5641
2010
eng
article
1
2012-03-02
--
--
Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration
Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.
urn:nbn:de:bvb:20-opus-68416
6841
PLOS BIOLOGY (2010) 8, 9, DOI: 10.1371/journal.pbio.1000479
Christoph Kleinschnitz
Henrike Grund
Kirstin Wingler
Melanie E. Armitage
Emma Jones
Manish Mittal
David Barit
Tobias Schwarz
Christian Geis
Peter Kraft
Konstanze Barthel
Michael K. Schuhmann
Alexander M. Herrmann
Sven G. Meuth
Guido Stoll
Sabine Meurer
Anja Schrewe
Lore Becker
Valerie Gailus-Durner
Helmut Fuchs
Thomas Klopstock
Martin Hrabe de Angelis
Karin Jandeleit-Dahm
Ajay M. Shah
Norbert Weissmann
Harald H. H. W. Schmidt
deu
swd
Schlaganfall
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5641/Kleinschnitz_journal.pbio.1000479.pdf
13401
2012
eng
e38741
6
7
article
1
2016-05-27
--
--
Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS
Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
PLoS One
10.1371/journal.pone.0038741
urn:nbn:de:bvb:20-opus-134013
PLoS ONE 7(6): e38741. doi:10.1371/journal.pone.0038741
Alexander U. Brandt
Hanna Zimmermann
Falko Kaufhold
Julia Promesberger
Sven Schippling
David Finis
Orhan Aktas
Christian Geis
Marius Ringelstein
E. Bernd Ringelstein
Hans-Peter Hartung
Friedemann Paul
Ilka Kleffner
Jan Dörr
eng
uncontrolled
optical coherence tomography
eng
uncontrolled
vasculopathy
eng
uncontrolled
artery occlusion
eng
uncontrolled
hearing loss
eng
uncontrolled
microangiopathy
eng
uncontrolled
brain
eng
uncontrolled
endotheliopathy
eng
uncontrolled
antibodies
eng
uncontrolled
multiple-sclerosis
eng
uncontrolled
retinocochleocerebral
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13401/Brandt_PLoS_One_2012.pdf
30090
2022
eng
11
article
1
--
--
--
Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo
Spontaneous correlated activity is a universal hallmark of immature neural circuits. However, the cellular dynamics and intrinsic mechanisms underlying network burstiness in the intact developing brain are largely unknown. Here, we use two-photon Ca\(^{2+}\) imaging to comprehensively map the developmental trajectories of spontaneous network activity in the hippocampal area CA1 of mice in vivo. We unexpectedly find that network burstiness peaks after the developmental emergence of effective synaptic inhibition in the second postnatal week. We demonstrate that the enhanced network burstiness reflects an increased functional coupling of individual neurons to local population activity. However, pairwise neuronal correlations are low, and network bursts (NBs) recruit CA1 pyramidal cells in a virtually random manner. Using a dynamic systems modeling approach, we reconcile these experimental findings and identify network bi-stability as a potential regime underlying network burstiness at this age. Our analyses reveal an important role of synaptic input characteristics and network instability dynamics for NB generation. Collectively, our data suggest a mechanism, whereby developing CA1 performs extensive input-discrimination learning prior to the onset of environmental exploration.
eLife
10.7554/eLife.82756
urn:nbn:de:bvb:20-opus-300906
@articleGraf.2022, author = Graf, Jürgen and Rahmati, Vahid and Majoros, Myrtill and Witte, Otto W. and Geis, Christian and Kiebel, Stefan J. and Holthoff, Knut and Kirmse, Knut, year = 2022, title = Network instability dynamics drive a transient bursting period in the developing hippocampus in vivo, volume = 11, journal = eLife, doi = 10.7554/eLife.82756,
md5:68d15444db1eeb666b827a9d9d78cd69
2023-01-23T07:20:57+00:00
/tmp/phpriU9my
bibtex
63ce355974e956.05775355
eLife 2022, 11:e82756. DOI: 10.7554/eLife.82756
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Jürgen Graf
Vahid Rahmati
Myrtill Majoros
Otto W. Witte
Christian Geis
Stefan J. Kiebel
Knut Holthoff
Knut Kirmse
eng
uncontrolled
hippocampus
eng
uncontrolled
spontaneous network activity
eng
uncontrolled
transient bursting
Humanphysiologie
open_access
Physiologisches Institut
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30090/elife_Graf.pdf
14050
2011
eng
e16775
2
6
article
1
2016-11-17
--
--
Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats
Background:
Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear.
