TY - JOUR A1 - Gabriel, Katharina M. A. A1 - Jírů-Hillmann, Steffi A1 - Kraft, Peter A1 - Selig, Udo A1 - Rücker, Victoria A1 - Mühler, Johannes A1 - Dötter, Klaus A1 - Keidel, Matthias A1 - Soda, Hassan A1 - Rascher, Alexandra A1 - Schneider, Rolf A1 - Pfau, Mathias A1 - Hoffmann, Roy A1 - Stenzel, Joachim A1 - Benghebrid, Mohamed A1 - Goebel, Tobias A1 - Doerck, Sebastian A1 - Kramer, Daniela A1 - Haeusler, Karl Georg A1 - Volkmann, Jens A1 - Heuschmann, Peter U. A1 - Fluri, Felix T1 - Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke) JF - BMC Neurology N2 - Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals. KW - pilot project KW - care tempis KW - ischemic stroke KW - thrombolysis KW - areas KW - time KW - hospitals KW - mortality KW - outcomes KW - quality Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229214 VL - 20 ER - TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Volkmann, Jens A1 - Schliesser, Mira A1 - Fluri, Felix T1 - Symptomatic vs. asymptomatic 20–40% internal carotid artery stenosis: Does the plaque size matter? JF - Frontiers in Neurology N2 - Background: Around 9–15% of ischemic strokes are related to internal carotid artery (ICA)-stenosis ≥50%. However, the extent to which ICA-stenosis <50% causes ischemic cerebrovascular events is uncertain. We examined the relation between plaque cross-sectional area and length and the risk of ischemic stroke or TIA among patients with ICA-stenosis of 20–40%. Methods: We retrospectively identified patients admitted to the Department of Neurology, University Hospital of Würzburg, from January 2011 until September 2016 with ischemic stroke or TIA and concomitant ICA-stenosis of 20–40%, either symptomatic or asymptomatic. Plaque length and cross-sectional area were assessed on ultrasound scans. Results: We identified 41 patients with ischemic stroke or TIA and ICA-stenosis of 20–40%; 14 symptomatic and 27 asymptomatic. The plaque cross-sectional area was significantly larger among symptomatic than asymptomatic ICA-stenosis; median values (IQR) were 0.45 (0.21–0.69) cm2 and 0.27 (0.21–0.38) cm2, p = 0.03, respectively. A plaque cross-sectional area ≥0.36 cm2 had a sensitivity of 71% and a specificity of 76% for symptomatic compared with asymptomatic ICA-stenosis. In a sex-adjusted multivariate logistic regression, a plaque cross-sectional area ≥0.36 cm2 and a plaque length ≥1.65 cm were associated with an OR (95% CI) of 5.54 (1.2–25.6), p = 0.028 and 1.78 (0.36–8.73), p = 0.48, respectively, for symptomatic ICA-stenosis. Conclusion: Large plaques might increase the risk of ischemic stroke or TIA among patients with low-grade ICA-stenosis of 20–40%. Sufficiently powered prospective longitudinal cohort studies are needed to definitively test the stroke risk stratification value of carotid plaque length and cross-sectional area in the setting of current optimal medical treatment. KW - ischemic stroke KW - carotid atherosclerosis KW - carotid stenosis KW - plaque cross-sectional area KW - length of stenosis KW - carotid ultrasound Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201262 VL - 10 IS - 960 ER - TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Heuschmann, Peter U. A1 - Pham, Mirko A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Stenosis length and degree interact with the risk of cerebrovascular events related to internal carotid artery stenosis JF - Frontiers in Neurology N2 - Background and Purpose: Internal carotid artery stenosis (ICAS)≥70% is a leading cause of ischemic cerebrovascular events (ICVEs). However, a considerable percentage of stroke survivors with symptomatic ICAS (sICAS) have <70% stenosis with a vulnerable plaque. Whether the length of ICAS is associated with high risk of ICVEs is poorly investigated. Our main aim was to investigate the relation between the length of ICAS and the development of ICVEs. Methods: In a retrospective cross-sectional study, we identified 95 arteries with sICAS and another 64 with asymptomatic internal carotid artery stenosis (aICAS) among 121 patients with ICVEs. The degree and length of ICAS as well as