TY - JOUR A1 - Gottschalk, Michael G. A1 - Richter, Jan A1 - Ziegler, Christiane A1 - Schiele, Miriam A. A1 - Mann, Julia A1 - Geiger, Maximilian J. A1 - Schartner, Christoph A1 - Homola, György A. A1 - Alpers, Georg W. A1 - Büchel, Christian A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Gloster, Andrew T. A1 - Helbig-Lang, Sylvia A1 - Kalisch, Raffael A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lonsdorf, Tina B. A1 - Pané-Farré, Christiane A. A1 - Ströhle, Andreas A1 - Weber, Heike A1 - Zwanzger, Peter A1 - Arolt, Volker A1 - Romanos, Marcel A1 - Wittchen, Hans-Ulrich A1 - Hamm, Alfons A1 - Pauli, Paul A1 - Reif, Andreas A1 - Deckert, Jürgen A1 - Neufang, Susanne A1 - Höfler, Michael A1 - Domschke, Katharina T1 - Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes JF - Translational Psychiatry N2 - Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system. KW - human behaviour KW - molecular neuroscience KW - personalized medicine KW - predictive markers KW - psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227479 VL - 9 ER - TY - JOUR A1 - Potreck, Arne A1 - Mutke, Matthias A. A1 - Weyland, Charlotte S. A1 - Pfaff, Johannes A. R. A1 - Ringleb, Peter A. A1 - Mundiyanapurath, Sibu A1 - Möhlenbruch, Markus A. A1 - Heiland, Sabine A1 - Pham, Mirko A1 - Bendszus, Martin A1 - Hoffmann, Angelika T1 - Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy JF - Translational Stroke Research N2 - Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression. KW - permeability imaging KW - perfusion imaging KW - mechanical thrombectomy KW - secondary stroke injury KW - hyperperfusion Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308946 SN - 1868-4483 SN - 1868-601X VL - 12 IS - 5 ER - TY - JOUR A1 - Adolph, Jonas E. A1 - Fleischhack, Gudrun A1 - Gaab, Christine A1 - Mikasch, Ruth A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Schüller, Ulrich A1 - Pfister, Stefan M. A1 - Pajtler, Kristian W. A1 - Milde, Till A1 - Witt, Olaf A1 - Bison, Brigitte A1 - Warmuth-Metz, Monika A1 - Kortmann, Rolf-Dieter A1 - Dietzsch, Stefan A1 - Pietsch, Torsten A1 - Timmermann, Beate A1 - Tippelt, Stephan T1 - Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies JF - Journal of Neuro-Oncology N2 - Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation. KW - ependymoma KW - chemotherapy KW - recurrence KW - children KW - sirolimus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308302 SN - 0167-594X SN - 1573-7373 VL - 155 IS - 2 ER - TY - JOUR A1 - Göpfert, Dennis A1 - Traub, Jan A1 - Sell, Roxane A1 - Homola, György A. A1 - Vogt, Marius A1 - Pham, Mirko A1 - Frantz, Stefan A1 - Störk, Stefan A1 - Stoll, Guido A1 - Frey, Anna T1 - Profiles of cognitive impairment in chronic heart failure—A cluster analytic approach JF - Frontiers in Human Neuroscience N2 - Background Cognitive impairment is a major comorbidity in patients with chronic heart failure (HF) with a wide range of phenotypes. In this study, we aimed to identify and compare different clusters of cognitive deficits. Methods The prospective cohort study “Cognition.Matters-HF” recruited 147 chronic HF patients (aged 64.5 ± 10.8 years; 16.2% female) of any etiology. All patients underwent extensive neuropsychological testing. We performed a hierarchical cluster analysis of the cognitive domains, such as intensity of attention, visual/verbal memory, and executive function. Generated clusters were compared exploratively with respect to the results of cardiological, neurological, and neuroradiological examinations without correction for multiple testing. Results Dendrogram and the scree plot suggested three distinct cognitive profiles: In the first cluster, 42 patients (28.6%) performed without any deficits in all domains. Exclusively, the intensity of attention deficits was seen in the second cluster, including 55 patients (37.4%). A third cluster with 50 patients (34.0%) was characterized by deficits in all cognitive domains. Age (p = 0.163) and typical clinical markers of chronic HF, such as ejection fraction (p = 