Methodology/Principal Findings:
We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11) C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats.
Conclusion/Significance:
The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
Plos One
10.1371/journal.pone.0016775
urn:nbn:de:bvb:20-opus-140506
PLoS ONE 6(2):e16775. doi:10.1371/journal.pone.0016775
Christian Geis
Andreas Weishaupt
Benedikt Grünewald
Thomas Wultsch
Andreas Reif
Manfred Gerlach
Ron Dirkx
Michele Solimena
Klaus V Toyka
Franco Folli
Daniela Perani
Manfred Heckmann
Claudia Sommer
eng
uncontrolled
Glutamic-acid decarboxylase anxiety
eng
uncontrolled
spinal-cord-injury
eng
uncontrolled
presynaptic inhibition
eng
uncontrolled
65-kda isoform
eng
uncontrolled
fear memory
eng
uncontrolled
antibodies
eng
uncontrolled
disorder
eng
uncontrolled
neurons
eng
uncontrolled
anxiety
eng
uncontrolled
autoantibodies
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14050/067_Geis_PLOS-ONE.PDF
6351
2011
eng
article
1
2013-01-11
--
--
Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats
Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient’s amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
urn:nbn:de:bvb:20-opus-74757
7475
In: PLOS ONE (2011) 6:2, 10.1371/journal.pone.0016775
Christian Geis
Andreas Weishaupt
Benedikt Grünewald
Thomas Wultsch
Andreas Reif
Manfred Gerlach
Ron Dirkx
Michele Solimena
Daniela Perani
Manfred Heckmann
Klaus V. Toyka
Franco Folli
Claudia Sommer
deu
swd
Medizin
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6351/Geis_journal.pone.0016775.pdf
21600
2020
eng
544
561
3
88
article
1
--
--
--
Glycine Receptor Autoantibodies Impair Receptor Function and Induce Motor Dysfunction
Objective
Impairment of glycinergic neurotransmission leads to complex movement and behavioral disorders. Patients harboring glycine receptor autoantibodies suffer from stiff‐person syndrome or its severe variant progressive encephalomyelitis with rigidity and myoclonus. Enhanced receptor internalization was proposed as the common molecular mechanism upon autoantibody binding. Although functional impairment of glycine receptors following autoantibody binding has recently been investigated, it is still incompletely understood.
Methods
A cell‐based assay was used for positive sample evaluation. Glycine receptor function was assessed by electrophysiological recordings and radioligand binding assays. The in vivo passive transfer of patient autoantibodies was done using the zebrafish animal model.
Results
Glycine receptor function as assessed by glycine dose–response curves showed significantly decreased glycine potency in the presence of patient sera. Upon binding of autoantibodies from 2 patients, a decreased fraction of desensitized receptors was observed, whereas closing of the ion channel remained fast. The glycine receptor N‐terminal residues \(^{29}\)A to \(^{62}\)G were mapped as a common epitope of glycine receptor autoantibodies. An in vivo transfer into the zebrafish animal model generated a phenotype with disturbed escape behavior accompanied by a reduced number of glycine receptor clusters in the spinal cord of affected animals.
Interpretation
Autoantibodies against the extracellular domain mediate alterations of glycine receptor physiology. Moreover, our in vivo data demonstrate that the autoantibodies are a direct cause of the disease, because the transfer of human glycine receptor autoantibodies to zebrafish larvae generated impaired escape behavior in the animal model compatible with abnormal startle response in stiff‐person syndrome or progressive encephalitis with rigidity and myoclonus patients.