plaque echolucency were assessed on ultrasound scans. Results: A statistically significant inverse correlation between the ultrasound-measured length and degree of ICAS was detected for sICAS≥70% (Spearman correlation coefficient ρ = –0.57, p < 0.001, n = 51) but neither for sICAS<70% (ρ = 0.15, p = 0.45, n = 27) nor for aICAS (ρ = 0.07, p = 0.64, n = 54). The median (IQR) length for sICAS<70% and ≥70% was 17 (15–20) and 15 (12–19) mm (p = 0.06), respectively, while that for sICAS<90% and sICAS 90% was 18 (15–21) and 13 (10–16) mm, respectively (p < 0.001). Among patients with ICAS <70%, a cut-off length of ≥16 mm was found for sICAS rather than aICAS with a sensitivity and specificity of 74.1% and 51.1%, respectively. Irrespective of the stenotic degree, plaques of the sICAS compared to aICAS were significantly more often echolucent (43.2 vs. 24.6%, p = 0.02). Conclusion: We found a statistically insignificant tendency for the ultrasound-measured length of sICAS<70% to be longer than that of sICAS≥70%. Moreover, the ultrasound-measured length of sICAS<90% was significantly longer than that of sICAS 90%. Among patients with sICAS≥70%, the degree and length of stenosis were inversely correlated. Larger studies are needed before a clinical implication can be drawn from these results. KW - ischemic stroke KW - carotid stenosis KW - carotid atherosclerosis KW - length of stenosis KW - degree of stenosis KW - carotid ultrasound KW - outcome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196225 SN - 1664-2295 VL - 10 IS - 317 ER - TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Abd El‐Raouf, Mervat A1 - Volkmann, Jens A1 - Fluri, Felix A1 - Elsalamawy, Doaa T1 - Relation of infarction location and volume to vertigo in vertebrobasilar stroke JF - Brain and Behavior N2 - Objective Vertigo is a common presentation of vertebrobasilar stroke. Anecdotal reports have shown that vertigo occurs more often in multiple than in single brainstem or cerebellar infarctions. We examined the relation between the location and volume of infarction and vertigo in patients with vertebrobasilar stroke. Methods Consecutive patients with vertebrobasilar stroke were prospectively recruited. The infarction location and volume were assessed in the diffusion‐weighted magnetic resonance imaging. Results Fifty‐nine patients were included, 32 (54.2%) with vertigo and 27 (45.8%) without vertigo. The infarction volume did not correlate with National Institute of Health Stroke Scale (NIHSS) score on admission (Spearman ρ = .077, p = .56) but correlated with modified Rankin Scale (ρ = .37, p = .004) on discharge. In the vertigo group, the proportion of men was lower (53.1% vs. 77.8%, p = .049), fewer patients had focal neurological deficits (65.6% vs. 96.3%, p = .004), patients tended to present later (median [IQR] was 7.5 [4–46] vs. 4 [2–12] hours, p = .052), numerically fewer patients received intravenous thrombolysis (15.6% vs. 37%, p = .06), and the total infarction volume was larger (5.6 vs. 0.42 cm3, p = .008) than in nonvertigo group. In multivariate logistic regression, infarction location either in the cerebellum or in the dorsal brainstem (odds ratio [OR] 16.97, 95% CI 3.1–92.95, p = .001) and a total infarction volume of >0.48 cm3 (OR 4.4, 95% CI 1.05–18.58, p = .043) were related to vertigo. In another multivariate logistic regression, after adjusting for age, sex, intravenous thrombolysis, serum level of white blood cells, and atrial fibrillation, vertigo independently predicted a total infarction volume of >0.48 cm3 (OR 5.75, 95% CI 1.43–23.08, p = .01). Conclusion Infarction location in the cerebellum and/or dorsal brainstem is an independent predictor of vertigo. Furthermore, larger infarction volume in these structures is associated with vertigo. A considerable proportion of patients with vascular vertigo present without focal neurological deficits posing a diagnostic challenge. National Institute of Health Stroke Scale is not sensitive for vertebrobasilar stroke. KW - brain stem KW - cerebellum KW - infarction volume KW - stroke KW - vertebrobasilar