0.222), 6-min walking test distance (p = 0.138), NT-proBNP (p = 0.364), and New York Heart Association class (p = 0.868) did not differ between clusters. However, we observed that women (p = 0.012) and patients with previous cardiac valve surgery (p = 0.005) prevailed in the “global deficits” cluster and the “no deficits” group had a lower prevalence of underlying arterial hypertension (p = 0.029). Total brain volume (p = 0.017) was smaller in the global deficit cluster, and serum levels of glial fibrillary acidic protein were increased (p = 0.048). Conclusion Apart from cognitively healthy and globally impaired HF patients, we identified a group with deficits only in the intensity of attention. Women and patients with previous cardiac valve surgery are at risk for global cognitive impairment when suffering HF and could benefit from special multimodal treatment addressing the psychosocial condition. KW - chronic heart failure KW - cluster analysis KW - cognitive impairment KW - intensity of attention KW - glial fibrillary acidic protein Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313429 VL - 17 ER - TY - JOUR A1 - Lehrieder, Dominik A1 - Zapantis, Nikolaos A1 - Pham, Mirko A1 - Schuhmann, Michael Klaus A1 - Haarmann, Axel T1 - Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report JF - Frontiers in Neurology N2 - Background Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively. Case presentation We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab. Conclusion Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive. KW - NMOSD KW - inebilizumab KW - AQP4 KW - longitudinally extensive transverse myelitis KW - optic neuritis KW - case report KW - CD19 KW - seronegative Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-354031 VL - 14 ER - TY - JOUR A1 - Stebani, Jannik A1 - Blaimer, Martin A1 - Zabler, Simon A1 - Neun, Tilmann A1 - Pelt, Daniël M. A1 - Rak, Kristen T1 - Towards fully automated inner ear analysis with deep-learning-based joint segmentation and landmark detection framework JF - Scientific Reports N2 - Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability. KW - anatomy KW - bone imaging KW - diagnosis KW - medical imaging KW - software KW - three-dimensional imaging KW - tomography Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357411 VL - 13 ER - TY - JOUR A1 - Vogel, P. A1 - Rückert, M. A. A1 - Greiner, C. A1 - Günther, J. A1 - Reichl, T. A1 - Kampf, T. A1 - Bley, T. A. A1 - Behr, V. C. A1 - Herz, S. T1 - iMPI: portable human-sized magnetic particle imaging scanner for real-time endovascular interventions JF - Scientific Reports N2 - Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model. KW - biomedical engineering KW - electrical and electronic engineering KW - imaging KW - three-dimensional imaging Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357794 VL - 13 ER - TY - THES A1 - Feick, Jörn T1 - Relevanz lokaler Blutgasparameter innerhalb des zerebralen Kollateralkreislaufs während akuter zerebraler Ischämie T1 - Distinct Alterations in Oxygenation, Ion Composition and Acid-Base Balance in Cerebral Collaterals During Large-Vessel Occlusion Stroke N2 - Störungen der Ionen- und Blutgas Homöostase mit Verschiebungen von Na+ und K+ in der regionalen Hypoxie sind ein Kennzeichen der experimentellen zerebralen Ischämie, wurden aber in ihrer Bedeutung für Schlaganfallpatienten noch nicht hinreichend untersucht. Wir berichten über eine prospektive, humane Querschnittsstudie an 366 Schlaganfallpatienten, die mit einer endovaskulären Rekanalisation bei einem akuten LVO der vorderen Zirkulation zwischen dem 18.Dezember 2018 und dem 31.August 2020 behandelt wurden. Im Rahmen der vorliegenden Dissertationsarbeit wurden intraprozedural arterielle Blutgasproben (1ml) aus dem lokal ischämischen Kollateralkreislauf und der intraindividuellen systemischen Referenzlokalisation in 51 Patienten gewonnen. Die Probengewinnung mit Hilfe eines Mikrokatheters erfolgte nach einem bereits veröffentlichten Protokoll. Diese Arbeit weist in der Perakutphase