@article{HoppAlbertWeissenberger2015,
  author    = {Hopp, Sarah and Albert-Weissenberger, Christiane},
  title     = {The kallikrein-kinin system: a promising therapeutic target for traumatic brain injury},
  series = {Neural Regeneration Research},
  volume    = {10},
  journal   = {Neural Regeneration Research},
  number    = {6},
  doi       = {10.4103/1673-5374.158339},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149416},
  pages     = {885-886},
  year      = {2015},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{BiegstraatenArngrimssonBarbeyetal.2015,
  author    = {Biegstraaten, Marieke and Arngr{\´i}msson, Reynir and Barbey, Frederic and Boks, Lut and Cecchi, Franco and Deegan, Patrick B and Feldt-Rasmussen, Ulla and Geberhiwot, Tarekegn and Germain, Dominique P and Hendriksz, Chris and Hughes, Derralynn A and Kantola, Ilkka and Karabul, Nesrin and Lavery, Christine and Linthorst, Gabor E and Mehta, Atul and van de Mheen, Erica and Oliveira, Jo{\~a}o P and Parini, Rossella and Ramaswami, Uma and Rudnicki, Michael and Serra, Andreas and Sommer, Claudia and Sunder-Plassmann, Gere and Svarstad, Einar and Sweeb, Annelies and Terryn, Wim and Tylki-Szymanska, Anna and T{\o}ndel, Camilla and Vujkovac, Bojan and Weidemann, Frank and Wijburg, Frits A and Woolfson, Peter and Hollak, Carla EM},
  title     = {Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {10},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {36},
  doi       = {10.1186/s13023-015-0253-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175374},
  year      = {2015},
  abstract  = {Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. Methods: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75\% agreement and no disagreement. Results: For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m\(^{2}\)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped. Conclusion: The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.},
  language  = {en}
}
@article{GulbertiMollHameletal.2015,
  author    = {Gulberti, A. and Moll, C.K.E. and Hamel, W. and Buhmann, C. and Koeppen, J.A. and Boelmans, K. and Zittel, S. and Gerloff, C. and Westphal, M. and Schneider, T.R. and Engel, A.K.},
  title     = {Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus Impaired beta-band timing functions in PD},
  series = {NeuroImage: Clinical},
  volume    = {9},
  journal   = {NeuroImage: Clinical},
  doi       = {10.1016/j.nicl.2015.09.013},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150049},
  pages     = {436-449},
  year      = {2015},
  abstract  = {Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.},
  language  = {en}
}
@article{FluriSchuhmannKleinschnitz2015,
  author    = {Fluri, Felix and Schuhmann, Michael K and Kleinschnitz, Christoph},
  title     = {Animal models of ischemic stroke and their application in clinical research},
  series = {Drug Design, Development and Therapy},
  volume    = {9},
  journal   = {Drug Design, Development and Therapy},
  doi       = {10.2147/DDDT.S56071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149157},
  pages     = {3445-3454},
  year      = {2015},
  abstract  = {This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.},
  language  = {en}
}
@article{KraftDrechslerGunrebenetal.2015,
  author    = {Kraft, Peter and Drechsler, Christiane and Gunreben, Ignaz and Heuschmann, Peter Ulrich and Kleinschnitz, Christoph},
  title     = {Case-control study of platelet glycoprotein receptor Ib and IIb/IIIa expression in patients with acute and chronic cerebrovascular disease},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0119810},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148806},
  pages     = {e0119810},
  year      = {2015},
  abstract  = {Background Animal models have been instrumental in defining thrombus formation, including the role of platelet surface glycoprotein (GP) receptors, in acute ischemic stroke (AIS). However, the involvement of GP receptors in human ischemic stroke pathophysiology and their utility as biomarkers for ischemic stroke risk and severity requires elucidation. Aims To determine whether platelet GPIb and GPIIb/IIIa receptors are differentially expressed in patients with AIS and chronic cerebrovascular disease (CCD) compared with healthy volunteers (HV) and to identify predictors of GPIb and GPIIb/IIIa expression. Methods This was a case-control study of 116 patients with AIS or transient ischemic attack (TIA), 117 patients with CCD, and 104 HV who were enrolled at our University hospital from 2010 to 2013. Blood sampling was performed once in the CCD and HV groups, and at several time