Annals of Neurology
10.1002/ana.25832
urn:nbn:de:bvb:20-opus-216005
2020-11-09T13:00:41+00:00
sword
swordwue
attachment; filename=deposit.zip
18850d8a4dc7a44d0ef5067395525605
Annals of Neurology 2020, 88(3):544–561. DOI: 10.1002/ana.25832
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Vera Rauschenberger
Niels von Wardenburg
Natascha Schaefer
Kazutoyo Ogino
Hiromi Hirata
Christina Lillesaar
Christoph J. Kluck
Hans‐Michael Meinck
Marc Borrmann
Andreas Weishaupt
Kathrin Doppler
Jonathan Wickel
Christian Geis
Claudia Sommer
Carmen Villmann
eng
uncontrolled
glycine receptor autoantibodies
eng
uncontrolled
behavioral disorders
eng
uncontrolled
neurology
Medizin und Gesundheit
open_access
Institut für Klinische Neurobiologie
Neurologische Klinik und Poliklinik
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21600/ANA_ANA25832.pdf
13026
2012
eng
e42800
8
7
article
1
2016-03-18
--
--
Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells
Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.
PLoS One
10.1371/journal.pone.0042800
urn:nbn:de:bvb:20-opus-130268
PLoS ONE 7(8): e42800. doi:10.1371/journal.pone.0042800
222943
Ruhel Ahmad
Wanja Wolber
Sigrid Eckardt
Philipp Koch
Jessica Schmitt
Ruslan Semechkin
Christian Geis
Manfred Heckmann
Oliver Brüstle
John K. McLaughlin
Anna-Leena Sirén
Albrecht M. Müller
eng
uncontrolled
methylation
eng
uncontrolled
derivation
eng
uncontrolled
blastocysts
eng
uncontrolled
pluripotent
eng
uncontrolled
differentiation
eng
uncontrolled
lines
eng
uncontrolled
brain development
eng
uncontrolled
in-vitro
eng
uncontrolled
mice
eng
uncontrolled
specification
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Institut für Medizinische Strahlenkunde und Zellforschung
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13026/journal.pone.0042800.pdf
16600
2016
eng
1407
9
17
article
1
2018-07-27
--
--
Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies
Neuromyelitis Optica Spectrum Disorders (NMOSD) are associated with autoantibodies (ABs) targeting the astrocytic aquaporin-4 water channels (AQP4-ABs). These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG), or of recombinant human AQP4-ABs (rAB-AQP4), provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg) using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7) or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7). We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders.
International Journal of Molecular Sciences
10.3390/ijms17091407
urn:nbn:de:bvb:20-opus-166000
International Journal of Molecular Sciences 2016, 17, 1407; doi:10.3390/ijms17091407
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Benedikt Grünewald
Jeffrey L. Bennett
Klaus V. Toyka
Claudia Sommer
Christian Geis
eng
uncontrolled
intrathecal application
eng
uncontrolled
NMOSD
eng
uncontrolled
aquaporin 4
eng
uncontrolled
autoantibody
eng
uncontrolled
IVIg
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16600/Grunewald_IJMS_2016.pdf
17000
2017
eng
e28685
6
article
1
2018-10-25
--
--
Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3\(^{Δex1-6}\)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
eLife
10.7554/eLife.28685
urn:nbn:de:bvb:20-opus-170004
eLife 2017, 6:e28685. DOI: 10.7554/eLife.28685
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Benedikt Grünewald
Maren D Lange
Christian Werner
Aet O'Leary
Andreas Weishaupt
Sandy Popp
David A Pearce
Heinz Wiendl
Andreas Reif
Hans C Pape
Klaus V Toyka
Claudia Sommer
Christian Geis
eng
uncontrolled
CLN3
eng
uncontrolled
mutation
eng
uncontrolled
mouse model
eng
uncontrolled
synaptic transmission
eng
uncontrolled
amygdala
eng
uncontrolled
hippocampus
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17000/011_Grunewald_eLIFE.pdf
13363
2012
eng
14
9
article
1
2016-05-17
--
--
Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Journal of Neuroinflammation