insufficiency KW - vertigo Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218047 VL - 10 IS - 3 ER - TY - JOUR A1 - Elhfnawy, Ahmed Mohamed A1 - Elsalamawy, Doaa A1 - Abdelraouf, Mervat A1 - Schliesser, Mira A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review JF - Acta Neurologica Belgica N2 - Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100%), but only five (7.9%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke. KW - giant cell arteritis KW - vertebrobasilar stroke KW - blood sedimentation KW - C-reactive protein KW - hemoglobin KW - stenosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315610 SN - 0300-9009 SN - 2240-2993 VL - 120 IS - 6 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Papp, Lena A1 - Stoll, Guido A1 - Blum, Robert A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Mesencephalic electrical stimulation reduces neuroinflammation after photothrombotic stroke in rats by targeting the cholinergic anti-inflammatory pathway JF - International Journal of Molecular Sciences N2 - Inflammation is crucial in the pathophysiology of stroke and thus a promising therapeutic target. High-frequency stimulation (HFS) of the mesencephalic locomotor region (MLR) reduces perilesional inflammation after photothrombotic stroke (PTS). However, the underlying mechanism is not completely understood. Since distinct neural and immune cells respond to electrical stimulation by releasing acetylcholine, we hypothesize that HFS might trigger the cholinergic anti-inflammatory pathway via activation of the α7 nicotinic acetylcholine receptor (α7nAchR). To test this hypothesis, rats underwent PTS and implantation of a microelectrode into the MLR. Three hours after intervention, either HFS or sham-stimulation of the MLR was applied for 24 h. IFN-γ, TNF-α, and IL-1α were quantified by cytometric bead array. Choline acetyltransferase (ChAT)\(^+\) CD4\(^+\)-cells and α7nAchR\(^+\)-cells were quantified visually using immunohistochemistry. Phosphorylation of NFĸB, ERK1/2, Akt, and Stat3 was determined by Western blot analyses. IFN-γ, TNF-α, and IL-1α were decreased in the perilesional area of stimulated rats compared to controls. The number of ChAT\(^+\) CD4\(^+\)-cells increased after MLR-HFS, whereas the amount of α7nAchR\(^+\)-cells was similar in both groups. Phospho-ERK1/2 was reduced significantly in stimulated rats. The present study suggests that MLR-HFS may trigger anti-inflammatory processes within the perilesional area by modulating the cholinergic system, probably via activation of the α7nAchR. KW - photothrombotic stroke KW - deep brain stimulation KW - mesencephalic locomotor region KW - neuroinflammation KW - choline acetyltransferase KW - alpha-7 nicotinic acetylcholine receptor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259099 SN - 1422-0067 VL - 22 IS - 3 ER - TY - JOUR A1 - Fluri, Felix A1 - Heinen, Florian A1 - Kleinschnitz, Christoph T1 - Intravenous Thrombolysis in a Stroke Patient Receiving Rivaroxaban JF - Cerebrovascular Disease Extra N2 - No abstract available. KW - anticoagulants KW - intravenous thrombolysis KW - acute ischemic stroke Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128816 VL - 2013 IS - 3 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Bittner, Stefan A1 - Meuth, Sven G. A1 - Kleinschnitz, Christoph A1 - Fluri, Felix T1 - Fingolimod (FTY720-P) does not stabilize the blood-brain barrier under inflammatory conditions in an in vitro model JF - International Journal of Molecular Sciences N2 - 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. KW - randomized controlled trial KW - Sphingosine 1-Phosphate KW - vascular permeability KW - rat brain microvascular endothelial cell culture KW - tight junctions KW - FTY720-P KW - blood-brain barrier KW - inflammation KW - novo renal transplantation KW - endothelial cells KW - experimental autoimmune encephalomyelitis KW - relapsing multiple sclerosis KW - Zonula Occludens-1 KW - matrix metalloproteinases Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145047 VL - 16 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Stoll, Guido