eines Großgefäßverschlusses signifikant nach, dass der lokal ischämische paO2 (-4,29%, paO2ischämisch=185,3 mmHg vs. paO2systemisch=193,6mmHg; p=0,035) und die Konzentration von K+ (-5,49%, K+ischämisch=3,44mmol/L vs. K+systemisch=3,64mmol/L; p=0,0081) signifikant reduziert war. Wir beobachteten, dass der Na+:K+-Quotient in der Kollateralzirkulation (+3,29%; Na+:K+-Quotientischämisch=41,74 vs. Na+:K+-Quotientsystemisch=40,38; p=0,0048) im Vergleich zur systemischen Zirkulation signifikant erhöht war, während die Na+-Konzentration signifikant positiv mit einer Zunahme des Infarktausmaßes assoziiert war (r=0,42, p=0,0033). Wir fanden eine alkaline Tendenz des zerebralen pH (+0,14%, pHischämisch=7,38 vs. pHsystemisch=7,37, p=0,0019), mit einer zeitabhängigen Verschiebung in den azidotischen Bereich (r=-0,36, p=0,0549). Schlussfolgernd deuten unsere Ergebnisse darauf hin, dass die durch den Schlaganfall verursachten Veränderungen der zerebralen Sauerstoffversorgung, der Ionenzusammensetzung und des Säure-Basen-Gleichgewichts dynamisch auftreten, während der okklusiven Ischämie fortschreiten und mit der akuten Gewebeschädigung im Zusammenhang stehen. Wünschenswert sind weitere prospektive Studien, um die Ergebnisse valide zu reproduzieren. N2 - Disturbances of ion and blood gas homeostasis encompassing massive sodium (Na+)/potassium (K+) shifts and regional hypoxia are a hallmark of experimental cerebral ischemia, but have not been sufficiently investigated for their relevance in stroke patients. We report a prospective observa-tional study on 366 stroke patients who underwent endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) of the anterior circulation (18 Dec 2018-31 Aug 2020). Intraprocedural blood gas samples (1ml) from within the cerebral collateral circulation (ischemic) and matched intraindividual systemic control samples were obtained according to a prespecified protocol in 51 patients. We observed a significant reduction in cerebral oxygen partial pressure (-4.29%, paO2ischemic=185.3 mmHg vs. paO2systemic=193.6; p=0.035) and potassium concentrations (-5.49%, K+ischemic=3.44 mmol/L vs. K+systemic=3.64 mmol/L; p=0.0081). The cerebral Na+: K+ ratio was signifi-cantly increased (Na+: K+ ratioischemic=41.74 vs. Na+: K+ ratiosystemic=40.38; p=0.0048) while sodium concentrations were positively correlated with tissue integrity (r=0.42, p=0.0033). We found more alkaline cerebral pH values (+0.14%, pHischemic=7.38 vs. pHsystemic=7.37, p=0.0019), with a time-dependent shift towards more acidotic conditions (r=-0.36, p=0.0549). These findings suggest that stroke-induced changes in cerebral oxygen supply, ion composition and acid-base balance dynamically occur and progress during occlusive ischemia, and are related to acute tissue damage. Further prospective studies are desirable in order to validly reproduce our results. KW - ischämischer Schlaganfall KW - Schlaganfall KW - Hirnkrankheit / Ischämie KW - zerebrale Ischämie KW - Großgefäßverschluss KW - arterielle Blutgasanalyse KW - mechanische Thrombektomie Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-351678 ER - TY - THES A1 - Krumma, Judith Josefine Birgitta T1 - Morphologie und bildgebende Veränderung in der Magnetresonanztomographie bei pädiatrischen Patienten/innen mit Rezidiven eines kranialen Ependymoms - Kohorte der Deutschen HIT- REZ Studie T1 - Morphology and imaging changes in magnetic resonance imaging in pediatric patients with recurrences of cranial ependymoma - cohort of the German HIT-REZ study N2 - In dieser Arbeit wurde einerseits retrospektiv untersucht, wie sich supratentorielle und infratentorielle Ependymome bildmorphologisch unterscheiden, ob Lokalrezidive eines Ependymoms dessen Bildeigenschaften teilen und welche Art von Rezidiven im Verlauf auftreten können. Die von uns beschriebenen Bildcharakteristika der Ependymome decken sich zum größten Teil mit bereits veröffentlichten Studien. Supratentorielle Ependymome unterscheiden sich signifikant in ihrer Bildmorphologie im Vergleich zu Ependymome der hintern