points in patients with AIS or TIA. Linear regression and analysis of variance were used to analyze correlations between platelet GPIb and GPIIb/IIIa receptor numbers and demographic and clinical parameters. Results GPIb and GPIIb/IIIa receptor numbers did not significantly differ between the AIS, CCD, and HV groups. GPIb receptor expression level correlated significantly with the magnitude of GPIIb/IIIa receptor expression and the neutrophil count. In contrast, GPIIb/IIIa receptor numbers were not associated with peripheral immune-cell sub-population counts. Creactive protein was an independent predictor of GPIIb/IIIa (not GPIb) receptor numbers. Conclusions Platelet GPIb and GPIIb/IIIa receptor numbers did not distinguish between patient or control groups in this study, negating their potential use as a biomarker for predicting stroke risk.},
  language  = {en}
}
@article{KleinschnitzNiemczykRehbergWeberetal.2015,
  author    = {Kleinschnitz, Christoph and Niemczyk, Gabriele and Rehberg-Weber, Karin and Wernsd{\"o}rfer, Colin},
  title     = {Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160715271},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148487},
  pages     = {15271-15286},
  year      = {2015},
  abstract  = {The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.},
  language  = {en}
}
@article{HaarmannNehenDeissetal.2015,
  author    = {Haarmann, Axel and Nehen, Mathias and Deiß, Annika and Buttmann, Mathias},
  title     = {Fumaric acid esters do not reduce inflammatory NF-\(\kappa\)B/p65 nuclear translocation, ICAM-1 expression and T-cell adhesiveness of human brain microvascular endothelial cells},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160819086},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148295},
  pages     = {19086-19095},
  year      = {2015},
  abstract  = {Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 \(\mu\)M blocked the IL-1\(\beta\)-induced nuclear translocation of NF-\(\kappa\)B/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1\(\beta\)-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1\(\beta\)-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells.},
  language  = {en}
}
@article{RovitusoDuffySchroeteretal.2015,
  author    = {Rovituso, Damiano M. and Duffy, Catharina E. and Schroeter, Michael and Kaiser, Claudia C. and Kleinschnitz, Christoph and Bayas, Antonios and Elsner, Rebecca and Kuerten, Stefanie},
  title     = {The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {14265},
  doi       = {10.1038/srep14265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148172},
  year      = {2015},
  abstract  = {B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-\(\beta\) (IFN-\(\beta\))-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.},
  language  = {en}
}
@article{SchuhmannBittnerMeuthetal.2015,
  author    = {Schuhmann, Michael K. and Bittner, Stefan and Meuth, Sven G. and Kleinschnitz, Christoph and Fluri, Felix},
  title     = {Fingolimod (FTY720-P) does not stabilize the blood-brain barrier under inflammatory conditions in an in vitro model},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms161226177},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145047},
  pages     = {29454-29466},
  year      = {2015},
  abstract  = {Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has not been well elucidated to date. In the present study, FTY720-P did not change the transendothelial electrical resistance in a rat brain microvascular endothelial cell (RBMEC) culture exposed to inflammatory conditions and thus did not decrease endothelial barrier permeability. In contrast, occludin was reduced in RBMEC culture after adding FTY720-P. Additionally, FTY720-P did not alter the amount of endothelial matrix metalloproteinase (MMP)-9 and MMP-2 in RBMEC cultures. Taken together, our observations support the assumption that S1P\(_1\) plays a dual role in vascular permeability, depending on its ligand. Thus, S1P\(_1\) provides a mechanistic basis for FTY720-P-associated disruption of endothelial barrierssuch as the blood-retinal barrierwhich might result in macular edema.},
  language  = {en}
}
@article{MezianeMoiselloPerfettietal.2015,
  author    = {Meziane, Hadj Boumediene and Moisello, Clara and Perfetti, Bernardo and Kvint, Svetlana and Isaias, Ioannis Ugo and Quartarone, Angelo and Di Rocco, Alessandro and Ghilardi, Maria Felice},
  title     = {Movement preparation and bilateral modulation of beta activity in aging and Parkinson's disease},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0114817},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144147},
