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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. Source

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. Source

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. Source

D'Adamo M.C.,University of Perugia | Gallenmuller C.,Ludwig Maximilians University of Munich | Gallenmuller C.,A+ Network | Gallenmuller C.,German Center for Neurodegenerative Diseases | And 18 more authors.
Frontiers in Physiology | Year: 2015

Episodic ataxia type 1 (EA1) is an autosomal dominant K+channelopathy which manifests with short attacks of cerebellar ataxia and dysarthria, and may also show interictal myokymia. Episodes can be triggered by emotional or physical stress, startle response, sudden postural change or fever. Here we describe a 31-year-old man displaying markedly atypical symptoms, including long-lasting attacks of jerking muscle contractions associated with hyperthermia, severe migraine, and a relatively short-sleep phenotype. A single nucleotide change in KCNA1 (c.555C>G) was identified that changes a highly conserved residue (p.C185W) in the first transmembrane segment of the voltage-gated K+channel Kv1.1. The patient is heterozygous and the mutation was inherited from his asymptomatic mother. Next generation sequencing revealed no variations in the CACNA1A, CACNB4, KCNC3, KCNJ10, PRRT2 or SCN8A genes of either the patient or mother, except for a benign variant in SLC1A3. Functional analysis of the p.C185W mutation in KCNA1 demonstrated a deleterious dominant-negative phenotype where the remaining current displayed slower activation kinetics, subtle changes in voltage-dependence and faster recovery from slow inactivation. Structural modeling also predicts the C185W mutation to be functionally deleterious. This description of novel clinical features, associated with a Kv1.1 mutation highlights a possibly unrecognized relationship between K+channel dysfunction, hyperthermia and migraine in EA1, and suggests that thorough assessments for these symptoms should be carefully considered for all patients affected by EA1. © 2015 D'Adamo, Gallenmüller, Servettini, Hartl, Tucker, Arning, Biskup, Grottesi, Guglielmi, Imbrici, Bernasconi, Di Giovanni, Franciolini, Catacuzzeno, Pessia and Klopstock. Source

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. Source

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