10.1186/1742-2094-9-14
urn:nbn:de:bvb:20-opus-133636
Journal of Neuroinflammation 2012, 9:14. doi:10.1186/1742-2094-9-14
Sven Jarius
Klemens Ruprecht
Brigitte Wildemann
Tania Kuempfel
Marius Ringelstein
Christian Geis
Ingo Kleiter
Christoph Kleinschnitz
Achim Berthele
Johannes Brettschneider
Kerstin Hellwig
Bernhard Hemmer
Ralf A. Linker
Florian Lauda
Christoph A. Hayrettin
Hayrettin Tumani
Arthur Melms
Corinna Trebst
Martin Stangel
Martin Marziniak
Frank Hoffmann
Sven Schippling
Jürgen H. Faiss
Oliver Neuhaus
Barbara Ettrich
Christian Zentner
Kersten Guthke
Ulrich Hofstadt-van Oy
Reinhard Reuss
Hannah Pellkofer
Ulf Ziemann
Peter Kern
Klaus P. Wandinger
Florian Then Bergh
Tobias Boettcher
Stefan Langel
Martin Liebetrau
Paulus S. Rommer
Sabine Niehaus
Christoph Münch
Alexander Winkelmann
Uwe K Zettl
Imke Metz
Christian Veauthier
Jörn P. Sieb
Christian Wilke
Hans P. Hartung
Orhan Aktas
Friedemann Paul
eng
uncontrolled
cerebrospinal-fluid
eng
uncontrolled
intractable hiccup
eng
uncontrolled
extensiv transverse myelitis
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
anti-aquaporin-4 antibody
eng
uncontrolled
NMO-IGG
eng
uncontrolled
aquaporin-4 autoantibodies
eng
uncontrolled
immune-response
eng
uncontrolled
myasthenia gravis
eng
uncontrolled
immunoglobulin-G
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13363/Jarius_1742-2094-9-14.pdf
1180
2004
deu
doctoralthesis
1
2005-07-11
--
2005-06-23
Charakterisierung von Spinalganglienneuronen intakter und lädierter Afferenzen
Characteristics of injured and spared dorsal root ganglia neurons
Am Tiermodell einer experimentellen Mononeuropathie (chronic constriction injury, CCI) wurde bei Ratten die Expression von Zytokinen (TNF-α, IL-10), Vanilloidrezeptor 1 (VR1) und Neuropeptiden in Spinalganglienneuronen immunhistochemisch analy-siert. Durch retrograde Anfärbung mit den Tracern Fluorogold (FG) und Fluoruby (FR) konnten intakte von geschädigten Neuronen unterschieden und Muskel- und Hautaffe-renzen getrennt untersucht werden. Nach CCI fand sich ein selektiver Anstieg der TNF-α Immunreaktivität in mittelgroßen und großen Spinalganglienneuronen, welche durch Vergleich mit anderen neuronalen Markern als A-Faser Neurone identifiziert werden konnten. Nicht nur geschädigte, sondern auch intakte Spinalganglienneurone wiesen eine erhöhte TNF-α Immunreaktivität auf und sowohl Muskel- als auch Hautafferenzen trugen zur vermehrten TNF-α Expression bei. IL-10, VR1 und IB4 Immunreaktivität fand sich vor allem in kleinen Neuronen und war nach CCI deutlich reduziert, während die Expression von CGRP in kleinen und mittel-großen Spinalganglienneuronen nachzuweisen war und keine Veränderung zeigte. Die Ergebnisse zeigen, dass intakt gebliebene A-Faser Neurone pathophysiologische Veränderungen im Sinne einer vermehrten Expression des pro-inflammatorischen Zyto-kins TNF-α erfahren. Dieser phänotypische Switch ist möglicherweise mit einer neuen Funktion dieser Neurone im nozizeptiven System verbunden. Die verminderte Expression des anti-inflammatorischen Zytokins IL-10 vier Tage nach CCI korrespondiert mit der frühen Schmerzentstehung nach peripherer Nervenläsion und der noch fehlenden Suppression der pro-inflammatorischen Zytokine zu diesem Zeitpunkt. Dagegen ist der Rückgang der VR1 und IB4 Konzentrationen im Spinal-ganglion am ehesten durch einen läsionsbedingten Mangel an neurotrophen Faktoren zu erklären. Die in dieser Arbeit gewonnenen Erkenntnisse unterstützen die These, dass pro-inflammatorischen Zytokinen, insbesondere TNF-α, eine besondere Bedeutung bei der Entstehung neuropathischer Schmerzen zukommt. Dies könnte ein Ansatzpunkt für wei-tere Studien sein, die Wirksamkeit TNF-α hemmender Medikamente bei neuropathi-schen Schmerzmodellen im Tierversuch und eventuell später klinisch zu untersuchen.