  pages     = {e0114817},
  year      = {2015},
  abstract  = {In previous studies of young subjects performing a reaction-time reaching task, we found that faster reaction times are associated with increased suppression of beta power over primary sensorimotor areas just before target presentation. Here we ascertain whether such beta decrease similarly occurs in normally aging subjects and also in patients with Parkinson's disease (PD), where deficits in movement execution and abnormalities of beta power are usually present. We found that in both groups, beta power decreased during the motor task in the electrodes over the two primary sensorimotor areas. However, before target presentation, beta decreases in PD were significantly smaller over the right than over the left areas, while they were symmetrical in controls. In both groups, functional connectivity between the two regions, measured with imaginary coherence, increased before the target appearance; however, in PD, it decreased immediately after, while in controls, it remained elevated throughout motor planning. As in previous studies with young subjects, the degree of beta power before target appearance correlated with reaction time. The values of coherence during motor planning, instead, correlated with movement time, peak velocity and acceleration. We conclude that planning of prompt and fast movements partially depends on coordinated beta activity of both sensorimotor areas, already at the time of target presentation. The delayed onset of beta decreases over the right region observed in PD is possibly related to a decreased functional connectivity between the two areas, and this might account for deficits in force programming, movement duration and velocity modulation.},
  language  = {en}
}
@article{GutknechtPoppWaideretal.2015,
  author    = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter},
  title     = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice},
  series = {Psychopharmacology},
  volume    = {232},
  journal   = {Psychopharmacology},
  doi       = {10.1007/s00213-015-3879-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586},
  pages     = {2429 -- 2441},
  year      = {2015},
  abstract  = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.},
  language  = {en}
}
@article{SimonRauskolbGunnersenetal.2015,
  author    = {Simon, Christian M. and Rauskolb, Stefanie and Gunnersen, Jennifer M. and Holtmann, Bettina and Drepper, Carsten and Dombert, Benjamin and Braga, Massimiliano and Wiese, Stefan and Jablonka, Sibylle and P{\"u}hringer, Dirk and Zielasek, J{\"u}rgen and Hoeflich, Andreas and Silani, Vincenzo and Wolf, Eckhard and Kneitz, Susanne and Sommer, Claudia and Toyka, Klaus V. and Sendtner, Michael},
  title     = {Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy},
  series = {Acta Neuropathologica},
  volume    = {130},
  journal   = {Acta Neuropathologica},
  doi       = {10.1007/s00401-015-1446-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154569},
  pages     = {373 -- 387},
  year      = {2015},
  abstract  = {Diabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen in DNP. Motor axon degeneration was also observed in mice in which the IGF1 receptor(IGF1R) was conditionally depleted in motoneurons, indicating that reduced activity of IGF1 on IGF1R in motoneurons is responsible for the observed effect. These data provide evidence that elevated expression of IGFBP5 in diabetic nerves reduces the availability of IGF1 for IGF1R on motor axons, thus leading to progressive neurodegeneration. Inhibition of IGFBP5 could thus offer novel treatment strategies for DNP.},
  language  = {en}
}
@article{CoenenAmtageVolkmannetal.2015,
  author    = {Coenen, Volker A. and Amtage, Florian and Volkmann, Jens and Schl{\"a}pfer, Thomas E.},
  title     = {Deep Brain Stimulation in Neurological and Psychiatric Disorders},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {112},
  journal   = {Deutsches {\"A}rzteblatt International},
  doi       = {10.3238/arztebl.2015.0519},
  pages     = {519 -- 526},
  year      = {2015},
