyzed: stride time, stride length, base of support, double support time percentage as well as the bilateral phase coordination index, and the coefficient of variation (CV) of stride time, stride length, and base of support. Results: Compared to the sham trial, nGVS improved stride time CV by 26.0% ± 8.4% (p < 0.041), stride length CV by 26.0% ± 7.7% (p < 0.029), base of support CV by 27.8% ± 2.9% (p < 0.037), and phase coordination index by 8.4% ± 8.8% (p < 0.013). The nGVS effects on walking performance were correlated with subjective ratings of walking balance (ρ 0.79, p < 0.001). Effect of nGVS on walking stability was most pronounced during slow walking. Conclusions: In patients with BVP, nGVS is effective in improving impaired gait performance, predominantly during slower walking speeds. It primarily targets the variability and bilateral coordination characteristics of the walking pattern, which are linked to dynamic walking stability. nGVS might present an effective treatment option to immediately improve walking performance and reduce the incidence of falls in patients with BVP. Classification of evidence: This study provides Class IV evidence that in patients with BVP, an imperceptible level of nGVS improves dynamic walking stability. © 2016 American Academy of Neurology.
PubMed | University of Southern Denmark and German Center for Vertigo and Balance Disorders
Type: | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2017
Some blind humans have developed echolocation, as a method of navigation in space. Echolocation is a truly active sense because subjects analyze echoes of dedicated, self-generated sounds to assess space around them. Using a special virtual space technique we assess how humans perceive enclosed spaces through echolocation, thereby revealing the interplay between sensory and vocal-motor neural activity while humans perform this task. Sighted subjects were trained to detect small changes in virtual room size analyzing real-time generated echoes of their vocalizations. Individual differences in performance were related to the type and number of vocalizations produced. We then asked subjects to estimate virtual-room size with either active or passive sounds, while measuring their brain activity with fMRI. Subjects were better at estimating room size when actively vocalizing. This was reflected in the hemodynamic activity of vocal-motor cortices, even after individual motor and sensory components were removed. Activity in these areas also varied with perceived room size, although the vocal-motor output was unchanged. In addition, thalamic and auditory-midbrain activity was correlated with perceived room size, a likely result of top-down auditory pathways for human echolocation, comparable to those described in echolocating bats. Our data provide evidence that human echolocation is supported by active sensing, both behaviorally and in terms of brain activity. The neural sensory-motor coupling complements the fundamental acoustic motor -- sensory coupling via the environment in echolocation.Passive listening is the predominant method for examining brain activity during echolocation, the auditory analysis of self-generated sounds. We show that sighted humans perform better when they actively vocalize than during passive listening. Correspondingly, vocal motor and cerebellar activity is greater during active echolocation than vocalization alone. Motor and subcortical auditory brain activity covaries with the auditory percept, although motor output is unchanged. Our results reveal behaviorally relevant neural sensory-motor coupling during echolocation.
PubMed | German Center for Vertigo and Balance Disorders
Type: Journal Article | Journal: Journal of neurosurgery | Year: 2016
OBJECTIVE The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH. METHODS In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1-8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]). RESULTS Twenty-four patients with a mean age of 76.1 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false-positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients. CONCLUSIONS Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24-48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP.
PubMed | University of Tübingen, DSGZ Neurology, Ludwig Maximilians University of Munich, Synergy Systems and 2 more.
Type: | Journal: Cerebral cortex (New York, N.Y. : 1991) | Year: 2015
Spatial orientation was tested during a horizontal and vertical real navigation task in humans. Video tracking of eye movements was used to analyse the behavioral strategy and combined with simultaneous measurements of brain activation and metabolism ([
Frejo L.,University of Granada |
Giegling I.,German Center for Vertigo and Balance Disorders |
Teggi R.,San Raffaele Scientific Institute |
Lopez-Escamez J.A.,University of Granada |
Rujescu D.,German Center for Vertigo and Balance Disorders
Journal of Neurology | Year: 2016
The two most common vestibular disorders are motion sickness and vestibular migraine, affecting 30 and 1–2 % of the population respectively. Both are related to migraine and show a familial trend. Bilateral vestibular hypofunction is a rare condition, and some of patients also present cerebellar ataxia and neuropathy. We present recent advances in the genetics of vestibular disorders with familial aggregation. The clinical heterogeneity observed in different relatives of the same families suggests a variable penetrance and the interaction of several genes in each family. Some Mendelian sensorineural hearing loss also exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. However, the most relevant finding during the past years is the familial clustering observed in Meniere’s disease. By using whole exome sequencing and combining bioinformatics tools, novel variants in DTNA and FAM136A genes have been identified in familial Meniere’s disease, and this genomic strategy will facilitate the discovery of the genetic basis of familial vestibular disorders. © 2015, The Author(s).
PubMed | San Raffaele Scientific Institute, German Center for Vertigo and Balance Disorders and University of Granada
Type: | Journal: Journal of neurology | Year: 2016
The two most common vestibular disorders are motion sickness and vestibular migraine, affecting 30 and 1-2% of the population respectively. Both are related to migraine and show a familial trend. Bilateral vestibular hypofunction is a rare condition, and some of patients also present cerebellar ataxia and neuropathy. We present recent advances in the genetics of vestibular disorders with familial aggregation. The clinical heterogeneity observed in different relatives of the same families suggests a variable penetrance and the interaction of several genes in each family. Some Mendelian sensorineural hearing loss also exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. However, the most relevant finding during the past years is the familial clustering observed in Menieres disease. By using whole exome sequencing and combining bioinformatics tools, novel variants in DTNA and FAM136A genes have been identified in familial Menieres disease, and this genomic strategy will facilitate the discovery of the genetic basis of familial vestibular disorders.