Schädelgrube. Alle pädiatrischen Ependymompatienten/innen in unserem Kollektiv erkrankten an mindestens einem Rezidiv. Am häufigsten traten Lokalrezidive gefolgt von Meningeosen im ersten Rezidiv auf. Seltener fanden sich transiente postradiogene Läsionen, Diffuse intrinsische Ponsgliome und extraneurale Metastasen. Der bildmorphologische Vergleich, Primarius versus Lokalrezidiv ergab überwiegend ähnliche bildgebende Eigenschaften vor allem im Signalverhalten, Tumorbegrenzung und KM-Aufnahme sowie KM anreichernder Tumoranteil. Die kranielle Meningeose präsentierte sich zum ersten Rezidivzeitpunkt different zum Primärtumor. Die extraneuralen Metastasen hatten bildcharakteristisch Ähnlichkeiten zum Primärtumor. Bei der Bewertung neuer intraparenchymaler Läsionen sollte immer der zeitliche Zusammenhang zur letzten Therapie und damit mögliche vorübergehende postradiologischen Veränderungen berücksichtigt werden. Letztlich ist das pädiatrische Ependymom und Ependymomrezidiv ein komplexes und immer noch unvollständiges erfasstes Krankheitsbild. Durch umfangreichere Studien und die Zusammenführung dieser Ergebnisse könnte schlussendlich die Komplexität des Krankheitsbildes und somit die Therapieoptionen verbessert werden. Durch unsere Studie gelang einerseits die Beschreibung und der Vergleich des primären Ependymoms bezüglich supra- und infratentorieller Lokalisation und andererseits gelang eine neuroradiologische Beschreibung von Ependymomrezidiven im Vergleich zum primären Ependymom, wodurch in Zukunft die Nachsorge der Ependymomrezidive und die Therapieoptionen optimiert werden könnten. N2 - On the one hand, this work retrospectively investigated how supratentorial and infratentorial ependymomas differ in image morphology, whether local recurrences of an ependymoma share its image characteristics and what kind of recurrences can occur in the course of the disease. The image characteristics of ependymomas we describe largely correspond with studies that have already been published. Supratentorial ependymomas differ significantly in their image morphology compared to ependymomas of the posterior cranial fossa. All pediatric ependymoma patients in our collective suffered from at least one recurrence. Local recurrences were most common, followed by meningiosis in the first recurrence. Transient post-radiogenic lesions, diffuse intrinsic pontine gliomas and extraneural metastases were found less frequently. The image morphological comparison, primarius versus local recurrence, showed predominantly similar imaging properties, especially in terms of signal behavior, tumor limitation and contrast-enhancement intensity and volume. Cranial meningiosis was different from the primary tumor at the first time of recurrence. Extraneural metastases had similarities imaging characteristics to the primary tumor. The interpretation of new intraparenchymal lesions should consider the recent therapies and so that possible temporary post-radiological changes are taken into account. Ultimately, pediatric ependymoma and ependymoma recurrence is a complex and still incompletely recorded clinical picture. Through more extensive studies and the consolidation of these results, the complexity of the clinical picture and thus the treatment options could ultimately be improved. On the one hand, our study succeeded in describing and comparing the primary ependymoma with regard to supra- and infratentorial localization and, on the other hand, a neuroradiological description of ependymoma recurrences compared to primary ependymomoma, which could optimize the follow-up of ependymoma recurrences and treatment options in the future. KW - Ependymom KW - Pädiatrie KW - Ependymoma KW - Neuroradiology KW - Paediatrics KW - Neuroradiologie KW - Kinderheilkunde Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-351498 ER - TY - JOUR A1 - Solymosi, László T1 - Clinical Neuroradiology: challenges and perspectives JF - Clinical Neuroradiology N2 - No abstract available. KW - Clinical Neuroradiology KW - editorial Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324537 VL - 32 IS - 3 ER - TY - JOUR A1 - Solymosi, László T1 - It’s time to go … JF - Clinical Neuroradiology N2 - No abstract available. KW - editorial Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324997 VL - 32 IS - 4 ER - TY - JOUR A1 - Guggenberger, Konstanze V. A1 - Vogt, Marius L. A1 - Song, Jae W. A1 - Weng, Andreas M. A1 - Fröhlich, Matthias A1 - Schmalzing, Marc A1 - Venhoff, Nils A1 - Hillenkamp, Jost A1 - Pham, Mirko A1 - Meckel, Stephan A1 - Bley, Thorsten A. T1 - Intraorbital findings in giant cell arteritis on black blood MRI JF - European Radiology N2 - Objective Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. Methods In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. Results Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. Conclusions BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. Key Points • Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms. KW - giant cell arteritis KW - magnetic resonance imaging KW - orbit KW - ophthalmic artery KW - optic nerve Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324978 VL - 33 IS - 4 ER - TY - JOUR A1 - Haarmann, Axel A1 - Vollmuth, Christoph A1 - Kollikowski, Alexander M. A1 - Heuschmann, Peter U. A1 - Pham, Mirko A1 - Stoll, Guido A1 - Neugebauer, Hermann A1 - Schuhmann, Michael K. T1 - Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion JF - Cells N2 - Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion. KW - endoglin KW - brain endothelium KW - stroke KW - shedding KW - mechanical thrombectomy KW - hypoxia KW - reperfusion injury KW - biomarker Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304995 SN - 2073-4409 VL - 12 IS - 2 ER - TY - JOUR A1 - Hackenberg, Stephan A1 - Meyer, Till Jasper A1 - Häfner, Johannes A1 - Scheich, Matthias A1 - Stöth, Manuel A1 - Al-Tinawi, Fadi A1 - Neun, Tilmann A1 - Mlynski, Robert A1 - Hagen, Rudolf A1 - Scherzad, Agmal T1 - Surgical management of tympanojugular paragangliomas using the flexible CO\(_2\) laser JF - European Archives of Oto-Rhino-Laryngology N2 - Purpose Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser. Methods Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. Results The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. Conclusion The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view. KW - tympanojugular paraganglioma KW - tympanic paraganglioma KW - jugular paraganglioma KW - surgical management of paraganglioma KW - laser surgery KW - flexible CO2 laser Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324164 VL - 279 IS - 12 ER - TY - JOUR A1 - Peters, Sarah A1 - Frisch, Sabine A1 - Stock, Annika A1 - Merta, Julien A1 - Bäumer, Christian A1 - Blase, Christoph A1 - Schuermann, Eicke A1 - Tippelt, Stephan A1 - Bison, Brigitte A1 - Frühwald, Michael A1 - Rutkowski, Stefan A1 - Fleischhack, Gudrun A1 - Timmermann, Beate T1 - Proton beam therapy for pediatric tumors of the central nervous system — experiences of clinical outcome and feasibility from the KiProReg study JF - Cancers N2 - As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT. KW - proton beam therapy KW - childhood cancer KW - brain cancer KW - adverse events KW - imaging changes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297489 SN - 2072-6694 VL - 14 IS - 23 ER - TY - JOUR A1 - Bieber, Michael A1 - Schuhmann, Michael K. A1 - Bellut, Maximilian A1 - Stegner, David A1 - Heinze, Katrin G. A1 - Pham, Mirko A1 - Nieswandt, Bernhard A1 - Stoll, Guido T1 - Blockade of platelet glycoprotein Ibα augments neuroprotection in Orai2-deficient mice during middle cerebral artery occlusion JF - International Journal of Molecular Sciences N2 - During ischemic stroke, infarct growth before recanalization diminishes functional outcome. Hence, adjunct treatment options to protect the ischemic penumbra before recanalization are eagerly awaited. In experimental stroke targeting two different pathways conferred protection from penumbral tissue loss: (1) enhancement of hypoxic tolerance of neurons by deletion of the