  abstract  = {Background: Deep brain stimulation (DBS) is the chronic electrical stimulation of selected target sites in the brain through stereotactically implanted electrodes. More than 150 000 patients around the world have been treated to date with DBS for medically intractable conditions. The indications for DBS include movement disorders, epilepsy, and some types of mental illness. Methods: This review is based on relevant publications retrieved by a selective search in PubMed and the Cochrane Library, and on the current guidelines of the German Neurological Society (Deutsche Gesellschaft fur Neurologie, DGN). Results: DBS is usually performed to treat neurological diseases, most often movement disorders and, in particular, Parkinson's disease. Multiple randomized controlled trials (RCTs) have shown that DBS improves tremor, dyskinesia, and quality of life in patients with Parkinson's disease by 25\% to 50\%, depending on the rating scales used. DBS for tremor usually involves stimulation in the cerebello-thalamo-cortical regulatory loop. In an RCT of DBS for the treatment of primary generalized dystonia, the patients who underwent DBS experienced a 39.3\% improvement of dystonia, compared to only 4.9\% in the control group. Two multicenter trials of DBS for depression were terminated early because of a lack of efficacy. Conclusion: DBS is an established treatment for various neurological and psychiatric diseases. It has been incorporated in the DGN guidelines and is now considered a standard treatment for advanced Parkinson's disease. The safety and efficacy of DBS can be expected to improve with the application of new technical developments in electrode geometry and new imaging techniques. Controlled trials would be helpful so that DBS could be extended to further indications, particularly psychiatric ones.},
  language  = {en}
}
@article{BittnerBobakHofmannetal.2015,
  author    = {Bittner, Stefan and Bobak, Nicole and Hofmann, Majella-Sophie and Schuhmann, Michael K. and Ruck, Tobias and G{\"o}bel, Kerstin and Br{\"u}ck, Wolfgang and Wiendl, Heinz and Meuth, Sven G.},
  title     = {Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160816880},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151454},
  pages     = {16880 -- 16896},
  year      = {2015},
  abstract  = {Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.},
  language  = {en}
}
@article{KleikersHooijmansGoebetal.2015,
  author    = {Kleikers, Pamela W. M. and Hooijmans, Carlijn and G{\"o}b, Eva and Langhauser, Friederike and Rewell, Sarah S. J. and Radermacher, Kim and Ritskes-Hoitinga, Merel and Howells, David W. and Kleinschnitz, Christoph and Schmidt, Harald H. H. W.},
  title     = {A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {13428},
  doi       = {10.1038/srep13428},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151401},
  year      = {2015},
  abstract  = {Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX\(_{2}\) as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.},
  language  = {en}
}
@article{MaggRieglerWiedmannetal.2015,
  author    = {Magg, Barbara and Riegler, Christoph and Wiedmann, Silke and Heuschmann, Peter and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Self-administered version of the Fabry-associated pain questionnaire for adult patients},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {10},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {113},
  doi       = {10.1186/s13023-015-0325-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145294},
  year      = {2015},
  abstract  = {Background Fabry-associated pain may be the first symptom of Fabry disease (FD) and presents with a unique phenotype including mostly acral burning triggerable pain attacks, evoked pain, pain crises, and permanent pain. We recently developed and validated the first Fabry Pain Questionnaire (FPQ) for adult patients. Here we report on the validation of the self-administered version of the FPQ that no longer requires a face-to-face interview but can be filled in by the patients themselves allowing more flexible data collection. Methods At our W{\"u}rzburg Fabry Center for Interdisciplinary Treatment, Germany, we have developed the self-administered version of the FPQ by adapting the questionnaire to a self-report version. To do this, consecutive Fabry patients with current or past pain history (n = 56) were first interviewed face-to-face. Two weeks later patients' self-reported questionnaire results were collected by mail (n = 55). We validated the self-administered version of the FPQ by assessing the inter-rater reliability agreement of scores obtained by supervised administration and self-administration of the FPQ. Results The FPQ contains 15 questions on the different pain phenotypes, on pain development during life with and without therapy, and on impairment due to pain. Statistical analysis showed that the majority of questions were answered in high agreement in both sessions with a mean AC1-statistic of 0.857 for 55 nominal-scaled items and a mean ICC of 0.587 for 9 scores. Conclusions This self-administered version of the first pain questionnaire for adult Fabry patients is a useful tool to assess Fabry-associated pain without a time-consuming face-to-face interview but via a self-reporting survey allowing more flexible usage.},