Chronic constriction of the sciatic nerve leading to a hyperalgesic state results in a partial lesion wherein some axons are injured and others remain intact. Here we sought to characterize reactive changes which occur in DRG cell bodies of injured and uninjured axons projecting to skin and muscle. Using immunohistochemistry combined with flurorogold and fluororuby retrograde labelling to define DRG cell bodies associated with injured and uninjured axons, we analyzed the DRG immunoreactivity (IR) for tumor necrosis factor-alpha (TNF), interleukin-10 (IL-10), the sensory neuron-specific channel vanilloid receptor 1 (VR1), isolectin B4 (IB4) and calcitonin-gene-related peptide (CGRP) 4 days after a unilateral chronic constriction (CCI) of the rat sciatic nerve. TNF IR was predominantly localized in neuronal DRG cells. In DRG with an intact nerve, TNF IR was present in 45 %, IL-10 IR in 46 %, VR1 IR in 44 %, IB4 IR in 51 % and CGRP IR in 40 % of all neuronal profiles. Four days after CCI, TNF IR was increased in medium-sized neurons, whereas IR for IL-10, VR1 and IB4, predominantly present in small neurons, was reduced. Importantly, not only injured, but also adjacent spared neurons contributed markedly to increased TNF IR. Neurons projecting to both muscle and skin displayed upregulated TNF IR after CCI. TNF in medium-sized neurons colocalized with neurofilament and trkB, but not with IB4, trkA and RET, suggesting a selective phenotypic switch in presumably low-threshold myelinated primary afferents. Spared myelinated fibers with intact sensory functions but upregulated TNF expression may contribute to behavioral changes observed after nerve injury.
urn:nbn:de:bvb:20-opus-13926
1392
European Journal of Neuroscience
X120241
Christian Geis
deu
uncontrolled
TNF alpha
deu
uncontrolled
Spinalganglion
deu
uncontrolled
Schmerz
deu
uncontrolled
Zytokine
deu
uncontrolled
retrograde Marker
eng
uncontrolled
TNF alpha
eng
uncontrolled
Dorsal root ganglion
eng
uncontrolled
Pain
eng
uncontrolled
Cytokines
eng
uncontrolled
retrograde tracers
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/1180/DissertationChGeis.pdf
9617
2013
eng
article
1
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Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report
Introduction
Sudden tetraparesis represents a neurological emergency and is most often caused by traumatic spinal cord injury, spinal epidural bleeding or brainstem ischemia and less frequently by medial disc herniation or spinal ischemia.
Case presentation
Here we report the rare case of an 82-year-old Caucasian man who developed severe tetraparesis four days after radical cystoprostatectomy. An emergency diagnostic study for spinal cord affection was normal. Brain magnetic resonance imaging revealed acute bilateral ischemic strokes in the precentral gyri as the underlying cause.
Conclusions
This case report underlines the need to also consider unusual causes of tetraparesis in an emergency situation apart from spinal cord or brain stem injury in order not to leave severe symptomatology unclear and possibly miss therapeutic options.
Journal of Medical Case Reports
10.1186/1752-1947-7-61
http://www.jmedicalcasereports.com/content/7/1/61
urn:nbn:de:bvb:20-opus-96179
In: Journal of Medical Case Reports (2013) 7: 61, doi:10.1186/1752-1947-7-61
Ignaz Gunreben
Christian Geis
Christoph Kleinschnitz
deu
uncontrolled
Medizin
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9617/Gunreben_1752-1947-7-61.pdf