calcium channel subunit Orai2 and (2) blocking of detrimental lymphocyte–platelet responses. However, until now, no preclinical stroke study has assessed the potential of combining neuroprotective with anti-thrombo-inflammatory interventions to augment therapeutic effects. We induced focal cerebral ischemia in Orai2-deficient (Orai2\(^{-/-}\)) mice by middle cerebral artery occlusion (MCAO). Animals were treated with anti-glycoprotein Ib alpha (GPIbα) Fab fragments (p0p/B Fab) blocking GPIbα–von Willebrand factor (vWF) interactions. Rat immunoglobulin G (IgG) Fab was used as the control treatment. The extent of infarct growth before recanalization was assessed at 4 h after MCAO. Moreover, infarct volumes were determined 6 h after recanalization (occlusion time: 4 h). Orai2 deficiency significantly halted cerebral infarct progression under occlusion. Inhibition of platelet GPIbα further reduced primary infarct growth in Orai2\(^{-/-}\) mice. During ischemia–reperfusion, upon recanalization, mice were likewise protected. All in all, we show that neuroprotection in Orai2\(^{-/-}\) mice can be augmented by targeting thrombo-inflammation. This supports the clinical development of combined neuroprotective/anti-platelet strategies in hyper-acute stroke. KW - ischemic penumbra KW - Orai2 KW - glycoprotein receptor Ibα KW - ischemic stroke KW - thrombo-inflammation KW - middle cerebral artery occlusion Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286038 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Bieber, Michael A1 - Foerster, Kathrin I. A1 - Haefeli, Walter E. A1 - Pham, Mirko A1 - Schuhmann, Michael K. A1 - Kraft, Peter T1 - Treatment with edoxaban attenuates acute stroke severity in mice by reducing blood–brain barrier damage and inflammation JF - International Journal of Molecular Sciences N2 - Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted. KW - edoxaban KW - thrombo-inflammation KW - blood–brain barrier KW - tMCAO KW - experimental stroke KW - hemorrhagic transformation KW - NOAC Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284481 SN - 1422-0067 VL - 22 IS - 18 ER - TY - JOUR A1 - Strinitz, Marc A1 - Pham, Mirko A1 - März, Alexander G. A1 - Feick, Jörn A1 - Weidner, Franziska A1 - Vogt, Marius L. A1 - Essig, Fabian A1 - Neugebauer, Hermann A1 - Stoll, Guido A1 - Schuhmann, Michael K. A1 - Kollikowski, Alexander M. T1 - Immune cells invade the collateral circulation during human stroke: prospective replication and extension JF - International Journal of Molecular Sciences N2 - It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R\(^2\) = 0.09696, p = 0.0373) and (4) greater infarct extent (R\(^2\) = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment. KW - ischemic stroke KW - cerebral ischemia KW - mechanical thrombectomy KW - large vessel occlusion KW - leukocytes KW - neutrophils KW - collateral circulation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284281 SN - 1422-0067 VL - 22 IS - 17 ER - TY - JOUR A1 - Nguemeni, Carine A1 - Hiew, Shawn A1 - Kögler, Stefanie A1 - Homola, György A. A1 - Volkmann, Jens A1 - Zeller, Daniel T1 - Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis JF - Brain Sciences N2 - The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes. KW - multiple sclerosis KW - split-belt treadmill KW - cerebellar tDCS KW - gait KW - balance KW - risk of fall Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252179 SN - 2076-3425 VL - 12 IS - 1 ER - TY - JOUR A1 - Vogel, Patrick A1 - Rückert, Martin Andreas A1 - Friedrich, Bernhard A1 - Tietze, Rainer A1 - Lyer, Stefan A1 - Kampf, Thomas A1 - Hennig, Thomas A1 - Dölken, Lars A1 - Alexiou, Christoph A1 - Behr, Volker Christian T1 - Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics JF - Nature Communications N2 - Magnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity. KW - biochemical assays KW - characterization and analytical techniques KW - magnetic properties and materials KW - nanoparticles Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300893 VL - 13 ER -