  language  = {en}
}
@article{SchreweLillLiuetal.2015,
  author    = {Schrewe, L. and Lill, C. M. and Liu, T. and Salmen, A. and Gerdes, L. A. and Guillot-Noel, L. and Akkad, D. A. and Blaschke, P. and Graetz, C. and Hoffjan, S. and Kroner, A. and Demir, S. and B{\"o}hme, A. and Rieckmann, P. and El Ali, A. and Hagemann, N. and Hermann, D. M. and Cournu-Rebeix, I. and Zipp, F. and K{\"u}mpfel, T. and Buttmann, M. and Zettl, U. K. and Fontaine, B. and Bertram, L. and Gold, R. and Chan, A.},
  title     = {Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS},
  series = {Journal of Neuroinflammation},
  volume    = {12},
  journal   = {Journal of Neuroinflammation},
  number    = {234},
  doi       = {10.1186/s12974-015-0429-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136252},
  year      = {2015},
  abstract  = {Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods: MOG\(_{35-55}\) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE\(^{-/-}\)) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE\(^{-/-}\) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.},
  language  = {en}
}
@article{RuckBittnerAfzalietal.2015,
  author    = {Ruck, Tobias and Bittner, Stefan and Afzali, Ali Maisam and G{\"o}bel, Kerstin and Glumm, Sarah and Kraft, Peter and Sommer, Claudia and Kleinschnitz, Christoph and Preusse, Corinna and Stenzel, Werner and Wiendl, Heinz and Meuth, Sven G.},
  title     = {The NKG2D-IL-15 signaling pathway contributes to T-cell mediated pathology in inflammatory myopathies},
  series = {Oncotarget},
  volume    = {6},
  journal   = {Oncotarget},
  number    = {41},
  doi       = {10.18632/oncotarget.6462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136047},
  year      = {2015},
  abstract  = {NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of the NKG2D - IL-15 signaling pathway. Primary human myoblasts expressed NKG2D ligands, which were further upregulated upon inflammatory stimuli. In parallel, shedding of the soluble NKG2D ligand MICA (sMICA) decreased upon inflammation potentially diminishing inhibition of NKG2D signaling. Membrane-related expression of IL-15 by myoblasts induced differentiation of naive CD8\(^+\) T cells into highly activated, cytotoxic \(CD8^+NKG2D^{high}\) T cells demonstrating NKG2D-dependent lysis of myoblasts in vitro. \(CD8^+NKG2D^{high}\) T cell frequencies were increased in the peripheral blood of polymyositis (PM) patients and correlated with serum creatinine kinase concentrations, while serum sMICA levels were not significantly changed. In muscle biopsy specimens from PM patients expression of the NKG2D ligand MICA/B was upregulated, IL-15 was expressed by muscle cells, CD68\(^+\) macrophages as well as CD4\(^+\) T cells, and \(CD8^+NKG2D^+\) cells were frequently detected within inflammatory infiltrates arguing for a local signaling circuit in the inflammatory muscle milieu. In conclusion, the NKG2D - IL-15 signaling pathway contributes to progressive muscle destruction in IIM potentially opening new therapeutic avenues.},
  language  = {en}
}
@article{FluriFleischerKleinschnitz2015,
  author    = {Fluri, Felix and Fleischer, Michael and Kleinschnitz, Christoph},
  title     = {Accidental Thrombolysis in a Stroke Patient Receiving Apixaban},
  series = {Cerebrovascular Diseases Extra},
  volume    = {5},
  journal   = {Cerebrovascular Diseases Extra},
  doi       = {10.1159/000375181},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126326},
  pages     = {55-56},
  year      = {2015},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KraftDrechslerSchuhmannetal.2015,
  author    = {Kraft, Peter and Drechsler, Christiane and Schuhmann, Michael K. and Gunreben, Ignaz and Kleinschnitz, Christoph},
  title     = {Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study},
  series = {International Journal of Molecular Science},
  volume    = {16},
  journal   = {International Journal of Molecular Science},
  number    = {10},
  doi       = {10.3390/ijms161025433},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126319},
  pages     = {25433-25449},
  year      = {2015},
  abstract  = {Immune cells (IC) play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA), chronic cerebrovascular disease (CCD) and healthy volunteers (HV). We conducted a case-control study of patients with AIS/TIA (n = 116) or CCD (n = 117), and HV (n = 104) who were enrolled at the University Hospital W{\"u}rzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.},