A1 - Papp, Lena A1 - Bohr, Arne A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Electrical stimulation of the mesencephalic locomotor region has no impact on blood–brain barrier alterations after cerebral photothrombosis in rats JF - International Journal of Molecular Science N2 - Blood–brain barrier (BBB) disruption is a critical event after ischemic stroke, which results in edema formation and hemorrhagic transformation of infarcted tissue. BBB dysfunction following stroke is partly mediated by proinflammatory agents. We recently have shown that high frequency stimulation of the mesencephalic locomotor region (MLR-HFS) exerts an antiapoptotic and anti-inflammatory effect in the border zone of cerebral photothrombotic stroke in rats. Whether MLR-HFS also has an impact on BBB dysfunction in the early stage of stroke is unknown. In this study, rats were subjected to photothrombotic stroke of the sensorimotor cortex and implantation of a stimulating microelectrode into the ipsilesional MLR. Thereafter, either HFS or sham stimulation of the MLR was applied for 24 h. After scarifying the rats, BBB disruption was assessed by determining albumin extravasation and tight junction integrity (claudin 3, claudin 5, and occludin) using Western blot analyses and immunohistochemistry. In addition, by applying zymography, expression of pro-metalloproteinase-9 (pro-MMP-9) was analyzed. No differences were found regarding infarct size and BBB dysfunction between stimulated and unstimulated animals 24 h after induction of stroke. Our results indicate that MLR-HFS neither improves nor worsens the damaged BBB after stroke. Attenuating cytokines/chemokines in the perilesional area, as mediated by MLR-HFS, tend to play a less significant role in preventing the BBB integrity. KW - photothrombotic stroke KW - deep brain stimulation KW - mesencephalic locomotor region KW - blood-brain barrier KW - tight junctions Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201284 SN - 1422-0067 VL - 20 IS - 16 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Stoll, Guido A1 - Bohr, Arne A1 - Volkmann, Jens A1 - Fluri, Felix T1 - Electrical stimulation of the mesencephalic locomotor region attenuates neuronal loss and cytokine expression in the perifocal region of photothrombotic stroke in rats JF - International Journal of Molecular Science N2 - Deep brain stimulation of the mesencephalic locomotor region (MLR) improves the motor symptoms in Parkinson’s disease and experimental stroke by intervening in the motor cerebral network. Whether high-frequency stimulation (HFS) of the MLR is involved in non-motor processes, such as neuroprotection and inflammation in the area surrounding the photothrombotic lesion, has not been elucidated. This study evaluates whether MLR-HFS exerts an anti-apoptotic and anti-inflammatory effect on the border zone of cerebral photothrombotic stroke. Rats underwent photothrombotic stroke of the right sensorimotor cortex and the implantation of a microelectrode into the ipsilesional MLR. After intervention, either HFS or sham stimulation of the MLR was applied for 24 h. The infarct volumes were calculated from consecutive brain sections. Neuronal apoptosis was analyzed by TUNEL staining. Flow cytometry and immunohistochemistry determined the perilesional inflammatory response. Neuronal apoptosis was significantly reduced in the ischemic penumbra after MLR-HFS, whereas the infarct volumes did not differ between the groups. MLR-HFS significantly reduced the release of cytokines and chemokines within the ischemic penumbra. MLR-HFS is neuroprotective and it reduces pro-inflammatory mediators in the area that surrounds the photothrombotic stroke without changing the number of immune cells, which indicates that MLR-HFS enables the function of inflammatory cells to be altered on a molecular level. KW - photothrombotic stroke KW - deep brain stimulation KW - mesencephalic locomotor region KW - neuroprotection KW - neuronal apoptosis KW - neuroinflammation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201355 SN - 1422-0067 VL - 20 IS - 9 ER -