Blanco S.,University of Cambridge |
Dietmann S.,University of Cambridge |
Flores J.V.,University of Cambridge |
Hussain S.,University of Cambridge |
And 23 more authors.
EMBO Journal | Year: 2014
Mutations in the cytosine-5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities in mice and human. How post-transcriptional methylation contributes to the human disease is currently unknown. By comparing gene expression data with global cytosine-5 RNA methylomes in patient fibroblasts and NSun2-deficient mice, we find that loss of cytosine-5 RNA methylation increases the angiogenin-mediated endonucleolytic cleavage of transfer RNAs (tRNA) leading to an accumulation of 5′ tRNA-derived small RNA fragments. Accumulation of 5′ tRNA fragments in the absence of NSun2 reduces protein translation rates and activates stress pathways leading to reduced cell size and increased apoptosis of cortical, hippocampal and striatal neurons. Mechanistically, we demonstrate that angiogenin binds with higher affinity to tRNAs lacking site-specific NSun2-mediated methylation and that the presence of 5′ tRNA fragments is sufficient and required to trigger cellular stress responses. Furthermore, the enhanced sensitivity of NSun2-deficient brains to oxidative stress can be rescued through inhibition of angiogenin during embryogenesis. In conclusion, failure in NSun2-mediated tRNA methylation contributes to human diseases via stress-induced RNA cleavage. Synopsis This study causally links post-transcriptional methylation-controlled tRNA identity and their stability to neurological disorders in human. NSun2-mediated tRNA methylation protects from endonucleolytic cleavage into small RNA fragments. tRNA-derived small RNA fragments are sufficient and required to induce cellular stress responses. Loss of cytosine-5 methylation in tRNAs contributes to neuro-developmental disease through accumulation of tRNA-derived small RNA fragments. This study causally links post-transcriptional methylation-controlled tRNA identity and their stability to neurological disorders in human. © 2014 The Authors.
Eggers S.D.Z.,Mayo Medical School |
Horn A.K.E.,Institute of Anatomy and Cell Biology I |
Horn A.K.E.,German Center for Vertigo and Balance Disorders |
Roeber S.,German Center for Vertigo and Balance Disorders |
And 5 more authors.
Annals of the New York Academy of Sciences | Year: 2015
The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction-such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN. © 2015 New York Academy of Sciences.
Radtke-Schuller S.,Ludwig Maximilians University of Munich |
Radtke-Schuller S.,German Center for Vertigo and Balance Disorders |
Seeler S.,Ludwig Maximilians University of Munich |
Grothe B.,Ludwig Maximilians University of Munich |
Grothe B.,German Center for Vertigo and Balance Disorders
Frontiers in Aging Neuroscience | Year: 2015
Degeneration of hearing and vertigo are symptoms of age-related auditory and vestibular disorders reflecting multifactorial changes in the peripheral and central nervous system whose interplay remains largely unknown. Originating bilaterally in the brain stem, vestibular and auditory efferent cholinergic projections exert feedback control on the peripheral sensory organs, and modulate sensory processing. We studied age-related changes in the auditory and vestibular efferent systems by evaluating number of cholinergic efferent neurons in young adult and aged gerbils, and in cholinergic trigeminal neurons serving as a control for efferents not related to the inner ear. We observed a significant loss of olivocochlear (OC) neurons in aged compared to young adult animals, whereas the overall number of lateral superior olive (LSO) cells was not reduced in aging. Although the loss of lateral and medial olivocochlear (MOC) neurons was uniform and equal on both sides of the brain, there were frequency-related differences within the lateral olivocochlear (LOC) neurons, where the decline was larger in the medial limb of the superior olivary nucleus (high frequency representation) than in the lateral limb (middle-to-low frequency representation). In contrast, neither the number of vestibular efferent neurons, nor the population of motor trigeminal neurons were significantly reduced in the aged animals. These observations suggest differential effects of aging on the respective cholinergic efferent brainstem systems. © 2015 Radtke-Schuller, Seeler and Grothe.
Baier B.,Edith Stein Clinic |
Muller N.G.,Otto Von Guericke University of Magdeburg |
Dieterich M.,Ludwig Maximilians University of Munich |
Dieterich M.,Synergy Systems |
Dieterich M.,German Center for Vertigo and Balance Disorders
Annals of Neurology | Year: 2014
Although there is evidence that the cerebellum is involved in working memory (WM), it remains unclear which functions within WM the cerebellum supports and which structures are involved in WM. We tested whether the cerebellum is involved in the filtering of incoming information or in its storage. Using a statistical brain mapping approach in 29 patients with cerebellar ischemic stroke, we found that the cerebellum plays a gatekeeper role, as lesions of the tonsil, the lobus semilunaris inferior, and parts of the vermal pyramid rendered WM susceptible to irrelevant information. We conclude that the cerebellum controls incoming WM information. © 2014 American Neurological Association.