  language  = {en}
}
@article{DopplerAppeltshauserKraemeretal.2015,
  author    = {Doppler, Kathrin and Appeltshauser, Luise and Kr{\"a}mer, Heidrun H. and King Man Ng, Judy and Meinl, Edgar and Villmann, Carmen and Brophy, Peter and Dib-Hajj, Sulayman D. and Waxman, Stephen G. and Weishaupt, Andreas and Sommer, Claudia},
  title     = {Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0134274},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126156},
  pages     = {e0134274},
  year      = {2015},
  abstract  = {Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50\% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60\% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.},
  language  = {en}
}
@article{WestermaierKoehlerLinsenmannetal.2015,
  author    = {Westermaier, Thomas and Koehler, Stefan and Linsenmann, Thomas and Kinderlen, Michael and Pakos, Paul and Ernestus, Ralf-Ingo},
  title     = {Intraoperative Myelography in Cervical Multilevel Stenosis Using 3D Rotational Fluoroscopy: Assessment of Feasibility and Image Quality},
  series = {Radiology Research and Practice},
  volume    = {2015},
  journal   = {Radiology Research and Practice},
  doi       = {10.1155/2015/498936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125779},
  pages     = {498936},
  year      = {2015},
  abstract  = {Background. Intraoperative myelography has been reported for decompression control in multilevel lumbar disease. Cervical myelography is technically more challenging. Modern 3D fluoroscopy may provide a new opportunity supplying multiplanar images. This study was performed to determine the feasibility and image quality of intraoperative cervical myelography using a 3D fluoroscope. Methods. The series included 9 patients with multilevel cervical stenosis. After decompression, 10 mL of water-soluble contrast agent was administered via a lumbar drainage and the operating table was tilted. Thereafter, a 3D fluoroscopy scan (O-Arm) was performed and visually evaluated. Findings. The quality of multiplanar images was sufficient to supply information about the presence of residual stenosis. After instrumentation, metal artifacts lowered image quality. In 3 cases, decompression was continued because myelography depicted residual stenosis. In one case, anterior corpectomy was not completed because myelography showed sufficient decompression after 2-level discectomy. Interpretation. Intraoperative myelography using 3D rotational fluoroscopy is useful for the control of surgical decompression in multilevel spinal stenosis providing images comparable to postmyelographic CT. The long duration of contrast delivery into the cervical spine may be solved by preoperative contrast administration. The method is susceptible to metal artifacts and, therefore, should be applied before metal implants are placed.},
  language  = {en}
}
@article{KleinschnitzLinkerMagnusetal.2015,
  author    = {Kleinschnitz, Christoph and Linker, Ralf A. and Magnus, Tim and Korn, Thomas and Meuth, Sven G.},
  title     = {Report on the 6th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 31th - Nov. 2nd, 2014},
  series = {Experimental \& Translational Stroke Medicine},
  volume    = {7},
  journal   = {Experimental \& Translational Stroke Medicine},
  number    = {1},
  organization    = {on behalf of the speakers at the 6'th NEUROWIND e.V. scientific meeting},
  doi       = {10.1186/s13231-014-0013-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125049},
  year      = {2015},
  abstract  = {From October 31th - November 2nd, 2014, the 6th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. 70 doctoral students and postdocs from over 25 different groups working in German and Swiss university hospitals or research institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. The meeting was regarded as a very well organized platform to support research of young investigators in Germany and all participants enjoyed the stimulating environment for lively in depth discussions. According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 4th NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Michael Breckwoldt on his work in the group of Thomas Misgeld (Institute of Neuronal Cell Biology, Technische Universit{\"a}t M{\"u}nchen, Germany). The successful project was published in Nature Medicine entitled "Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo". This outstanding paper deals with a molecular imaging approach in living mice to optically analyze the role of mitochondrial redox signals in axons in health and disease. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant). This year's keynote lecture was given by Bernhard Hemmer, Head of the Department of Neurology at the Klinikum rechts der Isar, Technische Universit{\"a}t M{\"u}nchen. Dr. Hemmer highlighted the particular role of B cells and (auto)antibodies in multiple sclerosis (MS). As a new highlight Dr. Urbahns, head of global discovery technologies at Merck research laboratories, gave insights from research practice in the pharmaceutical industry and introduced a shift in the view on present-day drug discovery paradigms.},
  language  = {en}
}
@article{KleinGrohWeishauptetal.2015,
  author    = {Klein, Dennis and Groh, Janos and Weishaupt, Andreas and Martini, Rudolf},
  title     = {Endogenous antibodies contribute to macrophage-mediated demyelination in a mouse model for CMT1B},
  series = {Journal of Neuroinflammation},
  volume    = {12},
  journal   = {Journal of Neuroinflammation},
  number    = {49},
  doi       = {10.1186/s12974-015-0267-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125036},
  year      = {2015},
  abstract  = {Background We could previously identify components of both the innate and the adaptive immune system as disease modifiers in the pathogenesis of models for Charcot-Marie-Tooth (CMT) neuropathies type 1B and 1X. As part of the adaptive immune system, here we investigated the role of antibodies in a model for CMT1B. Methods Antibodies were localized and characterized in peripheral nerves of the CMT1B model by immunohistochemistry and Western blot analysis. Experimental ablation of antibodies was performed by cross breeding the CMT1B models with mutants deficient in B-lymphocytes (JHD-/- mutants). Ameliorated demyelination by antibody deficiency was reverted by intravenous injection of mouse IgG fractions. Histopathological analysis was performed by immunocytochemistry and light and quantitative electron microscopy. Results We demonstrate that in peripheral nerves of a mouse model for CMT1B, endogenous antibodies strongly decorate endoneurial tubes of peripheral nerves. These antibodies comprise IgG and IgM subtypes and are preferentially, but not exclusively, associated with nerve fiber aspects nearby the nodes of Ranvier. In the absence of antibodies, the early demyelinating phenotype is substantially ameliorated. Reverting the neuropathy by reconstitution with murine IgG fractions identified accumulating antibodies as potentially pathogenic at this early stage of disease. Conclusions Our study demonstrates that in a mouse model for CMT1B, endogenous antibodies contribute to early macrophage-mediated demyelination and disease progression. Thus, both the innate and adaptive immune system are mutually interconnected in a genetic model for demyelination. Since in Wallerian degeneration antibodies have also been shown to be involved in myelin phagocytosis, our study supports our view that inherited demyelination and Wallerian degeneration share common mechanisms, which are detrimental when activated under nonlesion conditions.},
  language  = {en}
}
@article{UeceylerKewenigKittelSchneideretal.2015,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Kewenig, Susanne and Kittel-Schneider, Sarah and Fallgatter, Andreas J. and Sommer, Claudia},
  title     = {Increased cortical activation upon painful stimulation in fibromyalgia syndrome},
  series = {BMC Neurology},
  volume    = {15},
  journal   = {BMC Neurology},
  number    = {210},
  doi       = {10.1186/s12883-015-0472-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125230},
  year      = {2015},
  abstract  = {Background Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS). Methods Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy). Results FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05). Conclusion Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.},
  language  = {en}
}
@article{HansenKahnZelleretal.2015,
  author    = {Hansen, Niels and Kahn, Ann-Kathrin and Zeller, Daniel and Katsarava, Zaza and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Amplitudes of pain-related evoked potentials are useful to detect small fiber involvement in painful mixed fiber neuropathies in addition to quantitative sensory testing - an electrophysiological study},
  series = {Frontiers in Neurology},
  volume    = {6},
  journal   = {Frontiers in Neurology},
  doi       = {10.3389/fneur.2015.00244},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124824},
  pages     = {244},
  year      = {2015},
  abstract  = {To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal ­neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN.},
  language  = {en}
}